bluuebunny/crossref_metadata_2025 huggingface dataset:
679. Retrospective Analysis of Vancomycin and Fidaxomicin for the Treatment of Recurrent Clostridioides difficile Infection
Authors: Fabian Amy , Frantz Tyler , Patel Rachana , Kier Karen
Published: November 2023

Background

It is estimated that one out of every six patients with a Clostridioides difficile infection (CDI) will develop a recurrence. Guidelines recommend treatment with fidaxomicin rather than vancomycin standard course or tapered and pulsed regimens for the treatment of recurrent CDI (rCDI). The objective of this study is to evaluate clinical outcomes for three different pharmacological approaches for the treatment of rCDI.

Methods

This is a multi-centered, retrospective cohort of patients who have had more than one episode of CDI who received either fidaxomicin, conventional vancomycin dosing, or vancomycin tapered and pulsed. Inclusion criteria are adult patients who have received at least one dose of oral vancomycin or fidaxomicin and had a positive stool assay for CDI from October 1st, 2021 to September 30th, 2022. Patients who presented with an initial CDI, were pregnant, experienced in-hospital death prior to completion of antibiotic, were less than 18 years old, and elected palliative or hospice care were excluded. The primary outcome is the proportion of patients who develop rCDI at eight weeks. Secondary outcomes include time to recurrence, proportion of patients prescribed guideline-preferred therapy, and the proportion of patients with rCDI or mortality at three months and six months from starting therapy for rCDI. Primary and secondary outcomes will be analyzed using ANOVA testing, and a multi-variable regression analysis was performed to identify significant risk factors for rCDI.

Results

Among 71 patients, no difference was detected between fidaxomicin (n=11, 16%), vancomycin conventional dosing (n=48, 68%), and vancomycin tapered and pulsed (n=12, 17%) in the proportion of patients with rCDI at eight weeks (p = 0.335). A subgroup analysis of patients with infectious diseases (ID) consults (n=34, 47%) was performed, and they were more likely to be prescribed fidaxomicin (n=11, 32%; p = ≤ 0.001) and less likely to have rCDI (n=12, 17%; p = 0.008).

Conclusion

Compliance with guideline preferred therapy for rCDI in the community hospital setting is low among non-ID providers. Further research should be conducted to determine the impact that an ID consult can have on clinical outcomes in patients with rCDI.

Disclosures

All Authors: No reported disclosures
680. Comparison of Extended Duration Vancomycin Regimens for Clostridioides difficile Infection in Patients on Prolonged Antibiotic Courses
Authors: Garzia Christopher , Loo Angela , Kubin Christine J
Published: November 2023

Background

Antibiotic exposure is a primary risk factor for Clostridioides difficile infection (CDI) and recurrence. We compared CDI recurrence in patients who received extended oral vancomycin (poV) after diagnosis of CDI, at a dose of q12-24h compared to q6h, while on concomitant systemic antibiotic therapy.

Methods

Retrospective study of adult patients admitted 2/2020-9/2022 to NewYork-Presbyterian Hospital, diagnosed with CDI, and received at least 14 days poV including initial CDI therapy, and at least 2 days of extension with concomitant systemic antibiotics with no interruptions. Patients were grouped based on vancomycin extended dosing to either q6h or q12-24h. Patients were excluded if CDI regimen included vancomycin pulse/taper or fidaxomicin, >1 day interruption between final day of CDI treatment and extended dosing, and incomplete resolution of CDI at day 14. The primary outcome of recurrent CDI at 90 days was compared between the two groups via chi-squared test. Predictors of CDI recurrence were assessed using a logistic regression model.

Results

110 patients were included:77 received q6h and 33 received q12-24h extended poV. Median age was 63 years (IQR 55,74), 51% were hospital onset-CDI, and the median total duration of poV was 25 days (IQR 19,38 days). The only significant differences between q6h and q12-24h groups were total days of vancomycin (22 vs. 37 days; p< 0.001) and patients with previous CDI episodes (7% vs 24%; p=0.02). Recurrence at 90 days was similar between q6h and q12-24h groups (13.2% and 6.3% respectively; p=0.505). On multivariable analysis, while controlling for severe and fulminant CDI and patients with inflammatory bowel disease, poV regimen of q12h-24h did not impact recurrence (OR 0.428, 95% CI 0.08-2.21).

Conclusion

No significant differences were seen in CDI recurrence between extended poV q6h compared to q12-24h. For patients who require extended poV dosing beyond an initial treatment course, q12h-24h dosing may be an option with improved patient convenience and reduced drug cost. The long-term impact of this reduced dosing frequency remains to be determined.

Disclosures

All Authors: No reported disclosures
683. Understanding Clostridioides difficile toxinB gene conservation through surveillance of public data
Authors: Mulholland Kelly , Godfrey Victoria , Stanley Ann Marie , Brady Tyler , Sellman Bret R , Tkaczyk Christine , Gopalakrishnan Vancheswaran
Published: November 2023

Background

Clostridioides difficile infection (CDI) is the leading cause of antibiotic and healthcare-associated infective diarrhea. It is linked to 365,000 infections and causes approximately 20,000 deaths annually in the US. CDI is mediated by the action of toxin B (TcdB) in humans. Monoclonal antibodies (mAbs) that neutralize TcdB function have shown protection against CDI in preclinical models and more recently in the clinic. Several regions on the TcdB gene have been targeted by therapeutic mAbs including the glucosyltransferase (GTD) and the C-terminal combined repetitive oligopeptides (CROPS) domains. We have developed AZD5148, an anti-TcdB mAb targeting a region within the GTD. To understand its strain coverage, we examined sequence variations of GTD including the AZD5148 epitope in contemporary C. difficile strains utilizing a public data repository.

Methods

8,085 assembled C. difficile genomes collected between 2015-2022 were obtained from Enterobase. These were annotated with Prokka to identify the TcdB gene coding sequence, and subsequently aligned to the R20291 strain reference. Phylogeny was determined with ParSnp and visualized using iTol. From the aligned sequences, variants were identified using an in-house tool (RADAR).

Results

A majority of the C. difficile genomes deposited were from North America, specifically the United States. Ribotype (RT) information was available for 9.6% of the genomes with RT-078 being the most common. Phylogenetic analysis did not reveal any patterns by geography or collection year, though clades tended to be associated with ribotypes. Degree of conservation was calculated at each TcdB genomic residue and was evaluated both regionally and temporally. We found GTD to be highly conserved in US isolates as well as globally. Additionally, among contact residues for AZD5148, any variations observed were single, and were seen for positions 323 (Y-H), 329 (G-E), 349 (V-A), and 350 (L-I).

Conclusion

These findings have important implications for drug development including for AZD5148. Specifically, our findings reveal that the GTD domain of the TcdB gene has lower variance globally over the last 7 years making it a promising target for a C. difficile TcdB neutralizing mAb.

Disclosures

Kelly Mulholland, PhD, AstraZeneca: Employee|AstraZeneca: Stocks/Bonds Victoria Godfrey, MS, AstraZeneca: Employee|AstraZeneca: Stocks/Bonds Ann Marie Stanley, PhD, AstraZeneca: Employee|AstraZeneca: Stocks/Bonds Tyler Brady, MS, AstraZeneca: Employee|AstraZeneca: Stocks/Bonds Bret R. Sellman, PhD, AstraZeneca: Employee|AstraZeneca: Stocks/Bonds Christine Tkaczyk, PhD, AstraZeneca: Employee|AstraZeneca: Stocks/Bonds Vancheswaran Gopalakrishnan, PhD, AstraZeneca: Employee|AstraZeneca: Stocks/Bonds
690. Analysis of high-risk antibiotics for Clostridioides difficile infections in Korean hospitals: A nationwide multi-center study
Authors: Kim Bongyoung , Myung Rangmi , Kim Jieun , Kim Uh Jin , Kim Yeon-Sook , Kim Eu Suk , Kim Tark , Park Dae Won , Lee Mi Suk , Lee Sun Hee , Lee Chang-Seop , Chang Hyun-Ha , Lee Myoung-jae , Pai Hyunjoo
Published: November 2023

Background

Clostridioides difficile infection (CDI) is a representative healthcare-associated infection, and the incidence rate continues to increase in Korea. The purpose of this study is to identify antibiotics that are highly related to CDI incidence in Korean hospitals.

Methods

From January-December 2019, all antibiotic prescription records, CDI test results, and a daily number of hospitalized patients were retrospectively collected from 10 university-affiliated hospitals in Korea. To exclude duplication, CDI tests that were conducted within 10 days after conducting previous CDI tests were excluded. When a positive result was detected from C. difficile toxin assay or PCR tests, we considered it as CDI. Antibiotics were defined as drugs corresponding to J01 in the WHO ATC classification, excluding anti-tuberculosis drugs, anti-parasitic drugs, antiviral drugs, and local antibiotics. The antibiotic usage was calculated as Days of Therapy (DOT). The CDI incidence rate and antibiotic usage were collected on a weekly basis and then corrected to 1,000 patient days. The correlation between CDI incidence rate and antibiotic usage was analyzed using the cross-correlation function test.

Results

CDI incidence and total antibiotic usage in each hospital ranged from 0.49-1.58/1,000 patient-days and 588.7-1000.4 DOT/1,000 patient-days, respectively. Cross-correlation function test shows that antibiotics that are highly related to CDI incidence were 2nd generation cephalosporin that was prescribed 6 weeks prior to CDI event (coefficient 0.320, P = 0.021), 4th generation cephalosporin that was prescribed 1 week prior to CDI event (coefficient 0.307, P = 0.027), and beta-lactam/beta-lactamase inhibitors (with anti-pseudomonal effects) that was prescribed 1 week prior to CDI event (coefficient 0.272, P = 0.050), lincosamide that was prescribed 2 weeks prior to CDI event (coefficient 0.278, P = 0.045), and oxazolidinone that was prescribed 8 weeks prior to CDI event (coefficient 0.362, P = 0.008).

Cross-correlation coefficients between Clostridioides difficile infection incidence and antibiotic usage

Conclusion

Antibiotics highly associated with CDI incidence in Korean hospitals were second-generation cephalosporin, fourth-generation cephalosporin, beta-lactam/beta-lactamase inhibitors (with anti-pseudomonal effects), lincosamide, and oxazolidinone.

Disclosures

All Authors: No reported disclosures
692. The Role of Fidaxomicin for the Treatment of Clostridioides Difficile Infection in the Pediatric Population in the United States
Authors: Lee Yuman , Bradley Nicole , Smith Sarah , Rakhimova Shakhzoda
Published: November 2023

Background

In 2020, the FDA approved fidaxomicin (FDX) for the treatment of Clostridioides difficile infection (CDI) in children 6 months and older. The latest IDSA/SHEA guidelines recommend FDX use for adults only. A survey presented at IDWeek 2022 showed that only 35% of institutions used FDX as first line in adults despite its inclusion in the guidelines. The purpose of this study is to assess the use of FDX in US pediatric patients and identify barriers to use.

Methods

An anonymous, voluntary electronic survey was distributed to the American Society of Health-System Pharmacists and the Pediatric Pharmacy Association in January 2023. Baseline demographics, current practices, knowledge, comfort, and barriers to FDX use in pediatrics were collected. Fisher’s Exact Test was used to compare categorical variables.

Results

32 pharmacists responded to the survey. Majority were from children’s hospitals within an adult hospital (62.5%), stand-alone children's hospitals (18.8%), and adult hospitals with pediatric beds (15.6%). 37.5% (12/32) reported having institutional pediatric CDI guidelines. Of which, 75% (9/12) included FDX for the treatment of previous failure 77.8% (7/9), recurrent CDI 44.4% (4/9), and fulminant CDI 22.2% (2/9). In institutions without pediatric CDI guidelines (62.5%, 20/32), FDX was used for the treatment of previous failure 65% (13/20), recurrent CDI 5% (1/20), and fulminant CDI 5% (1/20). FDX use was significantly higher in institutions with CDI guidelines for recurrent CDI compared to those without guidelines (p< 0.05).

96.9% (31/32) of respondents reported at least one barrier to FDX use. Top 3 barriers were cost (71%, 22/31), inability of patients to afford upon discharge (64.5%, 20/31), and lack of provider familiarity (41.9%, 13/31). 53.1% (17/32) respondents were comfortable using FDX in pediatrics, 87.5% (28/32) were aware of its FDA approval in children, and 90.6% (29/32) were aware it was not in the IDSA guidelines.

Conclusion

Most respondents did not have institutional pediatric CDI guidelines. FDX use was most common in treatment failure. Most respondents reported at least one barrier to FDX use despite its FDA approval. Majority were comfortable using FDX in pediatrics. This study is limited by its small sample size as expected due to the studied population.

Disclosures

All Authors: No reported disclosures
695. Incidence and Risk Factors for Clostridioides difficile Infections in Non-COVID and COVID-19 Patients
Authors: Mathew Therese , Punnoose Rhema Maria
Published: November 2023

Background

Infections with Clostridioides difficile (CDIs) are a leading cause of healthcare-associated infections (HAIs) and impact public health globally. The aim of this study was to assess the incidence and the risk factors for healthcare-associated Clostridioides difficile infection (HA-CDI) in patients with COVID-19 and without this infection.

Methods

A single-center, prospective observational study was conducted at a tertiary care hospital in India, from January 2021 to December 2022. The entire hospital was a COVID-dedicated hospital for 12 months during the study period. The incidence density rates and risk factors for HA-CDI in patients with and without COVID-19 are presented.

Results

The incidence rates of HA-CDIs were three times higher in patients with COVID-19. The HA-CDI–COVID-patients were younger (69.9 ± 12.6 vs. 72.5 ± 11.6; p = 0.017), admitted from another hospital (20.5% vs. 2.9; p < 0.001), had antimicrobial therapy before CDI (99.1% vs. 91.3%, p < 0.001), received two or more antibiotics (p = 0.030) during a longer period (p = 0.035), received proton pump inhibitors (95.9% vs. 50.0%, p < 0.001) during a longer period (p = 0.012) and steroids (32.8% vs. 20.4%, p < 0.001). During the last month before their current hospitalization, a higher percentage of patients without COVID-19 disease were hospitalized in our hospital (p < 0.001). Independent predictors for HA-CDIs in patients with COVID-19 were admission from another hospital (p = 0.003), the length of antibiotic administration (0.020), and the use of steroids in therapy (p < 0.001). The HA-CDI predictors in the non-COVID patients were older age (p = 0.017), advanced-stage renal failure (p = 0.005), chemotherapy (p = 0.003), and a low albumin level (0.005).

Conclusion

Higher incidence rates of HAI-CDIs in COVID-19 patients did not occur due to reduced infection control precautions and hygiene measures but due to antibiotic therapy and therapy with other drugs used during the pandemic.

Disclosures

All Authors: No reported disclosures
698. Prevalence of Clostridioides difficile Infection in Patients with Isolated Glutamate Dehydrogenase (GDH) Positive
Authors: Pharnusopon Tanadhol , Chavapradit Natthakit
Published: November 2023

Background

Clostridioides difficile infection associated diarrhea is one of the world's health problems. The diagnosis method varies across guidelines. Nowadays, PCR for Clostridioides difficile is the standard modality in many institutions. But for resource-limited settings, a combination of GDH and Toxin A/B could be used. However, when an isolated positive GDH test with negative for toxin A/B, stool PCR should be done to confirm the diagnosis in highly suspected cases. This study aims to study the need for PCR testing by identifying the prevalence rate and specific characteristics associated with Clostridium difficile infection among isolated GDH-positive patients.

Methods

The prospective study collected data from patients who were admitted to Bhumibol Adulyadej Hospital, a tertiary hospital center in Bangkok, Thailand, from December 2021 to April 2023. The eligible criteria were patients over 18 years of age who were clinically suspected of Clostridioides difficile infection with stool GDH positive and toxin A/B negative. After informed consent, stool PCR for Clostridioides difficile was done, and patients characteristics, treatment, and outcomes were collected. The outcomes were to study the prevalence of Clostridioides difficile infection and identify characteristics among patients that helped predict the infection.

Results

There were 37 participants included in this study; 17 were male, and the median age was 63 years old. 5.4% of participants would be classified as having a fulminant Clostridioides difficile infection and 35.1% as having a severe infection if a PCR test was positive. The prevalence of PCR-confirmed Clostridioides difficile infection was 8 of 37 (21.6%). Factors that helped predict the infection included ICU admission (sensitivity 50%, specificity 79.3%), hypoalbuminemia (sensitivity 87.5%, specificity 10.3%), stool leukocytes (sensitivity 25%, specificity 65.5%), blood leukocytosis (sensitivity 37.5%, specificity 68.9%), and empirical treatment from a physician (sensitivity 50%, specificity 37.9%).

Conclusion

Among patients who have stool Clostridioides difficile GDH positive but Toxin A/B negative, even though the incidence rate of disease is low, stool PCR should be done in every case due to the lack of clinically specific characteristics.

Disclosures

All Authors: No reported disclosures
707. Molecular Epidemiology of Clostridioides difficile Colonization in Families with Infants
Authors: Toltzis Philip , Marlow Christine , Clayton Jason , Golonka Gregory , Maruskin Lynn , Jencson Annette , Choi Hosoon , Chatterjee Piyali , Whang Munok , Jinadatha Chetan , Cadnum Jennifer , Donskey Curtis
Published: November 2023

Background

We previously reported a high incidence of C. difficile colonization among parents caring for an asymptomatically-excreting infant (IDWeek 2022, Abs 2007), suggesting infants as a nidus of adult infection. Herein we define the molecular epidemiology of the organisms isolated within these families.

Methods

Families were enrolled at the baby’s 4-month well child visit at a suburban pediatric practice. Soiled diapers were mailed every two weeks for 4 months (total 8 time-point (TPs)) to a research laboratory. Stool was inoculated onto CDBA plates with portions broth- enriched. Simultaneously sent parental diaper wipes were handled identically. C. difficile was identified by colony morphology and GDH assay. Specimens from each family were assessed for relatedness by PCR ribotyping, and Whole Genome Sequencing (WGS) was utilized to determine genetic relatedness of repeatedly excreted organisms over time, both employing methods previously described (ICHE 2021;42:731).

Results

30 families (babies and mothers plus 22 fathers) participated, with 25 families submitting specimens at > 4 TPs. Prevalence of infant colonization/TP ranged from 50-72%, and cumulatively 90% were positive at least once (median 4 samples positive/subject). Prevalence among mothers was 18-39%/TP (cumulative 87%, median 2 samples positive/subject) and fathers 20-41%/TP (cumulative 86% positive, median 1 sample positive/subject). In 27 families C. difficile was isolated from > 1 member, with all but 1 including the infant. Isolates from 24 families could be ribotyped. In 6 families each member had a non-identical ribotype, in 3 families there was a single identical ribotype, and in 15 families some ribotypes were shared but > 1 member harbored > 1 ribotype. For example, one infant-mother pair shared two different ribotypes, but each harbored 1 additional distinct ribotype. WGS of persistently carried isolates with identical ribotypes from both infants and adults were related, usually exhibiting < 3 SNP differences.

Conclusion

C difficile is prevalent in families caring for infants. Molecular analysis revealed a previously unrecognized complex epidemiology, with most family members sharing at least 1 common strain but frequently accompanied by additional unrelated ribotypes.

Disclosures

All Authors: No reported disclosures
714. Genotypic Resistance in Acinetobacter as a Predictor for Patient Outcomes
Authors: Jinadatha Chetan , Dhar Sorabh , Coppin John David , Navarathna Thanuri , Kaye Keith S , Choi Hosoon , Chatterjee Piyali
Published: November 2023

Background

Infections caused by Acinetobacter baumannii are frequently difficult to treat with currently available antibiotics. Oxacillinases (blaOXA-23), beta-lactamase (blaTEM-1D) are known to contribute to antibiotic resistance. The purpose of this study was to identify if resistance genes such as blaOXA-23 and/or blaTEM-1D contribute to adverse patient outcomes such as prolonged infection leading to increased duration of stay and mortality in hospitalized patients.

Methods

Clinical patient isolates were collected from two acute care hospitals, a 383-bed, and a 248-bed hospital in the Detroit metropolitan area. A total of 115 isolates samples and with complete clinical data sets were collected from 2 medical ICUs, 2 surgical ICU wards and 12 non-ICU surgical wards between 2017-2021. Resistance genes were analyzed using Resfinder (version 4.0) following whole genome sequencing (Illumina, NextSeq). Separate Bayesian regression models were used for the outcomes of interest: length of stay (LOS) and 30-day mortality, for each gene, blaOXA-23 and blaTEM-1D, as a predictor and adjusting for age and sex, using negative binomial models for LOS and logistic regression for mortality. Full models were fit to each outcome that included the interaction of both genes and adjusted for age, gender, hospital unit, respiratory infection, diabetes, COPD, hypertension, and renal dysfunction.

Results

The patient clinical characteristics between the resistant and susceptible Acinetobacter groups were matched (Table1). There was little evidence for the genes affecting either 30-day mortality or LOS for the full models. There was some evidence for increased odds of mortality with the presence of blaOXA-23, 0.75 (95% uncertainty interval: -0.06, 1.60), or both blaOXA-23 and blaTEM-1D, 0.85 (-0.2, 2.0) but not at the 95% level (Figure 1, Table 2). There was little evidence for an effect for the genes on LOS.

Conclusion

Although there was a trend towards resistance genes affecting outcomes, the full analysis indicated no relationship between resistance genes and overall outcomes. Other factors such as advanced age, and comorbidities may be contributing to the mortality. In the future, factors that contribute to adverse clinical outcomes using a larger cohort will be explored.

Disclosures

Keith S. Kaye, MD, MPH, Abbvie: Advisor/Consultant|Abbvie: Honoraria|Entasis: Advisor/Consultant|Entasis: Honoraria|GSK: Advisor/Consultant|GSK: Honoraria|Merck: Advisor/Consultant|Merck: Honoraria|Shionogi: Advisor/Consultant|Shionogi: Honoraria|VenatoRx: Advisor/Consultant|VenatoRx: Honoraria
716. Effect of Carbapenem-resistant vs. Carbapenem-susceptible Enterobacterales infections on patient outcomes at an academic medical center
Authors: Clark Justin A , Burgess David , Moga Daniella
Published: November 2023

Background

Carbapenem-resistant Enterobacterales (CRE) infections have been shown to lead to excess mortality in patients. To estimate the impact of CRE at an academic medical center not in an endemic area for CRE infections, we sought to compare them against patients having infections by carbapenem-susceptible Enterobacterales (CSE).

Methods

This was a retrospective cohort study performed at UK Healthcare Medical Center which assessed admissions between January 1, 2010 – December 31, 2019. The index date was the first positive culture of E. coli, E. cloacae, K. aerogenes, K. oxytoca, and/or K. pneumoniae. Patients having a CRE culture on index were included in the exposure group, and those having all CSE cultures were included in the comparator group. Exclusion criteria were age < 18 years old, pregnancy, endocarditis, osteomyelitis, necrotizing fasciitis, or cystic fibrosis. Outcomes of interest were 14- and 30-day composite of all-cause mortality or discharge to hospice with follow-up beginning from the index culture. Relative risk (RR) and hazard ratio (HR) were utilized to compare outcomes and inverse probability of treatment weighting (IPTW) was used for statistical adjustment.

Results

Across the decade, 128 patients were included in the CRE group and 6,953 in the CSE group. IPTW-adjusted RR and HR [95% CI] of composite outcome were 1.11 [0.7, 1.74] and 0.98 [0.61, 1.57] after 14 days and 1.19 [0.8, 1.77] and 0.99 [0.65, 1.51] after 30 days, respectively. When utilizing an exposure definition of carbapenem non-susceptible Enterobacterales (CNSE), the RR and HR were

1.11 [0.79, 1.57] and 0.95 [0.66, 1.36] after 14 days and 1.25 [0.93, 1.68] and 1.02 [0.75, 1.4] after 30 days. When using the non-susceptible exposure and only including patients with bloodstream infections on index, the RR and HR were 1.50 [0.93, 2.43] and 1.42 [0.85, 2.36] after 14 days and 1.48 [0.96, 2.29] and 1.38 [0.85, 2.24] after 30 days.

Conclusion

Although the composite outcomes between the CRE and CSE groups were not statistically significantly different, an increased risk appeared to exist in follow-up analysis. Continued efforts including observations across multiple institutions are needed to further characterize risks associated with CRE infections.

Disclosures

All Authors: No reported disclosures
718. Sulbactam Susceptibility Testing by Gradient Diffusion Method (E-test) in Carbapenem-Resistant Acinetobacter baumannii (CRAB) from a Tertiary Care Hospital in Thailand
Authors: Fujitnirun Chris , Dungdonbom Sariya , Rungnobhakhun Pimpha
Published: November 2023

Background

Introduction: CRAB is one of the major pathogens of nosocomial infection in Thailand and also cause a great burden to global public heath. Current treatments for CRAB are limited because of multidrug resistance and drug toxicity especially renal toxicity associated with colistin. ESCMID guidelines and IDSA guidance in 2021 recommended sulbactam as the first line treatment for sulbactam susceptible CRAB. Here we reported susceptibility data of CRAB to sulbactam in a tertiary care hospital in Thailand.

Methods

CRAB were isolated from from inpatients admitted to Bhumibol Adulyadej Hospital, a 600-bed tertiary government hospital in Bangkok, Thailand, from February to April 2023. The minimal inhibitory concentration (MIC) of sulbactam was determined by the gradient diffusion method (E-test strip, Qilu Antibiotics) using Mueller-Hinton agar plates and reported by an experienced clinical microbiologist.

Results

Among 27 isolates of CRAB, sputum is the most common source of the organism (70%) (figure 1). The MIC range of sulbactam was 8 to ≥ 256 μg/ml. Median MIC was 32 μg/ml but the most frequently reported MIC was ≥ 256 μg/ml (41%) and 89% of the isolates showed MIC ≥ 24 μg/ml as shown in figure 2.

Figure 1

Source of A. baumannii isolates

Figure 2

MIC of A. baumannii isolates

Conclusion

At the present time, there was only breakpoint for sulbactam in combination with ampicillin. Clinical breakpoint of sulbactam alone for A. baumannii was not defined by current documents of both CLSI and EUCAST. Current recommendations which suggest 9 g/day of sulbactam for CRAB infection based on data from “less susceptible” CRAB (sulbactam MIC > 4 but ≤16 μg/ml). Our study reported isolates of CRAB that showed very high sulbactam MIC. These findings caution that local sulbactam susceptibility pattern should be defined before using sulbactam as the first line empirical treatment for CRAB infection.

Disclosures

All Authors: No reported disclosures
720. The clinical outcomes of hypervirulent carbapenem-resistant Klebsiella pneumoniae (CRKP) infection were not poorer than that of classical CRKP infection
Authors: Hu Ya , Zong Zhiyong
Published: November 2023

Background

Hypervirulent carbapenem-resistant Klebsiella pneumoniae (hv-CRKP) was superbug for patients. Despite the high resistance and virulence, the clinical outcomes of hv-CRKP induced infections were not ever measured before.

Methods

We conducted a retrospective observational study of patients hospitalized at a comprehensive teaching hospital from July 2019 to June 2022 with CRKP being detected from their clinical samples. Isolates presenting resistance to meropenem and carrying carbapenemase-producing genes were deemed as CRKP. Hypervirulence was defined by the existence of iuc and/or either rmpA or rmpA2. Hv-CRKP met both conditions of CRKP and hypervirulence, and cCRKP met only the condition of CRKP but not hypervirulence. The corresponding patients were subsequently aligned into hv-CRKP group and cCRKP group, respectively (Figure 1). Outcome variables were compared between hv-CRKP group and classical CRKP (cCRKP) group.Figure 1.Screening workflow

Results

In total, 534 patients were identified and included in this study, wherein 42.7% were of hv-CRKP infection and 57.3% were of cCRKP infection (Table 1). The 30-day all-cause mortality was 32.4% overall. The 30-day all-cause mortality of cCRKP group was a bit higher than hv-CRKP group (33.7% vs. 30.7%, p=0.513). Within BSI group, the hv-CRKP group presented higher 30-day all-cause mortality than cCRKP group (8.8% vs.7.5%, p=0.792). The 30-day infection attributable mortality was 79.8%. The length of stay (LOS) of CRKP infection patients ranged from 0 day to 1318 days with a median of 34 days. Only a half day difference in the mean LOS was seen between hv-CRKP group and cCRKP group (p=0.769). The mean post-culture LOS of CRKP infection was 14 days ranging from 0 to 1154. Comparing to cCRKP group, hv-CRKP group had a two-day shorter median of post-culture LOS (p=0.244). The survival of CRKP infection was 122 days in median and ranged from 0 to 1260 days. Hv-CRKP group had a diminished mean survival as to cCRKP group (18 days vs. 25 days, p=0.167). Survival curve presented a similar effect of both groups (Figure 2, p=0.926).

Table 1-1

Table 1-1 Table 1-2

Table 1-2Figure 2.Kaplan-Meier curve for 30-day mortality

Conclusion

Patients with hv-CRKP and patients with cCRKP had similar clinical outcomes.The clinical outcomes of hv-CRKP infection were not poorer than that of cCRKP infection.

Disclosures

All Authors: No reported disclosures
723. Clinical and demographic features associated with isolation of ESBL-producing Enterobacteriaceae in a private hospital in Kingston, Jamaica
Authors: Liu Eugene W , Mendoza Matthew , Fletcher Hansel , Coombs Fredricka
Published: November 2023

Background

Emergence of antibiotic resistant bacteria is a public health threat. Data on the burden of ESBL-producing bacteria is limited, particularly in low to middle income countries, such as Jamaica. Here we sought to identify clinical and demographic features associated with extended spectrum β-lactamase producing Enterobacterales (ESBLs) in patients at Andrews Memorial Hospital (AMH), a private hospital in Kingston, Jamaica.

Methods

This retrospective case control study compared patients with cultures with and without ESBLs. Cases and controls were identified from 2021 microbiology records. Case subjects were AMH patients with ≥ 1 Enterobacterales isolate resistant to ceftriaxone, and controls were individuals without any ESBLs isolated on culture in 2021 with at least one culture (including ones without growth) performed the first week each month. We included all possible cases and performed stratified random sampling by month of controls to reach a 1:2 case:control ratio. We identified cultures of interest, defined as the first culture with an ESBL isolate for each case and the first culture from the random sample for each control. For each culture of interest, we extracted electronic medical record data including antibiotics received in the preceding 6 months, organism, sex, and age.

Results

Among 35 cases and 48 controls, age (1.04; 95%CI 1.01-1.06); male sex (5.46; 1.93-15.50); and isolation of Enterobacter species (10.93; 1.23-97.04) were associated with increased odds of ESBL isolation on simple logistic regression. Bidirectional stepwise variable selection indicated these associated factors should be included in a multiple logistic regression model. In this model, age (1.05; 1.00-1.09) and isolation of Enterobacter species (17.53; 1.39-220.76) were independently associated with increased odds of ESBL isolation.

Table 1

Risk Factors for Isolation of ESBL in AMH Patients, as Estimated with Simple Logistic Regression Models—2021​

Table 2

Medication Risk Factors for Isolation of ESBL in AMH Patients, as Estimated with Simple Logistic Regression Models—2021​

Conclusion

Age was independently associated with increased odds of ESBLs and may be a marker for past exposure to β-lactam antibiotics or nosocomial infection with ESBLs. Past exposures may have greater influence on ESBL isolation compared to receipt of antibiotics in the past 6 months where we saw no associations. The association with isolation of Enterobacter species and ESBL isolation may be from confounding with ampC inducible resistance.

Disclosures

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724. Prevalence and Risk Factors for Carbapenem Resistant Enterobacterales Colonization on Admission to Two Intensive Care Units in India
Authors: Mansoor Armaghan-e-Rehman , Edathadathil Fabia , Suresh Devendhu , Krishna Yathu , George Anu , van Rheenen Jacaranda , Sinclair Dorothy , Olsen Margaret A , Vasudevan Anil K , Kwon Jennie H , Leekha Surbhi , Singh Sanjeev , Warren David K , Gandra Sumanth
Published: November 2023

Background

Carbapenem-resistant Enterobacterales (CRE) infections are endemic in Indian hospitals however, studies examining intestinal colonization of CRE on admission to intensive care units (ICUs) are very limited. This study examines the prevalence and risk factors for CRE colonization on admission to two ICUs in a tertiary-care hospital in India.

Methods

Peri-rectal swabs were collected from consented patients prospectively enrolled between December 16, 2022 and March 31, 2023 in the medical ICU (MICU) and surgical ICU (SICU). Swabs were plated on selective agar (CHROMagarTMmSuperCARBATM) within 24 hours of collection for CRE isolation. Identification and susceptibility of presumed CRE isolates were confirmed by VITEK2. The modified carbapenem inactivation (mCIM) test and the EDTA carbapenem inactivation method (eCIM) were used to assess carbapenemase production. Information on CRE colonization risk factors (hospitalization and ICU stay in last one year, transfer from outside hospital, long-term hemodialysis) was collected.

Results

A total of 453 patients were admitted to both ICUs during the study period and 158 patients gave consent. Overall CRE prevalence among 158 patients was 54% (86/158). Peri-rectal swab was obtained within 48 hours of admission for 78 patients (Figure 1), and CRE prevalence in this cohort was 42% [33/78], with significantly higher prevalence noted among patients in the MICU compared to SICU (63% [17/27] vs 31% [16/51], p=0.007). Hospitalization, or ICU admission within the last 1 year, and long-term dialysis were significantly associated with CRE colonization (Table 1).

Among 33 patients with CRE colonization on admission, the most common CRE isolated was Klebsiella pneumoniae (59% [20/34 isolates]) followed by Escherichia coli (38% [13/34 isolates]). Among the 34 CRE isolates, 19 were metallo-beta-lactamase producers and 15 were serine carbapenemase producers.

Table 1

Conclusion

High prevalence of CRE colonization on admission was observed in the two ICUs, with prior hospitalization significantly associated with CRE colonization. Significantly higher proportion of CRE colonization was seen in the MICU as compared to SICU. Future studies should examine the risk factors associated with CRE acquisition during hospitalization to design interventions.

Disclosures

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725. Characteristics and Risk Factors for Mortality in Patients with Infections Caused by Serratia marscescens in a Referral Hospital in Nicaragua
Authors: Mayorga Darwin Moisés , Marenco-Avilés Sunaya , Porras-Cortés Guillermo D
Published: November 2023

Background

Serratia marcescens is a relevant pathogen both for its ability to cause serious infections and for its resistance pattern. In Hospital Dr. Fernando Vélez Paiz (Nicaragua), S. marcescens is the second most frequent bacterium isolated in healthcare-associated infections. The aim of this study is to describe the epidemiology and characteristics associated with mortality in hospitalized patients with infections caused by this bacterium between January 2022 and December 2022.

Methods

This is a retrospective, analytical, and cross-sectional study. The universe consisted of 239 patients with documented infections and positive cultures for S. marcescens. A sample of 131 patients was obtained once the inclusion and exclusion criteria were applied (Figure 1). An analysis of survivors and non-survivors was performed to identify risk factors for mortality.Figure 1.Flowchart of Selection of Patients with Serratia marcescens Infection

Results

The mean age was 43.8 ± 17.1 years old, and 56.5% of the patients were female. At least one comorbidity was found in 53.4% of patients. The most common chronic conditions were diabetes (74.3%) and hypertension (58.5%). The most frequent sites of infection were surgical site (51.9%), skin and skin structure (24.4%), and bloodstream infection (10.7%) (Table 1). Of the 131 patients, 76 (58%) were categorized as having a healthcare-associated infection. The mortality rate was 15.3%. The non-survivors were older (56.5 ± 16.5 years old) than the survivors (41.6 ± 16.3 years old). The pneumonia was present in 15% of the non-survivors but only in 0.9% of the survivors. Extended-spectrum beta-lactamase (ESBL) production was detected in more than 80% of the strains of S. marcescens, and more than 50% were multidrug-resistant (Table 2). An analysis of multiple variables found factors associated with mortality such as: NEWS score ≥ 6 points [RM (95% CI): 84.0 (18.86-374.05)], cerebrovascular event and/or sequelae of this [RM (95% CI): 19.58 (1.92-199.3)], pneumonia [OR (95% CI): 19.41 (1.90-197.55)] among others (Table 3).

Conclusion

Serratia marcescens infections were mainly surgical site, and of skin and skin structure. Pneumonia was associated with a higher chance of death. Most strains were ESBL producers. Different factors were associated with mortality, including severity on the NEWS score at the time of diagnosis of the infection.

Disclosures

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726. Risk factor analysis for cefepime and piperacillin/tazobactam resistant organisms
Authors: Pham Tho H , Barletta Jeffrey , Huang Vanthida
Published: November 2023

Background

Carbapenems (CAR) are first line therapy for patients with infections caused by multidrug resistant organisms. As the prevalence of antibiotic resistance is increasing, CAR use has become a common choice for empiric therapy. This increase in use is concerning as prior CAR exposure is a risk factor for CAR resistance. Identification of risk factors associated with resistance for other beta-lactam antibiotics could aid in the appropriate use of CAR therapy while minimizing overuse. The objective of this study was to identify risk factors for cefepime (FEP) and piperacillin/tazobactam (PTZ) resistance and which population required CAR as an empiric therapy.

Methods

This is a retrospective cohort conducted at HonorHealth John C Lincoln Medical Center, Phoenix AZ between January 2020 to July 2021. The case patients will be those who had an infection which is resistant to FEP or PTZ, while control patients have infection which is susceptible to FEP or PTZ. Recurrence of infection after receiving appropriate antimicrobial therapy considered as a separate case. Patients who do not have antimicrobial susceptibilities were excluded. Variables were compared between groups. Multivariate analysis using logistic regression was used to control for confounding variables.

Results

Overall, 230 patients met inclusion criteria and were evenly distributed between cohorts. The mean age of the population at baseline was 64 ± 17.4, 111 (48.3%) patients were in an ICU and 103 (44.8%) patients required mechanical ventilation. Clinical variables which were significant in univariate analysis were included in multivariate analyses. Multivariate analyses revealed prior resistance to FEP or PTZ in the past 12 months (OR 8.35, 95% CI [2.28-30.50], p=0.001), transferred from outside facility (OR 3.40, 95% CI [1.80-6.42], p< 0.001), prior ICU admission in the past 90 days (OR 4.40, 95% CI [1.72-11.27], p=0.002), and prior antibiotic use in the past 30 days (OR 2.60, 95% CI [1.33-5.09], p=0.005) were associated with increased risk of FEP- or PTZ-resistant infections.

Conclusion

Patients with prior resistance to FEP and PTZ within the last 12 months can benefit by initiating empiric therapy with CAR due to the increased risk for subsequent FEP- or PTZ-resistant organisms. Further investigation is warranted.

Disclosures

All Authors: No reported disclosures
727. Following WHO priority pathogen list: Carbapenem-Resistant Enterobacterales infections in a hospital in the Dominican Republic
Authors: Hernandez-Landa Ricardo Ernesto , Guzman-Marte Anel E , Rojas-Fermin Rita A
Published: November 2023

Background

Enterobacterales resistant to third generation cephalosporins and carbapenems are included in the WHO priority pathogen list. Evaluating the frequency and carbapenemase production of Carbapenem-Resistant Enterobacterales (CRE) and clinical characteristics of patients in our institution would be a helpful tool in Antimicrobial Stewardship programs.

Methods

A retrospective case-control study was conducted including all CRE patients (42) and a sample of patients with Carbapenem-Susceptible Enterobacterales (CSE), from Jan 2020 to Oct 2022 in a 289-bed tertiary teaching hospital in the Dominican Republic. Demographics, comorbidities, infection source, length of stay (LOS) and antibiotic use were reviewed. Microbiology results were reviewed for resistance rate and carbapenemase production data. Univariable analysis was performed to calculate Odds Ratio (OR), significant correlations were included in multivariable analysis to identify risk factors for CRE infections. P-values ≤ 0.05 were considered statistically significant.

Results

The CRE rate during the 34-month period was 1.5% (45/3022) while 79.5% (36/45) of isolates showed carbapenemase production. The most frequent carbapenemases were KPC 44.4% (20/45) and MBL types 28.9% (13/45); Klebsiella spp. (44.4%) along with Enterobacter cloacae complex (24.24%) were the most frequent CRE genera. Blood cultures represented the most common source of isolation. Potential risks factors identified in a univariate analysis were LOS ≥15 days, COVID-19 in the previous 6 months, bloodstream infections (BSI), mechanical ventilation, indwelling catheter use and ICU stay, while COVID-19, LOS ≥15 days and BSI resulted as risk factors using logistic regression.

Conclusion

Even though our CRE rates can still be considered low, the incidence of CRE infections has risen since the COVID-19 pandemic. Patients with BSI, LOS ≥15 days and those who have had COVID-19 in the previous 6 months have the highest risk for CRE infections. Since carbapenemase production, mainly KPC and MBL types, complicates patient management and outcome, we emphasize the need of tests that allow us to rapidly detect and identify the type of carbapenemase produced or the presence of simultaneous production.

Disclosures

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730. Emerging patterns of multidrug resistance Gram negative bacterial infections and its clinical outcome at a tertiary medical center
Authors: Shetty Shriya C , Shenoy Shilpa , Asha Pai K B , Sudhindra Rao M , Ankeeta Menona J , Shetty Avinash K , Veena Shetty A
Published: November 2023

Background

Antimicrobial resistance (AMR) is a complex threat to global health security and universal health coverage. The continued escalation of AMR among Gram-negative bacteria (GNB) is a major concern due to the endemic presence of MDR and extremely drug-resistant (XDR) pathogens.In this regard, the present study aimed to asses the magnitude of MDR, its risk factors, and mortality in MDR/XDR - GNB.

Methods

GNB isolates were retrieved from patients, identified and assessed for antibiotic resistance pattern using VITEK® 2 compact system. The extended spectrum β-lactamase (ESBL) production in 100 GNB isolates was determined by double disk synergy test and genes confirmed by PCR in retrospective cohort study (2011-2012). The carbapenemase production in 100 isolates was confirmed by modified carbapenem inactivation method in prospective cross-sectional study (2021-2022). The metallo β-lactamase (MBLs) were screened by combined disk test and carbapenemase genes detected by multiplex-PCR. Minimum inhibitory concentration (MIC) of colistin was determined by Broth Micro dilution method and clonal relatedness was evaluated by Multilocus sequence typing (MLST).

Results

In retrospective study, all cases confirmed ESBL with high incidence of antibiotic

resistance in cephalosporins,chloramphenicol and ciprofloxacin. All isolates were susceptible to carbapenem. bla TEM and bla CTX-M were prevalent ESBL genes, with 7 % mortality. In prospective study, isolates were positive for carbapenemase with XDR pattern and 47% of mortality. 90% isolates were MBLs positive and 30% had at least two carbapenemase genes, the combination of bla OXA-48 and bla NDM-1 was highly prevalent. Colistin resistance was observed in 20% and 30% isolates with 8 and 4 µg/ml MICs, respectively. Further, multiplex-PCR confirmed the mcr genes and clonal relatedness was determined.

Conclusion

The high prevalence rate of MDR-GNB from producing ESBLs (2011-12) to carbapenemase (2021-2022) was observed. Our results emphasize on antibiotic stewardship policies and regular surveillance programmes for monitoring AMR and screening of drug resistance genes. MLST, molecular surveillance, is valuable tool for rapid epidemiological investigation with precision in determining clonal relatedness

Disclosures

All Authors: No reported disclosures