bluuebunny/crossref_metadata_2025_split huggingface dataset:
1467. Antimicrobial Susceptibility and Molecular Characterization of Extended-Spectrum β-Lactamase of Escherichia coli and Klebsiella pneumoniae of Urine Samples Isolated from Community Patients in South Brazil
Authors: Naomi Tano Zuleica , Vespero Eliana Carolina , Dias Juliana , Mestre Tejo Alexandre , Candido Evelyn P , Andrekowicz Andreia , Ramos Ana , Kobayashi Renata , Pavanelli Wander 
Published: October 2019

Abstract

Background
Enterobacteriaceae is the main pathogens of UTI. It is important to be aware the local epidemiological data for an appropriate initial treatment. Resistance to antimicrobial agents has increased, especially to first-choice antibiotics in the treatment of cystitis. Our objective is to asses the antimicrobial susceptibility profile from uropathogens isolated in community and evaluated the dissemination of extended-spectrum ß lactamase (ESBL), in E. coli and K. pneumoniae in south of Brazil.

Methods
From June 2016 to June 2017, all urine samples collected in the Basic Health Units and Emergency Departments were sent to a Central Laboratory. Identification and susceptibility tests were performed on the VITEK® 2 (bioMérieux, France) system. Clinical Laboratory Standards Institute (CLSI) breakpoints were used for the interpretation of susceptibility. Positive cultures were defined as those demonstrating ≥105 CFU / mL (colony-forming units). The presence of ESBL was also subjected to the Chrom ID BLEE® agar plate test (bioMérieux- Marcyl’Etoile, France). PCR technique uses specific primers for genes blaTEM and blaSHV. Detection of the blaCTX-M genes was performed by multiplex PCR.

Results
A total of 56,555 microbiologic tests were performed, 8189 were positive. Women were responsible for 89.4%, and 10% were pregnant. Table 1 shows uropathogens isolated. Graphic 1 shows antimicrobial susceptibility. Extended-spectrum ß lactamase production was present in 6.7% (n = 489). People older than 60 years had ESBL more frequent (P <0.05) as well as being pregnant is not related to ESBL (P <0.05). Table 2 shows the distribution of the bla genotypes.
Table 3: Distribution of blaCTX-M. Among blaCTX-M1 genotype, blaCTX-M15 was the most frequent.

Conclusion
In this study, the most frequent uropathogen isolated was E. coli followed by K. pneumoniae. Cotrimoxazol had high rates of resistance and nitrofurantoin the lowest. Quinolone resistance is more than 10%. Sensitivity to aminoglycosides and carbapenems remains high.We found relevant frequency of ESBL, CTX-M-1-group most commonly found. Among CTX-M-1, blaCTX-M15 was the most isolated.

Disclosures
All authors: No reported disclosures.
1474. Epidemiology and Outcomes of Hospitalized Patients with Urinary Tract Infections (UTI) Due to Multidrug-Resistant Organisms (MDRO)
Authors: Lahrman Frances J , Olsen Margaret A , Stwalley Dustin , Burnham Jason P , Kwon Jennie H 
Published: October 2019

Abstract

Background
MDROs are a threat to public health, and UTIs are the most common type of MDRO infection. The objective of this study was to describe risk factors and outcomes associated with MDRO UTIs.

Methods
A retrospective cohort study with IRB approval from Barnes-Jewish Hospital, January 1, 2006–November 8, 2017. Demographics, comorbidities, procedures, outcomes, and culture data were collected from the BJC Healthcare Informatics database for hospitalized patients with MDRO UTIs. MDROs were defined according to European and US CDC standards.

Results
A total of 7,945 hospitalized patients with MDRO UTI were identified. Demographics and comorbidities are described in Table 1. Notably, 69% of patients were female, 23% had underlying urinary system disease, and at least 20% had a foley catheter in place. Of these patients, 18% required an intensive care unit (ICU) stay within 48 hours before/after the positive urine culture, and 7% died during their hospitalization (Table 2). The most frequent cause of UTIs was MDR Enterobacteriaceae (Table 3).

Conclusion
Patients who are hospitalized with MDRO UTIs frequently have underlying urinary system disease and/or foley catheter. MDRO UTIs are a significant cause of morbidity and mortality in hospitalized patients, with 18% requiring an ICU stay, and death in 7% during the hospitalization. Further research is needed regarding risk factors and interventions to prevent, detect, and treat MDRO UTIs.

Disclosures
All authors: No reported disclosures.
1476. The Role of Empirical Antibiotics Determined by Pre-procedural Urinalysis and Urine Cultures in Elective Urological Interventions
Authors: Smith Georgia , Chung Kay Patrick , Catterwell Rick , Nelson Renjy , Warner Morgyn 
Published: October 2019

Abstract

Background
At a urology center in Australia, patients undergoing elective nonurgent urological surgery routinely receive empirical antibiotic treatment based on urinalysis (UA) prior to intervention to treat presumptive bacteriuria. Sterilization of urine with empirical antibiotics in procedures involving stone manipulation and mucosal disruption in the genitourinary system has been shown to reduce infection risks but whether this translates to low-risk urological interventions is not clear.

Methods
Patients undergoing outpatient elective urological procedures during a 3-month period between September and November 2017 were retrospectively reviewed. Patient demographics, results of urinalyses, empirical antibiotic use, and data surrounding post-intervention complications were collected and reviewed. Results were analyzed using SPSS v 25.

Results
Of 119 patients, 111 underwent a pre-procedure urinalysis. Fifty-eight percent (n = 64) of patients were treated with empiric antibiotics pre-operatively based on a positive UA (defined as the presence of urinary leukocytes or nitrites). Fifty-five percent (n = 41) of patients who received empirical antibiotics returned a positive urine culture, and only 49 percent (n = 20) of those receiving antibiotics cultured organisms susceptible to initial antibiotics prescribed. 1 Death, 3 incidences of bacteremia, and 10 incidences of bacteriuria up to 2 weeks occurred post-intervention in this cohort. There was no discernible risk of adverse events based on a composite of post-intervention death, bacteremia and bacteriuria in patients with a positive pre-procedural UA (n = 67/111, RR0.67 CI 0.49–0.91, P = 0.10). Pre-procedural sterilized urine similarly did not demonstrated any reduced risk of post-intervention adverse outcomes (n = 77/119, RR1.02 CI 0.64–1.63, P = 0.94).

Conclusion
This study demonstrated no increased risk of post-operative infection in patients with a positive urinalysis or urine culture with bacteriuria prior to intervention. There was a high use of broad-spectrum antibiotic as a reflex to positive urinalyses alone highlighting an avenue for improved anti-microbial stewardship. More research is needed to guide clinicians on the role of urine cultures and antibiotics prior to non-urgent urological procedures.

Disclosures
All authors: No reported disclosures.
1520. Streptococcus anginosus Group Organisms Are an Increasing Cause of Complicated Sinusitis and Otitis Media in Children
Authors: McNeil Jonathan C , Dunn James , Kaplan Sheldon L , Vallejo Jesus G 
Published: October 2019

Abstract

Background
The Streptococcus anginosus group (SAG), including S. anginosus, S. intermedius and S. constellatus, are common flora of the oral cavity, respiratory tree and gastrointestinal tract. However, these organisms have the potential to cause serious invasive infections and are notably pyogenic. We observed an apparent increase in the frequency of intraorbital and intracranial infections resulting from SAG at Texas Children’s Hospital (TCH). We undertook a retrospective review to describe the frequency and clinical features of these infections.

Methods
We reviewed the database of the clinical microbiology laboratory at TCH from 2011 to 2018 for SAG-positive cultures. For purposes of this study, cases included were those associated with 1) either otitis media or sinusitis and 2) Pott’s Puffy Tumor, orbital abscesses, epidural abscesses, subdural empyema, brain parenchymal abscesses, dural enhancement by imaging or mastoiditis. Similar methods were used for SAG identification throughout the study period. The number of cases per year was used along with annual hospital admissions data to estimate case rate; case rate trends were examined using linear regression.

Results
950 cultures positive for SAG were identified by the clinical lab; 95 cases met inclusion criteria. The median age of patients was 11.4 years. Specific diagnoses are presented in Figure 1. S. intermedius was most commonly isolated (81.1%) followed by S. constellatus (12.6%) and S. anginosus (7.4%); 50.5% of cases were polymicrobial. Among polymicrobial cases, S. aureus was most frequently isolated (25%). All patients underwent surgical intervention and 20.5% underwent ≥2 procedures (Figure 2). 16.8% were associated with intracranial thromboses and 4.2% with CNS infarcts; 8.4% of patients experienced persistent neurologic deficits. All isolates were susceptible to penicillin. We observed an increase in the annual disease rate during the study (Figure 3, P = 0.01).

Conclusion
Complications of otitis media and sinusitis due to SAG are associated with substantial morbidity. These infections are becomingly increasingly common at our center although the precise reason for this temporal trend is unclear. Multicenter studies are needed to validate these epidemiologic findings.

Disclosures
All authors: No reported disclosures.
1521. Evaluation of the Microbiology of Intraabdominal Infections in Children and Implications for Treatment and Outcomes
Authors: Villalobos-Fry Tibisay I , Schaffer Mahlon , Wheatley Kristin H 
Published: October 2019

Abstract

Background
Acute appendicitis is the most common surgical emergency in pediatric medicine. Pseudomonas aeruginosa has been reported in up to 23% of intraoperative cultures though current recommendations do not specify the need for antipseudomonal coverage for preoperative treatment. Prior to transitioning the empiric antibiotic regimen used in the management of perforated appendicitis from an antipseudomonal agent to a simplified daily antibiotic regimen, we conducted a retrospective review of bacterial cultures obtained from intraabdominal fluid collections and antibiotic regimens in children that underwent surgical treatment of perforated appendicitis and/or intraabdominal abscesses.

Methods
A retrospective chart review of electronic medical records was conducted for pediatric patients admitted with a diagnosis of perforated appendicitis and/or intraabdominal abscess between April 1, 2016 and April 30, 2018.

Results
Seventy-two patients met inclusion criteria for the study with abscess identified prior to surgery in 11 patients (42.3%). Intraabdominal cultures were obtained in 48 patients (66.7%). The predominant organisms isolated were Escherichia coli, Bacteroides fragilis, and alpha-hemolytic Streptococcus. P. aeruginosa was identified in 12 (24%) cultures and never as a single organism. The majority of patients received piperacillin/tazobactam empirically (91.7%) with a median duration of 5 days (IQR 2). Forty-four patients (61.1%) received oral antibiotics to continue therapy after discharge and 75% received amoxicillin/clavulanate. Of the 12 patients with P. aeruginosa isolated, all patients received piperacillin/tazobactam empirically and 8 (66.7%) were transitioned to oral antibiotics to complete therapy, of which only two regimens retained antipseudomonal coverage.

Conclusion
Majority of intraabdominal cultures were polymicrobial and the isolation of P. aeruginosa did not appear to impact the choice of definitive antimicrobial therapy. The predominant organisms identified suggest that a non-antipseudomonal regimen (i.e., cephalosporin with metronidazole) may be considered for empiric antibiotic therapy for cases of perforated appendicitis.

Disclosures
All authors: No reported disclosures.
1530. Parents’ Description of Febrile Episodes in Children Diagnosed with PFAPA
Authors: Desai Brinda , Sharon Bazak 
Published: October 2019

Abstract

Background
Periodic fever, aphthous stomatitis, pharyngitis, and adenitis (PFAPA) is the most common autoinflammatory condition in children. Several guidelines have been published but still, no consensus definition exists and it represents a diagnostic challenge for the clinician. As children do not always present with the classical symptoms, early consideration through a descriptive history from the parents is essential. Our aim was to summarize parental descriptions of febrile episodes in children with PFAPA and promote timely recognition and diagnosis.

Methods
This was a retrospective cohort study of children diagnosed and managed for PFAPA in a large academic health organization with review of their charts for parental descriptors and provider documentation of febrile episodes. Parental observation of aphthous stomatitis, pharyngitis, and adenitis, and other symptoms were recorded as well as description of general clinical state during an episode, its duration, and intervals between episodes.

Results
We identified aohort of 36 children with regular episodes of fever. Classic symptoms were absent in 28%, and regularly observed in only 44%. Children were noticed to be “fatigued,” “tired looking,” “decreased energy,” “cranky,” or “irritable.” However, the two most common parental descriptors in addition to fever were “ill-appearing” and decreased oral intake (Figure 1). When reporting episodes duration most parents estimated a few days range (Figure 2). Regular intervals of 3–4 weeks were described in 22 children (61%), while the rest had either longer intervals or wider range (Figure 3). Some variation was observed in the length and recurrences of episodes, but for individual patients, these intervals were rather consistent.

Conclusion
Repetitive febrile episodes are the hallmark of PFAPA. Classic supporting symptoms are often absent, but decreased energy and decreased oral intake are almost universal. Recognizing a pattern of febrile illnesses along with a parental description of abrupt onset in an ill-appearing child who is asking to be held, and refuses food should facilitate timely consideration for PFAPA rather than primary focus on the four classically attributed symptoms.

Disclosures
All authors: No reported disclosures.
1538. Who Will Benefit From Therapeutic Drug Monitoring of Ganciclovir?
Authors: Martson Anne-Grete , Sturkenboom Marieke G G , Berger Stefan P , Damman Kevin , Verschuuren Erik A M , Blokzijl Hans , Bakker Martijn , Span Lambert F R , Touw Daan J , van der Werf Tjip S , Knoester Marjolein , Alffenaar Jan-Willem C 
Published: October 2019

Abstract

Background
Oral valganciclovir and intravenous ganciclovir are used for prophylaxis, treatment, and pre-emptive treatment of cytomegalovirus and human herpesvirus 6. It is important to estimate the exposure to these antivirals, as deviating levels can cause adverse events or induce acquired drug resistance, which can both lead to treatment failure. Therapeutic drug monitoring (TDM) is a good tool to estimate drug exposure in these patients. With this observational study we aimed to evaluate which patients would benefit most from TDM.

Methods
An observational study was performed in adult solid-organ and stem cell transplant recipients on routine (val)ganciclovir (dosed according to renal function, weight and indication). As valganciclovir is a prodrug of ganciclovir, only the latter was measured. Ganciclovir trough (Ctrough) and peak (Cpeak) concentrations were measured with a validated LC-MS/MS assay. The target concentrations defined for the study were 1–2 mg/L and 2–4 mg/L for prophylaxis and treatment, respectively, and over 5 mg/L toxic.

Results
From June 2018 to April 2019, 66 patients were included. Within this timeframe, 236 Ctrough and 52 Cpeak were measured with median of 4 samples per patient. The median Ctrough was 1.1 mg/L and 2.3 mg/L for prophylaxis and treatment, respectively. Over 50% of the concentrations were out of the therapeutic window. The median creatinine for all measurements was 100 µmol/L. Observational analysis showed patients with kidney failure and on continuous renal replacement therapy (CVVH) had more concentrations measured out of the predefined range (Figures 1 and 2). For one individual with augmented renal clearance we observed significantly lower concentrations during routine dosing. 6 toxic concentrations were measured (5 subjects); creatinine concentrations ranged 71–527 µmol/L in these individuals. A preliminary linear-mixed model analysis did not show drug formulation, age or gender as a significant predictor for ganciclovir concentrations.

Conclusion
We believe that patients with decreased renal function, on CVVH or showing changes in renal function might benefit from TDM to guide therapy. TDM of ganciclovir for patients without renal failure remains debatable. Further studies with specific patient groups are needed to confirm these results.

Disclosures
All authors: No reported disclosures.
1539. Dalbavancin, Vancomycin, and Daptomycin Alone and in Combination with Cefazolin Against Vancomycin Intermediate-Resistant (VISA) and Daptomycin Non-Susceptible (DNS) Staphylococcus aureus
Authors: Abdul-Mutakabbir Jacinda , Kebriaei Razieh , Stamper Kyle , Maassen Philip , Rybak Michael J 
Published: October 2019

Abstract

Background
Glycopeptides and lipopeptides, more specifically vancomycin (VAN) and daptomycin (DAP) have been principally utilized in treating MRSA infections. Due to continued use, MRSA strains have developed resistance to these antibiotics including vancomycin intermediate susceptible Staphylococcus aureus (VISA) and daptomycin non-susceptible strains (DNS). Lipoglycopeptides; notably dalbavancin (DAL), have been employed due to their ease of administration and enhanced activity against highly resistant S. aureus. As previously demonstrated, the use of β-lactams, specifically cefazolin (CFZ) in combination with anti-MRSA drug therapy has been effective in eradicating S. aureus complicated by increased resistance. The objective of this study was to evaluate the activity of DAL, VAN, and DAP, alone and in combination with CFZ in a pharmacokinetic/pharmacodynamic (PK/PD) model.

Methods
The well-characterized DNS-VISA strain, D712, was evaluated in eight different regimens in duplicate via a one-compartment 7-day PK/PD model. The experimental regimens were as follows: D712 growth control, DAL 1500 mg given on day 1, VAN 2 g given every 12 hours, DAP 10 mg/kg once-daily, CFZ 2 g given every 8 hours and DAL, DAP, and VAN in combination with CFZ.

Results
The combinations of DAL+CFZ, VAN+CFZ, and DAP+CFZ demonstrated a significant log10 CFU/mL reduction (more than 5 log 10 CFU/mL and up to detection limit), compared with each drug used as monotherapy (P < 0.001). Neither DAP nor VAN demonstrated sustained bactericidal activity, (represented by a >3-log10 CFU/mL reduction from baseline) and resulted in significant regrowth, when administered alone. However, the DAP +CFZ, and VAN+CFZ combination models demonstrated bactericidal activity at 4 hours and 24 hours, respectively. While DAL alone did demonstrate bactericidal activity, the DAL+CFZ combination was more rapidly bactericidal, achieving a > 3-log reduction from baseline in 8 hours vs. 48 hours (P < 0.05).

Conclusion
The combination of DAL, VAN, or DAP with CFZ demonstrated significantly improved activity against this multiple drug-resistant S. aureus strain. Further research is warranted, both in vivo and in vitro, to explore the synergistic capabilities of anti-MRSA drug therapy in combination with β-lactams.

Disclosures
All authors: No reported disclosures.
1545. Development of a Linear Mixed-Effect Pharmacodynamic Model to Quantify the Effects of Frequently Prescribed Antimicrobials on QT Interval Prolongation in Hospitalized Patients
Authors: Farkas Andras , Woods Krystina L , Ciummo Francesco , Shah Ami , Sassine Joseph , Olivo Freites Christian , Daroczi Gergely , Yassin Arsheena 
Published: October 2019

Abstract

Background
Torsades de pointes is a life-threatening ventricular tachycardia associated with prolongation of the QT interval. Many diseases and medications have been implicated as potentially prolonging the QT interval, but little data exists regarding the means of quantifying this risk. The aim of this study was to describe the impact of commonly used antimicrobials on the QT interval in hospitalized patients.

Methods
Demographic, diseases, laboratory, medication administration history and ECG recording data were collected from the electronic records of adult patients admitted, from July 2018 to December 2018, to two urban hospitals. A model for the QT interval comprised of four sub-models: gender, heart rate, circadian rhythm, and the drug and disease effects. Fixed and random effects with between occasion variability were estimated for the parameters. A Bayesian approach using the NUTS in STAN was used via the brms package in the R® software.

Results
Data from 1,353 patients were used with baseline characteristics shown in Table 1. Observed vs. predicted plots based on the training (Figure 1A) and validation data set (Figure 1B) showed a great fit. The parameters for QTc0, α, gender, and circadian rhythm were accurately identified (Table 2). Similarly, the model correctly described the expected impact of acute or chronic diseases on the QT interval. Uncertainty interval estimates (Figure 2) show that patients treated with fluconazole and levofloxacin are likely to present with a QT interval [mean (95% CI) of 6.84 (0.22,21.45) and 5.05 (0.15, 16.70), respectively], that is > 5 ms longer vs. no treatment, the minimum cutoff that should evoke further risk assessment of QT interval prolongation.

Conclusion
The model developed correctly describes the impact baseline risk factors have on the QT interval. Point estimates of QT interval prolongation show that patients treated with fluconazole and levofloxacin may be at considerable risk; while those treated with azithromycin or ciprofloxacin are more likely to be at an insignificant risk for QT interval prolongation during hospital admission. Further workup to quantify the impact of concomitant treatment with these and other at-risk medications is underway.

Disclosures
All authors: No reported disclosures.