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Daptomycin for endocarditis and/or bacteraemia: a systematic review of the experimental and clinical evidence |
Falagas M E, Giannopoulou K P, Ntziora F, Vardakas K Z |
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CRD summary This review evaluated the effectiveness of daptomycin in the treatment of patients with Gram-positive cocci endocarditis and/or bacteraemia. It concluded that, although daptomycin appeared promising, there was limited clinical evidence available. Given the limitations of the included evidence, the cautious conclusion seems appropriate, but some studies may have been missed. Authors' objectives To evaluated the effectiveness of daptomycin in the treatment of patients with Gram-positive cocci endocarditis and/or bacteraemia. Searching PubMed (1985 to Jan 2007) and Scopus (1986 to 2006) were searched. Search terms were reported. Reference lists of retrieved articles and other relevant papers (not defined) were also searched. Study selection Studies of any design apart from reviews, evaluating the effectiveness and safety of daptomycin as a monotherapy or part of polytherapy, in the treatment of endocarditis (according to DUKE's criteria) or bacteraemia (definitions given) caused by bacteria susceptible to daptomycin, were eligible for inclusion. Case reports and case series had to provide the age, gender, medical history and reason for treatment and/or outcome of the infection. They also had to provide a sufficient duration of treatment considered adequate in patients (1 week or longer).
Where reported, the age of participants ranged from 13 to 92, 55% were men and the duration of therapy ranged from 3 to 91 days. Included patients had a range of comorbidities. All but one of the included studies were case series/reports.
The authors stated that electronic searches were conducted by two independent reviewers, but it is unclear whether the application of inclusion criteria was conducted in duplicate. Assessment of study quality The authors did not state that they assessed validity. Data extraction Outcomes were categorised as cured, improved, failed, dead, the incidence of adverse events and the development of drug resistance during treatment. Definitions were provided.
The authors did not state how data were extracted for the review or how many reviewers performed the data extraction. Methods of synthesis The studies were combined in a narrative synthesis, with the proportion of cases experiencing an outcome determined from the case series and case studies using the total number of cases as the denominator. Results of the randomised controlled trial (RCT) were reported separately, with the proportion in each arm of the trial experiencing an outcome and a p value. Results of the review One RCT of patients with endocarditis and/or bacteraemia, and 19 cases of endocarditis (across 12 publications) and 41 cases of bacteraemia (across 12 publications) were included.
The RCT (n=246 participants) used a computer generated randomisation method and all data were reviewed by an independent committee. However, 93% of the standard therapy group received gentamicin compared to 0.8% in the daptomycin group. Only a small number of enrolled patients had a final diagnosis of endocarditis. The RCT showed no significant difference between daptomycin and standard therapy (antistaphylococcal penicillins or vancomycin) in overall efficacy of the treatment of endocarditis and bacteraemia in patients with Staphylococcus aureus. The treatment also showed no significant difference when patients infected with methicillin-resistant Staphylococcus aureus (MRSA) or methicillin-sensitive Staphylococcus aureus (MSSA) were analysed separately. Patients treated with daptomycin more frequently had elevated creatine kinase levels (6.7% versus 0.9%, p=0.04) but less frequently had renal impairment (6.7% versus 18.1%, p=0.009).
From the case series and case studies, 11 out of 19 patients (58%) with endocarditis and 27 out of 41 patients (66%) with bacteraemia, had a good outcome (not defined) with treatment. Treatment failure was observed in five out of 19 patients (26%) with endocarditis and 14 out of 41 patients (34%) with bacteraemia. Seven patients with endocarditis (39%) and eleven patients with bacteraemia (27%) died. Six patients with bacteraemia were reported to have adverse events (one with elevated creatine kinase levels and five with renal failure). Five patients with endocarditis were reported to have developed adverse events (four with elevated creatine kinase levels and one with deterioration in renal function). Only five isolates developed resistance, all in patients with bacteraemia, though this was poorly assessed. Authors' conclusions Daptomycin appreared to be a promising antibiotic for the treatment of endocarditis and bacteraemia, but there was limited clinical evidence available. CRD commentary The review addressed a clear question with predefined inclusion criteria. Two relevant databases and references were searched, but there was no attempt to locate unpublished data. It was also unclear whether language restrictions were applied, so publication and language bias could not be ruled out. The authors did not state that they assessed validity but they did discuss some methodological issues of the included RCT. Data extraction was conducted in duplicate, but it was unclear whether similar methods were used to reduce error and bias during study selection. Given the limitations of the included evidence, the cautious conclusion seems appropriate. However, given the potential for publication and language bias, some studies may have been missed. Implications of the review for practice and research Practice: The authors stated that daptomycin should be used with caution, preferably when standard treatments have failed, in order to limit resistance and preserve the drug for future use.
Research: The authors stated that the impact of gentamicin on the number of treatment failures needs investigating, as does the potential to reduce the emergence of drug resistance by combining daptomycin with other antibiotics effective against Gram-positive bacteria. In addition, the most appropriate regimen for the treatment of patients with endocarditis due to resistant Gram-positive cocci, and the studies investigating the effectiveness of combination therapy with rifampicin and/or aminoglycosides, are required. Bibliographic details Falagas M E, Giannopoulou K P, Ntziora F, Vardakas K Z. Daptomycin for endocarditis and/or bacteraemia: a systematic review of the experimental and clinical evidence. Journal of Antimicrobial Chemotherapy 2007; 60(1): 7-19 Indexing Status Subject indexing assigned by NLM MeSH Adolescent; Adult; Aged; Aged, 80 and over; Animals; Anti-Bacterial Agents /therapeutic use; Bacteremia /drug therapy /microbiology; Daptomycin /therapeutic use; Disease Models, Animal; Endocarditis, Bacterial /drug therapy /microbiology; Female; Gram-Positive Bacterial Infections /drug therapy /microbiology; Gram-Positive Cocci /drug effects; Humans; Male; Middle Aged; Rabbits; Randomized Controlled Trials as Topic; Rats; Treatment Outcome AccessionNumber 12007006107 Date bibliographic record published 09/08/2008 Date abstract record published 22/07/2009 Record Status This is a critical abstract of a systematic review that meets the criteria for inclusion on DARE. Each critical abstract contains a brief summary of the review methods, results and conclusions followed by a detailed critical assessment on the reliability of the review and the conclusions drawn. |
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