Schuetz, Audrey N.

Abstract Antibiotics are critical complements to the immune response in combatting infection. Anaerobic bacteria are increasingly common causes of infection, and antibiotic resistance of anaerobes has been rising. Most laboratories do not perform antimicrobial susceptibility testing of anaerobes, and even fewer have compiled antibiogram data. Here we investigated antimicrobial susceptibility results of anaerobes from January 2012 to December 2021 obtained from inpatients at Mayo Clinic using reference agar dilution testing. Actinomyces (60–70 isolates annually), Bacteroides fragilis (30–80), Finegoldia magna (40–60), and Cutibacterium acnes (70–110) were included. Penicillin, clindamycin, metronidazole, ertapenem, piperacillin-tazobactam, and moxifloxacin were tested. Clinical and Laboratory Standards (CLSI) breakpoints were followed. B. fragilis showed ≥90% and Actinomyces 100% susceptibility to piperacillin-tazobactam and ertapenem. All F. magna and >95% B. fragilis were susceptible to metronidazole. The most striking fluctuations in percent susceptibility from year to year were observed for clindamycin, with Actinomyces ranging from 66–79%, B. fragilis 34–67%, and F. magna 47–85%. In the absence of local anaerobe antibiograms, providers may refer to such antibiogram data to guide empiric anti-anaerobic therapy at their institutions. In conclusion, anaerobe antibiotic susceptibility patterns must be monitored to ensure appropriate antibiotic empiric therapy and stewardship.

Genotypic testing for mecA / mecC is heavily relied upon for rapid optimization of antimicrobial therapy in infections due to Staphylococcus aureus . Little is known regarding optimal reporting and/or therapy for patients demonstrating lack of genotypic evidence of mecA or mecC but phenotypic oxacillin resistance.

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 susceptibility testing (AST) is a critical function of the clinical microbiology laboratory and is essential for optimizing care of patients with infectious diseases, monitoring antimicrobial resistance (AMR) trends, and informing public health initiatives. Several methods are available for performing AST including broth microdilution, agar dilution, and disk diffusion. Technological advances such as the development of commercial automated susceptibility testing platforms and the advent of rapid diagnostic tests have improved the rapidity, robustness, and clinical application of AST. Numerous accrediting and regulatory agencies are involved in the process of AST and setting and revising breakpoints, including the U.S. Food and Drug Administration and the Clinical and Laboratory Standards Institute. Challenges to optimizing AST include the emergence of new resistance mechanisms, the development of new antimicrobial agents, and generation of new data requiring updates and revisions to established methods and breakpoints. Together, the challenges in AST methods and their interpretation create important opportunities for well‐informed clinicians to improve patient outcomes and provide value to antimicrobial stewardship programs, especially in the setting of rapidly changing and increasing AMR. Addressing AST challenges will involve continued development of new technologies along with collaboration between clinicians and the laboratory to facilitate optimal antimicrobial use, combat the increasing burden of AMR, and inform the development of novel antimicrobials. This updated primer serves to reinforce important principles of AST, and to provide guidance on their implementation and optimization.

Leptotrichia species are anaerobic, Gram-negative bacilli increasingly recognized as pathogens capable of causing invasive infections such as bloodstream infection (BSI), particularly among immunocompromised patients. However, there is a paucity of data regarding epidemiology, antimicrobial susceptibility, optimal treatment, and clinical outcomes among patients with Leptotrichia bacteremia.

Abstract Background Leptotrichia spp. are anaerobic, gram-negative bacilli that are part of the normal oral and intestinal microbiota. Although traditionally considered non-pathogenic, these bacteria can result in invasive infections including bacteremia in immunosuppressed patients, particularly those with neutropenia. There are limited published data to inform best management strategies in those with Leptotrichia bacteremia. Methods All cases of Leptotrichia spp. bacteremia between January 2012 and 2022 at our tertiary academic medical center were retrospectively reviewed to determine patient risk factors, clinical outcomes, and antimicrobial susceptibilities. Descriptive statistical methods were used. Antimicrobial susceptibilities were performed by agar dilution. Results 26 cases of Leptotrichia spp. bacteremia were identified (Figure 1). The mean patient age was 55 years (SD 17), with 9 female patients (35%). All 26 patients were immunocompromised, predominantly due to hematologic malignancy (69%) or hematopoietic stem cell transplant (23%) (HSCT). 25 of 26 patients were actively neutropenic, with a median duration of neutropenia of 21 days (13-26) (Table 1). The most frequent sources of Leptotrichia bacteremia were gastrointestinal translocation (60%), followed by catheter-related infection (35%). 10 patients had polymicrobial bacteremia (38.5%). The primary antibiotics utilized to treat Leptotrichia bacteremia included metronidazole (42%), piperacillin-tazobactam (27%), and carbapenems (19%). Overall, the mean duration of treatment was 11 days, with a 60-day all-cause mortality of 19% (Table 1) with no cases of microbiologic relapse. In the 22 clinical isolates evaluated for susceptibility, Leptotrichia spp. were largely susceptible to metronidazole, penicillin, ertapenem, and piperacillin-tazobactam, but uniformly resistant to moxifloxacin (Table 2). Figure 1:Leptotrichia spp. identified as cause of bacteremia in 26 patientsTable 1:Baseline characteristics of patients with Leptotrichia bacteremia (n=26) between January 2012 to January 2022Table 2:Antimicrobial susceptibility profile of the Leptotrichia spp. (n=22) Conclusion Leptotrichia spp. may be a rare cause of bacteremia in neutropenic hosts, particularly those with underlying hematologic malignancies and HSCT. The pathogen has a favorable susceptibility profile to penicillins and carbapenems, but has high degree of resistance to fluoroquinolones. Disclosures All Authors: No reported disclosures.

Abstract Background We have previously reported on a US based national surveillance study from 6 geographically dispersed medical centers for the susceptibility and epidemiology of C. difficile isolates. This current survey was conducted with isolates collected in 2020-21 with specific attention to the susceptibility to ridinilazole as well as nine comparators. A summary of the susceptibilities of 300 isolates of C. difficile tested against 10 antimicrobial agents Methods in 2020-21 C. difficile isolates or stools from patients with C. difficile toxin positive antibiotic associated diarrhea were collected in 6 US medical centers and referred to a central lab. After confirmation of 300 isolates antibiotic susceptibilities were determined by agar dilution method (CLSI M11-A9) against 10 agents listed in Table below. Ribotyping was performed by PCR capillary gel electrophoresis on all isolates. Results A summary of the susceptibilities of the 300 isolates against 10 antimicrobial agents are shown in the Table. The most common ribotype was 014-020 (14.4% compared to 11.8% in 2016), followed by 106 (10%, compared to 15% in 2016), 027 (10% compared to 13.1% in 2016), 002 (8% compared to 8.5% in 2016, 078-126 (4.3% compared to 1.3% in 2016). Ridinilazole was very potent against all isolates collected in the US with an MIC 90 of 0.25 mcg/ml, including against all the hypervirulent ribotypes as well as those isolates with antibiotic resistances to other antibiotics in the test panel. Conclusion Ridinilazole showed excellent in-vitro activity against C. difficile isolates in the US, independent of ribotype. There has been a striking change in ribotype distribution compared to 2016, accompanied by a reduction in C. difficile resistance to moxifloxacin and imipenem. Disclosures Cheleste M. Thorpe, MD, Actelion: Grant/Research Support|Deinove: Advisor/Consultant|General Mills: Grant/Research Support|Merck: Grant/Research Support|Pfizer: Grant/Research Support|Summit: Advisor/Consultant|Summit: Grant/Research Support Stuart Johnson, M.D., Ferring Pharmaceuticals: Membership on Ferring Publication Steering Committee|Ferring Pharmaceuticals: Employee|Summit Plc: Advisor/Consultant Dale N. Gerding, MD, Destiny Pharma plc.: Advisor/Consultant Karen C. Carroll, MD, Abbott Diagnostics: Advisor/Consultant|BD Diagnostics: Advisor/Consultant|BD Diagnostics: Grant/Research Support|BioRad, Inc: Grant/Research Support|Meridian Biosciences: Grant/Research Support|Roche Diagnostics: Advisor/Consultant|Scanogen, Inc: Advisor/Consultant|Scanogen, Inc: Grant/Research Support|Thermo Fisher, Inc: Advisor/Consultant Kevin W. Garey, PharmD, MS, Acurx: Grant/Research Support|cidara: Advisor/Consultant|cidara: Grant/Research Support|Paratek: Grant/Research Support|Seres Health: Grant/Research Support|Summit: Grant/Research Support Esther Duperchy, PhD, Summit Plc: Employee David R. Snydman, MD, Merck: Advisor/Consultant|Merck and Company: Grant/Research Support|Prolacta: Advisor/Consultant|Prolacta: Grant/Research Support|Seres: Advisor/Consultant|Seres Health: Grant/Research Support|Summit Plc: Grant/Research Support|Takeda: Advisor/Consultant|Takeda: Grant/Research Support|Visterra: Advisor/Consultant.

Multidrug-resistant Pseudomonas aeruginosa isolates are a serious public health concern due to their resistance to nearly all or all of the available antibiotics, including carbapenems. Utilizing molecular approaches in conjunction with antibiotic susceptibility prediction software warrants investigation for use in the clinical laboratory workflow.

Abstract Background We reviewed the scientific literature to gain insight on the epidemiology and outcome of Strongyloides stercoralis infections after transplantation. Methods CINAHL, PUBMED, and OVID/MEDLINE were reviewed from inception through March 31, 2022 using key words Strongyloides and transplantation. Results Our review identified 108 episodes of Strongyloides infection among 91 solid organ transplant (SOT) and 15 hematopoietic cell transplant (HCT) recipients. Median time to infection was 10.8 (range, .14–417) and 8.8 (range, 0–208) weeks after SOT and HCT, respectively. Gastrointestinal symptoms were frequent (86/108 [79.6%]), while skin rash (22/108 [20.3%]) and fever (31/103 [30%]) were less common. Peripheral eosinophilia was observed in half of patients (41/77 [53.2%]). Bacteremia (31/59 [52.5%]) was frequently due to Gram‐negative organisms (24/31 [77.4%]). Abnormal chest radiologic findings were reported in half (56/108 [51.9%]). The majority had hyperinfection syndrome (97/108 [89.8%]) while disseminated strongyloidiasis was less common (11/108 [10.2%]). Thirty‐two cases were categorized as donor‐derived infection (DDI), with donors (23/24 [95.8%]) who had traveled to or lived in endemic areas. Median time to DDI was 8 weeks (range .5–34.3 weeks) after transplantation. Treatment consisted of ivermectin ( n = 26), a benzimidazole ( n = 27), or both drugs ( n = 28). There was high all‐cause mortality (48/107, 44.9%) and a high Strongyloides ‐attributable mortality (32/49, 65.3%). Conclusions Strongyloidiasis should be strongly considered among recipients with epidemiologic risk factors for infection, even in the absence of eosinophilia or rash. A policy that provides guidance on pro‐active screening is needed, to ensure preventive measures are provided to recipients at increased risk.

Elizabethkingia species are Gram-negative bacilli that were most recently linked to a cluster of infections in the Midwestern United States from 2016 to 2017. Inappropriate empirical and directed antibiotic selection for this organism is common among providers and is an independent risk factor for mortality.