Infectious Diseases in Critical Care Medicine

treated with vancomycin, in which the targeted trough vancomycin concentration was at least
four times the MIC (271). Strains of MRSA showing a high MIC of vancomycin ( 2 mg/mL)
were detected in 54% of patients. Despite achieving the target trough concentration, mortality
was higher among patients whose MRSA strain had a high MIC than patients whose MRSA
strain had a low MIC (24% vs. 10%). The addition of rifampin, aminoglycosides, or other drugs
has achieved little improvement (272).
The use of new antimicrobial agents against MRSA has also been explored. Thus,
quinupristin-dalfopristin has generated worse results than vancomycin (268). Linezolid, an
oxazolidinone antimicrobial agent, is active against MRSA and achieves better tissue
penetration than vancomycin, but is bacteriostatic rather than bactericidal (273,274). However,
a combined analysis of the results of two randomized trials comparing linezolid with
vancomycin for the treatment of nosocomial pneumonia (each in combination with aztreonam
for gram-negative coverage) suggests a therapeutic advantage of linezolid (275). In a further
analysis of a subset of patients with MRSA VAP, linezolid was associated with a significantly
higher probability of bacterial eradication, clinical cure, and hospital survival (276). Despite
higher costs, linezolid therapy for MRSA VAP was attributed an absolute mortality benefit of
22%, which translates to five patients as the number-needed-to-treat to save one life (276). On
the basis of these findings, linezolid is now recommended as therapy for MRSA VAP (24).

Table 6 Initial Empirical Antibiotic Treatment of VAP According to the Potential Pathogen

No known risk factors for MDR pathogens, early onset, and any disease severity

Potential pathogen Recommended AB Dosing

S. pneumoniae
H. influenzae
MSSA
Antibiotic sensitive
Gram-negative bacilli
(E. coli, K. pneumoniae,
Enterobacterspp.,
Proteusspp.,
S. marcescens)

Ceftriaxone

or

levofloxacin,

moxifloxacin or ciprofloxacin

or

ampicillin/sulbactam

or

ertapenem

2 g/day IV–IM

500 mg/day IV–PO

400 mg/day PO

750 mg/12 hr PO

400 mg/12 hr IV

1.5–3 g/6 hr IV

1g/day IV–IM

Risk factors for MDR pathogens, late-onset, and any disease severity

Potential pathogen Combination AB therapy Dosing

Pathogens above and
P. aeruginosa
K. pneumoniaeESBL
Acinetobacterspp.

Antipseudomonal cephalosporin

(cefepime,

ceftazidime)

Or

Antipseudomonal carbapenem

(imipenem,

meropenem,

doripenem)

or

b-lactam/b-lactamase inhibitor

(piperacillin-tazobactam)

plus

Antipseudomonal fluorquinolone

(ciprofloxacin,

levofloxacin)

or

Aminoglycoside

(amikacin,

gentamicin,

tobramycin)

1–2 g/8–12 hr IV

2 g/8 hr

500 mg/6 hr or 1 g/8 hr IV

1 g/8 hr

500 mg/8 hr infused over 4 hr

4.5 g/6 hr

400 mg/8 hr IV

750 mg/day

20 mg/kg/day, single dose
7 mg/kg/day, single dose
7 mg/kg/day, single dose
MRSA Linezolid
or
Vancomycin

600 mg/12 hr IV

15 mg/kg/12 hr IV

192 Bouza and Burillo