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Methicillin-resistant Staphylococcal periprosthetic joint infections can be effectively controlled by systemic and local daptomycin.

ABSTRACT: Methicillin-resistant Staphylococcus remains a serious problem in the treatment of periprosthetic joint infection (PJI). Higher failure rates were reported when vancomycin was used in 2-stage exchange arthroplasty. Therefore a better therapeutic drug is needed to treat PJI caused by methicillin-resistant organisms. The purpose of the study was to evaluate the safety and efficacy of daptomycin when administered in bone cement combined with systemic use for methicillin-resistant Staphylococci PJI.We conducted a retrospective study from January 2010 to December 2012. Twenty-two patients (10 knees and 12 hips) with PJI caused by methicillin-resistant Staphylococcus species underwent 2-stage revision arthroplasty. In the first stage, 10% daptomycin (weight daptomycin per weight bone cement) was incorporated into polymethylmethacrylate bone cement, and systemic daptomycin (6 mg/kg) was administered postoperatively for 14 days. In the second stage, 2.5% w/w daptomycin was used in the bone cement. The minimum follow-up was 2 years or until recurrence of infection.The infecting organisms included methicillin-resistant Staphylococcus aureus in 10 patients, methicillin-resistant Staphylococcus epidermidis in 8 patients and methicillin-resistant coagulase-negative Staphylococci in 4 patients. The mean follow-up duration was 33.7 months (range, 24-51 months). The treatment success rate was 100%. Only one patient developed asymptomatic transient elevation of the creatine phosphokinase level. No patient experienced any adverse effects related to daptomycin such as myositis, rhabdomyolysis, peripheral neuropathy, derangement of liver function, or eosinophilic pneumonia.In this series, no serious adverse events occurred. Our protocol, using daptomycin-impregnated cement combined with short duration of systemic daptomycin, appears to be an effective and safe treatment for methicillin-resistant Staphylococcus PJI.

SUBMITTER: Kuo FC

PROVIDER: S-EPMC4735949 | biostudies-other | 2016

REPOSITORIES: biostudies-other

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Project description:We examined the oxacillin resistance phenotype and genomic structure of staphylococcal cassette chromosome mec (SCCmec) elements from 77 veterinary methicillin-resistant Staphylococcus pseudintermedius (MRSP) isolates. Isolates were characterized by oxacillin broth microdilution, whole-genome sequencing, and bioformatics analysis. Five previously described SCCmec elements, and a sixth novel element, were identified: SCCmec III (also known as II-III), ?SCCmec 57395, and SCCmec NA45 (a SCCmec VII variant), all previously described in MRSP, and SCCmec IVg and SCCmec VT, previously described in both methicillin-resistant Staphylococcus aureus (MRSA) and MRSP. The sixth element was novel and found among nine geographically clustered isolates. This novel pseudostaphylococcal cassette chromosome (?SCCmec KW21) contained a class A mec gene complex but lacked ccr genes. It also harbored heavy metal (cadmium) resistance determinants. The median oxacillin MIC values among ?SCCmec KW21, SCCmec III, and SCCmec VT isolates were significantly higher than those determined for the SCCmec NA45 VII variant isolates and ?SCCmec 57395 and SCCmec IVg isolates. ?SCCmec KW21 was found exclusively in sequence type 497 (ST497), an MRSP clone that is locally successful in Victoria, Australia. Future studies are necessary to determine if this clone has disseminated further afield and if ?SCCmec KW21 has moved into other MRSP lineages or staphylococcal species.IMPORTANCE Staphylococcus pseudintermedius is a significant veterinary pathogen and occasional cause of infections in humans. ?-Lactams are an important group of antimicrobials used to treat staphylococcal infections in humans and animals. However, when staphylococci become methicillin resistant via the acquisition of a mobile genetic element called staphylococcal cassette chromosome mec (SCCmec), they become resistant to all ?-lactams. This study detected a novel SCCmec element among a cluster of methicillin-resistant S. pseudintermedius isolates from animals in Australia. It also detected SCCmec elements in S. pseudintermedius that had high similarity to those identified in methicillin-resistant Staphylococcus aureus, demonstrating how human and animal pathogens can share the same resistance determinants.

Project description:Vancomycin remains the mainstay treatment for methicillin-resistant Staphylococcus aureus (MRSA) bloodstream infections (BSIs) despite increased treatment failures. Daptomycin has been shown to improve clinical outcomes in patients with BSIs caused by MRSA isolates with vancomycin MICs of >1 mg/liter, but these studies relied on automated testing systems. We evaluated the outcomes of BSIs caused by MRSA isolates for which vancomycin MICs were determined by standard broth microdilution (BMD). A retrospective, matched cohort of patients with MRSA BSIs treated with vancomycin or daptomycin from January 2010 to March 2015 was completed. Patients were matched using propensity-adjusted logistic regression, which included age, Pitt bacteremia score, primary BSI source, and hospital of care. The primary endpoint was clinical failure, which was a composite endpoint of the following metrics: 30-day mortality, bacteremia with a duration of ?7 days, or a change in anti-MRSA therapy due to persistent or worsening signs or symptoms. Secondary endpoints included MRSA-attributable mortality and the number of days of MRSA bacteremia. Independent predictors of failure were determined through conditional backwards-stepwise logistic regression with vancomycin BMD MIC forced into the model. A total of 262 patients were matched. Clinical failure was significantly higher in the vancomycin cohort than in the daptomycin cohort (45.0% versus 29.0%; P = 0.007). All-cause 30-day mortality was significantly higher in the vancomycin cohort (15.3% versus 6.1%; P = 0.024). These outcomes remained significant when stratified by vancomycin BMD MIC. There was no significant difference in the length of MRSA bacteremia. Variables independently associated with treatment failure included vancomycin therapy (adjusted odds ratio [aOR] = 2.16, 95% confidence interval [CI] = 1.24 to 3.76), intensive care unit admission (aOR = 2.46, 95% CI = 1.34 to 4.54), and infective endocarditis as the primary source (aOR = 2.33, 95% CI = 1.16 to 4.68). Treatment of MRSA BSIs with daptomycin was associated with reduced clinical failure and 30-day mortality; these findings were independent of vancomycin BMD MIC.

Project description:BackgroundPrevious studies of both clinically-derived and in vitro passage-derived daptomycin-resistant (DAP-R) Staphylococcus aureus strains demonstrated the coincident emergence of increased DAP MICs and resistance to host defense cationic peptides (HDP-R).MethodsIn the present investigation, we studied a parental DAP-susceptible (DAP-S) methicillin-resistant Staphylococcus aureus (MRSA) strain and three isogenic variants with increased DAP MICs which were isolated from both DAP-treated and DAP-untreated rabbits with prosthetic joint infections. These strains were compared for: in vitro susceptibility to distinct HDPs differing in size, structure, and origin; i.e.; thrombin-induced platelet microbicidal proteins [tPMPs] and human neutrophil peptide-1 [hNP-1]; cell membrane (CM) phospholipid and fatty acid content; CM order; envelope surface charge; cell wall thickness; and mprF single nucleotide polymorphisms (SNPs) and expression profiles.ResultsIn comparison with the parental strain, both DAP-exposed and DAP-naive strains exhibited: (i) significantly reduced susceptibility to each HDP (P<0.05); (ii) thicker cell walls (P<0.05); (iii) increased synthesis of CM lysyl-phosphatidylglycerol (L-PG); (iv) reduced content of CM phosphatidylglycerol (PG); and (v) SNPs within the mprF locus No significant differences were observed between parental or variant strains in outer CM content of L-PG, CM fluidity, CM fatty acid contents, surface charge, mprF expression profiles or MprF protein content. An isolate which underwent identical in vivo passage, but without evolving increased DAP MICs, retained parental phenotypes and genotype.ConclusionsTHESE RESULTS SUGGEST: i) DAP MIC increases may occur in the absence of DAP exposures in vivo and may be triggered by organism exposure to endogenous HDPs: and ii) gain-in-function SNPs in mprF may contribute to such HDP-DAP cross-resistance phenotypes, although the mechanism of this relationship remains to be defined.

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Methicillin-resistant Staphylococcal periprosthetic joint infections can be effectively controlled by systemic and local daptomycin.

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