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Ceftriaxone
Haemophilus influenzae or
Methicillin-sensitive Staphylococcus aureus Levofloxacin, moxifloxacin, or ciprofloxacin
Antibiotic-sensitive enteric gram-negative bacilli or
Escherichia coli Ampicillin/sulbactam
Klebsiella pneumoniae or
Enterobacter species Ertapenem
Proteus species
Serratia marcescens
* See Table 5 for proper initial doses of antibiotics.
The frequency of penicillin-resistant S. pneumoniae and multidrug-resistant S. pneumoniae is increasing; levofloxacin or moxiflox-
acin are preferred to ciprofloxacin and the role of other new quinolones, such as gatifloxacin, has not been established.
Initial Empiric Antibiotic Therapy
The key decision in initial empiric therapy is whether the patient
has risk factors for MDR organisms. Previously, the time of
onset of HAP was used to classify patients as either early onset
or late onset, depending on whether the infection began within
the rst 4 days of hospitalization or later (5). However, many
patients are admitted after a recent hospitalization or from a
healthcare-associated facility (nursing home, dialysis center, etc.).
These patients should be classied as at risk for MDRpathogens,
regardless of when in the time course of the current hospitaliza-
tion the pneumonia begins. Healthcare-associated infections are
bacteriologically similar to hospital-acquired infections (4, 6, 43,
227). HCAP is dened by a positive respiratory tract culture,
obtained within 48 hours of hospital admission, in a patient who
has the criteria listed in Table 2 (43). Most patients with HCAP
are at risk for infection with MDR organisms, but in studies of
HAP and VAP, hospitalization for at least 5 days is required to
increase the risk of infection with these organisms (21, 103).
One of the consequences of increasing antimicrobial resis-
tance is an increased probability of inappropriate initial empiric
antimicrobial treatment of infections (228). Inappropriate anti-
microbial treatment represents the use of antibiotics with poor or
no in vitro activity against the identied microorganisms causing
infection at the tissue site of infection (e.g., empiric treatment
with nafcillin for pneumonia subsequently documented to be
MRSA). Because delays in the administration of appropriate
therapy have been associated with excess hospital mortality from
HAP (37, 111, 112, 229, 230), the prompt administration of em-
piric therapy for patients likely to have VAPis essential. Alvarez-
Lerma showed that, among 490 episodes of pneumonia acquired
inthe ICUsetting, 214 episodes (43.7%) required modicationof
the initial antibiotic regimen due to either isolation of a resistant
microorganism (62.1%) or lack of clinical response to therapy
(36.0%) (204). Attributable mortality from HAP was signi-
cantly lower among patients receiving initial appropriate antibi-
otic treatment compared with patients requiring a treatment
change (16.2 versus 24.7%; p 0.034).
Iregui and coworkers also documented an adverse outcome
with initially delayed appropriate antimicrobial therapy in 107
patients with VAP and examined factors leading to such delays
(112). Thirty-three (30.8%) patients received appropriate antibi-
otic treatment that was delayed 24 hours or more after patients
initially met diagnostic criteria for VAP, often because of a delay
in physician recognition of the presence of VAP and writing the
orders for antimicrobial treatment (n 25; 75.8%). Patients
receiving delayed antimicrobial treatment had greater hospital
402 AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE VOL 171 2005
TABLE 4. INITIAL EMPIRIC THERAPY FOR HOSPITAL-
ACQUIRED PNEUMONIA, VENTILATOR-ASSOCIATED
PNEUMONIA, AND HEALTHCARE-ASSOCIATED PNEUMONIA
IN PATIENTS WITH LATE-ONSET DISEASE OR RISK
FACTORS FOR MULTIDRUG-RESISTANT PATHOGENS
AND ALL DISEASE SEVERITY
Potential Pathogens Combination Antibiotic Therapy*
Pathogens listed in Table 3 and Antipseudomonal cephalosporin
MDR pathogens (cefepime, ceftazidime)
Pseudomonas aeruginosa or
Klebsiella pneumoniae (ESBL
Antipseudomonal carbepenem
Acinetobacter species
(imipenem or meropenem)
or
-Lactam/-lactamase inhibitor
(piperacillintazobactam)
plus
Antipseudomonal fluoroquinolone
(ciprofloxacin or levofloxacin)
or
Aminoglycoside
(amikacin, gentamicin, or tobramycin)
plus
Methicillin-resistant Staphylococcus Linezolid or vancomycin
aureus (MRSA)
Legionella pneumophila
* See Table 5 for adequate initial dosing of antibiotics. Initial antibiotic therapy
should be adjusted or streamlined on the basis of microbiologic data and clinical
response to therapy.
If an ESBL
Antipseudomonal quinolones
Levofloxacin 750 mg every d
Ciprofloxacin 400 mg every 8 h
Vancomycin 15 mg/kg every 12 h
Trough levels for gentamicin and tobramycin should be less than 1 g/ml,
and for amikacin they should be less than 45 g/ml.
Klebsiella
infections (281). Restriction of cephalosporins was accompanied
by a 44%reduction in infection and colonization with the ESBL