SHORT-COURSE EMPIRIC ANTIBIOTIC THERAPY FOR PATIENTS WITH PULMONARY INFILTRATES IN THE INTENSIVE CARE UNIT

	To the Editor :

Singh and colleagues (1) reported that 72 h of therapy with ciprofloxacine compared with standard antibiotherapy limited antimicrobial resistance, and reduced antimicrobial therapy costs and length of stay in the intensive care unit (ICU) among patients with pulmonary infiltrates. However, some points of the METHODS section of their article could be misleading.

First, according to the study design (Figure 1), patients with a clinical pulmonary infection score (CPIS)  6 (low likelihood of pneumonia [2]) were randomized and received antibiotics for different periods. A lower limit for CPIS was not indicated as an exclusion criteria. Treating patients in the study who only demonstrated diffuse infiltrate at pulmonary radiography with at least 72 h of antibiotics could be inappropriate.

Second, among patients with follow-up films (64 of 81), percentages of complete film resolution of pulmonary infiltrate after 5 to 7 d of antibiotherapy (Table 4) compared with the other film evolution (partial resolution, unchanged or worsening) were significantly higher in the experimental group than in the standard therapy group (16 of 30 versus 9 of 34; p < 0.03). We hypothesize that a predominant reversible pulmonary infiltrate as a result of pulmonary edema (3) in the experimental group may have influenced the study results. A left ventricular acute dysfunction and/or fluid overadministration (4) should have been evaluated and compared in the characteristics of the study groups at enrollment (Table 1), particularly among these elderly postoperative patients with a low likelihood of pneumonia.

Third, the study was interrupted after 81 patients because it was found unethical to continue with such a significant difference between groups, although the calculated sample size was 176 patients. If a physician-blinded study was unfeasible, a preplanned intermediate analysis should have been considered in order to keep the alpha risk at 0.05 in this randomized controlled trial.

Fourth, ciprofloxacine was chosen as empiric therapy because it has in vitro activity against all MRSA. Fluoroquinolone has in vivo antimicrobial resistance among 50% to 100% of MRSA in Europe and the US (5).

In order to reduce antimicrobial resistance and antibiotic costs, we believe that further studies are needed to clarify if pulmonary infiltrate with a low likelihood of pneumonia in ICU requires a systematic short-course empiric antibiotherapy with re-evaluation after 3 d; invasive strategies for diagnostic; or a simple clinical and X-ray daily surveillance with body weight monitoring and noninvasive myocardiac evaluation. Underlying cardiac disease should be equally stratified or at least compared in the different study groups of future randomized clinical trials.

Department of Intensive Critical Care, Côte de Nacre Hospital, Caen, France

1. Singh N, Rogers P, Atwood C, Wagener MM, Yu VL. Short-course empiric antibiotic therapy for patients with pulmonary infiltrates in the intensive care unit. Am J Respir Crit Care Med 2000; 162: 505-511 [Abstract/Free Full Text].

2. Pugin J, Auckenthaler R, Mili N, Janssens JP, Lew PD, Suter PM. Diagnosis of ventilator-assisted pneumonia by bacteriologic and nonbronchoscopic "blind" bronchoalveolar lavage fluid. Am Rev Respir Dis 1991; 143: 1121-1129 [Medline].

3. Singh N, Falestiny MN, Rogers P, Reed MJ, Pularsky J, Norris R, Yu VL. Pulmonary infiltrate in the surgical ICU: prospective assessment of predictors of etiology and mortality. Chest 1998; 114: 1129-1136 [Abstract/Free Full Text].

4. Sun X, Iles M, Weissman C. Physiologic variables and fluid resuscitation in the postoperative intensive care unit patient. Crit Care Med 1993; 21: 555-561 [Medline].

5. Goldstein FW, Acat JF. Epidemiology of quinolone resistance: Europe and North and South America. Drugs 1995;49(Suppl)2:36-42.

	From the Authors :

Dr. Parienti and colleagues have correctly stated that no lower limit for the clinical pulmonary infection score (CPIS) was considered an exclusion criteria. Patients were included if the physicians elected to initiate antibiotics in the presence of a new onset pulmonary infiltrate, regardless of the CPIS. This was precisely the reason for conducting the study. Mere presence of a pulmonary infiltrate is often considered sufficiently worrisome for "possible" pneumonia to warrant initiation of antibiotics.

The proportion of patients at risk for left ventricular dysfunction and number of postoperative patients was not significantly different between the two groups (1). When only the patients who had a follow-up film and who were alive at 5-7 d were included, the complete resolution was not significantly different for experimental as compared to the control group. Regardless, the primary finding of our study that antimicrobial resistance and superinfections were greater in the control group, would not have been influenced by the etiology of the pulmonary infiltrates.

Our choice of ciprofloxacin was based on the fact that coverage against Legionella was deemed desirable since it had been isolated from our water supply and Pseudomonas aeruginosa since it is common etiology of nosocomial pneumonia. We have explicitly stated that the overall approach and not the utilization of a particular antibiotic identified the essence of our strategy.

The efficacy and advantages of empiric antibiotics have been overrated and their disadvantages have gone largely unrecognized. In our study we show that there is considerable morbidity and possibly increased mortality associated with the overuse of antibiotics. We encourage all of those who are impressed by our article to conduct similar studies. Our results now make it ethical to conduct such a study. Interim analyses may be insufficient to prevent premature termination of the study. Patients in the standard therapy group will experience candidemia, MRSA catheter infections, multiply-resistant gram-negative urinary tract infections, superinfections, drug fever, Clostridium difficile colitis, and antibiotic nephrotoxicity under the current strategy of prescribing multiple antibiotics for prolonged duration. Thus, ICU physicians may abandon the current strategy when they see that early and uneventful discharge will occur for their patients randomized to the 3-d monotherapy course. The surprising result was how much harm is unwittingly done to our patients with the well intentioned and universal strategy of expeditious administration of empiric antibiotics to all patients with pulmonary infiltrates.

Veterans' Affairs Medical Center, Pittsburgh, Pennsylvania

1. Singh N, Rogers P, Atwood C, Wagener MM, Yu VL. Short-course empiric antibiotic therapy for patients with pulmonary infiltrates in the intensive care unit. Am J Respir Care Med 2000; 162: 505-511 .