Empiric Antibiotic Selection Research Articles

Impact of emergency medicine clinical pharmacist practitioner-driven sepsis antibiotic interventions

BackgroundThe 2021 Surviving Sepsis Campaign Guidelines recommend administration of antimicrobials within the first hour of recognition of sepsis. Over the last decade, several studies have demonstrated improved time-to-antibiotic administration and antibiotic appropriateness when a pharmacist was involved in the care of patients with sepsis. To our knowledge, no studies evaluating the appropriate use of antibiotics in sepsis driven entirely by an Emergency Medicine (EM) Clinical Pharmacist Practitioner (CPP) have been published. The purpose of this study is to evaluate the impact of an EM CPP-driven protocol on antimicrobial interventions in patients with sepsis in the emergency department (ED). MethodsThis was a retrospective comparison of patients with sepsis for whom antimicrobials were ordered in the ED without pharmacist intervention to patients whose antimicrobials were ordered by an EM CPP via a sepsis consult to pharmacy. An EM CPP reviewed individual patient profiles for pertinent historical admissions, culture data, and allergy profiles to guide antimicrobial selection for the suspected source of infection and entered orders under their scope of practice with formal documentation in the electronic medical record (EMR). The primary objective of this study was to compare the rates of appropriate empiric antibiotic utilization in septic patients admitted from the ED pre- and post-protocol implementation. Secondary endpoints included the following, broadening of ED-initiated empiric antibiotics on hospital admission, time-to-antibiotic administration, in-hospital mortality, Rapid Emergency Medicine Score (REMS) association with in-hospital mortality, and hospital length of stay. ResultsA total of 144 patients were included: 80 patients prescribed antibiotics without pharmacist intervention and 64 prescribed antibiotics by an EM CPP. Appropriate empiric antibiotic selection in the ED improved from 57.5% (46/80) to 86% (55/64) with EM CPP intervention (difference 28.5%; p < 0.01). Time-to-first antibiotic administration decreased by 64 min (p < 0.01). Administration of antibiotics within 60 min, broadening of antibiotics on admission, hospital length of stay, and in-hospital mortality did not significantly differ across groups. ConclusionsIn this small, single-center study, an EM Clinical Pharmacist Practitioner-driven protocol for patients with sepsis in the emergency department improved the rate of appropriate empiric antimicrobial selection and time-to-antibiotic administration.

Methicillin-resistant Staphylococcus aureus and Pseudomonas aeruginosa community acquired pneumonia: Prevalence and locally derived risk factors in a single hospital system.

Current American Thoracic Society/Infectious Disease Society of America (ATS/IDSA) community-acquired pneumonia (CAP) guidelines expand the CAP definition to include infections occurring in patients with recent health care exposure. The guidelines now recommend that hospital systems determine their own local prevalence and predictors of Pseudomonas aeruginosa and methicillin-resistant Staphylococcus aureus (MRSA) among patients satisfying this new broader CAP definition. We sought to carry out these recommendations in our system, focusing on the emergency department, where CAP diagnosis and initial empiric antibiotic selection usually ooccur. We performed a retrospective cohort study of patients admitted with CAP through any of 3 EDs in our hospital system in Northern California between November 2019 and October 2021. Inclusion criteria included an ED admission diagnosis of pneumonia or sepsis, fever or hypothermia, leukocytosis or leukopenia, and consistent chest imaging result. SARS-CoV-2-positive cases were excluded. We abstracted variables historically associated with P. aeruginosa and MRSA. Outcome measures were prevalence of P. aeruginosa and MRSA in the overall clinically defined cohort and among microbiologically confirmed cases and predictors of P. aeruginosa or MRSA isolation, as determined by univariate logistic regression, bootstrapped least absolute shrinkage and selection operator, and random forest analyses. Additionally, we describe the iterative process used and challenges encountered in carrying out the new ATS/IDSA guideline recommendations. There were 1133 unique patients who satisfied our definition of clinically defined CAP, of whom 109 (9.6%) had a bacterial pathogen isolated. There were 24 P. aeruginosa isolates and 11 MRSA isolates in 33 patients. Thus, the prevalence P. aeruginosa and MRSA was 2.9% in the overall CAP cohort, but 30.3% in the microbiologically confirmed cohort. The most important predictors of either P. aeruginosa or MRSA isolation were tracheostomy (odds ratio [OR] 22.08; 95% confidence interval [CI] 10.39-46.96) and gastrostomy tube (OR 14.7; 95% CI 7.14-30.26). Challenges included determining the suspected infection type in patients admitted simply for "sepsis"; interpreting dictated radiology reports; determining functional status, presence of indwelling lines and tubes, and long-term care facility residence from the electronic health record; and correctly attributing culture results to pneumonia. Prevalence of MRSA and P. aeruginosa was low among patients admitted in our medical system with CAP - now broadly defined - but high among those with a microbiologically confirmed bacterial etiology. Our locally derived predictors of MRSA and P. aeruginosa can be used to aid our emergency physicians in empiric antibiotic selection for CAP. Findings from this project might inform efforts at other institutions.

Antibiotic resistance patterns of pediatric community-acquired urinary tract infections in a tertiary care center in Jeddah, Saudi Arabia.

Urinary tract infections (UTIs) are common in children. UTIs can lead to serious and permanent damage to the urinary tract if treatment is delayed or insufficient, particularly in repeated infections. Knowledge of antibiotic resistance trends aids in the selection of appropriate empiric antibiotics. There is limited data regarding this in Saudi Arabia. This study aimed to investigate uropathogens and their antibiotic resistance patterns in the pediatric community in a tertiary care center. The study population included children aged 0 to 14 years old who had culture-proven UTIs evaluated in the Department of Pediatrics, King Abdulaziz University Hospital in Jeddah, Saudi Arabia from February 2019 to September 2021. Out of 510 UTI episodes, Escherichia coli (54.5%) was the predominant causative pathogen. Of the total episodes, 137 (26.8%) were caused by extended spectrum beta-lactamase (ESBL) producers. In general, the highest resistance was observed against ampicillin (73.2%), cefazolin (54.6%), co-trimoxazole (46%), and cefuroxime (40.6%), whereas amikacin (0.4%), imipenem (0.8%), and meropenem (0.8%) showed the lowest rates of resistance. Antibiotic resistance is a major concern worldwide due to misuse of antibiotics and subsequent rise of multidrug resistant organisms. Our findings highlight the rise in antibiotic resistance, particularly in E. coli strains. Furthermore, ESBL-producing bacteria were responsible for approximately one-third of UTIs. Our study emphasizes the importance of local antibiograms for pediatric community-acquired infections, as it guides clinicians in every center in the choice of appropriate empiric antibiotic treatment.

Brain abscess incidence and microbial etiology in Turkey: a nationwide cross-sectional study.

Brain abscess, a localized purulent central nervous system infection, arises from a variety of microorganisms. Expedited diagnosis and formulation of effective treatment strategies are crucial for mitigating mortality risks in patients with brain abscesses. A nuanced understanding of potential microbial agents is pivotal for the development of empirical antibiotic therapies. This study aimed to explore the incidence and microbial etiology of brain abscesses. This study is a nationwide cross-sectional analysis of patients diagnosed with brain abscesses in Turkey, employing the ICD 10 diagnosis code from January 1, 2015, to December 31, 2021. Data pertaining to age, sex, comorbidities, and microorganisms isolated from central nervous system samples were meticulously recorded and analyzed. This study included 11,536 patients diagnosed with brain abscesses. The incidence fluctuated between 0.98 and 3.68 during the review decrease post-2017, with a notable increase in male patients during time. Diabetes constituted 56.5% of the patients. The predominant isolated pathogens were Staphylococcus (37.6%), Streptococci (13.3%), and Klebsiella spp. (7.8%), Escherichia coli (6.4%), and Candida species (6.1%). The incidence of brain abscesses is decreasing in Turkey. Although staphylococci remain the most isolated agents, the frequent occurrence of Gram-negative bacteria and Candida species warrants consideration during empirical antibiotic selection.

46 Association of Empiric Antibiotic Selection on Clinical Outcomes in Hospitalized Children with Severe Orbital Infections: A Multicenter Cohort Study

Abstract Background Antibiotic selection in children with periorbital and orbital infections is often empiric and regimens vary widely among institutions in their spectrum and inclusion of anti-anaerobic and anti-staphylococcal agents. Objectives Currently, there are no national clinical guidelines for antibiotic selection and no studies comparing commonly used antibiotic regimens in orbital infections. We aimed to determine the association of initial empiric antibiotic regimens with clinical outcomes in children hospitalized with severe orbital infections. Design/Methods We conducted a multicentre cohort study of children with severe orbital infections admitted to ten hospitals between January 1, 2009, and December 31, 2018. The association between empiric antibiotic regimen in the first 24 hours of hospitalization with length of stay and surgical intervention were assessed with multivariable median regression and multivariate logistic regression, respectively. Results Of 1421 patients, 60.0% were male, and mean age was 6.4 years (SD 4.5). Median length of stay was 86.4 hours (IQR 56.9-137.5) and 180 (12.7%) received surgical intervention. The most frequently (23.6%) administered empiric regimen consisted of a third-generation cephalosporin, anaerobic agent, and staphylococcal agent. After adjustment, broad-spectrum empiric antibiotic regimens with dedicated anti-anaerobic and/or staphylococcal coverage were associated with increased length of stay, ranging from an additional 18.4 hours (95% CI, 6.82, 30.0) to 21.5 hours (95% CI, 11.0, 32.0). Only patients with staphylococcal coverage alone had a statistically significant increased odds of surgical intervention (4.45, 95% CI 1.03, 19.2). Conclusion In children hospitalized with severe orbital infections, broad-spectrum therapy with or without coverage for staphylococci and anaerobes were associated with similar clinical outcomes in a clinical setting with low methicillin-resistant Staphylococcus aureus prevalence. Clinical practice guidelines are needed to standardize antibiotic recommendations.

Treatment Failure and Adverse Events After Amoxicillin-Clavulanate vs Amoxicillin for Pediatric Acute Sinusitis

Acute sinusitis is one of the most common indications for antibiotic prescribing in children, with an estimated 4.9 million such prescriptions in the US annually. Consensus does not exist regarding the optimal empirical antibiotic. To compare amoxicillin-clavulanate vs amoxicillin for the treatment of acute sinusitis in outpatient children. Cohort study of children and adolescents aged 17 years or younger with a new outpatient diagnosis of acute sinusitis and a same-day new prescription dispensation of amoxicillin-clavulanate or amoxicillin in a nationwide health care utilization database. Propensity score matching was used to mitigate confounding. A new prescription dispensation of amoxicillin-clavulanate or amoxicillin. Treatment failure, defined as an aggregate of a new antibiotic dispensation, emergency department or inpatient encounter for acute sinusitis, or inpatient encounter for a sinusitis complication, was assessed 1 to 14 days after cohort enrollment. Adverse events were evaluated, including gastrointestinal symptoms, hypersensitivity and skin reactions, acute kidney injury, and secondary infections. The cohort included 320 141 patients. After propensity score matching, there were 198 942 patients (99 471 patients per group), including 100 340 (50.4%) who were female, 101 726 (51.1%) adolescents aged 12 to 17 years, 52 149 (26.2%) children aged 6 to 11 years, and 45 067 (22.7%) children aged 0 to 5 years. Treatment failure occurred in 1.7% overall; 0.01% had serious failure (an emergency department or inpatient encounter). There was no difference in the risk of treatment failure between the amoxicillin-clavulanate and amoxicillin groups (relative risk [RR], 0.98 [95% CI, 0.92-1.05]). The risk of gastrointestinal symptoms (RR, 1.15 [95% CI, 1.05-1.25]) and yeast infections (RR, 1.33 [95% CI, 1.16-1.54]) was higher with amoxicillin-clavulanate. After patients were stratified by age, the risk of treatment failure after amoxicillin-clavulanate was an RR of 0.98 (95% CI, 0.86-1.12) for ages 0 to 5 years; RR was 1.06 (95% CI, 0.92-1.21) for 6 to 11 years; and RR was 0.87 (95% CI, 0.79-0.95) for 12 to 17 years. The age-stratified risk of adverse events after amoxicillin-clavulanate was an RR of 1.23 (95% CI, 1.10-1.37) for ages 0 to 5 years; RR was 1.19 (95% CI, 1.04-1.35) for 6 to 11 years; and RR was 1.04 (95% CI, 0.95-1.14) for 12 to 17 years. In children with acute sinusitis who were treated as outpatients, there was no difference in the risk of treatment failure between those who received amoxicillin-clavulanate compared with amoxicillin, but amoxicillin-clavulanate was associated with a higher risk of gastrointestinal symptoms and yeast infections. These findings may help inform decisions for empirical antibiotic selection in acute sinusitis.

Translation of Machine Learning-Based Prediction Algorithms to Personalised Empiric Antibiotic Selection: A Population-Based Cohort Study

Prediction of antibiotic non-susceptibility based on patient characteristics and clinical status may support selection of empiric antibiotics for suspected hospital-acquired urinary tract infections (HA-UTIs). Prediction models were developed to predict non-susceptible results of eight antibiotic susceptibility tests ordered for suspected HA-UTI. Eligible patients were those with urine culture and susceptibility test results after 48 hours of admission between 2010-2021. Patient demographics, diagnosis, prescriptions, exposure to multidrug-resistant organisms, transfer history, and a daily calculated antibiogram were used as predictors. Lasso logistic regression (LLR), extreme gradient boosting (XGB), random forest, and stacked ensemble methods were used for development. Parsimonious models were also developed for clinical utility. Discrimination was assessed using the area under the receiver operating characteristic curve (AUROC). In 10 474 suspected HA-UTI cases, the mean age was 62.1 ± 16.2 years and 48.1% were male. Non-susceptibility prediction for ampicillin/sulbactam, cefepime, ciprofloxacin, imipenem, piperacillin/tazobactam, and trimethoprim/sulfamethoxazole performed best using the stacked ensemble (AUROC 76.9, 76.1, 77.0, 80.6, 76.1, and 76.5, respectively). The model for ampicillin performed best with LLR (AUROC 73.4). Extreme gradient boosting only performed best for gentamicin (AUROC 66.9). In the parsimonious models, the LLR yielded the highest AUROC for ampicillin, ampicillin/sulbactam, cefepime, gentamicin, and trimethoprim/sulfamethoxazole (AUROC 70.6, 71.8, 73.0, 65.9, and 73.0, respectively). The model for ciprofloxacin performed best with XGB (AUROC 70.3), while the model for imipenem performed best in the stacked ensemble (AUROC 71.3). A personalised application using the parsimonious models was publicly released. Prediction models for antibiotic non-susceptibility were developed to support empiric antibiotic selection for HA-UTI.

Comparisons of the Oral Microbiota from Seven Species of Wild Venomous Snakes in Taiwan Using the High-Throughput Amplicon Sequencing of the Full-Length 16S rRNA Gene.

A venomous snake's oral cavity may harbor pathogenic microorganisms that cause secondary infection at the wound site after being bitten. We collected oral samples from 37 individuals belonging to seven species of wild venomous snakes in Taiwan, including Naja atra (Na), Bungarus multicinctus (Bm), Protobothrops mucrosquamatus (Pm), Trimeresurus stejnegeri (Ts), Daboia siamensis (Ds), Deinagkistrodon acutus (Da), and alpine Trimeresurus gracilis (Tg). Bacterial species were identified using full-length 16S rRNA amplicon sequencing analysis, and this is the first study using this technique to investigate the oral microbiota of multiple Taiwanese snake species. Up to 1064 bacterial species were identified from the snake's oral cavities, with 24 pathogenic and 24 non-pathogenic species among the most abundant ones. The most abundant oral bacterial species detected in our study were different from those found in previous studies, which varied by snake species, collection sites, sampling tissues, culture dependence, and analysis methods. Multivariate analysis revealed that the oral bacterial species compositions in Na, Bm, and Pm each were significantly different from the other species, whereas those among Ts, Ds, Da, and Tg showed fewer differences. Herein, we reveal the microbial diversity in multiple species of wild snakes and provide potential therapeutic implications regarding empiric antibiotic selection for wildlife medicine and snakebite management.

Microbial isolates and antibiotic sensitivity in patients hospitalized with odontogenic infections at a tertiary center over 10 years.

This study investigated causative strains and their antibiotic sensitivity in patients who were hospitalized for maxillofacial odontogenic infections at a tertiary center in South Korea over the past 10 years with the aim of providing guidelines for the selection of appropriate empirical antibiotics. Patients with head and neck fascial space abscesses due to odontogenic infections who underwent incision and drainage surgery with pus culture tests between 2013 and 2022 at the Department of Oral and Maxillofacial Surgery, Dankook University Hospital were included. The bacterial isolates and antibiotic sensitivity of each strain were analyzed for 2013-2022, 2013-2017, and 2018-2022. The affected fascial spaces were classified into primary, secondary, and deep neck spaces. In the 192 patients included in this study, 302 strains were detected. Viridans streptococcus had the highest frequency (51.7%), followed by Prevotella spp. (16.9%), Staphylococcus spp. (5.6%), and Klebsiella pneumoniae (4.6%). The identification rate of viridans streptococcus significantly increased from 41.8% in 2013-2017 to 60.9% in 2018-2022. Viridans streptococcus showed an antibiotic sensitivity of 80.5% to ampicillin; the sensitivity to penicillin antibiotics decreased over the study period. Antibiotic susceptibility was approximately 94% for third-generation cephalosporins. K. pneumoniae, which was identified at a high percentage in patients with deep neck space infection, showed increasing antibiotic resistance to most antibiotics over the study period. Viridans streptococcus was identified in head and neck fascial space abscesses with the highest frequency. Empirical antibiotics should be effective against this strain; penicillin antibiotics are considered inappropriate. For effective treatment of deep neck space abscesses, bacterial culture and antibiotic sensitivity tests performed as soon as possible are essential.

A single-center study on the distribution and antibiotic resistance of pathogens causing bloodstream infection in patients with hematological malignancies

Objective: To study the incidence of bloodstream infections, pathogen distribution, and antibiotic resistance profile in patients with hematological malignancies. Methods: From January 2018 to December 2021, we retrospectively analyzed the clinical characteristics, pathogen distribution, and antibiotic resistance profiles of patients with malignant hematological diseases and bloodstream infections in the Department of Hematology, Nanfang Hospital, Southern Medical University. Results: A total of 582 incidences of bloodstream infections occurred in 22,717 inpatients. From 2018 to 2021, the incidence rates of bloodstream infections were 2.79%, 2.99%, 2.79%, and 2.02%, respectively. Five hundred ninety-nine types of bacteria were recovered from blood cultures, with 487 (81.3%) gram-negative bacteria, such as Klebsiella pneumonia, Escherichia coli, and Pseudomonas aeruginosa. Eighty-one (13.5%) were gram-positive bacteria, primarily Staphylococcus aureus, Staphylococcus epidermidis, and Enterococcus faecium, whereas the remaining 31 (5.2%) were fungi. Enterobacteriaceae resistance to carbapenems, piperacillin/tazobactam, cefoperazone sodium/sulbactam, and tigecycline were 11.0%, 15.3%, 15.4%, and 3.3%, with a descending trend year on year. Non-fermenters tolerated piperacillin/tazobactam, cefoperazone sodium/sulbactam, and quinolones at 29.6%, 13.3%, and 21.7%, respectively. However, only two gram-positive bacteria isolates were shown to be resistant to glycopeptide antibiotics. Conclusions: Bloodstream pathogens in hematological malignancies were broadly dispersed, most of which were gram-negative bacteria. Antibiotic resistance rates vary greatly between species. Our research serves as a valuable resource for the selection of empirical antibiotics.

Empiric antibiotic selection for community-acquired pneumonia in US hospitals, 2013–2020

Background: Community-acquired pneumonia (CAP) is a common indication for antibiotic prescribing in hospitalized patients. Professional societies’ clinical guidelines recommend specific antibiotics for empiric treatment of CAP based on clinical factors. Manual assessments of appropriateness are time-consuming and are often conducted on a smaller scale. We evaluated empiric antibiotic selection among a large cohort of adults hospitalized with CAP using electronic health records. Methods: In this study, we used the PINC-AI healthcare database to define a cohort of adults hospitalized with CAP from 2013 to 2020. CAP was identified by International Classification of Diseases (ICD) diagnosis codes. Exclusions were applied to identify uncomplicated CAP (Fig. 1). Treatment was only evaluated if a chest radiograph or computerized tomography (CT) scan was charged during the first 2 days of hospitalization, otherwise it was considered an inadequate CAP evaluation. Administrative billing data were used to identify antibiotics charged within the first 2 days of hospitalization. Empiric guideline-recommended treatment was determined based on 2019 CAP guidelines and more recent studies. Patients who received nonrecommended treatment were evaluated for antibiotic allergies in the current hospitalization or methicillin-resistant Staphylococcus aureus (MRSA) colonization or infection in the year prior or on admission using International Classification of Disease, Tenth Revision (ICD-10) diagnosis codes. Results: We identified 4.47 million adult hospitalizations with CAP from 2013 to 2020; 32% (1.43 million) were included in this analysis (Fig. 1). Among discharges with adequate CAP evaluation (1.37 million), 59.7% received recommended antibiotics in the first 2 days of hospitalization, ranging from 62.6% in 2013 to 57.5% in 2019. Overall, 34.8% of our study population received a nonrecommended antibiotic without documentation of an antibiotic allergy or MRSA colonization (2013: 32.5%; 2018: 36.7%) (Fig. 2). Most patients in our study population received &gt;1 antibiotic (92.3%) in the first 2 days of hospitalization. The most common antibiotics among patients receiving recommended treatment were ceftriaxone (74.2% of patients receiving recommended treatment), azithromycin (67.2%), and levofloxacin (31.8%) (Fig. 3a). The most common nonrecommended antibiotics were vancomycin (57.2% of patients receiving nonrecommended treatment), piperacillin-tazobactam (48.1%), and cefepime (25.7%) (Fig. 3b). From 2013 to 2020, cefepime charges consistently increased among CAP patients treated with nonrecommended antibiotics, whereas levofloxacin charges consistently decreased among CAP patients treated with only recommended antibiotics. Conclusions: Approximately one-third of patients with uncomplicated CAP received nonrecommended empiric antibiotics, and from 2013 to 2020 that proportion increased by 9%. Additional strategies are needed to help identify opportunities to optimize antibiotic selection among patients with CAP.Disclosures: None

Reducing the rate of guideline-discordant therapy for inpatients with community-acquired pneumonia

Background: Despite guidelines recommending shorter durations of therapy and empiric coverage of Pseudomonas aeruginosa and methicillin-resistant Staphylococcus aureus (MRSA) only for patients with certain risk factors, optimizing therapy for community-acquired pneumonia (CAP) remains a challenge for antimicrobial stewardship (AMS) teams. We investigated the impact of a multimodal AMS initiative on the rate of guideline-discordant empiric antibiotic selection and total duration of therapy for CAP. Methods: A quality improvement initiative was implemented at 9 community hospitals in 2022 to optimize CAP therapy. Education was provided to pharmacists and providers. Alerts were implemented within the electronic medical record to prompt the AMS team to review fluoroquinolones, antipseudomonal β-lactams, and anti-MRSA agents ordered for CAP. Clinical pharmacists reviewed antibiotic orders for CAP at hospital discharge and encouraged providers to prescribe a total antibiotic duration of 5–7 days. For the preintervention period (July– September 2021) and the postintervention period (July to September 2022), a random sample of 320 patients with an antibiotic order for CAP were evaluated retrospectively via chart review. Patients treated for an indication other than CAP were excluded. The primary outcome was the proportion of patients with a total duration of therapy &gt;7 days. Secondary outcomes included average duration of therapy, rate of guideline-discordant empiric therapy, and type of guideline discordance. Results: In total, 317 patients were included. The proportion of patients with a total duration of therapy &gt;7 days decreased from 29% to 14% (P &lt; .01). Average duration of therapy and guideline-discordant empiric therapy also decreased significantly (Table 1). Conclusions: This multifaceted AMS initiative was associated with decreased guideline-discordant empiric therapy and decreased total duration of therapy for CAP.Disclosures: None

Estimating antibiotic coverage from linked microbiological and clinical data from the Swiss Paediatric Sepsis Study to support empiric antibiotic regimen selection.

In light of rising antibiotic resistance, better methods for selection of empiric antibiotic treatment based on clinical and microbiological data are needed. Most guidelines target specific clinical infections, and variably adjust empiric antibiotic selection by certain patient characteristics. Coverage estimates reflect the probability that an antibiotic regimen will be active against the causative pathogen once confirmed and can provide an objective basis for empiric regimen selection. Coverage can be estimated for specific infections using a weighted incidence syndromic combination antibiograms (WISCAs) framework. However, no comprehensive data combining clinical and microbiological data for specific clinical syndromes are available in Switzerland. We therefore describe estimating coverage from semi-deterministically linked routine microbiological and cohort data of hospitalised children with sepsis. Coverage estimates were generated for each hospital and separately pooling data across ten contributing hospitals for five pre-defined patient risk groups. Data from 1,082 patients collected during the Swiss Paediatric Sepsis Study (SPSS) 2011-2015 were included. Preterm neonates were the most commonly represented group, and half of infants and children had a comorbidity. 67% of neonatal sepsis cases were hospital-acquired late-onset whereas in children 76% of infections were community-acquired. Escherichia coli, Coagulase-negative staphylococci (CoNS) and Staphylococcus aureus were the most common pathogens. At all hospitals, ceftazidime plus amikacin regimen had the lowest coverage, and coverage of amoxicillin plus gentamicin and meropenem were generally comparable. Coverage was improved when vancomycin was included in the regimen, reflecting uncertainty about the empirically targeted pathogen spectrum. Children with community-acquired infections had high coverage overall. It is feasible to estimate coverage of common empiric antibiotic regimens from linked data. Pooling data by patient risk groups with similar expected pathogen and susceptibility profiles may improve coverage estimate precision, supporting better differentiation of coverage between regimens. Identification of data sources, selection of regimens and consideration of pathogens to target for improved empiric coverage is important.

Digital Antimicrobial Stewardship Decision Support to Improve Antimicrobial Management.

We sought to create a digital application to support clinicians in empiric and pathogen-directed antibiotic ordering based on local susceptibility patterns and evidence-based treatment durations, thereby promoting antimicrobial stewardship. We formed a multidisciplinary team that met bimonthly from 2017 to 2018 to design and construct a web-based antimicrobial stewardship platform called Antibiogram + . We used an iterative and agile technical development process with frequent feedback from clinicians. Antibiogram+ is an online tool, accessible via the electronic health record and hospital intranet, which offers institutional antibiotic susceptibilities for major pathogens, recommendations for empiric antibiotic selection and treatment durations for common pediatric conditions, antimicrobial dosing and monitoring guidance, and links to other internal clinical decision support resources. The tool was accessed 11,823 times with 492 average monthly views during the first 2 years after release. Compared with use of a preexisting print antibiogram and dosing card, pediatric residents more frequently reported "often" being sure of antibiotic dosing with Antibiogram+ (58 vs. 15%, p < 0.01). Respondents also reported improved confidence in choice of antibiotic, but this finding did not reach statistical significance (55 vs. 35%, p = 0.26). We report the successful development of a digital antimicrobial stewardship platform with consistent rates of access during the first 2 years following release and improved provider comfort with antibiotic management.

Is adherence to national guidelines for parenteral empiric antibiotic therapy effective? Experience from a Sri Lankan center.

Guidelines for the selection of empirical antibiotics have been developed to improve patient outcomes and reduce unnecessary antibiotic use. We assessed the extent of adherence to the national guidelines for the selection of parenteral empirical antibiotics for three selected infections at a tertiary care center. A prospective cross-sectional study was conducted in medical and surgical wards of a tertiary care hospital in Sri Lanka. Adult patients with a positive culture for a lower respiratory tract infection (LRTI), skin and soft tissue infection (SSTI), or urinary tract infection (UTI) and who were prescribed parenteral empirical antibiotic therapy by the attending physician were included. Bacteria were identified and antibiotic susceptibility was determined by standard microbiological methods. Adherence to the guidelines was defined as prescribing the empiric antibiotic concordant with the national guidelines on the empirical use of antibiotics. A total of 160 bacterial isolates were obtained from 158 patients with positive cultures, the majority were from UTIs (n = 56). The selection of empirical antibiotics was concordant with the national guidelines in 92.4% of patients and 29.5% of the bacterial isolates obtained from these patients were resistant to the prescribed empiric antibiotic. Only 47.5% (76/160) of the bacterial isolates were sensitive to the empiric antibiotic and therefore can be considered an appropriate antibiotic prescription. Empirical antibiotic guidelines should be updated based on the latest surveillance data and information on prevailing bacterial spectra. Antibiotic prescribing patterns and guideline concordance should be periodically evaluated to ensure whether antimicrobial stewardship programs are moving in the right direction.

Risk Factors Associated with Multi-Drug Resistance in Neonatal Sepsis Caused by Escherichia coli.

An increasing number of cases of neonatal sepsis due to extended-spectrum beta-lactamase (ESBL)-producing multi-drug resistant (MDR) Escherichia coli (E. coli) have been reported worldwide. The aim of this study was to explore the risk factors associated with ESBL-producing MDR E. coli among neonates with culture-confirmed E. coli sepsis and thereby to help selection of appropriate empirical antibiotics. All newborn infants with a confirmed pathogen isolated from blood or cerebrospinal fluid (CSF) from 2016 to 2021 were identified and those with E. coli infection were included in this analysis. We compared a group of neonatal patients with ESBL-producing MDR E. coli sepsis (n=69) to a group with ESBL-negative E. coli (n=70) based on antimicrobial susceptibility reports. We used multivariable regression analysis to determine the risk factors associated with ESBL-producing MDR E. coli strains among the neonates with culture-confirmed E. coli sepsis. ESBL-producing MDR E. coli sepsis was more common in premature infants and newborns with hospital-acquired late-onset sepsis (HALOS). The mortality rate of neonatal sepsis caused by ESBL-producing E. coli was about twice as that of sepsis caused by ESBL-negative E. coli. Antepartum exposure to cephalosporins (OR=25.191, 95% CI: 3.184-199.326, P<0.01) and parenteral nutrition for more than 1 week (OR=4.495, 95% CI: 2.009-10.055, P<0.01) were independent risk factors for neonatal infection with ESBL-producing stains among infants with E. coli sepsis. E. coli remains the most common Gram-negative bacterial pathogen causing neonatal sepsis. A higher proportion of ESBL-producing MDR E. coli is seen in premature infants and those newborns with HALOS and is associated with higher mortality. Antepartum use of cephalosporins and prolonged use of parenteral nutrition may be important factors to consider in the selection of empirical antibiotics for use in neonatal sepsis caused by gram-negative rods prior to the availability of the results of antimicrobial susceptibility.

Challenges and recommendations when selecting empirical antibiotics in patients with cirrhosis.

There is abundant evidence that bacterial infections are severe complications in patients with cirrhosis, being the most frequent trigger of acute-on-chronic liver failure and causing death in one of every four patients during hospitalization. For these reasons, early diagnosis and effective treatment of infections are mandatory to improve patient outcomes. However, treating physicians are challenged in daily practice since diagnosing bacterial infections is not always straightforward. This situation might lead to delayed antibiotic initiation or prescription of ineffective regimens, which are associated with poor outcomes. On the other hand, prescribing broad-spectrum antibiotics to all patients suspected of bacterial infections might favor bacterial resistance development. This is a significant concern given the alarming number of infections caused by multidrug-resistant microorganisms worldwide. Therefore, it is paramount to know the local epidemiology to propose tailored guidelines for empirical antibiotic selection in patients with cirrhosis in whom bacterial infections are suspected or confirmed. In this article, we will revise current knowledge in this area and highlight the importance of surveillance programs.

Importance of antibiotic therapy in post-surgical patients

Antibiotics are the class of medication that prevent the infections that is caused by bacteria; antibiotics make it difficult to grow or multiply or directly killing them. But the widespread misuse of antibiotics can also lead to serious consequences. In the case of post-operative patients, the empirical antibiotics should be selected based on the site of infection, etiology, and pharmacokinetics of the antibiotics. Therefore, the rational use of empirical antibiotics is based on the increase in the total count and also the spike in temperature. The review focus on the time, duration, rationality, and selection of empirical antibiotics, and antibiotic prescription patterns in different departments and different age groups.

Norfloxacin prophylaxis effect on multidrug resistance in patients with cirrhosis and bacterial infections.

It is unclear whether norfloxacin predisposes to infections by multidrug-resistant organisms (MDROs). We aimed to evaluate if patients with cirrhosis receiving norfloxacin prophylaxis at the time of the diagnosis of bacterial infections were more likely to present a multidrug-resistant isolate than those without prophylaxis. This is a cross-sectional study of hospitalized patients with cirrhosis and bacterial infections from Argentina and Uruguay (NCT03919032) from September 2018 to December 2020. The outcome variable was a multidrug-resistant bacterial infection. We used inverse probability of treatment weighting to estimate the odds ratio (OR) of norfloxacin on infection caused by MDROs considering potential confounders. Among the 472 patients from 28 centers, 53 (11%) were receiving norfloxacin at the time of the bacterial infection. Patients receiving norfloxacin had higher MELD-sodium, were more likely to have ascites or encephalopathy, to receive rifaximin, beta-blockers, and proton-pump inhibitors, to have a nosocomial or health-care-associated infection, prior bacterial infections, admissions to critical care units or invasive procedures, and to be admitted in a liver transplant center. In addition, we found that 13 (24.5%) patients with norfloxacin and 90 (21.5%) of those not receiving it presented infections caused by MDROs (adjusted OR 1.55; 95% CI: 0.60-4.03; p = 0.360). The use of norfloxacin prophylaxis at the time of the diagnosis of bacterial infections was not associated with multidrug resistance. These results help empiric antibiotic selection and reassure the current indication of norfloxacin prophylaxis in well-selected patients.Study registration number: NCT03919032.

1302. Interactive Case-based Antimicrobial Stewardship Education Program to Pharmacists at a Large Community Health System

Abstract Background Education on antimicrobial stewardship (AMS) is one of the several elements outlined by the Center for Disease Control for hospital antibiotic stewardship programs. However, the Infectious Diseases Society of America guideline on implementing antimicrobial stewardship notes that passive education should not be a sole method for training as the effects are often short lived. AMS education strategies beyond didactic lectures and written material distribution are needed. We sought to describe the implementation of an interactive, case-based AMS educational program targeting pharmacists across a multi-hospital community health system licensed for over 1,500 beds. Methods Each month, a custom patient case was drafted by an infectious diseases trained pharmacist to highlight a common AMS principle encountered in practice. These topics were broadly categorized into appropriate empiric antibiotic selection, treatment plan modification, and identification of non-infectious clinical syndromes. A specific question with multiple choice answers was drafted. The case was disseminated to all hospital pharmacists via email using Microsoft Outlook. Pharmacists were prompted to use the voting buttons to select the correct answer (Figure 1). After a week, results of the survey was shared with the entire pharmacist staff along with information on the primary teaching point and detailed explanations for why each answer was correct or incorrect. Example Voting Buttons for Case-Based Education Results A total of eleven AMS cases were disseminated to 88 hospital pharmacists involved with direct patient care. Average number of responses per case was 27 (31%), range 17-41 (19%-47%). Average number of correct responses for each case was 74%, range 26%-100%. The highest rates of correct responses came from cases focusing on empiric antibiotic selection (87%), followed by identification of non-infectious clinical syndromes (73%). The lowest rate of correct responses were found with treatment plan modification cases (65%). Conclusion This case-based AMS education program leveraged existing technology to provide engagement across a large and geographically diverse pharmacist staff, provide opportunity to apply stewardship concepts, and assess staff pharmacist knowledge on general AMS principles. Disclosures Matthew Song, PharmD, BCIDP, Merck: Stocks/Bonds|ObsEva: Stocks/Bonds.