Citations

Abstract Background There are not established clinical breakpoints (CBP) for antifungals against Cryptococcus species; However, the analysis of their MICs using epidemiological cut-off values (ECVs) can help to distinguish wild-type (WT) isolates from non-WT strains that may harbor intrinsic or acquired resistance to antifungals. Herein, we analyze the MIC distribution of antifungals against Cryptococcus spp. isolated over the last decade at our reference laboratory. Methods We conducted a retrospective evaluation of antifungals MICs for Cryptococcus neoformans and Cryptococcus gattii complex isolates from various sources that were processed at the Mayo Clinic Laboratory from November 18, 2011 to June 7, 2021. Antifungal susceptibility testing was performed by the Clinical & Laboratory Standards Institute (CLSI) standards (CLSI M59-ED3:2020). We used recommended ECVs to define if the isolates were WT or non-WT, and described the change in the percentage of WT isolates over time. Results During the study period, C. neoformans was isolated from 632 samples collected from 533 patients. Sample sources included cultures from blood (n=301), cerebrospinal fluid (n=230), respiratory (n=71), and other sources (n=30). The overall percentage of WT isolates for amphotericin B (AMB), 5-flucytosine, and fluconazole were 77%, 98% and 91% respectively with no significant difference based on various sources (Table). We noticed an overall increase in MICs for AMB, with 100% WT isolates in 2011 compared to 79% in 2021. No such increase was seen for fluconazole or 5-Flucytosine (Figure). Irrespective of the source or the year of isolation, WT strains for itraconazole, voriconazole, and posaconazole were consistently > 93%. C. gattii was isolated from 16 samples, and 94% were WT strains for AMB and 100% for the other antifungals. CLSI, Clinical and Laboratory Standard Institute; CSF, cerebrospinal fluid; ECVs, epidemiologic cut-off values. AMB, amphotericin B; FLU, fluconazole; 5FC, 5-flucytosine. Conclusion In the last decade, we have observed an overall increase in MICs of AMB for C. neoformans. The number of WT strains for other antifungals was high and not significantly changed during the study frame. Further studies are needed to identify the clinical implications of these findings. Disclosures Paschalis Vergidis, MD, AbbVie: DSMB|Cidara: Grant/Research Support|Scynexis: Grant/Research Support.

Abstract Background Methicillin-susceptible Staphylococcus aureus (MSSA) bacteremia requires weeks of IV antimicrobial therapy for treatment with antistaphylococcal penicillins (ASP) and first-generation cephalosporins being mainstays of therapy. While effective, use of these agents in the outpatient setting requires frequent dosing along with close toxicity monitoring through the duration of therapy. Ceftriaxone is an appealing alternative given daily dosing and tolerability, but efficacy in this setting remains uncertain. We sought to review outcomes of patients who received ceftriaxone versus an ASP and first-generation cephalosporins for definitive therapy of MSSA bacteremia. Methods Following IRB approval, we reviewed medical records of a retrospective adult cohort diagnosed with MSSA bacteremia treated with ceftriaxone, cefazolin, or an ASP between January 2018 and December 2019 at Mayo Clinic campuses. Treatment was defined as the antibiotic used in the outpatient setting. The primary outcome was 90-day treatment failure, defined as a composite of mortality and microbiologic relapse. Secondary outcomes were 30-day treatment failure and individual components of treatment failure. Multivariable Cox regression analysis was performed to analyze for an association between ceftriaxone use and the primary outcome after adjusting for factors that may also impact outcomes. Kaplan-Meier curves were compared utilizing a log-rank test for survival between groups. Results A total of 223 patients with the accompanying characteristics met study criteria (Table 1). Thirty-seven received ceftriaxone (16.5%) and 186 (83.4%) were treated with cefazolin or an ASP. Ninety and 30-day treatment failure were higher in those treated with ceftriaxone (27%, 8.1%) compared to cefazolin or an ASP (8.6%, 3.8%). Multivariable analysis for risk of 90-day treatment failure revealed a hazard ratio of 2.91 for ceftriaxone (Table 2) and a significant difference in event-free survival for those treated with ceftriaxone compared to cefazolin or an ASP (Figure 1). Conclusion Patients receiving definitive therapy with ceftriaxone for MSSA bacteremia experienced a higher rate of 90 and 30-day treatment failure and a lower rate of event-free survival as compared to those treated with cefazolin or an ASP. Disclosures All Authors: No reported disclosures.

Abstract The diagnosis of Q fever can be challenging and a high index of suspicion is necessary. Within this case series, we highlight the utility of the microbial cell-free DNA next-generation sequencing or Karius Test in the timely diagnosis and management of acute Q fever.

Abstract Background Population-based studies of Staphylococcus aureus bacteremia (SAB) in the United States are limited. We provide a contemporary evaluation of SAB incidence in Olmsted County, Minnesota, from 2006 to 2020. Methods This was a retrospective population-based study of all adult patients with SAB residing in Olmsted County from 1 January 2006 through 31 December 2020. Initial episodes of SAB were identified using the microbiology laboratory databases at both Olmsted Medical Center and Mayo Clinic Rochester. Results Overall, 541 incident SAB cases were identified with a median age of 66.8 (interquartile range, 54.4–78.5) years, and 60.4% were male. Among these cases, 298 (56.2%) were due to methicillin-susceptible S aureus (MSSA) and 232 (43.8%) cases of methicillin-resistant S aureus (MRSA). The overall age- and sex-adjusted SAB incidence rate (IR) was 33.9 (95% confidence interval [CI], 31.0–36.8) cases/100 000 person-years (PY). Males had a higher age-adjusted IR of 46.0 (95% CI, 41.0–51.0) cases/100 000 PY compared to females (IR, 24.4 [95% CI, 21.1–27.7] cases/100 000 PY). Age- and sex-adjusted SAB IRs due to MSSA and MRSA were 18.7 and 14.6 cases/100 000 PY, respectively, and the percentage of incident SAB cases due to MRSA fluctuated across the study period. There was no apparent temporal trend in SAB incidence over the study period (P = .093). Conclusions Our investigation represents the only contemporary population-based study in the United States. Despite the impression that SAB incidence may have increased based on Centers for Disease Control and Prevention surveillance data, our finding of no change in SAB incidence was somewhat unanticipated.

Abstract Although there is a lack of data in trimethoprim-sulfamethoxazole (TMP-SMX) serum monitoring utility for invasive nocardial infections, therapeutic drug monitoring is widely used to optimize dosing and avoid adverse reactions that may cause treatment interruption. We retrospectively reviewed all adults who received TMP-SMX to treat nocardial brain abscess and had SMX serum level testing from 2010 to 2020. Twenty-two patients received treatment with TMP-SMX for Nocardia species brain abscess and 16 (72.7%) had a reported SMX level, with a median patient age of 65.5 years (interquartile range, IQR 59.5–72.5). Compared to those who did not have a documented SMX serum level, patients with SMX levels had a shorter median course of TMP-SMX treatment (322 days [IQR 188–365] vs. 365 [IQR 224–365]; P = .31) and higher therapeutic induction dose (10 [62.5%] vs. 3 [50%]; P = .92). Similarly, they were more frequently on hemodialysis (3 [13.6%] vs. 1 [4.5%]; P = > .99). The median peak level was 158.5 (IQR 120–218) μg/mL, collected at 2 hours (75%) post-administration in the induction phase (81.3%). Patients with documented SMX levels had fewer reported drug toxicity (5 [31.3%] vs. 4 [66.7%]; P = .1) than those without SMX levels. Among the five patients who reported TMP-SMX-related toxicity, 4 (80%) had an SMX peak level >150 μg/mL. There was no difference in the cure, relapse, and death rates among the two groups. While SMX level was not associated with Nocardia species brain abscess cure rates and mortality, most patients with SMX peak >150 μg/mL experienced drug toxicity.

Abstract Clinical significance of a single positive blood culture bottle (SPBCB) with Staphylococcus aureus is unclear. We aimed to assess the significance of an SPBCB by looking at the associated outcomes. We performed a retrospective, multicenter study of patients with an SPBCB with S aureus using data collected from both electronic health records and the clinical microbiology laboratory. Overall, 534 patients with S aureus bacteremia were identified and 118 (22.1%) had an SPBCB. Among cases with an SPBCB, 106 (89.8%) were classified as clinically significant whereas 12 (10.2%) were considered contaminated or of unclear significance. A majority (92.4%) of patients received antibiotic therapy, but patients with clinically significant bacteremia were treated with longer courses (25.9 vs 5.7 days, P < .001). Significant differences in both frequency of echocardiography (65.1% vs 84.6%, P < .001) and infective endocarditis diagnosis (3.8% vs 14.2%, P = .002) were seen in those with an SPBCB compared to those with multiple positive bottles. A longer hospital length of stay and higher 90-day, 6-month, and 1-year mortality rates were seen in patients with multiple positive blood culture bottles. An SPBCB with S aureus was common among our patients. While this syndrome has a more favorable prognosis as compared to those with multiple positive blood cultures, clinicians should remain concerned as it portends a risk of infective endocarditis and mortality.

Abstract Background Although trimethoprim-sulfamethoxazole (TMP-SMX) has consistently demonstrated significant interindividual variability, therapeutic drug monitoring is used to optimize dosing and avoid adverse reactions that may contribute to treatment interruption. While data exists on the use of SMX level monitoring in pneumocystis, there is a lack of data in SMX serum monitoring utility for invasive Nocardia infections. Methods We retrospectively reviewed adults who received TMP-SMX to treat nocardial brain abscess (BA) and underwent SMX testing level from January 2010 to December 2020. Results Overall, 24 patients had Nocardia spp. BA; Twenty-two (91.7%) were treated with TMP-SMX, and 16/22 (72.7%) had a documented SMX serum level. The median age was 64 (IQR 58-69) years, and the majority were males (77.3%). Compared to those who did not have a documented SMX serum level, patients with SMX levels had a higher prevalence of hemodialysis (HD, 42.9% vs. 33%; P=.99) and malignancy (50% vs. 33.3%; P=.65). The most common BA location was the frontal lobe (43.8% vs. 33.3%; P=.99), with a single (68.8% vs. 50%; P=.62) and smaller (1.3 vs. 1.9 cm; P=.58) brain fluid collection, and with fewer midline shift (6.3% vs. 16.7%; P=.48), respectively. The median TMP-SMX duration was 350 days (P=.31). The most common dosing was 2-double strength, three times a day (31.8%). The SMX median level was 158.5 (IQR 120-218) mcg/mL, collected at two hours (75%) post-administration in the induction phase (81.3%). The most common recommendation was to continue therapy based on the level results. Eleven (46%) patients had a level >150 mcg/mL, and 5 (45.5%) reported drug toxicity, including nausea in 3, acute kidney injury in 2, and thrombocytopenia in 2 patients. Ninety-four percent of the patients with SMX levels had surgical intervention for therapeutic purposes vs. 83% of those without it (P=.65). A total of 11 (50%) patients were cured, 3 (18.8%) relapsed, and 2 (12.5%) died. Conclusion Patients with SMX serum level monitoring are more likely to be on HD, during the induction phase and among those with higher and more frequent dosing. About half of patients with SMX levels >150 mcg/mL experienced drug toxicity; however, SMX levels did not impact patient outcome and length of treatment. Disclosures All Authors: No reported disclosures

Abstract Background Staphylococcus aureus bacteremia (SAB) is common and is characterized by high rates of morbidity and mortality. The clinical importance of a single positive blood culture bottle (SPBCB), however, is poorly defined despite it being a frequent laboratory finding. We therefore examined patients with SPBCB to determine its clinical significance and to understand the rationale of current practice. Methods We performed a retrospective, multicenter study of patients with a SPBCB for S. aureus in initial cultures from January 2019 to December 2019 using data collected from both electronic health records and the clinical microbiology laboratory. Results Overall, 534 patients with SAB were identified, and 118 (22.1%) had a SPBCB. Among SPBCB cases, 106 (89.3%) were classified as clinically significant while 12 were considered contaminated or of unclear clinical significance. Baseline characteristics were similar between the groups (Table 1). A majority (92.4%) received antibiotic therapy, but patients with clinically significant bacteremia were treated with a longer antibiotic course (25.9 vs 5.7 days, p< 0.001). Outcomes between those with SPBCB (contaminant vs clinically significant) were similar (Table 2). Of note, while there was no difference in use of echocardiography based on PREDICT criteria between the clinically significant SPBCB vs. the multiple positive blood culture bottles (MPBC) cohorts (Table 3), significant differences were seen in both frequency of echocardiography (65.1% vs. 84.6%, P< 0.001) and IE diagnosis (3.8% vs. 14.2%, P=0.002) for patients in the SPBCB vs. MPBC groups, respectively. In addition, those with MPBC had higher 90-day, 6-month and 1-year mortality rates. Conclusion SPBCB was documented in almost one-quarter of SAB cases and should trigger a thorough investigation as its associated mortality was high and complications, including IE, occurred. Although some SPBCB cases may represent contamination, antibiotic treatment of SPBCB was commonplace. Patients with clinically significant SPBCB were less likely to undergo echocardiography and had a reduced prevalence of an IE diagnosis as compared to those with MPBC. Patients with SPBCB may have a more favorable long-term prognosis as compared to that in patients with MPBC. Disclosures Muhammad R. Sohail, MD, Medtronic (Consultant)Philips (Consultant) Larry M. Baddour, MD, Boston Scientific (Individual(s) Involved: Self): Consultant; Botanix Pharmaceuticals (Individual(s) Involved: Self): Consultant; Roivant Sciences (Individual(s) Involved: Self): Consultant