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HAP/HCAP/VAP
Salim A Baharoon MD
Infectious Disease / Critical Care
King Saud Bin Abdulaziz University
Riyadh
DEFINITIONS
HAP: Pneumonia that occurs 48 hours or more after admission and did not appear to be
incubating at the time of admition.
DIAGNOSIS
Fever
Purulent sputum
Leukocytosis
Decline in oxygenation
69% sensitivity and 75% specificity for pneumonia (autopsy as reference)
BAL, PSBs do not differ from less invasive tests in terms of sensitivity, specificity or,
more importantly, morbidity and mortality.
Negative lower respiratory tract cultures can be used to stop antibiotic therapy in a patient
who has had cultures obtained in the absence of an antibiotic change in the past 72 hours.
EPIDEMIOLOGY
OUTCOME
P<.0001
P>.05
P<.0001
P<.001
50
P = .504
40
30
20
10
0
None
Early Onset
Late Onset
Nosocomial Pneumonia
MRSA INFECTION
ETIOLOGY
Gram-positive cocci
S. pneumonia.
H. influenzae
Staphylococcus aureus (50% in ICU due to MRSA)
More common in patients with diabetes mellitus, head trauma and those hospitalized in the ICU.
40
P = .003
Early-onset NP
Late-onset NP
35
30
P = .408
25
P = .043
20
15
MSSA
MRSA
OSSA =
Oxacillin-sensitive
S aureus
ORSA =
Oxacillin-resistant
S aureus
ES =
Enterobacter species
SM =
S marcescens
P = .144
ES
SM
5
PA
P aeruginosa
P = .985
10
PA =
Pathogen
Ibrahim, et al. Chest. 2000;117:1434-1442.
ETIOLOGY
ETIOLOGY
Colonization
Aspiration
HAP
PATHOGENESIS
Number and virulence of organisms entering the lower respiratory tract and
response of the host.
Disease state also plays a role: alteration in gastric pH due to illness, certain
medications, malnutrition and supplemental feedings.
Lam OLT, et al. Effectiveness of oral hygiene interventions against oral and oropharyngeal reservoirs
of aerobic and facultatively anaaerobic graminegative bacilli. AJIC 2012;40:175-82.
Leukemia
COPD
Cerebral palsy
MANAGEMENT
HOSPITAL ADMISSION
Decision to admit remain clinical
Severity scores can help.
CURB-65 criteria (>2, more-intensive treatment)
Confusion
Urea 7 mmol/L (20 mg/dL)
Increased respiratory rate >30
low blood pressure (SBP <90 or DBP <60)
Pneumonia Severity Index (PSI)
uses demographics, the coexistence of co-morbid illnesses findings
on physical examination, vital signs and essential laboratory findings
PSI SCORE
60
*P<.001
52*
50
42*
40
30
24
20
18
10
0
All-Cause Mortality
Inadequate antimicrobial treatment
(n=169)
Infection-Related Mortality
Adequate antimicrobial treatment
(n=486)
JAMA 2010
Antipseudomonalcephalosporin
OR
Antipseudomonalcarbepenem
OR
Lactam/lactamaseinhibitor
Plus
Antipseudomonalfluoroquinolone
OR
Aminoglycoside
Plus
Sever pneumonia, necrotizing or cavitary
AntiMRSA
infiltrates, empyema
AntiLegionellapneumophilaandanti
Viral
Recommended Antibiotic
Streptococcus pneumoniae
H influenzae
Methicillin-sensitive S aureus (MSSA)
Ceftriaxone/Azithromycin
Antibiotic-sensitive, enteric,
gram-negative bacilli
E coli
K pneumoniae (ESBL-)
Enterobacter spp
Proteus spp
Serratia marcescens
or
Levofloxacin, moxifloxacin, or
ciprofloxacin
or
Ampicillin/sulbactam/Azithromycin
or
Ertapenem/Azithromycin
KPC
Combination therapy
Synergistic testing
Suggested regimens include colistine plus tigecycline
plus carbapenem/rifampin
Other drugs include fosfomycin, aztreonam
PREVENTION
No straws
SUMMARY
HAP is a leading infection among all hospital acquired infections
HAP is associated with high mortality, long hospital stay, high
economic burden
HAP is still diagnosed with relatively non specific methods
HAP etiology vary between geographical locations and each region
should have real-time data
Treatment of MDR organism is posing a very significant problem
Prevention of HAP through established protocols
Thank you
Questions?
Intubation and mechanical ventilation increase the risk of HAP 6-21 fold.
NIPPV, data shows use to avoid reintubation may be associated with more incidence of
HAP.
Oral gastric and tracheal tubes rather than nasal may reduce incidence of sinusitis and
subsequent lower respiratory tract infection (HAP).
H2 blockers have shown an increased risk for VAP, risk vs. benefit for stress
bleeding should be considered
Multiple studies have identified allogeneic blood products as a risk factor for postoperative pneumonia, and the time length of blood storage as another risk factor.
Blood transfusion is usually limited to Hb <7 in the patient who has no active
bleeding.
Weber DJ, et al. Microbiology of ventilator associated pneumonia compared with that of hospital acquired pneumonia. Infect Control Hosp
Epidemiol 2007;28:825 31
RESULTS, EPIDEMIOLOGY
588 LOWER RESPIRATORY THERAPY TRACT INFECTIONS IN 556 PATIENTS
INCIDENCE OF PNEUMONIA: 0.37%
Assessment of Non-Responders
Wrong Organism
Wrong Diagnosis
Drug-resistant Pathogens:
(Bacteria, Mycobacteria, Virus, Fungus)
Inadequate Antimicrobial Therapy
Atelectasis
Pulmonary Embolism
ARDS
Pulmonary Hemorrhage
Underlying Decease
Neoplasm
Complications
RESULTS, PATHOGENS
PATHOGENS ISOLATED FROM 92.4% OF PATIENTS WITH VAP AND 76.6% FROM HAP
PATIENTS
VAP etiology
Other
Staph areus
Pseudomonas
25
S aureus
20
P aeruginosa
Enterobacter spp.
15
E coli
K pneumoniae
10
Serratia marcescens
Acinetobacter spp
5
0
19751
199219982
20031
1. Gaynes R, et al. Clin Infect Dis .2005; 41:848-54. NNIS system report. Am J Infect Control. 2000; 28(6):429-48.
2. Richards MJ, et al. Infect Control Hosp Epidemiol. 2000; 21:510-5.
Plasma and
pulmonary epithelial
lining fluid (ELF)
linezolid
concentrations
exceeded MIC90 for
staphylococci and
streptococci through
the dosing interval
Plasma
Concentration (g/L)
5 doses of linezolid
600 mg q12h were
administered orally
to 25 healthy
volunteers
MIC90 S aureus
MIC90 Enterococcus spp
MIC90 S pneumoniae
PHARMACOKINETIC CHARACTERISTICS OF
LINEZOLID IN ADULTS
Parameter
Effect
Oral bioavailability
100%
Ingestion of food
No dose adjustment
Volume of distribution
Dosage formulations
Distribution
Protein binding
Trough
Plasma (mg/L)
17.74
2.41.2
ELF (mg/L)
14.45.6
2.61.7
70
60
53
58
55
52
50
46
50
40
30
20
10
86/161 74/142
31/56
19/41
18/31
Intent-to-treat (ITT)
S aureus NP
10/20
MRSA NP
Vancomycin 1 g q12h IV
Safety and efficacy of linezolid versus vancomycin were compared in 402 patients with NP, including VAP;
398 patients received at least 1 dose of study medication. Patients were treated for 7 to 21 days, with
optional aztreonam 1 g to 2 g q8h. Clinical cure rates were assessed 12 to
28 days after end of therapy.
70
60
60
53
52
50
49
42
40
29
30
20
10
0
135/256 128/245
ITT
40/81
40/95
S aureus NP
Linezolid 600 mg q12h IV
18/30
12/41
MRSA NP
Vancomycin 1 g q12h IV
The safety and efficacy of linezolid IV versus vancomycin IV were compared in 623 patients with NP, including VAP. Patients were treated for 7
to 21 days, with optional aztreonam 1 g to 2 g q8h. Clinical cure rates were assessed 15 to 21 days after end of therapy.
Wunderink RG et al. Clin Ther. 2003;25:980-992.
Data on file. Pfizer Inc.
70
60
59
53
52
52
50
43
36
40
30
20
10
0
221/417 202/387
70/136 59/136
ITT
S aureus NP
Linezolid was equally effective in the ITT and S aureus NP populations (P=NS).
The outcome difference in the MRSA NP subgroup is provided as a descriptive measure only.
No further inference should be drawn due to the retrospective nature of the analysis (P<.01).
36/61
22/62
MRSA NP
Vancomycin 1 g q12h IV
62
49
45
37
35
21
103/227
76/207
43/88
32/91
Linezolid was equally effective in the ITT and S aureus NP populations (P=NS).
The outcome difference in the MRSA NP subgroup is provided as a descriptive measure only.
No further inference should be drawn due to the retrospective nature of the analysis (P<.01).
23/37
7/33
Vancomycin 1 g q12h IV
HETERORESISTANCE
eradication
Rubinstein,
CID 2001
Prospective
RCT, N=396
53% vs 52%
(p = 0.79)
67% vs 71%
(p = 0.69)
Wunderink,
52% vs 52%
(p = NS)
61% vs 53%
(p = NS)
Prospective
RCT, N=623
Wunderink,
Chest 2003
Retrospective
N=1019
MRSA
59% vs 35%
(p < 0.01)
MRSA
80% vs 63%
(p = 0.03)
Kollef,
ICM 2004
Retrospective
N=544
MRSA
62% vs 21%
(p = 0.001)
MRSA
60% vs 22%
(p = 0.001)
MRSA:
84% vs 61%
(p = 0.02)
LINEZOLID VS VANCOMYCIN IN
NOSOCOMIAL PNEUMONIA
(EMPIRICAL)
LINEZOLID VS VANCOMYCIN IN
NOSOCOMIAL PNEUMONIA
(EMPIRICAL)
LINEZOLID VS VANCOMYCIN IN
NOSOCOMIAL PNEUMONIA
(EMPIRICAL)
Reason for improved survival: poor penetration of
vancomycin into the lungs
Chest 2004:126(1):314-316.
Chest 2004:125(6):2370-2371.
Chest 2005:127(6):2298-2301.
Other study in pneumonia patients did not show sub-therapeutic lung concentration.
META-ANALYSIS
META-ANALYSIS
Target population
Comparator
Primary end-point
Suspected MRSA
nosocomial
pneumonia
Linezolid vs
glycopeptide
Clinical success
Nosocomial
pneumonia
Linezolid vs
glycopeptide
Clinical cure
Linezolid vs
Vancomycin
Treatment success
Beibei L, et al.
Gram-positive
International journal bacterial infections
of antimicrobial
agents 2010
GI events
Thrombocytopenia
Renal failure
META-ANALYSIS
Target population
Comparator
Primary end-point
Suspected MRSA
nosocomial
pneumonia
Linezolid vs
glycopeptide
Clinical success at
the test of cure
(TOC) among
clinically evaluable
subjects
Nosocomial
pneumonia
Linezolid vs
glycopeptide
Clinical cure
Linezolid vs
Vancomycin
Treatment success
Beibei L, et al.
Gram-positive
International journal bacterial infections
of antimicrobial
agents 2010
Clinical success rates at the end of study (study 7-30 days post end of treatment) , per-protocol
analysis
57.6 % (95/165) in Zyvox group
46.6 % (81/174) in Vancomycin group
95 % CI for the difference in response rates: 0.5%-21.6%
p=0.042
vancomyci
n
diarrhea
3.7
diarrhea
4.3
rash
2.7
nausea
1.9
constipation
1.0
rash
1.7
nausea
1.0
anemia
1.4
Acute renal
failure
1.4
SUMMARY
Retrospective study suggest survival benefit than vancomycin in MRSA pneumonia (Chest
2003;124;1789-1797.)
Latest randomized, double blinded trial suggest better (non-inferior) clinical success than
vancomycin (2010 idsa abstract)