Aminoglicozide

Antibiotics
Infectious Diseases Society of America (IDSA) Recommendations

for Initial First-Line Treatment in Adults
Skin and soft tissue infections
Infectious Disease Society of America (IDSA) recommendations for first-line treatment of skin and
soft tissue infections in adults
Recommendations for First-Line Treatment in Adults with Necrotizing Infections of Skin, Fascia,
and Muscle:
Recommended First-Line Agent for Patient with Severe
Infection Type
Treatment Penicillin Hypersensitivity
Clindamycin or
Piperacillin-tazobactam metronidazole with
3.375 g IV every 6-8 hours aminoglycoside or
PLUS fluoroquinolone
Vancomycin 30 mg/kg/day If Staphylococcus present
in 2 divided doses or suspected, add
appropriate agent
Imipenem-cilastatin 1 g IV every
NA
Polymicrobial infections 6-8 hours
Meropenem 1 g IV every 8 hours -
Ertapenem 1 g/day IV -
Cefotaxime 2 g IV every 6
hours PLUS
Metronidazole 500 mg IV
NA
every 6 hours OR
clindamycin 600-900 mg IV
every 8 hours
1 of
Penicillin 2-4 million units
IV every 4-6 hours PLUS Vancomycin
Streptococcus
Clindamycin 600-900 mg IV Linezolid
every 8 hours Quinupristin/dalfopristin
Daptomycin
Abbreviations: MRSA, methicillin-resistant S. aureus; NA, not applicable.
Reference - IDSA practice guideline on diagnosis and management of skin and soft tissue
infections: 2014 update can be found in Clin Infect Dis 2014 Jul 15;59(2):e10 full-text, executive
summary can be found in Clin Infect Dis 2014 Jul 15;59(2):147 full-text.
Recommended First-Line Agent for Patient with Severe
Infection Type
Treatment Penicillin Hypersensitivity
1 of
Vancomycin
Nafcillin 1-2 g IV every 4 hours
Linezolid
Quinupristin/dalfopristin
Daptomycin
Oxacillin 1-2 g IV every 4 hours -
Cefazolin 1 g IV every 8 hours -
Vancomycin 30 mg/kg/day IV in
-
2 divided doses
Staphylococcus aureus Bacteriostatic
Potential cross-resistance
and emergence of
resistance in
erythromycin-resistant
Clindamycin 600-900 mg IV strains
every 8 hours Inducible resistance in
MRSA
If MRSA suspected or
present, add vancomycin
not to exceed maximum
adult daily dose
Clindamycin 600-900 mg IV
every 8 hours PLUS
Clostridium species NA
Penicillin 2-4 million units
IV every 4-6 hours
Doxycycline 100 mg IV
every 12 hours PLUS
Ciprofloxacin 500 mg IV
Aeromonas hydrophila NA
every 12 hours OR
ceftriaxone 1-2 g IV every
24 hours
Doxycycline 100 mg IV
every 12 hours PLUS
Vibrio vulnificus Ceftriaxone 1 g IV 4 times NA
daily OR cefotaxime 2 g IV
3 times daily
Abbreviations: MRSA, methicillin-resistant S. aureus; NA, not applicable.
recommended treatment for staphylococcal and streptococcal skin and soft tissue infections
Recommendations for Treatment in Adults with Impetigo Caused by Staphylococcus and
Streptococcus:
Drug Dose* Additional Comments
Dicloxacillin 250 mg orally 4 times daily NA
Cephalexin 250 mg orally 4 times daily NA
Some strains of S. aureus and
Erythromycin 250 mg orally 4 times daily Streptococcus pyogenes may be
resistant
Erythromycin ethylsuccinate 400 mg orally 4 times daily NA
Clindamycin 300-400 mg orally 4 times daily NA
Amoxicillin-clavulanate 875/125 mg orally twice daily NA
Retapamulin ointment or For patients with limited
Apply to lesions twice daily
mupirocin ointment number of lesions
Abbreviation: NA, not applicable.
* Recommended duration 7 days.
Recommendations for Treatment in Adults with Staphylococcal and Streptococcal Skin and Soft
Tissue Infections :
Additional
Infection Type Drug Dose
Comments
MSSA skin and soft Parenteral drug
tissue infections 1-2 g IV every 4 of choice
Nafcillin or oxacillin
hours Inactive against
MRSA
For penicillin-
allergic patients
except those
with immediate
hypersensitivity
reactions
Cefazolin 1 g IV every 8 hours
More
convenient
than nafcillin
with less bone
marrow
suppression
Abbreviations: MRSA, methicillin-resistant Staphylococcal aureus; MSSA, methicillin-susceptible S.

aureus; NA, not applicable.
Additional
Comments
Bacteriostatic
Potential of
cross-resistance
600 mg IV every 8 and emergence
hours OR 300-450 of resistance in
Clindamycin
mg orally 4 times erythromycin-
daily resistant strains
Inducible
resistance in
MRSA
Oral agent of
choice for
500 mg orally 4
Dicloxacillin methicillin-
times daily
susceptible
strains in adults
For penicillin-
allergic patients
500 mg orally 4 except those
Cephalexin
times daily with immediate
hypersensitivity
reactions
Bacteriostatic
100 mg orally twice Limited recent
Doxycycline, minocycline
daily clinical
experience
Co-trimoxazole 1-2 double-strength Bacteriostatic
(trimethoprim/sulfamethoxazole, tablets orally twice Efficacy poorly
TMP/SMX) daily documented
MRSA skin and soft For penicillin-
tissue infections allergic patients
Parenteral drug
30 mg/kg/day IV in 2
Vancomycin of choice for
divided doses
infections
caused by
MRSA
Bacteriostatic
Limited clinical
experience
600 mg IV every 12
No cross-
Linezolid hours OR 600 mg
resistance with
orally twice daily
other antibiotic
classes
Expensive

Additional
Comments
Bacteriostatic
Potential of
cross-resistance
and emergence
600 mg IV every 8
of resistance in
Clindamycin hours or 300-450 mg
erythromycin-
orally 4 times daily
resistant strains
Inducible
resistance in
MRSA
Bactericidal
4 mg/kg IV every 24
Daptomycin Possible
hours
myopathy
600 mg IV twice
Ceftaroline Bactericidal
daily
Bacteriostatic
100 mg orally twice Limited recent
Doxycycline, minocycline
daily clinical
experience
Bactericidal
Co-trimoxazole 1-2 double-strength
Limited
(trimethoprim/sulfamethoxazole, tablets orally twice
published
TMP/SMX) daily
efficacy data
2-4 million units IV
Penicillin NA
every 4-6 hours
Clindamycin
600-900 mg IV every resistance < 1% but
Clindamycin
8 hours may be increasing in
Asia
Streptococcal skin 1-2 g IV every 4-6
infections Nafcillin NA
hours
Cefazolin 1 g IV every 8 hours NA
250-500 mg orally
Penicillin VK NA
every 6 hours
500 mg orally every
Cephalexin NA
6 hours
recommendations for incisional surgical site infections
Recommendations for Treatment in Patients with Incisional Surgical Site Infections by Site:
Surgery Type Recommended Treatment
Surgery Type Recommended Treatment
Ticarcillin-clavulanate 3.1 g IV every 6 hours
Piperacillin-tazobactam 3.375 g IV every 6 hours
Intestinal or genitourinary tract single-drug or 4.5 g IV every 8 hours
regimens Imipenem-cilastatin 500 mg IV every 6 hours
Meropenem 1 g IV every 8 hours
Ertapenem 1 g IV every 24 hours
Ceftriaxone 1 g IV every 24 hours PLUS
Metronidazole 500 mg IV every 8 hours
Ciprofloxacin 400 mg IV every 12 hours or
750 mg orally every 12 hours PLUS
Intestinal or genitourinary tract combination Levofloxacin 750 mg IV every 24 hours
regimens PLUS
Ampicillin-sulbactam 3 g IV every 6 hours
PLUS
Gentamicin or tobramycin 5 mg/kg IV every
24 hours
Oxacillin or nafcillin 2 g IV every 6 hours
Cefazolin 0.5-1 g IV every 8 hours
Trunk or extremity away from axilla or Cephalexin 500 mg orally every 6 hours
perineum Sulfamethoxazole-trimethoprim 160-800 mg
orally every 6 hours
Vancomycin 15 mg/kg IV every 12 hours
Metronidazole 500 mg IV every 8 hours, PLUS 1
of
Ciprofloxacin 400 mg IV every 12 hours or
Surgery of axilla or perineum*
750 mg orally every 12 hours
Levofloxacin 750 mg IV every 24 hours
Ceftriaxone 1 g IV every 24 hours
* May also need to cover for methicillin-resistant Staphylococcus aureus with vancomycin 15 mg/kg
IV every 12 hours.
mammalian bites
Recommendations for Treatment of Patients with Animal Bites:
Oral administration
Some gram-negative rods
Amoxicillin/clavulanate 875/125 mg twice daily are resistant
Misses MRSA
Excellent activity against
Pasteurella multocida
Doxycycline 100 mg twice daily
Some streptococci are
resistant
Penicillin plus dicloxacillin 500 mg 4 times daily for each NA
Good activity against
Co-trimoxazole
800/160 mg (1 double-strength aerobes
(trimethoprim/sulfamethoxazole,
tablet) twice daily Poor activity against
TMP/SMX)
anaerobes
Metronidazole 250-500 mg 3 times daily anaerobes
No activity against aerobes
staphylococci,
Clindamycin 300 mg 3 times daily streptococci, and
anaerobes
Misses P. multocida
Second-generation
cephalosporin
Cefuroxime 500 mg twice daily Good activity against P.
multocida
Misses anaerobes
Fluoroquinolone
Ciprofloxacin 500-750 mg twice daily Good activity against P.
multocida
Levofloxacin 750 mg/day Misses MRSA and some
anaerobes
Fluoroquinolone
Moxifloxacin 400 mg/day Monotherapy
Good for anaerobes also
IV administration
Ampicillin-sulbactam 1.5-3 g every 6-8 hours are resistant
Misses MRSA
Piperacillin-tazobactam 3.375 g every 6-8 hours Misses MRSA
P. multocida
Doxycycline 100 mg every 12 hours
resistant
Second-generation
Cefuroxime 1 g every 12 hours cephalosporins
Good activity against P.
Cefoxitin 1 g every 6-8 hours multocida
Misses anaerobes
Ceftriaxone 1 g every 12 hours Third-generation
Cefotaxime 1-2 g every 6-8 hours cephalosporins
Fluoroquinolones
Ciprofloxacin 400 mg every 12 hours Good activity against P.
multocida
Levofloxacin 750 mg/day Misses MRSA and some
anaerobes
Fluoroquinolone
Moxifloxacin 400 mg/day Monotherapy
Good for anaerobes also
Abbreviations: MRSA, methicillin-resistant Staphylococcus aureus; NA, not applicable.
* Preemptive early antimicrobial therapy for 3-5 days recommended for patients with dog or cat
bites who
are immunocompromised
are asplenic
have advanced liver disease
have preexisting or resultant edema of the affected area
have moderate-to-severe injuries, especially to hand or face
have injuries that may have penetrated periosteum or joint capsule
Recommendations for Treatment of Patients with Human Bites:
Drug Dose Comments
Oral administration
Amoxicillin/clavulanate 875/125 mg twice daily are resistant
Misses MRSA
Eikenella species,
staphylococci, and
anaerobes
resistant
IV administration
Ampicillin-sulbactam 1.5-3 g every 6 hours are resistant
Misses MRSA
Abbreviation: MRSA, methicillin-resistant Staphylococcus aureus.
Cystitis and pyelonephritis in women
recommendations from Infectious Diseases Society of America/European Society for Microbiology

and Infectious Diseases (IDSA/ESCMID) for acute uncomplicated cystitis and pyelonephritis in
women
Recommendations for First-Line Treatment for Acute Uncomplicated Cystitis:
Drug Dose Conditions
Reference - IDSA/ESCMID clinical practice guideline on treatment of acute uncomplicated cystitis
and pyelonephritis in women (Clin Infect Dis 2011 Mar 1;52(5):e103 full-text), commentary can be
found in Clin Infect Dis 2011 Aug 1;53(3):316.
Drug Dose Conditions
Nitrofurantoin Avoid if early pyelonephritis
100 mg twice daily for 5 days
monohydrate/macrocrystals suspected
Use if local resistance rates of
Co-trimoxazole uropathogens causing acute
160/800 mg (1 double-strength
(trimethoprim/sulfamethoxazole, uncomplicated cystitis are ≤
tablet) twice daily for 3 days
TMP/SMX) 20% or if infecting strain known
to be susceptible
Preferred agent in some
countries and considered
Trimethoprim 100 mg twice daily for 3 days equivalent to co-trimoxazole
(trimethoprim-
sulfamethoxazole)
Where available due to
minimal resistance and
Fosfomycin trometamol 3 g single dose propensity for collateral
damage, but appears to have
inferior efficacy
Where available due to
minimal resistance and
Pivmecillinam 400 mg twice daily for 3-7 days propensity for collateral
damage, but appears to have
inferior efficacy
When other recommended
agents cannot be used, but have
Beta-lactam agents 3-7 day regimens
inferior efficacy and more
adverse effects
Recommendations for First-Line Treatment for Acute Pyelonephritis:
Drug Conditions
Outpatients
Ciprofloxacin for 7 days If community prevalence is ≤ 10%
Co-trimoxazole (trimethoprim/sulfamethoxazole, TMP/SMX)
If organism is susceptible
for 14 days
Hospitalized patients
Options include
Fluoroquinolone Base choices on local resistance
Cephalosporin patterns
Carbapenem
Community-acquired pneumonia
Infectious Diseases Society of America/American Thoracic Society (IDSA/ATS) recommendations for

first-line treatment of community-acquired pneumonia in adult patients
IDSA/ATS Recommendations for First-Line Treatment of Community-Acquired Pneumonia in
Adults:
Patient Characteristics Drug
Outpatients
Previously healthy persons with no Macrolides (erythromycin, clarithromycin,
antimicrobial use within past 3 months azithromycin) OR doxycycline
Patients with
comorbidities (such as heart disease,
Respiratory fluoroquinolone (moxifloxacin,
diabetes, lung disease, liver disease,
gemifloxacin, or levofloxacin [750 mg]), OR
alcoholism, malignancies, asplenia,
Macrolide plus beta-lactam (amoxicillin [1 g
immunosuppression)
3 times daily] or amoxicillin-clavulanate [2
high risk of drug-resistant Streptococcus
g twice daily] preferred beta-lactams)
pneumoniae
antibiotic use within past 3 months
Hospitalized patients
Respiratory fluoroquinolone (moxifloxacin,
gemifloxacin, or levofloxacin)
Patients not in ICU Macrolide PLUS beta-lactam (cefotaxime,
ceftriaxone, ampicillin preferred beta-
lactams)
Beta-lactam (cefotaxime, ceftriaxone, or
ampicillin-sulbactam) PLUS either
azithromycin OR respiratory
ICU patients fluoroquinolone
Respiratory fluoroquinolone PLUS
aztreonam recommended for penicillin-
allergic patients
Antipneumococcal, antipseudomonal beta-
lactam (piperacillin-tazobactam, cefepime,
imipenem, or meropenem) plus 1 of
Ciprofloxacin
Levofloxacin
Patients with Pseudomonas infection
Aminoglycoside plus azithromycin
Aminoglycoside plus
antipneumococcal fluoroquinolone
Replace beta-lactam with aztreonam for
penicillin-allergic patients
Abbreviations: ICU, intensive care unit; MRSA, methicillin resistant Staphylococcus aureus.
* Duration of treatment for MRSA pneumonia 7-21 days, depending on extent of infection.
Reference - IDSA/ATS consensus guideline on management of community-acquired pneumonia in

adults (Clin Infect Dis 2007 Mar 1;44 Suppl 2:S27 full-text), commentary can be found in Clin Infect
Dis 2007 Jul 1;45(1):133, Clin Infect Dis 2007 Sep 1;45(5):670, and IDSA guideline for treatment of
methicillin-resistant S. aureus infection (Clin Infect Dis 2011 Feb 1;52(3):e18 full-text).
Add 1 of
Vancomycin IV
Loading dose 25-30 mg/kg
15-20 mg/kg/dose every 8-12
MRSA pneumonia* hours
Linezolid 600 mg IV or orally twice
daily
Clindamycin 600 mg IV or orally twice
daily
Abbreviations: ICU, intensive care unit; MRSA, methicillin resistant Staphylococcus aureus.
* Duration of treatment for MRSA pneumonia 7-21 days, depending on extent of infection.
Reference - IDSA/ATS consensus guideline on management of community-acquired pneumonia in

adults (Clin Infect Dis 2007 Mar 1;44 Suppl 2:S27 full-text), commentary can be found in Clin Infect
Dis 2007 Jul 1;45(1):133, Clin Infect Dis 2007 Sep 1;45(5):670, and IDSA guideline for treatment of
methicillin-resistant S. aureus infection (Clin Infect Dis 2011 Feb 1;52(3):e18 full-text).
Hospital-acquired pneumonia
American Thoracic Society/Infectious Diseases Society of America (ATS/IDSA) recommendations for

empiric treatment of hospital-acquired pneumonia in adult patients
ATS/IDSA Recommendations for Empiric Therapy for Hospital-Acquired Pneumonia in Adults:
Patient Characteristics Recommended Therapy
1 of
Ceftriaxone
No known risk factors for multidrug-resistant Levofloxacin, moxifloxacin, or
pathogens, early-onset, and any disease severity ciprofloxacin
Ampicillin/sulbactam
Ertapenem
Reference - ATS/IDSA guideline on management of adults with hospital-acquired, ventilator-

associated, and healthcare-associated pneumonia (Am J Respir Crit Care Med 2005 Feb
15;171(4):388 PDF), commentary can be found in Am J Respir Crit Care Med 2006 Jan 1;173(1):131.
Patient Characteristics Recommended Therapy
Combination IV therapy
1 of
Antipseudomonal cephalosporin
(cefepime 1-2 g every 8-12 hours,
ceftazidime 2 g every 8 hours)
Antipseudomonal carbapenem
(imipenem 500 mg every 6 hours or 1
g every 8 hours, or meropenem 1 g
every 8 hours)
Beta-lactam/beta-lactamase inhibitor
Late-onset disease or risk factors for multidrug-
(piperacillin-tazobactam 4.5 g every 6
resistant pathogens and all disease severity
hours)
PLUS 1 of
Antipseudomonal fluoroquinolone
(ciprofloxacin 400 mg every 8 hours
or levofloxacin 700 mg/day)
Aminoglycoside (amikacin 20
mg/kg/day, gentamycin 7 mg/kg/day, or
tobramycin 7 mg/kg/day)
If MRSA infection, ADD linezolid 600 mg
every 12 hours, or vancomycin 15 mg/kg
every 12 hours
Reference - ATS/IDSA guideline on management of adults with hospital-acquired, ventilator-

associated, and healthcare-associated pneumonia (Am J Respir Crit Care Med 2005 Feb
15;171(4):388 PDF), commentary can be found in Am J Respir Crit Care Med 2006 Jan 1;173(1):131.
Nontuberculous mycobacterial diseases
Infectious Diseases Society of America/American Thoracic Society (IDSA/ATS) recommended first-

line therapy for nontuberculous mycobacterial diseases
IDSA/ATS Recommendations for First-Line Therapy for Nontuberculous Mycobacterial Diseases:
Recommended First-Line
Infection/Disease Patient Condition
Therapy
Abbreviations: MAC, Mycobacterium avium complex; NTM, nontuberculous mycobacterial; RGM,

rapidly growing mycobacterial.
Reference - IDSA/ATS guideline on diagnosis, treatment, and prevention of nontuberculous

mycobacterial diseases (Am J Respir Crit Care Med 2007 Feb 15;175(4):367), correction can be
found in Am J Respir Crit Care Med 2007 Apr 1;175(7):744, commentary can be found in Am J
Respir Crit Care Med 2007 Aug 15;176(4):418.
Therapy
Clarithromycin 1,000 mg 3
times weekly OR
azithromycin 500-600 mg 3
times weekly, PLUS
Nodular/bronchiectatic disease
Ethambutol 25 mg/kg 3
times weekly, PLUS
Rifampin 600 mg 3 times
weekly
Clarithromycin 500-1,000
mg/day OR azithromycin
250-300 mg/day, PLUS
Ethambutol 15 mg/kg/day,
Cavitary disease PLUS
MAC pulmonary disease
Rifampin 450-600 mg/day,
WITH OR WITHOUT
Streptomycin or amikacin
3 times weekly
Clarithromycin 500-1,000
mg/day OR azithromycin
250-300 mg/day, PLUS
Ethambutol 15 mg/kg/day,
Advanced (severe) or previously
PLUS
treated disease
Rifampin 450-600 mg/day,
PLUS
Streptomycin or amikacin
3 times weekly
Clarithromycin orally 500
mg/day or azithromycin
Patients with HIV infection 500 mg/day PLUS
Disseminated MAC disease
(usually) Ethambutol 15 mg/kg/day
WITH OR WITHOUT
Rifampin 300-450 mg/day
Isoniazid 300 mg/day, PLUS
Mycobacterium kansasii
All Rifampin 600 mg/day, PLUS
pulmonary disease
Ethambutol 1 mg/kg/day
No regimens of proven or
predictable efficacy
Multiple drug regimens
Mycobacterium abscessus
All including clarithromycin
pulmonary disease
1,000 mg/day (may lead to
symptomatic improvement
and disease regression)


Therapy
Base on in vitro
RGM isolates (M. abscessus, susceptibilities
Mycobacterium chelonae, For patients with M.
All
Mycobacterium fortuitum) abscessus disease,
nonpulmonary disease macrolide-based regimen
frequently used
Consider macrolide-based
regimen in patients with
extensive MAC
NTM cervical lymphadenitis Due to MAC in majority
lymphadenitis or poor
response to surgical
therapy

Bacterial meningitis
Infectious Diseases Society of America (IDSA/) recommended first-line therapy for bacterial
meningitis
Empiric Therapy for Adults with Bacterial Meningitis:
Total Daily
Patient Antibiotic
Common Pathogens Dosages and Duration
Characteristics Regimen
Dosing Intervals
Vancomycin
30-45 mg/kg
every 8-12
Vancomycin
hours
plus either
Neisseria meningitidis Ceftriaxone 4 Pathogen-
Age < 50 years ceftriaxone
Streptococcus pneumoniae g every 12-24 dependent
or
hours
cefotaxime*
Cefotaxime 8-
12 g every 4-6
hours
Abbreviation: CSF, cerebrospinal fluid.
* Some experts would add rifampin if dexamethasone is also given.
Reference - IDSA practice guideline on management of bacterial meningitis (Clin Infect Dis 2004
Nov 1;39(9):1267 full-text), commentary can be found in Clin Infect Dis 2005 Apr 1;40(7):1061.
Total Daily
Patient Antibiotic
Common Pathogens Dosages and Duration
Characteristics Regimen
Dosing Intervals
Vancomycin
30-45 mg/kg
every 8-12
Vancomycin hours
S. pneumoniae plus Ampicillin 12
N. meningitidis ampicillin g every 4
Pathogen-
Age > 50 years Listeria monocytogenes plus either hours
dependent
Aerobic gram-negative ceftriaxone Ceftriaxone 4
bacilli or g every 12-24
cefotaxime* hours
Cefotaxime 8-
12 g every 4-6
hours
Vancomycin
30-45 mg/kg
Staphylococcus aureus
every 8-12
Coagulase-negative
Vancomycin hours
staphylococci (especially
Post neurosurgery, plus any of Cefepime 6 g
Staphylococcus epidermis)
penetrating head cefepime, every 8 hours Pathogen-
Aerobic gram-negative
trauma, or if CSF ceftazidime, Ceftazidime 6 dependent
bacilli (including
shunt present or g every 8
Pseudomonas aeruginosa)
meropenem hours
Propionibacterium acnes
Meropenem 6
(for CSF shunt infections)
g every 8
hours
Abbreviation: CSF, cerebrospinal fluid.
* Some experts would add rifampin if dexamethasone is also given.
recommendations for specific therapy based on isolated pathogen and susceptibility testing
IDSA Recommendations for First-Line Therapy for Bacterial Meningitis:
Microorganism Susceptibility
Therapy
Streptococcus pneumoniae Penicillin MIC < 0.1 mcg/mL Penicillin G or ampicillin
Penicillin MIC 0.1-1 mcg/mL
(ceftriaxone/cefotaxime- Ceftriaxone or cefotaxime
susceptible isolates)
Abbreviations: MIC, minimum inhibitory concentration; NA, not applicable.
Microorganism Susceptibility
Therapy
Vancomycin plus
Penicillin MIC ≥ 2 mcg/mL ceftriaxone or cefotaxime
Cefotaxime or ceftriaxone Consider adding rifampin
MIC ≥ 1 mcg/mL if MIC of ceftriaxone is > 2
mcg/mL
Penicillin MIC < 0.1 mcg/mL Penicillin G or ampicillin
Neisseria meningitidis
Penicillin MIC 0.1-1 mcg/mL Ceftriaxone or cefotaxime
Ampicillin or penicillin G
Listeria monocytogenes
NA Consider adding
Streptococcus agalactiae
aminoglycoside
Escherichia coli and other Choice must be guided by in
Third-generation cephalosporin
Enterobacteriaceae vitro susceptibility
Cefepime or ceftazidime
Choice must be guided by in
Pseudomonas aeruginosa Consider adding
vitro susceptibility
aminoglycoside
Beta-lactamase negative Ampicillin
Haemophilus influenzae
Beta-lactamase positive Third-generation cephalosporin
Methicillin-susceptible Nafcillin or oxacillin
Staphylococcus aureus Vancomycin
Methicillin-resistant
Consider adding rifampin
Vancomycin
Staphylococcus epidermis NA
Consider adding rifampin
Ampicillin-susceptible Ampicillin plus gentamicin
Ampicillin-resistant Vancomycin plus gentamicin
Enterococcus species
Ampicillin- and vancomycin-
Linezolid
resistant
Abbreviations: MIC, minimum inhibitory concentration; NA, not applicable.
Bacterial rhinosinusitis
Infectious Diseases Society of America (IDSA) recommendations for empiric therapy for adults with
bacterial rhinosinusitis
Empiric Therapy for Adults with Uncomplicated Bacterial Rhinosinusitis:
Patient Characteristics Duration
Therapy
Most adults Amoxicillin-clavulanate 5-7 days
Abbreviation: PNS, penicillin-nonsusceptible.
Reference - IDSA practice guideline on management of acute bacterial rhinosinusitis in children

and adults (Clin Infect Dis 2012 Apr;54(8):e72 full-text).
Patient Characteristics Duration
Therapy
Patients from geographic
regions with ≥ 10% rate of
invasive PNS Streptococcus
pneumoniae
Severe infection, such as
evidence of systemic toxicity
(fever ≥ 39 degrees C [102 High-dose amoxicillin-
degrees F] and threat of clavulanate (2 g orally twice
suppurative complications) daily)
Age > 65 years
Recent hospitalization
Antibiotic use within past
month
Patients who are
immunocompromised
Doxycycline
Respiratory
History of penicillin allergy fluoroquinolone
(levofloxacin or
moxifloxacin)
Abbreviation: PNS, penicillin-nonsusceptible.
Reference - IDSA practice guideline on management of acute bacterial rhinosinusitis in children

and adults (Clin Infect Dis 2012 Apr;54(8):e72 full-text).
Complicated intra-abdominal infections
Surgical Infection Society/Infectious Diseases Society of America (SIS/IDSA) recommendations on

first-line therapy for complicated intra-abdominal infection in adults
Empiric Therapy for Complicated Intra-Abdominal Infections:
Patient/Infection Recommended First-Line
Infection Type
Characteristics Therapy
Abbreviations: ESBL, extended-spectrum beta-lactamase; MRSA, methicillin-resistant

Staphylococcus aureus.
* Because of increasing resistance of Escherichia coli to fluoroquinolones, review local population

susceptibility profiles and isolate susceptibility, if available.
Reference - SIS/IDSA guideline on diagnosis and management of complicated intra-abdominal

infection in adults and children (Clin Infect Dis 2010 Jan 15;50(2):133 full-text), correction can be
found in Clin Infect Dis 2010 Jun 15;50(12):1695, commentary can be found in Clin Infect Dis 2010
Sep 15;51(6):755, Clin Infect Dis 2012 Dec;55(11):1583.
Infection Type
Single agent
Cefoxitin
Ertapenem
Moxifloxacin
Tigecycline
Ticarcillin-clavulanic acid
Mild-to-moderate severity:
perforated or abscessed In combination with
appendicitis and other mild-to- metronidazole*
moderate infections
Cefazolin
Cefuroxime
Ceftriaxone
Cefotaxime
Ciprofloxacin
Extrabilliary
Levofloxacin
Single agent:
Imipenem-cilastatin
Meropenem
Doripenem
High risk or severity: severe
Piperacillin-tazobactam
physiologic disturbance,
advanced age, or In combination with
immunocompromised state metronidazole*
Cefepime
Ceftazidime
Ciprofloxacin
Levofloxacin
Biliary Community-acquired acute Cefazolin
cholecystitis - mild-to-moderate Cefuroxime
severity Ceftriaxone



Infection Type
Community-acquired acute In combination with
cholecystitis with severe metronidazole*
physiologic disturbance, Imipenem-cilastatin
advanced age, or Meropenem
immunocompromised Doripenem
state Piperacillin-tazobactam
Acute cholangitis following Ciprofloxacin
bilio-enteric anastomosis Levofloxacin
Healthcare-associated Cefepime
biliary infection (also add
vancomycin)
If local rate of resistance to Carbapenem (imipenem-
Pseudomonas aeruginosa, ESBL- cilastatin, meropenem, or
producing Enterobacteriaceae, doripenem)
Acinetobacter, or other Piperacillin-tazobactam
multidrug-resistant gram- Ceftazidime or cefepime,
negative bacilli are low each with metronidazole
Healthcare-associated
Carbapenem (imipenem-
ESBL-producing
cilastatin, meropenem, or
Enterobacteriaceae
doripenem)
P. aeruginosa > 20%
resistant to ceftazidime
Aminoglycoside
MRSA Vancomycin


Initial IV Dosages for Empiric Treatment of Complicated Intra-Abdominal Infections:
Antibiotic Dosage*
* Limit duration of antimicrobial therapy of established infections to 4-7 days, unless difficult to
establish adequate source control.
** Consider serum drug-concentration monitoring for dosage individualization.

Antibiotic Dosage*
Beta-lactam/beta-lactamase inhibitor combination
3.375 g every 6 hours
For Pseudomonas aeruginosa infection,
dosage may be increased to 3.375 g every 4
hours or 4.5 g every 6 hours
3.1 g every 6 hours
FDA labeling indicates 200 mg/kg/day in
Ticarcillin-clavulanic acid divided doses every 6 hours for moderate
infection and 300 mg/kg/day in divided
doses every 4 hours for severe infection
Carbapenems
Doripenem 500 mg every 8 hours
Ertapenem 1 g every 24 hours
Imipenem/cilastatin 500 mg every 6 hours or 1 g every 8 hours
Meropenem 1 g every 8 hours
Cephalosporins
Cefazolin 1-2 g every 8 hours
Cefepime 2 g every 8-12 hours
Cefotaxime 1-2 g every 6-8 hours
Cefoxitin 2 g every 6 hours
Ceftazidime 2 g every 8 hours
Ceftriaxone 1-2 g every 12-24 hours
Cefuroxime 1.5 g every 8 hours
Fluoroquinolones
Ciprofloxacin 400 mg every 12 hours
Levofloxacin 750 mg every 24 hours
Moxifloxacin 400 mg every 24 hours
Aminoglycosides (base initial dosages on adjusted body weight)
Gentamicin or tobramycin 5-7 mg/kg every 24 hours**
Other antibiotics
Amikacin 15-20 mg/kg every 24 hours**
500 mg every 8-12 hours or 1,500 mg every 24
Metronidazole
hours
Tigecycline 100 mg initial dose, then 50 mg every 12 hours
Aztreonam 1-2 g every 6-8 hours

Antibiotic Dosage*
Vancomycin (base initial dosage on total body
15-20 mg/kg every 8-12 hours**
weight)

Clostridium difficile infection in adults
Infection Diseases Society of America/Society for Healthcare Epidemiology of America (IDSA/SHEA)

2017 recommendations for first line therapy for Clostridium difficile infection
IDSA/SHEA Recommendations on First-line Therapy for Clostridium difficile Infection:
Recommended First- Recommended First-
Disease Clinical
Line Therapy in Line Therapy in Duration
Type Characteristics
Adults Children
Vancomycin 125
Leukocytosis
mg orally 4 times
with a white
daily Metronidazole 7.5
blood cell
Fidaxomicin mg/kg (maximum
count ≤
Initial orally 200 mg 500 mg) orally 3-4
15,000
episode of twice daily times daily
cells/mL 10 days
nonsevere Alternative if Vancomycin 10
AND
disease above not mg/kg (maximum
Serum
available is 125 mg) orally 4
creatinine
metronidazole times daily
level < 1.5
orally 500 mg 3
mg/dL
times daily
Leukocytosis Vancomycin 10
with a white mg/kg (maximum
blood cell 500 mg) orally or
Vancomycin 125
Initial count ≥ rectally 4 times
mg orally 4 times
episode of 15,000 daily
daily 10 days
severe cells/mcL OR Consider addition
Fidaxomicin 200
disease Serum of metronidazole
mg twice daily
creatinine 10 mg/kg
level ≥ 1.5 (maximum 500 mg)
mg/dL IV 3 times daily
Abbreviation: IDSA/SHEA, Infectious Diseases Society of America/Society for Healthcare

Epidemiology of America; NA, Not applicable.
Reference - IDSA/SHEA clinical practice guideline on Clostridium difficile infection in adults and
children (Clin Infect Dis 2018 Mar 19;66(7):e1).
Disease Clinical
Adults Children
No
recommended
duration
given
DynaMed
commentary --
Vancomycin 500
for patients
mg orally or by Vancomycin 10
with
nasogastric tube mg/kg (maximum
fulminant C.
4 times daily 500 mg) orally or
difficile
Initial Hypotension PLUS rectally 4 times
infection, the
episode of or shock metronidazole daily
duration of
fulminant Ileus 500 mg IV every 8 Consider addition
treatment is
disease Megacolon hours of metronidazole
variable and
Consider rectal 10 mg/kg
typically
instillation of (maximum 500 mg)
individualized
vancomycin if IV 3 times daily
based on
complete ileus
expert
consultation,
response to
therapy and
need for
surgery

Disease Clinical
Adults Children
Treatment based
on initial
regimen
If metronidazole
used for initial
episode, use
vancomycin 125
mg 4 times daily
for 10 days
If standard
vancomycin
regimen used for For nonsevere first
initial episode, recurrence
consider either Metronidazole
Prolonged 7.5 mg/kg
tapered and (maximum
pulsed 500 mg) orally
First vancomycin 3-4 times daily
NA Variable
recurrence regimen for 10 days
(125 mg Vancomycin
orally 4 10 mg/kg
times daily (maximum
for 10-14 125 mg) orally
days, then 4 times daily
twice daily for 10 days
for 7 days,
then once
daily for 7
days, and
then every
2-3 days for
2-8 weeks)
Fidaxomicin
200 mg
twice daily
for 10 days

Disease Clinical
Adults Children
Vancomycin
recommended over
metronidazole for
second or greater
episode, with
dosing either
Vancomycin
10 mg/kg
(maximum
125 mg) 4
times daily for
10-14 days,
Vancomycin in
then twice
tapered and
daily for 7
pulsed regimen
days, then
as above
once daily for
Vancomycin 125
6 days, then
mg orally 4 times
every 2-3 days
daily for 10 days
for 2-8 weeks
followed by
Vancomycin
rifaximin 400 mg
10 mg/kg
Second or 3 times daily for
(maximum
subsequent NA 20 days Variable
500 mg) 4
recurrence (IDSA/SHEA
times daily for
Weak
10 days,
recommendation,
followed by
Low-quality
rifaximin 400
evidence)
mg 3 times
Fidaxomicin 200
daily for 20
mg twice daily
days
for 10 days
(rifaximin not
Fecal microbiota
approved for
transplantation
use in
children aged
< 12 years)
For children with
multiple
recurrences
following standard
antibiotic
treatments,
consider fecal
microbial
transplantation
Lyme disease, human granulocytic anaplasmosis (HGA), and babesiosis

Infectious Diseases Society of America (IDSA) recommendations for first-line treatment for patients
with Lyme disease, human granulocytic anaplasmosis, and babesiosis
Recommended Regimens for Initial Treatment of Patients with Lyme Disease, Anaplasmosis, or
Babesiosis:
Disease/Infection Patient Characteristics
Therapy
Doxycycline 200 mg single dose
Tick bite in United States
and/or observation
Oral regimen of 1 of
Doxycycline 100 mg twice
Erythema migrans daily for 10-21 days*
Cranial nerve palsy Amoxicillin 500 mg 3 times
Borrelial lymphocytoma daily for 14-21 days
Lyme disease
Cefuroxime axetil 500 mg
twice daily for 14-21 days
Ceftriaxone 2 g IV twice daily
Meningitis or radiculopathy
for 10-28 days
Either oral regimen as above or
Cardiac disease ceftriaxone 2 g IV twice daily for
10-28 days
Most adults
for 10 days*
Rifampin 300 mg orally
twice daily for 7-10 days**
If co-infected with Lyme
disease, add 1 of
Patients who are pregnant or Amoxicillin 500 mg 3
HGA have history of drug allergy times daily for 14-21
days
Cefuroxime axetil 500
mg twice daily for 14-
21 days
Asymptomatic patients
seropositive for Anaplasma Treatment not recommended
phagocytophilum
Atovaquone 750 mg orally every
Patients with mild-to-moderate 12 hours PLUS azithromycin
babesiosis 500-1,000 mg on day 1 and 250
mg/day for 7-10 days
Clindamycin 300-600 mg IV
every 6 hours or 600 mg orally
Babesiosis*** Patients with severe babesiosis every 8 hours PLUS quinine 650
mg orally every 6-8 hours for 7-
10 days
Atovaquone 750 mg orally every
12 hours plus azithromycin 600-
Immunocompromised patients
1,000 mg on day 1 and 200
mg/day orally for 7-10 days
Disease/Infection Patient Characteristics
Therapy
Abbreviations: HGA, human granulocytic anaplasmosis.
* Doxycycline contraindicated in pregnant or lactating women.
** Closely observe patients treated with rifampin to ensure resolution of clinical and laboratory
abnormalities.
*** Consider co-infection with Lyme disease or HGA and treat as above.
Reference - IDSA guideline on clinical assessment, treatment, and prevention of Lyme disease,
human granulocytic anaplasmosis, and babesiosis (Clin Infect Dis 2006 Nov 1;43(9):1089 full-text),
correction can be found in Clin Infect Dis 2007 Oct 1;45(7):941, commentary can be found in Clin
Infect Dis 2007 Apr 15;44(8):1133.
Antibiotics of Choice for Selected Pathogens

Antibiotics of Choice for Selected Pathogens*:
Pathogen Antibiotic(s)
Nafcillin
Oxacillin
Methicillin-susceptible Staphylococcus aureus
Dicloxacillin
Cefazolin
Sulfamethoxazole-trimethoprim
Minocycline
Clindamycin
Methicillin-resistant Staphylococcus aureus Linezolid
Vancomycin
Telavancin
Daptomycin
Coagulase-negative staphylococci Vancomycin
* Choice for antibiotic agent should be made based on local epidemiology, isolate susceptibility (if
known) and host factors (such as allergy, organ impairment).
Penicillin G
Cefazolin
Cephalexin
Streptococci
Ceftriaxone
Clindamycin
Vancomycin
Ampicillin
Amoxicillin
Linezolid
Enterococci
Doxycycline
Vancomycin
Daptomycin
Ceftriaxone
Ceftazidime
Cefepime
Enterobacteriaceae (such as Escherichia coli, Ampicillin-sulbactam
Klebsiella pneumoniae) Piperacillin-tazobactam
Imipenem
Meropenem
Ertapenem
Aztreonam
Ceftazidime
Cefepime
Pseudomonas aeruginosa Ticarcillin-clavulanate
Imipenem
Meropenem
Ampicillin-sulbactam
Cefepime
Acinetobacter baumannii
Imipenem
Meropenem
Metronidazole
Bacteroides fragilis Piperacillin-tazobactam
Ampicillin-sulbactam
Metronidazole
Clostridium difficile Vancomycin (oral)
Fidaxomicin
Azithromycin
Clarithromycin
Erythromycin
Atypical respiratory pathogens (such as Legionella
Doxycycline
species)
Levofloxacin
Ciprofloxacin
Moxifloxacin
Quinolones
General information
quinolone class includes original quinolone compounds and fluorinated derivatives,

fluoroquinolones(1, 2)
original quinolones include nalidixic acid, oxolinic acid, and cinoxacin
gemifloxacin, levofloxacin, and moxifloxacin are frequently referred to as the respiratory
fluoroquinolones (Clin Infect Dis 2007 Mar 1;44 Suppl 2:S27 full-text)
other available fluoroquinolones include norfloxacin, ciprofloxacin, ofloxacin, and
gatifloxacin
DynaMed commentary -- norfloxacin removed from market in 2014 in the United States
Mechanism of action
quinolones disrupt DNA replication to exert a bactericidal effect(1, 2)

quinolone binds enzyme-DNA complexes via interactions with DNA gyrase, type II
topoisomerases, and topoisomerase IV
binding prevents bacterial DNA replication and induces double strand breaks
Spectrum of activity
gram-negative aerobes, including(1, 2)

Enterobacteriaceae
Haemophilus species
Neisseria species
Moraxella catarrhalis
Salmonella species
Shigella species
increasing resistance has been noted among many gram-negative organisms, particularly
Klebsiella pneumoniae, Escherichia coli, and Enterobacter species
atypical agents of pneumonia(1, 2)
Legionella species
Chlamydophila pneumoniae
Mycobacterium tuberculosis, Mycobacterium fortuitum, Mycobacterium kansasii, some strains
Mycobacterium chelonae, but only weak activity against Mycobacterium avium-intracellulare
(all of which require multidrug regimens for treatment)
select gram-positive aerobes(1, 2)
quinolones have activity against but are not first-line for
methicillin-susceptible staphylococci
streptococci, with levofloxacin, gemifloxacin, and moxifloxacin comparatively more
potent than ciprofloxacin
enterococci, moxifloxacin has greater activity than most other fluoroquinolones (Clin
Microbiol Infect 1997 Aug;3(4):497)
DynaMed commentary -- quinolones are more often used for their gram-positive activity when
treating polymicrobial infections such as sinusitis; quinolones not typically used for
enterococcal infections particularly as monotherapy as serum concentrations are not reliably
higher than enterococcal minimum inhibitory concentrations (J Antimicrob Chemother 1988
Jan;21(1):113)
differences in activity among quinolones(1, 2)
both ciprofloxacin and levofloxacin have activity against Pseudomonas aeruginosa, although
ciprofloxacin generally more potent
for anaerobes
moxifloxacin has activity against many anaerobic bacteria, including most Bacteroides
fragilis strains
levofloxacin and ciprofloxacin have poor activity
Pharmacological considerations
Absorption
high bioavailability, nearing 100% for most fluoroquinolones(2)

norfloxacin bioavailability is less, about 30%-50%
offset administration of compounds containing aluminum, magnesium, sucralfate, calcium
carbonate, or ferrous sulfate ≥ 2 hours from time of fluoroquinolones, as these may reduce systemic
availability of fluoroquinolones(1, 2)
Drug interactions
fluoroquinolones may interact with warfarin by(1)

inhibiting warfarin elimination
reducing the number of vitamin K-producing bacteria in the gut
displacing warfarin from protein-binding sites
monitor INR upon initiation and discontinuation of fluoroquinolones (Clin Pharmacol Ther 2008
Nov;84(5):581)
ciprofloxacin is unique among available fluoroquinolones in interacting with cytochrome P450
enzymes (CYP)
moderately inhibits CYP1A2, thereby affecting metabolism of medications such as tizanidine
and theophylline(1, 2)
when given with ciprofloxacin
tizanidine area under the curve (AUC) increased by 10-fold, its half-life was prolonged
from 1.5 to 1.8 hours, and increased hypotension and sedation was noted (Clin
Pharmacol Ther 2004 Dec;76(6):598)
theophylline clearance reportedly reduced 19%-32% (Pharmaceutics 2011 Nov
18;3(4):865)
Metabolism and excretion
most fluoroquinolones excreted by renal pathway(1, 2)

ciprofloxacin, levofloxacin, and norfloxacin are eliminated predominantly by the renal route
dosages should be reduced in renal impairment (when creatinine clearance [CrCl] < 50
mL/minute)
gemifloxacin (1, 2)
excreted in both feces and urine
dosages should be reduced in renal impairment (when creatinine clearance [CrCl] < 40
mL/minute)
moxifloxacin(1)
excreted by the biliary pathway
no dose adjustment necessary in patients with renal impairment
Notable adverse events
General
FDA expands current warnings for fluoroquinolones including risks of serious blood sugar
disturbances and mental health adverse effects in addition to previous Black Box labeling
new required safety labeling changes are based on comprehensive review of FDA’s adverse
event reports and published case reports and includes
significant hypoglycemia which can result in life-threatening adverse events, including
coma (particularly in elderly patients and in patients with diabetes controlled by
medication)
mental health adverse effects added to or updated in drug labeling for all
fluoroquinolones include disturbances in attention, disorientation, agitation,
nervousness, memory impairment, and delirium
fluoroquinolones should remain available as a therapeutic option in treatment of serious
bacterial infections where benefits of these drugs outweigh risks
patient Medication Guide is required to be given to patient with each fluoroquinolone
prescription which describes the safety issues associated with these medicines
Reference - FDA Press Release 2018 Jul 10 , FDA Drug Safety Communication 2018 Jul 10
FDA advises restricting fluoroquinolone use in patients with certain uncomplicated infections who
have other treatment options due to risk of serious adverse events
FDA safety review concludes serious adverse effects of fluoroquinolones generally outweigh
benefits in patients with sinusitis, bronchitis, and uncomplicated urinary tract infection
systemic fluoroquinolone use associated with disabling and potentially permanent adverse
effects that can involve tendons, joints, muscles, nerves, and central nervous system
currently FDA approved fluoroquinolones for systemic use include ciprofloxacin,
gemifloxacin, levofloxacin, moxifloxacin, and ofloxacin
all fluoroquinolone drug labeling and Medication Guides will be updated to reflect this safety
information
Reference - FDA MedWatch 2016 May 12, FDA Drug Safety Communication
DynaMed commentary -- On Nov. 5, 2015, the FDA described a potential new syndrome,
“fluoroquinolone associated disability” (FQAD): adverse events involving ≥ 2 body systems
lasting for ≥ 30 days after fluoroquinolone use. 178 cases of FQAD were identified in FDA’s
Adverse Event Reporting System (FAERS) between November 1, 1997 and May 30, 2015, an
unusually high number of which came from patient-submitted reports. FAERS is a passive
reporting system, and the observational nature of this data leaves it prone to multiple
potential confounders. Further studies are ongoing. (FDA Advisory Committee Meeting 2015
Nov 5)
Peripheral neuropathy
fluoroquinolones may cause nerve damage when given systemically

peripheral neuropathy may be irreversible
use should be discontinued if symptoms occur
Reference - FDA Drug Safety Communication 15 August 2013
DynaMed commentary -- incidence rate and specific risk factors have not yet been identified
Tendonitis and tendon rupture

3-fold increased incidence of Achilles tendon rupture observed among patients within 90 days of
first use of fluoroquinolones (Eur J Clin Pharmacol 2007 May;63(5):499)
age ≥ 60 years, concomitant corticosteroid use, and body mass index < 30 kg/m2 associated with
increased risk of Achilles tendonitis in patients using fluoroquinolones (Am J Med 2012
Dec;125(12):1228.e23 full-text)
levofloxacin associated with greater rate of serious tendon disorders compared to other
fluoroquinolones (Drug Saf 2003;26(2):109)
kidney, heart, and lung transplant recipients appear to be at greater risk of tendonitis and tendon
rupture following fluoroquinolone use (FDA Information for Healthcare Professionals:
Fluoroquinolone Antimicrobial Drugs)
Cardiac effects
quinolones may induce QT prolongation via inhibition of hERG potassium channels(1)

torsades de pointes (TdP)(1)
fluoroquinolones associated with minimal risk for TdP, but risk may increase when given
concurrently with other QT prolonging agents, such as class Ia and III antiarrhythmic agents
(Drugs 2004;64(10):1091)
reports of TdP occur more frequently with levofloxacin and gatifloxacin than ciprofloxacin or
moxifloxacin (Pharmacotherapy 2001 Dec;21(12):1468)
Central nervous system toxicities
overall incidence 1%-2%

may include dizziness, headaches, and somnolence
seizures have been reported, usually in patients with underlying central nervous system (CNS)
disorders
certain quinolones, such as ciprofloxacin and norfloxacin, have chemical structures that may
displace gamma-aminobutyric acid (GABA) or compete with GABA binding, leading to CNS
stimulation
gemifloxacin, levofloxacin, and moxifloxacin have structures which are thought to lack this
stimulating potential and may be safer to use in high-risk patients
Reference - Clin Infect Dis 2005 Jul 15;41 Suppl 2:S144 full-text
oral fluoroquinolones may not increase risk of seizure
based on cohort study
1,457,964 patient prescribed oral fluoroquinolone between 2001 and 2013 from Clinical Data
Analysis and Reporting System (CDARS) (Hong Kong, China) and the Clinical Practice Research
Datalink (CPRD) (United Kingdom) were assessed
291,751 patients were from CDARS and 1,166,213 from CPRD
patients were excluded for unknown date of birth or sex, history of seizure (including
posttraumatic seizure and febrile convulsion), and fluoroquinolone prescription within
12 months of database entry
crude absolute risk of incident seizure during fluoroquinolone exposure period per 10,000
oral fluoroquinolone prescriptions
0.72 (95% CI 0.47-1.1) in CDARS
0.4 (95% CI 0.3-0.54) in CPRD
6,385 patients had incident seizure during study period (2,208 from CDARS and 4,177 from
CPRD)
evaluating seizure incidence by time of fluoroquinolone exposure
increased incidence before and during fluoroquinolone exposure
incident rate ratio (IRR) 1.64 (95% CI 1.06-2.54) 8-14 days pre-fluoroquinolone start
IRR 1.8 (95% CI 1.35-2.38) 1-7 days pre-fluoroquinolone start
IRR 1.57 (95% CI 1.22-2.01) during fluoroquinolone exposure
no significant difference in seizure incidence after fluoroquinolone exposure
IRR 1.1 (95% CI 0.78-1.55) 1-7 days post-fluoroquinolone completion
IRR 1.2 (95% CI 0.98-1.46) 8-28 days post-fluoroquinolone completion
in post hoc subgroup analysis including 1,398 patients with ≥ 2 seizures recorded, no
significant increase in seizure frequency attributed to any time period pre- or post-
fluoroquinolone exposure
Reference - Neurology 2016 May 3;86(18):1708 full-text
Major clinical uses
Respiratory infections
Infectious Diseases Society of America/American Thoracic Society (IDSA/ATS) guidelines on

management of community-acquired pneumonia in adults include respiratory fluoroquinolones
(levofloxacin, moxifloxacin, and gemifloxacin) as first-line agents for patients with comorbidities
such as heart disease (Clin Infect Dis 2007 Mar 1;44 Suppl 2:S27 full-text)
Abdominal infections
fluoroquinolones are active against many gram-negative pathogens known to cause gastroenteritis,
biliary infections, spontaneous bacterial peritonitis, and other intra-abdominal infections(1, 2)
ciprofloxacin plus metronidazole may be equivalent to imipenem in intra-abdominal
infections (Ann Surg 1996 Mar;223(3):303 full-text)
ciprofloxacin or levofloxacin plus metronidazole recommended by IDSA as a first-line
treatment option for mild-to-moderate community-acquired intra-abdominal infections (Surg
Infect (Larchmt) 2010 Feb;11(1):79)
norfloxacin was commonly used for spontaneous bacterial peritoneal prophylaxis, however
this should be weighed against concerns for quinolone resistance in subsequent spontaneous
bacterial peritoneal infections (Hepatology 1997 Mar;25(3):532, Hepatology 1999
Apr;29(4):1064, J Hepatol 1999 Aug;31(2):277, Hepatology 2002 Jan;35(1):140)
DynaMed commentary -- norfloxacin removed from United States market in 2014
Urinary tract infections and prostatitis
Infectious Diseases Society of America and the European Society for Microbiology and Infectious
Diseases (IDSA/ESCMID)
recommends quinolones as first-line therapy for uncomplicated pyelonephritis and as
alternate agents for uncomplicated cystitis
no longer recommends quinolones as first-line agents for uncomplicated cystitis due to rising
rate of quinolone resistance (first-line agents include nitrofurantoin, sulfamethoxazole-
trimethoprim, and fosfomycin)
Reference - Clin Infect Dis 2011 Mar 1;52(5):e103 full-text
quinolones are options for treatment of acute bacterial prostatitis due to adequate penetration of
prostatic tissue and antimicrobial activity against gram-negative bacilli (Clin Infect Dis 2010 Jun
15;50(12):1641 full-text)
Sexually transmitted infections
Centers for Disease Control and Prevention (CDC) guidelines on treatment of sexually transmitted
disease
quinolones no longer recommended treatment of Neisseria gonorrhoeae due to widely
reported quinolone resistance
either levofloxacin or ofloxacin are recommended as an alternative regimen for the treatment
of Chlamydia trachomatis
levofloxacin 500 mg orally once daily for 7 days
ofloxacin 300 mg orally twice daily for 7 days
azithromycin or doxycycline are preferred agents for C. trachomatis infection
Reference - MMWR Recomm Rep 2015 Jun 5;64(RR-03):1 full-text, correction can be found in
MMWR Recomm Rep 2015 Aug 28;64(33):924, commentary can be found in Ann Emerg Med
2015 Nov;66(5):527
Co-trimoxazole (trimethoprim-sulfamethoxazole, TMP-SMX)

Mechanism of action
co-trimoxazole (trimethoprim-sulfamethoxazole, TMP-SMX) is a combination of 2 agents that act in

synergy to inhibit the synthesis of folic acid and block bacterial growth(1, 2)
sulfamethoxazole inhibits production of dihydrofolate from para-aminobenzoic acid (PABA)
trimethoprim inhibits reduction of dihydrofolate tetrahydrofolate
synergistic effect results in sequential inhibition of the folic acid pathway
lack of folic acid exerts bacteriostatic effect
excellent activity against fungal organism Pneumocystis jirovecii(2)

demonstrated activity in aerobic bacteria such as(1, 2)
gram-positive cocci, including
methicillin-susceptible Staphylococcus aureus (MSSA)
some methicillin-resistant S. aureus (MRSA)
some coagulase-negative Staphylococcus species
Streptococcus pneumoniae, though resistance is increasing
DynaMed commentary -- activity against other streptococcal species is unclear; traditional
teaching is that co-trimoxazole has limited activity in part due to the development of
alternate folate synthesis pathways
gram-positive bacilli, including
Corynebacterium diphtheriae
Nocardia species
gram-negative aerobes, including
Enterobacteriaceae family
Stenotrophomonas maltophilia
Burkholderia cepacia
Pasteurella multocida
Bartonella species
Vibrio species
limited activity against enterococci(1)
Drug interactions
co-trimoxazole (trimethoprim-sulfamethoxazole, TMP-SMX) may(1, 2)

inhibit the activity of the cytochrome P450 2C9 hepatic enzyme system
compete for metabolism with phenytoin and subsequently increase phenytoin levels
displace other agents (such as warfarin and methotrexate) from albumin-binding sites
reduce warfarin doses during concurrent trimethoprim-sulfamethoxazole therapy(1)

metabolism(1, 2)
co-trimoxazole undergoes acetylation and glucuronidation in the liver
cytochrome P450 enzymes 2C9 and 3A4 involved in metabolism
excreted through the renal route(1, 2)
likely through glomerular filtration
doses should be reduced in patients with severe renal impairment (creatinine clearance [CrCl]
< 30 mL/minute)
Gastrointestinal adverse effects
nausea, vomiting, and diarrhea are among the most commonly reported adverse effects caused by
co-trimoxazole (trimethoprim-sulfamethoxazole, TMP-SMX), and may be related to high doses(1)
Nephrotoxicity
acute tubular necrosis may result from accumulation of conjugated sulfamethoxazole

metabolites(1)
renal failure usually reversible upon drug discontinuation(1)
increase in serum creatinine may occur
temporary and transient effect
likely occurs due to competitive inhibition of the tubular secretion of creatinine by
trimethoprim
Reference - J Antimicrob Chemother 1986 Jan;17(1):123
Hematologic adverse events
prolonged use of co-trimoxazole impairs folate usage which may lead to hematologic toxicities(1)
potentially life-threatening toxicities include thrombocytopenia (J Infect 2006 Feb;52(2):e49,
Ann Pharmacother 2002 Jan;36(1):78)
dosing at frequency of 3 times weekly may offer lower risk of hematologic toxicities compared
to daily dosing (Clin Infect Dis 1999 Oct;29(4):775)
Electrolyte disorders
both hyperkalemia and hypernatremia have been described in patients taking co-trimoxazole
hyperkalemia may be seen at standard and high doses due to activity of trimethoprim as a
potassium-sparing diuretic
hypernatremia can been seen in a dose-dependent manner
these effects can be corrected while receiving co-trimoxazole and are reversible upon drug
discontinuation
References - Am J Ther 1997 Sep-Oct;4(9-10):343, Intern Med 2003 Aug;42(8):665 PDF, Intern
Med 1995 Feb;34(2):96 PDF
Hypersensitivities
rashes are reported to occur in up to 8% of patients (J Infect Dis 1973 Nov;128:Suppl:607)

severe reactions, including Stevens-Johnson syndrome/toxic epidermal necrolysis, have been
reported (J Allergy Clin Immunol 1978 Aug;62(2):125)
among patients with HIV infection, co-trimoxazole was more likely to cause hypersensitivity
reactions in less immunocompromised patients and when given for less than 2 weeks (J Infect Dis
1993 Jan;167(1):180)
desensitization protocols may be used for patients who require co-trimoxazole but have a severe
allergy (Ann Allergy Asthma Immunol 1996 Nov;77(5):394, Clin Infect Dis 1997 Dec;25(6):1480 PDF)
Major clinical uses
Urinary tract infections (UTI)
co-trimoxazole (trimethoprim-sulfamethoxazole, TMP-SMX) is a primary treatment for urinary

tract infections due to activity against pathogens such as Escherichia coli
Infectious Diseases Society of America/European Society for Microbiology and Infectious
Diseases (IDSA/ESCMID) guideline for the treatment of acute uncomplicated cystitis and
pyelonephritis recommends co-trimoxazole as a first-line treatment choice for uncomplicated
urinary tract infection (UTI) if local rates of resistance are < 20% (Clin Infect Dis 2011 Mar
1;52(5):e103 full-text)
increasing resistance among gram-negative pathogens reported (Clin Infect Dis 2001 Sep
1;33(5):615)
Skin and soft tissue infections (SSTI)
IDSA guideline on skin and soft tissue infections recommends oral co-trimoxazole as a first-line
treatment option for mild skin and soft tissue infections suspected or confirmed to be caused by
Staphylococcus aureus, including methicillin-resistant strains (Clin Infect Dis 2014 Jul 15;59(2):e10)
Pneumocystis jirovecii infections
American Thoracic Society (ATS) guideline on treatment of fungal infections in adult pulmonary
and critical care patients recommends co-trimoxazole as preferred treatment for P. jirovecii
pneumonia in the immunocompromised patient (Am J Respir Crit Care Med 2011 Jan 1;183(1):96)
co-trimoxazole appears to be superior to
trimetrexate (J Infect Dis 1994 Jul;170(1):165)
pentamidine (N Engl J Med 1995 Mar 16;332(11):693 full-text)
atovaquone (N Engl J Med 1993 May 27;328(21):1521 full-text)
American Thoracic Society recommends co-trimoxazole as first-line prophylaxis in patients
receiving immunosuppressive regimens for inflammatory conditions when > 20 mg/day prednisone
is given for > 1 month, especially if patient is receiving other cytotoxic drugs or antitumor necrosis
factor (anti-TNF) agents; if patient has associated T-cell defects some experts recommend using
threshold of 200 CD4 cells/mcL as threshold for starting prophylaxis first-line prophylactic regimens
(Am J Respir Crit Care Med 2011 Jan 1;183(1):96)
Centers for Disease Control and Prevention/National Institutes of Health/HIV Medicine Association
of Infectious Diseases Society of America recommends co-trimoxazole as preferred agent for
prophylaxis of pneumocystis pneumonia in HIV-infected adults and adolescents (Clin Infect Dis
2014 May;58(9):1308 full-text)
Aminoglycosides
General information
aminoglycosides are a class of antimicrobials with concentration-dependent activity against most

aerobic gram-negative organisms(1, 2)
most commonly used systemic aminoglycosides are gentamicin, tobramycin, and amikacin
other aminoglycosides include streptomycin, kanamycin, neomycin, and paromomycin
Mechanism of action
aminoglycosides bind to proteins of the 30S subunit of bacterial ribosomes, causing misreading of
the genetic code, which exerts a bactericidal activity(1, 2)
exert a significant postantibiotic effect (PAE), which is a suppression of bacterial growth after
antimicrobial exposure(2)
potent activity against aerobic gram-negative organisms including Pseudomonas aeruginosa,

Acinetobacter species, and the Enterobacteriaceae group(2)
differences in activity among aminoglycosides(1, 2)
amikacin
P. aeruginosa and Enterobacteriaceae that are resistant to gentamicin and tobramycin
may retain sensitivity to amikacin (J Infect Dis 1976 Nov;134 SUPPL:S280, J Infect Dis 1976
Nov;134 SUPPL:S394)
active against Nocardia and Actinomycetes
amikacin and streptomycin are active against Mycobacteria species (but should not be used as
single agents for treatment)
gentamicin and streptomycin may have synergistic activity against select gram-positive
bacteria when given in combination with an active cell-wall antimicrobial
Staphylococcus aureus
Streptococcus species
not active against anaerobic bacteria(1)
Optimizing pharmacokinetics and pharmacodynamics
concentration dependent killing activity, whereby higher concentrations of the drug result in
increased bactericidal activity(1, 2)
to optimize therapy, many experts have adopted high-dose extended interval aminoglycoside
dosing for appropriate patient populations and indications (Antimicrob Agents Chemother
1995 Mar;39(3):650 full-text, Int J Antimicrob Agents 2002 Apr;19(4):341)
higher dosing was found to have similar clinical efficacy as traditional dosing, and may reduce
the risk of nephrotoxicity (Clin Infect Dis 1997 May;24(5):786 PDF, BMJ 1996 Feb
10;312(7027):338 full-text, Clin Infect Dis 1997 May;24(5):796 PDF)
higher doses may also result in increased postantibiotic effect
metabolism of aminoglycosides not well defined(2)

excretion(1, 2)
approximately 99% of the unchanged drug is excreted by the kidney
adjust doses and dosing intervals in patients with renal impairment
Ototoxicity
typically irreversible cochlear and vestibular toxicity(1, 2)

frequencies between 2% and 41% have been reported (J Infect Dis 1971 Dec;124 Suppl:S130, J
Antimicrob Chemother 1983 Oct;12(4):393, Antimicrob Agents Chemother 1989 Jun;33(6):797 PDF)
ototoxicity may be associated with older age (Antimicrob Agents Chemother 1987
Sep;31(9):1383 PDF)
Nephrotoxicity
significant nephrotoxicity
frequency ranges between 10% and 41% (Johns Hopkins Med J 1978 Mar;142(3):85, Ann Intern
Med 1984 Mar;100(3):352, Am J Med 1986 Jun;80(6):1093)
proximal tubular damage and sometimes glomerular or tubular dysfunction may occur (Am J
Kidney Dis 1986 Nov;8(5):308)
individualized pharmacokinetic monitoring may reduce the incidence of nephrotoxicity
(Pharmacotherapy 2001 Apr;21(4):443)
effects usually reversible (J Antimicrob Chemother 1983 Sep;12(3):285)
renal function should be closely monitored while patients are receiving aminoglycosides(1, 2)
risk factors for nephrotoxicity not clearly defined, but may include
liver disease
supratherapeutic serum levels
prolonged duration of therapy
References - Am J Med 1986 Jun;80(6):1093, Johns Hopkins Med J 1978 Mar;142(3):85,
Antimicrob Agents Chemother 1979 Jun;15(6):780 PDF
Neuromuscular blockade
neurotoxicity and neuromuscular blockade is rare, but may occur due to aminoglycoside mediated
inhibition of calcium uptake at N-type calcium channels (N Engl J Med 1987 Dec 24;317(26):1669,
JAMA 1971 Feb 15;215(7):1153)
Major clinical uses
Infections due to aerobic gram-negative organisms
beta-lactams have largely replaced aminoglycosides for gram-negative infections due to a superior
toxicity profile(1)
aminoglycosides may be useful for serious gram-negative infections with resistance to beta-lactams
and fluoroquinolones(1)
aminoglycoside monotherapy vs. aminoglycoside/beta-lactam combination therapy
aminoglycoside monotherapy appears efficacious for urinary tract infections (J Antimicrob
Chemother 2007 Aug;60(2):247 full-text)
monotherapy may be clinically inferior to combination therapy with beta-lactam when the
source of infection is other than urinary tract (Antimicrob Agents Chemother 1997
May;41(5):1127 PDF)
use of combination therapy with aminoglycosides plus beta-lactam controversial in patients
with sepsis or febrile neutropenia
addition of aminoglycoside to beta-lactam may not reduce mortality and may increase
nephrotoxicity in patients with sepsis (Cochrane Database Syst Rev 2014 Jan
7;1:CD003344, BMJ 2004 Mar 20;328(7441):668 full-text, BMJ 2003 May
24;326(7399):1111 full-text)
broad-spectrum beta-lactams associated with similar survival, but fewer adverse events
compared to combination with aminoglycoside in patients with cancer and febrile
neutropenia (Cochrane Database Syst Rev 2013 Jun 29;(6):CD003038)
see also Sepsis treatment in adults and Febrile neutropenia
Cystic fibrosis
aminoglycosides (primarily tobramycin) are routinely used in acute pulmonary exacerbations in

patients with cystic fibrosis(1, 2)
combination therapy with antipseudomonal beta-lactam has demonstrated improved forced
expiratory volume in 1 second (FEV1) response (Chest 2005 Oct;128(4):2336, J Cyst Fibros 2008
Mar;7(2):142)
once daily (high-dose, extended interval) dosing is preferred due to possible lower incidence
of nephrotoxicity (Lancet 2005 Feb 12-18;365(9459):573)
Endocarditis
American Heart Association and Infectious Diseases Society of America (AHA/IDSA) guideline on
infective endocarditis recommend addition of gentamicin to agents with activity against gram-
positive bacteria for synergistic effect in infections caused by certain organisms
dosing for gram-positive synergy with gentamicin is typically 3 mg/kg/day, adjusted for renal
function
gentamicin can be added to
penicillin, for endocarditis caused by viridans group streptococci and Streptococcus bovis
nafcillin, oxacillin, cefazolin, or vancomycin, for endocarditis caused by Staphylococcus
aureus, however
recommendation for gentamycin synergy is stronger for endocarditis caused by
enterococci due to relative resistance to penicillin, ampicillin, and vancomycin
combination therapy may have a higher risk of nephrotoxicity
Reference - Circulation 2005 Jun 14;111(23):e394 full-text, correction can be found in
Circulation 2005 Oct 11;112(15):2373, Circulation 2007 Nov 20;116(21):e547, Circulation 2007
Apr 17;115(15):e408, Circulation 2008 Sep 16;118(12):e497
streptomycin may retain activity in gram-positive endocarditis when high-level resistance to
gentamicin occurs (Clin Infect Dis 1994 Dec;19(6):1150)
Glycopeptides and Lipopeptides

General information
glycopeptides and lipopeptides include vancomycin, telavancin, daptomycin(1, 2)

new long-acting lipoglycopeptides include dalbavancin and oritavancin (FDA news release May
2014, FDA news release Aug 2014)
Mechanism of action
glycopeptides and lipopeptides achieve mostly bactericidal activity through action on the cell wall(1,
2)
vancomycin and telavancin inhibit cell wall synthesis by binding to the D-Ala-D-Ala residues of
peptidoglycan precursors in the cytoplasmic membrane of susceptible bacteria(1, 2)
dalbavancin acts similarly (Int J Clin Pract 2007 May;61(5):853)
daptomycin has 2 mechanisms of action(1, 2)
inhibition of peptidoglycan synthesis pathway
forms pores in cytoplasmic membrane
irreversibly inserts into and binds the cytoplasmic membrane through a calcium ion-
dependent pathway
drug forms membrane-spanning pores, leading to potassium efflux and cell death
oritavancin appears to have 3 mechanisms of action
inhibition of transpeptidation
inhibition of transglycosylation
cell membrane interaction/disruption
Reference - Clin Infect Dis 2012 Apr;54 Suppl 3:S214
active against most gram-positive bacteria(1, 2)

Staphylococcus species, including methicillin-resistant Staphylococcus aureus and coagulase-
negative staphylococci
differences in activity among glycopeptides and lipopeptides(1, 2)
vancomycin also has activity against, but may not be first-line for
gram-positive bacilli including Listeria monocytogenes, Bacillus species, and
Corynebacterium species
anaerobes including Peptostreptococcus species, Actinomyces species, Propionibacterium
species, and most Clostridium species (including Clostridium difficile)
telavancin and daptomycin
same aerobic gram-positive activity as vancomycin
may have some activity against vancomycin-resistant organisms, such as vancomycin-
intermediate S. aureus (VISA), vancomycin-resistant S. aureus, and vancomycin-resistant
enterococci (VRE)
telavancin anaerobic spectrum is similar to vancomycin
daptomycin has in vitro activity against Clostridium perfringens, C. difficile, and
Peptostreptococcus species
not active against gram-negative bacteria(1, 2)
Absorption
vancomycin(1, 2)
oral formulation has minimal systemic absorption and should be limited to treatment of
Clostridium difficile infection
only the IV formulation should be used to treat systemic gram-positive infections
vancomycin
American Society of Health-System Pharmacists, Infectious Diseases Society of America, and
Society of Infectious Diseases Pharmacists recommend therapeutic drug monitoring during
treatment with vancomycin (Am J Health Syst Pharm 2009 Jan 1;66(1):82 full-text)
target serum trough concentration
15-20 mg/L may correlate with area under the curve/minimum inhibitory concentration
(AUC/MIC) that predicts therapeutic concentrations of vancomycin against
Staphylococcus aureus (Am J Health Syst Pharm 2000 Oct 15;57 Suppl 2:S4, Clin
Pharmacokinet 2004;43(13):925, Clin Infect Dis 2011 Apr 15;52(8):975 full-text, Arch
Intern Med 2006 Oct 23;166(19):2138 full-text)
several studies did not find a similar correlation (Chest 2006 Oct;130(4):947 full-text,
Antimicrob Agents Chemother 2008 Sep;52(9):3315 full-text)
doses of 15-20 mg/kg every 8-12 hours in adults and 15 mg/kg every 6 hours in pediatric
patients may be used to reach target trough concentration ≥ 10 mg/L (Clin Infect Dis 1994
Apr;18(4):533, Am J Health Syst Pharm 2009 Jan 1;66(1):82 full-text)
lipopeptides and glycopeptides mainly excreted through the renal route(1, 2)

clearance is related to creatinine clearance (CrCl)
dosing intervals should be adjusted in renal impairment
vancomycin dosing intervals should be adjusted when CrCl < approximately 50
mL/minute
telavancin doses and intervals may need adjustment when CrCl < approximately 50
mL/minute
daptomycin dosing intervals should be adjusted when CrCl < approximately 30
mL/minute
Vancomycin
Ototoxicity
vancomycin-associated ototoxicity is rare and thought to be due to either(1, 2)

older formulations of vancomycin with impurities
concomitant administration with aminoglycosides
peak levels of vancomycin may not accurately predict the risk of ototoxicity (Am J Health Syst
Pharm 2009 Jan 1;66(1):82 full-text)
Nephrotoxicity
true incidence of nephrotoxicity due to vancomycin is unclear, but thought to be low(1, 2)

vancomycin was once thought to be significantly nephrotoxic, which may have been attributable to
older formulations with impurities(1)
risk factors for vancomycin-induced nephrotoxicity
trough levels > 20 mg/L
concurrent administration with other nephrotoxic agents
larger dose (≥ 4 g/day)
References - Clin Infect Dis 2011 Apr 15;52(8):975 full-text, Arch Intern Med 2006 Oct
23;166(19):2138 full-text, Antimicrob Agents Chemother 2008 Apr;52(4):1330 full-text
Red man syndrome
also called red neck syndrome (Arch Surg 1986 Jul;121(7):859)

hypersensitivity reaction, in part mediated by histamine release, that may occur with infusion
characterized by skin itching, flushing, angioedema, hypotension, tachycardia, and muscle
aches
likely caused by a histamine release
usually occurs immediately after the start of infusion
slowing infusion rate and antihistamine pretreatment can reduce incidence
Reference - (1), J Infect Dis 1991 Dec;164(6):1180; Antimicrob Agents Chemother 1990
Apr;34(4):550
Daptomycin
creatine phosphokinase (CPK) levels may be increased

frequency of CPK elevations during daptomycin therapy is approximately 10%
increased monitoring of CPK should be considered, especially when daptomycin and HMG-
CoA inhibitors are given concomitantly
Reference - Ann Pharmacother 2014 Mar;48(3):320
Major clinical uses
Bacteremia and endocarditis
American Heart Association scientific statement on infective endocarditis recommends vancomycin

as a treatment option for bacteremia and endocarditis caused by methicillin-resistant
Staphylococcus aureus (Circulation 2005 Jun 14;111(23):e394 full-text), correction can be found in
Circulation 2005 Oct 11;112(15):2373, Circulation 2007 Nov 20;116(21):e547, Circulation 2007 Apr
17;115(15):e408, Circulation 2008 Sep 16;118(12):e497
vancomycin associated with greater rates of treatment failure than antistaphylococcal beta-lactams
in patients with bacteremia due to methicillin-susceptible S. aureus (Clin Infect Dis 2007 Jan
15;44(2):190 full-text, Antimicrob Agents Chemother 2008 Jan;52(1):192 full-text)
daptomycin may be considered as alternative treatment for S. aureus bacteremia and right-sided
endocarditis (N Engl J Med 2006 Aug 17;355(7):653 full-text)
Infectious Diseases Society of America guidelines on skin and soft tissue infections include
recommendation for vancomycin or daptomycin for severe infections caused by gram-positive
organisms in hospitalized patients (Clin Infect Dis 2005 Nov 15;41(10):1373 full-text)
telavancin may be as effective as vancomycin for treatment of complicated skin and soft tissue
infections due to gram-positive organisms (Clin Infect Dis 2008 Jun 1;46(11):1683, full-text)
dalbavancin once weekly is as effective as vancomycin twice daily for acute bacterial skin and skin
structure infections in adults and has reduced rate of diarrhea or pruritus (N Engl J Med 2014 Jun
5;370(23):2169)
oritavancin single dose is as effective as vancomycin twice daily for acute bacterial skin and skin-
structure infections in adults (N Engl J Med 2014 Jun 5;370(23):2180)
dalbavancin (second-generation lipoglycopeptide) may be as effective as linezolid for treatment of
complicated skin and skin structure infections (Clin Infect Dis 2005 Nov 15;41(10):1407)
Hospital acquired MRSA pneumonia
American Thoracic Society and Infectious Diseases Society of America recommendations on

hospital-acquired pneumonia include recommendation for vancomycin in nosocomial respiratory
infections caused by methicillin-resistant S. aureus (Am J Respir Crit Care Med 2005 Feb
15;171(4):388)
telavancin is adequate alternative to vancomycin for hospital-acquired pneumonia due to gram-
positive pathogens (Clin Infect Dis 2011 Jan 1;52(1):31, full-text)
daptomycin is inactivated by lung surfactant and therefore should not be used for respiratory
infections (Intern Med 2013;52(22):2577 full-text)
Clostridium difficile associated colitis
Society for Healthcare Epidemiology of America (SHEA) and Infectious Diseases Society of America
(IDSA) guidelines on Clostridium difficile infections in adults recommend
oral vancomycin as first-line treatment of severe C. difficile infection
in complicated infections, oral vancomycin is given in combination with IV metronidazole
adjunct vancomycin through rectal administration may be considered in the presence of an
ileus
Reference - Infect Control Hosp Epidemiol 2010 May;31(5):431
Metronidazole
Mechanism of action
metronidazole is a prodrug that is activated intracellularly within susceptible organisms to exert a

bactericidal effect(1, 2)
reduction of the nitro group on the prodrug produces free radicals
released free radicals damage bacterial DNA, resulting in cell death
primarily active against anaerobic bacteria and some parasites, including(1, 2)
anaerobes
Clostridium species (including Clostridium difficile)
Prevotella
Fusobacterium
Bacteroides species (including Bacteroides fragilis)
Helicobacter pylori
protozoa
Giardia lamblia
Entamoeba histolytica
Trichomonas vaginalis
notable resistance in Propionibacterium propionicum and Propionibacterium acnes(1, 2)
Drug interactions
ethanol and metronidazole should not be used together, as a disulfiram-like reaction may occur (Br
J Clin Pract 1985 Jul;39(7):292)
metronidazole can increase the effect of warfarin; increased monitoring is required when
administered concomitantly (Mayo Clin Proc 1976 Dec;51(12):782, N Engl J Med 1976 Aug
12;295(7):354)
extensively metabolized by the liver(1, 2)

doses or dosing intervals may require adjustment in severe liver disease (Br J Clin Pharmacol 1995
Nov;40(5):477 full-text)
Neurotoxicity
peripheral neuropathy
associated with prolonged use of metronidazole
usually reversible upon drug discontinuation
Reference - J Clin Neuromuscul Dis 2001 Sep;3(1):8, DICP 1990 Jan;24(1):19
confusion, ataxia, and dysarthria may occur, and are slowly reversible upon drug discontinuation
(Ann Intern Med 1980 Jul;93(1):59, Am J Obstet Gynecol 1983 Mar 1;145(5):640)
Major clinical uses
Infections due to anaerobes
metronidazole has potent activity against anaerobes including Bacteroides fragilis and is an
important treatment option for infections with these organisms (Rev Infect Dis 1983 Mar-
Apr;5(2):235, Drugs 1983 Dec;26(6):520, Clin Infect Dis 2010 Jan 15;50(2):133 full-text)
Clostridium difficile infection
Society for Healthcare Epidemiology of America and Infectious Diseases Society of America
guidelines for Clostridium difficile infections in adults recommend
oral metronidazole as first-line treatment of mild-to-moderate C. difficile infection
in complicated infections, IV metronidazole in combination with oral vancomycin
Reference - Infect Control Hosp Epidemiol 2010 May;31(5):431
Oxazolidinones
Linezolid
Mechanism of action
binds to the 50S ribosomal subunit of susceptible bacteria(1, 2)

blocks initiation of protein synthesis to exert a bacteriostatic effect(1, 2)
aerobic bacteria(1, 2)
spectrum includes most gram-positive organisms
Staphylococcus species, including methicillin-resistant Staphylococcus aureus
Enterococcus species, including vancomycin-resistant enterococci (VRE)
Nocardia species
Mycobacterium species
anaerobic spectrum includes Actinomyces and Propionibacterium species(1)
not active against gram-negative pathogens(1)
Drug interactions
linezolid is a weak, reversible, nonselective inhibitor of monoamine oxidase and can prevent the
breakdown of serotonin
consider discontinuation of the serotonergic agent during linezolid therapy
monitor for serotonin syndrome when giving linezolid and serotonergic agents (for example,
fluoxetine) concomitantly
Reference - Ann Pharmacother 2013 Mar;47(3):388, Pharmacotherapy 2006 Feb;26(2):269
metabolized through a nonenzymatic process(1, 2)

linezolid is slowly oxidized by reactive oxygen species
not metabolized by the cytochrome P450 enzymes
primarily eliminated through the renal route
approximately 30% of unmetabolized linezolid is excreted through the urine
dose adjustment is not required in renal impairment
Reference - Clin Pharmacokinet 2003;42(13):1129
Neurotoxicity
peripheral and optic neuropathy may occur with long-term use of linezolid
onset typically occurs after weeks to months of treatment
neurotoxic effects are typically slowly reversible upon drug discontinuation
References - Lancet Infect Dis 2004 Aug;4(8):528, Am J Ophthalmol 2005 Jun;139(6):1114, Clin
Infect Dis 2003 Nov 15;37(10):1389 full-text, Clin Infect Dis 2004 Aug 1;39(3):439 full-text
Hematologic toxicity
associated with reversible myelosuppression
typically occurs after more than 2 weeks of therapy (Antimicrob Agents Chemother 2002
Aug;46(8):2723 full-text)
risk may be higher in patients with renal impairment, older age, and preexisting low
hemoglobin and platelet count (J Antimicrob Chemother 2004 Oct;54(4):798 full-text, J
Antimicrob Chemother 2005 Aug;56(2):440, J Antimicrob Chemother 2013 Sep;68(9):2128, Clin
Infect Dis 2006 Jan 1;42(1):66)
Lactic acidosis
prolonged treatment may cause hyperlactatemia

may be a result of an inhibition of mitochondrial protein synthesis
has been described as early as within 1 week of linezolid therapy
usually resolves upon drug discontinuation
References - Clin Infect Dis 2006 Feb 1;42(3):434 full-text, Pharmacotherapy 2007
May;27(5):771, Clin Infect Dis 2005 Jun 15;40(12):e113
Major clinical uses
Skin and soft tissue infections (SSTIs)
linezolid has demonstrated efficacy in skin and soft tissue infections caused by methicillin-resistant
Staphylococcus aureus (MRSA) and other gram-positive organisms (Antimicrob Agents Chemother
2000 Dec;44(12):3408 full-text, Antimicrob Agents Chemother 2005 Jun;49(6):2260 full-text)
Infectious Diseases Society of America (IDSA) guideline on skin and soft tissue infections
recommends linezolid as a preferred option for treatment of skin and soft tissue infections
suspected or confirmed to be caused by MRSA (Clin Infect Dis 2014 Jul 15;59(2):e10)
Hospital-acquired MRSA pneumonia
linezolid may be as effective as vancomycin for the treatment of MRSA nosocomial pneumonia (Clin
Infect Dis 2012 Mar 1;54(5):621 full-text)
Infections caused by vancomycin-resistant enterococci (VRE)
linezolid may be comparable to quinupristin/dalfopristin for the treatment of infections caused by

vancomycin-resistant enterococci (J Antimicrob Chemother 2004 Apr;53(4):646 full-text)
Tedizolid
Mechanism of action
binds to the 50S ribosomal subunit of susceptible bacteria

blocks protein synthesis to exert a bacteriostatic effect
Reference - FDA DailyMed 2014 Jun
gram-positive aerobic bacteria

Staphylococcus species, including methicillin-resistant Staphylococcus aureus
Enterococcus faecalis
Drug interactions
tedizolid is a reversible inhibitor of monoamine oxidase, however potential drug interactions could
not be evaluated in clinical trials due to study exclusions (FDA DailyMed 2014 Jun)
tedizolid phosphate (prodrug) converted to tedizolid (active) by phosphatases

unlikely metabolized by liver
excretion of inactive sulfate conjugate in both the feces and (to lesser extent) urine
Use in neutropenic patients
alternative treatment options should be considered in neutropenic patients due to reduced

antibacterial activity in absence of granulocytes in animal models (FDA DailyMed 2014 Jun)
Neurotoxicity
peripheral and optic neuropathy may occur with long-term use of related oxazolidinone (linezolid);
no data available to assess risk with tedizolid beyond 6 days of treatment (FDA DailyMed 2014 Jun)
phase I studies indicate possible dose- and duration-related myelosuppression in healthy adults
exposed to tedizolid for 21 days (FDA DailyMed 2014 Jun)
Major clinical uses
Skin and soft tissue infections (SSTIs)
oral tedizolid is as effective as oral linezolid for achieving treatment response at 48-72 hours in
adults with complicated acute bacterial skin and skin structure infection (ESTABLISH-1 trial JAMA
2013 Feb 13;309(6):559, editorial can be found in JAMA 2013 Feb 13;309(6):609
IV-to-oral tedizolid is as effective as IV linezolid for achieving early clinical response in patients
with acute bacterial skin and skin-structure infections (Lancet Infect Dis 2014 Aug;14(8):696)
tedizolid phosphate (Sivextro) FDA approved for intravenous and oral use in adults with acute
bacterial skin and skin structure infections caused by certain susceptible bacteria including
Staphylococcus aureus (including methicillin-resistant strains and methicillin-susceptible strains),
various Streptococcus species, and Enterococcus faecalis (FDA Press Release 2014 Jun 20)
Clindamycin
Mechanism of action
reversibly binds 23S rRNA nucleotides from the 50S subunit of bacterial ribosomes and prevents
protein synthesis(1, 2)
inhibits toxin production by group A Streptococcus and Staphylococcus aureus (Antimicrob Agents
Chemother 1997 Aug;41(8):1682, J Infect Dis 1984 Mar;149(3):471)
primarily active against gram-positive organisms(1, 2)

aerobes include
Staphylococcus species
Streptococcus species, including group A Streptococcus
Corynebacterium diphtheriae
anaerobes include
Bacteroides fragilis
some Clostridium species, not including Clostridium difficile
Peptococcus species
Peptostreptococcus species
Eubacterium species
Propionibacterium species
Bifidobacterium species
Lactobacillus species
Prevotella species
Fusobacterium species
synergistic activity against Pneumocystis jirovecii when given in combination with primaquine(2)
poor activity against Enterococcus species(1, 2)
Drug interactions
may enhance effect of neuromuscular blocking agents; close monitoring is required when giving
these agents concomitantly (Anesthesiology 1976 Jul;45(1):84)
likely metabolized by the liver(1, 2)

excretion occurs in both the feces and urine(1, 2)
dosage adjustments are not recommended in renal impairment, although drug accumulation may
occur in severe liver disease(1, 2)
Gastrointestinal effects
clindamycin may cause nausea, vomiting, and diarrhea(1, 2)

diarrhea and pseudomembranous colitis are of significant concern and may be due to changes to
the abdominal flora (J Infect Dis 1977 Mar;135 Suppl:S104, J Infect Dis 1977 Mar;135 Suppl:S120)
Major clinical uses
Respiratory tract infections
may be useful in the treatment of aspiration pneumonia, lung abscess, or other pneumonia due to
anaerobic pathogens (Arch Intern Med 1981 Oct;141(11):1424, J Infect Dis 1977 Mar;135 Suppl:S58,
Arch Intern Med 1990 Dec;150(12):2525)
Pelvic inflammatory disease (PID)
Centers for Disease Control and Prevention (CDC) recommends combination therapy with
clindamycin plus aminoglycoside as an alternative to cephalosporin/doxycycline for the treatment
of pelvic inflammatory disease (PID) (MMWR Recomm Rep 2010 Dec 17;59(RR-12):1 full-text, Rev
Infect Dis 1990 Jul-Aug;12 Suppl 6:S656)
Toxic shock syndrome and necrotizing fasciitis
Infectious Diseases Society of America recommends inclusion of clindamycin in treatment regimens

for
invasive group A streptococcal infections, in combination with beta-lactam antibiotics
necrotizing infections caused by Staphylococcus aureus, group A Streptococcus, and
Clostridium perfringens
streptococcal and staphylococcal toxic shock syndromes
References - Clin Infect Dis 2014 Jul 15;59(2):e10, J Infect Dis 2007 Jan 15;195(2):202 full-text,
Antimicrob Agents Chemother 2003 May;47(5):1752 full-text, Pediatr Infect Dis J 1999
Dec;18(12):1096
Alternative to penicillin
clindamycin often used as an alternative to penicillins and cephalosporins for perioperative

prophylaxis targeting skin flora (Am J Health Syst Pharm 2013 Feb 1;70(3):195 full-text)
Macrolides
General information
macrolides include erythromycin, clarithromycin, and azithromycin(1, 2)

azithromycin has become more widely used due to(1, 2)
convenient dosing
greater activity against gram-negative bacteria
less drug interaction potential
Mechanism of action
macrolides bind to the 50S ribosomal subunit and inhibit protein synthesis(1, 2)
gram-positive organisms, including(1, 2)

Staphylococcus species, including some strains of methicillin-resistant Staphylococcus aureus
(MRSA)
growing macrolide resistance of significant concern among these organisms
atypical bacterial, including(1, 2)
Mycobacterium species (should not be used as a single agent for treatment)
Chlamydia species
Legionella species
Mycoplasma pneumoniae
gram-negative organisms, including(1, 2)
Bordetella pertussis
Neisseria gonorrhoeae
Haemophilus ducreyi
Helicobacter pylori
Campylobacter jejuni
Gardnerella vaginalis (1)
clarithromycin and azithromycin have activity against Mycobacterium avium complex(1, 2)
Haemophilus influenzae may be resistant(2)
Drug interactions
cytochrome P450 3A4 enzyme inhibition can affect the levels of many CYP3A4 substrate drugs
erythromycin and clarithromycin are potent inhibitors
azithromycin interaction potential with CYP3A4 substrate drugs is variable
References - Antimicrob Agents Chemother 1997 Aug;41(8):1709 PDF, Pharmacotherapy 1998
Mar-Apr;18(2):386, Ann Pharmacother 1997 Jul-Aug;31(7-8):859, Br J Clin Pharmacol 2008
Jan;65(1):98, Br J Clin Pharmacol 2000 Oct;50(4):285, J Clin Pharmacol 2002 Apr;42(4):444
macrolide metabolism occurs in the liver(1, 2)

clarithromycin(1, 2)
excreted through the urine
requires a dose adjustment in renal failure (creatinine clearance [CrCl] < 50 mL/minute)
erythromycin and azithromycin primarily excreted in the bile(1, 2)
azithromycin can be detected in the serum for several weeks after administration due to its long
half-life (Clin Drug Investig 1998;16(2):161)
Cardiac effects
macrolides can prolong the QT interval by blocking hERG channel-dependent potassium current in
myocyte membranes
risk for potentially fatal heart rhythms may be increased in those with
existing QT interval prolongation
hypokalemia
hypomagnesemia
concomitant use of QT prolonging agents
References - Drugs 2004;64(10):1091, N Engl J Med 2013 May 2;368(18):1704 full-text, N Engl J Med
2012 May 17;366(20):1881
Major clinical uses
Respiratory tract infections
Infectious Diseases Society of America and American Thoracic Society guidelines on the
management of community-acquired pneumonia in adults recommend macrolides as monotherapy
or as part of combination therapy with a beta-lactam for community-acquired pneumonia (Clin
Infect Dis 2007 Mar 1;44 Suppl 2:S27 full-text)
Chlamydia trachomatis infections
Centers for Disease Control guidelines on treatment of sexually transmitted diseases recommend
azithromycin for the treatment of chlamydial genital infections (MMWR Recomm Rep 2010 Dec
17;59(RR-12):1 full-text)
Mycobacterial infections
American Thoracic Society and Infectious Diseases Society of America statement on

nontuberculosis mycobacterial diseases recommends combination therapy including
clarithromycin or azithromycin for the treatment of Mycobacterium avium complex and other
nontuberculosis mycobacterial infections (Am J Respir Crit Care Med 2007 Feb 15;175(4):367)
Helicobacter pylori infections
macrolides may be given with other agents (usually amoxicillin and omeprazole) for the
eradication of Helicobacter pylori (Gut 2007 Apr;56(4):475 full-text, Eur J Gastroenterol Hepatol 2002
Nov;14(11):1237, Am J Gastroenterol 2003 Mar;98(3):562)
Tetracyclines
General information
tetracycline family includes tetracycline, doxycycline, minocycline, and tigecycline(1, 2)

due to increased bioavailability, longer acting property, and increased spectrum, oral minocycline
and doxycycline are more widely used compared to oral tetracycline(1, 2)
tigecycline is the first glycylcycline and the newest agent(1, 2)
only available IV
FDA reports increased mortality risk associated with use of tigecycline for severe infections
based on meta-analysis of 10 clinical trials (FDA Drug Safety Communication 2013 Sep 27)
Mechanism of action
tetracyclines reversibly bind to the 30S subunits of susceptible bacterial ribosomes and inhibit the
elongation phase of RNA synthesis(1, 2)
broad spectrum of activity(1, 2)

gram-positive aerobes, including
Staphylococcus species, including some methicillin-resistant Staphylococcus aureus
strains
Enterococcus species, including some vancomycin-resistant enterococci (VRE) infection
gram-negative organisms, including
Enterobacteriaceae
Acinetobacter baumannii
Stenotrophomonas maltophilia
Burkholderia species
atypical respiratory pathogens, including
Mycoplasma pneumoniae
Legionella pneumophila
Chlamydophila pneumoniae
anaerobes, including
Actinomyces
differences in activity among tetracyclines(1, 2)
minocycline appears to have greater activity against some Nocardia species than doxycycline
doxycycline is often the agent of choice for infections caused by
Borrelia burgdorferi (causative agent of Lyme disease)
Vibrio species (causative agent of cholera)
Chlamydia trachomatis (causative agent of chlamydia genital infections)
tigecycline may retain activity against organisms resistant to the older tetracyclines
not active against Pseudomonas aeruginosa(1, 2)
Pharmacologic considerations
Drug interactions
doxycycline is a moderate inhibitor of cytochrome P450 3A4 enzymes and may increase levels of
other drugs that are substrates of this enzyme(1)
tetracyclines may increase digoxin levels, however this effect was not found with tigecycline (N
Engl J Med 1981 Oct 1;305(14):789, Drugs 2000 Feb;59(2):181, Pharmacotherapy 2007 Jun;27(6):835)
minocycline may decrease levels of atazanavir (Antimicrob Agents Chemother 2008
Sep;52(9):3035 full-text)
calcium, magnesium, iron, bismuth, and aluminum may decrease the absorption of oral
tetracyclines ((2), JAMA 1982 Apr 23;247(16):2266, Ann Pharmacother 1997 Dec;31(12):1460)
tetracycline is eliminated through the renal route, and should be avoided in patients with renal
failure(1, 2)
minocycline is metabolized by the liver and only a small portion is excreted into the urine and
feces(1, 2)
doxycycline and tigecycline are mainly eliminated through the feces and a small amount is excreted
through the urine(2)
dose adjustments for doxycycline, minocycline, and tigecycline not required in patients with renal
impairment(1, 2)
tigecycline maintenance doses require adjustment in patients with severe liver disease (Am J Health
Syst Pharm 2006 Jul 1;63(13):1235)
Notable adverse effects
Teeth and bone
tetracycline deposits in calcifying areas

can cause reversible bone growth inhibition and permanent discoloration of teeth
generally avoided in neonate and pediatric populations (specifically children < 8 years
old)
Reference - Can Med Assoc J 1968 Nov 2;99(17):849 PDF
All-cause mortality
FDA reports increased mortality risk associated with use of tigecycline for severe infections based
on meta-analysis of 10 clinical trials (FDA Drug Safety Communication 2013 Sep 27)
Major clinical uses
Peptic ulcer
tetracyclines are given with other agents (usually metronidazole, bismuth, and omeprazole) for
eradication of Helicobacter pylori (JAMA 2008 Sep 17;300(11):1346, Am J Gastroenterol 2003
Mar;98(3):562)
Lyme disease
Infectious Diseases Society of America guidelines on assessment, treatment, and prevention of
Lyme disease recommend doxycycline for treatment and prevention of Lyme disease (Clin Infect
Dis 2006 Nov 1;43(9):1089 full-text)
Respiratory infections
Infectious Diseases Society of America and American Thoracic Society guidelines on the
management of community-acquired pneumonia in adults recommend doxycycline as an
alternative to macrolides for outpatient therapy of community-acquired pneumonia (Clin Infect Dis
2007 Mar 1;44 Suppl 2:S27 full-text)
Beta-Lactam Antibiotics
General information
beta-lactams are a family of structurally related antimicrobials(1, 2)

penicillin
penicillin-related agents
cephalosporins
carbapenems
monobactams (aztreonam)
antimicrobial spectrum is generally enhanced with each newer derivative of penicillin
Mechanism of action
beta-lactams bind penicillin-binding proteins (PBPs) and block formation of cross-linkages in

peptidoglycan(1, 2)
disturbed morphogenesis may disrupt crucial event in cell division(2)
weakened cell walls can result in lysis and death of bacterial cells(2)
Penicillins and penicillin-related agents
many organisms that were originally susceptible to penicillin have now developed resistance
through beta-lactamase production(1, 2)
penicillin(1)
variable activity amongst Streptococcus species
highly active against group A, B, C, G, F, and R beta-hemolytic streptococci
active against nonenterococcal group D streptococci
variable susceptibility among alpha-hemolytic streptococci
penicillin-resistant Streptococcus pneumoniae well described
active against many gram-positive bacilli, including
Corynebacterium species, Listeria monocytogenes, Clostridium species, Actinomyces,
Eubacterium, Propionibacterium, Bifidobacterium, and Lactobacillus species
active against Neisseria meningitidis, however Neisseria gonorrhoeae is frequently resistant
highly active against Treponema pallidum, causative agent of syphilis
limited activity in
Staphylococcus species, which are mostly resistant
ampicillin and amoxicillin(1, 2)
similar spectrum to each other and to penicillin
compared to penicillin, increased activity against
enterococci
gram-negative aerobes including
Escherichia coli
Proteus mirabilis
Salmonella species
Shigella species
nafcillin, oxacillin, and dicloxacillin(1)
predominantly active against gram-positive organisms
potent antistaphylococcal activity, with exception of methicillin-resistant Staphylococcus
aureus (MRSA)
Cephalosporins
first-generation cephalosporins include cefazolin and cephalexin(1, 2)

gram-positive organisms
methicillin-susceptible S. aureus
oral anaerobes, including Peptococcus and Peptostreptococcus
not active against enterococci, L. monocytogenes, or most Enterobacteriaceae
second-generation cephalosporins include cefaclor, cefprozil, cefuroxime, and cefotetan(1, 2)
active against oral anaerobes (Antimicrob Agents Chemother 1978 Feb;13(2):210)
enhanced activity against H. influenzae, N. meningitidis, N. gonorrhea, Moraxella catarrhalis,
and Enterobacteriaceae
reduced activity against gram-positive organisms
possible resistance due to AmpC beta-lactamase production in strains of Citrobacter freundii,
Morganella morganii, Serratia marcescens, Providencia species, and Enterobacter species
third-generation cephalosporins include ceftriaxone, cefotaxime, ceftazidime, cefpodoxime, and
cefdinir(1, 2)
generally more active against gram-negative pathogens than gram-positive organisms, with
notable activity against
Enterobacteriaceae
Neisseria species
H. influenzae
ceftazidime is the only third-generation cephalosporin that has activity against P. aeruginosa
possible resistance due to AmpC beta-lactamase in strains of C. freundii, M. morganii, S.
marcescens, Providencia species, and Enterobacter species
fourth-generation cephalosporins include cefepime(1, 2)
cefepime has broad activity against both gram-positive and gram-negative pathogens
Staphylococcus species, not including MRSA
P. aeruginosa
retains activity in Enterobacteriaceae that produce AmpC beta-lactamase and may
occasionally remain efficacious in the presence of extended-spectrum beta-lactamase
(ESBL) production (Clin Infect Dis 2013 Sep;57(6):781 full-text, Clin Infect Dis 2013
Feb;56(4):488 full-text)
not active against enterococci or L. monocytogenes
FDA safety alert notes risk of seizure may be increased in patients with renal failure not
receiving dose adjustments reported
fifth-generation cephalosporins include ceftaroline(1)
ceftaroline has notable activity against MRSA
with the exception of MRSA activity, spectrum of ceftaroline is comparable to third-generation
cephalosporins
not active against P. aeruginosa, or Enterobacteriaceae that produce AmpC beta-lactamase or
ESBLs
Carbapenems
carbapenems include doripenem, imipenem, meropenem, and ertapenem(1, 2)

retain activity in the presence of AmpC production and extended-spectrum beta-lactamases(1, 2)
broad activity against both gram-positive and gram-negative aerobes(1, 2)
susceptible gram-positive aerobes include
Staphylococcus species, not including methicillin-resistant S. aureus strains
L. monocytogenes
susceptible gram-negative aerobes include
Enterobacteriaceae
P. aeruginosa
ertapenem is not active against P. aeruginosa
P. aeruginosa resistance to other carbapenems is growing
Neisseria species
H. influenzae
M. catarrhalis
potent against anaerobes, including(1, 2)
Clostridium species
B. fragilis
differences in activity among carbapenems(1, 2)
imipenem has enhanced activity against ampicillin-susceptible strains of enterococci
meropenem may have increased activity against Burkholderia species
imipenem and meropenem have enhanced activity against Acinetobacter species
meropenem and doripenem occasionally have increased potency against gram-negative
bacteria that produce ESBLs
ertapenem has poor or no activity against P. aeruginosa, Enterococcus species, and
Acinetobacter species
not active against Stenotrophomonas maltophilia(2)
Aztreonam
spectrum is limited to gram-negative aerobes, including(1)

Enterobacteriaceae
P. aeruginosa
H. influenzae
N. meningitidis
may have activity against Burkholderia cepacia
not active against S. maltophilia(1)
ineffective in the presence of AmpC production and extended-spectrum beta-lactamases(1)
Beta-lactam and beta-lactamase inhibitor combination products
beta-lactamase role in resistance

beta-lactamase enzymes are produced by bacteria to hydrolyze beta-lactams and are most
common mechanism of gram-negative bacterial resistance to beta-lactam antibiotics
beta-lactamases can be characterized by
which beta-lactam enzyme it efficiently hydrolyzes
penicillinase
cephalosporinases
cloxacillinase
extended-spectrum beta-lactamases (ESBLs) which hydrolyze most penicillins,
extended-spectrum cephalosporins, and aztreonam
carbapenemases which cause resistance to almost all beta-lactamases (for example,
KPC beta-lactamases)
metallo-beta-lactamases
degree to which their activity is inhibited by beta-lactamase inhibitors
enzyme location and expression (for example, ESBL expression [measured either via
phenotypic or genetic tests], is typically low in most pediatric populations, but may be
increasing)
References - J Pediatr Pharmacol Ther 2014 Jul;19(3):156 full-text Crit Care 2010;14(3):224 full-
text
beta-lactamase inhibitors(1, 2)
designed to be used in combination with beta-lactam antibiotics to overcome resistance
mediated by plasmid-borne beta-lactamases
provide enhanced activity against some beta-lactamase-producing bacteria including
methicillin-susceptible Staphylococcus aureus
Enterococcus faecalis
Escherichia coli
Klebsiella pneumoniae
ceftazidime/avibactam, ceftolozane/tazobactam, piperacillin/tazobactam, and
ticarcillin/clavulanate may have activity against Pseudomonas aeruginosa
when used alone beta-lactamase inhibitors typically lack clinical activity, with the exception of
sulbactam, which is effective against Neisseria and Acinetobacter species
mechanism and classification of beta-lactamase inhibitors
beta-lactamase inhibitors traditionally share a beta-lactam backbone, but assume long-lived,
stable intermediates with beta-lactamases, thus “tying up” beta-lactam enzymes and allowing
partner beta-lactam antibiotic to inhibit penicillin binding protein target
traditional beta-lactamase inhibitors include
sulbactam and tazobactam
clavulanic acid
novel beta-lactamase inhibitors (non beta-lactam beta-lactamase inhibitors) include
avibactam
vaborbactam
Reference - Antimicrob Agents Chemother 2014;58(4):1835
resistance to these agents develops as more versatile beta-lactamases (for example, Klebsiella
pneumoniae carbapenemases [KPCs]) continue to emerge and acquire ability to hydrolyze beta-
lactamase inhibitors faster Antimicrob Agents Chemother 2014;58(4):1835
beta-lactambeta-lactamase inhibitor combination products
ampicillin/sulbactam (Unasyn)
amoxicillin-clavulanate (Augmentin)
ticarcillin/clavulanate (Timentin)
piperacillin/tazobactam (Zosyn)
ceftolozane/tazobactam (Zerbaxa)
ceftazidime/avibactam (Avycaz)
meropenem-vaborbactam (Vabomere) FDA Press Release 2017 Aug 29
beta-lactams have time-dependent killing

some experts recommend giving continuous or prolonged infusions of antipseudomonal beta-
lactams to optimize bacterial killing (Clin Infect Dis 2007 Feb 1;44(3):357 full-text, Pharmacotherapy
2007 Nov;27(11):1490, Clin Infect Dis 2013 Jan;56(2):272 full-text)
Drug interactions
nafcillin is a moderate cytochrome P450 3A4 inducer and may decrease levels of CYP3A4 substrate
drugs (Pharmacotherapy 2007 Oct;27(10):1467, Br J Clin Pharmacol 2003 Jun;55(6):588 full-text)
carbapenems can decrease valproic acid levels, and monitoring of valproic acid levels is
recommended during concomitant use (Ther Drug Monit 2012 Oct;34(5):599, J Clin Pharmacol 2009
Nov;49(11):1363 full-text)
most beta-lactams accumulate in patients with renal failure and require dose adjustments to avoid
increased risk of seizures(1)
beta-lactams requiring dose adjustment include penicillin, ampicillin, cefazolin, amoxicillin-
clavulanate, piperacillin-tazobactam, ceftazidime, cefepime, carbapenems
notable examples of beta-lactams that do not require adjusted doses are ceftriaxone and
nafcillin
Hypersensitivity reactions
hypersensitivity reactions are well described with penicillins and penicillin-related agents
frequency is not clear but true penicillin allergy is thought to be rare
manifestations of hypersensitivity may include urticaria, anaphylaxis, cytopenias, serum
sickness, and interstitial nephritis
desensitization protocols may be useful for administrating a penicillin-related agent in an
individual with a history of penicillin allergy
Reference - Ann Allergy Asthma Immunol 2010 Oct;105(4):259
later generation cephalosporins and carbapenems may be safe for individuals with penicillin
allergy (J Am Pharm Assoc (2003) 2008 Jul-Aug;48(4):530)
aztreonam
does not have cross-reactivity with the other penicillins and cephalosporins
similar chemical structure to ceftazidime, and therefore caution should be exercised when
using aztreonam in individuals with a reported ceftazidime allergy
Reference - Ann Allergy Asthma Immunol 2010 Oct;105(4):259
Neurotoxicity
seizures, encephalopathy, and other neurotoxic effects have been reported with many beta-lactams,
including cefepime (Crit Care 2013 Nov 7;17(6):R264 full-text, Ann Pharmacother 2008
Dec;42(12):1843)
cefepime is associated with nonconvulsive status epilepticus seizure in patients with renal
impairment not receiving appropriate dosage adjustments (FDA Drug Safety Communication 26
June 2012)
imipenem(1)
may inhibit the gamma-aminobutyric acid (GABA) receptor
risk of seizures may be increased in individuals with a history of seizures and impaired renal
function
neutropenia may be associated with prolonged use or high doses (J Antimicrob Chemother 1990
Mar;25(3):449, Drug Saf 2007;30(4):295)
hemolytic anemia has been described with beta-lactamase inhibitor compounds such as ampicillin-
sulbactam (Br J Haematol 1998 Mar;100(4):777)
Major clinical uses

Surgical prophylaxis
American Society of Health-System Pharmacists/Infectious Diseases Society of America/Surgical

Infection Society/Society for Healthcare Epidemiology of America joint guideline on antimicrobial
prophylaxis in surgery describe
beta-lactams as first-line agents for various surgical procedures
cefazolin as the most commonly used agent due to its excellent activity against skin flora
Reference - Am J Health Syst Pharm 2013 Feb 1;70(3):195 full-text
Respiratory and sinus infections
Infectious Diseases Society of America guideline on acute bacterial rhinosinusitis in children and
adults recommend beta-lactams such as amoxicillin-clavulanate as first-line treatment (Clin Infect
Dis 2012 Apr;54(8):e72 full-text)
Infectious Diseases Society of America/American Thoracic Society consensus guideline on
community- and hospital-acquired pneumonias recommend beta-lactams as part of combination
therapy
in community-acquired pneumonia, beta-lactams plus either azithromycin or doxycycline are
an alternative to respiratory fluoroquinolones (Clin Infect Dis 2007 Mar 1;44 Suppl 2:S27 full-
text)
initial therapy for nosocomial pneumonia includes a beta-lactam with antipseudomonal
activity such as cefepime, ceftazidime, piperacillin-tazobactam, imipenem, or meropenem (Am
J Respir Crit Care Med 2005 Feb 15;171(4):388)
Bacterial meningitis
Infectious Diseases Society of America practice guideline on treatment of bacterial meningitis

include beta-lactams as the primary agents for most bacterial organisms causing meningitis
vancomycin plus third-generation cephalosporin recommended therapy for infection due to
Streptococcus pneumoniae
third-generation cephalosporin recommended therapy for Neisseria meningitidis, Haemophilus
influenzae, or Escherichia coli
ampicillin or penicillin G preferred therapy for infection due to Listeria monocytogenes and
Streptococcus agalactiae
Reference - Clin Infect Dis 2004 Nov 1;39(9):1267 full-text
Infectious Diseases Society of America guideline on skin and soft tissue infections recommends
beta-lactams for a wide array of skin and soft tissue infections, including
amoxicillin-clavulanate for the treatment of infections caused by dog or cat bites
narrower spectrum agents such as oxacillin and cefazolin are recommended for nonintestinal
surgical site infections
broader agents such as ampicillin-sulbactam, piperacillin-tazobactam, third-generation
cephalosporins, or carbapenems are recommended for surgical site infections involving the
intestinal or genital tract
penicillin plus clindamycin is recommended for necrotizing fasciitis due to Streptococcus
infection and streptococcal toxic shock syndrome
References - Clin Infect Dis 2005 Nov 15;41(10):1373 full-text
Endocarditis
American Heart Association and Infectious Diseases Society of America guideline on infective
endocarditis recommend
beta-lactams for many causative organisms, with specific selection varying with pathogen
penicillin G and ceftriaxone as first-line agents for infections due to viridans group
streptococci and Streptococcus bovis
Reference - Circulation 2005 Jun 14;111(23):e394 full-text, correction can be found in
Circulation 2005 Oct 11;112(15):2373, Circulation 2007 Nov 20;116(21):e547, Circulation 2007
Apr 17;115(15):e408, Circulation 2008 Sep 16;118(12):e497
Intra-abdominal infections
Surgical Infection Society and Infectious Diseases Society of America guidelines on complicated
intra-abdominal infection recommend empiric treatment regimens that include third-generation
cephalosporins with metronidazole, beta-lactam/beta-lactamase inhibitor combinations, or
carbapenems (Clin Infect Dis 2010 Jan 15;50(2):133 full-text)
Urinary tract infections (UTI)
Infectious Diseases Society of America and European Society for Microbiology and Infectious
Diseases guideline on treatment of acute uncomplicated cystitis and pyelonephritis in women
recommends
beta-lactams (such as amoxicillin-clavulanate, cefdinir, cefaclor, and cefpodoxime) as
alternative agents for uncomplicated cystitis after nitrofurantoin, sulfamethoxazole-
trimethoprim, and fosfomycin
consideration of IV beta-lactam as alternatives to fluoroquinolones and sulfamethoxazole-
trimethoprim in the treatment of pyelonephritis
Reference - Clin Infect Dis 2011 Mar 1;52(5):e103 full-text
Selected Antibiotic-Associated Adverse Events

Selected Adverse Effects Associated with Antibiotics:
Adverse Effect Antibiotic(s)
Beta-lactams
Hematologic toxicity Linezolid
Vancomycin
Myopathy Daptomycin
Beta-lactams
Neurotoxicity Fluoroquinolones
Linezolid
Clindamycin
Gastrointestinal adverse effects
Tetracyclines
Aminoglycosides
Nephrotoxicity Vancomycin
Telavancin
Macrolides
QT prolongation
Fluoroquinolones
Adverse Effect Antibiotic(s)
Beta-lactams
Hypersensitivity reactions
Vancomycin

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Antibiotics

Infectious Diseases Society of America (IDSA) Recommendations

Abbreviations: MRSA, methicillin-resistant S. aureus; NA, not applicable.

* Recommended duration 7 days.

Abbreviations: MRSA, methicillin-resistant Staphylococcal aureus; MSSA, methicillin-susceptible S.

Abbreviations: MRSA, methicillin-resistant Staphylococcal aureus; MSSA, methicillin-susceptible S.

Cystitis and pyelonephritis in women

recommendations from Infectious Diseases Society of America/European Society for Microbiology

Infectious Diseases Society of America/American Thoracic Society (IDSA/ATS) recommendations for

Reference - IDSA/ATS consensus guideline on management of community-acquired pneumonia in

Reference - IDSA/ATS consensus guideline on management of community-acquired pneumonia in

American Thoracic Society/Infectious Diseases Society of America (ATS/IDSA) recommendations for

Abbreviation: MRSA, methicillin-resistant Staphylococcus aureus.

Reference - ATS/IDSA guideline on management of adults with hospital-acquired, ventilator-

Reference - ATS/IDSA guideline on management of adults with hospital-acquired, ventilator-

Nontuberculous mycobacterial diseases

Infectious Diseases Society of America/American Thoracic Society (IDSA/ATS) recommended ﬁrst-

Abbreviations: MAC, Mycobacterium avium complex; NTM, nontuberculous mycobacterial; RGM,

Reference - IDSA/ATS guideline on diagnosis, treatment, and prevention of nontuberculous

Abbreviations: MAC, Mycobacterium avium complex; NTM, nontuberculous mycobacterial; RGM,

Reference - IDSA/ATS guideline on diagnosis, treatment, and prevention of nontuberculous

Reference - IDSA/ATS guideline on diagnosis, treatment, and prevention of nontuberculous

Abbreviation: CSF, cerebrospinal ﬂuid.

* Some experts would add rifampin if dexamethasone is also given.

* Some experts would add rifampin if dexamethasone is also given.

Abbreviations: MIC, minimum inhibitory concentration; NA, not applicable.

Abbreviation: PNS, penicillin-nonsusceptible.

Reference - IDSA practice guideline on management of acute bacterial rhinosinusitis in children

Reference - IDSA practice guideline on management of acute bacterial rhinosinusitis in children

Complicated intra-abdominal infections

Surgical Infection Society/Infectious Diseases Society of America (SIS/IDSA) recommendations on

Abbreviations: ESBL, extended-spectrum beta-lactamase; MRSA, methicillin-resistant

* Because of increasing resistance of Escherichia coli to ﬂuoroquinolones, review local population

Reference - SIS/IDSA guideline on diagnosis and management of complicated intra-abdominal

Abbreviations: ESBL, extended-spectrum beta-lactamase; MRSA, methicillin-resistant

* Because of increasing resistance of Escherichia coli to ﬂuoroquinolones, review local population

Reference - SIS/IDSA guideline on diagnosis and management of complicated intra-abdominal

* Because of increasing resistance of Escherichia coli to ﬂuoroquinolones, review local population

Reference - SIS/IDSA guideline on diagnosis and management of complicated intra-abdominal

** Consider serum drug-concentration monitoring for dosage individualization.

Reference - SIS/IDSA guideline on diagnosis and management of complicated intra-abdominal

** Consider serum drug-concentration monitoring for dosage individualization.

Reference - SIS/IDSA guideline on diagnosis and management of complicated intra-abdominal

** Consider serum drug-concentration monitoring for dosage individualization.

Reference - SIS/IDSA guideline on diagnosis and management of complicated intra-abdominal

Clostridium diﬃcile infection in adults

Infection Diseases Society of America/Society for Healthcare Epidemiology of America (IDSA/SHEA)

Abbreviation: IDSA/SHEA, Infectious Diseases Society of America/Society for Healthcare

Abbreviation: IDSA/SHEA, Infectious Diseases Society of America/Society for Healthcare

Abbreviation: IDSA/SHEA, Infectious Diseases Society of America/Society for Healthcare

Lyme disease, human granulocytic anaplasmosis (HGA), and babesiosis

* Doxycycline contraindicated in pregnant or lactating women.

Antibiotics of Choice for Selected Pathogens

Coagulase-negative staphylococci Vancomycin

quinolone class includes original quinolone compounds and ﬂuorinated derivatives,

quinolones disrupt DNA replication to exert a bactericidal effect(1, 2)

gram-negative aerobes, including(1, 2)

high bioavailability, nearing 100% for most ﬂuoroquinolones(2)

ﬂuoroquinolones may interact with warfarin by(1)

Metabolism and excretion

most ﬂuoroquinolones excreted by renal pathway(1, 2)

Notable adverse events

ﬂuoroquinolones may cause nerve damage when given systemically