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      Comparison of anti-anaerobic antimicrobial strategies in cancer patients with febrile neutropenia and gastrointestinal symptoms

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          Abstract

          Background

          The current study sought to compare 28-day mortality rates in cancer patients with febrile neutropenia (FN) and gastrointestinal (GI) symptoms who underwent monotherapy using an antibiotic with antipseudomonal and anti-anaerobic activity (piperacillin-tazobactam or a carbapenem) and a group treated with a combination of cefepime-metronidazole.

          Findings

          We performed a prospective cohort study in a single tertiary hospital from October 2009 to August 2011. All consecutive adult cancer patients admitted with FN secondary to intensive chemotherapy and GI symptoms (abdominal pain, diarrhea or perianal pain) were evaluated. Kaplan-Meier curves were used for calculating time-dependent occurence of death. In total, 37 patients with FN and GI symptoms were evaluated (15 in monotherapy arm and 22 in the combination therapy arm). Treatment with combination cefepime and metronidazole resulted in a lower 28-day mortality rate compared with piperacillin-tazobactam or carbapenem monotherapy (0% versus 40%; log-rank P=0.002).

          Conclusions

          Results of the present study suggest a significant reduction in mortality in cancer patients with FN and GI symptoms treated with combination cefepime-metronidazole therapy compared with monotherapy using agents with antipseudomonal and anti-anaerobic activity. Further randomized trials are warranted to confirm the superior results using combination therapy in patients with FN and GI symptoms.

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          Most cited references14

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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.

          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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            The Multinational Association for Supportive Care in Cancer risk index: A multinational scoring system for identifying low-risk febrile neutropenic cancer patients.

            Febrile neutropenia remains a potentially life-threatening complication of anticancer chemotherapy, but some patients are at low risk for serious medical complications. The purpose of this study was to develop an internationally validated scoring system to identify these patients. Febrile neutropenic cancer patients were observed in a prospective multinational study. Independent factors assessable at fever onset, predicting low risk of complications, on a randomly selected derivation set, were assigned integer weights to develop a risk-index score, which was subsequently tested on a validation set. On the derivation set (756 patients), predictive factors were a burden of illness indicating absence of symptoms or mild symptoms (weight, 5; odds ratio [OR], 8.21; 95% confidence interval [CI], 4.15 to 16.38) or moderate symptoms (weight, 3; OR, 3.70; 95% CI, 2.18 to 6.29); absence of hypotension (weight, 5; OR, 7.62; 95% CI, 2.91 to 19.89); absence of chronic obstructive pulmonary disease (weight, 4; OR, 5. 35; 95% CI, 1.86 to 15.46); presence of solid tumor or absence of previous fungal infection in patients with hematologic malignancies (weight, 4; OR, 5.07; 95% CI, 1.97 to 12.95); outpatient status (weight, 3; OR, 3.51; 95% CI, 2.02 to 6.04); absence of dehydration (weight, 3; OR, 3.81; 95% CI, 1.89 to 7.73); and age less than 60 years (weight, 2; OR, 2.45; 95% CI, 1.51 to 4.01). On the validation set, a Multinational Association for Supportive Care in Cancer risk-index score >/= 21 identified low-risk patients with a positive predictive value of 91%, specificity of 68%, and sensitivity of 71%. The risk index accurately identifies patients at low risk for complications and may be used to select patients for testing therapeutic strategies that may be more convenient or cost-effective.
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              Metronidazole is still the drug of choice for treatment of anaerobic infections.

              Metronidazole has been used for the treatment of infections for >45 years and is still successfully used for the treatment of trichomoniasis, amoebiasis, and giardiasis. Anaerobic bacterial infections caused by Bacteroides species, fusobacteria, and clostridia respond favorably to metronidazole therapy. Good clinical results in the treatment of vaginosis due to Gardnerella vaginalis have also been reported. Rates of resistance to metronidazole are still generally low; however, several studies have reported decreased susceptibility among Bacteroides species, as well as different mechanisms of resistance. Metronidazole-resistant Helicobacter pylori strains have been described, but combination therapy (eg, metronidazole, amoxicillin, or clarithromycin plus omeprazole) is still recommended for eradication of this pathogen in patients with gastroduodenal ulcers. Metronidazole is considered to be a cost-effective drug because of its low cost, good activity against pathogenic anaerobic bacteria, favorable pharmacokinetic and pharmacodynamic properties, and minor adverse effects. Metronidazole is still the criterion standard for therapy of anaerobic infections, as was described by Tally and colleagues 35 years ago.
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                Author and article information

                Contributors
                regisgoulartrosa@gmail.com
                rpsantos@hcpa.ufrgs.br
                lgoldani@ufrgs.br
                Journal
                BMC Res Notes
                BMC Res Notes
                BMC Research Notes
                BioMed Central (London )
                1756-0500
                8 September 2014
                8 September 2014
                2014
                : 7
                : 1
                : 614
                Affiliations
                [ ]Graduate Program in Medicine: Medical Sciences, Universidade Federal do Rio Grande do Sul, Porto Alegre, Brazil
                [ ]Infection Control Committee of Hospital de Clínicas, Universidade Federal do Rio Grande do Sul, Porto Alegre, Brazil
                [ ]Infectious Diseases Unit, Hospital de Clínicas de Porto Alegre, Ramiro Barcelos 2350, Room: 700, Porto Alegre, RS 90640-000 Brazil
                Article
                3125
                10.1186/1756-0500-7-614
                4162919
                25196668
                9613fed7-7880-4504-bbe2-16ca5f3cd086
                © Rosa et al.; licensee BioMed Central Ltd. 2014

                This article is published under license to BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution License ( http://creativecommons.org/licenses/by/4.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly credited. The Creative Commons Public Domain Dedication waiver ( http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.

                History
                : 15 August 2014
                : 4 September 2014
                Categories
                Short Report
                Custom metadata
                © The Author(s) 2014

                Medicine
                bacteria,anaerobic,anti-bacterial agents,febrile neutropenia,immunocompromised host
                Medicine
                bacteria, anaerobic, anti-bacterial agents, febrile neutropenia, immunocompromised host

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