Ambulatory consolidation chemotherapy for acute myeloid leukemia with antibacterial prophylaxis is associated with frequent bacteremia and the emergence of fluoroquinolone resistant E. Coli

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Abstract

Background

Ambulatory consolidation chemotherapy for acute myeloid leukemia (AML) is frequently associated with bloodstream infections but the spectrum of bacterial pathogens in this setting has not been well-described.

Methods

We evaluated the emergence of bacteremias and their respective antibiotic susceptibility patterns in AML patients receiving ambulatory-based consolidation therapy. Following achievement of complete remission, 207 patients received the first cycle (C1), and 195 the second cycle (C2), of consolidation on an ambulatory basis. Antimicrobial prophylaxis consisted of ciprofloxacin, amoxicillin and fluconazole.

Results

There were significantly more positive blood cultures for E. coli in C2 as compared to C1 (10 vs. 1, p=0.0045); all E. coli strains for which susceptibility testing was performed demonstrated resistance to ciprofloxacin. In patients under age 60 there was a significantly higher rate of Streptococccus spp. bacteremia in C2 vs. C1; despite amoxicillin prophylaxis all Streptococcus isolates in C2 were sensitive to penicillin. Patients with Staphylococcus bacteremia in C1 had significantly higher rates of Staphylococcus bacteremia in C2 (p=0.009, OR=8.6).

Conclusions

For AML patients undergoing outpatient-based intensive consolidation chemotherapy with antibiotic prophylaxis, the second cycle is associated with higher rates of ciprofloxacin resistant E. coli, penicillin-sensitive Streptococcus bacteremias and recurrent Staphylococcus infections.

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Most cited references 33

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Clinical practice guideline for the use of antimicrobial agents in neutropenic patients with cancer: 2010 Update by the Infectious Diseases Society of America.

Alison Freifeld, Eric Bow, Kent A. Sepkowitz … (2011)

This document updates and expands the initial Infectious Diseases Society of America (IDSA) Fever and Neutropenia Guideline that was published in 1997 and first updated in 2002. It is intended as a guide for the use of antimicrobial agents in managing patients with cancer who experience chemotherapy-induced fever and neutropenia. Recent advances in antimicrobial drug development and technology, clinical trial results, and extensive clinical experience have informed the approaches and recommendations herein. Because the previous iteration of this guideline in 2002, we have a developed a clearer definition of which populations of patients with cancer may benefit most from antibiotic, antifungal, and antiviral prophylaxis. Furthermore, categorizing neutropenic patients as being at high risk or low risk for infection according to presenting signs and symptoms, underlying cancer, type of therapy, and medical comorbidities has become essential to the treatment algorithm. Risk stratification is a recommended starting point for managing patients with fever and neutropenia. In addition, earlier detection of invasive fungal infections has led to debate regarding optimal use of empirical or preemptive antifungal therapy, although algorithms are still evolving. What has not changed is the indication for immediate empirical antibiotic therapy. It remains true that all patients who present with fever and neutropenia should be treated swiftly and broadly with antibiotics to treat both gram-positive and gram-negative pathogens. Finally, we note that all Panel members are from institutions in the United States or Canada; thus, these guidelines were developed in the context of North American practices. Some recommendations may not be as applicable outside of North America, in areas where differences in available antibiotics, in the predominant pathogens, and/or in health care-associated economic conditions exist. Regardless of venue, clinical vigilance and immediate treatment are the universal keys to managing neutropenic patients with fever and/or infection.

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Levofloxacin to prevent bacterial infection in patients with cancer and neutropenia.

Pietro Martino, B Allione, … (2005)

The prophylactic use of fluoroquinolones in patients with cancer and neutropenia is controversial and is not a recommended intervention. We randomly assigned 760 consecutive adult patients with cancer in whom chemotherapy-induced neutropenia (<1000 neutrophils per cubic millimeter) was expected to occur for more than seven days to receive either oral levofloxacin (500 mg daily) or placebo from the start of chemotherapy until the resolution of neutropenia. Patients were stratified according to their underlying disease (acute leukemia vs. solid tumor or lymphoma). An intention-to-treat analysis showed that fever was present for the duration of neutropenia in 65 percent of patients who received levofloxacin prophylaxis, as compared with 85 percent of those receiving placebo (243 of 375 vs. 308 of 363; relative risk, 0.76; absolute difference in risk, -20 percent; 95 percent confidence interval, -26 to -14 percent; P=0.001). The levofloxacin group had a lower rate of microbiologically documented infections (absolute difference in risk, -17 percent; 95 percent confidence interval, -24 to -10 percent; P<0.001), bacteremias (difference in risk, -16 percent; 95 percent confidence interval, -22 to -9 percent; P<0.001), and single-agent gram-negative bacteremias (difference in risk, -7 percent; 95 percent confidence interval, -10 to -2 percent; P<0.01) than did the placebo group. Mortality and tolerability were similar in the two groups. The effects of prophylaxis were also similar between patients with acute leukemia and those with solid tumors or lymphoma. Prophylactic treatment with levofloxacin is an effective and well-tolerated way of preventing febrile episodes and other relevant infection-related outcomes in patients with cancer and profound and protracted neutropenia. The long-term effect of this intervention on microbial resistance in the community is not known. Copyright 2005 Massachusetts Medical Society.

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Meta-analysis: antibiotic prophylaxis reduces mortality in neutropenic patients.

Abigail Fraser, Anat Gafter-Gvili, Mical Paul … (2005)

Bacterial infections are a major cause of illness and death in patients who are neutropenic after chemotherapy treatment for cancer. Trials have shown the efficacy of antibiotic prophylaxis in decreasing the incidence of bacterial infections but not in reducing mortality rates. To evaluate whether antibiotic prophylaxis in neutropenic patients reduces mortality and incidence of infection and to assess related adverse events. The Cochrane Cancer Network register of trials (2004), The Cochrane Library (Issue 4, 2004), EMBASE (1980-2004), MEDLINE (1966-2004), and references of identified studies. Randomized, controlled trials comparing antibiotic prophylaxis with placebo or no intervention or another antibiotic in afebrile neutropenic patients. Two reviewers independently appraised the quality of trials and extracted data. Ninety-five trials performed between 1973 and 2004 met inclusion criteria. Fifty-two trials addressed quinolone prophylaxis. Antibiotic prophylaxis significantly decreased the risk for death when compared with placebo or no treatment (relative risk, 0.67 [95% CI, 0.55 to 0.81]). All prophylactic antibiotics were associated with an increased risk for adverse events (relative risk, 1.69 [CI, 1.14 to 2.50]). Fluoroquinolone prophylaxis reduced the risk for all-cause mortality (relative risk, 0.52 [CI, 0.35 to 0.77]), as well as infection-related mortality, fever, clinically documented infections, and microbiologically documented infections. Fluoroquinolone prophylaxis increased the risk for harboring bacilli resistant to the specific drug after treatment and adverse events, but these results were not statistically significant (relative risks, 1.69 [CI, 0.73 to 3.92]) and 1.30 [CI, 0.61 to 2.76], respectively). Most trials involved patients with hematologic cancer. Data on all-cause mortality were missing in 10 of 50 trials comparing prophylaxis with no prophylaxis. Effect estimates were larger in trials of unclear methodologic quality compared with trials of adequate methodologic quality. Antibiotic prophylaxis for neutropenic patients undergoing cytotoxic therapy reduces mortality. Mortality was substantially reduced when analysis was limited to fluoroquinolones. Antibiotic prophylaxis, preferably with a fluoroquinolone, should be considered for neutropenic patients.

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Author and article information

Journal

Journal ID (nlm-ta): BMC Infect Dis

Journal ID (iso-abbrev): BMC Infect. Dis

Title: BMC Infectious Diseases

Publisher: BioMed Central

ISSN (Electronic): 1471-2334

Publication date Collection: 2013

Publication date (Electronic): 22 June 2013

Volume: 13

Page: 284

Affiliations

[1 ]Department of Medical Oncology and Hematology, Princess Margaret Hospital, University of Toronto, 610 University Avenue, Rm. 5-109, Toronto, ON M5G 2M9, Canada

[2 ]Division of Infectious Diseases, University Health Network, Toronto, ON, Canada

[3 ]Department of Biostatistics, Princess Margaret Hospital, University of Toronto, 610 University Avenue, Rm. 5-109, Toronto, ON M5G 2M9, Canada

Article

Publisher ID: 1471-2334-13-284

DOI: 10.1186/1471-2334-13-284

PMC ID: 3694510

PubMed ID: 23800256

SO-VID: 733c14c0-5109-47a9-9a36-73d6a903afc1

License:

This is an Open Access article distributed under the terms of the Creative Commons Attribution License ( http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

Ambulatory consolidation chemotherapy for acute myeloid leukemia with antibacterial prophylaxis is associated with frequent bacteremia and the emergence of fluoroquinolone resistant E. Coli

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Microbiology Independent Research Journal (MIR Journal)

Most cited references 33

Clinical practice guideline for the use of antimicrobial agents in neutropenic patients with cancer: 2010 Update by the Infectious Diseases Society of America.

Levofloxacin to prevent bacterial infection in patients with cancer and neutropenia.

Meta-analysis: antibiotic prophylaxis reduces mortality in neutropenic patients.

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