bluuebunny/crossref_metadata_2025 huggingface dataset:
1433. Predictive Models for Antibiotic Coverage of Gram-Negative Urinary Tract Infections
Authors: Hebert Courtney , Gao Yuan , Rahman Protiva , Dewart Courtney M , Shah Nirav , Lustberg Mark , Stevenson Kurt , Pancholi Preeti , Hade Erinn
Published: October 2019

Background

Providers use institutional recommendations, national guidelines, and antibiograms to decide on empiric antibiotics. As local antibiograms are most effective after organisms are known, we sought to use local microbiology and clinical data to develop predictive models for antibiotic coverage prior to identifying the organism. We focused on Gram-negative organisms as they are common urinary pathogens and are often the cause of sepsis originating in the urinary tract. As such, they are important to cover in hospitalized patients with urinary tract infections (UTI).

Methods

Hospitalized patients, with a diagnosis of UTI and a positive urine culture in the first 48 hours were included. Gram-positive organisms, yeast, and cultures without susceptibilities were excluded. Unknown susceptibilities were filled in using expert-derived rules. Clinical information from electronic health record (EHR) data were extracted on each patient. Penalized logistic regression with 10-fold cross validation was used to develop final models for coverage for five antibiotics (cefazolin, ceftriaxone, ciprofloxacin, cefepime, piperacillin–tazobactam). Final models were chosen based on their discrimination, calibration, and number of predictors, and then tested on a held-out validation dataset.

Results

Included were 5,096 patients (80% training; 20% validation). Coverage ranged from 65% for cefazolin to 90% for cefepime. Positive blood cultures were present in 544 (11%) with 388 (71%), including a urinary pathogen. In the first 24 hours, 2329 (46%) were hypotensive, 2179 (43%) had a respiratory rate > 22, 2049 (40%) had a WBC > 12, 1079 (21%) were febrile, and 584 (11%) required ICU care. Final model covariates included demographics, antibiotic exposure, prior resistant pathogens, and antibiotic allergies. The five predictive models had a point-estimate for the area under the ROC on the validation set that ranged from 0.70 for ciprofloxacin to 0.73 for ceftriaxone.

Conclusion

In this cohort of moderate to high acuity hospitalized patients with Gram-negative urinary pathogens, we used EHR data to develop 5 models that predict antibiotic coverage which could be used to support empiric prescribing. These models performed well in a held-out validation set.

Disclosures

All authors: No reported disclosures.
1438. Escherichia coli (EC) ST131-H30 Clonal Group is Associated with Antimicrobial Resistance, Illness Severity, Host Compromise, and Non-Cure among Patients with Bacteriuria
Authors: Mahoney Melanie T , Brigman Hunter V , Johnston Brian , Raux Brian R , Johnson James R , Hirsch Elizabeth B , Hirsch Elizabeth B
Published: October 2019

Background

EC sequence type ST131 is the leading cause of extraintestinal EC infections, and accounts for most fluoroquinolone (FQ)-resistant and extended-spectrum β-lactamase (ESBL)-producing EC clinical isolates. The ST131-H30 subclone (H30) is responsible for most antimicrobial resistance within ST131; however, H30’s impact on clinical outcomes is poorly defined. We compared empiric treatment patterns and clinical outcomes of patients with bacteriuria caused by ST131 vs. non-ST131 EC, and by H30 vs. non-H30 EC strains.

Methods

Phylogroups, ST131, H30, and CTX-M-type β-lactamase genes were detected by PCR for 142 non-duplicate EC isolates collected prospectively from hospitalized or emergency-department-attending adults with monomicrobial bacteriuria at a Boston academic medical center (August 2013–January 2014). Clinical and microbiologic data were collected retrospectively from electronic health records. Baseline characteristics, empiric treatment, and clinical cure rates were compared between ST131 vs. non-ST131, and H30 vs. non-H30, patient cohorts.

Results

Of 142 patients with EC bacteriuria, most (76%) were female and elderly (mean age 65.2 ± 21.2 years). Overall, 35% of isolates were ST131, of which 80% (39/49) were H30. Compared with other isolates, H30 isolates demonstrated a higher frequency of ESBL production (33% vs. 8%; P < 0.001) and FQ resistance (90% vs. 8%; P > 0.001). Patients with H30 isolates (vs. non-H30 isolates) were older (mean 73.4 ± 13.6 vs. 62.1 ± 22.7 years; P < 0.01), had higher median (interquartile range [IQR]) APACHE II scores (10 [4] vs. 8 [9.5]; P = 0.01), more commonly had underlying complicating conditions (100% vs. 83%; P = 0.03) and received in vitro-inactive empirical treatment (26% vs. 3%; P < 0.01), and had a numerically lower clinical cure rate (84% vs. 96%; P = 0.08). In contrast, patients with ST131 vs. non-ST131 isolates had similar median [IQR] APACHE II scores (9 [5] vs. 8 [9]), frequencies of symptomatic UTI (61% vs. 70%) and underlying complicating conditions (24% vs. 19%), and clinical cure rates (87% vs. 95%).

Conclusion

Among patients with EC bacteriuria, the ST131-H30 subclone was associated significantly with ESBL production, FQ resistance, illness severity, host compromise, and numerically lower clinical cure rates in symptomatic UTI.

Disclosures

Elizabeth B. Hirsch, PharmD, Merck: Grant/Research Support, Research Grant; Nabriva Therapeutics: Advisory Board; Paratek Pharmaceuticals: Advisory Board.
1449. Antibiotic Choice, Duration, and Outcome in Community-Acquired Urinary Tract Infections (UTI) in Male Patients
Authors: Chen Joshua C , Pham Jonathan , Yazdi Mona T
Published: October 2019

Background

It is common medical practice for all urinary tract infections (UTIs) in males to be diagnosed as “complicated” UTIs. Current guidelines recommend 7 to 14 days of antibiotics for complicated UTIs. Longer duration of antibiotics potentially exposes a patient to harm without sufficient evidence for benefit. This research will attempt to determine the optimal antibiotic and duration of treatment for males diagnosed with a UTI.

Methods

This study is a retrospective cohort study that utilized the electronic health record for Kaiser Permanente Southern California to search for male patients with a diagnosis of cystitis or UTI in the outpatient setting from 2011 to 2016. Only patients with confirmed bacteriuria >100,000 CFU/mL of a gram-negative organism were included. Exclusion criteria included Foley catheterization, intermittent self-catheterization, prostatitis and Pseudomonas infection. There were 10,662 patients in our database who fit these criteria, but only 134 patients were reviewed for preliminary analysis for this abstract. Outcomes included recurrence of UTI within 30 days of finishing treatment

Results

A total of 134 patients were included. Most patients were prescribed Ciprofloxacin (69%) or Cephalexin (19%). The prescription duration was >8 days for 52%, 7–8 days for 34% and <7 days for 14% of all the patients. There was a statistically significant difference in recurrence by antibiotic duration (Figure 1). The odds of recurrence were 3.9 times higher for people with <7 days prescription compared with those with > 8 days (95% CI, 1.28–11.89, P = .017) (Table 1). The odds of recurrence were 1.5 times higher for those with a prescription of 7–8 days compared with those with a prescription of > 8 days, but the difference was not statistically significant (95% CI: 0.59, 3.7, P = .38).

Conclusion

Male patients diagnosed with a UTI who were treated with a course of antibiotics for > 7 days were less likely to have a UTI recurrence than patients who were treated for < 7 days. However, there was no statistically significant difference between 7 to 8 days vs. >8 days of antibiotics in terms of recurrence. This study will be continued to increase study power. Determining the best treatment course will reduce healthcare cost and patient morbidity from UTI recurrences.

Disclosures

All authors: No reported disclosures.
1457. Antimicrobial Resistance of Urinary Tract Infection Pathogens in South Korea: A Surveillance Report of the One-Year Assessment in 2017
Authors: Liu Changseung , Yoon Eun-Jeong , Kim Dokyun , Hee Shin Jong , Hwan Shin Jeong , Seob Shin Kyeong , Ah Kim Young , Uh Young , Soo Kim Hyun , Ree Kim Young , Jeong Seok Hoon
Published: October 2019

Background

Korean Antimicrobial Surveillance System (Kor-GLASS) was established in 2016, which is compatible with the Global Antimicrobial Resistance Surveillance System launched by WHO. Here, we report a one-year assessment of Kor-GLASS in 2017, focusing on the antimicrobial resistance of urine isolates.

Methods

Non-duplicated clinical isolates of E. coli and K. pneumoniae recovered from urine cultures were collected from 8 sentinel hospitals. Demographic information, infection origin (hospital origin or community origin), and admission type were investigated. Bacterial species were confirmed using a matrix-assisted laser desorption/ionization time-of-flight mass spectrometer. Antimicrobial susceptibility was tested by disk diffusion and broth microdilution methods.

Results

During the one-year period of surveillance from January 2017 to December 2017, a total of 9,130 (11.9%) isolates of target pathogens were recovered from urine specimens of 76,625 patients with suspected urinary tract infection (UTI). The rate of culture-positive was the highest in the < 1 age group (AG) (22.5%), stiffly decreased in the 5–<15 AG to 3.4%, and gradually increased with age up to 19.6% in the ≥ 85 AG. The mean occurrence of UTI per 10,000 patient-days for inpatients was 19.3 (range, 3.4–46.1) for E. coli and 4.0 (range, 1.5–7.3) for K. pneumoniae. Resistance rate for cefotaxime was higher than those for ceftazidime both in E. coli (31.3% vs. 10.3%) and K. pneumoniae isolates (39.0% vs. 29.8%). Resistance rate for ciprofloxacin in E. coli isolates was 40.9%, and that in K. pneumoniae isolates was 31.9%. Only 4.9% and 10.9% of E. coli and K. pneumoniae isolates exhibited resistance phenotype to cefoxitin, respectively. Ertapenem-resistance was more frequently identified in K. pneumoniae isolates (1.6%) than in E. coli isolates (0.1%). Multidrug-resistance (MDR) phenotype was identified in 61.4% of the E. coli and 44.8% of K. pneumoniae urine isolates.

Conclusion

Kor-GLASS generated well-curated surveillance data devoid of collection bias or isolate duplication. Cefoxitin was an alternative treatment to ciprofloxacin for urinary tract infections caused by Enterobacteriaceae. About one-half of urine isolates belonged to either MDR or XDR.

Disclosures

All authors: No reported disclosures.
1460. The Effectiveness of Short vs. Long Antibiotic Therapy in Hospitalized Adult Patients with Urinary Tract Infections: A Systematic Review and Meta-Analysis
Authors: Ballouz Tala , Rizk Nesrine
Published: October 2019

Background

Urinary tract infections (UTIs) are a frequent cause of morbidity and mortality in hospitalized patients, if not adequately and promptly treated. The optimal treatment duration is controversial and most recommendations are based on clinical experience. Current guidelines recommend 5–14 days of treatment depending on the type and severity of infection and the antibiotic used. With the emergence of multi-drug resistance, shorter durations are increasingly favored. This systematic review of randomized controlled trials (RCTs) aims at providing updated evidence on the effectiveness of short (≤7 days) vs. long (>7 days) antibiotic regimens in hospitalized adult patients.

Methods

MEDLINE, EMBASE, and CENTRAL were searched to identify relevant RCTs. Trial quality was evaluated using Cochrane’s Risk of Bias Tool. The primary outcome was clinical success. Secondary outcomes included microbiological success, withdrawal due to adverse events (AE), relapse, and reinfection rates. A random-effect meta-analysis was performed using R.

Results

8 RCTs conducted between 1995 and 2018 were identified. Trial quality was considered poor in 5, fair in 1 and good in 2 RCTs. Clinical and microbiological success was reported in all studies. Withdrawal due to AE was reported in 5, relapse and reinfection in 3 studies. Overall, there was no difference in clinical success between short and long courses (OR = 0.92, 95% CI 0.66–1.29; 2111 patients) (figure). Similarly, microbiological success was comparable in the two arms (OR = 1.0, 95% CI 0.70–1.43; 2111 patients). There was a higher, but nonsignificant, number of withdrawals due to AE in the long duration arm (OR = 0.78, 95% CI 0.29–2.11; 1890 patients). Patients receiving short courses had a nonsignificant higher rate of relapse (OR = 2.65, 95% CI 0.31–22.39, 175 patients). However, there was no difference in reinfection rates (OR = 1.12, 95% CI 0.26–4.90; 175 patients). A subgroup analysis limited to complicated UTIs showed similar results.

Conclusion

Based on the limited available evidence, short antibiotic courses appear to be equally effective as longer courses in the management of inpatient UTIs. Further research is needed to determine appropriate antibiotic treatment durations and assess treatment-related development of drug resistance.

Disclosures

All authors: No reported disclosures.
1462. Derivation of a Prediction Model for Risk of Drug-Resistant Urinary Tract Infection
Authors: Ali Sabeen , Claeys Kimberly C
Published: October 2019

Background

Urinary tract infections (UTIs) are among the most common indications for antibiotic therapy. As antibiotic resistance continues to grow, it is critical to identify those at higher risk for drug-resistant (DR) UTIs to guide empiric therapy, improve clinical outcomes, and limit costs of care. The aim of this study was to identify risk factors for DR UTI and develop a risk scoring tool which could aid in empiric antibiotic prescribing.

Methods

Single-center retrospective pilot study of adult patients treated for UTI from August 1, 2015 to August 31, 2016. Patients who had asymptomatic bacteriuria, were pregnant within 4 months of admission, or had improperly collected urine cultures were excluded. DR was defined as phenotypic resistance to at least 1 agent in 3 or more antibiotic classes commonly used to treat UTIs. Risk factors for DR UTI were derived from previously published literature and multivariable logistic regression of individual patient data (IPD). Adjusted odds ratios (aORs) were developed by combining ORs from previous literature and IPD. A scoring tool was derived from weight-proportional integer-adjusted coefficients of the predictive model aORs.

Results

Risk factors were derived from 9 previously published studies and adapted using IPD (N = 77) and included: long-term care (aOR = 4.31), prior hospitalization (aOR = 1.8), previous antibiotics (aOR = 4.33), advanced age (aOR = 1.12), urinary catheterization (aOR = 2.2), immune suppression (aOR = 1.6), and male sex (aOR = 2.56). Previous DR UTI was forced into the model (OR = 1.1). Baseline incidence of DR UTI was 28.7%. A risk score from 1 to 20 was developed and applied to IPD and demonstrated an area under the receiver operator curve (AUROC) of 0.625 (95% CI 0.484–0.767). Removing sex from the score produced an AUROC of 0.64 (95% CI 0.497–783). A sensitivity analysis applying the score to only urinary isolates that exhibited resistance to third-generation cephalosporins (13.8%) produced similar results.

Conclusion

Residence in long-term care and previous antibiotics were among the risk factors most closely associated with DR UTI. Considering cumulative risk scores may be useful in predicting DR UTI however the current study was hindered by a large degree of heterogeneity in previous literature.

Disclosures

All authors: No reported disclosures.
1463. The Rates of UTI Outpatient and Inpatient Visits from 2001 to 2015 Among an Insured Population
Authors: Foster Kendra , Simmering Jacob E , Polgreen Philip M , Polgreen Linnea A
Published: October 2019

Background

Hospitalizations attributable to urinary tract infections (UTI) have increased in recent years. One possible reason for the increase in admissions is a lack of effective oral agents, due to increasing rates of antimicrobial resistance, necessitating treatment with IV antibiotics. Our objective was to compare the rates of inpatient vs. outpatient treatment for UTIs.

Methods

We used the MarketScan database to identify UTI inpatient and outpatient visits from January 2001 through September 2015. Incidence rates for inpatient and outpatient visits were determined as a function of people at risk for UTIs. A difference-in-difference model with a change point in 2007 was used.

Results

During our study period, we identified 32,521,146 outpatient visits for UTI and 297,470 inpatient UTI visits. Rates for inpatient and outpatient visits were rising at similar rates before 2007. After 2007, the slopes differed, and the incidence of outpatient visits increased statistically (P = 0.023) when compared with inpatient visits.

Conclusion

Incidence of UTI hospitalizations is increasing but not as quickly as UTI outpatient visits. Since 2007, patients are more likely to be treated in the outpatient setting rather than in the inpatient setting.

Disclosures

All authors: No reported disclosures.
1490. Vancomycin 125 mg vs. 250 mg for the Treatment of Non-Severe and Severe Clostridium difficile Infections
Authors: Hsu Amy , Richardson Caitlin , Kuriyama Steve M
Published: October 2019

Background

Infectious Diseases Society of America (IDSA) guidelines recommend oral vancomycin 125 mg four times daily for 10 to 14 days for both non-severe and severe Clostridium difficile infections (CDI). Although 125 mg achieves sufficient fecal concentrations, doses of 250 mg are still commonly used in practice. There is limited data available comparing vancomycin 125 mg to higher doses. To the best of our knowledge, there are no studies that compare the effectiveness of vancomycin 125 mg vs. 250 mg in the treatment of CDI.

Methods

Single-center, retrospective cohort analysis of oral vancomycin 125 mg vs. 250 mg for the treatment of CDI between June 2018 and February 2019. Diagnosis of CDI involved symptomatic patients with positive Clostridium difficile toxin by either polymerase chain reaction or toxin enzyme immunoassay. We used IDSA guideline criteria of severe and non-severe to evaluate those who received a 10- or 14-day course of oral vancomycin. We excluded patients with concomitant metronidazole or fidaxomicin use, history of CDI in the past 8 weeks, fulminant CDI, or mortality prior to completion of therapy. The primary outcome was resolution of clinically significant diarrhea. Secondary outcomes included duration of loose stools, relapse of CDI within 30 days of diagnosis, and 30-day all-cause mortality.

Results

A total of 93 patients were included in the study, with 71 patients (76.3%) in the 125 mg group and 22 patients (23.7%) in the 250 mg group. Both groups were well matched with no significant differences at baseline or during treatment. Results showed no statistical difference in clinical resolution between the 125 mg and 250 mg groups, with 70 patients (98.6%) and 22 patients (100%) achieving clinical resolution, respectively (P = 1.00). Secondary outcomes revealed no statistical difference in duration of symptoms, relapse, or 30-day all-cause mortality.

Conclusion

There was no difference in clinical resolution of CDI between the vancomycin 125 mg and 250 mg groups. Furthermore, the dose of vancomycin did not have a significant effect on duration of symptoms, relapse, or 30-day all-cause mortality. Using the lower, guideline-recommended dose of vancomycin could potentially reduce patient exposure and provide cost-savings benefits without sacrificing efficacy.

Disclosures

All authors: No reported disclosures.
1492. Comparison of Acute Cholangitis in Patients With or Without Cancer
Authors: Sokal Aurélien , Chawki Sylvain , Nguyen Yann , Sauvanet Alain , Ponsot Philippe , Fantin Bruno , de Lastours Victoire
Published: October 2019

Background

Cancer-associated acute cholangitis (CAAC) are becoming more frequent and their characteristics may be changing with the evolution of cancer management. Our aim was to compare clinical, microbiological and outcome characteristics of CAAC to those of cancer-free acute cholangitis (CFAC).

Methods

All consecutive cases of acute cholangitis (AC) from November 2015 to March 2017 were collected retrospectively in a single tertiary care hospital in Clichy, France, specialized in gastroenterology. Hospital stays referred as AC by coding were screened. Patients fulfilling the 2018 Tokyo Guidelines diagnostic criteria for definite AC were included. Data were collected using a standardized form. CAAC were defined as AC that occurred in patients who had active cancer or history of cancer in the five previous years. CFAC were defined as AC in patient who no history of cancer, or in remission for more than 5 years. Comparison was made using Fisher or Student’s t-test. P < 0.05 was considered as significant.

Results

156 episodes of AC in 130 patients were analyzed. 101 had CAAC and 55 had CFAC. Age and sex did not differ (table 1), but CAAC had a higher Charlson’s comorbidity index (4.4 vs. 1.7, P < 0.0001). Despite similar clinical presentation, CAAC had more pronounced cholestasis (Gamma GT 659 vs. 391UI/L; Alkaline phosphatases 526 vs. 309 UI/L; P < 0.0001 for both) and C-reactive protein level (133 vs. 97mg/L, P = 0.008, Table 2). E. coli was more common in CFAC (72.4% vs. 54% of positive blood cultures, P = 0.004). In bile cultures, Enterococci and multi-drug-resistant Gram negatives tended to be more frequent in CAAC than in CFAC (63 vs. 17%, P = 0.07 and 9.1% vs. 4.1%, P = 0.33, Table 2), respectively. CAAC more frequently required drainage (86.1% of cases vs. 43.6% in CFAC (P < 0.0001), including radiological drainage (42.5% vs. 12.5%; P = 0.008) and with multiple sessions (28.7% vs. 8.3%, P < 0.0001, Table 3). Antibiotherapy duration did not differ between the two groups. Despite similar initial severity, only 51.5% of patients with CAAC were alive, without febrile recurrence or other biliary drainage at day 28, vs. 85.5% of patients with CFAC (P < 0.0001, Table 3).

Conclusion

Despite comparable initial clinical presentation, management is more complex and outcome less favorable in CAAC vs. CFAC.

Disclosures

All authors: No reported disclosures.
1494. Clinical Factors Associated with a Positive C. difficile PCR Test
Authors: Cushman Teresa , Barron Michelle , Arbet Jaron , Weber Rachel , Zhuang Yaxu , Jeffers Alexiss , Huang Misha
Published: October 2019

Background

C. difficile infection (CDI) remains a significant cause of morbidity and mortality. The most appropriate clinical scenario for CDI testing is unclear. The IDSA/SHEA guideline recommends testing patients with unexplained new-onset ≥3 stools in 24 hours. This study sought to evaluate clinical factors associated with a positive C. difficile PCR test.

Methods

We conducted a retrospective cohort study of adults (age >18 years old) admitted to the University of Colorado Hospital for whom a C. difficile PCR, either as a standalone test or part of the Biofire® Filmarray® Gastrointestinal Panel (GI Panel), was ordered between October 1, 2015 and August 31, 2017. Data collected included time since admission to test order, hospital length of stay, history of CDI, antibiotic use in the past 90 days, clinical presentation in the 24 hours preceding test order (fever, leukocytosis, number of stools), and laxative or antibiotic administration within 24 hours of test order. Multivariate logistic regression was used to evaluate the association of the above variables with having a positive C. difficile PCR test. If multiple tests were ordered during a single hospital encounter, only the first test was included in our analysis.

Results

3,070 tests were performed; of these, 72% were ordered in the first 72 hours of admission. Overall, 19% of tests were positive. After adjusting for clinical variables, patients with a prior history of C. difficile or who had received antibiotics in the past 24 hours were significantly more likely to have a positive test [OR 2.2 95% CI (1.54, 3.18) P < 0.0001] and [OR 16 95% CI (8.22, 31.41) P < 0.0001], respectively. Patients who used laxatives were significantly less likely to have a positive test [OR 0.75 95% CI (0.61, 0.91) P = 0.004]. The number of stools and presence of fever or leukocytosis were not significantly associated with a positive test.

Conclusion

Prior history of C. difficile and antibiotics use was highly associated with a positive C. difficile test, while laxatives use was associated with a negative test. The number of stools was not significantly associated with a positive C. difficile test, suggesting this may be less important clinical factor than previously believed; however, restricting testing in patients receiving laxatives is likely warranted.

Disclosures

All authors: No reported disclosures.
1496. Bezlotoxumab Administered at the End of a Suppressive Drug Regimen for Patients with Multiply Recurrent Clostridioides difficile Infection
Authors: Tan Xing , Danziger Larry H , Gerding Dale N
Published: October 2019

Background

Recurrent Clostridioides difficile infection (CDI) remains a public health burden, affecting as many as 35% of patients with primary CDI. Bezlotoxumab, a monoclonal anti-toxin B antibody, was the first FDA-approved agent indicated for the prevention of recurrent CDI, but real-world experience is limited, particularly in patients with multiple CDI recurrences.

Methods

We conducted a retrospective case study of patients with multiple CDI recurrences who failed prior treatments with pulsed and tapered vancomycin and fidaxomicin regimens. Six patients in a single CDI specialty outpatient clinic received a single iv infusion of bezlotoxumab at the end of a suppressive vancomycin or fidaxomicin treatment regimen. The suppressive treatment was stopped immediately after the bezlotoxumab infusion and the patients were followed closely for recurrent symptoms and need for additional CDI treatment.

Results

Four of 6 patients who received bezlotoxumab at the end of a suppressive treatment regimen did not require subsequent CDI treatment and have been followed for 2 weeks to 1.5 years to date. These four patients experienced a single, self-limited episode of diarrhea within 2 weeks of the infusion, and did not require subsequent CDI treatment. Two patients had recurrent symptoms and positive stool C. difficile tests one month after infusion and were re-started on CDI treatment. One of the patients had longstanding underlying irritable bowel syndrome and variable initial response to re-starting vancomycin. The other patient responded to re-starting fidaxomicin.

Conclusion

Bezlotoxumab at the end of a prolonged suppressive treatment regimen may be an effective therapeutic strategy in preventing recurrent CDI in complicated, multiply recurrent CDI patients.

Disclosures

All authors: No reported disclosures.
1501. Risk Factors for Clostridium difficile Infection in Patients Hospitalized with Community-Acquired Pneumonia
Authors: Deshpande Abhishek , Zilberberg Marya , Yu Pei-Chun , Imrey Peter , Rothberg Michael
Published: October 2019

Background

Patients with community-acquired pneumonia (CAP) are often prescribed broad-spectrum antibiotics, putting them at risk for developing Clostridium difficile infection (CDI). Previous studies of risk factors for CDI in this population have suffered from small sample sizes. We examined the risk factors for CDI in patients hospitalized with CAP using a large US database.

Methods

We included adult patients admitted with CAP 2010–2015 to 175 US hospitals participating in Premier and providing administrative and microbiological data. Patients were identified as having CAP if they had a diagnosis of pneumonia, a chest radiograph, and were treated with antimicrobials on day 1 and for ≥3 days. Incident CDI was identified with ICD-9 diagnosis code (not present on admission) and a positive laboratory test. We used descriptive statistics and mixed multiple logistic regression modeling to mutually adjust and evaluate risk factors previously suggested in the CDI literature.

Results

Among 148,417 inpatients with pneumonia treated with antibiotics, 789 (0.53%) developed CDI. The median age was 75 years, and 53% were female. Compared with patients with no CDI, those with CDI were older (75 vs. 72 years), had more comorbidities (5 vs. 3), and were more likely to be admitted from SNF (15.7% vs. 7.3%) or hospitalized in the past 3 months (11.8% vs. 7.1) (all comparisons P < 0.001). After multivariable adjustment, factors significantly associated with development of CDI included increasing age, admission from a skilled nursing facility, and receipt of piperacillin/tazobactam, aztreonam or intravenous vancomycin (Figure 1). Receipt of third-generation cephalosporins or fluoroquinolones was not an independent predictor of CDI.

Conclusion

In a large US inpatient sample hospitalized for pneumonia and treated with antimicrobials, only 0.53% of the patients developed CDI as defined by an ICD-9 code and positive laboratory test. Reducing the exposure to healthcare facilities and certain high-risk antibiotics may reduce the burden of CDI in patients with CAP.

Disclosures

All authors: No reported disclosures.
1506. Outcomes of Standardized Neonatal Cephalexin Dosing
Authors: Robertson Melena J , Tran Van , Nuibe Andrew M
Published: October 2019

Background

The optimal dosing of cephalexin in infants ≤90 days old is not well known. Our Antimicrobial Stewardship Program (ASP) standardized cephalexin dosing for inpatients ≥30 days old using available literature and released an antimicrobial dosing guideline in September 2016. Recommended antimicrobial dosing for inpatients <30 days old followed in November 2017. We reviewed the indications, cephalexin dosing, and clinical outcomes of patients before and after the release of our ASP’s cephalexin dosing guidelines.

Methods

Webi Universe was queried for cephalexin orders for inpatients ≤ 90 days old at the Inova Children’s Hospital from January 2016 to November 2018. Manual chart review extracted clinical points of interest and ensured that inclusion criteria were met. For patients <30 days old, the pre-intervention period was January 2016 to October 2017 and the post-intervention period was November 2017 to October 2018. For patients ≥30 days old the pre-intervention period was January 2016 to August 2016 and the post-intervention period was September 2016 to October 2018. Aggregate data from the two pre-intervention and two post-intervention periods were pooled, respectively.

Results

41 patients were identified: 25 in the pre-intervention period and 16 in the post-intervention period. The median age of patients in the pre-intervention period was 16 days compared with 31 days in the post-intervention period (P = 0.02). No patients had acute kidney injury requiring cephalexin renal dosing. Skin and soft-tissue infections (18) and urinary tract infections (10) were the most common infections in both periods. 24% of patients received the recommended cephalexin dose in the pre-intervention period compared with 63% in the post-intervention period (P = 0.02). Logistic regression controlling for pathogens and area of care showed that patient age predicted the use of recommended cephalexin dosing (OR 1.1, 95% CI: 1.01–1.21). There were no deaths or recrudescent infections.

Conclusion

Our ASP’s interventions improved adherence to standardized cephalexin dosing in inpatients ≤90 days old without any adverse clinical outcomes. Patients ≥30 days old were more likely to receive recommended cephalexin dosing. Opportunities remain to best define the optimal dose of cephalexin in infants ≤90 days old.

Disclosures

All authors: No reported disclosures.
1510. Improving the Management of Pediatric Complicated Pneumonia
Authors: Nuibe Andrew M , Tran Van , Levorson Rebecca E
Published: October 2019

Background

Pneumonia is a leading cause of pediatric hospitalization in the United States. Our Antimicrobial Stewardship Program (ASP) recognized significant variation in the management of pediatric complicated pneumonia. We developed and implemented a quality improvement (QI) intervention to align the management of complicated pneumonia with national guidelines and compared the medical care and clinical outcomes between a pre-intervention period and two post-intervention periods.

Methods

We queried Webi Universe for all ICD-9 and ICD-10-related admissions for pneumonia at our facility from November 15, 2015 to February 28, 2019. Manual chart review was done to extract clinical points of interest and to ensure that all included patients met inclusion criteria. Our first intervention (period 1) consisted of education to providers to increase use of chest tubes instilled with fibrinolytics and to decrease empiric antistaphylococcal therapy. Our second intervention (period 2) consisted of a care process model which codified the standardized management made by the first intervention, followed by several didactic sessions.

Results

29 patients were identified in the pre-intervention period, 11 in post-intervention period 1, and 27 in post-intervention period 2. Streptococcal species were the most common pathogens recovered in all periods. Following our interventions the number of video-assisted thorascopic procedures to drain complicated parapneumonic effusions decreased three-fold in favor of chest tubes instilled with fibrinolytics (P < 0.01). Our interventions also reduced empiric antistaphylococcal therapy within the first 48 hours of admission (P = 0.02) and decreased the use of empiric vancomycin three-fold (P = 0.01). Our interventions did not affect the median length of stay, frequency of pulmonary complications, number of 30-day readmissions, or duration of antimicrobial therapy.

Conclusion

Our ASP’s QI intervention decreased surgical drainage of complicated parapneumonic effusions and decreased the use of empiric antistaphylococcal agents without an increase in complications or readmissions. Opportunities remain to decrease the use of multiple antimicrobial agents within the first 48 hours of admission and to decrease the empiric use of antistaphylococcal therapy.

Disclosures

All authors: No reported disclosures.
1516. Early-Onset Neonatal Sepsis Due to Haemophilus influenzae
Authors: Varghese Alyssa , Korgenski Kent , Crandall Hillary , Bonkowski Anne
Published: October 2019

Background

Haemophilus influenzae causes serious invasive disease across all ages, but has not been widely described in neonatal early-onset sepsis (EOS). EOS, likely caused by organisms acquired from the mother, can lead to significant morbidity and mortality, particularly for preterm infants. There are reports of increasing ampicillin resistance in H. influenzae. We describe a case series of EOS due to H. influenzae at our institution.

Methods

Neonatal H. influenzae EOS was identified based on positive sterile site cultures at <72 hours of life in infants hospitalized at an Intermountain Healthcare (IHC) facility from 2007–2017. Demographics, clinical and microbiologic data were obtained through an IRB-approved electronic chart and microbiology review.

Results

Twelve neonates with H. influenzae EOS were identified over 11 years. Nine were preterm (<37 weeks); five were extremely preterm (<28 weeks). Eight had low birth weight (<2,500 g); five had very low birth weight (<1,500 g). Most (66%) mothers were primigravida; median maternal age was 24.5 years. Only four (33%) mothers had prolonged rupture of membranes (>24 hours).

All infants had signs and symptoms of sepsis within 24 hours of birth. The majority (10/12) had a blood culture positive for H. influenzae from the time of delivery. Two infants had negative delivery blood cultures but a H. influenzae-positive placental culture. No infant had > 1 day of bacteremia. One H. influenzae isolate was serotype b, one serotype c and one non-typeable, but most isolates (9/12) were not serotyped. Only one isolate produced a β-lactamase. All infants were empirically started on ampicillin and gentamicin at delivery. Nine infants underwent lumbar puncture, two were suggestive of meningitis but cultures were negative. Five infants developed interventricular hemorrhage and six required vasoactive medications. No infant died.

Conclusion

H. influenzae is an infrequent but important cause of neonatal EOS. H. influenzae EOS occurred in infants with known risk factors, including prolonged rupture of membranes, prematurity, and low birth weight. Recognition of H. influenzae as a potential pathogen in EOS has implications for the use of empiric antibiotic therapy particularly ampicillin, in septic neonates.

Disclosures

All authors: No reported disclosures.
1523. Clinical Epidemiology of Children with Orbital Cellulitis
Authors: Sharma Meghna , Espinel Alexandra , Ansusinha Emily , Hamdy Rana F
Published: October 2019

Background

The microbiology of pathogens causing orbital cellulitis in children is evolving over time, with studies from around 10 years ago describing MRSA as responsible for anywhere from 0 to 13% of cases of orbital cellulitis. However, the prevalence of community-acquired MRSA infections has declined over the past decade. A current understanding of the bacteria most commonly found to be responsible for orbital cellulitis would be important to inform the empiric antibiotic regimens for cases of orbital cellulitis in which no microbiologic data are available.

Methods

This is a single-center retrospective cohort study of children ≤18 years hospitalized with orbital cellulitis at Children’s National Medical Center between January 1, 2017 and July 31, 2018. We excluded children with immunocompromising conditions, cystic fibrosis, underlying craniofacial abnormality, or recent craniofacial or otolaryngologic surgery. Baseline clinical characteristics, microbiologic data, clinical outcomes, and antibiotic treatment data were abstracted through structured chart review and summarized with descriptive statistics.

Results

We identified 68 children that met inclusion criteria, with an average age of 8.2 years; 66.2% were male, 48.5% were African American, and 14.7% were Hispanic. Most (67.6%) had no underlying medical problems, 14.7% had asthma, and 22.1% had allergic rhinitis. The median duration of symptoms prior to presentation was 4 days. An abscess or phlegmon was identified in 41 of the 68 (60.3%). Three patients (4.4%) developed intracranial complications. About one-quarter (27.9%) of all patients in the cohort underwent surgical drainage. The most commonly identified pathogens were viridans group streptococci (7/19, 36.8%), followed by Staphylococcus aureus (4/19, 21.1%). Anti-MRSA therapy was provided empirically in almost all (95.6%) of patients.

Conclusion

One-quarter of all patients hospitalized for orbital cellulitis underwent surgical drainage, and viridans group streptococci and S. aureus were the most commonly isolated pathogens. While MRSA was isolated in only one patient (5.2%), almost all received empiric anti-MRSA therapy.

Disclosures

All authors: No reported disclosures.
1533. Is Cation-Adjusted Mueller–Hinton Broth (CAMHB) Appropriate for Metallo-β-lactamase (MBL) Susceptibility Testing? Novel Insights in In Vitro–In Vivo Discordance Among MBL-Producing Enterobacteriaceae
Authors: Asempa Tomefa E , Abdelraouf Kamilia , Nicolau David P
Published: October 2019

Background

MBLs, which require Zn for catalytic activity, are a major contributor to high-level β-lactam resistance when tested using conventional CAMHB. We have previously reported marked reductions in meropenem (MEM) MICs in Zn-depleted media (Chelex-CAMHB and EDTA-CAMHB; Zn [C] <0.002 mg/L) compared with conventional CAMHB (Zn [C] 0.959 mg/L) against a variety of MBL-producing isolates, whereas Zn-depletion had no impact on levofloxacin (LVX) MICs (ASM Microbe 2019, San Francisco. Abstract P508). To explore in vivo implications, we evaluated the efficacy of MEM human simulated regimen (HSR) against MBL-producing isolates in a murine pneumonia model. In addition, LVX HSR was examined for model validation.

Methods

Nine MBL-producing isolates (NDM, n = 5; VIM, n = 2; IMP, n = 2) were utilized. CAMHB, Chelex-CAMHB, and EDTA-CAMHB MEM MICs ranged from 16 to > 64, ≤0.0625 to 0.5, and ≤ 0.0625 to 0.5 mg/L, respectively. LVX MICs ranged from ≤ 0.0625 – > 64 mg/L. Neutropenic lung-infected ICR mice received a MEM HSR of 2g q8h [1.5 hours infusion], 2 lower MEM exposures or LVX 750 mg q24h HSR. Zn [C] were determined in the epithelial lining fluid (ELF) of infected mice.

Results

LVX displayed predictable in vivo efficacy consistent with its phenotypic profile irrespective of the media utilized for MIC testing (figure). Despite attaining zero %T> MIC using values generated in CAMHB, MEM HSR produced marked bacterial reductions against all MBL-producing isolates (figure). Reductions in MEM exposures produced bacterial killing concordant with its pharmacodynamic profile using Zn-depleted CAMHB MIC values. Zn [C] in infected murine ELF were undetectable, i.e., <0.002 mg/L.

Conclusion

Our results indicate that MEM in vivo efficacy is best represented by the pharmacodynamic profile generated using MICs determined in Zn-depleted media for MBL-producing Enterobacteriaceae. These observations are consistent with the case reports describing positive outcomes in MBL-infected patients following treatment with carbapenems (Infection 2018;46:1–13). Our translational data suggest that the use of conventional CAMHB for MBL susceptibility testing is inappropriate in distinguishing meaningful in vivo resistance given that Zn [C] are supraphysiologic in conventional CAMHB and negligible at infection sites.

Disclosures

All authors: No reported disclosures.
1537. Multicenter Study with Therapeutic Drug Monitoring (TDM) of Voriconazole (VRCZ) in Japanese Patients
Authors: Ueda Takashi , Takesue Yoshio , Hamada Yukihiro , Fukunaga Keiko , Ikegame Kazuhiro , Ebihara Fumiya , Kimura Toshimi , Nakajima Kazuhiro , Miyazaki Taiga , Nakada-Motokawa Nana , Nagao Miki , Kawamura Hideki , Shigemi Akari , Miyazaki Yoshitsugu
Published: October 2019

Background

TDM of VRCZ might be useful, especially in Asian people because of CYP2C19 genetic polymorphisms. However, limited data are available because of the small sample size.

Methods

Patients who received VRCZ and had TDM were reviewed retrospectively at five institutions. Adequate VRCZ dosage was defined as a loading dose of 5–6 ± 0.5 mg/kg twice daily followed by a maintenance dose of 3–4 ± 0.5 mg/kg twice daily. For prophylaxis, the loading dose was left to the physician’s discretion. Optimal timing of TDM was defined as 4–7 days after starting therapy. Patients with adequate dosing and optimal timing of TDM were evaluated for analysis of trough levels (Cmin). Target Cmin was set at 1–5 µg/mL.

Results

The study included 584 patients (treatment: 402; prophylaxis: 182). TDM was conducted on days 4–7 in 66.5% of patients (>7, 30.2%). A low adequate dosage (44.5%) was observed for treatment mainly because of a low performance of the loading dose (46.8%). Achievement of target Cmin was obtained in 62.7% (>5 µg/mL, 32.2%) in the treatment group and in 67.6% (11.0%) in the prophylaxis group. Seventy-one of 81 (81.7%) patients who required a dose reduction reached target Cmin by the second TDM. In 38 patients whose dose was not altered at oral switching, Cmin was significantly reduced from 2.5 ± 1.6 to 1.2 ± 1.3 μg/mL (P = 0.002), which indicated the necessity of TDM after oral switching. Hepatotoxicity occurred in 4.6% and visual symptoms in 7.9% of patients. Visual symptoms resolved without discontinuation of VRCZ in 73.9% of patients. Because of dosage adjustment based on TDM, high Cmin did not cause hepatotoxicity. However, the incidence of visual symptoms was significantly higher in patients with a high Cmin (12.7% vs. 5.4%, P = 0.002).

Conclusion

One-third of Japanese patients who underwent VRCZ treatment with a loading dose showed high Cmin. Occurrence of hepatotoxicity was prevented with alteration of dosage in these patients (AMED, JP18fk0108045).

Disclosures

All authors: No reported disclosures.
1541. A Novel and Fast Liquid Chromatography Method for Determination of Fluoroquinolones in Human Plasma
Authors: Yildirim Sercan , Nur Karakoc Hanife , Yasar Ahmet , Koksal Iftikhar
Published: October 2019

Background

Fluoroquinolones (FQs) are frequently used antimicrobial agents. Considering that the FQs exhibit concentration-dependent bactericidal activity, concentrations of FQs in the biological fluids must be monitored to ensure treatment success. The literature search revealed that there is no method for the determination of levofloxacin (LEV), ciprofloxacin (CIP), moxifloxacin (MOX), and gemifloxacin (GEM) in plasma up to date. Consequently, the aim of this study was to develop and validate a new high-performance liquid chromatography (HPLC) method for determination of these FQs in plasma and evaluate effects of concomitant drugs on plasma FQ concentrations of patients.

Methods

Blank plasma samples spiked with FQs were employed for method validation studies. Validation studies were conducted in accordance with the recommendations of the US FDA. In order to demonstrate feasibility of method, 5 patients with polypharmacy, receiving orally CIP, LEV, or MOX as part of their treatment were included in the study. Blood samples were collected at two different times, just before and 2 hours after the second drug administration.

Results

The separation of FQs was accomplished within 7.5 minutes. The method was linear in the range of 0.1–10 µg/mL with the correlation coefficient >0.99. The RSD at four concentration levels (0.1, 0.3, 4, and 8 µg/mL) was less than 7% with accuracy in the range of 91.8–111.9%.The method was applied to the determination of CIP, LEV, and MOX levels in plasma samples of 5 patients with polypharmacy. Determined CIP and LEV levels were in accordance with literature. On the other hand, MOX concentration 2 hours after administration in plasma of one patient was found to be 6.1 ± 0.1 µg/mL which was higher than previously reported maximum plasma concentration of MOX (4.5 µg/mL). The patient had hypoalbuminemia and MOX is approximately 50% bound to serum proteins. Due to low level of albumin, the level of free MOX in plasma may be increased.

Conclusion

A simple, fast, and reliable HPLC method was developed and validated for the determination of LEV, CIP, MOX, and GEM in plasma. It is suitable therapeutic drug monitoring of these FQs and can be applied to other pharmacokinetic and toxicological studies.

Disclosures

All authors: No reported disclosures.