bluuebunny/crossref_metadata_2025_split huggingface dataset:
129. Antimicrobial Activity of Ceftazidime–avibactam and Comparator Agents Tested against Gram-Negative Organisms Isolated from Patients with Bloodstream Infections in United States Medical Centers (2017–2018)
Authors: Carvalhaes Cecilia G , Castanheira Mariana , Mendes Rodrigo E , Sader Helio S 
Published: October 2019

Abstract

Background
We evaluated the antimicrobial susceptibility of Enterobacterales (ENT) and P. aeruginosa (PSA) causing bloodstream infections (BSIs) in the United States (US) hospitals.

Methods
A total of 3,317 ENT and 331 PSA isolates were consecutively collected (1/patient) from patients with BSI in 68 US medical centers in 2017–2018 and tested for susceptibility (S) by reference broth microdilution methods in a central laboratory as part of the International Network for Optimal Resistance Monitoring (INFORM) Program. β-Lactamase screening was performed by whole-genome sequencing on ENT with decreased S to broad-spectrum cephalosporins (ESBL phenotype).

Results
The most common ENT species isolated from BSI were E. coli (EC; 41.9% of ENT), K. pneumoniae (KPN; 24.4%), and E. cloacae (ECL; 8.7%), and the most active agents against ENT were ceftazidime–avibactam (CAZ-AVI; 99.9%S), amikacin (AMK; 99.6%S) and meropenem (MEM; 99.3%S). CAZ-AVI was active against all EC and KPN isolates (100.0%S). Only 2 ENT isolates (0.06%) were CAZ-AVI resistant, 2 NDM-1-producing ECL isolated in the New York City area. Ceftolozane–tazobactam (C-T) and piperacillin–tazobactam (PIP-TAZ) showed good activity against EC and KPN (92.2–98.9%S; Table), with limited activity against ECL (81.9–83.7%S). The most common ESBLs were CTX-M-type, which was observed in 93% of ESBL producers (mainly CTX-M-15 [64% of ESBL producers] and CTX-M-27 [13%]), and OXA-1/OXA-30 (42%); 42% of ESBL producers (n = 333, excluding carbapenemase producers) displayed ≥2 ESBL genes, mainly CTX-M-15 and OXA-1/OXA-30 (40% of ESBL producers). The most active agents against ESBL producers were CAZ-AVI (100.0%S), imipenem (99.4%S), and colistin (COL; 99.1%S). Only CAZ-AVI (99.4%S), AMK (96.2%S) and MEM (92.8%S) were active against >90% of multidrug-resistant (MDR) ENT. Among 19 carbapenem-resistant ENT (CRE; 0.6% of ENT), 9 produced a KPC-like, 2 an NDM-1, and 2 an NMC-A; carbapenemase genes were not found in 6 CRE isolates. COL (100.0%S), CAZ-AVI (98.5%S), AMK (98.5%S), C-T (98.1%S), and tobramycin (97.0%S) were very active against PSA.

Conclusion
CAZ-AVI exhibited potent in vitro activity and great spectrum against ENT (99.9%S) and PSA (98.5%) isolated from patients with BSI from US hospitals.

Disclosures
All authors: No reported disclosures.
2369. Prescribing Choices and C. difficile Infection Risk: A Longitudinal Cohort Study of Nursing Home Residents in Ontario, Canada
Authors: Antoine. Brown Kevin , Schwartz Kevin , Langford Bradley , Diong Christina , Garber Gary , Daneman Nick 
Published: October 2019

Abstract

Background
Antibiotics are the primary modifiable risk factor for C. difficile infection (CDI). However, the comparative risks of different prescribing choices are not known. Our objective was to quantify the benefits of: (1) preventing antibiotic initiation, (2) substituting high-risk antibiotics for low-risk antibiotics, (3) reducing antibiotic duration.

Methods
We conducted a cohort study of residents of over 600 Ontario nursing homes in the 2014 to 2017 period. All non-acute care hospital antibiotic exposures were identified from the Ontario Drug Benefit database, while CDI was identified using outpatient billings and/or hospital ICD-10 codes. Logistic regression models were used to examine the risk of CDI as a function of time-varying antibiotic exposures, while controlling for 14 different risk factors. Based on the models, we estimated the comparative risks of specific antibiotic regimens.

Results
We identified 1,944 cases of CDI, for an incidence of 1.60 per 100,000 person-days. The 90-day risk among residents without antibiotics was 0.84 per 1,000 residents (‰), compared with 1.85‰ in those with a 7-day course of antibiotics. Preventing a 7-day course reduced CDI risk by 45% (see table, adjusted relative risk [RR] = 0.55, 95% confidence interval [CI] = 0.50, 0.60). The antibiotics conferring the highest risks were clindamycin at 4.1‰, moxifloxacin at 3.2‰, and amoxiclav at 3.0‰. Comparing 7-day courses of antibiotics with similar indications: nitrofurantoin engendered 37% less risk than ciprofloxacin, amoxicillin resulted in 31% less risk than amoxicillin-clavulanate, and cephalexin had 51% less risk than clindamycin. Reduced antibiotic durations were associated with less C. difficile risk. Compared with a 10-day course, a 7-day course was associated with 12% less risk, while a 5-day course was associated with 21% less risk.

Conclusion
We have quantified, using a real-world population-based cohort of nursing home residents, the reduction in CDI risk incurred by preventing unnecessary antibiotic initiations, preferring low-risk agents over high-risk agents, and reducing duration. These figures will help clinicians compare risks and benefits of different prescribing choices with regards to CDI prevention.

Disclosures
All authors: No reported disclosures.
2382. Recurrent Clostridioides difficile Infection (CDI) Worsens Anxiety-Related Patient-Reported Quality of Life
Authors: Garey Kevin W , Schroeder Claudia P , Hardin Thomas C , Hengel Richard L , Ritter Timothy E , Nathan Ramesh V , Dillon Ryan J , Van Anglen Lucinda J 
Published: October 2019

Abstract

Background
The Health-Related Quality of life (HR-QOL) instrument, the Cdiff32, allows studies on QOL changes associated with recurrent CDI. An ongoing real-world study of bezlotoxumab (BEZ) provided a unique opportunity to study anxiety-related HR-QOL in patients at high risk for recurrent CDI using the anxiety sub-domain of Cdiff32. The aims of this study were to assess baseline anxiety-related HR-QOL based on the number of prior episodes of CDI and to evaluate changes in patients with or without recurrence.

Methods
Patients at high risk for recurrent CDI given BEZ were administered the anxiety sub-domain questions of the Cdiff32 prior to infusion and at approximately 90 days after administration (0 = worst anxiety; 100 = no anxiety). The number of prior episodes of CDI were collected, along with demographics and co-morbid conditions. Patients were followed for 90 days for CDI recurrence, which was defined as new onset of diarrhea requiring CDI-active antibiotics.

Results
There were 107 patients evaluated, aged 68 ± 14 years (mean ± SD) with multiple co-morbid conditions (mean Charlson: 4 ± 3) and multiple previous CDI episodes (3 ± 1 episodes). Fourteen patients (13%) experienced a further CDI recurrence within 90 days following BEZ. Overall, baseline anxiety HR-QOL was 29 ± 22. Risk factors for lower baseline anxiety-related HR-QOL included immunocompromised conditions (P < 0.046) and receipt of a proton pump inhibitor (P < 0.018). Compared with patients with primary CDI disease (Score: 35 ± 20), baseline anxiety HR-QOL was worse with subsequent prior recurrences (Score: 26 ± 23) for CDI episodes 2–4, and then improved for subsequent episodes (Score: 38 ± 22). Anxiety-related HR-QOL improved by a mean of 32 ± 25 points compared with patients that experienced a further recurrence where HR-QOL declined (P < 0.0001). Results were confirmed in a multivariate model controlling for Charlson score and chronic renal failure.

Conclusion
Poor anxiety-related HR-QOL was observed at baseline in all patients regardless of number of prior episodes. QOL improved 90 days after BEZ infusion in patients without further recurrences of CDIs and worsened in patients with a subsequent recurrence.

Disclosures
All authors: No reported disclosures.
2389. Assessing the Time Course of Proton Pump Inhibitor Use and Clostridioides difficile Infection
Authors: Panagos Katherine , Blanco Natalia , Leekha Surbhi , von Rosenvinge Erik , Heil Emily 
Published: October 2019

Abstract

Background
Proton pump inhibitors (PPIs) are a known risk factor for Clostridioides difficile infection (CDI) and recurrence, even in the absence of antibiotic use. No studies have specifically assessed the increased risk for CDI based on PPI duration, given that PPIs are frequently newly prescribed during hospitalizations and infrequently discontinued, even when CDI has occurred. The aim of this project was to assess the time course of PPI utilization and risk of CDI.

Methods
We conducted a retrospective matched case–control study comparing patients who developed CDI (cases) with patients who did not develop CDI (controls, matched on age, gender, date of admission and hospital location) from a cohort of patients with a C.difficile PCR test order from an academic medical center. Patient charts were reviewed for PPI use prior to the date of the positive test and whether the PPI was started in the hospital or as a home medication (>30d, 30–90d, 90–180d, >180d). The primary comparison was odds of PPI use between cases and controls using conditional logistic regression adjusted for antibiotic exposure (SAS 9.4, Cary, NC).

Results
A total of 348 patients were included in the study, 174 cases and 174 matched controls. 65% of patients in the study received a PPI, 85% a PPI or H2 blocker and 95% of patients received antibiotics during their admission. Patients on PPIs as home medications were not at an increased risk of CDI (OR = 1.08 (95% CI 0.60–1.93)) compared with those not on PPIs. Patients whose PPIs were initiated in the hospital were at increased risk of CDI compared with those not on PPIs (OR = 1.4 (95% CI 0.81–2.41)). No significant difference was observed across time periods of PPI use prior to admission and development of CDI.

Conclusion
Patients who started PPIs during inpatient stays were at a higher risk of developing CDI than patients not exposed to PPIs. However, PPI use was not found to be significantly associated with CDI in this analysis, regardless of the time or duration of PPI prescription. The results may be confounded by the high frequency of PPI use and concomitant antibiotic use in both cases and controls. Further study is needed to evaluate the impact of short-course PPI prescriptions in inpatient settings on CDI.

Disclosures
All authors: No reported disclosures.
2390. Acquisition of Clostridium difficile Infection Following Exposure from Roommate Defined by Concordance on Genotyping
Authors: Aslam Anoshé , McMillen Tracy , Wills Jonathan , Bayoumi Nagla , Usiak Shauna , Kamboj Mini 
Published: October 2019

Abstract

Background
Observational studies have identified same room occupancy with a hospital-onset Clostridium difficile infection (HO-CDI) case as a risk factor for subsequent CDI diagnosis. Despite this, the risk remains poorly characterized in endemic settings. Furthermore, genotyping techniques have not been applied to examine concordance between infecting strains in index patients and exposed roommates who eventually develop CDI. The study seeks to quantify transmission of C. difficile from an index case to their roommates and identify if concordance was present among strain types by the application of multi-locus sequence typing (MLST).

Methods
Laboratory-identified cases of hospital onset C. difficile infection (CDI) from October 1, 2017 through March 31, 2018, were included in the study. Patients with HO-CDI are placed in private room once diagnosis is established. Roommates who were in the same room as cases for at least 24 hours prior to diagnosis, regardless of duration of overlap, were identified through of the hospital patient tracking database to establish spatial link. Next, all exposed roommates who developed CDI within 3 months after exposure (defined as date of CDI diagnosis of index case) were identified. Strain types of linked cases was examined by MLST.

Results
During the 6-month period, 279 cases of CDI were diagnosed. Of these cases, 156 were hospitalized at the time of diagnosis including 83 (53%) in a room with shared occupancy. These 83 patients had 109 roommates that met exposure criteria. Four (3.7%) roommates developed CDI over a 90-day follow-up period. None of the examined pairs were genetically concordant.

Conclusion
Indirect patient to patient transmission of C. difficile from newly diagnosed CDI cases to roommates is not common despite the spatial proximity with shared occupancy.

Disclosures
All authors: No reported disclosures.
2391. Increased Risk of Systemic Infections with Multidrug-Resistant Organisms in Patients with Severe Clostridioides difficile Infection
Authors: Dotson Kierra M , Gonzales-Luna Anne J , McPherson Jacob , Lancaster Chris , Endres Bradley T , Zasowski Evan J , Begum Khurshida , Alam M Jahangir , Garey Kevin W 
Published: October 2019

Abstract

Background
The gut microbiota is a defense mechanism against colonization of multidrug-resistant organisms (MDROs), including carbapenem-resistant Enterobacteriacae (CRE). Gut dysbiosis caused by broad-spectrum antibiotics favors MDRO colonization and increased susceptibility of intestinal infections, including C. difficile infection (CDI). Increased CDI severity may increase the risk of bacterial translocation due to damage to colonic epithelial layer. The aim of this study was to assess CDI disease severity and subsequent risk for MDRO systemic infection.

Methods
This was a prospective, observational study of adult hospitalized patients tested for CDI at a large, university-affiliated tertiary care hospital. Patients with a history of systemic MDRO infection in the past 90-days of stool testing were excluded. Patients were stratified by test positivity (CDI vs. antibiotic-associated diarrhea (AAD)), as well as, CDI disease severity and followed for 30-days for subsequent MDRO infections defined as presence of MDRO cultures from systemic, normally sterile sites (blood, urine, cerebrospinal fluid). Stool samples were collected and grown for MDRO colonization.

Results
A total of 335 CDI-positive and 135 antibiotic-associated diarrhea (AAD) hospitalized patients were included. No differences were found in rates of MDRO colonization by test positivity or disease severity (overall 68% VRE, 53% Candida spp., 30.4% MRSA, and 1.8% CRE). Significantly more patients with severe CDI had higher rates of developing systemic MDROs compared with mild-moderate CDI and AAD (23.2%, n = 112 vs. 8.1%, n = 223 P < 0.001; vs. 11.9%, p = 0.018). Severe CDI was found to be an independent risk factor for subsequent systemic MDRO infection via logistic regression.

Conclusion
Severe CDI disease is associated with an increased risk of systemic MDRO infections.

Disclosures
All authors: No reported disclosures.
2395. Analysis of Countywide Clostridium difficile Infection using Descriptive Statistics and Geographic Information Systems Mapping
Authors: Li Jeanne , Mwenda Kevin , Stanfield Leslie , Beswick Richard 
Published: October 2019

Abstract

Background
Clostridium difficile infection (CDI) is now the most common pathogen causing nosocomial infectious diarrhea in the United States, and more than 500,000 people are estimated to have either healthcare-associated (HA) or community acquired (CA) CDI. The epidemiology of CDI is incompletely understood with more than 50% of all CDI cases occurring in the outpatient community and growing at a pace that is greater than HA-CDI.

Methods
Patients with CDI within Santa Barbara County, California were identified via three types of tests: Clostridium difficile PCR, gastrointestinal panel by PCR, and enzyme immunoassay (EIA) via local laboratory. Basic patient characteristics were analyzed using descriptive statistics. Changes with CA-CDI incidence were examined on a quarterly basis to identify and compare quarterly trends in CA-CDI incidence. Geographic Information Systems (GIS) mapping was utilized to provide better spatial understanding of disease distribution across communities.

Results
Over 2,000 unique patients with CDI were identified between January 1, 2013 and January 31, 2019. Median age of these patients was 64 years (interquartile range: 45 – 78) and 60% were female. Hot spots of CDI within Santa Barbara County were localized to three major cities: Santa Barbara, Goleta, and Lompoc. Our results show that based on seasonal quarterly data CDI occurred most frequently in winter months.

Conclusion
In conclusion, CDI hot spots occurred most frequently during winter months and could possibly be associated with increased antibiotic treatment during flu season. Using the results from this study, we believe that by utilizing spatial and seasonal trends associated with CDI, physicians may be able to identify, diagnose and treat patients with CDI more promptly in Santa Barbara County.

Disclosures
All authors: No reported disclosures.
2399. Ribotype Diversity of Clostridioides difficile strains obtained during screening tests
Authors: Munoz-Price L Silvia , Ledeboer Nathan A , Tickler Isabella A , Johnson Rebecca L , Park Taylor , Goering Richard , Oppenheim Beryl , Tenover Fred C 
Published: October 2019

Abstract

Background
Clostridioides difficile is an organism acquired not only in healthcare settings but also in community settings. For the past several years our hospital has performed screening tests to detect asymptomatic carriage of C. difficile. We now aim to better understand the ribotypes and degree of diversity among these C. difficile strains obtained in a systematic screening.

Methods
This study was performed at a 600 bed teaching affiliated hospital in Milwaukee, WI, where surveillance testing is performed in selected units upon admission and weekly thereafter using nucleic acid amplification test (NAAT; Xpert® C. difficile; Cepheid, Sunnyvale, CA). Screening tests are obtained regardless of symptoms. NAAT positive samples underwent anaerobic cultures in C. difficile selective broth (CCMB-TAL) for 24–48 hr and then to Brucella blood agar plates (BA) for 48–72 hr to conﬁrm C. difficile presence. PCR-ribotyping was performed as previously described by Stubbs et al. with minor modifications. The results were compared with a database containing >3,000 clinical isolates including C. difficile reference strains from the Cardiff ribotype collection.

Results
A total of 104 strains belonging to 93 unique patients were processed. Patients had a mean age of 60 years (range: 18 - 89) and 49% were females. Most patients were hospitalized in the hematology oncology units (55.7%) or in the solid-organ transplant step down unit (9.6%). A total of 25 different ribotypes were identified. The most common ribotype was 014/020 (23; 22%), followed by ribotype 56 (13; 12.5%), 106 (12; 11.5%), 027 (11; 10.5%), 002 (6; 5.7%), and 078/126 (5; 4.81).
Regarding the timing of admission, 70 strains were obtained within 4 days from hospital admission and the remaining 34 were obtained afterwards. Both groups had ribotype 014/020 as the most frequently detected ribotype but 027 were the second most commonly detected at the time of admission (table). A total of 7 patients had more than one stool sample processed and 5 of them had discordant ribotypes at different time points.

Conclusion
Systematic screening tests for C. difficile carriage in a single center showed a large heterogeneity of ribotypes with the majority not being 027. Additionally, most patients tested more than once carried different ribotypes.

Disclosures
All authors: No reported disclosures.
2403. Clostridium difficile ribotypes and human microbiota differ in Taiwan and the United States with respect to diarrheal patients
Authors: Motyka Jonathan , Cheng Hao-Tsai , Lin Cheng-Yu , Keidan Micah , Young Vincent B , Kao John , Rao Krishna 
Published: October 2019

Abstract

Background
Clostridium difficile infection (CDI) has high incidence in the United States, but less so in East Asian countries such as Taiwan. The reason for this is not understood, but microbial studies could reveal important epidemiologic insights. We hypothesized that the circulating strains of C. difficile and the gut microbiota differ between the United States and Taiwan.

Methods
Patients with diarrhea ± CDI from the University of Michigan and Chang Gung Memorial Hospital were included. CDI was defined by + enzyme immunoassay for the glutamate dehydrogenase gene and toxins A/B, with reflex to tcdB gene PCR for discordants. C. difficile was isolated by anaerobic culture and characterized by PCR ribotype. The fecal microbiota was assessed by sequence analysis of 16S rRNA-encoding gene amplicons targeting the V4 region. Amplicon sequences were processed using the mothur bioinformatics pipeline, with an operational taxonomic unit (OTU) defined by < = 3% sequence homology. Analysis was performed via logistic regression, principal coordinates (PCoA), and ANOVA.

Results
Community diversity by Shannon index of CDI- patients was lower (Figure 1); this difference was greater in Taiwan (P < .001, OR = 3.9 per unit Shannon). Taiwanese CDI- patients had lower Bacteroidetes relative abundance (RA) (Figure 2). The Taiwanese CDI- group also differed on PCoA and ANOVA (Figure 3, P < .001). OTU1 (genus Firmicutes) was depleted in CDI+ patients (P < .001, OR = 0.69 per 10% RA increase). Circulating ribotypes (Table 1) differ between countries, with no epidemic strains (R027/R078) present in Taiwan (P = .027). R027 and 014/020 comprised > 50% of US isolates while > 50% of Taiwanese isolates were R002.

Conclusion
Taiwan and US CDI+ patients differ in dominant ribotypes. It is overall difficult to differentiate diarrheal CDI+ and CDI- patients by the microbiome. Taiwanese CDI- patients are outliers, and possible reasons (e.g., differential burden of parasitic infection; diet) require further study. The increased diversity and lower Bacteroidetes in CDI+ vs. CDI- diarrheal patients contrast with prior studies that instead compared with CDI- non-diarrheal patients. Circulating strains in Taiwan include no epidemic variants; whether this explains the differential incidence needs further study.

Disclosures
All authors: No reported disclosures.