Patel, Robin

AbstractIncreasing rates of chronic wound infections caused by antibiotic‐resistant bacteria are a crisis in healthcare settings. Biofilms formed by bacterial communities in these wounds create a complex environment, enabling bacteria to persist, even with antibiotic treatment. Wound infections caused by methicillin‐resistant Staphylococcus aureus (MRSA) are major causes of morbidity in clinical practice. There is a need for new therapeutic interventions not based on antibiotics. Hydrogen peroxide (H2O2) is a known antibacterial/antibiofilm agent, continuous delivery of which has been challenging. A conductive electrochemical scaffold (e‐scaffold) is developed, which is composed of carbon fabric that electrochemically reduces dissolved oxygen into H2O2 when polarized at −0.6 VAg/AgCl, as a novel antibiofilm wound dressing material. In this study, the in vitro antibiofilm activity of the e‐scaffold against MRSA is investigated. The developed e‐scaffold efficiently eradicates MRSA biofilms, based on bacterial quantitation and ATP measurements. Moreover, imaging hinted at the possibility of cell‐membrane damage as a mechanism of action. These results suggest that an H2O2‐generating e‐scaffold may be a novel platform for eliminating MRSA biofilms without using antibiotics and may be useful to treat chronic MRSA wound infections.

As a result of its being inexpensive, easy to perform, fast and accurate, matrix-assisted laser desorption ionization time-of-flight mass spectrometry (MALDI-ToF MS) is quickly becoming the standard means of bacterial identification from cultures in clinical microbiology laboratories. Its adoption for routine identification of yeasts and even dimorphic and filamentous fungi in cultures, while slower, is now being realized, with many of the same benefits as have been recognized on the bacterial side. In this review, the use of MALDI-ToF MS for identification of yeasts, and dimorphic and filamentous fungi grown in culture will be reviewed, with strengths and limitations addressed.

Diagnosis of persistent infection at the time of reimplantation for staged revision of infected arthroplasties is challenging. Implant sonication culture for the diagnosis of prosthetic joint infection (PJI) has improved sensitivity compared to standard periprosthetic tissue culture.

Abstract Background The BioFire FilmArray Gastrointestinal Panel (BioFire Diagnostics) (GIP) is a multiplex stool PCR test that detects 22 organisms. Studies in adults suggest that the diagnostic yield of the GIP in hospitalized patients is low. The utility of the GIP among hospitalized pediatric patients and indications for diagnostic stewardship of this test are not well described. Methods We conducted a retrospective chart review of hospitalized pediatric patients who had a GIP ordered between October 2015 and October 2017. Demographic, clinical, and laboratory information was extracted from the medical record. Statistical analysis was completed using JMP Pro 13.0.0 (SAS Institute Inc.). Results Over the 2-year study period, 193 GIPs were obtained on 155 individual pediatric patients. The mean patient age was 8 years and 59% were male. Forty-four percent of patients were immunocompromised and 21% had inflammatory bowel disease. The pediatric infectious disease (PID) team was consulted in 15% of patients at the time the test was ordered. The overall positivity rate of the GIP for one or more pathogens was 42% (Figure 1), with 76% of GIPs positive for one, 23% for two, and 1% for three pathogens. No parasitic infections were diagnosed. The GIP was more likely to be positive if GI symptom onset was prior to admission (48% vs. 24%, P = 0.004), if GI symptoms had been present for < 2 weeks vs. ≥2 weeks (52% vs. 20%, P = 0.0001), and if GI symptoms were the primary reason for the hospital admission (50% vs. 32%, P = 0.012). Only Clostridioides difficile or viral pathogens were detected in patients whose symptoms began in the hospital (Figure 2). Among patients with a positive test, 40% received treatment targeted at one or more of the detected pathogens (Figure 1). Enteropathogenic E.coli (EPEC) and Enteroaggregative E.coli (EAEC) were never treated (Figure 3). Conclusion The GIP was positive for one or more pathogens in 42% of hospitalized children for whom the test was ordered, and led to specific therapy in 40% of those with a positive test. EPEC and EAEC were not treated. The diagnostic yield of the GIP was higher if GI symptoms were present for <2 weeks, began before hospitalization, and were the primary reason for admission. The GIP was frequently obtained without guidance from the PID team. Disclosures R. Patel, CD Diagnostics, BioFire, Curetis, Merck, Hutchison Biofilm Medical Solutions, Accelerate Diagnostics, Allergan, and The Medicines Company: Grant Investigator, Research grant – monies paid to Mayo Clinic. Curetis, Specific Technologies, Selux Dx, GenMark Diagnostics, PathoQuest and Genentech: Consultant and Scientific Advisor, Consulting fee – monies paid to Mayo Clinic. ASM and IDSA: Travel reimbursement and editor’s stipends, Travel reimbursement and editor’s stipends. NBME, Up-to-Date and the Infectious Diseases Board Review Course: Varies, Honoraria. Mayo Clinic: Employee, Salary.

Abstract Background Achieving appropriate therapy for BSI caused by Gram-negative rods (GNR) is challenging. The availability of AST results allows de-escalation from broad- to narrow-spectrum agents. De-escalation is a goal of antimicrobial stewardship (AS). Through the analysis of inpatient BL antibiotic regimens in a nationwide cohort of patients with Escherichia coli and Klebsiella pneumoniae BSI, we compared the relative spectrum of empiric and definitive treatments to AST results and identified opportunities for de-escalation. Methods Using a cohort of patients hospitalized within VHA, we identified patients with a blood culture positive for E. coli or K. pneumoniae between 2006 and 2015. We analyzed the subset of patients receiving inpatient BLs before and after Gram stain (GS) and AST results. BLs were grouped into five tiers of increasing spectrum, both with and without a requirement for anaerobic activity (Figure 1). Tiers of BLs across the treatment periods were summarized and compared with the lowest-spectrum tier with an active agent. Rates of inactive, optimal, and overly broad BL therapy were summarized by organism and treatment period. Results Of 36,531 BSI identified, we analyzed a subset of 10,825 (7,100 E. coli, 3,725 K. pneumoniae) that met our inclusion criteria (Figure 2). The use of inactive BL agents decreased across time, falling from 11% in early empiric to 4.5% in definitive treatments. The proportion of patients receiving the narrowest available effective BL therapy (“optimal” therapy) increased from 5% to 8% after GS results and to 14% after AST results (Figure 3). De-escalation to optimal therapy after AST results was observed in only 7% of opportunities. If anaerobic activity was required, a smaller proportion of cases would be considered overtreated in the empiric periods (45–46%), but de-escalation after AST results was observed in only 10% of these cases. Conclusion Changes in BL agents across treatment periods reflect an escalation to active treatment, but the absence of de-escalation after AST results was available. This was true both with and without considering a need for anaerobic activity. Expansion of this analysis to include additional classes such as fluoroquinolones may reveal opportunities for AS and de-escalation to optimal therapy in the treatment of E. coli and K. pneumoniae BSI. Disclosures R. Patel, CD Diagnostics, BioFire, Curetis, Merck, Hutchison Biofilm Medical Solutions, Accelerate Diagnostics, Allergan, and The Medicines Company: Grant Investigator, Research grant – monies paid to Mayo Clinic. Curetis, Specific Technologies, Selux Dx, GenMark Diagnostics, PathoQuest and Genentech: Consultant and Scientific Advisor, Consulting fee – monies paid to Mayo Clinic. ASM and IDSA: Travel reimbursement and editor’s stipends, Travel reimbursement and editor’s stipends. NBME, Up-to-Date and the Infectious Diseases Board Review Course: Varies, Honoraria. Mayo Clinic: Employee, Salary. R. Banerjee, Accelerate Diagnostics, Biomerieux, BioFire: Grant Investigator, Research grant and Research support.

We previously demonstrated that shotgun metagenomic sequencing can detect bacteria in sonicate fluid, providing a diagnosis of prosthetic joint infection (PJI). A limitation of the approach that we used is that data analysis was time-consuming and specialized bioinformatics expertise was required, both of which are barriers to routine clinical use.