Citations

Abstract Background Carbapenem-resistant Acinetobacter baumannii (CRAb) is 1 of the most problematic antimicrobial-resistant bacteria. We sought to elucidate the international epidemiology and clinical impact of CRAb. Methods In a prospective observational cohort study, 842 hospitalized patients with a clinical CRAb culture were enrolled at 46 hospitals in five global regions between 2017 and 2019. The primary outcome was all-cause mortality at 30 days from the index culture. The strains underwent whole-genome analysis. Results Of 842 cases, 536 (64%) represented infection. By 30 days, 128 (24%) of the infected patients died, ranging from 1 (6%) of 18 in Australia-Singapore to 54 (25%) of 216 in the United States and 24 (49%) of 49 in South-Central America, whereas 42 (14%) of non-infected patients died. Bacteremia was associated with a higher risk of death compared with other types of infection (40 [42%] of 96 vs 88 [20%] of 440). In a multivariable logistic regression analysis, bloodstream infection and higher age-adjusted Charlson comorbidity index were independently associated with 30-day mortality. Clonal group 2 (CG2) strains predominated except in South-Central America, ranging from 216 (59%) of 369 in the United States to 282 (97%) of 291 in China. Acquired carbapenemase genes were carried by 769 (91%) of the 842 isolates. CG2 strains were significantly associated with higher levels of meropenem resistance, yet non-CG2 cases were over-represented among the deaths compared with CG2 cases. Conclusions CRAb infection types and clinical outcomes differed significantly across regions. Although CG2 strains remained predominant, non-CG2 strains were associated with higher mortality. Clinical Trials Registration. NCT03646227.

Rapid detection of Klebsiella pneumoniae carbapenemase (KPC) in the Klebsiella species is desirable. The MALDI Biotyper® MBT Subtyping Module (Bruker Daltonics) uses an algorithm that detects a peak at ~11,109 m/z corresponding to a protein encoded by the p019 gene to detect KPC simultaneously with organism identification by a matrix-assisted laser desorption ionization–time-of-flight mass spectrometry (MALDI-ToF MS). Here, the subtyping module was evaluated using 795 clinical Klebsiella isolates, with whole genome sequences used to assess for blaKPC and p019. For the isolates identified as KPC positive by sequencing, the overall sensitivity of the MALDI-ToF MS subtyping module was 239/574 (42%) with 100% specificity. For the isolates harboring p019, the subtyping module showed a sensitivity of 97% (239/246) and a specificity of 100%. The subtyping module had poor sensitivity for the detection of blaKPC-positive Klebsiella isolates, albeit exhibiting excellent specificity. The poor sensitivity was a result of p019 being present in only 43% of the blaKPC-positive Klebsiella isolates.

Abstract Aims As antimicrobial resistance is on the rise, treating chronic wound infections is becoming more complex. The presence of biofilms in wound beds contributes to this challenge. Here, the activity of a novel hypochlorous acid (HOCl) producing electrochemical bandage (e-bandage) against monospecies and dual-species bacterial biofilms formed by bacteria commonly found in wound infections was assessed. Methods and results The system was controlled by a wearable potentiostat powered by a 3V lithium-ion battery and maintaining a constant voltage of + 1.5V Ag/AgCl, allowing continuous generation of HOCl. A total of 19 monospecies and 10 dual-species bacterial biofilms grown on polycarbonate membranes placed on tryptic soy agar (TSA) plates were used as wound biofilm models, with HOCl producing e-bandages placed over the biofilms. Viable cell counts were quantified after e-bandages were continuously polarized for 2, 4, 6, and 12 hours. Time-dependent reductions in colony forming units (CFUs) were observed for all studied isolates. After 12 hours, average CFU reductions of 7.75 ± 1.37 and 7.74 ± 0.60 log10 CFU/cm2 were observed for monospecies and dual-species biofilms, respectively. Conclusions HOCl producing e-bandages reduce viable cell counts of in vitro monospecies and dual-species bacterial biofilms in a time-dependent manner in vitro. After 12 hours, >99.999% reduction in cell viability was observed for both monospecies and dual-species biofilms.

Sequencing is increasingly used for infective endocarditis (IE) diagnosis. Here, the performance of 16S rRNA gene PCR/sequencing of heart valves utilized in routine clinical practice was compared with conventional IE diagnostics.

In this study, we report for the first time the in vivo emergence of dual resistance to levofloxacin and rifampin in C. avidum isolated from a patient who received both antibiotics orally in the setting of a salvage debridement and implant retention of an ODRI. Aside from the molecular insights reported here, this study highlights potential limitations of the combination of oral rifampin and levofloxacin in patients undergoing these surgical procedures and the potential need to evaluate specific optimal therapy for emerging ODRI pathogens.

Abstract Background Carbapenemase-producing (CP) Escherichia coli (CP-Ec) are a global public health threat. We aimed to describe the clinical and molecular epidemiology and outcomes of patients from several countries with CP-Ec isolates obtained from a prospective cohort. Methods Patients with CP-Ec were enrolled from 26 hospitals in 6 countries. Clinical data were collected, and isolates underwent whole-genome sequencing. Clinical and molecular features and outcomes associated with isolates with or without metallo-β-lactamases (MBLs) were compared. The primary outcome was desirability of outcome ranking (DOOR) at 30 days after the index culture. Results Of the 114 CP-Ec isolates in Consortium on resistance against carbapenems in Klebsiella and other Enterobacterales-2 (CRACKLE-2), 49 harbored an MBL, most commonly blaNDM-5 (38/49, 78%). Strong regional variations were noted with MBL-Ec predominantly found among patients in China (23/49). Clinically, MBL-Ec were more often from urine sources (49% vs 29%), less often met criteria for infection (39% vs 58%, P = .04), and had lower acuity of illness when compared with non–MBL-Ec. Among patients with infection, the probability of a better DOOR outcome for a randomly selected patient with MBL-Ec as compared with non–MBL-Ec was 62% (95% CI: 48.2–74.3%). Among infected patients, non–MBL-Ec had increased 30-day (26% vs 0%; P = .02) and 90-day (39% vs 0%; P = .001) mortality compared with MBL-Ec. Conclusions Emergence of CP-Ec was observed with important geographic variations. Bacterial characteristics, clinical presentations, and outcomes differed between MBL-Ec and non–MBL-Ec. Mortality was higher among non-MBL isolates, which were more frequently isolated from blood, but these findings may be confounded by regional variations.

AbstractPurposeThis pilot study aimed to use proteomic profiling of sonicate fluid samples to compare host response during Staphylococcus aureus‐associated periprosthetic joint infection (PJI) and non‐infected arthroplasty failure (NIAF) and identify potential novel biomarkers differentiating the two.Experimental designIn this pilot study, eight sonicate fluid samples (four from NIAF and four from S. aureus PJI) were studied. Samples were reduced, alkylated, and trypsinized overnight, followed by analysis using liquid chromatography‐tandem mass spectrometry (LC‐MS/MS) on a high‐resolution Orbitrap Eclipse mass spectrometer. MaxQuant software suite was used for protein identification, filtering, and label‐free quantitation.ResultsPrincipal component analysis of the identified proteins clearly separated S. aureus PJI and NIAF samples. Overall, 810 proteins were identified based on their detection in at least three out of four samples from each group; 35 statistically significant differentially abundant proteins (DAPs) were found (two‐sample t‐test p‐values ≤0.05 and log2fold‐change values ≥2 or ≤−2). Gene ontology pathway analysis found that microbial defense responses, specifically those related to neutrophil activation, to be increased in S. aureus PJI compared to NIAF samples.Conclusion and clinical relevanceProteomic profiling of sonicate fluid using LC‐MS/MS differentiated S. aureus PJI and NIAF in this pilot study. Further work is needed using a larger sample size and including non‐S. aureus PJI and a diversty of NIAF‐types.

AbstractBiofilms formed by antibiotic‐resistant bacteria in wound beds challenge the treatment of wound infections. In this work, the activity of a novel electrochemical bandage (e‐bandage) composed of carbon fabric and controlled by a wearable potentiostat, designed to continuously deliver low amounts of hydrogen peroxide (H2O2), is evaluated against methicillin‐resistant Staphylococcus aureus (MRSA), multidrug‐resistant Pseudomonas aeruginosa (MDR‐PA) and mixed‐species (MRSA and MDR‐PA) wound infections. Wounds created on Swiss Webster mice are infected with the above‐named bacteria and biofilms allow to establish in wound beds for 3 days. e‐Bandages, which electrochemically reduce dissolved oxygen to H2O2 when polarized at −0.6 VAg/AgCl, are placed atop infected wound beds and polarized continuously for 48 h. Polarized e‐bandage treatment results in significant reductions (p <0.001) of both monospecies and mixed‐species wound infections. After e‐bandage treatment, electron microscopy shows degradation of bacterial cells, and histopathology shows no obvious alterations to the inflammatory host response. Blood biochemistries show no abnormalities. Taken all together, results of this work suggest that the described H2O2‐producing e‐bandage can reduce in vivo MRSA, MDR‐PA, and mixed‐species wound biofilms, and should be further developed as a potential antibiotic‐free strategy for treatment of wound infections.

Abstract Antimicrobial resistance (AMR) among bacteria is an escalating public health emergency that has worsened during the COVID-19 pandemic. When making antibiotic treatment decisions, clinicians rely heavily on determination of antibiotic susceptibility or resistance by the microbiology laboratory, but conventional methods often take several days to identify AMR. There are now several commercially available molecular methods that detect antibiotic resistance genes within hours rather than days. While these methods have limitations, they offer promise for optimizing treatment and patient outcomes, and reducing further emergence of AMR. This review provides an overview of commercially available genotypic assays that detect individual resistance genes and/or resistance-associated mutations in a variety of specimen types and discusses how clinical outcomes studies may be used to demonstrate clinical utility of such diagnostics.

Arthroplasty failure is a major complication of joint replacement surgery. It can be caused by periprosthetic joint infection (PJI) or non-infectious etiologies, and often requires surgical intervention and (in select scenarios) resection and reimplantation of implanted devices. Fast and accurate diagnosis of PJI and non-infectious arthroplasty failure (NIAF) is critical to direct medical and surgical treatment; differentiation of PJI from NIAF may, however, be unclear in some cases. Traditional culture, nucleic acid amplification tests, metagenomic, and metatranscriptomic techniques for microbial detection have had success in differentiating the two entities, although microbiologically negative apparent PJI remains a challenge. Single host biomarkers or, alternatively, more advanced immune response profiling-based approaches may be applied to differentiate PJI from NIAF, overcoming limitations of microbial-based detection methods and possibly, especially with newer approaches, augmenting them. In this review, current approaches to arthroplasty failure diagnosis are briefly overviewed, followed by a review of host-based approaches for differentiation of PJI from NIAF, including exciting futuristic combinational multi-omics methodologies that may both detect pathogens and assess biological responses, illuminating causes of arthroplasty failure.