Comparison of daptomycin and glycopeptide efficacy and safety for the treatment of Gram-positive infections: a systematic review and meta-analysis

Author:

Boulekbache Abdelwahab1,Maldonado Fanny2,Kavafian Raphael2,Ferry Tristan345,Bourguignon Laurent467,Goutelle Sylvain467ORCID,Lega Jean-Christophe1246,Garreau Romain467ORCID

Affiliation:

1. Service hospitalo-universitaire de pharmacotoxicologie, Hospices Civils de Lyon , 69310 Pierre-Bénite , France

2. Commission du médicament et des dispositifs médicaux stériles, Hospices Civils de Lyon , Lyon 69008 , France

3. Service de maladie infectieuse, Hospices Civils de Lyon, Groupement Hospitalier Nord , Lyon 69004 , France

4. ISPB-Faculté de Pharmacie de Lyon, Université Claude Bernard Lyon 1 , Lyon , France

5. Centre international de recherche en infectiologie, Univ Lyon, Université Claude Bernard Lyon 1, UMR 1111 , Lyon 69008 , France

6. Laboratoire de Biométrie et Biologie Évolutive, Univ Lyon, Université Claude Bernard Lyon 1, UMR CNRS 5558 , Villeurbanne , France

7. Service de Pharmacie, Hospices Civils de Lyon, Groupement Hospitalier Nord , Lyon 69004 , France

Abstract

Abstract Background The indications of daptomycin have been extended to off-label indications including prosthesis-related infection, and bone and joint infection (BJI). However, efficacy and safety have not been thoroughly demonstrated compared with the standard of care. This systematic review and meta-analysis aimed to compare the treatment effect of daptomycin and glycopeptides for complicated infections. Materials and methods MEDLINE, Embase and Web of Science were searched for randomized controlled trials (RCTs) comparing daptomycin and standard of care for Gram-positive infections, published until 30 June 2021. The primary outcome was defined as all-cause mortality. Secondary outcomes were clinical and microbiological success. The main safety outcome was any severe adverse event (SAE) (grade  ≥3). Results Overall, eight RCTs were included in the meta-analysis, totalling 1095 patients. Six (75%) were in complicated skin and soft-structure infections, one (12.5%) in bacteraemia and one (12.5%) in a BJI setting. Six RCTs used vancomycin as a comparator and two used either vancomycin or teicoplanin. All-cause mortality and clinical cure were not different between groups. The microbiological cure rate was superior in patients who received daptomycin [risk ratio (RR) = 1.17 (95% CI: 1.01–1.35)]. The risk of SAEs [RR = 0.57 (95% CI: 0.36–0.90)] was lower in the daptomycin arm. Conclusions While daptomycin is associated with a significantly lower risk of SAEs and a better microbiological eradication, substantial uncertainty remains about the best treatment strategy in the absence of good-quality evidence, especially in bacteraemia and endocarditis where further RCTs should be conducted.

Publisher

Oxford University Press (OUP)

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