Search

Background In 2003, many hospitals in Québec, Canada experienced an increase in the incidence of healthcare-associated C. difficile infection (HA-CDI) associated with increased morbidity and mortality. This increase was associated with the dissemination of the NAP1/027 strain. The objective of this study was to describe the epidemiology of HA-CDI in two tertiary care hospitals based in Montréal from 2003 to 2019. Methods Surveillance for HA-CDI was performed using standard definitions from 2003 to 2019 at the Montreal General Hospital (MGH) and Royal Victoria Hospital (RVH), in Montréal, Québec. C. difficile was isolated from stool specimens using standard methods. Pulsed field gel electrophoresis and ribotyping were performed to determine genotype. Antibiotic utilization and infection control interventions implemented over the same time period were reviewed. Results A total of 4314 cases of CDAD were identified during the study period: 2295 at the RVH and 2019 at the MGH. The incidence decreased from 29.5 to 5.9 cases per 10,000 patient-days between 2003 and 2019 at the RVH and from 23.8 to 3.9 cases per 10,000 patient-days at the MGH. Of the 124 isolates available for genotyping in 2003, 112 were NAP1 (90.3%) compared to 5 out of 53 (9.4%) in 2019. Fluoroquinolone utilization decreased from 230 to 139 DDDs per 1,000 patient-days between 2003 and 2019, whereas total antibiotic utilization increased from 1296 to 1550 DDDs per 1,000 patient-days. Infection Control interventions included empirically placing patients with diarrhea on precautions, intensified cleaning measures, formal antibiotic stewardship, introduction of a real-time PCR C. difficile test in June 2010, and a move to a facility with only single rooms at the RVH in April 2015. Incidence of HA-CDI at the RVH and MGH and antibiotic utilization between 2003 and 2019 Conclusion An important change in HA-CDI epidemiology was observed in two Canadian tertiary care hospitals based in Montréal between 2003 and 2019. There was a significant decrease in incidence of HA-CDI and a genotype shift from a predominance of NAP1 strains to non-NAP1 strains. Utilization of fluoroquinolones, to which the NAP1 strain is resistant, concurrently decreased. Infection control interventions targeting isolation, diagnosis, disinfection, and antibiotic stewardship have contributed to the major observed reduction in HA-CDI incidence. Disclosures All Authors: No reported disclosures

Background Rapid bacterial strain typing for nosocomial outbreak surveillance is critical for timely outbreak detection and implementation of appropriate infection control protocols in hospitals. Pulsed-field gel electrophoresis (PFGE) remains the gold standard for strain typing, but it has the disadvantages of being time-consuming and costly. Transflection Fourier transform infrared (FTIR) spectroscopy is a nondestructive and reagent-free technique for rapid microbial identification and subspecies-level discrimination. The potential of employing transflection FTIR spectroscopy as a rapid, real-time typing technique was evaluated in the present study. Methods Transflection FTIR spectra were acquired from vancomycin-resistant Enterococcus faecium (VRE) isolates obtained from rectal swabs (n = 36) of patients in 6 units at a Montreal hospital over a 3-month period and from environmental screening samples (n = 2). Upon confirmation as VRE using a transflection FTIR spectral database previously developed in our laboratory, isolates were further typed by unsupervised hierarchical cluster analysis and principal component analysis of the FTIR spectral data with the use of a feature selection algorithm. Results Analysis of the FTIR data identified independent cases of VRE outbreak in 2 of 6 units; these outbreaks were confirmed retrospectively by PFGE. Based on the PFGE typing results for all 38 isolates included in this study, FTIR spectral analyses successfully identified 95% (n = 18) of isolates related to the outbreaks and 95% (n = 18) of non-outbreak-related isolates, resulting in a false-positive (n = 1), and a false-negative (n = 1), rate of 5%. Additionally, the two environmental isolates were identified as part of the outbreak from one of the outbreak-positive units. Conclusion The results in this study indicate that transflection FTIR spectroscopy-based typing can be considered as an alternative typing technique to PFGE, providing real-time results to track the spread of antibiotic-resistant pathogens within hospitals. Furthermore, when combined with the use of a transflection FTIR spectral database, both identification and typing of an isolate can be achieved from a single spectral measurement, thereby reducing the time and cost required for outbreak investigation. Disclosures All authors: No reported disclosures.

Purpose: Tirapazamine (SR 4233) is a benzotriazine di-N-oxide which acts as a hypoxic cytotoxic agent and as a radiation enhancer when given shortly before or after radiation. Three Phase I clinical trials were designed to determine the maximum tolerated dose, toxicities, pharmacokinetics, and effects on irradiated tumors and normal tissues. Methods and Materials: Tirapazamine 9 mg/m2 to 21 mg/m2 was given IV sol|1/2 to 1 h prior to irradiation on a multiple dose schedule of 10 consecutive doses. This was later revised to a three times-per-week schedule for 12 doses. In a second clinical trial, tirapazamine was given in a single dose of 18 mg/m2 to 293 mg/m2 IV after irradiation. In a third trial, tirapazamine was administered without irradiation in single doses of 36 mg/m2 to 250 mg/m2, with an option for retreatment. Results: Subjects reported muscle cramping of varying degrees of severity on all three dose schedules. One patient experienced Grade 3 cramping and treatment was discontinued. The most frequent site of cramping were the lower extremities. Creatine phosphokinase (CPK) values were elevated in three patients with associated muscle soreness in one patient. MB (cardiac) isoenzymes were elevated in one patient with no evidence of cardiac muscle damage, and returned to baseline at drug completion. No consistent abnormalities in clinical laboratory values were found. Stretching of the muscle was most effective in relieving the cramping. Conclusion: Muscle cramping has been the most frequently reported toxicity in Phase I studies of tirapazamine, though it does not appear to be dose limiting. Dose escalation on the three clinical trials continues. In vitro studies to investigate the cramping are ongoing.

Purpose: Patients with refractory solid tumors were treated with the combination of fractionated radiation therapy and multiple-dose intravenous tirapazamine to determine the toxicities and maximum tolerated dose of tirapazamine when given concurrently with radiation therapy. Methods: Patients received radiation therapy in accordance with standard treatment practice in relation to fraction size and number of fractions for their particular cancer. In all cases, the course of radiation therapy exceeded the time of tirapazamine administration. Initially, tirapazamine was administered 5 days per week for 2 weeks for a total of 10 doses. After the first 8 patients, the schedule was changed to 3 times per week (Monday, Wednesday, Friday) for 4 weeks for a total of 12 doses. Between 3 and 6 patients were treated at each dose level. Results: A total of 43 patients were treated in the study between 1991 and 1995. All patients were 18 years old or older, had a Karnofsky performance status of ≥ 60% and had adequate hematologic, hepatic, and renal function. Dose escalation began at 9 mg/m 2 /dose and was increased using a modified Fibonacci schema. The maximum tolerated dose was not reached and dose escalation was stopped at 260 mg/m 2 because of other data that became available suggesting 330 mg/m 2 was associated with dose-limiting toxicity (1, 2). Conclusion: Tirapazamine in doses of up to 260 mg/m 2 times 12 doses can be given safely with fractionated radiation therapy. This dose appears to result in adequate plasma exposure (2) for radiation sensitization, and this schedule is being tested in a Phase II trial by the Radiation Therapy Oncology Group to determine if tirapazamine is a radiation enhancer in the clinic.