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Ciprofloxacin Prophylaxis in Children With Acute Leukemia in an Era of Increasing Antibiotic Resistance

Castagnola, Elio MD, PhD; Moroni, Cristina MD; Bandettini, Roberto MD; Caprino, Daniela MD; Haupt, Riccardo MD

The Pediatric Infectious Disease Journal: May 2013 - Volume 32 - Issue 5 - p 581
doi: 10.1097/INF.0b013e318286f91f
Letters to the Editor

Infectious Diseases UnitIstituto Giannina Gaslini

Laboratory of MicrobiologyIstituto Giannina Gaslini

Home Care ServiceHematology and Oncology UnitIstituto Giannina Gaslini

Epidemiology and Biostatistics SectionIstituto Giannina GasliniGenova, Italy

The authors have no funding or conflicts of interest to disclose.

To the Editors:

We read with great interest the results of the randomized placebo-controlled trial from Laoprasopwattana and coworkers1 regarding the effectiveness of ciproflaxacin prophylaxis for preventing fever in neutropenic children with acute leukemia or lymphoma. In this study, there was a 23% reduction of febrile episodes in patients receiving ciprofloxacin, with a consequent decrease in the number of patients who needed to be treated to prevent 1 febrile episode to 4. In a similar, multicenter study comparing amoxicillin–clavulanate with placebo in a homologous patient population,2 we observed a 21% reduction of febrile events, with a number needed to be treated of 5. What becomes apparent from both studies is that for every 100 neutropenic patients receiving prophylaxis, 75–80 of them are treated unnecessarily to prevent the remaining 20–25 from developing fever and neutropenia. If we consider that the incidence of Gram-negative bacteremia, the most feared complication because of high mortality, generally represents no more than 10–15% of all febrile neutropenic episodes,3 we estimate that we would administer unnecessarily prophylaxis in 96–97 patients to prevent Gram-negative bacteremia in 3–4 patients. This number could still be considered as acceptable, if antibiotic resistance was not an emerging problem. In the Laoprasopwattana study, the proportion of ciprofloxacin resistant Gram-negatives colonizing patients after 2 weeks of intervention was 95%, whereas it was 27% in those randomized to receive placebo.1 To the contrary, in our institution where ciprofloxacin is not administered for prophylaxis, resistance to ciprofloxacin is 17% (25/145) of Gram-negative organisms causing bacteremia in children with cancer during an 8-year period (2004 to 2011). We consider this proportion as worrisome and worth strictly monitoring.4 The prolonged use of fluoroquinolone prophylaxis is associated with appearance of resistant strains,4,5 with the emergence of bacteria displaying cross-resistance to β-lactams, and aminoglycosides. This limits its use for empirical therapy, at least in low-risk conditions. Moreover, there is no proof of its efficacy in repeated episodes of neutropenia.

We believe that now is the time when antibacterial prophylaxis in neutropenic children with cancer should be abandoned at least during chemotherapeutic regimens.

Elio Castagnola, MD, PhD

Cristina Moroni, MD

Infectious Diseases Unit

Istituto Giannina Gaslini

Roberto Bandettini, MD

Laboratory of Microbiology

Istituto Giannina Gaslini

Daniela Caprino, MD

Home Care Service

Hematology and Oncology Unit

Istituto Giannina Gaslini

Riccardo Haupt, MD

Epidemiology and Biostatistics Section

Istituto Giannina Gaslini

Genova, Italy

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1. Laoprasopwattana K, Khwanna T, Suwankeeree P, et al. Ciprofloxacin reduces occurrence of fever in children with acute leukemia who develop neutropenia during chemotherapy. Pediatr Infect Dis J. 2012 Oct 17 [Epub ahead of print] DOI: 10.1097/INF.0b013e3182793610
2. Castagnola E, Boni L, Giacchino M, et al.Infectious Diseases Study Group of the Italian Association of Pediatric Hematology and Oncology. A multicenter, randomized, double blind placebo-controlled trial of amoxicillin/clavulanate for the prophylaxis of fever and infection in neutropenic children with cancer. Pediatr Infect Dis J. 2003;22:359–365
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5. Ng ES, Liew Y, Koh LP, et al. Fluoroquinolone prophylaxis against febrile neutropenia in areas with high fluoroquinolone resistance–an Asian perspective. J Formos Med Assoc. 2010;109:624–631
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