Staphylococcus epidermidis is the most important pathogen in infections related to implanted foreign materials, especially prosthetic joint infections (PJIs). The aim of this study was to investigate the antimicrobial activities of 16 antibiotics against S. epidermidis isolated from PJIs, with special focus on rifampicin and rpoB variability. Ninety-one per cent of the isolates were multiresistant (i.e. resistant to members of more than three classes of antibiotics). Thirty-nine per cent were resistant to rifampicin, associated with one or two single-nucleotide polymorphisms (SNPs) in rpoB. Using IsoSensitest agar with supplements, 61% were resistant to oxacillin, and using Mueller-Hinton II agar with supplement, 84% were resistant. Using the Etest, 58% were resistant to cefoxitin, and using the disk diffusion test, 91% were resistant. The mecA gene was detected in 85% of the isolates. Regarding recently available antibiotics, all isolates were susceptible to tigecycline and linezolid, and 97% were susceptible to daptomycin. In addition, two novel antibiotics, dalbavancin and ceftobiprole, were tested, although not yet available for routine use. The MIC(50) and MIC(90) values of these novel antibiotics were 0.032 and 0.047 mg/L and 0.5 and 1.5 mg/L, respectively. Among the other antibiotics, the rates of resistance varied between 0% (vancomycin) and 82% (trimethoprim-sulphamethoxazole). S. epidermidis strains causing PJIs often show multiresistance, including resistance to rifampicin, which is mainly caused by one or two SNPs. Some of the newer antimicrobial agents may provide alternatives for monotherapy or combination therapy with rifampicin. Detection of mecA is necessary before initiating treatment of infections due to S. epidermidis when it displays intermediate susceptibility to cefoxitin.
Further knowledge about the clinical and microbiological characteristics of prosthetic joint infections (PJIs) caused by different coagulase-negative staphylococci (CoNS) may facilitate interpretation of microbiological findings and improve treatment algorithms. Staphylococcus capitis is a CoNS with documented potential for both human disease and nosocomial spread. As data on orthopaedic infections are scarce, our aim was to describe the clinical and microbiological characteristics of PJIs caused by S. capitis. This retrospective cohort study included three centres and 21 patients with significant growth of S. capitis during revision surgery for PJI between 2005 and 2014. Clinical data were extracted and further microbiological characterisation of the S. capitis isolates was performed. Multidrug-resistant (≥3 antibiotic groups) S. capitis was detected in 28.6 % of isolates, methicillin resistance in 38.1 % and fluoroquinolone resistance in 14.3 %; no isolates were rifampin-resistant. Heterogeneous glycopeptide-intermediate resistance was detected in 38.1 %. Biofilm-forming ability was common. All episodes were either early post-interventional or chronic, and there were no haematogenous infections. Ten patients experienced monomicrobial infections. Among patients available for evaluation, 86 % of chronic infections and 70 % of early post-interventional infections achieved clinical cure; 90 % of monomicrobial infections remained infection-free. Genetic fingerprinting with repetitive sequence-based polymerase chain reaction (rep-PCR; DiversiLab®) displayed clustering of isolates, suggesting that nosocomial spread might be present. Staphylococcus capitis has the potential to cause PJIs, with infection most likely being contracted during surgery or in the early postoperative period. As S. capitis might be an emerging nosocomial pathogen, surveillance of the prevalence of PJIs caused by S. capitis could be recommended.
Carbapenem antibiotics are one of the last-resort agents against multidrug-resistant (MDR) bacteria. The occurrence of carbapenemase-producing Enterobacteriaceae (CPE) in wastewater and aquatic environments is an indication of MDR bacteria in the community. This study evaluated CPE in aquatic environments and compared them to the local hospital isolates in Sweden. Phenotypic and genotypic analyses of antibiotic resistance of environmental and clinical CPE were performed. The relatedness of the isolates and possible clonal dissemination was evaluated using phylogenetic and phyloproteomic analysis. Klebsiella oxytoca carrying carbapenemase genes (bla, bla) were isolated from wastewater and the recipient river, while K. oxytoca (bla) and Klebsiella pneumoniae (bla, bla, bla, bla) were isolated from patients at the local clinics or hospital. The K. oxytoca classified as sequence type 172 (ST172) isolated from the river was genotypically related to two clinical isolates recovered from patients. The similarity between environmental and clinical isolates suggests the dispersion of bla producing K. oxytoca ST172 from hospital to aquatic environment and the likelihood of its presence in the community. This is the first report of CPE in aquatic environments in Sweden; therefore, surveillance of aquatic and hospital environments for CPE in other urban areas is important to determine the major transfer routes in order to formulate strategies to prevent the spread of MDR bacteria.
Staphylococcus epidermidis is a versatile agent, being both a commensal and a nosocomial pathogen usually with an opportunistic role in association with implanted foreign body materials. Pre-operative antiseptic preparation is an important strategy for reducing the risk of complications such as surgical site infection (SSI). Currently, the most widely used antiseptics are alcohols, quaternary ammonium compounds (QACs), and the bisbiguanide chlorhexidine. Occurrence of resistance to the latter agent has drawn increasing attention. The aim of this study was to investigate if decreased susceptibility to chlorhexidine among S. epidermidis was present in our setting, a Swedish university hospital. Staphylococcus epidermidis (n = 143), retrospectively collected, were obtained from prosthetic joint infections (PJI) (n = 61), post-operative infections after cardiac surgery (n = 31), and the skin of the chest after routine disinfection prior to cardiac surgery (n = 27). In addition, 24 commensal isolates were included. Minimum inhibitory concentration (MIC) of chlorhexidine was determined on Mueller Hinton agar plates supplemented with serial dilutions of chlorhexidine. Five QAC resistance genes, qacA/B, smr, qacH, qacJ, and qacG, were detected using PCR. Decreased susceptibility to chlorhexidine was found in 54% of PJI isolates, 68% of cardiac isolates, 21% of commensal isolates, and 7% of skin isolates from cardiac patients, respectively. The qacA/B gene was present in 62/143 isolates (43%), smr in 8/143 (6%), and qacH in one isolate (0.7%). The qacA/B gene was found in 52% of PJI isolates, 61% of cardiac isolates, 25% of commensal isolates, and 19% of the skin isolates. In conclusion, decreased susceptibility to chlorhexidine, as well as QAC resistance genes, were prevalent among S. epidermidis isolates associated with deep SSIs.
The use of conventional antibiotics has substantial clinical efficacy, however these vital antimicrobial agents are becoming less effective due to the dramatic increase in antibiotic-resistant bacteria. Novel approaches to combat bacterial infections are urgently needed and bacteriocins represent a promising alternative. In this study, the activities of the two-peptide bacteriocin PLNC8 αβ were investigated against different Staphylococcus spp. The peptide sequences of PLNC8 α and β were modified, either through truncation or replacement of all L-amino acids with D-amino acids. Both Land D-PLNC8 αβ caused rapid disruption of lipid membrane integrity and were effective against both susceptible and antibiotic resistant strains. the D-enantiomer was stable against proteolytic degradation by trypsin compared to the L-enantiomer. Of the truncated peptides, β1-22, β7-34 and β1-20 retained an inhibitory activity. The peptides diffused rapidly (2 min) through the bacterial cell wall and permeabilized the cell membrane, causing swelling with a disorganized peptidoglycan layer. Interestingly, sub-MIC concentrations of PLNC8 αβ substantially enhanced the effects of different antibiotics in an additive or synergistic manner. This study shows that PLNC8 αβ is active against Staphylococcus spp. and may be developed as adjuvant in combination therapy to potentiate the effects of antibiotics and reduce their overall use. Although antibiotics are the most effective treatment against bacteria of the genus Staphylococcus (including the species S. aureus and S. epidermidis), these opportunistic pathogens are one of the leading causes of severe bacterial infections in humans connected to chronic wounds and medical devices, e.g. catheters and prosthetic implants 1. These persistent infections are generally difficult to treat, which increases the risk for bacterial dissemination and development of systemic complications 2,3. Furthermore, considering the gradual increase in antimicrobial resistance, treatment may be even more difficult to achieve as the available options become limited 4. Consequently, there is an urgent need to find new approaches in human medicine against bacterial infections, and bacteriocins represent a promising avenue that requires more consideration 5,6. Bacteriocins are antimicrobial peptides that are produced by most microorganisms that contribute their defence mechanisms. These peptides are divided into class I-V based on their structural characteristics. Class I includes small peptides (<5 kDa) with unusual amino acids, such as lanthionine and β-methyllanthionine that are post-translationally introduced and class II peptides are synthesized in precursor forms and processed (<10 kDa), and includes bacteriocins composed of two peptides (class IIb), such as PLNC8 αβ. Class III bacteriocins are large (>10 kDa) and sensitive to heat, class IV are small (<10 kDa) and circular peptides. Class V are small (<5 kDa), circular or linear peptides that are characterized by containing cross-linkages between cysteine residu...
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