Antibiotic treatment for Burkholderia cepacia complex in people with cystic fibrosis experiencing a pulmonary exacerbation.

Oct 2012

Horsley A, Jones AM.

Source

School of Translational Medicine, University Hospital of South Manchester, Southmoor Road, Manchester, UK, M23 9LT.

Abstract

BACKGROUND:

Chronic pulmonary infection is one of the hallmarks of lung disease in cystic fibrosis. Infections dominated by organisms of the Burkholderia cepacia complex, a group of at least 17 closely-related species of gram-negative bacteria, are particularly difficult to treat. These infections may be associated with a fulminant necrotising pneumonia, and are greatly feared by patients. Burkholderia cepacia bacteria are innately resistant to many common antibiotics and able to acquire resistance against many more. Since strict patient segregation was introduced to cystic fibrosis medical care, the incidence of the more virulent epidemic strains has fallen, and new infections are more likely to be with environmentally-acquired strains which seem to exhibit less virulence. Nonetheless, exacerbations of respiratory symptoms require effective therapy directed against the dominant bacterial species. Although evidence-based guidelines exist for the treatment of respiratory exacerbations involving Pseudomonas aeruginosa, the most common chronic infection in cystic fibrosis, these cannot be directly extended to Burkholderia cepacia complex infections. The aim of this review is to assess the available trial evidence for choice and application of treatments for Burkholderia cepacia complex infections.

OBJECTIVES:

To assess the effectiveness and safety of different antibiotic regimens in people with cystic fibrosis experiencing an exacerbation, who are chronically infected with organisms of the Burkholderia cepacia complex.

SEARCH METHODS:

We searched the Cochrane Cystic Fibrosis Trials Register, compiled from electronic database searches and handsearching of journals and conference abstract books. We also searched the reference lists of relevant articles and reviews.Date of latest search: 29 November 2011.

SELECTION CRITERIA:

Randomised and quasi-randomised controlled trials of treatments for exacerbations of pulmonary symptoms in cystic fibrosis patients chronically infected with organisms of the Burkholderia cepacia complex.

DATA COLLECTION AND ANALYSIS: No trials were included in this review.

MAIN RESULTS: No trials were included in this review.

AUTHORS' CONCLUSIONS:

Burkholderia cepacia complex infections present a significant challenge for cystic fibrosis clinicians and patients alike. The incidence is likely to increase as the cystic fibrosis population ages and the problem of how to manage and treat these infections becomes more important. There is a lack of trial evidence to guide decision making and no conclusions can be drawn from this review about the optimal antibiotic regimens for cystic fibrosis patients with chronic Burkholderia cepacia complex infections. Clinicians must continue to assess each patient individually, taking into account in vitro antibiotic susceptibility data, previous clinical responses and their own experience. There is a clear need for multi-centre randomised clinical trials to assess the effectiveness of different antibiotic regimens in cystic fibrosis patients infected with organisms of the Burkholderia cepacia complex.

PubMed

Antibiotics for adults with clinically diagnosed acute rhinosinusitis: a meta-analysis of individual patient data.

Antibiotics for adults with clinically diagnosed acute rhinosinusitis: a meta-analysis of individual patient data.

Lancet. 2008 Mar

Young J, De Sutter A, Merenstein D, van Essen GA, Kaiser L, Varonen H, Williamson I, Bucher HC.

Correspondence to: Jim Young, Basel Institute for Clinical Epidemiology, Hebelstrasse 10, University Hospital Basel, CH-4031 Basel, Switzerland

Basel Institute for Clinical Epidemiology, University Hospital Basel, Basel, Switzerland. jyoung@uhbs.ch

BACKGROUND: Primary-care physicians continue to overprescribe antibiotics for acute rhinosinusitis because distinction between viral and bacterial sinus infection is difficult. We undertook a meta-analysis of randomised trials based on individual patients' data to assess whether common signs and symptoms can be used to identify a subgroup of patients who benefit from antibiotics.

METHODS: We identified suitable trials--in which adult patients with rhinosinusitis-like complaints were randomly assigned to treatment with an antibiotic or a placebo--by searching the Cochrane Central Register of Controlled Trials, Medline, and Embase, and reference lists of reports describing such trials. Individual patients' data from 2547 adults in nine trials were checked and re-analysed. We assessed the overall effect of antibiotic treatment and the prognostic value of common signs and symptoms by the number needed to treat (NNT) with antibiotics to cure one additional patient.

FINDINGS: 15 patients with rhinosinusitis-like complaints would have to be given antibiotics before an additional patient was cured (95% CI NNT[benefit] 7 to NNT[harm] 190). Patients with purulent discharge in the pharynx took longer to cure than those without this sign; the NNT was 8 patients with this sign before one additional patient was cured (95% CI NNT[benefit] 4 to NNT[harm] 47). Patients who were older, reported symptoms for longer, or reported more severe symptoms also took longer to cure but were no more likely to benefit from antibiotics than other patients.

INTERPRETATION: Common clinical signs and symptoms cannot identify patients with rhinosinusitis for whom treatment is clearly justified. Antibiotics are not justified even if a patient reports symptoms for longer than 7-10 days.

The Lancet

Antibiotic treatment for Clostridium difficile-associated diarrhea in adults

Antibiotic treatment for Clostridium difficile-associated diarrhea in adults

Cochrane Database Syst Rev. 2007 Jul

Nelson R.
Northern General Hospital, Department of General Surgery, Herries Road, Sheffield, Yorkshire, UK, S5 7AU. altohorn@btinternet.com

BACKGROUND: Clostridium difficile (C. difficile) is recognized as a frequent cause of antibiotic-associated diarrhea and colitis.

OBJECTIVES: The aim of this review is to establish the efficacy of antibiotic therapy for C. difficile-associated diarrhea (CDAD), to identify the most effective antibiotic treatment for CDAD in adults and to determine the need for stopping the causative antibiotic during therapy.

SEARCH STRATEGY: MEDLINE (1966 to 2006), EMBASE (1980 to 2006), Cochrane Central Database of Controlled Trials and the Cochrane IBD Review Group Specialized Trials Register were searched using the following search terms: "pseudomembranous colitis and randomized trial"; "Clostridium difficile and randomized trial"; "antibiotic associated diarrhea and randomized trial".

SELECTION CRITERIA: Only randomized, controlled trials assessing antibiotic treatment for CDAD were included in the review. Probiotic trials are excluded. The following outcomes were sought: initial resolution of diarrhea; initial conversion of stool to C. difficile cytotoxin and/or stool culture negative; recurrence of diarrhea; recurrence of fecal C. difficile cytotoxin and/or positive stool culture; patient response to cessation of prior antibiotic therapy; sepsis; emergent surgery: fecal diversion or colectomy; and death.

DATA COLLECTION AND ANALYSIS: Data were analyzed using the MetaView statistical package in Review Manager. For dichotomous outcomes, relative risks (RR) and 95% confidence intervals (CI) were derived from each study. When appropriate, the results of included studies were combined for each outcome. For dichotomous outcomes, pooled RR and 95% CI were calculated using a fixed effect model, except where significant heterogeneity was detected, at which time the random effects model was used. Data heterogeneity was calculated using MetaView.

MAIN RESULTS: Twelve studies (total of 1157 participants) involving patients with diarrhea who recently received antibiotics for an infection other than C. difficile were included. The definition of diarrhea ranged from at least two loose stools per day with an associated symptom such as rectal temperature > 38 (o)C, to at least six loose stools in 36 hours. Eight different antibiotics were investigated: vancomycin, metronidazole, fusidic acid, nitazoxanide, teicoplanin, rifampin, rifaximin and bacitracin. In paired comparisons, no single antibiotic was clearly superior to others, though teicoplanin, an antibiotic of limited availability and great cost, showed in some outcomes significant benefit over vancomycin and fusidic acid, and a trend towards benefit compared to metronidazole. Only one placebo controlled trial was done and no conclusions can be drawn from it due to small size and classification error. Only one study investigated synergistic antibiotic combination, metronidazole and rifampin, and there was no advantage to the drug combination.

AUTHORS' CONCLUSIONS: Current evidence leads to uncertainty whether mild CDAD needs to be treated. Patients with mild CDAD may resolve their symptoms as quickly without treatment. The only placebo-controlled study shows vancomycin's superior efficacy. However, this result should be treated with caution due to the small number of patients enrolled and the poor methodological quality of the trial. The Johnson study of asymptomatic carriers also shows that placebo is better than vancomycin or metronidazole for eliminating C. difficile in stool during follow-up. If one does decide to treat, then two goals of therapy need to be kept in mind: improvement of the patient's clinical condition and prevention of spread of C. difficile infection to other patients. Given these two considerations, one should choose the antibiotic that brings both symptomatic cure and bacteriologic cure.

In this regard, teicoplanin appears to be the best choice because the available evidence suggests that it is better than vancomycin for bacteriologic cure and has borderline superior effectiveness in terms of symptomatic cure. Teicoplanin is not readily available in the United States, which must be taken into account when making treatment decisions in that country.

Plain language summary

Antibiotic therapy for Clostridium difficile-associated diarrhea (CDAD) needs further investigation.Diarrhea may be a side effect of many commonly used antibiotics, and this is in some cases due to overgrowth of a bacterium called Clostridium difficile (C. difficile) in the colon after other bacteria have been killed. The seriousness of C. difficile-associated diarrhea can range from being a nuisance to a life threatening or even fatal disease. The treatment of CDAD is usually cessation of the initiating antibiotic and immediate administration of a new antibiotic. However each of these three strategies, cessation of the original antibiotic, immediate retreatment, and the choice of a new antibiotic are poorly supported by currently available evidence. The antibiotic that is most tested, vancomycin, is the one most prone to serious side effects. Seven other antibiotics are included in this review and within the limitations of the included studies, they each seem to be as effective as vancomycin.

The Cochrane Library