Citations

ABSTRACT Phenotypic variants of Staphylococcus aureus that display small colonies, reduced pigmentation, and decreased hemolysis and/or coagulase activity are periodically isolated by the clinical laboratory. Antimicrobial susceptibility testing (AST) of these isolates is complicated, because many do not grow on routine AST media, including Mueller-Hinton agar (MHA) and cation-adjusted Mueller-Hinton broth. This multicenter study evaluated cefoxitin disk diffusion for 37 atypical S. aureus isolates (156 readings) with MHA supplemented with 5% sheep's blood (BMHA), using mecA PCR as the reference standard. The correlation of two commercial PBP2a assays with mecA PCR was also assessed. Ten isolates were negative and 27 positive for mecA . No major errors for cefoxitin were observed, but 19.5% very major errors (VMEs) were observed at 24 h of incubation, and 17.2% VMEs were observed at 48 h. The proportions of VMEs ranged from 14.7 to 23.0% at 24 h, and from 13.3 to 17.6% at 48 h, across three testing laboratories. PBP2a tests were performed from growth on BMHA and blood agar plates (BAP), with and without cefoxitin disk induction. The Alere PBP2a SA culture colony test sensitivities for mecA were 90.0% with uninduced growth and 97.4% with induced growth from BMHA. On BAP, sensitivity was 96.0% with induced growth. The sensitivities of the Oxoid PBP2′ latex agglutination test were 85.7% with uninduced growth and 93.9% with induced growth from BMHA and 95.9% with induced growth on BAP. On the basis of these data, we recommend that laboratories perform only mecA PCR and/or PBP2a tests when requested to perform AST on atypical isolates of S. aureus .

Abstract Clinical trial Data and Safety Monitoring Boards (DSMBs) have a primary obligation of ensuring study participant safety, while maintaining trial integrity. The role of DSMBs is expanding, and ideally should include post-hoc reporting of deliberative processes related to clinically important safety issues or factors that could impact on future trial designs. We describe how the TOPCAT DSMB detected, investigated, and adjudicated an unexpectedly large renal adverse event signal midway through the trial, and offer general guidelines for dealing with similar unanticipated occurrences in future trials. The detection of a greater than expected incidence of deterioration in renal function, occurring in 6.1% of patients in the spironolactone arm compared with 3.9% in the placebo arm (P = 0.009), led to an in-depth DSMB review of associated study medication withdrawals and adverse events. The trial continued uninterrupted throughout the review, which reached the conclusions that spironolactone-associated renal dysfunction did not compromise overall patient safety or interfere with a perceived efficacy signal. Although no discrete mechanism for the spironolactone-associated renal adverse event signal was identified, likely possibilities are discussed. In clinical trials, DSMBs and co-ordinating centres should have the resources to detect, investigate, and adjudicate unexpected safety issues, with goals of ensuring patient safety and preserving the potential for detection of therapeutic effectiveness. In TOPCAT, spironolactone-associated renal dysfunction emerged as a potentially trial-threatening adverse event and, although clinically important, did not lead to compromise of patient safety, trial interruption, termination, or apparent loss of treatment effectiveness.

ABSTRACT Staphylococcal prosthetic joint infections (PJIs) are associated with biofilm formation, making them difficult to treat; if managed with debridement and implant retention, rifampin-based therapy is usually employed. Rifampin resistance potentially challenges PJI treatment. In investigating the effects of rifampin monotherapy on methicillin-resistant Staphylococcus aureus (MRSA) foreign-body osteomyelitis in rats, we previously demonstrated that rifampin resistance was selected but that it disappeared 14 days following rifampin monotherapy (1) and that rifampin resistance occurred less frequently following two rounds than following one round of rifampin monotherapy (2). Here, we compared rifampin monotherapy followed by rifampin-vancomycin combination therapy to rifampin-vancomycin combination therapy alone in experimental MRSA foreign-body osteomyelitis. Animals treated with rifampin monotherapy followed by rifampin-vancomycin combination therapy had decreased quantities of bacteria 14 days following treatment completion ( P = 0.034) compared to those in animals treated with combination therapy alone. Additionally, some isolates recovered from animals treated with combination therapy alone, although still susceptible to rifampin, had higher MIC, minimum biofilm-inhibitory concentration (MBIC), and minimum biofilm-bactericidal concentration (MBBC) values than those of the inoculating strain. This suggests that rifampin may remain a feasible treatment option in foreign-body-associated orthopedic infections following the selection of rifampin resistance.

ABSTRACT We developed a rat model of methicillin-resistant Staphylococcus epidermidis (MRSE) foreign body-associated osteomyelitis and used it to compare tedizolid alone and in combination with rifampin against rifampin alone, vancomycin plus rifampin, and vancomycin alone. A clinical strain of MRSE was inoculated into the proximal tibia, and a stainless steel wire with a precolonized MRSE biofilm was implanted. Following a 1-week infection period, 92 rats received either no treatment ( n = 17) or 14 days of intraperitoneal tedizolid ( n = 15), tedizolid plus rifampin ( n = 15), rifampin ( n = 15), vancomycin plus rifampin ( n = 15), or vancomycin ( n = 15). Quantitative bone and wire cultures were performed after treatment completion and also 1 week after infection in a separate group of five rats. The median quantity of staphylococci in bone after the 1-week infection period was 4.89 log 10 CFU/g bone (interquartile range, 3.83 to 5.33 log 10 CFU/g bone); staphylococci were recovered from all associated wires. A median quantity of staphylococci of 3.70 log 10 CFU/g bone was detected in bones of untreated control rats after 3 weeks. Quantities of staphylococci in bones of all treatment groups except the group receiving vancomycin alone (2.78 log 10 CFU/g) were significantly lower than those for untreated controls, with no staphylococci being detected in the groups receiving rifampin monotherapy, tedizolid-plus-rifampin combination therapy, and vancomycin-plus-rifampin combination therapy. Quantities of staphylococci on wires from all treatment groups that included rifampin were significantly lower than those for untreated controls. No resistance to rifampin, tedizolid, or vancomycin was detected. Tedizolid combined with rifampin was active in a rat model of MRSE foreign body-associated osteomyelitis.

ABSTRACT Foreign-body-associated infections are often difficult to treat, given that the associated microorganisms are in a biofilm state. Previously, we showed that a low-amperage direct electrical current (DC) reduces Propionibacterium acnes biofilms formed on implant-associated materials in vitro . In this study, low-amperage DC was compared to ceftriaxone treatment or no treatment in a novel rat femur model of foreign-body osteomyelitis. A platinum implant seeded with a P. acnes biofilm (10 7 CFU/cm 2 ) and 10 9 CFU of planktonic P. acnes was placed in the femoral medullary cavity. One week later, rats were assigned to one of three treatment groups: no treatment, ceftriaxone treatment, or 200-μA-DC treatment. After 2 weeks of treatment, there were fewer bacteria in the bones of the ceftriaxone group (3.06 log 10 CFU/g of bone [ P = 0.0209]) and the 200-μA-DC group (0.5 log 10 CFU/g [ P = 0.0015]) than in those of the control group (6.58 log 10 CFU/g). The DC-exposed animals exhibited fewer bacteria than the ceftriaxone-treated animals ( P = 0.0330). There were fewer bacteria on the implanted wires in the groups treated with ceftriaxone (0.1 log 10 CFU/cm 2 ) or a 200-μA DC (0.1 log 10 CFU/cm 2 ) than in the control group (2.53 log 10 CFU/cm 2 [ P , 0.0003 for both comparisons]). Low-amperage DC may be useful for treating, or aiding in the treatment of, foreign-body infections caused by P. acnes .

ABSTRACT We recently demonstrated improved sensitivity of prosthetic joint infection (PJI) diagnosis using an automated blood culture bottle system for periprosthetic tissue culture [T. N. Peel et al., mBio 7(1):e01776-15, 2016, https://doi.org/10.1128/mBio.01776-15 ]. This study builds on the prior research by examining the optimal number of periprosthetic tissue specimens required for accurate PJI diagnosis. Current guidelines recommend five to six, which is impractical. We applied Bayesian latent class modeling techniques for estimating diagnostic test properties of conventional culture techniques (aerobic and anaerobic agars and thioglycolate broth) compared to inoculation into blood culture bottles. Conventional, frequentist receiver operating characteristic curve analysis was conducted as a sensitivity analysis. The study was conducted at Mayo Clinic, Rochester, MN, from August 2013 through April 2014 and included 499 consecutive patients undergoing revision arthroplasty from whom 1,437 periprosthetic tissue samples were collected and processed. For conventional periprosthetic tissue culture techniques, the greatest accuracy was observed when four specimens were obtained (91%; 95% credible interval, 77 to 100%), whereas when using inoculation of periprosthetic tissues into blood culture bottles, the greatest accuracy of diagnosis was observed when three specimens were cultured (92%; 95% credible intervals, 79 to 100%). Results of this study show that the greatest accuracy of PJI diagnosis is obtained when three periprosthetic tissue specimens are obtained and inoculated into blood culture bottles or four periprosthetic tissue specimens are obtained and cultured using standard plate and broth cultures. Increasing the number of specimens to five or more, per current recommendations, does not improve accuracy of PJI diagnosis.

ABSTRACT The widespread dissemination of carbapenem-resistant Acinetobacter spp. has created significant therapeutic challenges. At present, rapid molecular diagnostics (RMDs) that can identify this phenotype are not commercially available. Two RMD platforms, PCR combined with electrospray ionization mass spectrometry (PCR/ESI-MS) and molecular beacons (MB), for detecting genes conferring resistance/susceptibility to carbapenems in Acinetobacter spp. were evaluated. An archived collection of 200 clinical Acinetobacter sp. isolates was tested. Predictive values for susceptibility and resistance were estimated as a function of susceptibility prevalence and were based on the absence or presence of beta-lactamase ( bla ) NDM, VIM, IMP, KPC, and OXA carbapenemase genes (e.g., bla OXA-23 , bla OXA-24/40 , and bla OXA-58 found in this study) against the reference standard of MIC determinations. According to the interpretation of MICs, 49% ( n = 98) of the isolates were carbapenem resistant (as defined by either resistance or intermediate resistance to imipenem). The susceptibility sensitivities (95% confidence interval [CI]) for imipenem were 82% (74%, 89%) and 92% (85%, 97%) for PCR/ESI-MS and MB, respectively. Resistance sensitivities (95% CI) for imipenem were 95% (88%, 98%) and 88% (80%, 94%) for PCR/ESI-MS and MB, respectively. PRIMERS III establishes that RMDs can discriminate between carbapenem resistance and susceptibility in Acinetobacter spp. In the context of a known prevalence of resistance, SPVs and RPVs can inform clinicians regarding the best choice for empiric antimicrobial therapy against this multidrug-resistant pathogen.

Abstract In 2001, The American Association of Immunologists Committee on the Status of Women conducted a survey examining the percentage of women faculty members within immunology departments or women in immunology graduate programs across 27 institutions in the United States, comparing it to the percentage of women receiving a Ph.D. Here, we examine the representation of women across these same 27 immunology departments and programs to examine changes in gender equity over the last 15 years.