981. An Investigation into Possible Nosocomial Clusters and On-Treatment Resistance Patterns in Candidemia

Abstract Background Candidemia has significant clinical implications, due to high rates of mortality and increasing resistance to antifungal drugs. Candida auris shows person-to-person transmission and survival on fomites. We aimed to determine if similar hospital transmission of Candida species, other than C. auris, is occurring. We analyzed candidemia infections for species, geographical, and temporal clusters, and clonality. We also aimed to study resistance patterns in individual patients on antifungal treatment. Here we present our current data from December 2019 – March 2021. Methods Patients with candidemia were identified with the help of the clinical microbiology lab serving an urban health system. Isolates were stored prospectively as glycerol stocks at -80 C. Data were collected by retrospective chart review and described in terms of frequency distributions and percentages. Patient locations within the hospital setting were traced by Infection Prevention. A cluster was defined as the same species being isolated from ≥ 2 patients in the same unit within a 90-day period. Genomic DNA was isolated and whole genome sequencing was performed. Genomic data were visualized using the Yeast Mapping Analysis Pipeline. The Minimum Inhibitory Concentration (MIC) was determined using broth microdilution. Results 105 patients were identified from six hospitals (Table 1). Seven clusters of candidemia were identified (Table 2). Genome sequencing supported that all isolates from an individual patient were genetically related. No clonality was observed for isolates from different patients, including those representing two of the seven clusters (Figure 1). Loss of heterozygosity was detected in isolates collected 15 minutes apart in the same patient, indicating distinct populations. MICs remained the same at 0.5 ug/ml over 6 days in Patients l and m (Table 1). For Patient n, MICs remained at 0.5-1 ug/ml Day 1-8, but increased to 4 ug/ml on Day 9. No copy number variation was observed in these isolates. Table 1. Species and resistance patterns of candidemia Table 2. Clusters of candidemia Figure 1. Yeast Mapping Analysis Pipeline for Clusters 3 and 4 – Candida albicans Conclusion We have not found evidence of hospital transmission of candida isolates in our investigations to date. We plan to evaluate clonality in the remaining 5 clusters. Future single nucleotide polymorphism analysis will determine if acquisition of point mutations is causing the increased MIC in Patient n. Disclosures All Authors: No reported disclosures


An Investigation into Possible Nosocomial Clusters and On-Treatment Resistance Patterns in Candidemia
Background. Candidemia has significant clinical implications, due to high rates of mortality and increasing resistance to antifungal drugs. Candida auris shows person-to-person transmission and survival on fomites. We aimed to determine if similar hospital transmission of Candida species, other than C. auris, is occurring. We analyzed candidemia infections for species, geographical, and temporal clusters, and clonality. We also aimed to study resistance patterns in individual patients on antifungal treatment. Here we present our current data from December 2019 -March 2021.
Methods. Patients with candidemia were identified with the help of the clinical microbiology lab serving an urban health system. Isolates were stored prospectively as glycerol stocks at -80 C. Data were collected by retrospective chart review and described in terms of frequency distributions and percentages. Patient locations within the hospital setting were traced by Infection Prevention. A cluster was defined as the same species being isolated from ≥ 2 patients in the same unit within a 90-day period. Genomic DNA was isolated and whole genome sequencing was performed. Genomic data were visualized using the Yeast Mapping Analysis Pipeline. The Minimum Inhibitory Concentration (MIC) was determined using broth microdilution.
Results. 105 patients were identified from six hospitals (Table 1). Seven clusters of candidemia were identified (Table 2). Genome sequencing supported that all isolates from an individual patient were genetically related. No clonality was observed for isolates from different patients, including those representing two of the seven clusters ( Figure 1). Loss of heterozygosity was detected in isolates collected 15 minutes apart in the same patient, indicating distinct populations. MICs remained the same at 0.5 ug/ml over 6 days in Patients l and m (Table 1). For Patient n, MICs remained at 0.5-1 ug/ml Day 1-8, but increased to 4 ug/ml on Day 9. No copy number variation was observed in these isolates.  Conclusion. We have not found evidence of hospital transmission of candida isolates in our investigations to date. We plan to evaluate clonality in the remaining 5 clusters. Future single nucleotide polymorphism analysis will determine if acquisition of point mutations is causing the increased MIC in Patient n.
Disclosures. Background. Rezafungin (RZF) is a novel echinocandin antifungal being developed for treatment of candidemia and invasive candidiasis, and for prevention of invasive fungal diseases among immunosuppressed patients. In the Phase 2 and Phase 3 treatment trials of rezafungin compared with caspofungin (STRIVE [NCT02734862] and ReSTORE [NCT03667690], respectively), patients with severe hepatic impairment (HI) were not included due to lack of caspofungin data in this population. Rezafungin was previously evaluated in patients with moderate hepatic impairment. Here we report an open-label, single-dose study on rezafungin in patients with HI (Child-Pugh class C).
Methods. To investigate the safety, tolerability, and pharmacokinetics (PK) of RZF in subjects with HI and healthy subjects (HS), 8 subjects with HI and 8 HS matched for age, sex, and body mass index (BMI) were enrolled and received a single 400-mg intravenous 1-hour infusion of RZF. Plasma PK sampling was performed at various time points through 336 hours postdose. RZF PK parameters were derived using non-compartmental analysis. Safety was assessed throughout the study.
Results. The majority of the HI subjects were White (87.5%) and male (75%) while equal distribution between White and Black or African American was observed among HS (50%) and 75% were male. The mean age of HI subjects was 58 years (range, 41-68 years) and 56.6 years (range, 50-61 years) for the HS. Mean BMI was 29.7 kg/ m 2 (range, 24.5-34.3 kg/m 2 ) for HI subjects and 29.7 kg/m 2 (range, 25.4-34.2 kg/m 2 ) for the HS. RZF exposure (C max and AUC) in subjects with HI was ~30% lower than that in HS (Table 1), while half-life was generally similar (HI: 121 h, HS:124 h; Figure  1). Three HI subjects had one adverse event (AE) each (bronchitis, worsening hepatic encephalopathy, hyponatremia), all moderate in severity; one HS had 1 AE of infusion site infiltration mild in severity. No AEs were considered related to RZF, and all were resolved or resolving by the end of the study.