Beta-lactam Agents Research Articles

Nationwide analysis of antimicrobial prescription in Korean hospitals between 2018 and 2021: The 2023 KONAS report

Background: Data on antimicrobial use at the national level is crucial to establish domestic antimicrobial stewardship policies and enable medical institutions to benchmark against each other. This study aimed to analyze antimicrobial use in Korean hospitals. Methods: We investigated the antimicrobials prescribed in Korean hospitals between 2018 and 2021, using data from the Health Insurance Review and Assessment. Primary care hospitals (PCHs), secondary care hospitals (SCHs), and tertiary care hospitals (TCHs) were included in this analysis. Antimicrobials were categorized according to the Korea National Antimicrobial Use Analysis System (KONAS) classification, which is suitable for measuring antimicrobial use in Korean hospitals. Results: Out of more than 1,900 hospitals, PCHs and TCHs represented the largest and lowest percentage of hospitals, respectively. The most frequently prescribed antimicrobial in 2021 was piperacillin/β-lactamase inhibitor (9.3%) in TCHs, ceftriaxone (11.0%) in SCHs, and cefazedone (18.9%) in PCHs. Between 2018 and 2021, the most used antimicrobial class according to the KONAS classification was ‘broad-spectrum antibacterial agents predominantly used for community-acquired infections’ in TCHs and SCHs, and 'narrow spectrum beta-lactam agents' in PCH. Total consumption of antimicrobials has decreased from 951.7 to 929.9 days of therapy (DOT)/1,000 patient-days in TCHs and from 817.8 to 752.2 DOT/1,000 patient-days in SCHs during study period, but not in PCHs (from 504.3 to 527.2 DOT/1,000 patient-days). Moreover, in 2021, while use of reserve antimicrobials has decreased from 13.6 to 10.7 DOT/1,000 patient-days in TCHs and from 4.6 to 3.3 DOT/1,000 patient-days in SCHs, it has increased from 0.7 to 0.8 DOT/1,000 patient-days in PCHs. Conclusion: This study confirms that antimicrobial use differs by hospital type in Korea. Recent increases of use of antimicrobials, including reserve antimicrobials, in PCHs reflect the challenges that must be addressed.

Uncut Gemella Haemolysans: A Case of Bacteremia with No Clear Entry Site

Background: Gemella haemolysans is a gram-positive coccus that colonizes the genitourinary system, gastrointestinal system, and upper respiratory tract as an opportunistic pathogen. Berge et al. found that the frequency of Gemella species bacteremia was 4.5 and infective endocarditis was 0.31 per 1,000,000 inhabitants yearly. We report the first case of G. haemolysans bacteremia presenting as new-onset atrial fibrillation with rapid ventricular response (RVR) and acute respiratory failure and present a case series on G. haemolysans bacteremia and infective endocarditis. Case Presentation: A 58-year-old male with a past medical history including aortic valve bioprosthetic replacement, type 2 diabetes, hypertension, and coronary artery stenting and bypass surgery presented with shortness of breath and confusion. Examination and testing revealed a 40.4°C fever, acute respiratory failure, atrial fibrillation with RVR, congestive heart failure, lactic acidosis, and acute renal failure, with no drug use, dental wounds, or pneumonia. Diltiazem, metoprolol, aspirin, atorvastatin, insulin, heparin, and ceftriaxone were started. TTE and TEE revealed no clear vegetations. Blood cultures revealed Gemella haemolysans. He became stable after 4 days, was electrically cardioverted to sinus rhythm with first-degree AV block, progressed to complete heart block, then had a temporary pacer placed. A repeat TEE demonstrated an aortic root abscess. He underwent redo sternotomy and homograft placement with no complications and was discharged with instructions to complete a six-week course of ceftriaxone. Discussion: Our patient presented with multiple comorbidities at a younger age compared to the mean (66) and median (70) age of the 4 bacteremia cases in our 8-case series. Preemptive antibiotic treatment may be warranted for prosthetic heart valve patients, with the possibility of urgent valve replacement surgery. Several antibiotics were previously reported in case studies with varying results. The shortest course was 16 days, with most courses lasting 4 to 7 weeks. With no standard treatment, this case series suggests G. haemolysans tends to be susceptible to beta-lactam agents. Conclusion: Our case highlights the importance of a multidisciplinary approach in the diagnosis and management of Gemella haemolysans bacteremia, particularly in patients with complex medical histories and prosthetic heart valves.

Imipenem/Cilastatin/Relebactam for Complicated Infections: A Real-World Evidence.

(1) Background: Infections caused by multidrug-resistant (MDR) bacteria represent one of the major global public health problems of the 21st century. Beta-lactam antibacterial agents are commonly used to treat infections due to Gram-negative pathogens. New β-lactam/β-lactamase inhibitor combinations are urgently needed. Combining relebactam (REL) with imipenem (IMI) and cilastatin (CS) can restore its activity against many imipenem-nonsusceptible Gram-negative pathogens. (2) Methods: we performed a systematic review of the studies reporting on the use of in vivo REAL/IPM/CS. (3) Results: A total of eight studies were included in this review. The primary diagnosis was as follows: complicated urinary tract infection (n = 234), complicated intra-abdominal infections (n = 220), hospital-acquired pneumonia (n = 276), and ventilator-associated pneumonia (n = 157). Patients with normal renal function received REL/IPM/CS (250 mg/500 mg/500 mg). The most frequently reported AEs occurring in patients treated with imipenem/cilastatin plus REL/IPM/CS were nausea (11.5%), diarrhea (9.8%), vomiting (9.8%), and infusion site disorders (4.0%). Treatment outcomes in these high-risk patients receiving REL/IPM/CS were generally favorable. A total of 70.6% of patients treated with REL/IPM/CS reported a favorable clinical response at follow-up. (4) Conclusions: this review indicates that REL/IPM/CS is active against important MDR Gram-negative organisms.

Nationwide Analysis of Antimicrobial Prescription in Korean Hospitals between 2018 and 2021: The 2023 KONAS Report.

Data on antimicrobial use at the national level are crucial for establishing domestic antimicrobial stewardship policies and enabling medical institutions to benchmark each other. This study aimed to analyze antimicrobial use in Korean hospitals. We investigated antimicrobials prescribed in Korean hospitals between 2018 and 2021 using data from the Health Insurance Review and Assessment. Primary care hospitals (PCHs), secondary care hospitals (SCHs), and tertiary care hospitals (TCHs) were included in this analysis. Antimicrobials were categorized according to the Korea National Antimicrobial Use Analysis System (KONAS) classification, which is suitable for measuring antimicrobial use in Korean hospitals. Among over 1,900 hospitals, PCHs constituted the highest proportion, whereas TCHs had the lowest representation. The most frequently prescribed antimicrobials in 2021 were piperacillin/β-lactamase inhibitor (9.3%) in TCHs, ceftriaxone (11.0%) in SCHs, and cefazedone (18.9%) in PCHs. Between 2018 and 2021, the most used antimicrobial classes according to the KONAS classification were 'broad-spectrum antibacterial agents predominantly used for community-acquired infections' in SCHs and TCHs and 'narrow spectrum beta-lactam agents' in PCHs. Total consumption of antimicrobials decreased from 951.7 to 929.9 days of therapy (DOT)/1,000 patient-days in TCHs and 817.8 to 752.2 DOT/1,000 patient-days in SCHs during study period; however, no reduction was noted in PCHs (from 504.3 to 527.2 DOT/1,000 patient-days). Moreover, in 2021, the use of reserve antimicrobials decreased from 13.6 to 10.7 DOT/1,000 patient-days in TCHs and from 4.6 to 3.3 DOT/1,000 patient-days in SCHs. However, in PCHs, the use increased from 0.7 to 0.8 DOT/1,000 patient-days. This study confirmed that antimicrobial use differed according to hospital type in Korea. Recent increases in the use of total and reserve antimicrobials in PCHs reflect the challenges that must be addressed.

Systematic Review of Carbapenem Resistant Gram-negative Infective Endocarditis, Treatment Options and Outcomes

Background: Gram negative infective endocarditis is rare and usually associated with intravenous drug use or significant healthcare exposure and prosthetic cardiac valves or devices. Carbapenem resistance is a growing concern worldwide with limited drug options for these infections especially serious high inoculum infections such as endocarditis.
 Methods: A systematic review examining treatment options and outcomes was conducted with identification of 12 cases in the literature.
 Results: Pseudomonas aeruginosa was the most common organism with left sided valvular involvement being most common. 18 different antibiotic regimens were used with surgery occurring in 5 cases (42%). In hospital mortality was 33% which increased at 6 months post episode. Increased age (p= 0.056) and CCI (p=0.006) appeared to be associated with death. Microbiological cure was more common in patients who received combination therapy with 2 active agents (75% successful) and combination therapy including an active beta-lactam agent (100% successful) but these did not meet statistical significance.
 Conclusions: Recommendations for management of this rare condition based on this systematic review and other available evidence are summarised in this review. Management should generally involve multidisciplinary teams, combination therapy with at least 2 active agents including a beta-lactam agent where possible with consideration of surgery in all cases. Evidence is however limited with need for ongoing publication of cases and further research to guide therapy in the future.

193. Standard of Care versus Alternative Beta-lactams for Treatment of Infections due to Serratia marcescens

Abstract Background The threat of inducible resistance and treatment failure positioned cefepime and carbapenems as the standard of care (SOC) treatment agents for infections due to AmpC-producing Enterobacterales regardless of antimicrobial susceptibility testing results. Recently published Infectious Diseases Society of America Guidance (IDSA) classifies the overall risk of clinically relevant AmpC expression for Serratia marcescens as low (< 5%). We aimed to compare the clinical outcomes of patients treated with a SOC antibiotic (carbapenem or cefepime) to those treated with an alternative beta-lactam agent for S. marcescens bloodstream infection (BSI). Methods This multisite, retrospective study included patients from five hospitals in the Atlanta-Metropolitan area with S. marcescens BSIs between January 1, 2018 and December 31, 2022. Patients were included if they received at least 72 hours of therapy with a beta-lactam antibiotic whose in vitro susceptibility was confirmed. Patients with polymicrobial bacteremia, those receiving combination therapy for > 72 hours, or those with a diagnosis of endovascular infection were excluded. We used a desirability of outcome ranking (DOOR) analysis to determine the probability of having a more desirable outcome receiving SOC antibiotics compared to receiving an alternative beta-lactam agent. The DOOR analysis includes counting undesirable events (Figure 1) and was performed using an online calculator (https://methods.bsc.gwu.edu).Figure 1:Primary endpoint - Desirability of outcome ranking. Abbreviations: AKI = acute kidney injury; CDI = Clostridioides difficile infection; EMR = electronic medical record; SCr = serum creatinine Results Of the 175 S. marcescens blood cultures reviewed, 66 patients met criteria for study inclusion, 43 in the SOC group and 23 in the alternative group. Baseline characteristics were comparable in both groups (Figure 2). The DOOR distribution between treatment groups was similar (Figure 3) and there was no significant difference in the probability of a more desirable outcome for patients who received an alternative beta-lactam compared to SOC (54.2% [95% CI, 40.3 - 67.5%]; Figure 4).Figure 2:Baseline patient characteristics. Abbreviations: BMT = bone marrow transplant within previous 12 months; Corticosteroid = ≥15 mg prednisolone daily equivalents; HIV = human immunodeficiency virus; ICU = intensive care unit; IQR = interquartile range; NS = non-significant; SOC = standard of care; SOT = any history of solid organ transplantFigure 3:Desirability of Outcome Ranking Distribution Summary Desirability of outcome ranking distribution for the standard of care and alternative beta-lactam treatment groups; SOC = standard of careFigure 4:Desirability of Outcome Ranking Probability Summary Forest plot of desirability of outcome ranking probabilities by overall treatment group and individual ranking components; CI = confidence interval, DOOR = desirability of outcome ranking, SOC = standard of care Conclusion The overall outcome of patients receiving alternative beta-lactam antibiotics was similar to those receiving SOC antibiotics in this study. These results support use of alternative beta-lactams for treatment of susceptible S. marcescens BSIs as recommended by IDSA guidance. Disclosures Joseph Torrisi, PharmD, BCIDP, Clinical Care Operations: Honoraria Ahmed Babiker, MBBS, Roche: Advisor/Consultant

1253. Optimization of empiric gram-negative infections with the combination antibiogram

Abstract Background Anti-pseudomonal beta-lactam drugs such as aztreonam (AZR), cefepime (CEF), piperacillin-tazobactam (P/T), meropenem (MER) are drugs used for empiric gram-negative (GN) infections. They are used with other drugs as empiric combination therapy (CT) for patients with sepsis. The antibiogram is used to provide data for empiric therapy and gauge susceptibility pattern shifts over time. Combining different classes of drugs might enhance the susceptibility to various pathogens. This project assessed which empiric combination of drugs will yield optimal coverage for various GN pathogens from different sources. Methods In 2022 antimicrobial susceptibility data from 8288 isolates from blood, respiratory, wound and urine sources were collected and analyzed. Percent susceptibility was calculated for 11 gram-negative species with >30 isolates. Susceptibility testing was done by BD Phoenix™ automated identification and susceptibility testing system. A threshold of >90% susceptibility was used to indicate optimal coverage for the antimicrobial agents. CT is calculated as the % susceptible to either of two antibiotics. Results In respiratory sources AZR, CEF and P/T were the lowest at 73%, 83% and 77% susceptible. MER had the best overall coverage for all specimen types. Adding either an aminoglycoside (AG) or fluoroquinolone (FQ) increased susceptibility in all sources. AGs had a slightly better coverage than FQs. For blood isolates > 90% susceptibility was attained for single antibiotics without combination. CT was often required to achieve optimal coverage for respiratory sources, specifically for Pseudomonas, Enterobacter, E coli, Klebsiella and Proteus species.Figure 1.Combination antibiogram for beta-lactam agents for gram-negative respiratory isolates as monotherapy or in combination with ciprofloxacin, gentamicin, or tobramycin.*All gram-negative isolates included Serratia and Providencia species that were not included in the subgroups. Conclusion Using > 90% susceptibility as cut-off, monotherapy AZR and P/T are suboptimal for empiric coverage for certain GN respiratory infections. Blood specimens may not require CT. Adding either AGs or FQs enhanced susceptibility coverage to all tested pathogens but not uniformly. AGs enhancement was slightly better than FQs. Respiratory infections with Pseudomonas, Enterobacter cloacae, E coli, Proteus and Klebsiella species all showed enhanced coverage with CT especially for P/T and AZR. Every hospital should create a combination antibiogram to gain insight into whether empiric coverage with CT is needed. Disclosures All Authors: No reported disclosures

189. Outcomes of High-dose Oral Beta-lactam Step-down Therapy Compared to Alternative Oral Therapy for Bacteremic Urinary Tract Infections

Abstract Background Pyelonephritis and associated bacteremia are often treated with intravenous antibiotics followed by oral step-down therapy to a fluoroquinolone (FQ) or trimethoprim/sulfamethoxazole (TMP/SMX). Oral beta-lactams were historically utilized less often due to concern for treatment failure. Literature suggests oral beta-lactams are effective, but there are no preferred oral beta-lactam agents or dosing recommendations. This study evaluates outcomes of high-dose oral beta-lactam therapy for Enterobacterales bacteremia due to a urinary tract infection (UTI) compared to alternative therapy. Methods A retrospective, multicenter, observational cohort study was conducted evaluating patients admitted from February 1, 2020, to October 1, 2022, with gram-negative bacteremia from a urinary source. Adult patients were included if they received empiric intravenous antibiotic active against the bacteria isolated and transitioned to appropriately dosed oral cephalexin, amoxicillin, TMP/SMX, or FQ (Table 1). Excluded were patients who received less than 72 hours of oral therapy, had a diagnosis of renal abscess or lobar nephronia, and those who expired during admission. The primary outcome compared the composite of recurrent bacteremia or mortality within 30 days of completing oral therapy. Secondary outcomes included recurrent UTI, emergency department (ED) or hospital readmission, and Clostridioides difficile infections within 30 days of treatment completion. Results There were 194 patients who met inclusion criteria. The primary outcome occurred in 1/75 (1.3%) patients in the oral beta-lactam group and 2/119 (1.7%) patients in the FQ or TMP/SMX group (p=1.0). Two patients in the FQ or TMP/SMX expired within 30 days and 1 patient in the beta-lactam group had a recurrent bacteremia. There were 16 (21.3%) and 14 (11.8%) patients in the beta-lactam and FQ or TMP/SMX group, respectively, treated for recurrent UTI (p=0.073). Twenty (27%) patients in the beta-lactam group required ED re-evaluation or hospital readmission compared to 30 (25%) patients who received a FQ or TMP/SMX (p=0.74). Zero patients had a Clostridioides difficile infection. Conclusion Oral beta-lactams are as effective as oral FQ and TMP/SMX for the treatment of bacteremia from a urinary source. Disclosures All Authors: No reported disclosures

Use of a beta-lactam graded challenge process for inpatients with self-reported penicillin allergies at an academic medical center.

The Antimicrobial Stewardship Program (ASP) at Nebraska Medicine collaborated with a board-certified allergist to develop a penicillin allergy guidance document for treating inpatients with self-reported allergy. This guidance contains an algorithm for evaluating and safely challenging penicillin-allergic patients with beta-lactams without inpatient allergy consults being available. Following multi-disciplinary review, an order set for beta-lactam graded challenges (GC) was implemented in 2018. This contains recommended monitoring and detailed medication orders to challenge patients with various beta-lactam agents. Inpatient orders for GC from 3/2018-6/2022 were retrospectively reviewed to evaluate ordering characteristics, outcomes of the challenge, and whether documentation of the allergy history was updated. All beta-lactam challenges administered to inpatients were included, and descriptive statistics were performed. Overall, 157 GC were administered; 13 with oral amoxicillin and 144 with intravenous (IV) beta-lactams. Ceftriaxone accounted for the most challenges (43%). All oral challenges were recommended by an Infectious Diseases consult service, as were a majority of IV challenges (60%). Less than one in five were administered in an ICU (19%). Almost all (n = 150, 96%) were tolerated without any adverse event. There was one reaction (1%) of hives and six (4%) involving a rash, none of which had persistent effects. Allergy information was updated in the electronic health record after 92% of the challenges. Both intravenous and oral beta-lactam graded challenges were implemented successfully in a hospital without a regular inpatient allergy consult service. They were well-tolerated, administered primarily in non-ICU settings, and were often ordered by non-specialist services. In patients with a self-reported penicillin allergy, these results demonstrate the utility and safety of a broadly adopted beta-lactam GC process.

Efficacy of a Pharmacy Resident-Driven Beta-Lactam Allergy Assessment at a Community Hospital

Abstract Background Beta-lactams are the most commonly used antibiotics, although they are also associated with hypersensitivity reactions. Although approximately 10% of the population report an allergy to a beta-lactam, identifying erroneous beta-lactam allergies can lead to improved patient outcomes and lower rates of antimicrobial resistance. Methods This study was a single-center, retrospective review of a pharmacy resident driven beta-lactam allergy assessment. The allergy assessment consisted of a chart review and a 3-question interview. The primary outcome of this study was a composite of the following interventions: beta-lactam allergy delabeling, reaction specification, and/or identification of previously tolerated beta-lactams. Secondary outcomes included patients who were relabeled if delabeling occurred, patients who received beta-lactam therapy after changes occurred to their charted allergy, and impact on hospital utilization of beta-lactam alternative antibiotics. Results A total of 42 patients were interviewed between September 13, 2021, and December 17, 2021, with follow-up occurring 90 days after the initial interview. The most common beta-lactam allergy reported was penicillin (90.5%). Of the patients who were assessed, 95.2% met at least one of the components of the primary endpoint. Specifying the previous toleration of beta-lactam agents was the most common intervention, occurring after 78.6% of assessments. Complete delabeling of the patient's beta-lactam allergy occurred after 38.1% of the interviews conducted. Conclusions A pharmacy-resident driven beta-lactam allergy assessment was effective at clarifying beta-lactam allergies, including the complete delabeling of erroneous beta-lactam allergies.

Antibiotic-Induced Neutropenia in Patients Receiving Outpatient Parenteral Antibiotic Therapy: a Retrospective Cohort Study.

Our research objective was to describe the incidence and management of antibiotic-induced neutropenia in patients receiving outpatient parenteral antibiotic therapy (OPAT) at our institution over a 7-year period. We conducted a retrospective cohort study of patients followed by the OPAT clinic from 1 July 2016 to 30 March 2022 who developed antibiotic-induced neutropenia (defined as an absolute neutrophil count of ≤1.5 × 109/L). Patients receiving vancomycin in the OPAT clinic received weekly laboratory monitoring, while those receiving other antibiotics received laboratory monitoring at week 3 of therapy. Out of the 2,513 treatment courses, 55 cases of antibiotic-induced neutropenia were identified, resulting in an incidence of 2.2 cases per 100 treatment courses (95% confidence interval [CI], 1.7 to 2.9). Of the 45 cases for which a sole cause was identified, the three most common intravenous antibiotic culprits were vancomycin (21/541; 3.9%), ceftriaxone (10/490; 2.0%), and cloxacillin (2/103; 1.9%). Five (9.1%) patients had symptoms accompanying neutropenia that warranted hospital admission. There were no deaths, and all patients recovered their neutrophil count after antibiotic discontinuation or completion. In nine cases (16.3%), the culprit beta-lactam antibiotic was changed to another beta-lactam agent containing a structurally different side chain, with successful recovery of the neutrophil count in 9/9 (100%). The highest risk of antibiotic-induced neutropenia was associated with vancomycin, ceftriaxone, and cloxacillin in our cohort. With standardized outpatient monitoring during the third week of OPAT, cases of neutropenia can be detected early and managed without hospitalization. Data from our study also support the safety of switching to alternate beta-lactams with structurally different side chains.

Analysis of Changes in Antibiotic Use Patterns in Korean Hospitals during the COVID-19 Pandemic

With the onset of the coronavirus disease 2019 (COVID-19) pandemic, changes in patient care and antibiotic use have occurred in hospitals. The data of the National Health Insurance System's claims of inpatients from all hospitals in Korea between January 2019 and December 2020 were obtained from the Health Insurance Review & Assessment Service and analyzed. The trend in the use of all antibacterial agents in both hospitals declined for the total number of COVID-19 patients at the bottom 10% and those in the top 10%. Specifically, a decreasing trend in the use of broad-spectrum antibacterial agents predominantly prescribed for community-acquired cases and narrow-spectrum beta-lactam agents were observed in both hospitals. In the aftermath of the COVID-19 pandemic, the total use of antibacterial agents has gradually decreased among patients with pneumonia and those with severe COVID-19. In contrast, its use has increased gradually among those with mild to moderate COVID-19. A decreasing trend in overall antibiotic use was observed during the COVID-19 pandemic, and an increasing trend in antibiotic use was observed in patients with mild to moderate COVID-19 in Korean hospitals.

891. Challenging the Dogma of Beta-Lactam Allergies: Impact of an Antimicrobial Stewardship Program

Abstract Background Penicillin allergies are reported in approximately 10% of patients in the US but ∼90% of these allergies can be de-labeled. Consequences of inappropriate allergy labeling leads to use of alternative agents associated with increased adverse events and resistance rates, leading to worse outcomes. Though all beta-lactam agents share the core beta-lactam ring, the R1 side chain has been identified as the focus of cross-reactivity. Agents that do not share the same or similar R1 side chain are likely to have negligible risk of hypersensitivity reactions. The purpose of this study was to assess the incidence of hypersensitivity reactions in patients with a documented beta-lactam allergy that received a beta-lactam agent with a different side chain based on recommendation by an antimicrobial stewardship clinical pharmacist. Methods This was a retrospective, single-center, observational study of patients admitted to NYU Langone Hospital – Long Island from October 2019 to February 2022. Data was collected by review of the electronic medical record and descriptive statistics were generated as appropriate. The primary outcome was the proportion of patients that experienced a hypersensitivity reaction to a beta-lactam agent with a different side chain. Secondary outcomes included impact of antimicrobial stewardship intervention by clinical pharmacists, avoidance of alternative antibiotics, and cost comparison between agents requested and recommended. Results A total of 181 patients were included in the final analysis, including 37 patients with a history of anaphylaxis. No patients with a documented beta-lactam allergy experienced a hypersensitivity reaction upon receiving a beta-lactam agent with a different side chain. Within the cost comparison, meropenem accounted for 45.6% and 75.9% of the total minimum and maximum wholesale costs of requested agents, respectively. Conclusion The results of this study suggest that receipt of a beta-lactam agent with a different side chain is safe in patients with a history of beta-lactam allergy, including anaphylaxis history, and supports 'in the moment' antimicrobial stewardship intervention to ensure patients receive optimal therapy when access to in-depth allergy history or detailed patient interview is not feasible. Disclosures All Authors: No reported disclosures.

423. Molecular Epidemiology of ESBL E. coli Over a 2 Year Period in Worcester Massachusetts USA

Abstract Background Extended-spectrum beta-lactamase (ESBL) producing Escherichia coli are an increasing health burden contributing to a pandemic of resistant bacteria. Methods To better understand the population genomics of ESBL E. coli, 129 phenotypically identified ESBL isolates collected between 2017-04 to 2018-11 from a single academic medical center underwent whole genome sequencing with the presence of antibiotic resistance genes identified by screening against the CARD database. The odds of phenotypic resistance to beta-lactam agents were calculated for each known resistance gene. A novel approach based on k-mer-enrichment among antibiotic resistance gene groups was developed to predict genes associated with phenotypic resistance. Results Genomic analysis revealed that 60% of the ESBL isolates collected were pandemic strain ST131. All isolates contained at least 1 gene in the beta-lactamase family with a median of 3 different beta-lactamase genes being present. Ninety-five percent of isolates contained a CTX-M gene with 52% CTX-M-15, 43% CTX-M-27, 5% other CTX-M; 24% had OXA and 34% had TEM. The presence of CTX-M-15 significantly increased the odds of resistance to ampicillin-sulbactam (95% confidence interval 5.9-116.5, p-value < 1e-7), ceftazidime (4.2-25.9, p< 1e-6) and cefepime (3.6-20.1, p< 1e-5) but not to piperacillin-tazobactam (0.9-6.3, p 1). CTX-M-27 decreased the odds of resistance to these 4 beta-lactams (0.003-0.07, p< 1e-13; 0.04-0.3, p< 1e-05; 0.06-0.4, p< 0.001; 0.03-0.6, p 0.11). TEM-1 significantly increased the odds for ampicillin-sulbactam resistance (3.8-1036.7, p< 1e-3) but not for other beta-lactams. Our de novo sequence approach was able to identify the known genes listed above and also identified a 683 bp open reading frame with unknown function that had increased odds of resistance to piperacillin-tazobactam resistance (2.1-43.6, p< 1e-3). This 683 bp open reading frame did not share any homology with known beta-lactamases. Conclusion The majority of phenotypic ESBL isolates contain multiple beta-lactamase genes. The presence of CTX-M-15 appears to increase the odds of resistance to key beta-lactam agents. Our novel k-mer-enrichment approach identified a novel marker of piperacillin-tazobactam resistance. Disclosures All Authors: No reported disclosures.

1776. Overcoming barriers and expanding an existing Antimicrobial Stewardship Program: Allergy Collaboration to de-label Penicillin allergy

Abstract Background The pandemic placed barriers to face-face visits and repurposed Antimicrobial Stewards. During the pandemic, our existing Antimicrobial Stewardship Program: Allergy PCN or beta-lactam de-labeling program (PDLP) collaborated with a medical center within our network to adopt an existing EMR-based screening tool and CDSS tracking system to overcome barriers. Methods Between April 2021-March 2022 we expanded our PDLP by off-loading the workload through EMR beta-lactam assessment (BLA) notes targeting inpatient PharmDs. The ability to de-label was expanded by ‘chart’ delabeling using a BLA note template adopted from the Memphis VAMC. The BLA allowed historical allergy (duration, tolerability of other beta-lactams) or drug-related side effect to be challenged. Referrals to allergy were identified using the BLA; ASP Pharmacists conducted PharmD training and fielded referrals to either de-label with BLA vs PCN testing. BLA notes were tracked over time in CDSS (TheraDoc, DSS Inc) and after evaluation, the EMR was updated to reflect PCN allergy status post-assessment. Results Over one year the new BLA note was used in 113 patients; assessments were completed by the targeted audience (Inpatient Medicine PharmD) by the 3rd month of the adoption period; subsequently BLA use increased 180% compared to the 3 month lead-in period. BLAs gave inpatient providers guidance on drug selection, referral for formal PCN-testing or Pharmacist/Allergy review, a “chart only” de-label . With pandemic constraints few patients (17/113, 15%) were referred for skin testing with 65% of those successfully de-labeled. Among those not requiring PCN testing, when EMR records demonstrating tolerability to other beta-lactam agents, non-allergic reactions were clarified and/or patients were well enough during the hospital stay to provide accurate historical information nearly a third of those patients (19/66, 29%) were successfully de-labeled. Conclusion The pandemic provided clinical barriers, however we successfully adopted an EMR-based BLA tool. Engagement and buy-in from providers resulted in chart documentation and allergy de-labeling. Allergy working with ASPs can leverage both EMR and CDSS tools to de-label allergies to beta-lactams. Disclosures All Authors: No reported disclosures.

1806. The gap in the amount of monthly antimicrobial use according to the data source: Electronic Health Record Data vs. National Health Insurance Claim Data in Korea

Abstract Background Korea has single health insurance system and insurance claim information on almost all medical practices in Korean hospitals is collected and processed by the Health Insurance Review and Assessment Service (HIRA). Since information about prescription of almost all hospitals is available in National Health Insurance (NHI) claim data, recently established the Korea National Antimicrobial Use Analysis System (KONAS) has been using NHI claim data as data source. The purpose of this study is to validate the accuracy of NHI claim data. Methods Data on all antimicrobial agents prescribed in four tertiary-care hospitals in Korea between January 2019 and December 2019 were obtained using NHI claim data extracted by HIRA and data extracted by common data model based on electronic health record (EHR) in each hospital. Antibiotics and antifungal agents according to the Anatomical Therapeutic Chemical class J01 and J02 were included while antiviral, antitubercular, antiparasitic, and topical antimicrobial agents were excluded. Antimicrobial consumption was measured as days of therapy (DOT) and standardized to per 1,000 patient-days. The ratio of monthly antimicrobial consumption calculated using the NHI claim data compared to that calculated using the common data model was demonstrated (HIRA/EHR ratio). Results The monthly HIRA/EHR ratio of broad-spectrum antibiotics predominantly used for hospital-onset infections was 1.08-1.12 and that of broad-spectrum antibiotics predominantly used for community-acquired infections was 1.11-1.21. The monthly HIRA/EHR ratio of other antimicrobial classes are as follows: antibacterial agents predominantly used for resistant gram-positive infections 1.15-1.31, narrow-spectrum beta-lactam agents 1.00-1.05, antifungal agents predominantly used for invasive candidiasis 1.00-1.27, and antibacterial agents predominantly used for extensive antibiotic-resistant gram-negative bacteria 0.70-1.09. Conclusion The monthly antimicrobial consumption calculated using NHI claim data differs from that calculated using EHR data by up to 30%. It would be desirable to establish a system that can analyze and monitor antimicrobial consumption using EHR data in each hospital in Korea in the future. Disclosures Hyunki Woo, BS, Evidnet Inc.: Employee changhui Kim, BS, Evidnet Inc.: Employee.

Genetic Diversity of Escherichia coli Coharboring mcr-1 and Extended Spectrum Beta-Lactamases from Poultry

Background The emergence of resistance to beta-lactam agents in poultry results in multidrug-resistant (MDR) phenotypes in Escherichia coli isolates from poultry birds. The appearance of mobile colistin resistance (mcr) genes in the poultry sector has further worsened the situation. Therefore, the current study is aimed at investigating the molecular epidemiology of mcr harboring colistin-resistant E. coli among poultry. Methods The isolation and identification of colistin-resistant E. coli (CR-Ec) were done from the broiler's fecal samples through culturing using selective media supplemented with colistin sulfate (4 μg/ml). The antibiogram studies of the isolates were performed using the disc diffusion method and broth microdilution method as per CLSI guidelines. The screening for the genes conferring resistance to colistin as well as beta-lactam agents was performed by PCR. The genetic diversity of mcr-positive strains was assessed by multilocus sequencing typing (MLST). Results Out of 500 fecal samples, 7% (35/500) were found positive for the presence of colistin-resistant E. coli (CR-Ec). Among the CR-Ec isolates, 74.28% (26/35) were detected as ESBL producers carrying the blaCTX-M-1 gene in 15/35 (42.85%) isolates and blaCTX-M-15 and blaTEM genes in 21/35 (60%) and 35/35 (100%) isolates, respectively. E. coli isolates were found positive for the presence of mcr-1, although none of the isolates exhibited the mcr-2 or mcr-3 genes. The MLST of CR-Ec has shown the ST1035 as the most prevalent genotype, while 82.85% (29/35) of CR-Ec strains belonged to clonal complex (CC) 131 comprising ST1035, ST131, ST1215, ST1650, and ST2279. Conclusions The findings suggest a continuous monitoring system in veterinary and clinical settings to avoid unnecessary antibiotics. Further studies are needed at the national level to help control the increasing resistance among Enterobacterales in poultry settings.

Comparative susceptibility of Gemella morbillorum to 13 antimicrobial agents

The in vitro activity of 13 antimicrobials against clinical isolates of Gemella morbillorum showed good susceptibility to clindamycin, all beta-lactams agents studied except cefoxitin (MIC90, 4 μg/ml) and fluoroquinolones. There was 36% metronidazole resistance.

SITUATION OF DRUG ALLERGY AT HUE UNIVERSITY OF MEDICINE AND PHARMACY HOSPITAL

Background: Drug allergy is an immunosensitivity-mediated hypersensitivity reaction. Allergic reactions range from mild itching, skin rashes to severe, life-threatening cases such as anaphylaxis, Stevens-Johnson syndrome, and toxic epidermal necrolysis syndrome... Monitoring and timely management of drug allergic reactions plays an important role in ensuring patient safety. Objectives: (1) To investigate drugs that caused drug allergy at Hue University of Medicine and Pharmacy Hospital; (2) To analyze drug allergic reactions at Hue University of Medicine and Pharmacy Hospital. Materials and methods: 90 reports of adverse drug reations belonging to the type of drug allergic reaction at Hue University of Medicine and Pharmacy Hospital in the period of 2017-2019. A descriptive, cross-sectional study. Results and Conclusions: In 3 years, 90 cases of drug allergy were recorded, accounting for 65.2% of the total adverse drug reations. Drug allergy is common at all ages, most commonly in the 18-60 year olds group (48.9%) and more in women than in men (64.4% versus 35.6%). Other beta-lactam antibacterial agents (including cephalosporins, monobactam and carbapenem) were the most commonly suspected group of drugs (44.4%), with the most suspected active ingredient ceftriaxon (20.0%). Injection/intravenous infusion was the main route to cause drug allergy (81.1%). Serious allergic reactions account for 22.2% (20/90) of all allergic cases, and 69.0% of all severe adverse drug reations. The majority of reported allergic reactions occurred 1 hour after taking the drug (71.1%). Key words: Drug allergy, anaphylaxis, Stevens-Johnson syndrome

Do antimicrobial stewardship programs improve the quality of care in ICU patients diagnosed with infectious diseases following consultation? Experience in a tertiary care hospital

One of the most important public health concerns is the ever-growing problem of antibiotic resistance. Importantly, the rate of introduction of new molecules into clinical practice has slowed down considerably. Moreover, the rapid emergence of resistance shortens the effective 'lifespan' of these molecules. The quality of care before and after active intervention and feedback was evaluated in patients diagnosed with sepsis/septic shock or ventilator-associated pneumonia (VAP) in the ICUs of Hacettepe University Adult and Oncology Hospitals. There was a significant increase in total scores. Significant improvements were achieved in the management of these patients in terms of requests for necessary diagnostic tests, and the prolonged infusion of beta-lactam agents. Implementation of an ASP in centers where antimicrobial management of ICU patients is largely controlled by infectious diseases specialists remains a feasible strategy that leads to better patient care.