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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:Elasnin is a recently reported antibiofilm agent that is effective against Gram-positive bacteria including methicillin-resistant Staphylococcus aureus (MRSA). Remarkably, we observed that elasnin has a superior activity in eradicating daptomycin-resistant MRSA strain biofilm, with a lower minimum biofilm eradication concentration (MBEC) value of 0.625 μg/mL, compared to 2.5 μg/mL for the wild type. Confocal microscopy further confirmed the higher biofilm eradication on the daptomycin-resistant strain, displaying ∼53% decrease in cell density upon elasnin treatment, while the wild-type strain was only decreased by ∼15%. Quantitative proteomics revealed that the daptomycin-resistant strain has a lower expression of the membrane, cell wall, and extracellular proteins, and also proteins involved in the arginine biosynthesis, pathogenesis, and cell adhesion compared to the wild type, which may result in weaker biofilm development. This study highlights the potential clinical application of elasnin through its superior biofilm eradication activity against a daptomycin-resistant MRSA strain, and revealed the associated processes governing this superior activity through proteomics analysis. IMPORTANCE Due to the increased use of daptomycin for the treatment of MRSA infections, the emergence of daptomycin-resistant strains has become prevalent in recent years. In this study, we discovered that elasnin, a newly reported antibiofilm compound, has a superior activity in eradicating daptomycin-resistant MRSA strain biofilms compared to the wild type. Follow-up analysis revealed the reason behind this superior activity, which is the lower expression of key proteins that play a role in pathogenesis and cell adhesion in the daptomycin-resistant strain, leading to weaker biofilm development. This showcases the potential use of elasnin in clinical settings where daptomycin-resistant strains and biofilm formation are prevalent. Altogether, our study provides new insights into the mechanism of elasnin in MRSA biofilm cells and identified its superior biofilm eradicating activity in the daptomycin-resistant strain.

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.

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

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