Clonal diversity of Cutibacterium acnes (formerly Propionibacterium acnes) in prosthetic joint infections.

Prosthetic joint infections (PJIs) are rare but feared complications following joint replacement surgery. Cutibacterium acnes is a skin commensal that is best known for its role in acne vulgaris but can also cause invasive infections such as PJIs. Some phylotypes might be associated with specific diseases, and recently, a plasmid was detected that might harbour important virulence genes. In this study, we characterized C. acnes isolates from 63 patients with PJIs (n = 140 isolates) and from the skin of 56 healthy individuals (n = 56 isolates), using molecular methods to determine the phylotype and investigate the presence of the plasmid. Single-locus sequence typing and a polymerase chain reaction designed to detect the plasmid were performed on all 196 isolates. No statistically significant differences in sequence types were seen between the two study groups indicating that the C. acnes that causes PJIs originates from the patients own normal skin microbiota. Of the 27 patients with multiple tissue samples, 19 displayed the same sequence types among all their samples. Single-locus sequence typing identified different genotypes among consecutive C. acnes isolates from four patients with recurrent infections. The plasmid was found among 17 isolates distributed in both groups, indicating that it might not be a marker for virulence regarding PJIs. Patients presenting multiple sequence types in tissue samples may represent contamination or a true polyclonal infection due to C. acnes.

In vitro activity of tedizolid and linezolid against Staphylococcus epidermidis isolated from prosthetic joint infections.

Prosthetic joint infections (PJIs) are rare but long-lasting and are serious complications without any spontaneous resolution, requiring additional surgery and long-term treatment with antibiotics. Staphylococci are the most important aetiological agents of PJIs, and among the coagulase-negative staphylococci Staphylococcus epidermidis is the most common. However, S. epidermidis often displays multidrug resistance (MDR), demanding additional treatment options. The objective was to examine the effectiveness of tedizolid and linezolid against S. epidermidis isolated from PJIs. The standard antibiotic susceptibility pattern of S. epidermidis (n = 183) obtained from PJIs was determined by disc diffusion test, and MIC was determined by Etest for tedizolid, linezolid, and vancomycin. Tedizolid displayed MIC values ranging from 0.094 to 0.5 mg/L (MIC50: 0.19 mg/L, MIC90: 0.38 mg/L), linezolid MIC values ranging from 0.25 to 2 mg/L (MIC50: 0.75 mg/L, MIC90: 1 mg/L), and vancomycin MIC values ranging from 0.5 to 3 mg/L (MIC50 and MIC90 both 2 mg/L). According to the disc diffusion test, 153/183 (84%) isolates were resistant to ≥3 antibiotic groups, indicating MDR. In conclusion, S. epidermidis isolates from PJIs were fully susceptible, and the MIC50 and MIC90 values for tedizolid were two- to four-fold dilution steps lower compared with linezolid. Tedizolid is not approved, and there are no reports of long-term treatment, but it may display better tolerability and fewer adverse effects than linezolid; it thus could be a possible treatment option for PJIs, alone or in combination with rifampicin.

Staphylococcus capitis isolated from prosthetic joint infections.

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.

Heterogeneous glycopeptide intermediate Staphylococcus epidermidis isolated from prosthetic joint infections.

Methicillin-resistant Staphylococcus epidermidis (MRSE) poses a major problem in prosthetic joint infections (PJIs). Vancomycin is often considered the drug of choice in the empirical treatment of staphylococcal PJIs. As recent decades have seen reports of heterogeneous glycopeptide intermediate S. aureus (hGISA), our aim was to examine the prevalence of heterogeneous glycopeptide intermediate S. epidermidis (hGISE) in PJIs. S. epidermidis isolates (n = 122) from 119 patients in three Swedish counties between 1993 and 2012 were included. All were isolated from perioperative tissue samples from revision surgery in clinically verified PJIs. Antimicrobial susceptibility testing against staphylococcal antibiotics was performed. The macromethod Etest (MME) and glycopeptide resistance detection (GRD) Etest were used to detect hGISE. Standard minimal inhibitory concentration (MIC) determination revealed no vancomycin-resistant isolates, while teicoplanin resistance was detected in 14 out of 122 isolates (11.5%). hGISE was found in 95 out of 122 isolates (77.9%), 64 out of 67 of isolates with teicoplanin MIC >2 mg/L (95.5%) and 31 out of 55 of isolates with teicoplanin MIC ≤2 mg/L (56.4%). Thus, the presence of hGISE cannot be ruled out by teicoplanin MIC ≤2 mg/L alone. Multidrug resistance was detected in 86 out of 95 hGISE isolates (90.5%) and in 16 out of 27 isolates (59.3%), where hGISE could not be detected. In conclusion, hGISE detected by MME or GRD was common in this material. However, hGISE is difficult to detect with standard laboratory diagnostic routines. Glycopeptide treatment may not be sufficient in many of these PJIs, even if standard MIC classifies the isolated S. epidermidis as susceptible.

Staphylococcal cassette chromosome mec (SCCmec) and arginine catabolic mobile element (ACME) in Staphylococcus epidermidis isolated from prosthetic joint infections.

The aim of the present study was to characterise the staphylococcal cassette chromosome mec (SCCmec) in Staphylococcus epidermidis isolated from prosthetic joint infections (PJIs) and, if possible, assign them to any of the presently known SCCmec types. In addition, the isolates were examined for the presence of the arginine catabolic mobile element (ACME). Sixty-one S. epidermidis isolates obtained from PJIs and 24 commensal S. epidermidis isolates were analysed. The mecA gene was detected in 49 of the 61 (80 %) PJI isolates and in four of the 24 (17 %) commensal isolates, and the composition of the SCCmec was further analysed. SCCmec types I and IV were the most common types among the PJI isolates. However, for over half (57 %) of the isolates, it was not possible to assign an SCCmec type. ACME was detected in eight (13 %) of the PJI isolates and in 14 (58 %) of the commensal isolates. The characterisation of the SCCmec elements revealed a large heterogeneity, with a high frequency of isolates carrying more than one type of the ccr gene complex. ACME was more common among the commensal isolates and may represent a survival benefit for S. epidermidis colonising healthy individuals in the community.

In vitro antimicrobial synergy testing of coagulase-negative staphylococci isolated from prosthetic joint infections using Etest and with a focus on rifampicin and linezolid.

In recent years, coagulase-negative staphylococci (CoNS) have been increasingly recognised as causative agents of various infections, especially in immunocompromised patients and related to implanted foreign body materials. CoNS, and especially Staphylococcus epidermidis, transform into a stationary growth phase and produce biofilm when involved in a foreign body infection, making them difficult to eradicate with antimicrobials. Rifampicin has the ability to penetrate biofilm, but resistance may develop rapidly. To reduce the emergence of resistance, rifampicin should be combined with additional antimicrobials, of which several different ones have been proposed, including the relatively new class of antimicrobials, oxazolidinones, represented by linezolid. Thirty-seven CoNS isolates from patients with prosthetic joint infection were investigated by synergy testing using Etest. Nine antimicrobial combinations, based on either rifampicin or linezolid, were tested. For 16 (43%) of the isolates, a synergistic (n = 5), additive (n = 14) and/or antagonistic (n = 11) effect were identified. In conclusion, Etest is an objective and easily performed in vitro method for antimicrobial synergy testing. However, each isolate requires testing for the specific combination considered for treatment.

Antibiotic susceptibility among Staphylococcus epidermidis isolated from prosthetic joint infections with special focus on rifampicin and variability of the rpoB gene.

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.

Prevalence of the ica operon and insertion sequence IS256 among Staphylococcus epidermidis prosthetic joint infection isolates.

Joint replacement surgery has improved the quality of life for hundreds of thousands of patients. However, the infection of a joint implant is an important and serious complication, though the prevalence is low. Staphylococcus epidermidis is the most important pathogen involved in foreign-body infections. S. epidermidis is also a commensal that comprises a substantial part of the normal skin flora of humans. The possibility to demonstrate potential specific virulence markers may facilitate the interpretation of the bacteriological findings, as well as the clinical decision. The prevalence of the ica locus and insertion sequence IS256 by using polymerase chain reaction (PCR) among 32 clinical S. epidermidis isolates from prosthetic joint infections (PJIs) and 24 commensal isolates from nares and skin was investigated. Sixteen (50%) of the 32 PJI isolates harbored the ica operon compared with one-third of the commensal isolates obtained from the samples of the skin and nares of healthy individuals. The IS256 was demonstrated in 26 (81%) out of 32 PJI isolates. By contrast, IS256 was found in one of 24 commensal isolates. In conclusion, IS256 may be superior to the ica operon as a marker of the invasive capacity of S. epidermidis, since it was found in most of the PJI isolates, but rarely among commensals.

Characterization of coagulase-negative staphylococci isolated from patients with infected hip prostheses: use of phenotypic and genotypic analyses, including tests for the presence of the ica operon.

The aim of this study was to investigate phenotypic and/or genotypic heterogeneity in coagulase-negative staphylococci (CoNS) obtained from multiple tissue samples taken perioperatively during exchange surgery from each of 19 patients with clinically and/or microbiologically proven hip prosthesis infections. CoNS are important pathogens in prosthetic hip joint infections. Several virulence factors have been suggested for CoNS, such as phenotypic variation, yet the pathogenic processes that are involved remain unclear. The PhenePlate system (PhPlate AB, Stockholm Sweden) was used for phenotyping and pulsed-field gel electrophoresis for genotyping of polymorphisms in isolates of CoNS. Furthermore, polymerase chain reaction was used to determine the presence of the icaADB gene complex in the isolates. Some patients were infected with CoNS and other species, some were infected with multiple CoNS species, although infections with Staphylococcus epidermidis alone were most common, and some were infected with different S. epidermidis clones. Phenotypic variation was found among isolates both from the same tissue sample and from different samples from the same patient, and in some cases such variation represented the presence of different clones. One-third of the patients infected with S. epidermidis carried the icaADB genes. CoNS isolates showing phenotypic and/or genotypic heterogeneity were identified in tissue samples from half of the patients. The presence of the intercellular adhesion (ica) operon does not seem to be a prerequisite for establishing infection with CoNS.