Clement, Josh

Itraconazole is the recommended first-line antifungal agent in blastomycosis treatment. However, pharmacokinetic limitations and adverse drug events may necessitate the use of alternative antifungal agents. The primary objective of the study was to retrospectively describe a cohort of patients with blastomycosis who received voriconazole (as partial or complete therapy), for complete or partial treatment, compared to those who received itraconazole alone. Secondary objectives included rationale for voriconazole selection, treatment response, mortality, and adverse drug events. This retrospective multicenter cohort study included adult patients with proven/probable blastomycosis who received itraconazole or voriconazole. Treatment response was evaluated at one year or end of therapy, whichever came first. Mortality outcomes were assessed within 7 days of the last documented azole dose. Propensity score weighting and subgroup analysis were utilized to control confounding variables between cohorts. A total of 119 patients receiving itraconazole and 25 receiving voriconazole as complete or partial treatment were included. Voriconazole was often selected for CNS involvement or after intolerance to alternative azoles. After propensity score weighting, no significant difference in complete or partial treatment response was observed. Rates of all-cause mortality and blastomycosis-related mortality were numerically higher in the voriconazole cohort. Adverse drug event rates were similar between cohorts; however, discontinuation due to adverse events was more common in the voriconazole cohort. Voriconazole was most utilized for the treatment of blastomycosis in cases with CNS involvement or intolerance to other azoles. A statistically significant difference in response rate was not identified between voriconazole-containing or itraconazole-treated patients; however, given limited sample sizes, further data is needed to assess the equivalency of these agents in the treatment of blastomycosis.

Abstract Background Antibiograms are an important stewardship tool that can inform optimal empiric therapy; most antibiograms are hospital-wide. Unit-specific antibiogram data for unique patient populations including intensive care unit and pediatrics is robust; however, published experience with unit-specific antibiograms in the hematology-oncology (heme-onc) population is limited. These patients are unique because of the common use of antimicrobial prophylaxis, prolonged broad-spectrum antibiotics, and an immunocompromised state. We sought to examine the trends in antibiogram antimicrobial susceptibility over time. Methods This retrospective quality initiative included microbiology results (first isolates per patient per timeframe) from Mayo Clinic Rochester from 2012 to 2022. Eligible cultures were those identified as being obtained from one of 8 hematology, oncology, or bone marrow transplant inpatient units. Agar dilution susceptibility testing and Clinical and Laboratory Standards Institute (CLSI) breakpoints were used. Screening PCRs (eg, VRE PCR) were excluded. Culture and susceptibilities were identified by an EMR based report, compiled annually, and reported for two-year periods. Susceptibility rates were compared using the Chi-square test and Chi-square analysis for trends. Results There were 4 gram-negative and 5 gram-positive organism groups that met CLSI antibiogram criteria of ≥ 30 isolates and were included (tables 1-4). There were several significant differences in comparison to the hospital-wide antibiogram, with lower antibiotic susceptibility rates in the heme-onc units for multiple organisms, notably fluoroquinolones to E.coli and P. aeruginosa and several cephalosporins to Enterobacterales as well as penicillin and levofloxacin to Viridans group Streptococcus and vancomycin to E. faecium (tables 1&2). Over the period of 2012-2013 to 2021-2022, susceptibility rates remained stable among the heme-onc antibiogram, with few significant changes (tables 3&4). Conclusion Heme-onc antibiograms illustrated susceptibility rate differences compared to our hospital-wide antibiograms, particularly for antimicrobials used as prophylaxis. Through population-specific antibiograms, providers may be able to improve empiric antibiotic selection. Disclosures Christina G. Rivera (O'Connor), Pharm.D, Gilead Sciences: Board Member

Abstract Nocardiosis is an uncommon yet potentially devastating infection. Nocardia tends to affect individuals with chronic lung disease or immunocompromising conditions, 2 groups increasing in number. Incidence of nocardiosis is likely to increase as well, and it is vital to have an approach to this complex disease. Here, we aim to review the presentation, diagnosis, and management of Nocardia in the modern era. We will also highlight areas of uncertainty in our understanding of nocardiosis and propose a general approach to nocardiosis therapy, accounting for response and tolerance of Nocardia treatment.

ABSTRACT Campylobacter fetus is known to cause human disease, particularly in elderly and immunocompromised hosts. There are limited published data for antimicrobial susceptibility patterns with this organism, and no interpretive criteria are available. We reviewed antimicrobial susceptibilities of C. fetus isolates tested at a tertiary care center and reference laboratory over an 11-year period. C. fetus isolates from patients treated at Mayo Clinic and those sent as referrals for identification and susceptibility were included. Antimicrobial susceptibility testing was performed using agar dilution for ciprofloxacin, doxycycline, erythromycin, gentamicin, meropenem, and tetracycline. Geographic distribution, culture source, organism minimal inhibitory concentration (MIC) distributions, and MIC 50 and MIC 90 were examined. Excluding duplicates, 105 unique isolates were identified from 110 positive cultures. Blood cultures represented the most common source, followed by body fluids, skin and soft tissue, and central nervous system. Gentamicin and meropenem had favorable MIC 50 and MIC 90 of 1 µg/mL. Ciprofloxacin demonstrated an MIC 50 of 1 µg/mL; however, the MIC 90 was >2 µg/mL. Erythromycin demonstrated MIC 50 and MIC 90 of 2 µg/mL. Tetracycline and doxycycline were tested on a limited number of isolates and showed a wide range of MICs. Gentamicin and meropenem demonstrated favorable MICs in C. fetus isolates. These may represent therapeutic options for consideration in serious C. fetus infections, pending susceptibility results. Ciprofloxacin, which showed variable results, may be more appropriate for use only after susceptibility testing. C. fetus interpretive criteria are needed to aid clinicians in selection of both empiric and definitive therapies. IMPORTANCE Our findings contribute to the scant literature on Campylobacter fetus antimicrobial susceptibility test results. We used a reference test method of agar dilution and provide MICs for a large number of organisms and antimicrobial agents.

Abstract Background Asymptomatic patients colonized with Clostridioides difficile are at risk of progressing to C. difficile infection (CDI), but the risk factors associated with progression are poorly defined. The objectives of this study were to identify the prevalence and risk factors to progression of hospital-onset CDI (HO-CDI) among colonized patients. Methods This was a retrospective cohort study conducted at a large academic medical center. Patients were included if they were ≥ 18 years of age and colonized with C. difficile, detected via polymerase chain reaction (PCR) on a rectal swab collected on admission from 2017 to 2020. Patients were excluded if they had prior CDI, CDI symptoms on admission, neutropenia, prior rectal surgery, or were hospitalized for less than 24 hours. CDI toxin positive patients were matched 1:3 to CDI negative patients using PCR colonization test date. The primary endpoints were the prevalence of HO-CDI and the risk factors for progression to HO-CDI. Descriptive analyses were used to describe the population and univariate analysis was used to determine risk factors associated with HO-CDI. Results A total of 2,150 patients were colonized with C. difficile; 109 CDI toxin positive patients were matched to 327 CDI toxin negative patients. 134 patients were included and 3.2% (69/2150) developed HO-CDI. The median age was 64 and 68 patients (50.7%) were male. Malignancy (OR 2.89, 95% CI: 1.24-6.75; P = 0.01), hospitalization within one month (OR 2.2, 95% CI: 1.1-4.38; P = 0.03), antibiotic use within one month (OR 3.23, 95% CI: 1.59-6.56; P = 0.001), antibiotic use within three months (OR 2.16, 95% CI: 1.07-4.35; P = 0.03), intensive care unit (ICU) admission (OR 5.14, 95% CI: 2.47-10.73; P < 0.0001), immunosuppressant use (OR 3.33, 95% CI: 1.14-9.78; P = 0.03), and use of a third generation cephalosporin within three months (OR 4.5, 95% CI: 1.12-18.13; P = 0.03) were associated with HO-CDI. Conclusion Progression to HO-CDI was uncommon among colonized patients at our institution. This data suggests that in hospitalized patients colonized with C. difficile, malignancy, hospitalization within one month, antibiotic use within one or three months, ICU admission, receipt of immunosuppressants, and use of a third generation cephalosporin within three months are associated with HO-CDI. Disclosures All Authors: No reported disclosures.