Citations

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.

AbstractBackgroundScreening for vancomycin‐resistant Enterococcus (VRE) is performed at many transplant centers, but data on the impact of VRE colonization and bloodstream infection (BSI) on hematopoietic cell transplantation (HCT) outcomes remain conflicting.MethodsConsecutive adults with acute myeloid leukemia who underwent allogeneic HCT between 2004 and 2014 were retrospectively reviewed. Patients were screened by perirectal PCR swabs targeting vanA and vanB twice weekly while inpatient.ResultsOf a total of 203 patients (median age 54 years), 73 (36%) were VRE colonized prior to HCT, 23 (11%) became colonized within the first 100 days, and 107 (53%) remained non‐colonized through day 100 post HCT. A landmark analysis on HCT day 0 revealed no significant difference in overall survival according to pre‐transplant colonization status (P=.20). However, patients with subsequent VRE colonization within the first 100 days of HCT had a significantly worse survival on both univariable (P=.04) and multivariable (P=.03) analyses. During the first 30 days post HCT, 11 (5% of total and 11% of the VRE colonized) patients developed VRE BSI. Ten (91%) of these had screened positive for VRE colonization before the bacteremia. Age ≥60 years, HCT‐comorbidity index ≥3, and VRE colonization were independent risk factors for VRE BSI on multivariable analysis (P=.04, .03, .003, respectively). Only 1 (9%) patient with VRE BSI died within the first 100 days post HCT.ConclusionVRE colonization is a surrogate marker and not an independent predictor of worse outcomes post HCT. VRE BSI is associated with increased morbidity, but does not impact post‐HCT survival.

ABSTRACT We compared tedizolid alone and tedizolid with rifampin to rifampin and vancomycin plus rifampin in a rat model of methicillin-resistant Staphylococcus aureus (MRSA) foreign body-associated osteomyelitis. The study strain was a prosthetic joint infection-associated isolate. Steady-state pharmacokinetics for intraperitoneal administration of tedizolid, vancomycin, and rifampin were determined in uninfected rats. MRSA was inoculated into the proximal tibia, and a wire was implanted. Four weeks later, the rats were treated intraperitoneally for 21 days with tedizolid ( n = 14), tedizolid plus rifampin ( n = 11), rifampin ( n = 16), or vancomycin plus rifampin ( n = 13). Seventeen rats received no treatment. After treatment, quantitative bone cultures were performed. Blood was obtained for determination of drug trough concentrations in the tedizolid and tedizolid plus rifampin groups. The mean peak plasma concentration and mean area under the concentration-time curve from time zero to 24 h for tedizolid were 12 μg/ml and 60 μg · h/ml, respectively. The bacterial loads in all treatment groups were significantly lower than those in the control group; those in the tedizolid- plus rifampin-treated animals were not significantly different from those in the vancomycin- plus rifampin-treated animals. The range of mean plasma trough concentrations in the tedizolid group was 0.44 to 0.73 μg/ml. Although neither tedizolid nor vancomycin resistance was detected in isolates recovered from bones, rifampin resistance was detected in 10 animals (63%) in the rifampin group, 8 animals (73%) in the tedizolid plus rifampin group, and a single animal (8%) in the vancomycin plus rifampin group. Tedizolid alone or tedizolid combined with rifampin was active in a rat model of MRSA foreign body-associated osteomyelitis. The emergence of rifampin resistance was noted in animals receiving tedizolid plus rifampin.

SummaryBackgroundClostridium difficile infection (CDI) may not respond to initial therapy and frequently recurs, but predictors of response and recurrence are inconsistent. The impact of specific alterations in the gut microbiota determining treatment response and recurrence in patients with CDI is unknown.AimTo assess microbial signatures as predictors of treatment response and recurrence in CDI.MethodsPre‐treatment stool samples and clinical metadata including outcomes were collected prospectively from patients with their first CDI episode. Next generation 16s rRNA sequencing using MiSeq Illumina platform was performed and changes in microbial community structure were correlated with CDI outcomes.ResultsEighty‐eight patients (median age 52.7 years, 60.2% female) were included. Treatment failure occurred in 12.5% and recurrence after response in 28.5%. Patients who responded to treatment had an increase in Ruminococcaceae, Rikenellaceae, Clostridiaceae, Bacteroides, Faecalibacterium and Rothia compared to nonresponders. A risk‐index built from this panel of microbes differentiated responders (mean 0.07 ± 0.24) from nonresponders (0.52 ± 0.42; P = 0.0002). Receiver operating characteristic (ROC) curve demonstrated that risk‐index was a strong predictor of treatment response with an area under the curve (AUC) of 0.85. Among clinical parameters tested, only proton pump inhibitor use predicted recurrent CDI (OR 3.75, 95% CI 1.27–11.1, P = 0.01). Patients with recurrent CDI had statistically significant increases in Veillonella, Enterobacteriaceae, Streptococci, Parabacteroides and Lachnospiraceae compared to patients without recurrence and a risk index was able to predict recurrence (AUC = 0.78).ConclusionGut microbiota signatures predict treatment response and recurrence potentially, allowing identification of patients with Clostridium difficile infection that may benefit from early institution of alternate therapies.