Antibiotics

Things to keep in your lab coat.

The Sanford Guide to Antimicrobial

Therapy
Johns Hopkins Abx Guide (not free any

more)
Palm
o iSilo program
o Epocrates

Tips for the boards

Study hard and efficiently. Dont waste time on a
resource that isnt making sense.
Get the landscape first then the landmarks.
Dont be afraid to study outside of the review
books.
Think like a question writer. Anticipate questions
for each topic.
Forget about learning everything because the
gaps in your knowledge will be random.

Grampositives
Anti-staph PCNs
(nafcillin, methicillin,
oxacillins)

Imipenem
Meropene
m
Amoxicilli
n
Ampicillin
Macrolides

Penicillin G/V

Gramnegatives
Anti-pseudomonal PCNs
(pipercillin, ticarcillin,
carbenicillin)

Clindamycin
Linezolid
Fluoroquinolines
Vancomycin

Rifampin
Sulfonamides

Aztreona
m

Aminoglycosides
Tetracyclines

1st
Generation

Cephalosporin
s3rd
Generation

2nd
Generation

How to approach the daunting task

of learning antibiotics

Create a general rule and know the

exception to the rule.

Rule: All cell-wall inhibitors are beta-lactams,

except vancomycin.

Beta-lactam ABX
o Penicillins
o Cephalosporins
o Aztreonam
o Carbapenems

Exception
o Vancomycin

Beta-lactam structure

Gram-positive vs. Gram-negative

Mechanism of Action
1.All beta-lactams bind penicillin-binding
proteins (PBPs)
2.All beta-lactams block transpeptidase
cross-linking of cell wall
3.Activate autolytic enzymes, causing
osmotic damage (bactericidal)

Beta-lactams:
1st mechanism of resistance
Beta-lactamase production (i.e. S. aureus)
We can get around this mode of resistance by
making beta-lactamase resistant penicillins (i.e.
nafcillin)

Beta-lactams:
2nd mechanism of resistance
Change the structure of PBPs
(i.e. Methicillin-Resistant S. Aureus)
Once bugs have changed their PBPs, we only
have one drug that will work, vancomycin.

Beta-lactams:
3rd mechanism of resistance
Efflux pump or change in porin structure:
Relevant for gram-negative bacteria

Summary of resistances to betalactamases

1st beta-lactamase production (S. aureus)
2nd change in PBP (MRSA)
3rd efflux pump or change in porin structure
(gram-negatives i.e. pseudomonas)

1st Generation
Drugs
o Penicillin G and V

Clinical use
o Narrow spectrum (mainly gram-positives)

Sensitive to beta-lactamases
o Means: on an exam, penicillin G or V is never the
answer for treating Staph

Exam questions:
o DOC for syphillis (benzathine penicillin),
o DOC in strep infections, especially to prevent
rheumatic fever
o DOC for susceptible pneumococci

2nd Generation
Drugs
o Nafcillin, Methicillin, Oxacillin, Cloxacillin,
Diclaxicillin
To overcome the beta-lactamase resistance,
these drugs were developed but they became so
narrow spectrum that they only clinically are
used for Staph.
These drugs created the superbug MRSA
o Beta-lactamase
o

3rd Generation
Drugs
o Aminopenicillins
Ampicillin
Amoxicillin

Clinical use
o Broad spectrum (gram positive and gram negatives, but NOT
beta-lactamase resistant)
Famous for treating:
H. flu and Listeria (ampicillin)
Lyme Disease (amox) DOC in peds and pregnancy
Enterococci

o Drug companies made body guards, clavulanic acid and

sulbactam, to protect the aminopenicillins from beta-lactamases.

4th Generation
Drugs
o Anti-pseudomonal penicillins
Ticarcillin
Piperacillin
Carbenicillin

Clinical use
Pseudomonas
Synergistic effect when combined with aminoglycosides.
Parenteral penicillins usually combined with beta-lactamase
inhibitors

Pharmacokinetics of Penicillins
Rule: All penicillins are water soluble, except nafcillin.
Water soluble substances:
o Are excreted by the kidneys.
Means adjustments in renal failure and are potentially renal toxic

o Do not cross the blood brain barrier

Means no good for meningitis

Lipid soluble substances:

o Are metabolized in the liver
Means many p450 interactions

o Cross the blood brain barrier

Means could potentially be used for meningitis

Toxicity
Rule: Penicillins cause allergies
o Come from fungal organisms
Means already immunogenic

o Contain sulfur to enhance solubility

Means bad for allergies

o Can cause ANY hypersensitivity reaction (Type I-IV)

Methicillin famous for interstitial nephritis (type III)
Hapten mediated hemolysis
About 5-10% cross-allergenicity with cephalosporins

Toxicity
Jarisch-Herxheimer reaction in Rx of syphilis
o Fever, chills, headache, myalgias, and
exacerbation of syphilitic cutaneous lesions
Ampicillin causes a famous maculopapular rash
when given to patients with infectious mono
(EBV).

Cephalosporins
Mechanism of action and resistance:
o same as penicillins

1st Generation Cephalosporins

Drugs
o Any drug with ph in name b/c from Europe
Cephalexin, cephradine
Except cefazolin (famous for surgical prophylaxis b/c of long
half-life)

Clinical use
o Gram positives
And a few gram negatives PEcK (Proteus, E. coli, Klebsiella)

Pharmacokinetics
o Do not enter CNS

2nd Generation Cephalosporins

Drugs
o Cefoxitin, cefaclor, cefuroxime

Clinical use
o Gram negatives: HEN PEcKS (H. flu,
Enterobacter, Neisseria, Proteus, E. coli,
Klebsiella, Serratia)

Pharmacokinetics
o Do not enter CNS, except cefuroxime

3rd Generation Cephalosporins

Drugs
o Ceftriaxone, cefotaxime, ceftazidime
o notice the ts

Clinical use
o 1st generation + 2nd generation = 3rd generation (gram positive
and negative) +anaerobes

Pharmacokinetics
o Ceftriaxone is lipid soluble
Means good entry into CNS
Means metabolized and excreted into bowel
Can cause sludge in gallbladder

Boards:
o Ceftazidime for pseudomonaz
o Ceftriaxone for gonorrhea and meningitis

4th Generation Cephalosporins

Drugs
o Cefepime
o Cefpirome

Clinical use
o 3rd Generation + more beta-lactamase
resistance

Toxicity
Same as penicillins
Disuliram-like reaction w/ ethanol
o In cephalosporins with a methylthiotetrazole
group, i.e. cefamandole, cefoperazone,
cefotetan
azole portion gives us the disulfiram-like reaction
Metronidazole

Aztreonam
Mechanism:
o Monobactam resistant to beta-lactamases
o Inhibits cell wall synthesis (same as
penicillins)
o Synergistic with aminoglycosides

Clinical use
o Gram negative rods only (pseudomonas)

Toxicity
o No cross-allergenicity w/ penicillins

Imipenem/cilastatin, Meropenem
Mechanism
o Carbapenems resistant to beta-lactamases
o Inhibits cell wall synthesis (same as penicillins)
o Cilastatin inhibits renal dihydropeptidase I which
decreased inactivation of imipenem in kidney.

Clinical use
o Decerebrate Antibiotics
Dont need to think about coverage, can work on almost
anything

Toxicity
o Imipenem famous for CNS toxicity (seizures)
o Meropenem has reduced risk of seizures

Vancomycin
Mechanism
o Inhibits cell wall mucopeptide formation by binding
o D-ala D-ala portion of cell wall precursors (USMLE TQ)
Resistance occurs when changed to D-ala D-lac

Clinical use
o Gram positive multidrug-resistant organisms
MRSA (IV)
C. difficile (PO)

Toxicity
o Nephro and ototoxic
o Red man syndrome with rapid infusion
Can prevent w/ antihistamine pretreatment

Grampositives
Anti-staph PCNs
(nafcillin, methicillin,
oxacillins)
Penicillin G/V

Imipenem
Meropene
m
Amoxicilli
n
Ampicillin

Gramnegatives
Anti-pseudomonal PCNs
(pipercillin, ticarcillin,
carbenicillin)

50s ribosome
Vancomycin

Nucleus

Aztreona
m

30s ribosome

1st
Generation

Cephalosporin
s3rd
Generation

2nd
Generation

Protein Synthesis Inhibitors

Rule: All protein synthesis inhibitors are

bacteriostatic, except for the
aminoglycosides.

Tetracyclines
Drugs
o Doxycycline
o Minocycline
o Demeclocycline
o Tetracycline

Mechanism
o Reversibly bind to the

30S ribosome and

inhibit binding of
aminoacyl-t-RNA to the

Tetracyclines
Clinical use
o Very broad spectrum
o Important use for spirochetes and intracellular bugs
Rickettsial Infections
Chlamydia

Toxicity
o Chelators of divalent ions
Means they deposit in bones and teeth
Means contraindicated in pregnancy and in kids who are still growing
Means cant take with antacids or iron.

o GI distress
o Fanconis syndrome
o Photosensitivity

Boards:
o Doxycycline is lipid soluble; means good STDs and prostatitis
o Minocycline is very water soluble and enters all secretions, especially saliva;
means useful for meningococcus prophylaxis
o Demeclocycline inhibits the release of ADH; means can be used for SIADH

Aminoglycosides
Drugs
o Gentamycin, neomycin, amikacin, tobramycin, streptomycin

Mechanism
o Taken up by an oxygen dependent pump and bind to the 30S ribosomal unit
and Induce the binding of the wrong t-RNA-AA complex, resulting in the
synthesis of false proteins. (Bactericidal)

Aminoglycosides
Clinical use
o Gram negative aerobes only!
(pseudomonas)
o Synergistic w/ beta-lactams
o Neomycin for bowel surgery
o Tobramycin for Pseudomonas

Toxicity
o Amino (NH3) + glycoside (OH) makes
extremely polar
Means membrane penetration in a
bacteria is dependent on a special
oxygen pump and only covers gram
negative aerobes
Means renally excreted and renal toxic
Means can be trapped in inner ear and
is ototoxic

o Neuromuscular blockade

Macrolides
Drugs:
o Erythromycin
o Azithromycin
o Clarithromycin

Mechanism
o Inhibit protein synthesis
by blocking
translocation, bind to
50S ribosomal subunit
(resistance is through
methylation at binding
site)

Macrolides
Clinical use
o Same broad coverage as tetracyclines
o URIs and atypical pneumonias (Mycoplasma,
Legionella, Chlamydia)
o Neisseria
o Alternative for penicillin allergic patients

Toxicities
o Stimulate motilin receptor (erythromycin) causing GI
upset
o Lipid soluble, except azithromycin
Means P450 interactions (erythromycin is a famous inhibitor)
and liver problems (acute cholestatic hepatitis)

Clindamycin
Mechanism
o Blocks peptide bond formation at 50S
ribosomal subunit (bacteriostatic)

Clinical use
o Gram-positives and anaerobes
Means can easily cause C. diff colitis

o Good penetration into bones

Means can be used for S. aureus osteomyelitis

Linezolid
Mechanism
o Linezolid binds on the 23S portion of the 50S subunit close to the
peptidyl transferase and chloramphenicol binding sites.

Clinical
o Famous for treating gram-positive drug resistant bugs (MRSA,
and multidrug resistant pneumococcus)

Toxicity
o Usually well tolerated
o Thrombocytopenia
o MAOI (avoid tyramine containing food)

Quinupristin/Dalfopristin
Mechanism
o Protein synthesis inhibitors that bind the 50S

ribosomal subunit

Clinical use
o VRE

Toxicity
o P-450 inhibitor

Inhibitors of DNA synthesis

Fluoroquinolones
Rifampin
Sulfonamides

Fluoroquinolones
Drugs
o Ciprofloxacin
o Gatifloxacin
o Levofloxacin
o Moxifloxacin
o Ofloxacin

Mechanism
o Inhibits DNA gyrase (topoisomerase II) (Bactericidal)

Fluoroquinolones
Clinical use
o Gram-negative rods of UTI and diarrhea
o Were 1st oral treatment of gram-negative sepsis
Means were overused, leading to resistance

o Distributes into all tissues and fluids (including bones)

Means can inhibit cartilage and tendon damage leading to tendonitis
and tendon rupture in adults
Means can be used for Salmonella osteomyelitis
Means contraindicated in pregnancy and in children
o Respiratory fluoroquinolones (levofloxacin) for drug resistant
pneumococcus
o Anthrax (ciprofloxacin)

Toxicity
o QT prolongation and arrhythmias
o Hypo/hyperglycemia
o Achilles tendon rupture or tendinitis has occurred rarely

Rifampin
Mechanism
o Inhibits DNA-dependent RNA polymerase

Clinical use
o TB (in combo and in prophylaxis)
o Famous for prophylaxis of meningococcus and H. flu

Toxicity
o Hepatotoxic
o Revs up P-450
o Rs:
RNA polymerase inhibitor
Revs up P-450
Red/orange body fluids

Sulfonamides and Trimethoprim

Sulfonamides
Mechanism
o Inhibits bacterial dihydropteroate synthase
by competing for binding sites with paminobenzoic acid (PABA), a precursor
required for bacterial synthesis of folic acid.
o Trimethoprim binds tightly to bacterial
dihydrofolate reductase. Synergistic with
sulfonamides.

Sulfonamides
Clinical use
o Resistance to sulfonamides is common
o PCP prophylaxis (PO) and treatment (IV)
TrimethoprimSulfamethoxazole, (TMP-SMX)
If sulfa allergy use pentamidine (antiprotozoal agent)

o Toxoplasmosis (Pyrimethamine + Sulfadiazine)

Toxicity
o Allergies (sulfa allergies, hemolytic anemia, SJS)
o Carried by albumin
Means can cause kernicterus

o Crystalluria
o Folic acid can be given to avoid some toxicities

Metronidazole
Mechanism
o Toxic metabolites
Means causes GI disturbance, glossitis (metallic taste in
mouth), urethritis

Clinical use
o Anaerobes
o G.E.T. on the Metro (Giardia, Entamoeba,
Trichomonas)
o C. diff colitis (PO)

Toxicity
o Metronidazole
Disulfiram-like reaction w/ ethanol

Mechanisms of Resistance

How to approach antibiotic

coverage

Rule: Every bacteria is gram negative,

except for the gram-positives and oddballs.

Exceptions to everything is gramnegative

Gram-positives

Oddballs

o Staph/Strep

o Mycoplasma (no cell wall)

o Listeria

o Ureaplasma (no cell wall)

o Bacillus

o Legionella (silver stain)

o Clostridium

o Chlamydia (obligate

o Corynebacterium

intracellular)

o Rickettsia (obligate
intracellular)

o Mycobacterium (acid-fast)
o Treponema (spirochete)
o Borrelia (spirochete)

Grampositives

Gramnegatives

Cell Wall

50s ribosome
Nucleus
30s ribosome

Grampositives

Gramnegatives

Cell Wall

50s ribosome
Vancomycin

Nucleus
30s ribosome

Aztreona
m

Grampositives
Anti-staph PCNs
(nafcillin, methicillin,
oxacillins)

Cell Wall

Gramnegatives
Anti-pseudomonal PCNs
(pipercillin, ticarcillin,
carbenicillin)

Penicillin G/V
50s ribosome
Vancomycin

Nucleus
30s ribosome

Aztreona
m

Grampositives
Anti-staph PCNs
(nafcillin, methicillin,
oxacillins)

Cell Wall

Gramnegatives
Anti-pseudomonal PCNs
(pipercillin, ticarcillin,
carbenicillin)

Penicillin G/V
50s ribosome
Vancomycin

Nucleus

Aztreona
m

30s ribosome

1st
Generation

Cephalosporin
s3rd
Generation

2nd
Generation

Grampositives
Anti-staph PCNs
(nafcillin, methicillin,
oxacillins)
Penicillin G/V

Amoxicilli
n
Ampicillin

Gramnegatives
Anti-pseudomonal PCNs
(pipercillin, ticarcillin,
carbenicillin)

50s ribosome
Vancomycin

Nucleus

Aztreona
m

30s ribosome

1st
Generation

Cephalosporin
s3rd
Generation

2nd
Generation

Grampositives
Anti-staph PCNs
(nafcillin, methicillin,
oxacillins)
Penicillin G/V

Imipenem
Meropene
m
Amoxicilli
n
Ampicillin

Gramnegatives
Anti-pseudomonal PCNs
(pipercillin, ticarcillin,
carbenicillin)

50s ribosome
Vancomycin

Nucleus

Aztreona
m

30s ribosome

1st
Generation

Cephalosporin
s3rd
Generation

2nd
Generation

Grampositives
Anti-staph PCNs
(nafcillin, methicillin,
oxacillins)

Imipenem
Meropene
m
Amoxicilli
n
Ampicillin
Macrolides

Penicillin G/V

Gramnegatives
Anti-pseudomonal PCNs
(pipercillin, ticarcillin,
carbenicillin)

Clindamycin
Linezolid
Vancomycin

Nucleus

Aztreona
m

Aminoglycosides
Tetracyclines

1st
Generation

Cephalosporin
s3rd
Generation

2nd
Generation

Grampositives
Anti-staph PCNs
(nafcillin, methicillin,
oxacillins)

Imipenem
Meropene
m
Amoxicilli
n
Ampicillin
Macrolides

Penicillin G/V

Gramnegatives
Anti-pseudomonal PCNs
(pipercillin, ticarcillin,
carbenicillin)

Clindamycin
Linezolid
Fluoroquinolines
Vancomycin

Rifampin
Sulfonamides

Aztreona
m

Aminoglycosides
Tetracyclines

1st
Generation

Cephalosporin
s3rd
Generation

2nd
Generation

My rules for antibiotics questions.

Is the bug gram-positive or gram-negative?
o Use the chart we just made for what antibiotic to use

Look for contraindications to using your

antibiotic. Is the patient too young or too
pregnant?
o Dont use tetracyclines, aminoglycosides,

fluoroquinolones, sulfonamides.

Is the bug intracellular

o Use a tetracycline or macrolide

Antibacterial Drugs in Pregnancy

Antibacterial
Drug
Aminoglycosides

Toxicity in Pregnancy

Recommendation

Possible 8th nerve toxicity

Cautiona

Chloramphenicol

Gray syndrome in newborn

Caution at term

Fluoroquinolones

Arthropathy in immature animals

Caution

Clarithromycin

Teratogenicity in animals

Contraindicated

Ertapenem

Decreased weight in animals

Caution

Erythromycin
estolate
Imipenem/cilastatin

Cholestatic hepatitis

Contraindicated

Toxicity in some pregnant animals

Caution

Linezolid

Embryonic and fetal toxicity in rats

Caution

Meropenem

Unknown

Caution

Metronidazole

None known, but carcinogenic in rats

Caution

Nitrofurantoin

Hemolytic anemia in newborns

Caution; contraindicated at
term

Quinupristin/dalfop
ristin
Sulfonamides

Unknown

Caution

Hemolysis in newborn with G6PDb deficiency; kernicterus in

newborn

Caution; contraindicated at
term

Tetracyclines

Tooth discoloration, inhibition of bone growth in fetus; hepatotoxicity

Contraindicated

Vancomycin

Unknown

Caution

GBS, E. coli, H. flu, Listeria, Meningococcus, Pneumococcus

Newbor
n

Adul
t

Practice Question
A 16-year-old high school cheerleader presents
with low grade fever, pleuritic pain and a nonproductive cough. A sample tube of her blood was
placed in ice, and "grains of sand" appeared in the
glass portion of the tube. Therapy should include
which of the following?
A. Ampicillin
B. Erythromycin
C. Oxygen and external cooling
D. Penicillin G
E. Ribavirin

Practice Question
A 58-year-old alcoholic man with multiple dental caries
develops a pulmonary abscess and is treated with
antibiotics. Several days later, he develops nausea,
vomiting, abdominal pain, and voluminous green diarrhea.
Which of the following antibiotics is most likely responsible
for this patient's symptoms?
A. Chloramphenicol
B. Clindamycin
C. Gentamicin
D. Metronidazole
E. Vancomycin

Practice Question
Which of the following organisms is most
likely to be implicated as a cause of
urethritis that persists after antibiotic therapy
for gonorrhea?
A. Actinomyces
B. Chlamydia
C. Mycobacteria
D. Nocardia
E. Rickettsia

Practice Question
A 33-year-old woman presents with fever, vomiting, severe
irritative voiding symptoms, and pronounced costovertebral
angle tenderness. Laboratory evaluation reveals
leukocytosis with a left shift; blood cultures indicate
bacteremia. Urinalysis shows pyuria, mild hematuria, and
gram-negative bacteria. Which of the following drugs would
best treat this patient's infection?
A. Ampicillin and gentamicin
B. Erythromycin
C. Gentamicin and vancomycin
D. Tetracycline

Practice Question

A 35-year-old male undergoes an appendectomy. Several days later,

an abscess has formed at the surgical site. It does not improve with
administration of a cephalosporin, but does respond to nafcillin. The
infecting organism most likely produced an enzyme that would
hydrolyze which bond in the above molecule?
A. A
B. B
C. C
D. D