Optimal Antibiotic Therapy Research Articles

Impact of direct disk-diffusion testing on time to optimal antibiotic therapy

Abstract We evaluated the impact of preliminary blood-culture antibiotic susceptibility testing on time to optimal antibiotic therapy in a cohort of 503 patients with monomicrobial bloodstream infections. The median time from blood-culture collection to optimal antibiotics was 17 hours earlier in the preliminary antibiotic susceptibility testing group.

968. The Impact of Film Array Detection of High-risk and Resistant Pathogens on the Time to Optimal Antibiotic Therapy at a Community Health System

Abstract Background The importance of effective antibiotic therapy for the treatment of bloodstream infections has been well described. Rapid diagnostic testing platforms like the BioFire® FilmArray® blood culture identification (BCID) have the potential to decrease time to effective antibiotics when acted on appropriately. The Cone Health stewardship team has collaborated with clinical pharmacists and infectious diseases physicians to define a process to optimize antibiotic therapy. This process involves microbiology calling a pharmacist with newly positive blood cultures, and the pharmacist notifies the attending physician with the results and evidence-based treatment recommendations. We transitioned from BCID to BCID2 in August, 2021. As CTX-M (marker for extended spectrum beta-lactamase production) was not a target on BCID, we were interested in how the addition of this marker could improve care in this subset of patients. Procedure for Positive Blood Culture Workup and Notification Treatment Recommendations for Selected Organisms Methods From August 2021 - March 2022, the times to administration of effective and optimal antibiotics were evaluated in patients with the following BCID2 organism and resistance gene targets identified: S. aureus, P. aeruginosa, CTX-M, KPC, OXA-48 like, IMP, VIM, NDM, and vancomycin resistant enterococci. An effective antibiotic was defined as an antibiotic with in vitro activity to the organism, and an optimal antibiotic was defined as the preferred agent based on institutional guidelines. For CTX-M isolates, we compared effective and optimal times to a historical control of ceftriaxone resistant enterobacterales and analyzed by student’s t-test. Results The combined mean time from BCID2 to administration of effective antibiotics = 1.2 hours (range 0-7.9 hours) and to optimal therapy =7.6 hours (range 0 – 113.8 hours). Prior to the BCID2 transition, patients found to be growing ceftriaxone resistant enterobacterales had an average time to optimal antibiotic administration of 17.7 hours, which improved to 2.8 hours after BCID2 implementation (p=0.0041). Time to Effective and Optimal Antibiotics after implementation of BCID2 (August 2021 – March 2022) Time to Effective and Optimal Antibiotics for Ceftriaxone Resistant Enterobacterales Prior to BCID2 Implementation (January 2021 - July 2021) Conclusion BioFire® FilmArray® coupled with antibiotic stewardship team support can help optimize time to effective and optimal antibiotic therapy in bloodstream infection. The addition of the CTX-M target to BCID2 was a helpful addition to the panel which allowed for decreased time to optimal antibiotic therapy. Disclosures All Authors: No reported disclosures.

189. Optimizing Empiric Antibiotic Therapy: a Probabilistic Approach

Abstract Background How to start optimal antibiotic therapy before the results of cultures and antimicrobial susceptibility tests are available? Here, we use the law of total probability to present a probabilistic approach based on antibiograms of bacterial isolates from healthcare and community-acquired infections to optimizing empiric antibiotic therapy. Methods Data on the microbiology of healthcare and community-acquired infections were analyzed from hospitals in Belo Horizonte, a three million inhabitants city from Brazil. Healthcare infections were defined by the National Healthcare Safety Network (NHSN)/CDC protocols. Only data obtained from infections with positive culture, both hospital and community, were considered. The success rate of an antibiotic (ATB) regimen, considering just one drug individually (monotherapy), was calculated by Law of Total Probability (Fig 1). In this sense, if a microorganism has not been tested for a specific antimicrobial, then, by definition, it was considered an antibiotic failure. For a regimen with more than one antibiotic, if the microorganism is sensitive to one of them, then it was considered a success of the scheme. For calculating the success probability of two or three antimicrobials A, B, and C, simultaneously (Fig 2), i.e., P(A and B) or P(A and B and C), the sensitivity to an antimicrobial was considered independent of sensitivity to any other. Then, P(A and B) = P(A) * P(B), and P(A and B and C) = P(A)*P(B) *P(C). Figure 1– Law of total probability: success rate of an antibiotic considering just one drug individually (monotherapy).Figure 2– Probability of the union of two events, success of ATB A or ATB B, and union of three events, success of ATB A or ATB B or ATB C. Results Microbiologic data from hospital acquired infections (HAI) and community-acquired infections (CAI) are analyzed once a year. Empiric antibiotic therapy to HAI were proposed for urinary tract infections (UTI), bloodstream infections (BSI), and pneumonia (Figures 2 and 3). Empiric antibiotic therapy to community-acquired infections were developed for UTI, pneumonia, gastrointestinal system infection, bone and joint infection, and skin and soft tissue infection. Figure 3– Success rate of each antibiotic alone, considering just one drug individually (monotherapy): analysis of hospital-acquired pneumonia.Figure 4– Success rate of one, two or three antibiotics: analysis of hospital-acquired pneumonia.Fig 5- Probability of the antimicrobial regimen being successful in treating an infection according to the length of stay at hospital. Conclusion We presented here a probabilistic approach to empiric antibiotic therapy. The next step is to validate all proposed regimens, that can be used to improve the success likelihood of empiric antibiotic decision making. Disclosures All Authors: No reported disclosures.

678. Title: Treatment Outcomes with Carbapenems vs. Non-Carbapenem Beta-Lactams in Infections with Carbapenem-Discordant Enterobacter cloacae Complex

Abstract Background Carbapenem-discordant Enterobacter cloacae complex (CDECC) isolates are defined as ertapenem non-susceptible and meropenem susceptible drug phenotype. The optimal treatment of these infections is unknown. In 2021, the Infectious Diseases Society of America released guidance recommending extended infusion meropenem as the preferred treatment option. Newer agents, including ceftazidime-avibactam, may be effective but comparative data is lacking. Evaluation of treatment outcomes for use in infections with CDECC is necessary to establish optimal therapy. Methods This single center, retrospective, cohort study was conducted at The University of Kansas Hospital from January 2016 to June 2021. Individuals at least 18 years of age with non-urinary culture positive for CDECC that were treated with either meropenem (MEM) or a non-carbapenem beta-lactam (NCBL) were included. Individuals with polymicrobial infections, infections from a urinary source, or death within 72 hours of admission were excluded. The primary outcome was clinical failure, which was a composite endpoint. Secondary outcomes included individual components of the primary outcome. Results There were 29 unique episodes of monomicrobial, carbapenem-discordant Enterobacter cloacae complex infections during the study period. The primary outcome was met in 6 patients receiving a NCBL and 6 patients receiving MEM, respectively (67% vs. 30%, p=0.11). A total of 8 patients died within 30 days, 4 in the MEM group and 4 in the NCBL group (20% vs. 44%, p = 0.21). Univariate logistic regression analysis demonstrated a significant increase in need to modify antibiotic therapy in the NCBL group (OR 15.2, 95% CI, 1.37-168; p=0.02), with a trend towards increased risk for in-hospital 30-day mortality (OR, 3.2; 95% CI, 0.58-17.72; p = 0.18). Conclusion There was no difference in clinical failure rates between the MEM and NCBL treatment groups. However, treatment with NCBLs was associated with a trend towards increased in-hospital mortality and need for antibiotic modifications due to clinical decompensation. Larger studies are needed to assess treatment outcomes in carbapenem-discordant Enterobacter cloacae complex infections to define optimal antibiotic therapy. Disclosures All Authors: No reported disclosures.

АНАЛИЗ РЕЗУЛЬТАТОВ АНКЕТИРОВАНИЯ СТУДЕНТОВ СТАРШИХ КУРСОВ МЕДИЦИНСКОГО УНИВЕРСИТЕТА ПО ВОПРОСАМ РАЦИОНАЛЬНОЙ АНТИБИОТИКОТЕРАПИИ ИНФЕКЦИЙ ВЕРХНИХ ДЫХАТЕЛЬНЫХ ПУТЕЙ И ЛОР-ОРГАНОВ У ДЕТЕЙ

Despite the availability of clinical guidelines, the issues of choosing the optimal first-line antibiotic therapy in the treatment of infections of the upper respiratory tract and ENT organs in children still remain relevant. Knowledge of the etiology of infections and the rational apply of systemic antibiotics are formed in senior medical students. Therefore, the purpose of this study is to analyze the knowledge of 6th year students of a medical university on the etiology and antibiotic therapy of upper respiratory tract infections and ENT organs in children, as well as comparing the results with knowledge on these issues of pediatricians. The article presents the results of a survey among the 350 volunteer students of the 6th year of the pediatric faculty on the etiology and antibacterial treatment of upper respiratory tract infections and ENT organs in children. These data have been compaired with the results of the large-scale multicenter study «PATRIOT» (2011-2013) among the pediatricians from 18 cities of Russia. It was revealed that most students overestimate the role of Staphylococcus aureus as the main pathogen in acute otitis media and acute tonsillopharyngitis (tonsillitis) in children. The main group of empirical antibiotic therapy were called aminopenicillins, often inhibitor-protected, whereas the role of natural penicillins in streptococcal tonsillopharyngitis and amoxicillin in acute otitis media and acute sinusitis was underestimated. Among district pediatricians, the frequency of correct answers to questions regarding the etiology and antibiotic therapy of these diseases was significantly higher than among students. It was found that only 9.4% of students and 6.1% of doctors would prescribe antibiotics for uncomplicated acute respiratory infection (ARI), but in real clinical practice they were prescribed in 59.6% of cases. These data indicate a different level of knowledge between students and doctors, as well as the difference in approaches to rational antibiotic therapy in theory and in real practice.

Early appropriate diagnostics and treatment of MDR Gram-negative infections.

The term difficult-to-treat resistance has been recently coined to identify Gram-negative bacteria exhibiting resistance to all fluoroquinolones and all β-lactam categories, including carbapenems. Such bacteria are posing serious challenges to clinicians trying to identify the best therapeutic option for any given patient. Delayed appropriate therapy has been associated with worse outcomes including increase in length of stay, increase in total in-hospital costs and ∼20% increase in the risk of in-hospital mortality. In addition, time to appropriate antibiotic therapy has been shown to be an independent predictor of 30 day mortality in patients with resistant organisms. Improving and anticipating aetiological diagnosis through optimizing not only the identification of phenotypic resistance to antibiotic classes/agents, but also the identification of specific resistance mechanisms, would have a major impact on reducing the frequency and duration of inappropriate early antibiotic therapy. In light of these considerations, the present paper reviews the increasing need for rapid diagnosis of bacterial infections and efficient laboratory workflows to confirm diagnoses and facilitate prompt de-escalation to targeted therapy, in line with antimicrobial stewardship principles. Rapid diagnostic tests currently available and future perspectives for their use are discussed. Early appropriate diagnostics and treatment of MDR Gram-negative infections require a multidisciplinary approach that includes multiple different diagnostic methods and further consensus of algorithms, protocols and guidelines to select the optimal antibiotic therapy.

Implementation of antimicrobial stewardship programs

Background: The antimicrobial stewardship program (ASP) is a coordinated intervention designed to improve and measure the appropriate antibiotics use by selecting an optimal antibiotic drug regimen, including dosing, therapy duration, and administration route. The implementation of ASPs decreases the consumption, cost, and adverse effects of antibiotic use. Additionally, it improves the clinical outcomes, and decreases Clostridium difficile infection and antimicrobial resistance.Current Concepts: To overcome the antimicrobial resistance and implement ASPs worldwide, various efforts are underway, such as enacting ASP guidelines, developing core elements for ASP implementation, introducing ASPs to the healthcare accreditation system, and providing healthcare facilities with adequate incentives to implement ASPs. In Korea, ASP guidelines were published in September 2021, and core elements for ASP implementation are being developed at the time of writing. However, there is a shortage of personnel required for the ASP team, including healthcare workforce and infectious disease specialists for leading the team Moreover, financial support for ASP implementation in the National Health Insurance Service is not provided yet. The awareness of hospital leadership and clinicians prescribing antibiotics for ASP implementation is still low. The reimbursement system establishment and workforce for ASPs are prerequisite for the implementation of ASPs.Discussion and Conclusion: At the national level, it is necessary to provide financial support for ASPs in healthcare facilities, nurture the healthcare workforce in performing ASPs, and advocate ASP education and publicity.

Spontaneous Bacterial Peritonitis: The Incremental Value of a Fast and Direct Bacterial Identification from Ascitic Fluids Inoculated in Blood Culture Bottles by MALDI-TOF MS for a Better Management of Patients.

Spontaneous bacterial peritonitis (SBP) is a severe infection that requires fast and accurate antibiotic therapy to improve the patient outcome. Direct bacterial identification using MALDI-TOF mass spectrometry from ascitic fluid inoculated in blood culture bottles (BCBs) could therefore improve patients’ management. We evaluated the impact of the implementation of this method for the treatment of patients. Our identification protocol was performed on 136 positive BCBs collected from 61 patients between December 2018 and December 2020. The therapeutic impact of our protocol was evaluated using a before (2015–2016) and after (2019–2020) case–control study in two populations of 41 patients diagnosed with SBP and treated with antibiotics. The decrease in time to first identification and the optimization of antibiotic therapy following communication of the identification result were evaluated. Our protocol allowed us to identify 78% of bacteria in ascitic fluids. The transmission of the direct identification allowed the introduction or adaption of the antibiotic therapy early in 37% of SBP, with a mean decrease in time to first antibiotic change of 17 h. Our direct identification protocol for positive inoculated ascitic fluids is fast, reliable and inexpensive. Its routine integration into a microbiology laboratory allows the early introduction of appropriate antibiotic therapy and improves the management of patients with SBP.

Prevalence and Antimicrobial Resistance of Causative Agents to Ocular Infections.

Bacterial ocular infections are a worldwide health problem and, if untreated, can damage the structure of the eye and contribute to permanent disability. Knowledge of the prevalence and antimicrobial susceptibility patterns of the main causative agents involved in ocular infections is necessary for defining an optimal antibiotic therapy. The aim of this study was to analyse bacterial species involved in ocular infections and the antimicrobial susceptibility patterns. Conjunctival swab samples were collected from patients with bacterial conjunctivitis at the University Hospital San Giovanni di Dio e Ruggi d’Aragona between January 2015 and December 2019. The identification and antibiotic sensitivity tests were performed using the VITEK 2 system. A total of 281 causative agents of ocular infections were isolated, 81.8% of which were Gram-positive bacteria. Coagulase-negative staphylococci (CoNS) were the most commonly isolated species among Gram-positive bacteria, followed by Staphylococcus aureus. In contrast, Pseudomonas spp. and Escherichia coli were the main species isolated among Gram-negative bacteria (18.2%). Overall, linezolid, teicoplanin, tigecycline and vancomycin were the most effective antimicrobials. Analysis of resistance rates over time highlighted increasing resistance for azithromycin, clarithromycin and erythromycin among CoNS, and clindamycin and erythromycin among Staphylococcus aureus. This study has identified the profiles of the major pathogens involved in ocular infection and their susceptibility patterns, which will help improve the treatments and the choice of antibiotics in ocular infections.

The Use of Comparative Genomic Analysis for the Development of Subspecies-Specific PCR Assays for Mycobacterium abscessus.

Mycobacterium abscessus complex (MABC) is an important pathogen of immunocompromised patients. Accurate and rapid determination of MABC at the subspecies level is vital for optimal antibiotic therapy. Here we have used comparative genomics to design MABC subspecies-specific PCR assays. Analysis of single nucleotide polymorphisms and core genome multilocus sequence typing showed clustering of genomes into three distinct clusters representing the MABC subspecies M. abscessus, M. bolletii and M. massiliense. Pangenome analysis of 318 MABC genomes from the three subspecies allowed for the identification of 15 MABC subspecies-specific genes. In silico testing of primer sets against 1,663 publicly available MABC genomes and 66 other closely related Mycobacterium genomes showed that all assays had >97% sensitivity and >98% specificity. Subsequent experimental validation of two subspecies-specific genes each showed the PCR assays worked well in individual and multiplex format with no false-positivity with 5 other mycobacteria of clinical importance. In conclusion, we have developed a rapid, accurate, multiplex PCR-assay for discriminating MABC subspecies that could improve their detection, diagnosis and inform correct treatment choice.

Treatment of Severe Infections Due to Metallo-Betalactamases Enterobacterales in Critically Ill Patients.

Metallo-beta-lactamases-producing (MBL) Enterobacterales is a growing problem worldwide. The optimization of antibiotic therapy is challenging. The pivotal available therapeutic options are either the combination of ceftazidime/avibactam and aztreonam or cefiderocol. Colistin, fosfomycin, tetracyclines and aminoglycosides are also frequently effective in vitro, but are associated with less bactericidal activity or more toxicity. Prior to the availability of antibiotic susceptibility testing, severe infections should be treated with a combination therapy. A careful optimization of the pharmacokinetic/pharmacodynamic properties of antimicrobials is instrumental in severe infections. The rules of antibiotic therapy are also reported and discussed. To conclude, treatment of severe MBL infections in critically ill patients is difficult. It should be individualized with a close collaboration of intensivists with microbiologists, pharmacists and infection control practitioners.

Antibiotic Therapy in 2-Stage Revision for Periprosthetic Joint Infection: A Systematic Review.

Patients undergoing total joint arthroplasty (TJA) are at risk for developing periprosthetic joint infection (PJI). To treat PJI, orthopaedic surgeons can perform 1-stage or 2-stage revision arthroplasty. Although 2-stage revision yields superior long-term outcomes, the optimal antibiotic therapy duration and route of administration between stages remain uncertain. In this systematic review, we aimed to identify if variations in antibiotic therapy, duration, and administration during 2-stage hip or knee revision arthroplasty affect PJI eradication rates and surgical outcome measures. A literature search was performed using the PubMed and Google Scholar databases to identify all original reports from January 2000 to June 2021 involving 2-stage revision arthroplasty to treat PJI. Studies were included if they specified antibiotic duration, an intravenous (IV) route of antibiotic administration, type of antibiotic, and 2-stage revision PJI eradication rate and had a mean or median follow-up of at least 2 years after the second-stage operation. Included studies were classified into 3 groups based on the length of IV antibiotic therapy after prosthesis explantation: prolonged IV antibiotic therapy of 4 to 6 weeks, shortened IV antibiotic therapy of ≤2 weeks, and shortened course of IV antibiotic therapy followed by 6 to 12 weeks of oral antibiotics. Nine studies were included. Three studies utilizing a prolonged IV antibiotic therapy had PJI eradication rates of 79% to 96%. Four studies using a shortened IV antibiotic therapy showed PJI eradication rates of 88% to 100%. Finally, 2 studies utilizing a shortened course of IV antibiotic therapy with oral antibiotics had PJI eradication rates of 95% and 97%. There was no significant difference in eradication rates across IV antibiotic duration strategies, despite a diverse array of cultured microorganisms across the studies. Although the numbers are small, this systematic review suggests that prolonged IV antibiotic duration, shortened IV antibiotic duration, and shortened IV antibiotic duration supplemented with oral antibiotics confer similar PJI eradication rates after hip or knee arthroplasty. Therapeutic Level IV. See Instructions for Authors for a complete description of levels of evidence.

Real Life Clinical Impact of Antimicrobial Stewardship Actions on the Blood Culture Workflow from a Microbiology Laboratory.

Background: Accelerating the diagnosis of bacteremia is one of the biggest challenges in clinical microbiology departments. The fast establishment of a correct treatment is determinant on bacteremic patients’ outcomes. Our objective was to evaluate the impact of antimicrobial therapy and clinical outcomes of a rapid blood culture workflow protocol in positive blood cultures with Gram-negative bacilli (GNB). Methods: A quasi-experimental before–after study was performed with two groups: (i) control group (conventional work-protocol) and (ii) intervention group (rapid workflow-protocol: rapid identification by Matrix-Assisted Laser Desorption/Ionization-Time-Of-Flight (MALDI-TOF) and antimicrobial susceptibility testing (AST) from bacterial pellet without overnight incubation). Patients were divided into different categories according to the type of intervention over treatment. Outcomes were compared between both groups. Results: A total of 313 patients with GNB-bacteremia were included: 125 patients in the control group and 188 in the intervention. The time from positive blood culture to intervention on antibiotic treatment decreased from 2.0 days in the control group to 1.0 in the intervention group (p < 0.001). On the maintenance of correct empirical treatment, the control group reported 2.0 median days until the clinical decision, while in the intervention group was 1.0 (p < 0.001). In the case of treatment de-escalation, a significant difference between both groups (4.0 vs. 2.0, p < 0.001) was found. A decreasing trend on the change from inappropriate treatments to appropriate ones was observed: 3.5 vs. 1.5; p = 0.12. No significant differences were found between both groups on 7-days mortality or on readmissions in the first 30-days. Conclusions: Routine implementation of a rapid workflow protocol anticipates the report of antimicrobial susceptibility testing results in patients with GNB-bacteremia, decreasing the time to effective and optimal antibiotic therapy.

A new path for CF clinical trials through the use of historical controls

BackgroundGiven future challenges in conducting large randomized, placebo controlled trials for future CF therapeutics development, we evaluated the potential for using external historical controls to either enrich or replace traditional concurrent placebo groups in CF trials. MethodsThe study included data from sequentially completed, randomized, controlled clinical trials, EPIC and OPTIMIZE respectively, evaluating optimal antibiotic therapy to reduce the risk of pulmonary exacerbation in children with early Pseudomonas aeruginosa infection. The primary treatment effect in OPTIMIZE, the risk of pulmonary exacerbation associated with azithromycin, was re-estimated in alternative designs incorporating varying numbers of participants from the earlier trial (EPIC) as historical controls. Bias and precision of these estimates were characterized. Propensity scores were derived to adjust for baseline differences across study populations, and both Poisson and Cox regression were used to estimate treatment efficacy. ResultsReplacing 86 OPTIMIZE placebo participants with 304 controls from EPIC to mimic a fully historically controlled trial resulted an 8% reduction in risk of pulmonary exacerbations (Hazard ratio (HR):0.92 95% CI 0.61, 1.34) when not adjusting for key baseline differences between study populations. After adjustment, a 37% decrease in risk of exacerbation (HR:0.63, 95% CI 0.50, 0.80) was estimated, comparable to the estimate from the original trial comparing the 86 placebo participants to 77 azithromycin participants on azithromycin (45%, HR:0.55, 95% CI: 0.34, 0.86). Other adjusted approaches provided similar estimates for the efficacy of azithromycin in reducing exacerbation risk: pooling all controls from both studies provided a HR of 0.60 (95% x`CI 0.46, 0.77) and augmenting half the OPTIMIZE placebo participants with EPIC controls gave a HR 0.63 (95% CI 0.48, 0.82). ConclusionsThe potential exists for future CF trials to utilize historical control data. Careful consideration of both the comparability of controls and of optimal methods can reduce the potential for biased estimation of treatment effects.

653. Direct Identification of Microorganisms in Positive Blood Cultures by the BioFire® FilmArray® Blood Culture Identification Panel Leads to Faster Optimal Antibiotic Therapy: A Before–After Study

BackgroundRapid pathogen identification from positive blood cultures may help optimize empiric antibiotic therapy quickly by reducing unnecessary broad spectrum antibiotic use and may improve patient outcomes. The BioFire® FilmArray® Blood Culture Identification Panel 1 (BF-FA-BCIP) identifies 24 pathogens directly from positive blood cultures without subculture. 3 resistance genes are included. We aimed to compare the time to optimal antibiotic therapy between BF-FA-BCIP and conventional identification.MethodsWe performed a single-center retrospective case-control before-after study of 386 cases (November 2018 to October 2019) with BF-FA-BCIP compared to 414 controls (August 2017 to July 2018) with conventional identification. The primary study endpoint was the time from blood sampling to implementation of optimal antimicrobial therapy. Secondary endpoints were time to effective therapy, length of hospital stay, and in-hospital and 30-day mortality. Outcomes were assessed using cause-specific Cox Proportional Hazard models and logistic regressions.ResultsWe included 800 patients with comparable baseline characteristics. Main sources of blood stream infection (BSI) were urinary tract infection and intra-abdominal infection (19.2% vs. 22.0% and 16.8% vs. 15.7% for case and control groups, respectively). Overall, 212 positive blood cultures were considered as contaminations. Identification results were available after a median of 21.9 hours by the BF-FA-BCIP and 44.3 hours by the conventional method. Patients with BF-FA-BCIP received the optimal therapy after a median of 25.5 hours (95%CI 21.0 - 31.2) as compared to 45.7 hours (95%CI 37.7 - 51.2) in the control group (Figure 1). We found no effect of the identification method on secondary outcomes.Kaplan-Meier curve representing the probability of implementing the optimal therapy at any given time according to the identification method (Standard vs. BF-FA-BCIP). Shaded ribbons represent the 95 % confidence interval (CI). The vertical dashes represent censored data. The vertical dotted lines represent the median time, i.e. the time at which 50 % of the patients obtained the optimal therapy, for the two methods. Median (95 % CI) time to optimal therapy is 45.7 (37.7 - 51.4) hours with the Standard method and 25.5 (21.0- 31.2) hours with Biofire. The tables below the curves present the numbers expecting optimal therapy according to the bacteria identification method, as well as the number of censored data in parenthesis. Panel A shows data from 0 to 900 hours. Panel B shows the data from 0 to 90 hours to better visualize how the probability to implement optimal therapy varies in the first 72 hours.ConclusionIn conclusion, rapid pathogen identification by BF-FA-BCIP was associated with an almost 24h earlier initiation of the optimal antibiotic therapy in BSI. However, the overall benefit for individual patients seems to be limited. Future studies should assess the cost-effectiveness and impact on the prevention of antibiotic resistance using this diagnostic approach.Disclosures All Authors: No reported disclosures

Antibiogram Profile of Bacteria Colonizing the Endotracheal Tubes (ETTs) of Patients Admitted to Intensive Care Units (ICUs) in a Tertiary Care Hospital of Nepal

Hospital acquired infection (HAI) in intensive care units (ICU) are responsible for high morbidities and mortalities worldwide due to emergence of resistant bacteria. In developing countries, due to lack of knowledge of proper surveillance, proper resources and proper guidance this burden was somewhat underestimated. Thus, the aim of this study was to look for the spectrum of bacteria colonizing the ETTs and to determine proper empirical antibiotic therapy. We collected endotracheal tube aspirates from 188 patients of admitted in ICU of Manipal Teaching Hospital, Pokhara. All bacteria were identified by conventional techniques. Antimicrobial sensitivity testing was performed on Mueller-Hinton agar plates with commercially available antibiotic discs using Kirby-Bauer disc diffusion techniques and interpreted as per the guidelines of CLSI. The antibiotic discs (conc.) used were: piperacillin/tazobactam (100/10mcg), ciprofloxacin (5mcg), amikacin (30mcg), imipenem (10mcg), gentamicin (10mcg), cefaperazone sulbactum(75/10mcg), for Gram negative bacteria and erythromycin (15mcg), amikacin (30mcg), gentamicin (10mcg), ciprofloxacin (5mcg), and clindamycin (2mcg) for Gram positive bacteria. A total of 188 ETTs investigated, 128(68.08%) yielded positive culture. Single type of organisms was found in 119 (63.29%) and 9 (4.7%) cases yielded mixed type of growth. Acinetobacter spp. were the most predominant organism among all gram-negative organisms, which was found to be in 71 (51.82%) cases, followed by Klebsiella pneumoniae in 27 (19.7%), Pseudomonas aeruginosa in 23 (16.78%), Escherichia coli in 5 (3.64%), Enterobacter in 2 (1.46%). Whereas, Staphylococcus aureus (4.37%) was the commonest among all gram-positive organism followed by coagulase negative Staphylococcus in 2 (1.46%) and Enterococcus in 1 (0.73%). Most of Acinetobacter spp. showed resistance to ciprofloxacin (84.5%), while 74.6% were resistant to amikacin, 73.2% to gentamicin, 71.83% to piperacillin-tazobactam and 42.2% towards imipenem. Out of the 6 strains of S. aureus, 5 (83.3%) were methicillin resistant. Due to the increasing incidence of organisms in ICUs, an early and correct diagnosis of ETT associated infections is a challenge for optimal antibiotic therapy. Therefore, the best approach to manage the respiratory infections following ETT application will be appropriate use of antibiotics with adaptation of proper infection control measures, which could help to prevent further spread of infection.

Simplified therapeutic guidelines: the main tool of antimicrobial stewardship programs associated with optimal antibiotic therapy.

Hospitals regularly seek to upgrade their antimicrobial stewardship program (ASP). Our aim was to evaluate the impact of simplified therapeutic guidelines (STGs) compared to various established tools for ASP on the rate of optimal antibiotic therapy (OAT) and antibiotic consumption. Audits of antibiotic prescriptions were carried out over a 24-month period. Feedback information led to STGs (e.g., ≤ 15 drugs). The impact of STGs was based on the rate of OAT, defined as a diagnosis of the infectious disease in the patient's medical records associated with the corresponding therapy indicated in the STGs or in other guidelines. STGs were compared to five other means of ASP: internal or national guidelines, audit, information regarding antibiotic consumption and bacterial resistance, and restricted access to targeted antibiotics. Antibiotic consumption was measured in defined daily doses/1000days of hospital stay, focusing on third-generation cephalosporins (TGC) and fluoroquinolones (FQ). Twenty-six hospitals were audited from April 2017 to June 2019. A total of 1,028 antibiotic prescriptions were analyzed, including 204 (20%) after STG implementation in seven hospitals. In multivariate analysis, OAT (n = 176, 17%) was associated with STGs, AOR 2.21 [1.51-3.22], and with three tools in place, 1.75 [1.24-2.48]. The relative variations of consumption of TGC and FQ for hospitals with or without STGs were - 13.1 vs. + 9.4% and - 18.5 vs. - 2.7%, respectively, from 2018 to 2019. STGs were more likely than other ASP tools to improve the rate of OAT and to reduce the consumption of antibiotics.

MICROBIOLOGICAL PROFILE, ANTIBIOTIC SENSITIVITY AND PROGNOSIS OF PATIENTS WITH FOURNIER’S GANGRENE: A PROSPECTIVE, HOSPITAL BASED STUDY FROM NORTH INDIA

Background: Fournier's gangrene (FG) is a devastating disease that is characterized by necrotizing fasciitis of the perineal, genital, or perianal region. Broad-spectrum antibiotics are the key component of its treatment. However, there is paucity of data regarding the optimal empirical antibiotic therapy for FG. Materials and Methods: Data from patients who underwent surgery for FG was retrieved from a prospectively collected departmental FG database. Demographics, clinical characteristics, causative pathogens and drug susceptibility/resistance were evaluated. Outcome was also assessed in terms of mortality. Results: Fifty patients with a median age of 58.5 (40-83) years were included. The perianal region and scrotum (88%) were the most commonly affected. Diabetes mellitus (DM) was the most common comorbidity (92%). The median time to onset of symptoms was 7 (2-15) days, and the median duration of hospital stay was 22 (4-65) days. Ventilator requirement was required in 15 (30%) patients. The median UFGSI score was 9.5 (3-15). The overall mortality rate was 26%. A positive growth was found in specimen cultures of 48 (96%) patients. The median number of bacterial strains that grew in the cultures was 3 (0-10). Amikacin was the antibiotic with the highest frequency of sensitivity (74%), while the highest resistance was observed against ampicillin-sulbactam (64%). Escherichia coli was the most common microorganism (68%). Acinetobacter baumannii and Klebsiella pneumonia were signicantly more common in patients who required mechanical ventilation. The mortality rate was 26%. An Uludag Fournier's Gangrene Severity Index (UFGSI) score of &gt; 9.5 and ventilatory support requirement were factors associated with an increased rate of mortality. Acinetobacter baumannii was the only microorganism which was associated with an increased mortality rate. Conclusion: Causative pathogens in FG appeared to be shifting; thus, empirical antibiotic treatment for this disease should be modied. We recommend 3rd-generation cephalosporin, metronidazole and amikacin for empirical therapy.

A new model to assist decision-making of optimal antibiotics duration for treating asymptomatic bacteriuria or pyuria prior to retrograde intrarenal surgery.

The aim of this study was to establish a model that predicts postoperative fever and enables decision-making regarding optimal antibiotic therapy duration for asymptomatic bacteriuria or pyuria prior to retrograde intrarenal surgery (RIRS). We retrospectively investigated 667 consecutive patients with asymptomatic bacteriuria or pyuria who underwent RIRS between September 2016 and December 2019. We constructed a predictive nomogram for risk quantification of postoperative infection. A preoperative score model was used for risk stratification. The effect of antibiotic therapy duration (short-course [2-3 days] vs. long-course [≥4 days]) was evaluated. Infections occurred in 113 (16.9%) patients. The incidence of fever was marginally lower in long-course group than in short-course group (15% vs. 19%, P=0.173). Hydronephrosis, stone size, multi-drug resistant bacteriuria, and degree of pyuria were used to construct a preoperative score model (the H-SMP score). Using the H-SMP score, the patients were stratified into low- and high-risk groups based on varying incidence rates of postoperative fever (11.0% vs. 29.9%, P<0.001). Significant reduction in fever occurred only among high-risk patients in the long-course group (23.5% vs. 38.0%, P=0.022), and no such reduction in postoperative fever rates occurred in low-risk patients (10.4% vs. 11.5%, P=0.712). Even after propensity score matching, the low-risk group showed no improvement in postoperative fever incidence with long-course antibiotic therapy (7.5% vs. 10.0%, P=0.419). Based on the newly developed H-SMP score, we concluded that long-course antibiotics (≥4 days) recommended in high-risk patients may not bring in more benefit in low-risk patients for treating asymptomatic bacteriuria or pyuria prior to RIRS.

Association of Penicillin or Cephalosporin Allergy Documentation and Antibiotic Use in Hospitalized Patients with Pneumonia

Treatment guidelines for pneumonia recommend beta-lactam antibiotic-based therapy. Although reported penicillin allergy is common, more than 90% of patients with reported penicillin allergy are not allergic. We evaluated the association of a documented penicillin and/or cephalosporin (P/C) allergy to antibiotic use for the treatment of inpatient pneumonia. This was a national cross-sectional study conducted among Vizient, Inc., network hospitals that voluntarily contributed data. Among hospitalized patients with pneumonia, we examined the relation of a documented P/C allergy in the electronic health record to prevalence of first-line beta-lactam antibiotic administration and alternative antibiotics using multivariable log-binomial regression with generalized estimating equations. Of 2,276 inpatients receiving antibiotics for pneumonia at 95 U.S. hospitals, 450 (20%) had a documented P/C allergy. Compared with pneumonia patients without a documented P/C allergy, patients with a documented P/C allergy had reduced prevalence of first-line beta-lactam antibiotic use (adjusted prevalence ratio [aPR] 0.79; 95% confidence interval [95% CI] 0.69-0.89]). Patients with high-risk P/C reactions (n= 91) had even lower prevalence of first-line beta-lactam antibiotic use (aPR 0.47; 95% CI 0.35-0.64). Alternative antibiotics associated with a higher use in pneumonia patients with a documented P/C allergy included carbapenems (aPR 1.61; 95% CI 1.22-2.13) and fluoroquinolones (aPR 1.52; 95% CI 1.21-1.91). Inpatients with documented P/C allergy and pneumonia were less likely to receive recommended beta-lactams and more likely to receive carbapenems and fluoroquinolones. Inpatient allergy assessment may improve optimal antibiotic therapy for the 20% of inpatients with pneumonia and a documented P/C allergy.