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Antibiotic prophylaxis in neutropenic patients: to be or not to be?
Submit responseVarious trials have shown the efficacy of antibiotic prophylaxis in reducing the incidence of bacterial infections in neutropenic patients following chemotherapy for malignancy. But these trials have not shown any impact in reducing the mortality rates. We need to address the pros and cons of administering prophylactic antibiotic in such cases.
Lack of survival benefit and risk of inducing antibiotic resistance due to irrational use goes against prescribing antibiotic prophylaxis. However benefit of antibiotic prophylaxis as highlighted by the meta analysis [1] cannot be ruled out.
We recommend administering prophylactic antibiotic based on local microbiological data, the efficacy of the antibiotic in question, cost and tolerability for the patient in malignancy. Fluoroquinoles are so far the most favoured group of antibiotics for such condition [2]. The risk:benefit analysis along with rational antibiotic usage should be the priority. With ever increasing threat of Methicillin resistant staphylococcus aureus (MRSA) in the hospital as well as community, development of antibiotic policy at local level will be helpful to prevent hospital-acquired infections in an already debilitated patient as antibiotic prophylaxis is not avoidable.
References:
1.Anat Gafter-Gvili, Abigail Fraser, Mical Paul and Leonard Leibovici . Meta-Analysis: Antibiotic Prophylaxis Reduces Mortality in Neutropenic Patients. Ann Intern Med, May 2, 2006; 144(9): 704 - 704.
2.Lo N, Cullen M. Antibiotic prophylaxis in chemotherapy-induced neutropenia: time to reconsider. Hematol Oncol. 2006 Jun 19; [Epub ahead of print]
Conflict of Interest:
None declared
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Meta-analysis of antibacterial prophylaxis in neutropenic patients
Submit responseSir, in their meta-analysis Gafter-Gvili and co-workers (1) demonstrated that prophylaxis significantly reduced both total and infection-related mortality in neutropenic patients, with an estimated low risk of development of resistance. However, the use of clinical trials (and meta- analysis derived from them) for driving epidemiological data, such as prevalence of antibiotic resistant bacterial strains, may be misleading. Clinical trials use only a subset of the population of cancer patients, i.e. only those eligible for the trial, so the overall prevalence estimates of a particular event (in this case resistance) do not necessarily represent the entire patient population. Moreover, for methodological reasons, in the last years patients cannot be enrolled more than once and therefore, second or third episodes occurring in the same patient are generally missed. This leads to an underestimate of particular events, that, on the contrary, can occur in the everyday practice. Since clinical trials of prophylaxis in neutropenic cancer patients do not routinely collect resistance data or have a too short follow-up to detect emergence of resistance, the risk of resistant strain selection induced by antibacterial prophylaxis can be studied only by means of ad hoc studies.
Fluoroquinolone resistant Gram-negatives have been observed not only in cancer patients receiving prophylaxis (2,3), but also in children who did not received it, but that shared an environment with adults who were receiving ciprofloxacin prophylaxis (4).
We agree that the reductions in mortality, infection rates and incidence of fever in neutropenic cancer patients have important implications that could outweighs the detriments associated with emergence of resistant microorganisms (1). However, since it is an easy bet that after the results of this meta-analysis broad spectrum antibacterial prophylaxis will be administered to an increasing number of patients, we believe that strong recommendations should be given on the activation of careful and continuous monitoring of antibacterial resistance in isolated strains.
1. Gafter-Gvili A, Fraser A, Paul M, Leibovici L. Meta-analysis: antibiotic prophylaxis reduces mortality in neutropenic patients. Ann Intern Med. 2005;142:979-995.
2. Caratalla J, Fernandez-Sevilla A, Dominguez MA et al. Emergence of fluoroquinolone-resistant flora of cancer patients receiving norfloxacin prophylaxis. Antimicrob Agents Chemother 1996; 40: 503–505.
3. Lautenbach E, Fishman NO, Bilker WB et al. Risk factors for fluoroquinolone resistance in nosocomial Escherichia coli and Klebsiella pneumoniae infections. Arch Intern Med 2002; 25: 2469–2477.
4. Castagnola E, Haupt R, Micozzi A, Caviglia I, Testi AM, Giona F, Parodi S, Girmenia C. Differences in the proportions of fluoroquinolone- resistant Gram-negative bacteria isolated from bacteraemic children with cancer in two Italian centres. Clin Microbiol Infect. 2005 Jun;11(6):505-7
Conflict of Interest:
None declared