commonly due to vascular access lines. Gram-positive cocci including methicillin-
resistant coagulase-negative staphylococci (MRSE), MRSA, gram-negative rods, and
yeasts (notably,Candidaspp.) are the usual culprits.- The severity of the patient’s underlying illness: Studies in the older literature classified
patients’ underlying illnesses as “rapidly fatal” (that is, likely to result in death
during the present hospitalization), “ultimately fatal” (that is, likely to result in death
within 5 years), and “nonfatal.” Dating to the landmark 1962 paper by McCabe and
Jackson, such studies demonstrated a powerful effect of underlying illness on
mortality rates, especially from sepsis due to gram-negative bacilli (16). More recent
studies extend those observations using newer tools, notably the APACHE II and
SOFA scoring systems for disease severity (17). The take-home point is that one
should err toward broader-spectrum empiric therapy for patients with serious
underlying diseases on account of the smaller margin for error. - Local epidemiology and antibiotic susceptibility data: There are data to indicate that
prescribing by an “on-call” infectious diseases specialist correlates with appropriate
prescribing (in one study, 78% vs. 54% for other physicians) and improved survival
(18). Infectious diseases specialists presumably performed better by dint of greater
awareness of the most likely pathogens and their susceptibilities. The question arises
whether this benefit might likewise be achieved through greater awareness of local
epidemiology and antimicrobial susceptibility data, informed by knowledge of the
most likely pathogens for this or that disease syndrome. Such local data on resistant
pathogens is now being taken into account in computer-based prescribing tools
tailored to individual hospitals and ICUs. Even traditional workhorses such as
piperacillin/tazobactam and to some extent the carbapenems are now facing
resistant bacteria. In a recent article from France, 16% ofE. coliisolates from
clinically relevant specimens were resistant or intermediate to pip/tazo (10). High-
level penicillinase production was the main mechanism of resistance, and prior
amoxicillin therapy was a risk factor.
Trouillet et al. identified the following significant independent factors for
piperacillin-resistant VAP: presence of an underlying fatal medical condition,
previous fluoroquinolone use, and initial disease severity (19). The antimicrobial
resistance rates among gram-negative bacilli in ICUs across the United States were
evaluated in a Merck-sponsored database. During the 12-year period from 1993 to
2004, 74,394 gram-negative bacillus isolates were evaluated. The organisms most
frequently isolated wereP. aeruginosa(22.2%),E. coli(18.8%),Enterobacter cloacae
(9.1%),Acinetobacterspp. (6.2%), andSerratia(5.5%). The investigators found a greater
than fourfold increase in the prevalence of multidrug resistance (defined as
resistance to at least one extended-spectrum cephalosporin, one aminoglycoside
and ciprofloxacin) forP. aeruginosaandAcinetobacterspp. (20). - Cost: Cost becomes a relatively minor consideration when a patient’s life is at stake.
Moreover, the cost of antimicrobial agents is relatively minor compared to the cost of
other modalities (including newer biological agents such as activated protein C) and
the total cost of ICU stay. Nevertheless, the cost of antimicrobial therapy is far from
trivial and, moreover, newer agents can be extremely expensive compared with the
tried-and-true old standbys. Examples include the cost of linezolid or daptomycin
versus generic vancomycin for MRSA and MRSE infections and the cost of lipid
formulations of amphotericin B versus amphotericin B deoxycholate. It therefore
behooves prescribing physicians to be broadly familiar with which agents are the
most cost-effective. Many hospitals provide this information in a general way (e.g., $,
$$, $$$, or $$$$), since indicating the exact cost presents problems for both the
hospital and the prescriber.
DE-ESCALATION: LIMITING THE DURATION OF BROAD-SPECTRUM THERAPY
Except in the direst emergencies, appropriate specimens should be obtained for cultures before
instituting empiric antimicrobial therapy. While a thorough discussion of appropriate
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