Empiric Antibiotic Recommendations Research Articles

An Institutional Febrile Neutropenia Protocol Improved the Antibacterial Treatment and Encouraged the Development of a Computerized Clinical Decision Support System.

We investigated the influence of a local guideline on the quality of febrile neutropenia (FN) management and the applicability of a computerized decision support system (CDSS) using real-life data. The study included 227 FN patients between April 2016 and January 2019. The primary outcome measure was the achievement of a 20% increase in the rate of appropriate empirical treatment of FN in bacteremic patients. The compatibility of the CDSS (the development of which was completed in November 2021) with local protocols was tested using standard patient scenarios and empirical antibiotic recommendations for bacteremic FN patients. In total, 91 patients were evaluated before (P1: between April 2016 and May 2017) and 136 after (P2: between May 2017 and January 2019) the guideline's release (May 2017). The demographic characteristics were similar. Appropriate empirical antibacterial treatment was achieved in 58.3% of P1 and 88.1% of P2 patients (p = 0.006). The need for escalation of antibacterial treatment was significantly lower in P2 (49.5% vs. 35.3%; p = 0.03). In P2, the performance of the CDSS and consulting physicians was similar (CDSS 88.8% vs. physician 88.83%; p = 1) regarding appropriate empirical antibacterial treatment. The introduction of the local guideline improved the appropriateness of initial empirical treatment and reduced escalation rates in FN patients. The high rate of compliance of the CDSS with the local guideline-based decisions in P2 highlights the usefulness of the CDSS for these patients.

Towards evidence-based empiric antibiotic recommendations for spontaneous infections in patients with cirrhosis

BackgroundWith the emergence of multidrug-resistant infections, healthcare professionals must evaluate the effectiveness of empiric antibiotic treatments. AimsTo assess the antibiotic susceptibility patterns of microorganisms causing spontaneous infections in patients with cirrhosis and to evaluate the suitability of empiric antibiotic treatments based on major clinical guidelines. MethodsThis cross-sectional study utilized two datasets from prospective studies of patients with cirrhosis and culture-positive spontaneous bacterial infections in Argentina and Uruguay. We estimated susceptibility to commonly used antibiotics and assessed coverage following European and American recommendations. ResultsWe analyzed 238 episodes of culture-positive spontaneous infections in 229 patients. When implementing the recommendations for empiric treatment of community-acquired spontaneous infections, ceftazidime would result in 39 % coverage, whereas ceftriaxone would reach 70 %. Cefepime, which is not included in the recommendations, would have provided coverage of 74 %. Using ertapenem for nosocomial infections would have only covered 56 % of these episodes, whereas meropenem or imipenem reached 73 % coverage. Only the combination of meropenem or imipenem plus vancomycin would achieve a coverage surpassing 85 % in healthcare-associated or nosocomial spontaneous bacterial infections. ConclusionsOur study uncovers inadequate coverage in specific clinical scenarios when adhering to recommendations, underscoring the necessity of guidelines based on local epidemiological data.

An Emergent Change in Epidemiologic and Microbiological Characteristics of Bloodstream Infections in Adults With Febrile Neutropenia Resulting From Chemotherapy for Acute Leukemia and Lymphoma at Reference Centers in Chile, Ecuador, and Peru.

Febrile neutropenia is a life-threatening condition commonly observed in patients with hematologic malignancies. The aim of this article is to provide updated knowledge about bloodstream infections in febrile neutropenia episodes within the Andean region of Latin America. This retrospective study was based in 6 hospitals in Chile, Ecuador, and Peru and included adult patients with acute leukemia or lymphoma and febrile neutropenia between January 2019 and December 2020. Of the 416 febrile neutropenia episodes, 38.7% had a bloodstream infection, 86% of which were caused by gram-negative rods, with Klebsiella pneumoniae, Escherichia coli, and Pseudomonas aeruginosa being the most frequently identified bacteria. K pneumoniae isolates were more frequently resistant than E coli to cefotaxime (65% vs 39.6%), piperacillin-tazobactam (56.7% vs 27.1%), and imipenem (35% vs 2.1%) and were more frequently multidrug resistant (61.7% vs 12.5%). Among P aeruginosa, 26.7% were resistant to ceftazidime, piperacillin-tazobactam, and imipenem, and 23.3% were multidrug resistant. Overall 30-day mortality was 19.8%, being higher with vs without a bloodstream infection (26.7% vs 15.3%, P = .005). Fever duration was also significantly longer, as well as periods of neutropenia and length of hospital stay for patients with bloodstream infection. Additionally, the 30-day mortality rate was higher for episodes with inappropriate vs appropriate empirical antibiotic therapy (41.2% vs 26.6%, P = .139). Considering the high rates of bacteria-resistant infection and 30-day mortality, it is imperative to establish strategies that reduce the frequency of bloodstream infections, increasing early identification of patients at higher risks of multidrug bacteria resistance, and updating existing empirical antibiotic recommendations.

Antimicrobial resistance and its detection in Staphylococcus saprophyticus urinary isolates

The aim of this study was to describe the antibiotic susceptibility of clinical Staphylococcus saprophyticus isolates collected prospectively from urine specimens over a 2-month period from September to October 2022 at a single centre in Melbourne, Australia. Species identification was performed by MALDI-TOF MS. All isolates underwent phenotypic antibiotic susceptibility testing by disc diffusion using European Committee on Antimicrobial Susceptibility Testing (EUCAST) and Clinical and Laboratory Standards Institute (CLSI) guidelines and VITEK2, and mecA polymerase chain reaction. A total of 302 S.saprophyticus isolates from 298 patients were included in this study. Most specimens (91.1%) were referred by community general practitioners from non-hospitalised patients. Antimicrobial resistance to non-β-lactam antibiotics was uncommon; trimethoprim susceptibility was 97%; trimethoprim/sulfamethoxazole, 98%; nitrofurantoin, 100%; and ciprofloxacin, 100% (100% ciprofloxacin susceptible, increased exposure by EUCAST breakpoints). Methicillin resistance (by mecA detection) was the most common form of urinary antibiotic resistance at 5.6%. VITEK2 susceptibility testing for methicillin resistance had a poor specificity of 61.8% (95% CI 55.8-67.4%) compared to mecA detection. These findings indicate that empiric antibiotic recommendations of trimethoprim, trimethoprim/sulfamethoxazole, and nitrofurantoin for treatment of urinary S.saprophyticus remain appropriate.

Neonatal sepsis: Challenges in data access, harmonisation and analysis to inform empirical antibiotic recommendations in South African neonatal units


 
 
 Severe bacterial and fungal infections (sepsis) are a leading cause of mortality among neonates in sub-Saharan Africa. In African neonatal units, most sepsis episodes are hospital acquired, and caused by Gram-negative, antimicrobial-resistant pathogens. With rising rates of antimicrobial resistance (AMR) in neonatal sepsis pathogens, there is an increasing probability of inappropriate empirical antibiotic therapy (so called ‘bug-drug’ mismatch or discordant therapy), as confirmation of pathogen identity and antibiotic susceptibility pattern is either not available or delayed. The impact of AMR and discordant empirical treatment on neonatal sepsis outcomes in Africa is largely unknown owing to the lack of the infection surveillance data needed to derive empirical antibiotic treatment recommendations. The Antibiotics for Neonatal Sepsis in Africa (ANSA) study will address this data gap by pooling and harmonising available single-centre research datasets and/or routine laboratory blood culture data to determine which antibiotics should be used for empirical treatment of neonatal sepsis. However, many challenges hamper these datasets, including: variable laboratory methods for pathogen identification and susceptibility testing; difficulty in collating and harmonising data from multiple sites; problems of record linkage in the absence of a single patient identifier; lack of centralised health data capturing systems; and difficulty accessing data due to complex data sharing agreements and custodian permissions. To overcome some of these challenges, minimum guidelines for the collection of neonatal sepsis data need to be defined, to ensure consistency between datasets. Greater collection of, access to and sharing of neonatal sepsis data from institutional, provincial and national laboratories, as well as individual neonatal units, would enable the establishment of a neonatal surveillance network. Development of a sustainably-funded neonatal sepsis surveillance network is a national priority, to ensure effective, evidence-based antimicrobial treatment of hospitalised neonates in South Africa.
 
 

Neonatal sepsis: Challenges in data access, harmonisation and analysis to inform empirical antibiotic recommendations in South African neonatal units


 
 
 Severe bacterial and fungal infections (sepsis) are a leading cause of mortality among neonates in sub-Saharan Africa. In African neonatal units, most sepsis episodes are hospital acquired, and caused by Gram-negative, antimicrobial-resistant pathogens. With rising rates of antimicrobial resistance (AMR) in neonatal sepsis pathogens, there is an increasing probability of inappropriate empirical antibiotic therapy (so called ‘bug-drug’ mismatch or discordant therapy), as confirmation of pathogen identity and antibiotic susceptibility pattern is either not available or delayed. The impact of AMR and discordant empirical treatment on neonatal sepsis outcomes in Africa is largely unknown owing to the lack of the infection surveillance data needed to derive empirical antibiotic treatment recommendations. The Antibiotics for Neonatal Sepsis in Africa (ANSA) study will address this data gap by pooling and harmonising available single-centre research datasets and/or routine laboratory blood culture data to determine which antibiotics should be used for empirical treatment of neonatal sepsis. However, many challenges hamper these datasets, including: variable laboratory methods for pathogen identification and susceptibility testing; difficulty in collating and harmonising data from multiple sites; problems of record linkage in the absence of a single patient identifier; lack of centralised health data capturing systems; and difficulty accessing data due to complex data sharing agreements and custodian permissions. To overcome some of these challenges, minimum guidelines for the collection of neonatal sepsis data need to be defined, to ensure consistency between datasets. Greater collection of, access to and sharing of neonatal sepsis data from institutional, provincial and national laboratories, as well as individual neonatal units, would enable the establishment of a neonatal surveillance network. Development of a sustainably-funded neonatal sepsis surveillance network is a national priority, to ensure effective, evidence-based antimicrobial treatment of hospitalised neonates in South Africa.
 
 

Antimicrobial resistance of clinical Enterobacterales isolates from urine samples, Germany, 2016 to 2021.

IntroductionEmpirical therapy for the treatment of urinary tract infections should be tailored to the current distribution and susceptibility of potential pathogens to ensure optimal treatment.AimWe aimed to provide an up-to-date overview of the epidemiology and susceptibility of Enterobacterales isolated from urine in Germany.MethodsWe retrospectively analysed antimicrobial susceptibility data from 201,152 urine specimens collected between January 2016 and June 2021 from in- and outpatients. Multiple logistic regression analysis was used to evaluate the association between year of investigation and antibiotic resistance, adjusted for age, sex and species subgroup. Subgroup analyses were performed for midstream urine samples obtained from (i) female outpatients aged 15 to 50 years, (ii) female outpatients older than 50 years and (iii) male outpatients.ResultsResistance rates of less than 20% were observed for nitroxoline (3.9%), fosfomycin (4.6%), nitrofurantoin (11.7%), cefuroxime (13.5%) and ciprofloxacin (14.2%). Resistance to trimethoprim/sulfamethoxazole (SXT) (20.1%), amoxicillin-clavulanic acid (20.5%), trimethoprim (24.2%), pivmecillinam (29.9%) and ampicillin (53.7%) was considerably higher. In the subgroup of outpatient women aged 15-50 years, resistance rates were generally lower. Resistance rates of all antibiotics decreased from 2016 to 2021. Multiple logistic regression revealed the lowest adjusted odds ratio (ORadj) of 0.838 (95% confidence interval (CI): 0.819-0.858; p < 0.001) for pivmecillinam and the highest ORadj of 0.989 (95% CI: 0.972-1.007; p = 0.226) for nitrofurantoin.ConclusionsResistance has generally decreased over the past years, independent of sex, age and causative pathogen. Our data provide an important basis for empirical antibiotic recommendations in various settings and patient collectives.

Gram-negative neonatal sepsis in low- and lower-middle-income countries and WHO empirical antibiotic recommendations: A systematic review and meta-analysis.

BackgroundNeonatal sepsis is a significant global health issue associated with marked regional disparities in mortality. Antimicrobial resistance (AMR) is a growing concern in Gram-negative organisms, which increasingly predominate in neonatal sepsis, and existing WHO empirical antibiotic recommendations may no longer be appropriate. Previous systematic reviews have been limited to specific low- and middle-income countries. We therefore completed a systematic review and meta-analysis of available data from all low- and lower-middle-income countries (LLMICs) since 2010, with a focus on regional differences in Gram-negative infections and AMR.Methods and findingsAll studies published from 1 January 2010 to 21 April 2021 about microbiologically confirmed bloodstream infections or meningitis in neonates and AMR in LLMICs were assessed for eligibility. Small case series, studies with a small number of Gram-negative isolates (<10), and studies with a majority of isolates prior to 2010 were excluded. Main outcomes were pooled proportions of Escherichia coli, Klebsiella, Enterobacter, Pseudomonas, Acinetobacter and AMR. We included 88 studies (4 cohort studies, 3 randomised controlled studies, and 81 cross-sectional studies) comprising 10,458 Gram-negative isolates from 19 LLMICs. No studies were identified outside of Africa and Asia. The estimated pooled proportion of neonatal sepsis caused by Gram-negative organisms was 60% (95% CI 55% to 65%). Klebsiella spp. was the most common, with a pooled proportion of 38% of Gram-negative sepsis (95% CI 33% to 43%). Regional differences were observed, with higher proportions of Acinetobacter spp. in Asia and Klebsiella spp. in Africa. Resistance to aminoglycosides and third-generation cephalosporins ranged from 42% to 69% and from 59% to 84%, respectively. Study limitations include significant heterogeneity among included studies, exclusion of upper-middle-income countries, and potential sampling bias, with the majority of studies from tertiary hospital settings, which may overestimate the burden caused by Gram-negative bacteria.ConclusionsGram-negative bacteria are an important cause of neonatal sepsis in LLMICs and are associated with significant rates of resistance to WHO-recommended first- and second-line empirical antibiotics. AMR surveillance should underpin region-specific empirical treatment recommendations. Meanwhile, a significant global commitment to accessible and effective antimicrobials for neonates is required.

A retrospective analysis of pathogen profile, antimicrobial resistance and mortality in neonatal hospital-acquired bloodstream infections from 2009-2018 at Tygerberg Hospital, South Africa.

Analysis of hospital-acquired bloodstream infection (HA-BSI) trends is important to monitor emerging antimicrobial resistance (AMR) threats and guide empiric antibiotic choices. A retrospective 10-year review of neonatal HA-BSI was performed at Tygerberg Hospital's neonatal unit in Cape Town, South Africa. Neonatal clinical and laboratory data from 2014 to 2018 (Period 2) was compared with published data from 2009 to 2013 (Period 1). The neonatal unit's HA-BSI rate declined between periods from 3.9/1000 inpatient-days in Period 1 to 3.3/1000 inpatient-days in Period 2 (p = 0.002). Pathogen yield and blood culture contamination rate were unchanged (11.0% to 10.4%, p = 0.233; 5.1% to 5.3%, p = 0.636 respectively). Gram-negative pathogens predominated (1047/1636; 64.0%); Klebsiella species, Staphylococcus aureus, Serratia marcescens, Enterococcus species and Acinetobacter baumannii were the most frequent pathogens. Extended spectrum beta-lactamase production was observed in 319/432 (73.8%) of Klebsiella species, methicillin resistance in 171/246 (69.5%) of Staphylococcus aureus and extensive drug resistance in 115/137 (83.9%) of Acinetobacter species (2009-2018). The crude mortality rate of neonatal HA-BSI episodes increased from Period 1 to Period 2 from 139/717 (19.4%) to 179/718 (24.9%) (p = 0.014), but HA-BSI attributable mortality remained unchanged (97/139 [69.8%] vs 118/179 [65.9%], p = 0.542). The in-vitro activity of piperacillin-tazobactam and amikacin declined during Period 2 (74.6% to 61.4%; p<0.001). Although HA-BSI rates declined in the neonatal unit, antimicrobial resistance rates in BSI pathogens remained high. Continuous BSI surveillance is a valuable tool to detect changes in pathogen and AMR profiles and inform empiric antibiotic recommendations for neonatal units in resource-limited settings.

Gram-Negative Neonatal Sepsis in Low- and Middle- Income Countries: How Appropriate are the WHO Recommended Empirical Sepsis Antibiotic Regimens? A Systematic Review and Meta-Analysis

Background: Neonatal sepsis is a significant global health issue associated with marked regional disparities in mortality. Antimicrobial resistance (AMR) is a growing concern in Gram-negative organisms which increasingly predominate in neonatal sepsis, and existing WHO empirical antibiotic recommendations may no longer be appropriate. Previous systematic reviews have been limited to specific low- and middle-income countries (LMICs). We therefore completed a systematic review and meta-analysis of available data from all LMICs since 2010, with a focus on regional differences in Gram-negative infections and AMR. Methods: All studies published from 2010 with microbiologically confirmed bloodstream infections or meningitis in neonates and AMR from LMICs were assessed for eligibility. Small case series or number of Gram-negative isolates (<10), and studies with a majority of isolates prior to 2010 were excluded. Main outcomes were pooled proportions of E.coli, Klebsiella, Enterobacter, Pseudomonas, Acinetobacter and AMR. Findings: We included 75 studies comprising 17,066 positive blood cultures from 16 LMICs. No studies were identified outside of Africa and Asia. The estimated pooled proportion of neonatal sepsis caused by Gram-negative organisms was 60% (95% CI 54-65%). Klebsiella spp was the most common, with a pooled proportion of 37% of Gram-negative sepsis (95% CI 32-43%). Resistance to aminoglycosides and 3rd generation cephalosporins ranged from 42-69% and 59-84%, respectively. Interpretation: Gram-negative bacteria are an important cause of neonatal sepsis in LMICs and associated with significant rates of resistance to WHO recommended first and second line empirical antibiotics. AMR surveillance should underpin region-specific empirical treatment recommendations. Meanwhile, a significant global commitment to accessible and effective antimicrobials for neonates is required. Funding Statement: Sophie CH Wen is supported by a Queensland Health Clinical Research Fellowship. Geoff Spurling, David L Paterson, Adam D Irwin, and Colleen L Lau are supported by National Health and Medical Research Council (NHMRC) Investigator Grants. Declaration of Interests: None to declare.

Antimicrobial stewardship and antibiograms: importance of moving beyond traditional antibiograms.

The rapid evolution of resistance, particularly among Gram-negative bacteria, requires appropriate identification of patients at risk followed by administration of appropriate empiric antibiotic therapy. A primary tenet of antimicrobial stewardship programs (ASPs) is the establishment of empiric antibiotic recommendations for commonly encountered infections. An important tool in providing empiric antibiotic therapy recommendations is the use of an antibiogram. While the majority of institutions use a traditional antibiogram, ASPs have an opportunity to enhance antibiogram data. The authors provide the rationale for why ASPs should implement alternative antibiograms, and the importance of incorporating an antibiogram into clinical decision support systems with the goal of providing effective empiric antibiotic therapy.

A Randomized Controlled Trial of an Electronic Clinical Decision Support Tool for Inpatient Antimicrobial Stewardship.

The weighted incidence syndromic combination antibiogram (WISCA) is an antimicrobial stewardship tool that utilizes electronic medical record data to provide real-time clinical decision support regarding empiric antibiotic prescription in the hospital setting. The aim of this study was to determine the impact of WISCA utilization for empiric antibiotic prescription on hospital length of stay (LOS). We performed a crossover randomized controlled trial of the WISCA tool at 4 hospitals. Study participants included adult inpatients receiving empiric antibiotics for urinary tract infection (UTI), abdominal-biliary infection (ABI), pneumonia, or nonpurulent cellulitis. Antimicrobial stewardship (ASP) physicians utilized WISCA and clinical guidelines to provide empiric antibiotic recommendations. The primary outcome was LOS. Secondary outcomes included 30-day mortality, 30-day readmission, Clostridioides difficile infection, acquisition of multidrug-resistant gram-negative organism (MDRO), and antibiotics costs. In total, 6849 participants enrolled in the study. There were no overall differences in outcomes among the intervention versus control groups. Participants with cellulitis in the intervention group had significantly shorter mean LOS compared to participants with cellulitis in the control group (coefficient estimate = 0.53 [-0.97, -0.09], P = .0186). For patients with community acquired pneumonia (CAP), the intervention group had significantly lower odds of 30-day mortality compared to the control group (adjusted odds ratio [aOR] .58, 95% confidence interval [CI], .396, .854, P = .02). Use of WISCA was not associated with improved outcomes for UTI and ABI. Guidelines-based interventions were associated with decreased LOS for cellulitis and decreased mortality for CAP.

1147. Improving Accessibility and Antibiotic Prescribing with an Enhanced Digital Antibiogram

BackgroundInstitutional antibiograms play a key role in antimicrobial stewardship and may provide a venue for clinical decision support. Our institution recently transitioned our paper antibiogram to an enhanced digital antibiogram with antibiotic recommendations for common pediatric infections. The objectives of this study were (1) to improve the accessibility of our institutional antibiogram through a digital platform and (2) to improve trainee confidence when selecting empiric antibiotics by integrating clinical decision support.MethodsThe digital antibiogram was developed and evaluated at a tertiary children’s hospital. The tool was developed iteratively over one year by our innovation and digital health accelerator with recommendations for empiric antibiotic selection provided by experts in pediatric infectious diseases (see Figure 1 for example). Usability pilot testing was performed with a group of ordering providers and the tool was released internally in October 2018. A paired pre- and post- implementation survey evaluated residents’ perceptions of the accessibility of the paper vs. digital antibiogram and their confidence when selecting empiric antibiotics. Data were analyzed by Fisher exact test.ResultsDuring the 3 months after release, the digital antibiogram was accessed 1014 times with similar proportions of views for susceptibility data, dosing, and empiric antibiotic recommendations. Of the 31 pediatric residents who responded to both pre- and post- implementation surveys, only 59% had access to a copy of the paper antibiogram. Following release of the digital antibiogram, residents referred to antibiotic susceptibilities more frequently (P < 0.05, Figure 2) and were more frequently more confident when selecting the correct antibiotic dose (P < 0.01, Figure 3). See Figure 4 for dosing recommendation example.ConclusionProviding antibiotic susceptibility and dosing recommendations digitally improved accessibility and resident confidence during antibiotic prescribing. Our digital tool provides a successful platform for displaying the antibiotic data and recommendations that enable appropriate antibiotic use. Disclosures All authors: No reported disclosures.

What can we learn by examining variations in the use of urine culture in the management of acute cystitis? A retrospective cohort study with linked administrative data in British Columbia, Canada, 2005-2011.

IntroductionUrinary tract infections (UTI) are common community-based bacterial infections. Empiric antibiotic recommendations are guided by local resistance rates. Previous research suggests that cultures are overused for uncomplicated cystitis, but practice patterns have not been described in detail. Variations in culturing have implications for the interpretation of antibiotic resistance rates.MethodsWe used a retrospective cohort study to analyze variations in urine culturing among physicians, controlling for patient and physician characteristics. We identified all outpatient physician visits among adults and children for cystitis in British Columbia between 2005 and 2011 using administrative data and linked these to laboratory data on urine cultures. Using hierarchical generalized linear mixed models we explored variations in urine culture submissions for cystitis (ICD code 595) and the associations with patient and physician characteristics, stratified by patient sex.ResultsUrine cultures were associated with 16% of visits for cystitis among females and 9% among males, and 59% of visits overall were associated with antibiotic treatment. Older patients, patients with a recent antibiotic prescription, and long term care residents were significantly less likely to have a culture associated with a cystitis visit, whether male or female. Female physicians and physicians with 16–35 years’ experience were more likely to culture, while international medical graduates were less likely–particularly for female visits. Notably, there was substantial unexplained variation among physicians after controlling for physician characteristics: we found a 24-fold variation in the odds of culturing a female UTI between physicians who were otherwise similar.ConclusionIndividual physicians show substantial variation in their propensity to submit cultures for cystitis visits. Reducing such variation and encouraging appropriate levels of culturing would support effective antibiotic use.

188. A Novel Inpatient Antibiotic Stewardship Assistance Program (ASAP) Using Real-Time Electronic Health Record Data, Prediction Modeling and Epidemiologic Data to Provide Personalized Empiric Antibiotic Recommendations

BackgroundAntibiotic prescribing varies amongst clinicians, which can result in inappropriate or overuse. Inappropriate antibiotics can increase the risk of adverse drug events and multi-drug-resistant organisms (MDRO). Decreasing variability and increasing alignment with guideline-based therapy may improve antimicrobial stewardship and outcomes.MethodsWe developed a point of care stewardship tool embedded in the electronic health record (EHR) that provides empiric antibiotic recommendations for four syndromes, urinary tract infection (UTI), abdominal biliary infection (ABI), pneumonia, and cellulitis. We identified key variables that alter antibiotic selection or need for infectious disease (ID) consultation such as allergy history, immunosuppression and risk factors for MDRO, and mortality. We created algorithms of preferred empiric antibiotic choices based on national and hospital guidelines using these risk factors. We used a weighted incidence syndromic combined antibiogram (WISCA) prediction model to recommend ID consultation when likelihood of coverage was below a defined threshold. We also incorporated a home-grown epidemiologic tool that takes real-time data from outpatient clinics on incidence of influenza-like-illness (ILI) to recommend influenza PCR testing during periods of high ILI risk. Data on risk factors and WISCA variables including demographics, allergy history, ICD10 codes, vitals, laboratories, and microbiology results were extracted in real-time from the EHR and sent via URL into a web server which has an embedded Windows ASP.NET C# web site and an SQL server database. The web server was then embedded back into the EHR. This tool stores recommendations into the database for stewardship auditing.ResultsThirteen key and 20 WISCA variables are extracted from the EHR in real-time. There are eight distinct antibiotic recommendations for UTI and ABI, 12 for cellulitis, and 40 for pneumonia. An illustration of the ASAP tool is shown in Figure 1.ConclusionASAP is an HER-embedded platform that provides clinicians access to personalized antibiotic prescribing tied to best practices and optimal stewardship initiatives. Future work will look into the tool’s effect on variation in care, antibiotic prescribing, and outcomes.Figure 1:Disclosures All authors: No reported disclosures.

Empiric Antibiotic Use and Susceptibility in Infants With Bacterial Infections: A Multicenter Retrospective Cohort Study.

To assess hospital differences in empirical antibiotic use, bacterial epidemiology, and antimicrobial susceptibility for common antibiotic regimens among young infants with urinary tract infection (UTI), bacteremia, or bacterial meningitis. We reviewed medical records from infants <90 days old presenting to 8 US children's hospitals with UTI, bacteremia, or meningitis. We used the Pediatric Health Information System database to identify cases and empirical antibiotic use and medical record review to determine infection, pathogen, and antimicrobial susceptibility patterns. We compared hospital-level differences in antimicrobial use, pathogen, infection site, and antimicrobial susceptibility. We identified 470 infants with bacterial infections: 362 (77%) with UTI alone and 108 (23%) with meningitis or bacteremia. Infection type did not differ across hospitals (P = .85). Empirical antibiotic use varied across hospitals (P < .01), although antimicrobial susceptibility patterns for common empirical regimens were similar. A third-generation cephalosporin would have empirically treated 90% of all ages, 89% in 7- to 28-day-olds, and 91% in 29- to 89-day-olds. The addition of ampicillin would have improved coverage in only 4 cases of bacteremia and meningitis. Ampicillin plus gentamicin would have treated 95%, 89%, and 97% in these age groups, respectively. Empirical antibiotic use differed across regionally diverse US children's hospitals in infants <90 days old with UTI, bacteremia, or meningitis. Antimicrobial susceptibility to common antibiotic regimens was similar across hospitals, and adding ampicillin to a third-generation cephalosporin minimally improves coverage. Our findings support incorporating empirical antibiotic recommendations into national guidelines for infants with suspected bacterial infection.

Clinical Pathway and Monthly Feedback Improve Adherence to Antibiotic Guideline Recommendations for Community-Acquired Pneumonia.

BackgroundCompliance with community-acquired pneumonia (CAP) guidelines remains poor despite a substantial body of evidence indicating that guideline-concordant care improves patient outcomes. The aim of this study was to compare the relative effectiveness of a general educational and a targeted emergency department intervention on improving physicians’ concordance with CAP guidelines.MethodsTwo distinct interventions were implemented over specific time periods. The first intervention was educational, focusing on the development of local CAP guidelines and their dissemination through hospital-wide educational programmes. The second intervention was a targeted one for the emergency department, where a clinical pathway for the initial management of CAP patients was introduced, followed by monthly feedback to the emergency department (ED) physicians about concordance rates with the guidelines. Data on the concordance rate to CAP guidelines was collected from a retrospective chart review.ResultsA total of 398 eligible patient records were reviewed to measure concordance to CAP guidelines over the study period. Concordance rates during the baseline and educational intervention periods were similar (28.1% vs. 31.2%; p > 0.05). Significantly more patients were treated in accordance with the CAP guidelines after the ED focused intervention when compared to the baseline (61.5% vs. 28.1%; p < 0.05) or educational period (61.5% vs. 31.2%; p < 0.05).ConclusionsA targeted intervention with a CAP clinical pathway and monthly feedback was a successful strategy to increase adherence to empirical antibiotic recommendations in CAP guidelines.

P14.17 Surveillance for sexually transmitted infections among female sex workers in inner-city johannesburg

Introduction Sexually transmitted infection (STI) surveillance informs empiric antibiotic recommendations for syndromic management. Asymptomatic STIs are an important source of new infections which increase the risk of HIV transmission and acquisition. As female sex-workers (FSW) are key HIV/STI transmitters, microbiological studies within this population provide critical HIV/STI strategic information. Methods Female sex workers (FSW) attending a sex-worker clinic or outreach brothel services, between March and December 2014 in inner-city Johannesburg were enrolled. A questionnaire and clinical examination were completed. Specimens were collected from the throat, urethra, cervix, vagina and rectum. Laboratory investigations included (i) culture for Neisseria gonorrhoeae (NG) with susceptibility testing for cefixime and ceftriaxone, (ii) DNA amplification using a multiplex PCR for NG, C. trachomatis (CT), M. genitalium (MG) and T. vaginalis (TV), (iii) microscopic examination for bacterial vaginosis (BV), and (iv) serological testing for syphilis, hepatitis B and HIV. Participants with STIs were treated either at the initial visit (symptomatics) or following recall (asymptomatics). Results The mean age of the 268 enrolled FSW was 31.5(IQR 27–35) and mean duration of sex work was 4.9 years (range 2 months–30 years). Condom use was consistent among 88(32.8%) FSW. The self-reported mean number of sexual partners in the past 4 weeks was 125(range 8–440) translating to 33,496 sex acts/month overall. HIV prevalence was 76.0%. Infectious hepatitis B was present in 13 (4.9%) and treponemal antibodies were detected in 54(20.1%). Most (73.7%) of 196 FSW tested had evidence of one or more genital tract infection with: BV 173 (88.3%), MG 57 (29.1%), NG 28 (14.3%), TV 23 (11.7%) and CT 16 (8.2%). Only 49 (25%) FSW with laboratory-confirmed infections would qualify for syndromic management. All 21 cultured gonococci were susceptible to cephalosporins. Conclusion There is a high prevalence of HIV and STIs among those FSW tested. The majority of STIs are asymptomatic. Disclosure of interest statement The study was funded by USAID/PEPFAR and AIDS Fonds. SD bioline tests were provided by SD diagnostics.

Bacillus Cereus: A Leukemia-Specific, Neuroinvasive Pathogen?

BackgroundBacillus cereus has been associated with central nervous system (CNS) infections in immunocompromised patients.1 We report 5 cases of neuroinvasive B.cereus infections (4 fatal) in patients with acute myelogenous leukemia (AML) at Brigham and Women’s Hospital (BWH) in Boston from May 2013 to February 2014.MethodsClinical Investigation: Cases were defined as patients with positive blood or CNS cultures for B.cereus and/or positive PCR tests from CNS specimens and radiological evidence of acute CNS disease >48 hours after admission. Infection control practices were observed. A case-control analysis of medications and exposures was conducted; odds ratios and p-values were calculated via Fisher’s exact test.Genomic Analysis: Genomic DNA was extracted from patient-derived and environmental B. cereus isolates. Sequencing libraries were prepared and paired-end whole genome sequencing (WGS) was performed. Sequencing reads were computationally assembled using several existing tools (SPAdes, AllPaths-LG, VELVET, and Newbler). Draft genome annotation was performed using RAST and Prodigal. All single copy core genes were aligned using MUSCLE and a phylogenetic tree was generated using FastTree and RAxML.ResultsClinical Investigation: All 5 cases were AML patients who received chemotherapy. All had neutropenic fevers early in their course that resolved with empiric antibiotics. Fever recurred > 1 week into hospitalization (median onset 17 days, range 9-20) with headaches, neurological changes, and abnormal CNS imaging. Three had documented B. cereus bacteremia with bacilli identified on CNS pathological stains; two had positive CNS cultures. Four patients expired. Autopsies were notable for intestinal ulcers with Gram-positive bacilli in 2 patients.No infection control breaches were observed. Of 43 environmental samples, 4 tested positive for B.cereus, including a kitchen cart where bananas were stored, the shelf of a blanket warmer, and an air sample near a construction site. On case-control analysis, no medications were associated with cases. The only significant food exposures were bananas (OR 9.3, p=0.04) and cranberry juice (OR 9.6, p=0.04).Genomic Analysis:WGS data was obtained for all B. cereus isolates from BWH (n=4) and swabs of environmental screening efforts from BWH (n=4). Two patient isolates (7299 and 6254) were taken forward for pilot analysis. A comparison of various computational assembly tools demonstrated that the SPAdes assembler exhibited superior performance. SPAdes was thus used for draft genome assembly for the remaining isolates. Phylogenetic analysis of isolates 7299 and 6254 revealed that the organisms were genetically distinct from one another (Fig. 1). Genomic analysis and multilocus sequence typing (performed by WGS and independently by PCR amplification/Sanger sequencing) confirmed that all strains were genetically distinct from one another, and suggested that the environmental strains were relatively divergent from the pathogenic strains studied.ConclusionsNeuroinvasive B.cereus infection should be suspected in febrile AML patients with acute neurological symptoms, even those with negative blood cultures.The clinical investigation suggests the outbreak may have been attributable to gastrointestinal inoculation, possibly secondary to bananas. Of note, the B. cereus strain cultured from the suspected banana source was not identical to the pathogenic strains. Multiple changes in practice were instituted as a consequence of this outbreak including enhanced environmental cleanings, temporary modification of empiric antibiotic recommendations for recurrent neutropenic fever (vancomycin, cefepime, and ciprofloxacin) and the placement of all AML patients on diets that excluded fresh fruits, vegetables, and rice. Six months have elapsed since the last case.WGS demonstrated that the case series was not the result of a single, hyper-virulent B. cereus organism. Rather, the infections appear to have been attributable to distinct B. cereus strains that fall into two distinct genotypic clusters. Ongoing comparative microbial genomic and biological efforts are underway and have identified candidate bacterial and host factors that may induce heightened virulence in this patient population.1. Inoue et al. Leukemia & lymphoma. 2010;51(5):860-9. [Display omitted] DisclosuresNo relevant conflicts of interest to declare.

Impact of guideline-concordant antibiotics and macrolide/β-lactam combinations in 3203 patients hospitalized with pneumonia: prospective cohort study

For patients hospitalized with pneumonia, guidelines provide empirical antibiotic recommendations and some studies suggest that macrolide/β-lactam combinations are preferable. We hypothesized that guideline-concordant regimens, particularly macrolide/β-lactams, would reduce mortality and ICU admissions. All patients hospitalized with pneumonia in Edmonton, Alberta, Canada, were managed according to a clinical pathway and enrolled in a population-based registry. Clinical data, Pneumonia Severity Index and treatments were collected. Guideline-concordant regimens were macrolides/β-lactams or respiratory fluoroquinolone monotherapy. The main outcome was in-hospital mortality. The study included 3203 patients and most had severe pneumonia (63% PSI Class IV-V). Three hundred and twenty-one (10.0%) patients died, 306 (9.6%) were admitted to the ICU and 570 (17.8%) achieved the composite of death or ICU admission. Most (n = 2506) patients received guideline-concordant antibiotics. Receipt of guideline-concordant antibiotics was not associated with a reduction in mortality alone (231 (9.2%) vs. 90 (12.9%); adjusted odds ratio (aOR), 0.82; 95% CI, 0.61–1.09; p 0.16), but was associated with decreased death or ICU admission (14.7% vs. 29.0%; aOR, 0.44; 95% CI, 0.36–0.54; p <0.0001). Within guideline-concordant subgroups, there was no difference in mortality between macrolide/β-lactams and respiratory fluoroquinolone monotherapy (22 (8.3%) vs. 209 (9.3%); aOR, 1.09; 95% CI, 0.66–1.81; p 0.73) but macrolide/β-lactams were associated with increased odds of death or ICU admission (17.4% vs. 14.4%; aOR, 1.58; 95% CI, 1.09–2.27; p 0.01). In conclusion, guideline-concordant antibiotics were not associated with decreased mortality for patients hospitalized with pneumonia, but were associated with a decrease in the composite endpoint of death or ICU admission. Our findings do not support any clinical advantage of macrolide/β-lactam compared with respiratory fluoroquinolone monotherapy.