bluuebunny/crossref_metadata_2025 huggingface dataset:
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

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

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

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

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

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

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.
1547. Modeling Pharmacokinetics and Pharmacodynamics of Meropenem Utilizing a Novel Infusion Method of Bolus to Prolonged Infusion
Authors: Moore Sarah E , Cheatham S Christian , Kays Michael B
Published: October 2019

Background

Dose optimization of antibiotics has been shown to increase the likelihood of achieving pharmacodynamic efficacy targets and improve clinical outcomes. For carbapenems, achieving greater than 40% time above minimum inhibitory concentration (T>MIC) has been shown to be correlated with clinical efficacy. Increasing bacterial resistance and rising MICs makes it more difficult for clinicians to rely on traditional dosing strategies to meet pharmacodynamic goals. Further optimization methods beyond extended infusion may be necessary to achieve certain pharmacodynamics goals.

Methods

We performed a Monte Carlo simulation investigating a novel method of meropenem administration, bolus to prolonged infusion (BPI). Multiple meropenem dosing regimens utilizing BPI were evaluated over 5000 patients utilizing pharmacokinetic profiles from 30 total patients. Patients were studied in 3 separate groups: <120 kg, ≥120 kg/non-critically ill and ≥120 kg/critically-ill. Bolus doses varied from 250–1000 mg and were paired with infusion doses varying from 500–1500 mg. Bolus plus infusion time totaled 3 hours and each dose was modeled with an 8-hour interval for both first dose and at steady state; BPI dosing was utilized for each dose. The primary outcome was probability of target attainment (PTA) of 40% time above minimum inhibitory concentration (T>MIC). Secondary outcomes included PTA 54% T>MIC and PTA 100% T>MIC.

Results

All doses studied achieved > 90% PTA of 40% T>MIC for MICs of ≤8 μg/mL at both first dose and steady state in the <120 kg and ≥120 kg/non-critically ill patient groups. In the ≥120 kg/critically ill patient group, all doses achieved > 90% PTA of 40% T>MIC for MICs of ≤4 μg/mL.

Conclusion

BPI achieves high probability of target attainment at nonresistant MICs for Pseudomonas aeruginosa and enteric Gram-negative organisms across the 3 patient groups studied.

Disclosures

All authors: No reported disclosures.
1550. PK-PD Relationship and PK Driver of Efficacy of the Novel Antibacterial Lysin Exebacase (CF-301) in Pre-Clinical Models
Authors: Ghahramani Parviz , Chiu Joannellyn , Asempa Tomefa E , Abdelraouf Kamilia , Nicolau David P , Abdel Hady Wessam , Xiong Yan , Bayer Arnold , Carabeo Teresa , Cassino Cara , Schuch Raymond , Lehoux Dario
Published: October 2019

Background

Exebacase (CF-301) is a novel lysin with rapid bacteriolytic and anti-biofilm activity against S. aureus, pronounced synergy with antibiotics and low propensity for resistance. Exebacase has undergone Phase 1–2 trials. This work was to develop pharmacokinetic (PK) model in animal and determine the relationship between exebacase exposure and efficacy in animals.

Methods

PK data in 592 animals (4 species) included in population PK model. A range of linear and nonlinear mammillary models with allometric scaling fitted to the PK data using NONMEM and the most parsimonious model was selected by improvement in objective function value (P < 0.01). To evaluate efficacy, 349 animals with 177 mice (neutropenic thigh infection) and 172 rabbits (aortic valve infective endocarditis were treated with exebacase in addition to suboptimal doses of daptomycin (DAP). Full PK profiles were simulated for individual animals. Fifty-nine dosing regimens of exebacase in mice (0–90 mg/kg) and 18 regimens in rabbits (0–1.4 mg/kg) with q24h, q12h and q8h frequencies. Relationship between AUC/MIC, Cmax/MIC, T> MIC, and log-CFU was examined using a range of functions by comparing residual standard error (RSE).

Results

3-compartment model with allometric scaling best described the PK data and was validated by bootstrap and Goodness of Fit. Maximum drop in log10CFU/g in target tissues was at AUC/MIC< 0.2 for exebacase when added to DAP that was associated with CF reduction of -5 logs in rabbits (Figure (a)) with similar magnitudes in cardiac vegetations, kidney and spleen, and -4 logs in mice (Figure (b)). Treatment with DAP alone had log10CFU reduction of -1 in mice; and -2 in rabbits. AUC/MIC was an appropriate predictor of CFU reductions.

Conclusion

PK model adequately described the data for 4 animal species. Exebacase addition to DAP has a synergistic effect on efficacy measured by CFU reductions in target tissues in the animal models. Results support previously presented determinations of AUC/MIC as predictor of efficacy. Maximum reductions in CFU in rabbits and mice were observed at AUC/MIC ratios <0.2. These results further indicate that rabbit is the most appropriate efficacy model with MICs and antibacterial activity reflective of previously reported observations in human serum.

Disclosures

All authors: No reported disclosures.
1572. Evaluation of Vancomycin Levels Following Weight-Based Pre-operative and Re-warming Vancomycin Dosing in Cardiac Surgery
Authors: Ruggero Michael , Redline Gretchen , Weiss Stuart , Binkley Shawn , Hamilton Keith W
Published: October 2019

Background

Weight-based dosing of vancomycin in the pre-operative setting is standard practice at our institution based on the 2013 Clinical Practice Guidelines for Antimicrobial Prophylaxis in Surgery. Our antimicrobial subcommittee recommended a weight-based dosing (15 mg/kg/dose) approach to negate the need for a subsequent vancomycin dose during rewarming in cases requiring cardiopulmonary bypass (CPB). However, after discussion with all perioperative stakeholders, administration of vancomycin 1 g intravenously for all patients on CPB at rewarming continued. The aim of this study was to determine whether subsequent rewarming vancomycin doses contributed to the development of postoperative acute kidney injury (AKI).

Methods

This was a prospective cohort study of all cardiac surgery patients undergoing surgery from April 16, 2018 through April 27, 2018 for the development of AKI as defined by RIFLE criteria. Institutional guidelines recommend vancomycin as perioperative prophylaxis in all cardiac surgery cases with a preoperative 15 mg/kg dose, a 1 g rewarming dose, and nomogram-based post-operative dosing. Vancomycin troughs were obtained prior to the first post-operative dose in the intensive care unit. Serum creatinine was recorded on the post-op day (POD) 0, POD 1, and POD 7.

Results

Data were collected on 54 patients over a 2-week period. The median age was 64 years of age, with 41 (76%) male patients. Seven patients (13%) had a prior diagnosis of chronic kidney disease (CKD). Post-op AKI developed in 8 patients (15%) by POD 7; two of which had CKD at baseline. All patients received appropriate preoperative and postoperative dosing. Forty-nine (91%) patients had trough levels obtained, with the median trough 7.6 μg/mL (range 2 – 15.9 μg/mL) prior to the first nomogram-based post-operative vancomycin dose. Higher rates of AKI were associated with a longer duration of CPB rather than vancomycin levels obtained.

Conclusion

The current practice of redosing 1 g vancomycin at rewarming did not appear to contribute higher rates of AKI. In addition, all vancomycin trough levels reviewed were less than 20 μg/mL. Levels observed in this study are lower than previously described in the literature to cause nephrotoxicity. Further evaluation of vancomycin use in this setting is warranted

Disclosures

All authors: No reported disclosures.
1582. Delafloxacin Activity Against Drug-Resistant Streptococcus pneumoniae, Haemophilus influenzae, Haemophilus parainfluenzae, and Moraxella catarrhalis from US Medical Centers (2014–2018)
Authors: Shortridge Dee , Streit Jennifer M , Huband Michael D , Flamm Robert K
Published: October 2019

Background

Delafloxacin (DLX) is an anionic fluoroquinolone (FQ) antimicrobial that was approved in 2017 by the United States (US) Food and Drug Administration for the treatment of acute bacterial skin and skin structure infections. DLX recently successfully completed a clinical trial for the treatment of community-acquired bacterial pneumonia (CABP). In the present study, in vitro susceptibility (S) results for DLX and comparator agents were determined for CABP pathogens including Streptococcus pneumoniae (SPN), Haemophilus influenzae (HI), H. parainfluenzae (HP) and Moraxella catarrhalis (MC) clinical isolates from US hospitals participating in the SENTRY Program during 2014–2018.

Methods

A total of 1,975 SPN, 1,128 HI, 684 MC, and 43 HP isolates were collected from community-acquired respiratory tract infections (CARTI) during 2014–2018 from US hospitals. Sites included only 1 isolate/patient/infection episode. Isolate identifications were confirmed at JMI Laboratories. Susceptibility testing was performed according to CLSI broth microdilution methodology, and CLSI (2019) breakpoints were applied where applicable. Other antimicrobials tested included levofloxacin (LEV) and moxifloxacin (MOX; not tested in 2015). Multidrug-resistant (MDR) SPN isolates were categorized as being nonsusceptible (NS) to amoxicillin-clavulanate, erythromycin, and tetracycline; other SPN phenotypes were LEV-NS or penicillin (PEN)-NS. β-Lactamase (BL) presence was determined for HI, HP, and MC.

Results

The activities of the 3 FQs are shown in the table. The most active agent against SPN was DLX, with the lowest MIC50/90 values of 0.015/0.03 mg/L. DLX activities were similar when tested against the MDR or PEN-NS for SPN phenotypes. LEV-NS isolates had DLX MIC50/90 results of 0.12/0.25 mg/L. DLX was the most active FQ against HI, HP, and MC. BL presence did not affect FQ MIC values for HI or MC; only 2 HP isolates were BL-positive.

Conclusion

DLX demonstrated potent in vitro antibacterial activity against SPN, HI, HP, and MC. DLX was active against MDR SPN that were NS to the agents commonly used as treatments for CABP. DLX had excellent activity against LEV-NS SPN. These data support the continued study of DLX as a potential treatment for CABP.

Disclosures

All authors: No reported disclosures.
1584. Minocycline Activity Against Stenotrophomonas maltophilia Isolated From Patients in US Hospitals
Authors: Shortridge Dee , Ryan Arends S J , Streit Jennifer M , Castanheira Mariana , Flamm Robert K
Published: October 2019

Background

Stenotrophomonas maltophilia (SM) has emerged as a common hospital-associated opportunistic pathogen found in immunocompromised and immunocompetent patients. SM is intrinsically resistant to many common drug classes, including carbapenems, cephalosporins, and aminoglycosides. Only 4 antibiotics have CLSI breakpoints for SM: minocycline (MIN), ceftazidime (CAZ), levofloxacin (LVX) and trimethoprim-sulfamethoxazole (TMP-SMX). Minocycline is frequently used to treat SM infections. In this study, we analyzed susceptibilities of SM isolates collected as part of the SENTRY Program. We also examined the frequency of SM isolation from pneumonia in hospitalized patients (PIHP) among all Gram-negative (GN) species.

Methods

From 2014 to 2018, 990 SM isolates were collected from hospitalized patients in 32 US hospitals. Hospitals submitted 1 isolate per patient per infection episode that met local criteria for being the likely causative pathogen and submitted consecutive isolates from pneumonia. Isolates were tested for MIN susceptibility (S) using the CLSI broth microdilution method at JMI Laboratories. Other antimicrobials tested were CAZ, LVX, and TMP-SMX. TMP-SMX was tested 3 of 5 years. All infection types were included in the susceptibility analysis. The prevalence of SM isolates in PIHP during this period was also analyzed.

Results

There were 9,120 GN pathogens isolated from PIHP. The most commonly isolated species was P. aeruginosa (34.7%), followed by Klebsiella pneumoniae (12.6%), Escherichia coli (10.1%), and SM (7.9%). Among the 990 infections caused by SM, PIHP was the most common at 72.4%, followed by bloodstream infections (14.4%) and skin/skin structure infections (6.9%). The %S and MIC50/90 values of the 4 antimicrobials tested in this study are shown in the table.

Conclusion

SM was the fourth most frequent cause of GN PIHP in US medical centers. MIN was the most active drug tested against SM with 99.5%S, followed by TMP-SMX (94.7%), and CAZ was the least active with 28.5%S. This study suggests that MIN may be a consideration as a treatment for infections caused by SM, with a very low resistance rate based on CLSI breakpoints.

Disclosures

All authors: No reported disclosures.
1608. Use of Selective Reporting of Antimicrobial Susceptibilities and Its Impact on Antimicrobial Resistance Surveillance—National Healthcare Safety Network, 2017–2018
Authors: Wu Hsiu , Zhou Liang , SOE MINN M , Edwards Jonathan R , Pollock Daniel
Published: October 2019

Background

Selective reporting (SR), recommended by the 2016 IDSA/SHEA antimicrobial stewardship guidelines, is a strategy to guide prescribing decisions by limiting the antimicrobial susceptibility testing (AST) results available to prescribers. Yet, SR carries risks that cumulative antibiograms reflect only partial AST results. The Clinical Laboratory Standards Institute (CLSI) M100 performance standards stipulate that AST results should be routinely reported for some antimicrobials (Group A agents) while SR is appropriate for other antimicrobials (Group B agents). We assessed the extent of SR use and its impact on national antimicrobial resistance (AR) surveillance.

Methods

We used Enterobacteriaceae (EB) and Staphylococcus aureus (SA) blood culture AST results that hospitals reported for group A and B agents to the CDC’s National Healthcare Safety Network’s AR option from 2017 through 2018. Routine reporting for an organism-agent combination was defined as results reported for ≥ 90% isolates for the hospital’s most frequently reported agents. SR was defined as a shortfall of > 20% in results reported for an agent compared with a routinely reported agent in a hospital that reported ≥ 30 isolates. We compared hospital antibiograms between SR and non-SR hospitals. We also identified isolate characteristics associated with AST reporting in SR hospitals.

Results

Among 242 and 185 hospitals reported ≥ 30 isolates, many showed patterns of SR (Figure 1). Of 437 and 425 hospitals reported ≥ 1 isolate, only 112 (26%) and 152 (36%) routinely reported AST results for all group A agents for EB and SA, respectively. For EB, 345 (79%) hospitals routinely reported AST results for ciprofloxacin or levofloxacin, although both are group B agents. For SA, 324 (76%) routinely reported vancomycin (Figure 2). Antibiograms for many agents differed between SR and non-SR hospitals (Figure 3, 4). In SR hospitals, non-susceptibility to narrower-spectrum drugs, patient location, age, and some species among EB were associated with AST reporting.

Conclusion

AST results reporting vary across hospitals and agents, and CLSI’s SR standards are used inconsistently. For AR surveillance, complete reporting calls for solutions that bypass SR. In the meantime, SR should be taken into account in national AR benchmarking.

Disclosures

All authors: No reported disclosures.
1627. Outbreaks of Klebsiella pneumoniae in Special Care Nurseries (SCN) in Jamaica: Role of Whole-Genome Sequencing
Authors: Aziz Maliha , Nicholson Alison M , Nadimpalli Maya , Sariya Sanjeev , Price Lance , Singh Nalini , Liu Cindy
Published: October 2019

Background

Klebsiella pneumoniae is a frequent cause of neonatal sepsis and carries a high mortality rate in lower and middle-income countries (LMICs). From March-November 2015, two Jamaican hospitals experienced K. pneumoniae outbreaks in their Special Care Nurseries (SCNs). New admissions to both SCNs were temporarily halted while additional infection control strategies were implemented. 31 babies were infected, of which 15 died. International collaboration was requested to help investigate if the sepsis cases were nosocomial transmission, repeated introductions from the community, or both using whole-genome sequencing

Methods

We sequenced DNA from 19 outbreak isolates (n = 13 from Hospital A, n = 6 from Hospital B) on an Illumina HiSeq2500 instrument and assembled short-reads using SPAdes. We used ResFinder v3.1.0 to screen resistance genes and assigned MLSTs using in-house scripts. To compare the outbreak isolates, we selected a reference genome from among the assembled isolates, aligned raw reads using the Burrows–Wheeler Aligner (BWA), identified SNPs using GATK UnifiedGenotyper, and removed the recombined regions using Gubbins v2.3.4. We further contextualized the 19 outbreak isolates against a global collection of more than 300 K. pneumoniae genomes.

Results

All 13 isolates from Hospital A appeared to be from a single source. All were ST45 and encoded blaCTX-M-15, which confers extended-spectrum β-lactam (ESBL) resistance. Five of 6 isolates from Hospital B appeared to be from a separate, single source. These 5 isolates were ST268 and susceptible to most antibiotics. 1 isolate from Hospital B was ST628, encoded blaCTX-M-15, and grouped separately from other Hospital B outbreak isolates. Hospital A and B outbreak isolates formed independent, unique clades within a global K. pneumoniae collection.

Conclusion

Our findings indicate nosocomial transmission was responsible for both neonatal K. pneumoniae outbreaks, rather than repeat introductions from the community. The main sequence types we detected (ST45 and ST268) are not known pandemic clones and may circulate regionally. Multifaceted infection control measures were implemented for effectively halting outbreaks.

Disclosures

All authors: No reported disclosures.
1628. Clinical, Epidemiological and Microbiological Characterization of Invasive Streptococcus pneumoniae Disease in Hospitalized Adults from 5 Tertiary Hospitals in Bogotá, Colombia: A Descriptive Study
Authors: Lucia Leal Castro Aura , Camacho Moreno Germán , Montañez Ayala Anita , Varon Fabio , Alvarez Rodríguez Camilo , Valderrama Sandra , Elena Ariza Beatriz , Pancha Oscar , Yadira Santana Ana , Sánchez Flórez Nella , Reyes Pabón Patricia , Ruiz Jaime , Beltrán Claudia , Emilia Prieto , Rojas Rojas Monica Maria
Published: October 2019

Background

In Colombia, clinical characteristics related to invasive pneumococcal disease (IPD) and circulating pneumococcal serotypes (ST) in adults are scarce. We aimed to describe the clinical and microbiological characteristics of IPD in hospitalized adults ≥18 years old in 5 tertiary hospitals in Colombia from 2011 to 2017.

Methods

A descriptive, observational, retrospective study was conducted in 5 tertiary care hospitals during a 7-year period. Demographic, clinical data and in-hospital outcomes were collected through chart review from all culture-confirmed invasive S. pneumoniae cases in each hospital. The National Health Institute laboratory database was assessed to obtain information about ST (Quellung) and antimicrobial susceptibility (Broth microdilution).

Results

128 cases of IPD were included in this interim analysis, 70(54.7%) were males. The median age was 58 ± 16.7 years. Main underlying conditions were cardiovascular disease (32%), smoking (27.9%), diabetes (20.3%), autoimmune diseases (18.8%), and cancer (18%). The main clinical presentation was bacteremic pneumonia (66.4%), followed by meningitis (14.8%), bacteremia (14.1%) and other (3.1%). Critical care management was required in more than half of the patients: ICU (60.2%), mechanical ventilation (53%) and inotropic support (51.6%). The overall in-hospital mortality rate was 43% and was 39%, 52.6% and 61% for pneumonia, meningitis and bacteremia, respectively. ST was known for 82(64%) cases, most frequent ST were: 3(10.9%), 14(7.3%), 19A(6,1%), 1(4.8%), 4/8/11A/22F (3.65% for each one). ST contained in 13-valent conjugate vaccine (PCV13), 23-valent pneumococcal vaccine (PPVS23) and non-vaccine serotypes accounted for 43.9%, 54.9%, and 40.2% of IPD cases, respectively (Figure 1). 83% and 80.7% strains were susceptible to penicillin and ceftriaxone, respectively.

Conclusion

Pneumonia is the most common clinical presentation of IPD among adults. The clinical outcome was severe with high mortality rate and need of critical care management. ST contained in PCV13 and PPVS23 accounted for 43.9% and 54.9% of IPD cases. This study highlights the importance to strengthen local surveillance and the implementation of pneumococcal immunization programs in high-risk population.

Disclosures

All authors: No reported disclosures.
1629. Herpes Zoster Risk in Immunocompromised Adults in the United States: A Systematic Review
Authors: Dooling Kathleen L , Guo Angela , Pergam Steven A , McKay Susannah
Published: October 2019

Background

The two known primary risk factors for herpes zoster (HZ) are age and immunodeficiency yet estimates of HZ risk by immunocompromising medical condition have not been well characterized. We undertook a systematic review of the literature to estimate HZ risk in six categories of immunocompromised patients.

Methods

We conducted a systematic review of evidence for HZ in patients with hematopoietic cell transplants (HCT), cancer (blood and solid tumor), HIV, and solid-organ transplant (SOT; kidney and other). We identified studies in Pubmed, Embase, Cochrane, Scopus and clinicaltrials.gov using the following outcome search terms: Herpes Zoster, Shingles, VZV, chickenpox, Varicella-zoster virus, or opportunistic infection. We included articles that presented original data from studies in the United States on risk of HZ in adults and were published after 1992 (1996 for HIV). Case reports and conference abstracts were excluded. We assessed risk of bias with Cochrane (clinical trials) or GRADE (observational) methods and categorized studies as high, medium, or low risk.

Results

We identified and screened 3,765 records; 57 articles were abstracted and 34 deemed low or moderate risk of bias (Figure 1). All articles reported at least one estimate of HZ cumulative incidence, which ranged from 0% to 41%. Thirteen studies estimated HZ incidence, which varied widely within and between immunocompromised populations (Figure 2). The highest estimates were seen in HCT (median = 52 HZ cases/1000 patient-years), followed by blood cancers and SOT, and then solid tumor cancers and HIV (median = 13 HZ cases/1,000 patient-years). Among 17 studies of HCT patients, longer follow-up time and absent or <1 year of post-transplant antiviral prophylaxis were associated with higher HZ cumulative incidence (Figure 3).

Conclusion

HZ is common among all immunocompromised populations studied—exceeding expected HZ incidence in immunocompetent middle-age adults. Antiviral prophylaxis among HCT patients has an ameliorating effect but long-term HZ risk following discontinuation is unclear. Better evidence for incidence and severity of HZ in immunocompromised populations is needed to inform economic and HZ vaccine policy analyses.

Disclosures

All authors: No reported disclosures.
1633. Human Co-infection with Borrelia burgdorferi and Babesia microti Among High-Risk Hispanic/Latino Workers on Eastern Long Island, New York: A Preliminary Cross-Sectional Analysis in 2016
Authors: Vilcarromero Stalin , Nunez Ana M , Vivas Katherine , Mahmood Saadia , Russo Julianna , Wellins Anna-Marie , Xu Yun , Yang Xiaohua , Arcan Chrisa , Luft Benjamin J
Published: October 2019

Background

Lyme disease has serious public health implications and has a high prevalence in Suffolk County, NY. Furthermore, there is a high risk for coinfection with Babesiosis, a potentially life-threatening tick-borne infection in the same area. This population-based cohort study was implemented in 2016 to assess the risk factors for Borreliosis among the Hispanic/Latino work population, which gave us the opportunity to measure clinical and epidemiological features of co-infection.

Methods

Invitation to participate in the study occurred during a Spanish educational lecture about tick-borne diseases. Following signed informed consent, a questionnaire and blood sample were obtained for each participant Borreliosis was defined based on 2-tiered serologic testing. Antibodies to B. microti were detected by indirect immunofluorescence assay (IFA). Between June and December 2016, 126/199 (66%) with a completed visit 1 (survey and blood draw) were included in the first analysis.

Results

Sample characteristics include 60% 18–39 years old, 75% male, 79% had elementary school education or less, 86% reported having tick exposure, 79% lived in Eastern North Fork, 65% lived 10 or more years in the United States, and 48% were gardeners and landscapers. The seroprevalence for Borreliosis burgdorferi, Babesiosis microti, and co-infection were n = 13(10.3%), n = 36 (28.6%), and n = 7 (5.6%), respectively. In the univariate analysis having a fatigue severity score of <4 or having fatigue most of the time or stiff neck or joint pain or facial paralysis, or a previous diagnosis of other tick-borne diseases were associated with co-infection (Pearson chi-square, P < 0.05).

Conclusion

However, none of these factors were statistically significant in the multivariate analysis after adjusting for the above variables. In this initial study, a high prevalence of Babesiosis was found. A larger sample size may be needed to better assess the risk of coinfection in this Lyme endemic area.

Disclosures

All authors: No reported disclosures.
1670. Access to Antibiotics Without Prescription for Travelers and Colombian Citizens at Community Pharmacies in Bogotá, Colombia: A Cross-Sectional Study
Authors: Kasbaum Marie , Lizarraga Catalina V , De la Hoz Alejandro , Reyes Jinnethe , Arias Cesar A
Published: October 2019

Background

Antimicrobial-resistant pathogens often emerge in communities where antibiotics are frequently sold without prescriptions. In Colombia, nonprescription sale of antibiotics still occurs despite national regulations. Use of antimicrobials in international travelers has been linked to the rapid dissemination of multidrug-resistant pathogens around the globe. Despite the exponential increase of international visitors to Colombia recently, there is a notable lack of studies investigating the accessibility of antibiotics to foreign travelers without prescriptions in Colombian pharmacies.

Methods

This cross-sectional study compares the access to antibiotics without prescription in community pharmacies between travelers from the United States and local Colombian citizens in Bogotá. Both groups visited 91 pharmacies and conducted trials as covert simulated clients (SCs). The SCs followed a standardized script when interacting with pharmacy personnel, acting as though they were seeking antibiotics for moderate Traveler’s Diarrhea (TD), without a prescription. Data were gathered on the employees’ responses, including the level of “prompting” needed for an employee to offer antibiotics, reasons given to the SCs for refusing to sell antibiotics if no sale was offered, and generic brand of compounds offered.

Results

Antibiotics were offered to the US travelers in 62 (68.13%) pharmacies, and to the Colombian group in 57 (62.64%) pharmacies. The traveler group was significantly more likely than the comparator group to be offered antibiotics without any prompting (P = 0.003). When pharmacy employees refused to sell antibiotics during trials, the traveler group was significantly more likely to be given a clinical reason not to receive antibiotics. Refusal to Colombian citizens was more frequently due legal reasons (P < 0.001).

Conclusion

Antibiotics were accessible without prescriptions at similarly high frequencies, regardless of the customers’ nationality. The US travelers were more likely than the Colombian group to be offered antibiotics without needing to prompt the pharmacist. Additionally, pharmacists were much more likely to deny antibiotics to the Colombian group due to legal reasons, as opposed to clinical reasons for US travelers.

Disclosures

All authors: No reported disclosures.
1681. Assessment of the Impact of Infectious Events in a Cohort of Pediatric Leukemia Patients in the Dominican Republic
Authors: Burns Julianne E , Reyes Pérez Dominga , Li Yimei , Gómez García Wendy , Garcia F Jay , Penélope Gil Jiménez Johanna , Castillo Bueno María , Sánchez Jacqueline , Hunger Stephen P , Deverlis Adriana , Steenhoff Andrew P , Fisher Brian T
Published: October 2019

Background

Infections are a leading cause of morbidity and mortality in children with cancer. Although data are limited, the impact of infection in this population appears to be amplified in low- and middle-income countries. Defining the epidemiology of infection in a specific region is paramount to developing effective interventions. This study aims to define the epidemiology of and outcomes from infection in children with leukemia in the Dominican Republic.

Methods

A retrospective cohort was assembled of children newly diagnosed with leukemia between July 1, 2015 and June 30, 2017 at Hospital Infantil Dr. Robert Reid Cabral in Santo Domingo. Patients were identified from the Pediatric Oncology Network Database and hospital admissions from the Oncology admissions logbook. Medical records and microbiology results were reviewed to identify all inpatient invasive infections. Distance from a child’s home to the hospital was determined using ArcGIS 10.5.1. Infection rates were described in discrete time periods after diagnosis and risk factors for invasive infection were explored using Poisson regression.

Results

The cohort included 68 patients; 54 (79.4%) with acute lymphoblastic leukemia and 14 (20.6%) with acute myeloblastic leukemia. The cohort was 48.5% female, had a median age at diagnosis of 7.3 years (range 1.1–16.6), and a median weight-for-age of 45.5 percentile (range 0–99.9). There were 1.2 invasive infections per 100 days at risk in the first 60 days after diagnosis, 0.8 from > 60–100 days, and 0.4 from > 100–180 days. Gastroenteritis, skin/soft-tissue infection, and pneumonia were most frequent, with bacteremia most common in the first 60 days. In a multivariate Poisson regression model, age ≥10 years (IRR 0.49, 95% CI 0.28–0.85) and distance from the hospital >100 km (IRR 0.34, 95% CI 0.14 – 0.81) were each protective against infection in the first 180 days after diagnosis. During the 2-year period, 8 of 22 (36%) patient deaths were related to infection.

Conclusion

Invasive infections were common and a prominent source of death in this cohort. Interventions aimed at reducing infection should target the first 60 days after diagnosis. Decreased infection incidence among children of older age and farther distance from the hospital were unexpected and warrant further investigation.

Disclosures

All authors: No reported disclosures.
1713. Impact of False-Positive Low-Titer Cryptococcal Antigen Testing
Authors: Bhatt Mahesh , Ribes Julie A , Arora Vaneet , Myint Thein
Published: October 2019

Background

At University of Kentucky (UK) HealthCare, the transition from latex agglutination testing (Remel, Lenexa, KS) to IMMY Cryptococcal Antigen Lateral Flow Assay (CrAg LFA) occurred in September 2016. A few months later, it was noticed that several cryptococcal cases were diagnosed with weak positive test results where the diagnosis could not be confirmed by additional testing. The purpose of this study was to analyze the characteristics of these patients, and to assess the interventions they received based on positive results.

Methods

This was a retrospective study of the patients with positive CrAg LFA treated at UK HealthCare from November to December 2016. Low antigen titers (≤ 1:20) were considered to be false positive if repeat testing with the Remel Cryptococcal Latex assay, IMMY latex and IMMY microwell EIA were negative, cultures and histopathology were negative and there was no clear clinical evidence of infection.

Results

During this 2-month period, CrAg LFA was positive in 12 patients. The diagnosis of cryptococcosis could not be confirmed by additional testing in 9 (75%) individuals. Cirrhosis/liver disease was present in 3 (33.3%) patients, 5 (55.6%) underwent lumber puncture and antifungal therapy was administered in 8 (88.9%) patients (Table 1). CrAg LFA was false positive in 1/2 (50%) HIV, 3/3 (100%) transplant, and 5/7 (71.4%) non-HIV/non-transplant patients (Figure 1). Among the false positives, 4 (44.4%) patients had titer of 1:5, two (22.2%) had 1:20, and the original positive screen was not detected upon titration in 3 (33.3%) other patients. One HIV patient received a complete treatment course for unconfirmed cryptococcal meningitis because an LP could not be performed.

Conclusion

False-positive low CrAg LFA titers led to unnecessary tests, antifungal treatments and prolonged hospitalization in some patients. One-third of these individuals had cirrhosis/liver disease. Other institutions also reported false-positive low CrAg LFA titers. As a result, the company staged a recall of the specific lot and corrected the problem in reagent manufacturing. Low-positive titers using CrAg LFA should be interpreted carefully and further testing should be considered as determined by the clinical situation.

Disclosures

All authors: No reported disclosures.