bluuebunny/crossref_metadata_2025 huggingface dataset:
2021. Comparison of Patterns of National Oral Antibiotic Use Between All Dentists and Medical Doctors in Japan in 2016 Using the National Database of Health Insurance Claims and Specific Health Checkups of Japan (NDB)
Authors: Ishikane Masahiro , Tanaka Chika , Kusama Yoshiki , Tsuzuki Shinya , Muraki Yuichi , Yamasaki Daisuke , Tanabe Masaki , Ohmagari Norio
Published: October 2019

Background

Antimicrobial resistance (AMR) is a global threat for both dentists and medical doctors. The Japanese national action plan on AMR targets a 50% reduction in the use of oral broad-spectrum antimicrobials by 2020 compared with its use in 2013. However, no study has compared the pattern of oral antimicrobial use (AMU) in outpatient settings between all dentists and medical doctors in Japan using the national database of health insurance claims and specific health checkups (NDB).

Methods

Data of oral AMU in outpatient settings prescribed by both all dentists (n = 104,533) and medical doctors (n = 319,480) in Japan in 2016 were evaluated using NDB collected by the Ministry of Health, Labor and Welfare of Japan; the data accounted for 98% of the total claim data in Japan. Antimicrobials were classified by the World Health Organization (WHO) defined Anatomical Therapeutic Chemicals Classification. WHO measures the number of AMU using defined daily dose per 1,000 inhabitant-days (DIDs).

The pattern of oral AMU between all dentists and medical doctors in Japan in 2016 was compared.

Results

The values of oral AMU in outpatient settings among all dentists (n = 104,533) and medical doctors (n = 319,480) in Japan were 1.20 and 12.11, respectively. The proportions of AMU among dentists were cephalosporins, 65.1%; macrolides, 18.9%; quinolones, 5.5%; and penicillin, 8.7%. In contrast, the proportions of AMU among medical doctors were cephalosporins, 23.1%; macrolides, 36.9%; quinolones, 22.2%; and penicillin, 8.1%. There were differences in the pattern of oral AMU between dentists and medical doctors (P < 0.001) (Table 1).

Conclusion

Although the value of total oral AMU among dentists was 9.9% of medical doctors, the proportion of cephalosporin use, which was thought to be inappropriate prescribing, was higher among dentists than among medical doctors. Further studies that are adjusted to patients’ characteristics are needed.

Disclosures

All authors: No reported disclosures.
2039. Antibiotic Stewardship in Burn and Chronic Wound Centers in Nepal
Authors: Nauriyal Varidhi , Dhoj. Joshi Rajesh , Raj Poudel Suresh , Banstola Laxman , Joshi Anip , Acharya Arjun , Bahadur Thapa Buddhi , Shrestha Basudha , Maki Gina , Shakya Malika , Man. Joshi Nilesh , Karki Kshitij , Bajracharya Deepak , Gudipati Smitha , Zervos Marcus , Kaljee Linda , Prentiss Tyler , Rai Shankar
Published: October 2019

Background

Data surrounding antibiotic stewardship (AMS) in burn and chronic wound centers in low- and middle-income countries (LMIC) are limited. Given the long-term nature of the wounds, increased risk of infection and the potential for further infections being treated with antibiotics, burn and chronic wound centers represent a unique opportunity for antimicrobial stewardship.

Methods

Three hospitals that maintain long-term burn or chronic wound wards were selected in two regions in Nepal. A post-prescription review and feedback program (PPRF) was instituted in these departments, and locally salient antibiotic practice guidelines were developed based on international and local standards by the research team and local experts. Chosen physicians at each facility were trained as master physician champions. Champions subsequently trained physicians in their wards and ensured that guidelines were followed by prescribing physicians. Baseline and post-intervention phases covered 5 months each during 2018–2019. During the post-intervention phase, physician champions reviewed antimicrobial use at 72 hours and made one of the three recommendations if the antibiotic course was deemed unjustified: changing the antibiotic, stopping the antibiotic course, or de-escalation of the antibiotic.

Results

482 patients were enrolled throughout the duration of the study, with 241 patients in each of the baseline and post-intervention periods. The average length of stay was 8.0 days in baseline (range 3–48 days) vs. 6.4 days (range 3–70 days) during post-intervention. Between baseline and post-intervention, IV antibiotics decreased from 1,161 antibiotic-days per 1,000 patient-days (PD/1,000) to 1,137 PD/1,000. Oral antibiotics decreased from 101 PD/1,000 to 77 PD/1,000. In addition, cephalosporins decreased from 526 PD/1,000 to 474 PD/1,000, and aminoglycosides decreased from 264 PD/1,000 to 117 PD/1,000.

Conclusion

Appropriate antimicrobial use is vital in patients with a long length of stays in the hospital to reduce the development of multi-drug-resistant organisms. This intervention showed that a post-prescription review and feedback model can have impact in chronic wound and burn centers in Nepal and be further adapted for use in other LMIC.

Disclosures

All authors: No reported disclosures.
2064. Applying Human Factors and Ergonomics to Inform a Successful Fluoroquinolone Restriction Intervention: A Mixed Methods Pilot Study
Authors: Tischendorf Jessica , Brunner Matthew , Schulz Lucas , Barker Anna K , Lepak Alexander , Lepak Alexander , Knobloch Mary J , Wright Marc-Oliver , Safdar Nasia
Published: October 2019

Background

Antimicrobial stewardship programs (ASPs) can reduce the incidence of hospital-onset Clostridioides difficile infection (HO-CDI) by limiting unnecessary exposure to high-risk antibiotics, including fluoroquinolones (FQ). However, restriction policies are challenging to implement and sustain. In a mixed methods study, we explored the barriers, facilitators and efficacy of an FQ restriction policy to reduce HO-CDIs among high-risk patients.

Methods

Our ASP instituted a pilot FQ restriction policy in our ICU and solid-organ transplant wards. We evaluated 24 months of pre- and post-intervention data, including: FQ and alternative agent use, length of stay (LOS), readmission rate, mortality and HO-CDI. We conducted 12 semi-structured interviews with front-line providers, applying the Systems Engineering Initiative for Patient Safety framework to examine perceptions of FQ use, prescribing indications, perceived relationships between FQ use and HO-CDI, and barriers imposed by FQ restrictions. Time-series analysis was performed to evaluate FQ and HO-CDI data.

Results

FQ use decreased from an average of 111.6 days of therapy (DOT) per 1,000 patient-days pre-intervention to 19.8 DOT/1,000 patient-days (P < 0.0001). Average readmission rate, LOS on pilot units, total antibiotic use, and use of cefepime decreased after FQ restriction. Conversely, use of ceftriaxone, aminoglycosides and piperacillin–tazobactam all increased. The average HO-CDI rate was significantly lower post-intervention, although time series analysis showed a post-intervention increase in the trend in infection rate compared with the pre-intervention trend. Qualitative analysis of interviews revealed β-lactam allergy and pending discharge were barriers to FQ restriction; a patient’s history of CDI and pharmacist involvement in antimicrobial decision-making facilitated FQ restriction.

Conclusion

An FQ restriction policy significantly decreased FQ use without adversely affecting readmission rate, LOS or mortality. Knowledge of barriers and facilitators to FQ use optimization among front-line staff can inform future successful ASP interventions. Further investigation into the effect of FQ restriction on HO-CDI is needed.

Disclosures

Alexander Lepak, MD, Paratek Pharmaceuticals: Research Grant; Tetraphase Pharmaceuticals: Research Grant.
2069. A Unique Approach to Outpatient Antibiotic Stewardship in Rural Southern Ohio
Authors: Ramey Lara K , Byers David K , DeLille Eli
Published: October 2019

Background

A five county rural community in southern Ohio was identified as having significantly higher than average rates of antibiotic use. The hospital system serving this area, Southern Ohio Medical Center (SOMC), began initial efforts in antimicrobial stewardship focusing on inpatient prescribing. However, most antimicrobial consumption occurs in the outpatient setting. Early attempts to improve antibiotic prescribing focused on only provider education and resulted in little change. Providers felt they were performing well, or their patients were more complex and prescribing the antibiotics was warranted. SOMC partnered with the state Quality Improvement Organization, HSAG, to design an intervention to address these challenges.

Methods

All outpatient and emergency room encounters with acute bronchitis and upper respiratory infection (URI) (ICD-10 codes [J00, J06.9, and J20.X]) were included in the analysis. Using criteria from a National Quality Forum measure, concomitant diagnoses were excluded to identify encounters where an associated condition may indicate the case is more complex. A 6-month baseline and two additional 6-month remeasurement periods were analyzed. Providers were given letters, peer-to-peer antimicrobial data comparison, and in-person feedback with guideline-driven recommendations for these conditions.

Results

Baseline analysis indicated 50% of all encounters without a coded concomitant diagnosis resulted in antibiotic prescriptions. There was a reduction in the overall rate at each remeasurement period, to 34% and then 12%. This resulted in a 76% relative improvement rate (RIR) overall at the final remeasurement period. At baseline, the highest volume setting, urgent care, had a prescribing rate of 71%. Urgent-care prescriptions reduced each remeasurement to 45% and 13%, resulting in an 81% RIR.

Conclusion

Implementing a robust outpatient stewardship program in a rural nonacademic setting is not without unique challenges. By using peer comparison of provider performance data on prescribing habits in uncomplicated patients with URI and acute bronchitis in addition to education, the rate of appropriate antibiotic use improved.

Disclosures

All authors: No reported disclosures.
2075. Transforming Outpatient Antimicrobial Stewardship Through a Clinical Surveillance System
Authors: Portman David B , Pattison Victoria M
Published: October 2019

Background

Multiple studies have highlighted the predominance of inappropriate antibiotic prescribing in the outpatient setting, thus making an area ripe for antimicrobial stewardship interventions. One way to identify intervention opportunities and monitor performance metrics is through utilization of a clinical surveillance system (CSS).

Methods

In October 2017, TheraDoc (DSS Inc.) was obtained which serves as a CSS. Upon installation, the antimicrobial stewardship committee designed the alerts found in Figure 1 that would be utilized to identify potential interventions. Alerts that were deemed to be of high value or time sensitive were to be emailed to pharmacists involved with antimicrobial stewardship. It was theorized that this method would help transform outpatient antimicrobial stewardship from a predominately retrospective approach, to a prospective approach. Outpatient stewardship metrics were compared for pre- and post-CSS implementation to evaluate the impact of a CSS. The pre-implementation group (PreCSS) represented outpatient stewardship interventions that occurred January 2017 through June 2017 where all antibiotic prescriptions were reviewed. The post-implementation group (PostCSS) represented outpatient stewardship interventions that occurred April 2018 through September 2018 which were predominantly driven by CSS alerts.

Results

The PostCSS group had substantially fewer charts reviewed compared with the PreCSS group (267 vs. 1,415). In addition, the PostCSS group completed 77.6% more interventions compared with the PreCSS group (87 vs. 49). Thirty-one less charts were reviewed per one intervention, which led to 469 less minutes of chart review per one intervention. See Figure 2 for list of interventions. The PostCSS group received a significant increase in consults due to the direct approach to interventions compared with the PreCSS group (45 vs. 11).

Conclusion

The use of a clinical surveillance system has demonstrated an efficient way to transition outpatient antimicrobial stewardship to a prospective, interventional approach.

Disclosures

All authors: No reported disclosures.
2109. Liposomal Amphotericin B-associated Nephrotoxicity in Obese and Non-obese Patients
Authors: Tritle Brandon , Peterson Logan , Olson Jared , Benefield Emily , Cariello Paloma F , Benefield Russell J
Published: October 2019

Background

Liposomal amphotericin B (L-amb) is an important antifungal agent which exhibits significant rates of dose-dependent nephrotoxicity. Animal studies demonstrate only small amounts of L-amb distribute into adipose tissue and obese animals show greater risk of nephrotoxicity with L-amb administration. This study aims to determine whether obese patients are at a higher risk of nephrotoxicity with weight-based doses of L-amb.

Methods

We performed a multi-center, retrospective cohort study of nephrotoxicity with L-amb in obese (BMI > 30) and non-obese adult patients at University of Utah Health and Intermountain Healthcare from January 1, 2014 through December 31, 2018. Our primary outcome was the rate of nephrotoxicity as determined by AKIN criteria. Patients receiving at least one dose of L-amb were identified for inclusion. Patients were excluded if they were already on a renal replacement at the time of L-amb initiation or they received L-amb prior to admission.

Results

We included 221 patients, 47 (21%) were obese and 174 (79%) were non-obese. Median total body weight was 109 kg in obese patients compared with 70 kg in non-obese patients. Dosage based on ideal body weight was higher in the obese group (median 6.9 mg/kg vs. 4.9 mg/kg). Obese patients were significantly more likely to experience acute kidney injury (AKI) than non-obese patients (55% vs. 37%, P = 0.03). Patients who experienced nephrotoxicity received a higher average daily dose than those who did not (365 mg vs. 333 mg, P = 0.03), had a higher median cumulative dose (3,130 mg vs. 1,700 mg, P < 0.001), and had a higher median total body weight (79.6 kg vs. 71.9 kg, P = 0.04.). Additionally, daily dose normalized to total body weight was not associated with AKI (median 4.7 mg/kg in patients with AKI vs. 4.8 mg/kg in patients without AKI, P = 0.86). However, daily dose normalized to ideal body weight was associated with AKI (median 5.5 mg/kg in patients with AKI vs. 4.9 mg/kg in patients without AKI, P = 0.02).

Conclusion

We identified a higher rate of nephrotoxicity among obese patients receiving L-amb compared with non-obese patients. These data suggest that dosing L-amb based on total body weight places obese patients at a higher risk of nephrotoxicity. This should be considered when assessing the risks and benefits of this dosing strategy in obese patients.

Disclosures

All authors: No reported disclosures.
2131. Multicenter Evaluation of Meropenem/Vaborbactam MIC Results for Enterobacteriaceae Using MicroScan Dried Gram-Negative MIC Panels
Authors: Garner Omai , Traczewski Maria M , Beasley Denise , Harrington Amanda , DesJarlais Sharon , Hastey Christine , Brookman Regina , Lockett Zabrina , Chau Jennifer , Zimmer Barbara
Published: October 2019

Background

A multicenter study was performed to evaluate the accuracy of meropenem/vaborbactam on a MicroScan Dried Gram-negative MIC (MSDGN) Panel when compared with a frozen CLSI broth microdilution reference panel.

Methods

For efficacy, an evaluation was conducted at three US sites by comparing MIC values obtained using the MSDGN to MICs using a CLSI broth microdilution reference panel. A total of 560 Enterobacteriaceae clinical isolates were tested using the turbidity and Prompt®* methods of inoculation. For challenge, 95 Enterobacteriaceae isolates were tested on MSDGN panels at one site. For reproducibility, a subset of 14 organisms was tested on MSDGN panels at each site. MSDGN panels were incubated at 35 ± 2°C and read on the WalkAway System, the autoSCAN-4 instrument, and read visually. Read times for the MSDGN panels were at 16–20 hours. Frozen reference panels, prepared according to CLSI/ISO methodology, were inoculated using the turbidity inoculation method. All frozen reference panels were incubated at 35 ± 2°C and read visually. Frozen reference panels were read at 16–20 hours. FDA/CLSI breakpoints (µg/ml) used for interpretation of MIC results were: Enterobacteriaceae ≤ 4/8 S, 8/8 I, and ≥ 16/8 R.

Results

When compared with frozen reference panel results, essential and categorical agreements for isolates tested in the Efficacy and Challenge are as follows (see table). Reproducibility among the three sites were greater than 95% for all read methods for both the turbidity and Prompt* inoculation methods.

Conclusion

This multicenter study showed that meropenem/vaborbactam MIC results for Enterobacteriaceae obtained with the MSDGN panel correlate well with MICs obtained using frozen reference panels using FDA/CLSI interpretive criteria. * PROMPT® is a registered trademark of 3M Company, St. Paul, MN, USA. Beckman Coulter, the stylized logo and the Beckman Coulter product and service marks mentioned herein are trademarks or registered trademarks of Beckman Coulter, Inc. in the United States and other countries. Vabomere® (Meropenem/Vaborbactam) is a registered trademark of Melinta Therapeutics, Inc.

Disclosures

All authors: No reported disclosures.
2133. Clinical Impact of Implementation of Rapid Diagnostic Testing of Blood Cultures on Patient Outcomes
Authors: Gritte Anndee , Hopkins Teri , Morneau Kathleen , Frei Christopher R , Cadena-Zuluaga Jose , Walter Elizabeth
Published: October 2019

Background

Rapid diagnostic testing (RDT) in microbiology labs shortens the time to identification of bacteria in blood cultures. This study evaluates the impact of implementation of Cepheid® GeneXpert® to detect methicillin-resistant Staphylococcus aureus and S. aureus in Gram-positive blood cultures.

Methods

Patients with positive blood cultures for Staphylococcus spp. before (November 2015–August 2016) and after (November 2017–8/2018) implementation of a new rapid diagnostic technology were evaluated. RDT results were reviewed once daily by the antimicrobial stewardship team. The primary outcome was time to appropriate antimicrobial therapy. Secondary outcomes included the duration of antimicrobial therapy from time of positive culture, duration of vancomycin therapy, and length of hospital stay (LOS).

Results

A total of 113 patients were in the pre- and 73 patients were in the post-implementation cohort. Patients treated post-RDT demonstrated significantly shorter median time to appropriate therapy (20.6 hours vs. 49.8 hours, P = 0.03) and numerically shorter median duration of vancomycin therapy (3.0 days vs. 1.0 days, P = 0.32). These numerical differences were present despite the post-RDT cohort having significantly more MSSA and MRSA infections. Differences in duration of antimicrobial therapy were not statistically significant. Patients treated pre-RDT demonstrated a shorter median LOS than those treated post-implementation (7.0 days vs. 8.5 days, P = 0.03).

Conclusion

The use of RDT significantly decreased time to appropriate antimicrobial therapy. Patients in the post-RDT cohort had longer LOS, which may due to a higher incidence of S. aureus infections, compared with coagulase-negative Staphylococcus, in this cohort These results are promising for future RDT interventions.

Disclosures

All authors: No reported disclosures.
2139. Rickettsia typhi Detection in Clinical Infections by the Karius Test, a Plasma Microbial Cell-free DNA Next-Generation Sequencing Test
Authors: Centeno Fernando H , Ahmed Asim A , Hong David K , Dalai Sudeb , Woc-Colburn Laila
Published: October 2019

Background

Rickettsia typhi typically causes a nonspecific syndrome characterized by fever, rash, and headache but can rarely progress to severe disease. R. typhi is transmitted by the rat flea and there has been an increased incidence in Houston, TX. Establishing the diagnosis can be challenging and is often made by serological studies. Prompt therapy with doxycycline is important especially in severe disease.

Methods

Karius Test results from the prior 2 years (Redwood City, CA) were reviewed for detections of R. typhi. The Karius Test is a CLIA-certified/CAP-accredited next-generation sequencing (NGS) plasma test that detects microbial cell free DNA (mcfDNA). After mcfDNA is extracted and NGS performed, human sequences are removed and remaining sequences are aligned to a curated pathogen database of >1,000 organisms. Organisms present above a statistical threshold are reported. Chart review was conducted on the cases of R. typhi identified by the Karius Test.

Results

The Karius Test detected R. typhi in 6 adult patients, 4 women and 2 men, from a medical center in Houston, TX. In 2 patients, R. typhi mcfDNA was present in the raw sequencing data but at an abundance below validated statistical thresholds. R. typhi mcfDNA was not found in negative controls run simultaneously with the samples. All patients presented with fever, 4 presented with headache, 3 presented with gastrointestinal symptoms, 3 developed rash, one presented with hypotension. Laboratory data were available for 5 patients. Four patients developed thrombocytopenia, 5 had anemia, 4 patients had WBC < 5, 4 had transaminase elevation and 3 developed hyponatremia. 3 out of 5 had R. typhi serologies sent; all 3 were positive (including two of the patients with R. typhi mcfDNA levels below threshold). In the two other patients the Karius test was the means of establishing the diagnosis. 3 out of 5 patients where data were available were treated with doxycyline.

Conclusion

The Karius test was able to detect R. typhi in a cluster of 6 patients in one medical center in Houston, TX. NGS for mcfDNA offers a rapid means of detecting R. typhi infection. Accurate, rapid diagnosis of R. typhi has important public health implications given its vector-borne mechanism of transmission.

Disclosures

All authors: No reported disclosures.
2170. Xpert Carba-R Assay on Flagged Blood Culture Samples: Clinical Utility in Intensive Care Unit Patients with Gram-Negative Bacteremia
Authors: Rajendran Surendran , Gopalakrishnan Ram , Tarigopula Anil , Dorairajan Sureshkumar , Nambi Panchatcharam Senthur , Sethuraman Nandini , V Ramasubramanian
Published: October 2019

Background

Rapid molecular diagnostics that predict carbapenem resistance (CR) well before the availability of routine drug sensitivity testing (DST) can serve as an antimicrobial stewardship tool in the context of high rates of carbapenem-resistant enterobacteriaceae (CRE).

Methods

A retrospective observational study of patients more than 18 years of age on whom Xpert Carba-R (FDA approved for rectal swab specimen) was done on Gram-negative bacteria (GNB) flagged blood culture samples, in a tertiary care Indian intensive care unit between January 2015 and November 2018.

Results

The study included 160 patients who had a median (Sequential Organ Failure Assessment) SOFA score of 16. A total of 164 GNB were isolated with 4 patients having polymicrobial bacteremia. Klebsiella pneumoniae and Escherichia coli were the predominant isolates (Figure 1). Carba-R was positive in 58/164 (35.36%) samples (Figure 2) and 73/161 isolates (45.34%) were CR (after excluding intrinsic CR organisms) on routine DST. The distribution of CR genes overall was: OXA-48 like (29/58–50%), followed by NDM (19/58–32.7%), followed by OXA-48 and NDM co-expression (9/58–15.51%) and in individual groups as in Figure 3. The sensitivity, specificity, positive likelihood ratio, negative likelihood ratio, positive predictive value (PPV) and negative predictive value (NPV) of Carba-R vs. routine DST were 90.74%, 93.15%, 13.25, 0.10, 83.58% and 96.31% for enterobacteriaceae (Figure 4). The median time to obtaining the Carba-R report was 30 hours 34 minutes vs. 74 hours and 20 minutes for carbapenem resistance on routine DST. Based on the Carba-R report, 9.72% of patients had escalation of antibiotics (e.g., colistin) to cover CR organisms and 27.08% had de-escalation from CR cover that had already been started.

Conclusion

Xpert Carba-R serves as a rapid diagnostic tool for CR Gram-negative bacteremia, particularly hospital-acquired enterobacteriaceae in intensive care units with a high CRE prevalence. It assists in initiating early appropriate therapy and early institution of infection control measures in these patients, as well as in de-escalation of colistin in patients without carbapenem resistance. We recommend that clinicians consider routinely utilizing this test in this setting.

Disclosures

All authors: No reported disclosures.
2180. Novel Method for Determining Rapid E.coli Antibiotic Susceptibility (AST) Results for Urinary Tract Infections
Authors: Kon Shelley , France Danielle , Walls Fred , Price Connie S
Published: October 2019

Background

Measuring changes in phase noise from bacteria on a quartz crystal resonator has been shown to effectively distinguish viable from non-viable E. coli. We report using this method to rapidly perform AST for E. coli isolated from a leftover clinical urinary tract infection (UTI) specimen.

Methods

An experimental system was designed to sense changes in bacterial mechanics through changes in phase noise generated by bacterial cells (Figure 1). The system includes a quartz-crystal resonator with thin-film gold electrodes on opposite surfaces housed within a module. The module provides electrical contact to the crystal’s electrodes, and incorporates channels through which fluids can be pumped (Figure 2). E. coli was isolated from a leftover positive urine culture specimen, cultured overnight and resuspended in phosphate-buffered saline (PBS). The suspension was run through the experimental system. E.coli cells were adhered to the surface of the quartz resonant crystal coated with a cationic polymer. After a growth phase, the cells were exposed to antibiotic (ampicillin). Phase noise was monitored throughout the test. The power spectral density of the noise was averaged each 5 minutes. E.coli was classified as ampicillin susceptible if the spectral power of the added phase noise was at least 50% lower compared with controls. Controls were in growth media only (Figure 3). Automated microscopy was utilized to monitor cell growth.

Results

The method correctly classified the E.coli as ampicillin susceptible. Power spectral density increased in untreated cells and dropped or stayed steady in cells treated with Ampicillin. Corresponding loss of E. coli viability was confirmed microscopically. Results were compared with standard of care antibiotic susceptibility testing.

Conclusion

The phase noise measurement method correctly identified ampicillin susceptible E.coli isolated from a leftover patient urine sample in three and one half hours. It shows promise for providing rapid AST results to treat UTIs.

Disclosures

All authors: No reported disclosures.
2185. Group A Streptococcus (GAS) Detection by PCR in Children with Viral Acute Respiratory Illness and Healthy Children
Authors: Banerjee Dithi , Crawford Jordan , Harrison Christopher J , Rha Brian , Lively Joana Y , Selvarangan Rangaraj
Published: October 2019

Background

Acute pharyngitis is mostly of viral etiology; GAS, the leading bacterial cause, comprises 20%–30% of pediatric pharyngitis. Patients with pharyngitis and additional acute respiratory illness (ARI) symptoms more suggestive of viral etiology, including cough, rhinorrhea and conjunctivitis, are not recommended for GAS testing. The use of highly sensitive GAS PCR assays in patients with sore throat and viral ARI symptoms may detect GAS colonization and lead to antibiotic overuse. We evaluated GAS PCR in viral ARI inpatients and asymptomatic healthy controls (HC) to illustrate the potential negative impact of offering GAS PCR test in poorly selected patients.

Methods

In November 2015–June 2016, 458 ARI inpatients (< 18 years) and 205 HC (< 5 years, no ARI symptoms within 72 hours) in Kansas City were enrolled in the New Vaccine Surveillance Network study. Mid-turbinate and throat swabs were tested by multiplex respiratory panel PCR and leftover nucleic acid extracts were further tested by real-time GAS PCR. Presenting symptoms of cough, rhinorrhea and/or conjunctivitis, plus sore throat were assessed by parent interview.

Results

Overall, 6.3% of HC < 5 years old and 8.7% of ARI subjects < 18 years were GAS (+); mostly in the 3–15 year old age group (25/40, 62.5%). Among 3–15 year old GAS (+) ARI subjects, 92.8% had cough, 76.2% rhinorrhea and 37.2% conjunctivitis; 80% had > 2 of 3 symptoms noted above. Among 40 GAS (+) ARI subjects, a virus was co-detected in 34 (85%), among which Rhinovirus/Enterovirus were predominant 22/34 (55%). Of the 130 (28%) ARI subjects with sore throat, more tested positive for viruses (107/130, 82.3%) than for GAS (9/130, 6.9%). All GAS (+) HC (13/205, 6.3% overall) were < 3 year olds.

Conclusion

PCR detected GAS in 6.3% HC < 5 years old and 8.7% ARI subjects < 18 years old; mostly in 3- to 15-year-old ARI subjects. Most GAS (+) ARI children had cough, rhinorrhea or conjunctivitis and/or virus co-detection suggesting GAS carriage. Our data demonstrate that GAS may be detected in patients with a low clinical suspicion for acute GAS pharyngitis. These findings highlight the need to review patient selection and exercise caution in implementing highly sensitive GAS PCR assays especially in such clinical settings.

Disclosures

All authors: No reported disclosures.
2202. Validation of a Rabbit Model of Pseudomonas aeruginosa Acute Pneumonia
Authors: Gras Emmanuelle , Vu Trang , Vu Vi Tran Giang , Quynh Nhu Nguyen Tran , Schneider-Smith Erika , Povoa Natalia , Povoa Helvecio , Delaye Thomas , Valour Florent , An Diep Binh
Published: October 2019

Background

Severity and antimicrobial resistance of P. aeruginosa (PA) hospital-acquired pneumonia led the FDA to encourage the development of animal models for preclinical evaluation of new therapeutic strategies. We present here the validation of a rabbit model of PA acute pneumonia.

Methods

Rabbits were infected by endotracheal instillation of 1.8 mL of a standardized inoculum containing 9 × 107 CFU of PA clinical strain 6206 (predetermined 100% lethal dose). The natural history of the disease was described by the following parameters evaluated at 3, 4, 5, 6, 10 hours post-infection (hpi) and at the time of spontaneous death (6 rabbits/group): lung-to-body weight ratio (LW/BW), pulmonary, splenic and renal bacterial counts, pulmonary histology and blood markers (blood cell counts, blood gas and IL-8). Three groups of 12 rabbits were then treated with saline (controls), tobramycin or meropenem at doses determined by PK/PD analysis to confirm the efficacy of a human-equivalent dosing regimen.

Results

PA strain 6,206 caused fatal pneumonia in 13–23 hours by acute respiratory distress syndrome (pulmonary edema and necrosis with LW/BW > 10, pO2 <40 mmHg) and/or sepsis (hyperlactatemia, hypoglycemia, cytopenias). LW/BW and pulmonary bacterial counts increased significantly over time. The splenic and renal bacterial spread was constant after 6 hpi. Hypoxemia <60 mmHg appeared at 5 hpi for 4/6 rabbits, associated with elevated plasma IL-8 concentration, massive neutrophilic influx into the airspace, lung necrosis, hemorrhage, and pulmonary edema formation. Consequently, 5 hpi appeared as the most appropriate time to trigger a therapeutic intervention. Meropenem (80 mg/kg/q2h) or tobramycin (1 injection of 2.5 mg/kg, then saline/q2h) showed superiority over saline, with a mortality rate of 33% and 17% vs. 100%, and an LW/BW ratio of 8.53 and 8.54 vs. 13.9, respectively. Tobramycin was less effective than meropenem in clearing bacteria, with, respectively, 1 and 9 out of 12 rabbits having sterile samples.

Conclusion

This rabbit model of PA acute pneumonia is a reliable evaluation tool for new therapeutic strategies. Our study also provides guidance for the development of animal models by describing the natural history of disease and therapeutic validation.

Disclosures

All authors: No reported disclosures.
2239. Randomized Controlled Trial of a PROcalcitonin-Guided Antibiotic Treatment Algorithm Plus Antibiotic Stewardship the Pediatric Intensive Care Unit (ProPICU)
Authors: Katz Sophie , Crook Jennifer , Gillon Jessica , Szeles Andras , Stanford J Eric , Wang Li , Colby Jennifer , Banerjee Ritu , Banerjee Ritu
Published: October 2019

Background

Procalcitonin (PCT) testing enables earlier antibiotic (abx) de-escalation in adult intensive care units (ICUs); similar data in children are lacking.

Methods

Single-center pragmatic randomized controlled trial of children admitted to the pediatric ICU and started on intravenous (IV) abx February 2018–April 2019 to evaluate whether a PCT-guided testing and treatment algorithm implemented through antibiotic stewardship (AS) audit and feedback promotes abx de-escalation in the pediatric ICU. Patients were randomized by month to either control or PCT arm. Exclusion criteria were receipt of IV abx within 7 days prior to enrollment, immune compromise, neonates < 34 weeks gestation, or receipt of abx for an infection requiring prolonged abx. All subjects had baseline AS review. Subjects in the PCT arm had PCT testing on days 0, 1, 2, and 4 and AS guidance. Some subjects in the control arm had baseline PCT testing that was not available to providers. Abx de-escalation = stopping or narrowing spectrum of abx; Abx escalation = broadening spectrum or starting an additional abx. The primary outcome was abx days of therapy (DOT) per patient in the first 14 days after enrollment. Kruskal–Wallis, Chi-square, and ANOVA tests were used.

Results

The modified intention to treat analysis included 270 patients: 133 control and 137 PCT. Significantly more males and febrile patients were in the PCT-guided arm (Table 1). Overall, abx DOT did not differ between arms (Table 2). In 85 patients with pneumonia, median DOT per patient was shorter in the PCT than control arm (8.0 vs. 9.3 days, P = 0.04). Among patients in the PCT arm, those with initial PCT level > 0.5 mg/L (n = 93) (4.3 vs. 7.1 days, P = 0.006). More AS recommendations (recs) were made in the PCT arm (53 PCT vs. 35 control, P = 0.03). Compliance with AS recs was similar (70%) between arms.

Conclusion

In the pediatric ICU, the use of a PCT testing and treatment algorithm with AS audit and feedback resulted in shorter abx DOT for patients with pneumonia and more AS recs compared with no PCT testing. PCT testing implemented with AS can reduce abx duration in select populations of critically ill children.

Disclosures

Ritu Banerjee, MD, PhD, Accelerate Diagnostics: Grant/Research Support; BioFire: Research Grant; Biomerieux: Research Grant; Roche: Research Grant.
2257. BDG-Guided Management of Empirical Antifungal Therapy: a Real-life Experience in a Hospital-Wide Context with High Incidence of Non-albicans Candida Infection
Authors: Marconi Lorenzo , Maccaro Angelo , Cimatti Matteo , Scotto Riccardo , Venturelli Claudia , Appolloni Lucia , Furii Francesca , Morotti Marta , Puggioli Cristina , Giannella Maddalena , Viale Pierluigi
Published: October 2019

Background

BDG-guided management of empirical antifungal therapy (AT) has been suggested as a tool to rule out invasive candidiasis (IC) and discontinue AT in critically ill patients. However, some authors reported lower BDG sensibility for non-albicans Candida (NAC) infection. Impact of BDG use in a hospital wide setting has yet to be determined.

Methods

We performed a retrospective observational study of consecutive patients admitted to a 1535-bed teaching hospital from November 2015 to August 2017. Adult patients starting empirical AT and performing at least one BDG test for a suspected fungal infection were included. According to first BDG result and AT management, patients were classified in 3 groups: (G1) negative index BDG and early AT withdrawal; (G2) negative index BDG and AT continued; (G3) positive index BDG and AT continued. IC was defined as monomicrobial Candida spp. isolation from blood cultures and/or surgical specimen. Comparison of the 3 groups was made using post-hoc Bonferroni correction. Univariate and multivariate analyses of risk factors for all-cause 30 days mortality were performed using binary logistic regression model.

Results

Study population consisted of 208 patients, of which 46 (22.1%) were included in G1, 79 (38.0%) in G2, and 83 (39.9%) in G3. NAC species were more commonly isolated from patients with IC and negative BDG (P = 0.005). IC was diagnosed in 2.2%, 13.9%, and 19.3% of G1, G2, and G3, respectively (P < 0.01 for G1 vs. G3). Median AT DDD were 8, 28, and 20 (P < 0.01 for G1 vs. G2 and G1 vs. G3) and 30-day mortality rate was 21.4%, 16.5%, and 30.1%, respectively. Factors associated with 30-day mortality were age, Charlson Comorbidity Index (CCI), ICU admission, SOFA score, septic shock, orotracheal intubation, CVVH and index BDG ≥ 80 pg/mL. At multivariate model, independent risk factors for 30-day mortality were CCI (OR 1.4, 95% CI 1.2–1.6, P < 0.001), SOFA score (OR 1.2, 95% CI 1.1–1.3, P < 0.001) and index BDG≥80 pg/mL (OR 2.4, 95% CI 1.2–4.8, p = 0.012). Model fit was P = 0.65 by Hosmer–Lemeshow test and accuracy according with ROC analysis was 0.82 (95% CI 0.76–0.88).

Conclusion

BDG positivity is a strong predictor of poor outcome, but its accuracy for NAC infection may be suboptimal. Caution may be necessary for AT discontinuation based on a negative BDG result in patients at high risk for NAC infection.

Disclosures

All authors: No reported disclosures.
2262. Ceftazidime–Avibactam vs. Polymyxin B in the Treatment of Infections Due to Carbapenem-Resistant Enterobacteriaceae
Authors: John Jamie , Nelson Brian , Macesic Nenad
Published: October 2019

Background

Pharmacotherapy for carbapenem-resistant Enterobacteriaceae (CRE) infections is limited. There is a paucity of evidence to guide optimal management of CRE infections. Ceftazidime–avibactam, a novel cephalosporin/β-lactamase inhibitor, may be a reasonable alternative to colistin for CRE infections, but data on polymyxin B (PB) are lacking. Given the improved pharmacokinetic profile of PB compared with colistin, we sought to evaluate clinical and microbiological outcomes of patients treated with CAZ-AVI vs. PB for CRE infections.

Methods

We conducted retrospective cohort study in adult patients treated with CAZ-AVI or PB for a CRE infection between June 2010 and August 2018. The primary outcome was all-cause mortality at 30 days. Secondary outcomes included clinical cure, microbiological cure, and development of resistance. Endpoints were analyzed using standard statistical measures. The influence of clinical variables other than antimicrobial therapy was assessed in a multivariable regression analysis.

Results

The study included 117 patients, with 42 patients receiving CAZ-AVI and 75 receiving PB. Respiratory and urinary tract infections were most common, occurring in 37.6% and 20.5% of patients, respectively. Bloodstream infections occurred in 45 (35.9%) patients. In the CAZ-AVI group, there were 9 deaths (21.4%), compared with 19 deaths (25.3%) in the PB group (P = 0.653). No statistically significant differences were found in clinical cure or microbiologic cure between CAZ-AVI and PB. PB was associated with a higher incidence of nephrotoxicity (19% vs. 43%; P = 0.048). After adjustment for duration of therapy, combination therapy, and initial WBC, use of PB was not an independent predictor of mortality.

Conclusion

No statistically significant differences between CAZ-AVI and PB were found in clinical or microbiologic outcomes in this cohort of patients treated for CRE infection. Further studies are necessary to confirm these preliminary findings to optimize clinical practice.

Disclosures

All authors: No reported disclosures.
2317. Excess Influenza-Attributable Mortality in Los Angeles County (LAC) for the 2013–2014 Through 2017–2018 Seasons
Authors: Traub Elizabeth , Rollin Louise , Gounder Prabhu
Published: October 2019

Background

Deaths caused by seasonal influenza are impossible to measure directly and are typically estimated using statistical models. We applied a previously developed model to Los Angeles County (LAC) data for the 2013–2014 through 2017–2018 influenza seasons.

Methods

Excess deaths attributable to influenza were estimated using a negative binomial regression model incorporating laboratory surveillance data and weekly counts of deaths with an underlying respiratory or circulatory cause of death. We obtained death data from the National Vital Statistics System. Population estimates for LAC were prepared by Hedderson Demographic Services for LAC Internal Services Department. The weekly total number of respiratory specimens tested and number positive for influenza or respiratory syncytial virus were provided by nine healthcare systems in LAC. Influenza-associated deaths in all ages are reportable to LAC Department of Public Health; confirmed reports are counted as observed deaths.

Results

The midyear LAC population increased from 10,019,362 in 2013 to 10,272,648 in 2017. The median number of observed influenza deaths reported to public health was 81 in 2015–2016 (minimum [min]: 56 in 2015–2015, maximum [max]: 288 in 2017–2018). The median number of seasonal deaths with an underlying respiratory or circulatory cause was 27,455 (min: 25,828, max: 28,732). The median estimate of influenza-attributable deaths was 1,478 (95% confidence interval [CI]: 823–2,613) in 2015–2016, with a min of 1,045 deaths (CI: 629–2,258) in 2013–2014 and a max of 1,905 (CI: 1,075–3,269) in 2017–2018.

Conclusion

Although influenza-associated deaths at all ages are reportable in LAC, a variety of barriers to reporting exist. Our estimates indicate that influenza-associated deaths in LAC are underreported. The more comprehensive modeled estimate of the burden of influenza can better inform local policy and planning decisions.

Disclosures

All authors: No reported disclosures.
2320. The Role of Ultraviolet Light, Atmospheric Ozone, and Humidity in Influenza Activity
Authors: Cano Cevallos Edison J , Tande Aaron J , O’Horo John C
Published: October 2019

Background

The interaction between influenza activity and environemental factor such as ultraviolet light index (UVI), atmospheric ozone (AO), and other related meteorological variables remains poorly understood. In the midst of climate change and increasingly poor performance of influenza vaccination, more information on influenza activity and its interaction with meteorological variables is critically needed.

Methods

Influenza A and B tests results by PCR from respiratory sources were collected from two large hospitals in Phoenix, AZ and Jacksonville, FL from January 1, 2014 to December 31, 2017. Publicly available meteorological data for each location was obtained from the National Oceanic and Atmospheric Administration. We excluded cases residing beyond 0.5° of longitude and latitude radius of the given meteorological data. A weekly index activity and maximum weekly values of meteorological variables were matched, and performed a correlation and regression analysis.

Results

A total of 5,238 influenza tests were performed during the study period. The influenza index showed an statistically significant weakly positive correlation with maximum CSUVI (r = 0.14; P = 0.0227) and mean zenith (r = 0.17; P = 0.0047). An statistically significant, positive correlation was observed between influenza index and atmospheric ozone (r = 0.23; P = 0.0001). Significant negative correlations were also observed with DBT, DPT, RH and HI (r = −0.27, r = −0.39, r = −0.13, r = −0.33, respectively; P < 0.04). The influenza index showed significant interactions in a univariate linear regression (Table 1). A relationship between influenza index and dew point temperature was observed in a multivariate model (OR = 0.66; CI95% 0.44–0.97).

Conclusion

To the best of our knowledge, this is the first report showing a significant interactions between influenza index, UVI and atmospheric ozone in two geographically distant locations. Further studies are needed to define the role of complex climatological patterns and influenza.

Disclosures

All authors: No reported disclosures.
2321. FluMex: A New Clinical Severity Index in Mexican Hospitalized Patients with Influenza
Authors: Aguirre-García Gloria Mayela , Magdalena Gamboa-Alonso Carmen , Purón-González Emma , Camacho-Ortiz Adrian
Published: October 2019

Background

Influenza virus infection is frequently characterized by a complex clinical behavior and outcomes can be fatal. There are many published scoring methods aimed for pulmonary infections and sepsis severity nevertheless they lack adequate sensitivity and specificity in patients with Influenza.

Methods

From 2013 to 2018, hospitalized patients from five hospitals from the Christus Muguerza health group from Monterrey, Mexico who had a positive rapid influenza-test and/or positive PCR for Influenza virus were enrolled. Risk factors for severity and mortality were evaluated calculating odds ratio with a binary logistic regression model and were adjusted for other factors. The new index was then compared with pneumonia severity scores by assessing area under the curve(AUC), sensitivity and specificity.

Results

We analyzed data from 125 patients hospitalized with confirmed Influenza infection. Less than 1% had received the corresponding seasonal influenza vaccine. Type 2 diabetes (T2D) and hypertension (HT) were the most prevalent comorbidities. Odds ratios were significant for age > 65 years, body mass index (BMI) > 30, T2D, HT, pulsoximetry < 90%, respiratory rate > 22 per minute, altered mental status, blood urea nitrogen (BUN) > 19 mg/dL, elevated lactate dehydrogenase (LDH), and an abnormal chest X-ray. The FluMex score was applied to a control group of 125 admitted patients with confirmed Influenza infection. AUC was 0.63 (CI 95%, 0.52–0.74; P < 0.05) for severity and 0.90 (IC 95%, 0.83–0.97; P < 0.05) for mortality, showing better predictive performance than other pneumonia and sepsis scores such as CURB-65, PSI, CROMI, SIRS, SOFA, qSOFA and ILI (Table 1).

Conclusion

The FluMex scoring system can be a useful tool for patients with suspected Influenza infection in predicting severity and mortality, helping to improve care and resource management.

Disclosures

All authors: No reported disclosures.