title: Insights and clinical perspectives of daptomycin resistance in Staphylococcus aureus: A review of the available evidence.
abstract: The emergence of glycopeptide reduced susceptibility and resistance in Staphylococcus aureus strains is a growing clinical problem that poses significant clinical challenges in treatment. Its development is a complex and novel process involving many subtle physiological changes in the micro-organism. Daptomycin is the first cyclic lipopeptide approved for clinical use. Unlike most other antimicrobials, a trend towards increased daptomycin resistance has not been reported, although several cases of daptomycin non-susceptibility have been reported. The present review will present the available evidence on daptomycin resistance of S. aureus, with particular attention to its development. In addition to a literature overview, we have compiled the reported cases of daptomycin non-susceptibility to shed light on possible clinical mechanisms of resistance. In the 36 reports describing 62 clinical cases, infections caused by meticillin-resistant S. aureus (MRSA) strains with a vancomycin minimum inhibitory concentration (MIC) between 1mg/L and 2mg/L often led to vancomycin treatment failure, which may be associated with the development of non-susceptibility to daptomycin. Additional evidence suggests that underdosage of daptomycin is an important clinical aspect that merits further study. The current analysis highlights the importance of determining the MIC when using vancomycin to treat patients with severe S. aureus infections and that when failure is suspected, testing for heterogeneous vancomycin-intermediate S. aureus (hVISA) may also be necessary. Whilst further investigation is needed, it can be hypothesised that MRSA strains become hVISA during prolonged bacteraemia, which may predispose to the development of daptomycin resistance.
authors.affiliation: Department of Biomedical and Biotechnological Sciences, MMAR Laboratory, University of Catania, Via Androne 81, 95124 Catania, Italy. Electronic address: stefanis@unict.it.
authors.forename: Stefania
authors.initials: S
authors.lastname: Stefani
authors.affiliation: Department of Biomedical and Biotechnological Sciences, MMAR Laboratory, University of Catania, Via Androne 81, 95124 Catania, Italy.
authors.forename: Floriana
authors.initials: F
authors.lastname: Campanile
authors.affiliation: Department of Biomedical and Biotechnological Sciences, MMAR Laboratory, University of Catania, Via Androne 81, 95124 Catania, Italy.
authors.forename: Maria
authors.initials: M
authors.lastname: Santagati
authors.affiliation: Department of Biomedical and Biotechnological Sciences, MMAR Laboratory, University of Catania, Via Androne 81, 95124 Catania, Italy.
authors.forename: Maria Lina
authors.initials: ML
authors.lastname: Mezzatesta
authors.affiliation: Department of Biomedical and Biotechnological Sciences, MMAR Laboratory, University of Catania, Via Androne 81, 95124 Catania, Italy.
authors.forename: Viviana
authors.initials: V
authors.lastname: Cafiso
authors.affiliation: Medical Department, Novartis Farma SpA, Largo U. Boccioni 1, 21040 Origgio, Italy.
authors.forename: Giovanni
authors.initials: G
authors.lastname: Pacini
mesh_terms: D000900:Anti-Bacterial Agents / Q000494:pharmacology* / Q000627:therapeutic use*; D017576:Daptomycin / Q000494:pharmacology* / Q000627:therapeutic use*; D024881:Drug Resistance, Bacterial; D006801:Humans; D008826:Microbial Sensitivity Tests; D013203:Staphylococcal Infections / Q000188:drug therapy* / Q000453:epidemiology / Q000382:microbiology; D013211:Staphylococcus aureus / Q000187:drug effects* / Q000302:isolation & purification; D017211:Treatment Failure
chemical_list: D000900:Anti-Bacterial Agents; D017576:Daptomycin
keywords: Daptomycin; MRSA; Resistance; β-Lactam