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Reappraisal With Meta-Analysis of the Addition of Gram-Positive Prophylaxis to Fluoroquinolone in Neutropenic Patients

Mario Cruciani, Marina Malena, Oliviero Bosco, Stefano Nardi, Giovanni Serpelloni, Carlo Mengoli

From the Center of Preventive Medicine, Verona; and the Institute of Microbiology, University of Padua, Padua, Italy.

Address reprint requests to Mario Cruciani, MD, Center of Preventive Medicine/HIV Outpatient Clinic, ULSS 20, V Germania, 20-37135 Verona, Italy; e-mail: crucianimario{at}virgilio.it.

Purpose: Past reports and meta-analyses indicate that fluoroquinolones are highly effective in preventing Gram-negative infections in neutropenic cancer patients, but offer inadequate coverage for Gram-positive infections. We evaluated by meta-analysis the efficacy of the addition of antimicrobial agents with enhanced Gram-positive activity to prophylaxis with quinolones.

Materials and Methods: Randomized trials comparing fluoroquinolones alone (ciprofloxacin, ofloxacin, pefloxacin, or norfloxacin) with fluoroquinolone in combination with Gram-positive prophylaxis (rifampin, vancomycin, amoxicillin, roxithromycin, or penicillin) were retrieved. We pooled relative risks (RRs) using a fixed-effects model.

Results: Nine trials (1,202 patients) published between 1993 and 2000 meet inclusion criteria. Compared with fluoroquinolone alone, Gram-positive prophylaxis reduced total bacteremic episodes (RR, 1.54; 95% CI, 1.26 to 1.88), streptococcal infections (RR, 2.20; 95% CI, 1.44 to 3.37), coagulase-negative staphylococcal infections (RR, 1.46; 95% CI, 1.04 to 2.04), and rate of febrile patients (RR 1.08; 95% CI, 1.00 to 1.16). Occurrence of clinically documented infections, unexplained fever, and infectious mortality was similar in the two groups. The addition of Gram-positive prophylaxis, however, significantly increased side effects (RR, 0.46; 95% CI, 0.28 to 0.76). Rifampin use resulted in a higher incidence of undesirable effects.

Conclusion: Considering the lack of cut-clear benefit on some parameters of morbidity and mortality, routine use of Gram-positive prophylaxis is not advisable. This strategy, however, should be particularly valuable in subgroups of patients at high risk of streptococcal infection (eg, those with severe and prolonged neutropenia or mucositis, and those receiving cytarabine). Problems of tolerability and the potential for the emergence of resistant microorganisms should be considered when prescribing prophylaxis with enhanced Gram-positive activity to neutropenic patients.

Part of this study was presented at the 42nd Interscience Conference on Antimicrobial Agents and Chemotherapy, San Diego, CA, September 27–30, 2002.

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