JAC Advance Access originally published online on May 12, 2006
Journal of Antimicrobial Chemotherapy 2006 58(2):478; doi:10.1093/jac/dkl193
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Correspondence |
Comment on: Empirical antibiotic monotherapy for febrile neutropenia: systematic review and meta-analysis of randomized controlled trials
Department of Infectious Diseases, Infection Control and Employee Health, The University of Texas M.D. Anderson Cancer Center Houston, TX, USA
*Corresponding author. Tel: +1-713-792-6830; Fax: +1-713-745-6839; E-mail: krolston{at}mdanderson.org
Keywords: febrile neutropenia , monotherapy , ceftazidime
Sir,
The meta-analysis conducted by Paul et al.1 regarding empirical antibiotic monotherapy for febrile neutropenia illustrates the dangers of relying on such analyses to make therapeutic recommendations in an area characterized by rapid changes. We are particularly concerned with the conclusions that ceftazidime is suitable as monotherapy in such patients. In the meta-analysis, the authors included studies in which a glycopeptide was part of the regimen if it was administered in all arms of the study and considered this approach to be ‘monotherapy’ based on current guidelines issued by the Infectious Diseases Society of America (IDSA).2 Having helped co-author these guidelines, we wish to point out that monotherapy is defined as the use of a ‘single’ broad-spectrum agent whereas the use of broad-spectrum ß-lactams with vancomycin is considered combination therapy. Current epidemiological trends indicate that Gram-positive organisms account for 44–76% of documented bacterial infections in neutropenic patients.3–6 By the authors own account, several agents including cefepime, piperacillin/tazobactam and the carbapenems offer better Gram-positive coverage than ceftazidime. Considering glycopeptide/ß-lactam combinations as monotherapy is a serious methodological flaw which obscures the advantage of the superior Gram-positive coverage provided by other broad-spectrum agents.
An additional area of concern is that a large number of studies with ceftazidime were conducted before the emergence of extended-spectrum ß-lactamases (ESBLs) as a significant problem [15 of 19 studies (79%) with ceftazidime in this analysis were conducted before 2001]. There are reports of increasing resistance to ceftazidime among the Enterobacteriaceae due to ESBLs, which have been detected worldwide and are increasing in frequency. Based on in vitro data from the SENTRY surveillance programme, Jones et al.7 concluded that the carbapenems and fourth-generation cephalosporins represent the best agents for empirical therapy against Klebsiella spp. and Enterobacter spp. which are frequent pathogens in febrile neutropenic patients. Another report from the MYSTIC surveillance programme indicated that the carbapenems were the most active agents against Gram-negative bacilli.8 This meta-analysis demonstrated advantages of carbapenems over ceftazidime including fewer treatment failures and fewer modifications of the original regimen. A recent, evidence-based evaluation of empirical therapy in febrile neutropenic patients does not support the use of ceftazidime monotherapy (without modification) since it was associated with significantly inferior response rates when compared with other antibiotics.9
Selection of appropriate agent(s) for empirical therapy of fever in neutropenic patients is a complex process that continues to evolve.10 Epidemiological trends and susceptibility/resistance patterns vary considerably between institutions. Making general therapeutic recommendations based solely on statistical analysis of old data, without duly considering current epidemiology and resistance patterns, can be misleading. Based on current local information and the proper definition of monotherapy, ceftazidime is not a suitable agent for this indication at our institution. We strongly urge colleagues at other institutions to make therapeutic decisions based on current epidemiological/resistance patterns as well.
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References
1
Paul M, Yahav D, Fraser A, et al. (2006) Empirical antibiotic monotherapy for febrile neutropenia: systematic review and meta-analysis of randomized controlled trials. J Antimicrob Chemother 57:176–89.
2 Hughes WT, Pizzo PA, Wade JC, et al. (1992) Evaluation of new anti-infective drugs for the treatment of febrile episodes in neutropenic patients. Clin Infect Dis 15:Suppl 1, 206–15.
3 Wisplinghoff H, Seifert H, Wenzel RP, et al. (2003) Current trends in the epidemiology of nosocomial bloodstream infections in patients with hematological malignancies and solid neoplasms in hospitals in the United States. Clin Infect Dis 36:1103–10.[CrossRef][Web of Science][Medline]
4 Winston DJ, Lazarus HM, Beveridge RA, et al. (2001) Randomized, double-blind, multicenter trial comparing clinafloxacin with imipenem as empirical monotherapy for febrile granulocytopenic patients. Clin Infect Dis 32:381–90.[CrossRef][Web of Science][Medline]
5 Del Favero A, Menichetti F, Martino P, et al. (2001) A multicenter, double-blind, placebo-controlled trial comparing piperacillin-tazobactam with and without amikacin as empiric therapy for febrile neutropenia. Clin Infect Dis 33:1295–301.[CrossRef][Web of Science][Medline]
6 Yadegarynia D, Tarrand J, Raad I, et al. (2003) Current spectrum of bacterial infections in cancer patients. Clin Infect Dis 37:1144–5.[CrossRef][Web of Science][Medline]
7 Jones RN, Biedenbach DJ, Gales AC. (2003) Sustained activity and spectrum of selected extended-spectrum ß-lactams (carbapenems and cefepime) against Enterobacter spp. and ESBL-producing Klebsiella spp.: report from the SENTRY antimicrobial surveillance program (USA, 1997–2000). Int J Antimicrob Agents 21:1–7.[CrossRef][Web of Science][Medline]
8 Masterton RG and Turner PJ. (2006) Trends in antimicrobial susceptibility in UK centres: the MYSTIC Programme (1997–2002). Int J Antimicrob Agents 27:69–72.[CrossRef][Web of Science][Medline]
9 Glasmacher A, von Lilienfeld- Toal M, Schulte S, et al. (2005) An evidence-based evaluation of important aspects of empirical antibiotic therapy in febrile neutropenic patients. Clin Microbiol Infect 11:Suppl 5, 17–23.
10 Rolston KVI. (2005) Challenges in the treatment of infections caused by gram-positive and gram-negative bacteria in patients with cancer and neutropenia. Clin Infect Dis 40:S246–52.
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  M. Paul, A. Fraser, and L. Leibovici Empirical antibiotic monotherapy for febrile neutropenia: systematic review and meta-analysis of randomized controlled trials: authors' response J. Antimicrob. Chemother., August 1, 2006; 58(2): 479 - 480. [Full Text] [PDF]
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