Search

Widespread use of antimicrobials in human and veterinary medicine drives the emergence and dissemination of resistant bacteria in human, animal, and environmental reservoirs. The AVMA and FDA Center for Veterinary Medicine have both taken public positions emphasizing the importance of incorporating antimicrobial stewardship in veterinary clinical settings; however, a model for implementing a comprehensive antimicrobial stewardship program in veterinary practice is not readily available. In 2015, The Ohio State University College of Veterinary Medicine began developing a veterinary antimicrobial stewardship program modeled on existing programs in human health-care institutions and the 7 core elements of a successful hospital antimicrobial stewardship program, as defined by the CDC. The program includes comprehensive antimicrobial use guidelines, active environmental surveillance, and enhanced infection control procedures in The Ohio State University Veterinary Medical Center, along with routine monitoring and reporting of antimicrobial prescribing practices and antimicrobial susceptibility patterns of common pathogens isolated from patients and the hospital environment. Finally, programs have been developed to educate clinicians, staff, and students on antimicrobial resistance and appropriate antimicrobial prescribing practices. The antimicrobial stewardship program has been designed to help clinicians and students confidently make judicious antimicrobial use decisions and provide them with actionable steps that can help them act as strong stewards while providing the best care for their patients. This report describes our program and the process involved in developing it, with the intent that the program could serve as a potential model for other veterinary medical institutions.

Background: Methicillin-resistant Staphylococcus aureus (MRSA) can be found in emergency medical services (EMS) ambulances. This poses an occupational risk and patient safety hazard. Screening for environmental contamination is often not performed due to limited resources and logistical challenges. This study’s objective was to compare traditional screening of individual surfaces versus “pooled sampling” to efficiently identify contamination. Methods: A cross-sectional study, conducted among 145 Ohio EMS ambulances from 84 agencies, tested a novel pooled sampling methodology to detect MRSA contaminated ambulances. For ambulances screened using pooled sampling, 3 samples were collected within each ambulance. Pool One included cabinets, doorways, and ceiling bar. Pool Two included cot, seats, and backboard. Pool Three included steering wheel, kits, and clipboard. For ambulances screened with the traditional detection technique, each of the 9 aforementioned surfaces were sampled individually. Descriptive statistics and unadjusted and adjusted odds ratios (OR) were calculated to compare the 2 methods. Results: Forty-seven of 145 ambulances (32.4%) had at least 1 of the 9 locations contaminated with MRSA. When comparing the 2 screening methodologies, no significant difference was observed regarding the overall detection of MRSA contaminated ambulances (24/60 [40%] versus 23/85 [27.6%], P value: 0.1000). This indicates that pooled sampling appears as an efficient method for identification of MRSA contaminated ambulances. Conclusion: One-third of Ohio ambulances had MRSA contamination in this study. Therefore, an efficient methodology to identify contaminated ambulances with hazardous pathogens is incredibly valuable. Pooling can help save resources and simplify sampling logistics, all which could positively impact infection control practices in emergency medical services.

Increasing rates of infection and multidrug-resistant pathogens, along with a high use of antimicrobial therapy, make the intensive care unit (ICU) an ideal setting for implementing and supporting antimicrobial stewardship efforts. Overuse of antimicrobial agents is common in the ICU, as practitioners are challenged daily with achieving early, appropriate empiric antimicrobial therapy to improve patient outcomes. While early antimicrobial stewardship programs focused on the financial implications of antimicrobial overuse, current goals of stewardship programs align closely with those of critical care providers—to optimize patient outcomes, reduce development of resistance, and minimize adverse outcomes associated with antibiotic overuse and misuse such as acute kidney injury and Clostridioides difficile-associated disease. Significant opportunities exist in the ICU for critical care clinicians to support stewardship practices at the bedside, including thoughtful and restrained initiation of antimicrobial therapy, use of biomarkers in addition to rapid diagnostics, Staphylococcus aureus screening, and traditional microbiologic culture and susceptibilities to guide antibiotic de-escalation, and use of the shortest duration of therapy that is clinically appropriate. Integration of critical care practitioners into the initiatives of antimicrobial stewardship programs is key to their success. This review summarizes key components of antimicrobial stewardship programs and mechanisms for critical care practitioners to share the responsibility for antimicrobial stewardship.

Rapid synovial fluid-induced aggregation of Staphylococcus aureus is currently being investigated as an important factor in the establishment of periprosthetic joint infections (PJIs). Pathogenic advantages of aggregate formation have been well documented in vitro, including recalcitrance to antibiotics and protection from host immune defenses. The objective of the present work was to determine the strain dependency of synovial fluid-induced aggregation by measuring the degree of aggregation of 21 clinical S. aureus isolates cultured from either PJI or bloodstream infections using imaging and flow cytometry. Furthermore, by measuring attached bacterial biomass using a conventional crystal violet assay, we assessed whether there is a correlation between the aggregative phenotype and surface-associated biofilm formation. While all of the isolates were stimulated to aggregate upon exposure to bovine synovial fluid (BSF) and human serum (HS), the extent of aggregation was highly variable between individual strains. Interestingly, the PJI isolates aggregated significantly more upon BSF exposure than those isolated from bloodstream infections. While we were able to stimulate biofilm formation with all of the isolates in growth medium, supplementation with either synovial fluid or human serum inhibited bacterial surface attachment over a 24 h incubation. Surprisingly, there was no correlation between the degree of synovial fluid-induced aggregation and quantity of surface-associated biofilm as measured by a conventional biofilm assay without host fluid supplementation. Taken together, our findings suggest that synovial fluid-induced aggregation appears to be widespread among S. aureus strains and mechanistically independent of biofilm formation. IMPORTANCE Bacterial infections of hip and knee implants are rare but devastating complications of orthopedic surgery. Despite a widespread appreciation of the considerable financial, physical, and emotional burden associated with the development of a prosthetic joint infection, the establishment of bacteria in the synovial joint remains poorly understood. It has been shown that immediately upon exposure to synovial fluid, the viscous fluid in the joint, Staphylococcus aureus rapidly forms aggregates which are resistant to antibiotics and host immune cell clearance. The bacterial virulence associated with aggregate formation is likely a step in the establishment of prosthetic joint infection, and as such, it has the potential to be a potent target of prevention. We hope that this work contributes to the future development of therapeutics targeting synovial fluid-induced aggregation to better prevent and treat these infections.

Background: Various strategies aimed at limiting inappropriate antimicrobial use including antibiotic time out (ATO) have been proposed to combat the development of antimicrobial resistance, yet there are limited studies that have assessed the impact of ATO on clinical outcomes. Methods: This single-center retrospective study reviewed the effect of a passive ATO strategy by comparing 100 adult patients with an ATO matched by infection type to 100 antibiotic-treated adult patients lacking an ATO note. Results: No difference in clinical outcomes was observed, however, ATO did result in improved optimization of antibiotic selection and duration, and reduction of piperacillin/tazobactam and vancomycin use. Conclusion: Further studies are warranted to evaluate the impact of ATO on clinical outcomes of a larger homogenous population with specified infectious diagnoses and clinical characteristics.

The primary objectives were to determine the prevalence of and identify variables associated with respiratory bacterial co-infection in COVID-19 inpatients. Secondary outcomes included length of stay and in-hospital mortality. Eighty-two (11.2%) of 735 COVID-19 inpatients had respiratory bacterial co-infection. Fifty-seven patients met inclusion criteria and were matched to three patients lacking co-infection (N = 228 patients). Patients with co-infection were more likely to receive antibiotics [57 (100%) vs. 130 (76%), p < 0.0001] and for a longer duration [19 (13-33) vs. 8 (4-13) days, p

What is known and objective The 2017 IDSA/SHEA Clinical Practice Guidelines for Clostridioides difficile infection (CDI) recommend treating recurrent episodes with fidaxomicin or oral vancomycin, but there is little evidence to support one strategy over another, particularly beyond the first recurrence. The aim of this study was to compare clinical outcomes in patients with recurrent CDI treated with vancomycin vs. fidaxomicin. Methods This retrospective study evaluated inpatients with recurrent CDI treated with vancomycin or fidaxomicin between 1 January 2013 and 1 May 2019. The primary outcome was CDI recurrence. Secondary outcomes included re-infection, treatment failure, infection-related length of stay (IRLOS) and in-hospital all-cause mortality (IHACM). The Wilcoxon rank-sum test, Pearson's chi-square test or Fisher's exact test was utilized, as appropriate. A multivariable logistic regression (MLR) model was used to estimate the adjusted odds ratio and 95% confidence interval assessing recurrence while adjusting for confounding variables. A survival analysis was also conducted. Results 135 patients met the inclusion criteria (35 fidaxomicin vs. 100 vancomycin). There was no difference in CDI recurrence [7 (20%) fidaxomicin vs. 11 (11%) vancomycin, p = 0.18]; this persisted in the MLR model (OR: 0.85 [95% CI 0.27-2.7]) and survival analysis (p = 0.1954). Additionally, there was no difference in re-infection rate (p = 0.73), treatment failure (p = 0.13), IRLOS (p = 0.19) or IHACM (p = 0.65). What is new and conclusion This represents the first analysis of CDI recurrence that included patients with >2 prior episodes of CDI. The study found no difference in additional recurrences when patients were treated with oral vancomycin vs fidaxomicin for recurrent CDI. However, the current study is limited by the small sample size available for inclusion. Prospective randomized studies with larger sample sizes are needed to confirm this study's conclusions.

Background Proper specimen collection is central to improving patient care by ensuring optimal yield of diagnostic tests, guiding appropriate management, and targeting treatment. The purpose of this article is to describe the development and implementation of a training-of-trainers educational program designed to improve clinical culture specimen collection among healthcare personnel (HCP) in Ethiopia. Methods A Clinical Specimen Collection training package was created consisting of a Trainer’s Manual, Reference Manual, Assessment Tools, Step-by-Step Instruction Guides (i.e., job aides), and Core Module PowerPoint Slides. Results A two-day course was used in training 16 master trainers and 47 facility-based trainers responsible for cascading trainings on clinical specimen collection to HCP at the pre-service, in-service, or national-levels. The Clinical Specimen Collection Package is offered online via The Ohio State University’s CANVAS online platform. Conclusions The training-of-trainers approach may be an effective model for development of enhanced specimen collection practices in low-resource countries.

Empiric antibiotic prescribing can be supported by guidelines and/or local antibiograms, but these have limitations. We sought to use data from a comprehensive electronic health record to use statistical learning to develop predictive models for individual antibiotics that incorporate patient- and hospital-specific factors. This paper reports on the development and validation of these models with a large retrospective cohort. This was a retrospective cohort study including hospitalized patients with positive urine cultures in the first 48 h of hospitalization at a 1,500-bed tertiary-care hospital over a 4.5-year period. All first urine cultures with susceptibilities were included. Statistical learning techniques, including penalized logistic regression, were used to create predictive models for cefazolin, ceftriaxone, ciprofloxacin, cefepime, and piperacillin-tazobactam. These were validated on a held-out cohort. The final data set used for analysis included 6,366 patients. Final model covariates included demographics, comorbidity score, recent antibiotic use, recent antimicrobial resistance, and antibiotic allergies. Models had acceptable to good discrimination in the training data set and acceptable performance in the validation data set, with a point estimate for area under the receiver operating characteristic curve (AUC) that ranged from 0.65 for ceftriaxone to 0.69 for cefazolin. All models had excellent calibration. We used electronic health record data to create predictive models to estimate antibiotic susceptibilities for urinary tract infections in hospitalized patients. Our models had acceptable performance in a held-out validation cohort.

Objectives To determine if nonspecific symptoms and fever affect the posttest probability of acute bacterial infection in older patients in the emergency department (ED). Design Preplanned, secondary analysis of a prospective observational study. Setting Tertiary care, academic ED. Participants A total of 424 patients in the ED, 65 years or older, including all chief complaints. Measurements We identified presence of altered mental status, malaise/lethargy, and fever, as reported by the patient, as documented in the chart, or both. Bacterial infection was adjudicated by agreement among two or more of three expert reviewers. Odds ratios were calculated using univariable logistic regression. Positive and negative likelihood ratios (PLR and NLR, respectively) were used to determine each symptom's effect on posttest probability of infection. Results Of 424 subjects, 77 (18%) had bacterial infection. Accounting for different reporting methods, presence of altered mental status (PLR range, 1.40-2.53) or malaise/lethargy (PLR range, 1.25-1.34) only slightly increased posttest probability of infection. Their absence did not assist with ruling out infection (NLR, greater than 0.50 for both). Fever of 38°C or higher either before or during the ED visit had moderate to large increases in probability of infection (PLR, 5.15-18.10), with initial fever in the ED perfectly predictive, but absence of fever did not rule out infection (NLR, 0.79-0.92). Results were similar when analyzing lower respiratory, gastrointestinal, and urinary tract infections (UTIs) individually. Of older adults diagnosed as having UTIs, 47% did not complain of UTI symptoms. Conclusions The presence of either altered mental status or malaise/lethargy does not substantially increase the probability of bacterial infection in older adults in the ED and should not be used alone to indicate infection in this population. Fever of 38°C or higher is associated with increased probability of infection. J Am Geriatr Soc 67:484-492, 2019.

OBJECTIVES To identify the impact of penicillin versus alternative β-lactams on clinical outcomes in patients with penicillin-susceptible Staphylococcus aureus (PSSA) bacteremia. DESIGN Retrospective cohort study. SETTING Academic medical center. PATIENTS Adult patients with PSSA bacteremia treated with a β-lactam as definitive therapy. MEASUREMENTS The primary outcome was a composite end point of 30-day clinical failure (change in PSSA therapy due to persistent or worsening signs and symptoms, PSSA bacteremia recurrence or persistence, and/or infection-related mortality) in patients treated with penicillin versus alternative β-lactams. Secondary outcomes included infection-related and hospital length of stay (LOS), 90-day recurrence, 90-day infection-related readmission, 30-day all-cause mortality, adverse drug events (ADEs), and 30-day change in PSSA therapy due to ADEs. A subgroup analysis comparing penicillin, nafcillin, and cefazolin was also conducted. MAIN RESULTS For the 122 patients who were included, the most common definitive therapies were nafcillin (37%), cefazolin (29%), and penicillin (21%). No difference was found in 30-day clinical failure (4% vs 11%, p=0.46), infection-related LOS (12 days vs 11 days, p=0.39), hospital LOS (12.5 days vs 12 days, p=0.69), 90-day recurrence (p=1.00), 90-day infection-related readmission (p=1.00), or 30-day all-cause mortality (p=0.45) between penicillin and other β-lactams. The prevalence of ADEs was different among penicillin, nafcillin, and cefazolin (p=0.049), with nafcillin requiring more changes in therapy (p=0.005). CONCLUSIONS Definitive therapy with penicillin had similar efficacy compared with alternative β-lactams for the treatment of PSSA bacteremia. However, nafcillin was associated with more ADEs requiring a change in therapy.

Our objective is to operationalize a novel antibiotic advisor, called the personalized weighted incidence syndromic combination antibiogram (pWISCA), intended to help physicians with initial antibiotic choice in hospitals. Clinical decision support tools are a promising technology for providing evidence-based guidance that incorporates data about patients from electronic health records. Nevertheless, congruence with policies and procedures and local experts’ opinions, as well as taking into account local resistance data for the medical center’s patient population, is needed when selecting and ordering the antibiotic medication options provided by pWISCA. This paper presents findings from applying a mixed methods approach to identify and prioritize antibiotic medications and associated contextual data to display in a CDS tailored to the local hospital. We discuss implications of these findings.

Background: Vancomycin and linezolid are standard treatment options for nosocomial methicillin-resistant Staphylococcus aureus (MRSA) pneumonia. While acute kidney injury (AKI) is commonly attributed to vancomycin, existing data has not definitely confirmed vancomycin as an independent risk factor for AKI. Aims: This study aimed to quantify the incidence of AKI in Surgical Intensive Care Unit (ICU) patients receiving empiric vancomycin or linezolid for nosocomial pneumonia and to identify risk factors for AKI with a focus on MRSA antibiotic therapy. Materials and Methods: A retrospective cohort analysis of surgical ICU patients who received at least 48 h of vancomycin or linezolid for pneumonia was performed. Patients who received vancomycin were compared to those who received linezolid with a primary endpoint of AKI as defined by the risk/injury/failure/loss/end-stage renal disease (RIFLE) criteria. A modified RIFLE criteria assessing only changes in serum creatinine was also used. Results: One hundred one patients were evaluated (63 vancomycin and 38 linezolid). AKI occurred in 51 (81.0%) and 32 (84.2%) patients in the vancomycin and linezolid groups (P = 0.79), respectively. Using the modified RIFLE criteria, AKI occurred in 19 (30.2%) and 14 (36.8%) patients in the vancomycin and linezolid groups (P = 0.448). After adjustment for age, diabetes mellitus, Charlson comorbidity index, and concomitant nephrotoxins, there was no difference in risk of AKI between groups (P = 0.773). Conclusions: Patients who received empiric vancomycin or linezolid for nosocomial pneumonia experienced high, but similar rates of AKI. The results suggest MRSA antibacterial therapy in this setting may not be independently indicative of AKI risk, rather the risk is likely multifactorial.

We describe a prospective observational cohort (N = 187) to evaluate peripherally inserted central catheter line complications concurrently from the time of placement until removal. A significantly higher percentage of patients who experienced intraluminal thrombosis were receiving total parenteral nutrition ( P ≤ .001) and had a dual lumen catheter ( P = .01). Among patients with a confirmed or suspected infection, a significantly higher proportion received total parenteral nutrition ( P = .01), had dual-lumen catheters ( P = .04), and were neutropenic ( P = .04).

Objectives To compare the accuracy of the Loeb criteria, emergency department (ED) physicians’ diagnoses, and Centers for Disease Control and Prevention (CDC) guidelines for acute bacterial infection in older adults with a criterion standard expert review. Design Prospective, observational study. Setting Urban, tertiary-care ED. Participants Individuals aged 65 and older in the ED, excluding those who were incarcerated, underwent a trauma, did not speak English, or were unable to consent. Measurements Two physician experts identified bacterial infections using clinical judgement, participant surveys, and medical records; a third adjudicated in cases of disagreement. Agreement and test characteristics were measured for ED physician diagnosis, Loeb criteria, and CDC surveillance guidelines. Results Criterion-standard review identified bacterial infection in 77 of 424 participants (18%) (18 (4.2%) lower respiratory, 19 (4.5%) urinary tract (UTI), 22 (5.2%) gastrointestinal, 15 (3.5%) skin and soft tissue). ED physicians diagnosed infection in 71 (17%), but there were 33 with under- and 27 with overdiagnosis. Physician agreement with the criterion standard was moderate for infection overall and each infection type (κ = 0.48–0.59), but sensitivity was low (

Background The 2017 IDSA/SHEA clinical practice guidelines for Clostridioides difficile infection (CDI) recommend treating recurrent episodes with fidaxomicin or oral vancomycin, but there is little evidence to support one strategy over another, particularly beyond the first recurrence. The aim of this study was to compare clinical outcomes in patients with recurrent CDI treated with vancomycin vs. fidaxomicin. Methods This was a retrospective study evaluating inpatients with recurrent CDI treated with vancomycin or fidaxomicin between January 1, 2013 and May 1, 2019. The primary outcome was CDI recurrence. Secondary outcomes included re-infection, treatment failure, infection-related length of stay (IRLOS), and in-hospital all-cause mortality (IHACM). Data collected included demographics; number of previous CDI episodes; CDI therapy; time to recurrence and re-infection; exposure to broad-spectrum antibiotics, proton pump inhibitors, and probiotics. Wilcoxon rank sum, Pearson chi-square, or Fisher’s exact tests were utilized, as appropriate. A multivariable logistic regression (MLR) model was used to estimate the adjusted odds ratio and 95% confidence interval assessing recurrence while adjusting for confounding variables. A survival analysis was also conducted. Results One hundred thirty-five patients met inclusion criteria (n = 35 fidaxomicin vs. n = 100 vancomycin). Of these, 42 (31%) had experienced at least 2 CDI episodes prior to their index recurrence. There was no difference in CDI recurrence [7 (20%) fidaxomicin vs. 11 (11%) vancomycin, p=0.18]; this persisted in the MLR model (OR 0.85 [95% CI 0.27-2.7]) and survival analysis (P = 0.1954). Additionally, there was no difference in re-infection rate (p=0.73), treatment failure (p=0.13), IRLOS (p=0.19), or IHACM (p=0.65). Conclusion Oral vancomycin and fidaxomicin are both suitable treatment options in the setting of recurrent CDI. Disclosures All Authors: No reported disclosures

Background Methicillin-resistant Staphylococcus aureus (MRSA) is a leading cause of health care–associated infections, and the role that the hospital environment might play in the transmission cycle remains undefined. We determined the distribution of environmental MRSA isolates, studied contamination patterns of MRSA clones, and evaluated the association between MRSA patient load and environmental contamination. Methods High-contact surfaces were sampled for 12 consecutive months in 2 inpatient wards. Concurrently, aggregated data of MRSA patient infection burden were analyzed. Antimicrobial susceptibility testing and molecular epidemiologic tools were used to characterize and analyze all isolates. Results Overall, 23.7% of the surfaces were MRSA positive. Handrails (58.3%), the medicine room (50.0%), chart holders (41.7%), and access doors (33.3%) were the most contaminated surfaces. Thirty-four different MRSA pulsotypes were identified. Forty-six percent of the isolates were SCC mec II/USA100. Recurrent introduction and reintroduction of clones and hot spot surfaces frequently contaminated with different MRSA strains were observed. However, long-term contamination (maintenance) was not observed. The burden of clinical MRSA cases was not an indicator of the level of environmental contamination. Conclusions MRSA frequently contaminates hospital surfaces during nonoutbreak periods and is not associated with the number of clinical MRSA cases. Monitoring and thorough cleaning and disinfection of hot spot surfaces are necessary to minimize the presence of MRSA in the hospital.

Background: Antimicrobial resistance (AMR) is an increasingly critical global public health challenge. An initial step in prevention is the understanding of resistance patterns with accurate surveillance. To improve accurate surveillance and good clinical care, we developed training materials to improve the appropriate collection of clinical culture samples in Ethiopia. Methods: Specimen-collection training materials were initially developed by a team of infectious diseases physicians, a clinical microbiologist, and a monitoring and evaluation specialist using a training of trainers (ToT) platform. Revisions after each training session were provided by Ethiopian attendees including the addition of regional and culturally relevant material. The training format involved didactic presentations, interactive practice sessions with participants providing feedback and training to each other and the entire group as well as assessments of all training activities. Results: Overall, 4 rounds of training were conducted from August 2017 to September 2019. The first 2 rounds of training were conducted by The Ohio State University (OSU) staff, and Ethiopian trainers conducted the last 2 rounds. Initial training was primarily in lecture format outlining use of microbiology laboratory findings in clinical practice and steps for collecting specimens correctly. Appropriate specimen collection was demonstrated and practiced. Essential feedback from this early audience provided input for the final development of the training manual and visual aids. The ToT for master trainers took place in July 2018 and was conducted by OSU staff. In sessions held in February and August 2019, these master trainers provided training to facility trainers, who provide training to personnel directly responsible for specimen collection. In total, 144 healthcare personnel (including physicians, nurses, and laboratory staff), from 12 representative Ethiopian public and academic hospitals participated in the trainings. Participants were satisfied with the quality of the training (typically ranked >4.5 of 5.0) and strongly agreed that the objectives were clearly defined and that the information was relevant to their work. Posttraining scores increased by 23%. Conclusions: Training materials for clinical specimen collection have been developed for use in low- and middle-resource settings and with initial pilot testing and adoption in Ethiopia. The trainings were well accepted, and Ethiopian personnel were able to successfully lead the trainings and improve their knowledge and skills regarding specimen collection. The materials are being finalized in an online format for easier open access dissemination. Further studies are planned to determine the effectiveness of the trainings in improving the quality of clinical specimen submissions to the microbiology laboratory.Funding: NoneDisclosures: None

Background Stenotrophomonas maltophilia is intrinsically resistant to several antibiotics, making it potentially challenging to treat. Studies have demonstrated treatment failures and resistance development with monotherapy (MT); however, clinical data are limited with combination therapy (CT). Objectives To compare clinical outcomes with CT versus MT for S. maltophilia pneumonia. Methods This was a retrospective cohort study of patients admitted between November 2011 and October 2017 with S. maltophilia pneumonia who received at least 48 h of effective therapy. The primary outcome was clinical response after 7 days of effective therapy with CT versus MT. Secondary outcomes included development of a non-susceptible isolate, 30 day microbiological cure, infection recurrence, infection-related mortality and all-cause mortality. The Wilcoxon rank sum test, the Pearson χ2 test and Fisher's exact test were utilized for univariate analyses. A multivariable logistic regression model was used to assess clinical response while adjusting for confounding variables. Results Of 252 patients with S. maltophilia pneumonia included, 38 received CT and 214 received MT. There was no difference in 7 day clinical response with CT versus MT (47.4% versus 39.7%, P = 0.38), even after controlling for immune status, APACHE II score and polymicrobial pneumonia (adjusted OR 1.51, 95% CI 0.63-3.65). Thirty day microbiological cure (P = 0.44), recurrence (P = 0.53), infection-related mortality (P = 0.19) and isolation of a non-susceptible isolate during or after therapy (P = 1.00 each) were also similar between both groups; however, 30 day all-cause mortality was greater with CT (P = 0.03). Conclusions CT had similar rates of clinical efficacy and resistance development compared with MT for S. maltophilia pneumonia.

Background The Infectious Diseases Society of America’s guideline for implementing antibiotic (abx) stewardship recommends routine review of abx use. Several studies demonstrate antibiotic time out (ATO) programs result in de-escalation, but there is limited evidence of improved outcomes. The aim of this study was to evaluate the clinical impact of ATO. Methods This retrospective study included hospitalized patients at The Ohio State University Wexner Medical Center receiving abx and a documented ATO from 7/1/2017 to 6/30/2018. ATO patients were matched by infection type to abx-treated patients lacking an ATO note. Patients were excluded if they were identified as a protected population, were in the ICU at the time of ATO, had an ATO within 48 hours of discharge, cystic fibrosis, or febrile neutropenia. The primary objective was to evaluate abx optimization in patients with documented ATO vs. those without ATO. Abx optimization was defined as the selection of ideal abx based on guidelines, culture and susceptibility results, or expert opinion when undefined. Secondary outcomes included vancomycin-associated acute kidney injury (VAN-AKI), infection-related length of stay (LOS), all-cause 30-day readmission or mortality, abx days, and nosocomial C. difficile infection (CDI) rates. The Student t-test/Fisher’s exact test and Wilcoxon-rank sum were utilized as appropriate. Results One hundred ATO patients were compared with 100 non-ATO patients. Baseline characteristics and infection types were similar between groups. ATO resulted in improved optimization of abx selection (P = 0.05) and duration (P < 0.01), and reduced piperacillin/tazobactam (P/T) and vancomycin (VAN) utilization. No difference was observed in VAN-AKI (22 vs. 20%, P = 0.73), 30-day readmission (28 vs. 27%, P = 0.87), mortality (5 vs. 5%, P = 1), or CDI rates (6 vs. 5%, p = 0.76) in the ATO vs. non-ATO group. However, inpatient abx days (12 vs. 8, P = 0.004) and infection-related LOS (10 vs. 8, P = 0.0006) were shorter in the non-ATO group. Conclusion ATO improved optimization of abx selection and duration, and reduced P/T and VAN use. Despite this, clinical outcomes were not improved. Disclosures All authors: No reported disclosures.

The objective was to determine the nasal carriage prevalence of methicillin-resistant Staphylococcus aureus (MRSA) among emergency medical service (EMS) personnel and the associated risk factors. A cross-sectional study was conducted among Ohio EMS personnel randomly sampled from 84 urban and rural agencies. Surveys assessing demographics, occupational history, health, cohabitation status, and hygiene practice were collected with nasal swabs from those who enrolled. Survey weight adjusted analysis was performed (1) to estimate MRSA nasal carriage prevalence of Ohio EMS providers, and (2) to identify variables associated with MRSA. MRSA was detected in 4.6% (13/280) EMS personnel sampled. After employing a survey-weighted analysis the following risk factors associated with MRSA carriage were identified: those who did not practice frequent hand hygiene after glove use (OR, 10.51; 95% CI, 2.54-43.45; P = 0.0012), living with someone with a recent staphylococcal infection (OR, 9.02; 95% CI, 1.03-78.98; P = 0.0470), and individuals with low frequency of hand washing (< 8 times per shift) (OR, 4.20; 95% CI 1.02-17.27; P = 0.0468). An additional risk factor identified through the logistic regression analysis on the study population was EMS workers with an open wound or skin infection (OR, 6.75; 95% CI, 1.25-36.36; P = 0.0262). However, this was not significant in the survey-weighted analysis. The high prevalence of MRSA in Ohio EMS personnel is both an occupational hazard and patient safety concern. Implementing methods to reinforce CDC guidelines for proper hygiene could decrease MRSA found in the EMS setting. Previous literature suggests that a reduction in MRSA colonization can lead to decreases in transmission and improved health for both patients and personnel.

Background Studies evaluating the impact of passive cost visibility tools on antibiotic prescribing are lacking. Objective The objective of this study was to evaluate whether the implementation of a passive antibiotic cost visibility tool would impact antibiotic prescribing and decrease antibiotic spending. Methods An efficiency and effectiveness initiative (EEI) was implemented in October 2012. To support the EEI, an antibiotic cost visibility tool was created in June 2013 displaying the relative cost of antibiotics. Using an observational study of interrupted time series design, 3 time frames were studied: pre EEI, post EEI, and post cost visibility tool implementation. The primary outcome was antibiotic cost per 1,000 patient days. Secondary outcomes included case mix index (CMI)-adjusted antibiotic cost per 1,000 patient days and utilization of the cost visibility tool. Results Initiation of the EEI was associated with a $4,675 decrease in antibiotic cost per 1,000 patient days ( P = .003), and costs continued to decrease in the months following EEI ( P = .009). After implementation of the cost visibility tool, costs remained stable ( P = .844). Despite CMI increasing over time, adjustment for CMI had no impact on the directionality or statistical significance of the results. Conclusion Our study demonstrated a significant and sustained decrease in antibiotic cost per 1,000 patient days when focused medication cost reduction efforts were implemented, but passive cost visibility tool implementation was not associated with additional cost reduction. Antibiotic cost visibility tools may be of most benefit when prior medication cost reduction efforts are lacking or when an active intervention is incorporated.

Pets can be a source of disease (zoonoses) for humans. The disease risks associated with pet contact are highest among young children, the elderly, pregnant women, and immunocompromised hosts. These individuals and household members display limited knowledge of pet-associated disease, rarely recall receipt of pet-associated disease information, and report pet ownership practices that are often at odds with established disease prevention recommendations. Veterinary staff are in a key position to promote safe pet ownership and contact practices. Encouraging and safeguarding client disclosure of immunocompromising health conditions and promoting veterinarian-physician communications are critical for effectively providing this service.

The USA300 North American epidemic (USA300-NAE) clone of methicillin-resistant Staphylococcus aureus has caused a wave of severe skin and soft tissue infections in the United States since it emerged in the early 2000s, but its geographic origin is obscure. Here we use the population genomic signatures expected from the serial founder effects of a geographic range expansion to infer the origin of USA300-NAE and identify polymorphisms associated with its spread. Genome sequences from 357 isolates from 22 U.S. states and territories and seven other countries are compared. We observe two significant signatures of range expansion, including decreases in genetic diversity and increases in derived allele frequency with geographic distance from the Pennsylvania region. These signatures account for approximately half of the core nucleotide variation of this clone, occur genome wide, and are robust to heterogeneity in temporal sampling of isolates, human population density, and recombination detection methods. The potential for positive selection of a gyrA fluoroquinolone resistance allele and several intergenic regions, along with a 2.4 times higher recombination rate in a resistant subclade, is noted. These results are the first to show a pattern of genetic variation that is consistent with a range expansion of an epidemic bacterial clone, and they highlight a rarely considered but potentially common mechanism by which genetic drift may profoundly influence bacterial genetic variation., IMPORTANCE The process of geographic spread of an origin population by a series of smaller populations can result in distinctive patterns of genetic variation. We detect these patterns for the first time with an epidemic bacterial clone and use them to uncover the clone’s geographic origin and variants associated with its spread. We study the USA300 clone of methicillin-resistant Staphylococcus aureus, which was first noticed in the early 2000s and subsequently became the leading cause of skin and soft tissue infections in the United States. The eastern United States is the most likely origin of epidemic USA300. Relatively few variants, which include an antibiotic resistance mutation, have persisted during this clone’s spread. Our study suggests that an early chapter in the genetic history of this epidemic bacterial clone was greatly influenced by random subsampling of isolates during the clone’s geographic spread.

In 2014, as part of the Global Health Security Agenda, Ethiopia was provided the technical and financial resources needed to prioritize antimicrobial resistance (AMR) in the national public health sphere. Under the direction of a multi-stakeholder working group, AMR surveillance was launched in July 2017 at 4 sentinel sites across the country. The AMR surveillance initiative in Ethiopia represents one of the first systematic efforts to prospectively collect, analyze, and report national-level microbiology results from a network of hospitals and public health laboratories in the country. Baseline readiness assessments were conducted to identify potential challenges to implementation to be addressed through capacity-building efforts. As part of these efforts, the working group leveraged existing resources, initiated laboratory capacity building through mentorship, and established infrastructure and systems for quality assurance, data management, and improved coordination. As a result, AMR surveillance data are being reported and analyzed for use; data from more than 1,700 patients were collected between July 2017 and March 2018. The critical challenges and effective solutions identified through surveillance planning and implementation have provided lessons to help guide successful AMR surveillance in other settings. Ultimately, the surveillance infrastructure, laboratory expertise, and communication frameworks built specifically for AMR surveillance in Ethiopia can be extended for use with other infectious diseases and potential public health emergencies. Thus, building AMR surveillance in Ethiopia has illustrated how laying the foundation for a specific public health initiative can develop capacity for core public health functions with potential benefit.

Repetitive element polymerase chain reaction (rep-PCR) typing has been used for methicillin-resistant Staphylococcus aureus (MRSA) strain characterization. The goal of this study was to determine if a rapid commercial rep-PCR system, DiversiLab™ (DL; bioMérieux, Durham, NC, USA), could be used for MRSA surveillance at a large medical center and community hospitals. A total of 1286 MRSA isolates genotyped by the DL system were distributed into 84 distinct rep-PCR patterns: 737/1286 (57%) were clustered into 6 major rep-PCR patterns. A subset of 220 isolates was further typed by pulsed-field gel electrophoresis (PFGE), spa typing, and SCCmec typing. The 220 isolates were distributed into 80 rep-PCR patterns, 94 PFGE pulsotypes, 27 spa, and 3 SCCmec types. The DL rep-PCR system is sufficient for surveillance, but the DL system alone cannot be used to compare data to other institutions until a standardized nomenclature is established and the DL MRSA reference library is expanded.

Background The preferred management of patients with MSSA bacteremia includes definitive therapy with intravenous anti-staphylococcal β-lactam antibiotics. In β-lactam allergic or intolerant patients, daptomycin has been targeted as a viable alternative. The objective of this study was to assess clinical outcomes of daptomycin compared with nafcillin or cefazolin for the treatment of MSSA bacteremia. Methods This was a retrospective cohort study of patients hospitalized from November 1, 2011 to October 31, 2018 at The Ohio State University Wexner Medical Center with MSSA bacteremia. Patients treated with nafcillin, cefazolin or daptomycin were included with 1:1:1 random selection. The primary outcome was a composite of clinical failure, defined as a change in therapy due to persistent/worsening signs and symptoms, bacteremia recurrence or persistence, or inpatient infection-related mortality. Secondary endpoints included 30-day infection-related mortality, duration of bacteremia, 30-day all-cause mortality and adverse events (AEs) necessitating a change in therapy. Results Among patients with MSSA bacteremia, 162 received at least one dose of daptomycin. Of those, 29 received at least 14 days of daptomycin and/or received daptomycin as definitive therapy and thus were included in the analysis. There was no difference in the primary outcome of composite clinical failure comparing daptomycin vs. nafcillin/cefazolin (P = 0.71). In addition, no difference was observed in 30-day infection-related mortality (P = 0.51), duration of MSSA bacteremia (P = 0.9), or 30-day all-cause mortality (P = 0.64). A higher number of AEs necessitating change in therapy were seen in the daptomycin group (P = 0.0002), reflecting initial β-lactam intolerance. Conclusion No difference in clinical failure was identified in patients treated with daptomycin vs. nafcillin/cefazolin suggesting that daptomycin may serve as a non-inferior alternative for treatment of MSSA bacteremia. A higher number of AEs occurred in the daptomycin group indicating β-lactam intolerance as a primary indication for daptomycin therapy. Given the small sample size, subsequent studies are needed to further evaluate the use of daptomycin in the treatment of MSSA bacteremia. Disclosures All authors: No reported disclosures.

Background Monitoring antimicrobial use and resistance are key components of initiatives to promote antimicrobial stewardship and prevent antimicrobial-resistant infections. In this surveillance study, we evaluated trends in resistance among healthcare-associated P. aeruginosa isolates and potential associations with antimicrobial consumption. Methods We established a retrospective cohort of P. aeruginosa isolates collected ≥48 hours after inpatient admission at a 1,300-bed academic medical center from July 1, 2013 to July 31, 2018. We included isolates from all clinical cultures and retained the first isolate for a patient encounter. We defined the multidrug-resistant (MDR) status in accordance with the phenotype definitions established by the Centers for Disease Control and Prevention. We calculated the monthly percentage of class-specific resistance and MDR status among isolates. We measured monthly antimicrobial consumption as days of therapy per 1,000 patient-days. To evaluate potential associations between identified trends in resistance and antimicrobial use, we constructed autoregressive integrated moving average models (ARIMA) with transfer functions. Results Of 1,897 isolates included in the analysis, 303 (16.0%) were classified as MDR P. aeruginosa. The rate of healthcare-associated P. aeruginosa infections and percent of MDR isolates remained stable over the five-year study period. However, we identified trends in resistance to specific antimicrobial classes: there was a significant increase in resistance to antipseudomonal carbapenems, while resistance to aminoglycosides and extended-spectrum cephalosporins decreased. Using the ARIMA modeling strategy, bivariable analyses of resistance and antimicrobial use revealed that carbapenem-resistant P. aeruginosa was positively correlated with the use of antipseudomonal carbapenems at a 1-month lag and ertapenem at a 5-month lag. Conclusion Risk assessments that only measure rates of MDR organisms may miss underlying trends in class resistance. Increasing carbapenem resistance despite a stable proportion of MDR isolates highlights a critical area for continued monitoring and antimicrobial stewardship initiatives targeted at carbapenem use in our hospital. Disclosures All authors: No reported disclosures.

Background Predictive models for empiric antibiotic prescribing often estimate the probability of infection with multidrug-resistant organisms. In this work, we developed models to predict coverage of specific treatment regimens to better target antibiotics to high- and low-risk patients. Methods We established a retrospective cohort of adults admitted to the ICU in a 1,300-bed teaching hospital from November 1, 2011 to June 30, 2016. We included patients with a diagnosis of pneumonia and positive respiratory culture collected during their ICU stay. We collected demographics, comorbidities, and medical history from the electronic health record. We evaluated three penalized regression methods for predicting infection susceptibility to 11 treatment regimens: least absolute selection and shrinkage operator (LASSO), minimax concave penalty (MCP), and smoothly clipped absolute deviation (SCAD). We developed models for susceptibility prediction at two stages of the diagnostic process: for all pathogenic bacteria and for infections with Gram-negative organisms only. We selected final models based on higher area under the receiver operating characteristic (AUROC), acceptable goodness of fit, lower variability of the AUROCs in the cross-validation run, and fewer predictors. Results Among 1,917 cases of pneumonia, 54 different pathogens were identified. The most frequently isolated organisms were: Pseudomonas aeruginosa (16.6%), methicillin-resistant Staphylococcus aureus (16.1%), and Staphylococcus aureus (13.5%). Frequently selected variables included age, Elixhauser score, tracheostomy status, recent antimicrobial use, and prior infection with a carbapenem-resistant organism. All final models used MCP or SCAD methods. Point estimates for the AUROCs in the training set ranged from 0.70 to 0.80, and estimates in the internal validation set ranged from 0.64 to 0.77. Conclusion MCP and SCAD outperformed LASSO. For some regimens, models predicted infection susceptibility with fair accuracy. These models have potential to help antibiotic stewardship efforts to better target appropriate antibiotic use. Disclosures All authors: No reported disclosures.

Background Burkholderia cepacia complex (Burkholderia cenocepacia and Burkholderia multivorans) (BCC) are uncommon, yet serious often drug-resistant pathogens of immunocompromised patients, especially in lung transplants; pre-operative infection/colonization is seen as a contraindication to transplant. Optimal treatment for these difficult infections is not known. We examined impact of single vs. combination therapy on patient outcomes. Methods All cases of BCC positive pulmonary or blood cultures at The Ohio State University Wexner Medical Center between January 1, 2012 and June 30, 2018 were analyzed. No cystic fibrosis patients were included. All combinations thereof were evaluated. The primary outcomes were 30 all-cause mortality and 30-day infection-related mortality. Secondary outcomes included sterilization of cultures, isolation of a non-susceptible isolate within 30 days of therapy, hospital and intensive care unit (ICU) length of stay, and adverse drug effects (ADE) of therapy including: hyperkalemia, acute kidney injury (AKI), transaminitis, and QTc prolongation. Results There were 90 unique patients who grew BCC (22 patients with 92 positive blood cultures; 54 patients with 87 positive pulmonary cultures). Four patients had mixed pulmonary and blood cultures. Ten patients died prior to having treatment for their cultures and were not evaluated. Overall, there were 85 evaluable infection events. Overall 30-day all-cause mortality was 20/85 (23.5%); mortality in blood culture monotherapy 3/14 (21.4%); combination therapy 3/18 (16.7%) (P = 1.00). Mortality in pulmonary culture monotherapy was 6/32 (18.75%); combination 10/30 (33.3%) (P = 0.19). Among blood cultures monotherapy was associated with 8 ADE while combination therapy was 11 (P = 0.82). In pulmonary patients, monotherapy had 16 ADE while combination had 23 (P = 0.03). Conclusion Overall mortality trends improved with combination therapy in blood culture patients and with monotherapy patients in pulmonary cultures. These findings are influenced by the limited number of patients available, and the medical co-morbidities of these patients. In lung patients there were significantly fewer ADE associated with monotherapy as opposed to combination therapy. Disclosures All authors: No reported disclosures.

Background Providers use institutional recommendations, national guidelines, and antibiograms to decide on empiric antibiotics. As local antibiograms are most effective after organisms are known, we sought to use local microbiology and clinical data to develop predictive models for antibiotic coverage prior to identifying the organism. We focused on Gram-negative organisms as they are common urinary pathogens and are often the cause of sepsis originating in the urinary tract. As such, they are important to cover in hospitalized patients with urinary tract infections (UTI). Methods Hospitalized patients, with a diagnosis of UTI and a positive urine culture in the first 48 hours were included. Gram-positive organisms, yeast, and cultures without susceptibilities were excluded. Unknown susceptibilities were filled in using expert-derived rules. Clinical information from electronic health record (EHR) data were extracted on each patient. Penalized logistic regression with 10-fold cross validation was used to develop final models for coverage for five antibiotics (cefazolin, ceftriaxone, ciprofloxacin, cefepime, piperacillin–tazobactam). Final models were chosen based on their discrimination, calibration, and number of predictors, and then tested on a held-out validation dataset. Results Included were 5,096 patients (80% training; 20% validation). Coverage ranged from 65% for cefazolin to 90% for cefepime. Positive blood cultures were present in 544 (11%) with 388 (71%), including a urinary pathogen. In the first 24 hours, 2329 (46%) were hypotensive, 2179 (43%) had a respiratory rate > 22, 2049 (40%) had a WBC > 12, 1079 (21%) were febrile, and 584 (11%) required ICU care. Final model covariates included demographics, antibiotic exposure, prior resistant pathogens, and antibiotic allergies. The five predictive models had a point-estimate for the area under the ROC on the validation set that ranged from 0.70 for ciprofloxacin to 0.73 for ceftriaxone. Conclusion In this cohort of moderate to high acuity hospitalized patients with Gram-negative urinary pathogens, we used EHR data to develop 5 models that predict antibiotic coverage which could be used to support empiric prescribing. These models performed well in a held-out validation set. Disclosures All authors: No reported disclosures.

Background Antimicrobial stewardship plays an integral role in ensuring appropriate antimicrobial use in the inpatient hospital setting and is now required by The Joint Commission. Although it is well established that antimicrobial misuse and overuse has societal and ecological implications, the same regulations do not yet apply to our veterinary and agricultural counterparts. Methods At The Ohio State University Wexner Medical Center (OSUWMC), the Antimicrobial Stewardship Program (ASP) was created in 2007. A partnership was formed with The Ohio State University Veterinary Medical Center (OSUVMC) in 2017 and was leveraged through a pre-existing campus-wide One Health initiative. The goal was to develop a comprehensive Veterinary Hospital ASP. “The Core Elements of Hospital Antibiotic Stewardship Programs” (Centers for Disease Control and Prevention) and “The Core Principles of Antibiotic Stewardship in Veterinary Medicine” (American Veterinary Medical Association) were also referenced for guidance. Results Specific initiatives within the OSUVMC ASP were modeled after similar interventions in the OSUWMC including development of antibiotic use guidelines by animal type for commonly encountered infections, antimicrobial utilization tracking, antibiogram creation, and both active and passive surveillance of targeted resistant pathogens. A mobile-friendly website was created to allow providers easy access to these ASP tools. Overall antimicrobial prescriptions decreased 22.4% following the first year of program implementation. Planning is currently underway for an ASP outreach program to local veterinary practices to increase awareness of ASP and improve antimicrobial prescribing. A parallel outreach program with rural Ohio hospitals is underway at OSUWMC. Conclusion A comprehensive veterinary hospital ASP was successfully implemented in collaboration with OSUWMC counterparts using successful human interventions applied in the animal setting. Optimizing antimicrobial use and resistance at both sites will likely prevent resistance transmission between these geographically proximate hospitals. Sharing the details of our approach may benefit other institutions looking to expand their stewardship reach. Disclosures All authors: No reported disclosures.

Background Methicillin-resistant Staphylococcus spp (MRS), such as methicillin-resistant Staphylococcus aureus (MRSA), is a nosocomial pathogen of significant concern. This study evaluates the prevalence and determinants of airborne MRS and methicillin-susceptible Staphylococcus spp (MSS) in a veterinary teaching hospital during periods of no known active clinical cases of Staphylococci infections. Methods Airborne MRS and MRSA were sampled from 10 areas on 3 days each over 3 consecutive months in a veterinary teaching hospital. Each location was sampled twice each day (daytime and evening). Hospital clinical personnel were surveyed for activity levels across the areas sampled. Results Airborne MSS was detected in 52% (25/48) of samples and mecA -confirmed airborne MRS in 12.5% (6/48) of samples. Among daytime air samples, Staphylococcus spp varied by functional area ( P P = .011) with the hallway posing the greatest risk for both. Conclusion Our results indicate that (1) Staphylococcus spp is present in air in clinical environments during periods of no known clinical Staphylococci cases and (2) levels of airborne Staphylococcus spp are associated with functional space and human activity level. Applying these findings to MRSA surveillance creates opportunities for improving the accuracy and precision of exposure classification and risk mitigation.

The subjectivity and complexity of surveillance definitions for ventilator-associated pneumonia preclude meaningful internal or external benchmarking and therefore hamper quality improvement initiatives for ventilated patients. We explored the feasibility of creating objective surveillance definitions for ventilator-associated pneumonia.We identified clinical signs suitable for inclusion in objective definitions, proposed candidate definitions incorporating these objective signs, and then applied these definitions to retrospective clinical data to measure their frequencies and associations with adverse outcomes using multivariate regression models for cases and matched controls.Medical and surgical intensive care units in eight U.S. hospitals (four tertiary centers, three community hospitals, and one Veterans Affairs institution).Eight thousand seven hundred thirty-five consecutive episodes of mechanical ventilation for adult patients.We evaluated 32 different candidate definitions composed of different combinations of the following signs: three thresholds for respiratory deterioration defined by sustained increases in daily minimum positive end-expiratory pressure or FIO2 after either 2 or 3 days of stable or decreasing ventilator settings, abnormal temperature, abnormal white blood cell count, purulent pulmonary secretions defined by neutrophils on Gram stain, and positive cultures for pathogenic organisms.Ventilator-associated pneumonia incidence, attributable ventilator days, hospital days, and hospital mortality. All candidate definitions were significantly associated with increased ventilator days and hospital days, but only definitions requiring objective evidence of respiratory deterioration were significantly associated with increased hospital mortality. Significant odds ratios for hospital mortality ranged from 1.9 (95% confidence interval 1.2-2.9) to 6.1 (95% confidence interval 2.2-17). Requiring additional clinical signs beyond respiratory deterioration alone decreased event rates, had little impact on attributable lengths of stay, and diminished sensitivity and positive predictive values for hospital mortality.Objective surveillance definitions that include quantitative evidence of respiratory deterioration after a period of stability strongly predict increased length of stay and hospital mortality. These definitions merit further evaluation of their utility for hospital quality and safety improvement programs.

In an era of increasing antimicrobial resistance and few antimicrobials in the developmental pipeline, many institutions have developed antimicrobial stewardship programs (ASPs) to help implement evidence-based (EB) strategies for ensuring appropriate utilization of these agents. EB strategies for accomplishing this include formulary restriction with prior authorization. Potential limitations to this particular strategy include delays in therapy, prescriber pushback, and unintended increases in use of un-restricted antimicrobials; however, our ASP found that implementing prior authorization for select antimicrobials along with making a significant effort to educate clinicians on criteria for use ensured more appropriate prescribing of these agents, hopefully helping to preserve their utility for years to come.

ACADEMIC EMERGENCY MEDICINE 2012; 19:908–915 © 2012 by the Society for Academic Emergency Medicine Abstract Objectives: Older adults with infection are at increased risk of misdiagnosis while they are patients in the emergency department (ED) due to the common presence of nonspecific signs and symptoms. The primary objective was to determine the proportion of admitted older adult patients thought by the emergency physician (EP) to be infected, as compared with the diagnostic impression of inpatient physicians. The secondary objective was to determine the agreement between EP and inpatient physician diagnosis of specific infection types. Methods: The authors conducted a prospective, observational, convenience sampling of a cohort of ED patients ≥65 years old admitted to the hospital with diagnoses of acute infection. EPs noted at least one suspected source of infection. Inpatient diagnosis of infection was determined by chart review of the inpatient chart. Outcomes included the presence of any infection and of specific infectious sources diagnosed within 48 hours of admission. EP and inpatient diagnoses were compared using proportions, positive and negative likelihood ratios (LR+ and LR−), and the phi coefficient. Results: The study included 103 patients diagnosed with a suspected infection by the EP. Nineteen patients (18.4%, 95% confidence interval [CI] = 11.5% to 27.3%) were not diagnosed with any infection by the inpatient physician. For specific infection sources, ED diagnosis of bloodstream infection often did not agree with the inpatient diagnosis. Sensitivity was 40.0% and specificity 78.4% with an LR+ of 1.85 and LR− of 0.76. The phi coefficient was 0.15. EPs overdiagnosed pulmonary infection, with 72.1% specificity and an LR+ of 3.24. EP diagnosis had good accuracy for skin and soft tissue infection (sensitivity = 78.6% and specificity = 96.6%), with adequate LRs (LR+ of 23.3 and LR− of 0.22). Urinary tract infection (UTI) was underdiagnosed in the ED (sensitivity = 58.3%), but it is unclear if this is due to true ED underdiagnosis or due to overdiagnosis of UTI in the inpatient setting. Conclusions: In older patients admitted from the ED, the provisional ED diagnosis and the inpatient diagnosis of an acute infection often disagree. In this sample, 18% of older ED patients diagnosed with infection during an ED stay were not diagnosed as infected by the inpatient physician. Regarding infection types, EPs were poor at diagnosing bacteremia and overdiagnosed pulmonary infections. EP diagnosis of skin and soft tissue infection generally agreed with the inpatient physician. There was also disagreement regarding presence of UTI, but the true nature of this difference is unclear from the data obtained in this study.

A new antimicrobial stewardship program can be overwhelmed at the breadth of interventions and education required to conduct a successful program. The expression "low-hanging fruit," in reference to stewardship, refers to selecting the most obtainable targets rather than confronting more complicated management issues. These targets include intravenous-to-oral conversions, batching of intravenous antimicrobials, therapeutic substitutions, and formulary restriction. These strategies require fewer resources and less effort than other stewardship activities; however, they are applicable to a variety of healthcare settings, including limited-resource hospitals, and have demonstrated significant financial savings. Our stewardship program found that staged and systematic interventions that focus on obvious areas of need, that is, low hanging fruit, provided early successes in our expanded program with a substantial cumulative cost savings of $832,590.

Automated surveillance using electronically available data has been found to be accurate and save time. An automated Clostridium difficile infection (CDI) surveillance algorithm was validated at 4 Centers for Disease Control and Prevention Epicenter hospitals. Electronic surveillance was highly sensitive, specific, and showed good to excellent agreement for hospital-onset; community-onset, study facility-associated; indeterminate; and recurrent CDI.Infect Control Hosp Epidemiol 2012;33(3):305-308

Objectives: To identify the relationship between functional status and complicated clinical course in older adults in the emergency department (ED) with suspected infection and to identify other independent predictors of complicated clinical course. Design: A prospective observational cohort study. Setting: An academic, tertiary care ED with 70,000 visits per year. Participants: Aged 65 and older, blood cultures obtained in the ED, and final ED physician diagnosis of acute infection. Measurements: Functional status was obtained using the Older Americans Resources Scale (OARS). Complicated clinical course was defined as in-hospital mortality, need for intensive care unit (ICU)-level care, or worsening in sepsis criteria within 48 hours. Analysis was performed using multivariable logistic regression. Results: One hundred five participants were enrolled, 34 with the primary outcome. OARS was not predictive of complicated clinical course in univariate (P = .13) or multivariable (P = .90) models. An OARS score of 25 or less was also not significant (P = .22). Independent predictors were immunosuppression (odds ratio (OR) = 3.45, 95% confidence interval (CI) = 1.06�11.20), systolic blood pressure (OR = 0.98, 95% CI = 0.96�1.00), pulse (OR = 1.03, 95% CI = 1.00�1.06), metabolic acidosis (OR = 3.46, 95% CI = 1.08�11.09), severe sepsis or septic shock (OR = 10.24, 95% CI = 1.44�72.79), and suspected bloodstream infection (OR = 3.56, 95% CI = 1.13�11.16). Conclusion; For older adults admitted to the ED with infection, functional status did not predict complicated clinical course, but several other variables were predictive, including immunosuppression, several variables associated with hypoperfusion, and suspected bloodstream infection. Emergency physicians could consider these variables as potential indicators of complicated clinical course when making disposition decisions for this population.

Purpose Economic factors, market dynamics, and safety issues are largely responsible for decisions to withdraw pharmaceutical products from the market. In this study, new molecular entities (NMEs) approved by the Food and Drug Administration (FDA) were examined in the USA from 1980 to 2009. Methods Data were obtained from the FDA, Micromedex, Medline, and Lexis-Nexis. Descriptive analyses were used to classify product discontinuations by therapeutic category, time frame for discontinuation, and reason for withdrawal. Results There were 740 NMEs approved by the FDA during the study period. As of 1 December 2010, the number of drugs discontinued was 118 (15.9%). Discontinuations were the highest for antiparasitic products, insecticides, and repellents (6, 33.3% of approvals), systemic hormonal preparations excluding sex hormones and insulins (5, 33.3%), musculo-skeletal system (11, 32.4%), diagnostic agents (16, 28.1%), and anti-infectives for systemic use (27, 25.2%). Safety was the primary reason for withdrawing 26 drugs (3.5% of approvals). Conclusions Approximately one in seven approved NMEs were discontinued from the market in the period of 1980–2009. Less than one-quarter (22%) of the total withdrawals were attributed to safety reasons. An ongoing evaluation of new drugs throughout their product life cycle is important to determine their efficacy, safety, and value to society. Copyright © 2011 John Wiley & Sons, Ltd.

Background Stenotrophomonas maltophilia is an emerging nosocomial pathogen with intrinsic resistance to several antibiotics, making it potentially challenging to treat. Studies have demonstrated treatment failures and resistance development with monotherapy (MT); however, limited clinical data have demonstrated improved outcomes with combination therapy (CT). The aim of this study was to compare clinical outcomes with CT vs. MT for S. maltophilia pneumonia. Methods This was a retrospective cohort study of patients admitted to OSUWMC between November 2011 and October 2017 with S. maltophilia pneumonia who received at least 48 hours of effective therapy. Data collected included baseline characteristics, APACHE II, immune status, and therapy received. The primary outcome was clinical response after seven days of effective therapy with CT vs. MT (i.e., improvement in signs and symptoms of infection, absence of fever for 24 hours, WBC normalization if immunocompetent, and negative blood cultures if concurrently bacteremic). Secondary outcomes included development of a nonsusceptible isolate; adverse drug events (ADEs); and 30-day microbiological cure, infection recurrence, and all-cause mortality. The Wilcoxon Rank-sum test, Pearson chi-squared test, and Fisher’s exact test were utilized as appropriate. A multivariable logistic regression model was used to assess clinical response while adjusting for confounding variables. Results There were 252 patients with S. maltophilia pneumonia who met inclusion criteria, of which 38 received CT and 214 received MT. There was no difference in clinical response with CT vs. MT (47.4% vs. 39.7%, P = 0.38), even after controlling for immune status, APACHE II, and polymicrobial pulmonary infection (adjusted OR 1.49, 95% CI 0.62–3.60). Thirty-day microbiological cure (P = 0.44), recurrence (P = 0.53), all-cause mortality (P = 0.07), and isolation of a nonsusceptible isolate during (P = 0.96) or after (P = 0.85) therapy were also similar when comparing CT vs. MT. The most commonly reported ADEs were hyperkalemia and GI intolerance with trimethoprim/sulfamethoxazole and fluoroquinolones, respectively. Conclusion CT had similar efficacy and development of nonsusceptibility compared with MT for S. maltophilia pneumonia. Disclosures All authors: No reported disclosures.

Background Antimicrobial stewardship programs are nonexistent in most resource limited settings like Ethiopia. This has resulted in inappropriate use of antibiotics and widespread development of antibiotic resistance. Targeted initiatives surrounding antimicrobial use are needed to tackle this global health threat. Therefore, a program was established to generate data on antibiotic consumption, resistance, and facilitate appropriate use of antibiotics at an academic hospital in northwestern Ethiopia. Methods A committee was developed with a multidisciplinary team of clinicians, microbiologist, pharmacists and nurses. A baseline assessment of antibiotic use in the hospital was conducted through review of patient prescriptions and antibiotic inventory changes over time. To understand patterns, listed indication for use was recorded. Clinical audits, provider feedback mechanisms, and a quarterly antibiogram were also developed. Results Among 384 records of patients with infectious diseases, 250 adult and 134 pediatric cases were identified. Community acquired pneumonia (CAP) was the most common reason for use of antibiotics, accounting for 33.6% of adults and 22.2% of pediatric cases. Cephalosporins and penicillins were used in adults with CAP in 48.8% and 51.2% of cases, respectively, with or without macrolides or tetracycline. For severe CAP (30 cases), WHO or IDSA guideline concordance was identified as follows: appropriate antibiotic selection in 23 (76.6%), appropriate treatment duration in 15 (50.0%), and timely switch to oral therapy in 20 (66.7%) of the cases. The quarterly antibiogram included 516 bacterial isolates over one year. The most common organisms were Staphylococcus aureus and Escherichia coli, accounting for 34.7% and 16.8% isolates, respectively. The challenges faced in establishing the program were lack of electronic medical records for tracking antibiotic use and inconsistent supply of microbiologic reagents for microbial surveillance. Conclusion An effective antimicrobial stewardship program can be established in a resource limited setting with a committed team. Data generated by the program will be used to guide appropriate use of antibiotics and design interventions. Disclosures All authors: No reported disclosures.