High Resistance Rates Research Articles

Antimicrobial Susceptibility of Toxin-Producing Corynebacterium diphtheriae and C. ulcerans in Belgium

Background/Objectives: Despite a significant reduction in diphtheria incidence and mortality due to vaccination, antitoxin therapy and antibiotic treatments, a concerning resurgence is occurring in Europe. Resistance to penicillins and macrolides is emerging, resulting in a growing challenge for diphtheria management. This retrospective study aims to evaluate and compare antibiotic susceptibilities of both toxigenic Corynebacterium diphtheriae and C. ulcerans. Methods: Susceptibilities were assessed using broth microdilution—the gold standard—disk diffusion and the gradient method, and analyzed on the basis of the EUCAST breakpoint tables for the interpretation of MICs and zone diameters. Antimicrobial resistance genes and mutations were detected by analyzing whole-genome sequences (WGS). Results: A small number of C. diphtheriae isolates were resistant to the first-choice antimicrobial classes, penicillins and macrolides, while higher resistance rates were observed for ciprofloxacin (29%), tetracycline (38%) and trimethoprim-sulfamethoxazole (SXT, 85%). A good correlation was found with resistance genes and mutations detected by WGS. C. ulcerans isolates were susceptible to all tested antibiotics, except clindamycin, to which this species is naturally resistant, and a few ciprofloxacin resistances not confirmed by WGS. Diffusion techniques were found to be acceptable alternatives, but false susceptible results were detected for ciprofloxacin and tetracycline by disk diffusion and ciprofloxacin and SXT by gradient diffusion. Conclusions: Penicillins and macrolides remain the first-choice antibiotics for the treatment of diphtheria. However, antimicrobial susceptibility testing is needed for all toxigenic C. diphtheriae and C. ulcerans isolates, as resistance is emerging. Antimicrobial susceptibility testing should not be limited to penicillins and macrolides, but be extended to other antibiotics. When WGS is performed for epidemiological purposes, resistance genes and mutations should be looked for.

Study on Isolation of Organism and Antibiotic Sensitivity Pattern in Blood Culture of Enteric Fever Patients in a Tertiary Care Hospital in Bangladesh

A cross-sectional, observational study was conducted in the Department of Medicine, Mugda Medical College Hospital, Dhaka, Bangladesh, between March 2022 and September 2023, to observe the changing pattern of antibiotic sensitivity pattern among enteric pathogens causing enteric fever. A total of 50 blood culture and sensitivity reports were analyzed. Blood samples were derived from 50 patients included in this study, who were admitted into the medicine inpatient department of Mugda Medical College Hospital suffering from fever for at least 2 weeks and were confirmed having enteric fever. The predominant growth of two bacteria was observed in all (100%) samples. The most common organisms isolated were Salmonella typhi as typhoid fever pathogens and Salmonella paratyphi A as paratyphoid fever pathogens; these represented 88% and 12% of isolates respectively. Salmonella typhi organisms were found 100% sensitive to amoxycillin, trimethoprim-sulfamethoxazole, chloramphenicol, gentamicin, meropenem, cefepime, followed by imipenem (85%), ampicillin (81%), ceftriaxone (78%), levofloxacin (77%) and cefuroxime (77%). However, amoxicillin, trimethoprimsulfamethoxazole, ceftazidime, cefotaxime, ceftriaxone and chloramphenicol were found 100% sensitive to paratyphoid pathogens. Very high rate of resistance was seen against nalidixic acid (88%), piperacillin-tazobactam (50%), azithromycin (47%), co-amoxiclav (40%) and doxycycline (40%) in salmonella typhi infections, while nalidixic acid and azithromycin were found 100% resistant to Salmonella paratyphi A infection. Mugda Med Coll J. 2024; 7(2): 108-113

Antibiotic Susceptibility Patterns in Adenotonsillar Bacterial Isolates in a Tertiary Hospital in Sub-Saharan Africa

Background: The adenoids and tonsils are parts of Waldeyer's ring and are essentially the first line of immunological defense of the upper respiratory tract. These lymphoid tissues can frequently become infected, resulting in hypertrophy and recurrent tonsillitis. Bacterial infections are the main causative agents in chronic adenotonsillitis. Frequently implicated organisms seen ln the adenoids and tonsils include Streptococcus pyogenes, Staphylococcus aureus, Haemophilus influenzae, Moraxella catarrhalis and sometimes anaerobic bacteria. The rise of antimicrobial resistance has greatly diminished the effectiveness of widely used antibiotics. Objective: The aim of this study is to examine the microbiological characteristics and antibiotic susceptibility patterns of bacterial isolates obtained from adenotonsillar tissues of children undergoing tonsillectomy in a tertiary hospital in Nigeria. Methods: A hospital based cross-sectional study among patients undergoing adenotonsillectomy. Swab was taken from adenoid and tonsillar tissues and sent for sent for microbiology culture and sensitivity. Data entry and analysis was done using the Statistical Product and Service Solutions (SPSS) version 20. Tables and charts were used as appropriate to represent data. Numerical variables were summarized as means and standard deviation for age while categorical variables were expressed as frequencies and percentages. Results: A total of 50 patients aged 3 years to 7 years were included in the study. A median age of 4.0 years and mean age of 4.4± 1.5 years was gotten. Most (62% of the patients were under five male/female ratio of 1.3: 1. Most of the adenoid (40%) and tonsillar (32%) tissues did not yield growth. Viridan group of Streptococcus seen 20% of tonsils was the commonest organism isolated from the tonsils. Staphylococcus aureus as seen in 22% of cases was commonest bacterial isolate from the adenoid. Regarding antibiotic susceptibility, aerobic bacteria was resistant to most of the antibiotics. The sensitivity pattern of Staphylococcus aureus was as follows; erythromycin (59.5%), cefuroxime (54.1%), ciprofloxacin(51.2%) and amoxicillin/clavulanic acid (51.2%). The antibiogram of organisms showed a high rate of resistance of aerobic bacteria to antibiotics which was statistically significant. However, the predominant organisms were most sensitive to erythromycin, cefuroxime and amoxicillin/clavulanic acid.

Molecular Profiling of Antibiotic-resistant Pseudomonas aeruginosa Isolated from Patients with Urinary Tract Infections in Rivers State University Teaching Hospital

Background: Antibiotic-resistant Pseudomonas aeruginosa poses a significant challenge in urinary tract infections (UTIs), particularly in hospital settings. Aim: The aim of this study was to analyze the molecular profile of antibiotic-resistant P. aeruginosa strains isolated from patients with urinary tract infections at the Rivers State University Teaching Hospital, Port Harcourt. Methods: As part of a cross-sectional study, 199 patients were interviewed, and urine samples were collected from subjects with symptoms of a urinary tract infection. A semiquantitative urine culture method was used to detect significant bacteriuria. Suspected uropathogenic P. aeruginosa isolates were then identified using conventional and molecular techniques for identification and gene detection. The data generated from this study was presented as frequencies and percentages using Microsoft Excel 365. Results: Of the 199 urine samples analyzed, P. aeruginosa was isolated in 17 cases, corresponding to a prevalence rate of 8.5%. Among the antimicrobial classes tested, aminoglycosides showed different resistance rates: amikacin (23.5%) and gentamicin (35.3%). Fluoroquinolones, including ofloxacin and ciprofloxacin, had resistance rates of 52.9%. Cephalosporins showed high resistance, particularly cefuroxime sodium (88.2%) and cefpodoxime (100%). Amoxicillin + clavulanic acid showed a resistance rate of 94.1%, while resistance to cefotaxime was 47.1%. Imipenem remained effective without resistance being observed. Several antimicrobial resistance indices (MAR) indices revealed complex resistance patterns across isolates, with the highest MAR index at 0.92. Genotypic analysis identified CTX-M as the most prevalent resistance gene (77.8%), followed by TEM (44.4%) and SHV (33.3%). Notably, no isolates harbored NDM or VIM genes, indicating the absence of carbapenem resistance genes among the studied isolates. Conclusion: This study highlights the prevalence of antibiotic-resistant P. aeruginosa in UTIs at Rivers State University Teaching Hospital, the study also evaluated the antimicrobial susceptibility of Pseudomonas isolates, and key finding is the high resistance rates of the Pseudomonas isolates to multiple antibiotics, especially within the fluoroquinolone and cephalosporin classes, while maintaining susceptibility to Imipenem.

Antimicrobial Resistance Patterns in Pediatric Urinary Tract Infections: Insights from Hospitalized Children in Sudan

Introduction: Urinary tract infections (UTIs) are among the most common bacterial diseases in children, affecting 3–5% of girls and 1% of boys, and leading to significant antibiotic exposure in this population. Initial UTI treatment is often empirical, based on symptomatology without microbiological confirmation. Objective: This study aimed to identify the causative agents of UTIs in children, evaluate antimicrobial resistance rates, and recommend appropriate antibiotics. Materials and Methods: A cross-sectional study was conducted on 67 urine samples collected from hospitalized children at Gaafar Bin Ouf Children's Hospital in Khartoum, Sudan. Samples were processed for bacterial isolation, identification, and antimicrobial susceptibility testing using the Kirby-Bauer method. Results: Among the isolates, 24 (35.8%) were Staphylococcus aureus, 20 (29.9%) Klebsiella spp., 14 (20.9%) Escherichia coli, 8 (11.9%) Pseudomonas spp., and 1 (1.5%) Proteus spp. The highest resistance rates were observed for Amoxyclav (68.7%) and Erythromycin (61.2%), while Gentamicin (40.3%), Ciprofloxacin (43.3%), and Penicillin (46.3%) showed lower resistance rates. Conclusion: Staphylococcus aureus was the most common UTI pathogen in hospitalized children, with high resistance rates to Amoxyclav and Erythromycin. These findings highlight the need for regular resistance monitoring and revising empirical antibiotic protocols to improve treatment outcomes.

Multi-locus sequence typing of Candida tropicalis among Candiduria shows an outbreak in azole-susceptible isolates and clonal cluster enriched in azole-resistant isolates.

The increasing detection rate of C.tropicalis and its azole resistance have made clinical treatment difficult. The presence of candiduria seems to correlate with invasive candida infection, especially for patients admitted to ICUs. However, the prevalence and antifungal resistance of C.tropicalis isolates in urine samples has not been well studied. To retrospectively investigate the clinical features, antifungal resistance, and genetic relatedness of C.tropicalis isolates from urine samples. A total of 107 clinical C.tropicalis isolates were retrospectively studied, including phenotypes of isolates and characteristics of patients. The genetic profiles of 107 isolates were genotyped using multi-locus sequence typing (MLST). Phylogenetic analysis was inferred using unweighted pair group method with arithmetic averages. MLST clonal clusters (CCs) were analysed by goeBURST. Of the 107 isolates, 27.1% were resistant to fluconazole, and there was a notable increasing trend of fluconazole resistance from 16.1% in 2019 to 40.0% in 2021. Forty-seven diploid sequence types (DSTs) were assigned to ten major CCs. CC1 was the predominant fluconazole-susceptible group; 24 isolates from CC1 belonged to DST333, an outbreak clone in NICU ward. The azole-resistant CC4 contained 19 isolates, accounting for 65.5% of the azole-resistant isolates in this study. CC4 belongs to a prevalent FNS CC1 globally, of which the putative founder genotype was DST225. This study revealed an outbreak of azole-susceptible C.tropicalis isolates in urine specimens and a high azole resistance rate of C. tropicalis in candiduria, and the MLST type showed clonal aggregation in azole-resistant isolates from urine samples.

Antimicrobial and anti-biofilm effects of dihydroartemisinin-loaded chitosan nanoparticles against methicillin-resistant Staphylococcus aureus.

The formation of biofilms enhances bacterial antibiotic resistance, posing significant challenges to clinical treatment. Methicillin-resistant Staphylococcus aureus (MRSA) is a primary pathogen in biofilm-associated infections. Its high antibiotic resistance and incidence rates make it a major clinical challenge, underscoring the urgent need for novel therapeutic strategies. Building on previous research, this study employs nanotechnology to fabricate dihydroartemisinin-chitosan nanoparticles (DHA-CS NPs) and, for the first time, applies them to the treatment of MRSA biofilm infections. The antibacterial and anti-biofilm activities of these compounds were evaluated, and their potential mechanisms of action were preliminarily explored. The results demonstrated that the DHA-CS NPs exhibited a minimum inhibitory concentration (MIC) of15μg/mLand a minimum bactericidal concentration (MBC) of 30μg/mL. At 15μg/mL, the DHA-CS NPs significantly inhibited MRSA biofilm formation (P<0.001),while at 7.5μg/mL, they dispersed 67.4±3.77% of the preformed biofilms (P<0.001). Scanning electron microscopy (SEM) and confocal laser scanning microscopy (CLSM) confirmed the disruption of MRSA biofilms. Mechanistic studies, including phenol-sulfuric acid assays, static biofilm microtiter plate assays, and RT-qPCR, revealed that the DHA-CS NPs inhibited the synthesis of extracellular polymeric substances (EPS), suppressed the release of extracellular DNA (eDNA), and downregulated key biofilm-related genes (icaA, sarA, cidA, and agrA). These findings suggest that DHA-CS NPs hold significant promise for inhibiting and eradicating MRSA biofilms, providing a theoretical basis for the development of novel antibiofilm therapies.

Predictors of Mortality in Gram-Negative Bloodstream İnfections

Purpose: Bloodstream infection (BSI) is the most common healthcare-associated infection in intensive care units (ICUs) and is associated with high mortality rates. In this study, we aimed to evaluate the etiological pathogens and susceptibility distribution and factors affecting mortality in patients followed up in the ICU with the diagnosis of healthcare-associated gram-negative BSI. Material and Methods: This study was designed as a retrospective cohort study. Patients diagnosed with healthcare-associated BSI during ICU follow-up were included in the study. Patients demographic data, source of BSI, causative microorganisms and their antimicrobial susceptibility and mortality (any cause) rates were collected retrospectively from patient files and patient information sheets. Patients were divided into survival and non- survival groups according to the prognosis and differences in clinical data between the two groups were compared. Results: The study included 162 patients with gram-negative BSI, of whom 85 (52.5%) died during their ICU stay. The three most common pathogens detected in patients were; Klebsiella pneumoniae [60/162(37%)], Acinetobacter baumannii [32/162(19.75%)] and Stenotrophomonas maltophilia [25/162(15.43%)]. The highest carbapenem resistance rates belonged to A. baumannii and K. pneumoniae with 93.75% and 81.66%, respectively. Multivariate logistic regression analysis identified, patients requiring invasive mechanical ventilation (IMV) had over three times the odds of death (OR: 3.10, 95% CI: 1.23–7.80, P = 0.016). Septic shock was associated with a nearly threefold increased risk of mortality (OR: 2.78, 95% CI: 1.29–6.00, P = 0.009), and continuous renal replacement therapy also significantly increased mortality risk (OR: 2.52, 95% CI: 1.11–5.71, P = 0.026). Conclusion: : IMV, septic shock, and the need for CRRT during ICU follow-up are risk factors for mortality in gram-negative BSI patients followed in the ICU. Among the etiologic pathogens, the highest resistance rates were found in A. baumannii and K. pneumoniae, respectively.

Distribution, Drug Resistance, and Risk Factors of Infection in Liver Transplant Recipients With Liver Failure.

The aim of this study was to explore strategies for postoperative infection prevention and treatment, and how they might help to improve the prognosis in liver transplant recipients with liver failure. We retrospectively investigated 98 recipients with liver failure in the Surgical Intensive Care Unit of The First Affiliated Hospital of Xi'an Jiaotong University from January 2019 to December 2023, and the pathogens distribution, drug resistance, and risk factors of infection after liver transplantation were analyzed. The incidence of infection was 48.0%, with common infection sites including the respiratory tract, abdominal cavity, biliary tract, and bloodstream. A total of 145 pathogens were isolated, 110 (75.9%) of which were Gram-negative bacteria, 30 (20.7%) were Gram-positive bacteria, and 5 (3.4%) were fungi. The most common pathogenic bacteria were Klebsiella pneumoniae, Acinetobacter baumannii, Enterococcus faecalis, Pseudomonas aeruginosa, and Stenotrophomonas maltophilia. Drug sensitivity data showed that Klebsiella pneumoniae showed a high resistance rate (over 70%) to all tested antibiotics except for tigecycline, colistin, and ceftazidime avibactam. Acinetobacter baumannii was highly sensitive to colistin and tigecycline, with a sensitivity of over 50% to minocycline and aminoglycosides, and a resistance rate of over 70% to other tested antibiotics. No Gram-positive strain was resistant to tigecycline, linezolid, vancomycin, and teicoplanin. Risk factor analysis suggested that preoperative infection within 2 months was an independent risk factor for infection after liver transplantation in recipients with liver failure. The incidence of postoperative infection in liver failure recipients was high, and the respiratory tract and abdomen were the most common sites. The pathogenic bacteria were mainly Gram-negative bacteria, which showed an extensive and high drug resistance. Patients with liver failure who underwent liver transplantation with a preoperative infection within 2 months of the transplantation were more likely to develop an infection after surgery.

Incidence and resistance rates of Pseudomonas aeruginosa bloodstream infections in Switzerland: a nationwide surveillance study (2010-2022).

Bloodstream infections (BSIs) cause significant morbidity and mortality worldwide. Pseudomonas aeruginosa is an important microorganism in BSIs. The aim of this study was to analyze recent trends in the incidence and resistance rates of P. aeruginosa BSIs in Switzerland and its different linguistic regions. This retrospective, nationwide observational study analyzed the incidence (using Poisson regression models) and antimicrobial resistance (using logistic regression models) of P. aeruginosa BSIs in Switzerland from 2010 to 2022. The annual incidence of P. aeruginosa BSIs in Switzerland increased from 5.5 BSIs per 100,000 inhabitants in 2010 to 7.6 BSIs per 100,000 inhabitants in 2022 (p < 0.001). The incidence was higher in the French-speaking region than in the German-speaking region. The resistance rates increased significantly for cefepime (2.4% in 2010, 8.8% in 2022; p < 0.001), ceftazidime (5.6% in 2010, 9.4% in 2022; p = 0.014), ciprofloxacin (3.3% in 2010, 6.5% in 2022; p = 0.014), and piperacillin-tazobactam (6.4% in 2010, 11.2% in 2022; p = 0.002). No significant trends were observed for carbapenem-, aminoglycoside-, or multidrug-resistant P. aeruginosa. A high incidence was observed in patients ≥ 80 years, whereas resistance rates were high in young patients. The increase in the incidence of P. aeruginosa BSIs emphasizes the importance of monitoring resistant and susceptible P. aeruginosa BSIs. Compared to the population-weighted mean resistance rates in Europe in 2022, those in Switzerland were lower, but an increase was observed for most antibiotics. The high resistance rates in young patients require further investigation.

P-1516. Addition of Single-Dose Aminoglycosides to Empiric Beta-Lactam Therapy in Septic Shock in a Setting with High Antimicrobial Resistance Rates

Abstract Background At the Detroit Medical Center (DMC), the addition of an aminoglycoside (AMG) to β-lactam therapy is recommended in patients with septic shock due to high resistance rates; however, studies assessing the benefit of such combinations have yielded conflicting results. The objective of this study is to compare the outcomes of patients with septic shock who receive empiric β-lactam therapy with and without an AMG.Figure 1.Mortality Outcomes Methods This is a retrospective cohort study from 5/2021 to 7/2023. Patients were included if they met the following: 2 of 4 SIRS criteria, received vasopressors, serum lactate &amp;gt; 2 mmol/L, and appropriate empiric antimicrobial therapy within 24 hrs of admission . Patients who received an AMG within 24 hrs of admission were included in the AMG cohort, and those who did not were included in the control group. Key exclusion criteria were COVID-19, burn injury, and transfer to hospice care within 4 days of admission. The primary outcome was all-cause mortality at 7 days ; secondary outcomes included 30-day mortality, vasopressor-free days by day 7, ventilator-free days by day 28, and nephrotoxicity by day 7.Table 1.Patient and treatment characteristics Results Seventy-six patients were included (AMG=38; Control=38). The most common source of infection in AMG and control groups was pulmonary (44% vs. 31%, p=0.18). More AMG patients had a presumed SSTI source (17% vs. 0.0%, p=0.0049) patients, positive blood culture (79% vs. 26%, p&amp;lt; 0.0001), prior history of MDRO pathogen (22% vs. 0.0%, p=0.003), and received meropenem as initial empiric therapy (40% vs. 3%, p&amp;lt; 0.0001). APACHE II scores were similar (30 vs. 28, p=0.09). Time to appropriate antibiotic therapy was 4.8 hrs in the AMG group vs. 6.4 hrs in the control group, p=0.81. There were no differences in 7-day mortality (47% vs. 40%, p=0.49), 30-day mortality (63% vs. 53%, p=0.3527), vasopressor-free days by day 7 (2 vs. 2, p=0.08), or ventilator-free days by day 28 (2.5 vs. 8.5, p=0.31). There were also no differences in nephrotoxicity by day 7 (50% vs. 67%, p=0.23).Table 1.Patient and treatment characteristics, continued Conclusion Further evaluations should be conducted to determine whether an AMG in combination with β-lactams should be used in patients with septic shock.Table 2.Other clinical outcomes Disclosures All Authors: No reported disclosures

P-1653. Current Prescribing Practices and Guideline Concordance for the Treatment of Community-Acquired Bacterial Pneumonia (CABP) across Outpatient and Urgent Care Visits

Abstract Background Resources and support for antibiotic stewardship programs (ASP) have focused on hospitalized patients and there is minimal prescribing data and interventions among outpatients. We aimed to assess the treatment of CABP in adults in order to develop interventions to improve antibiotic utilization. Methods This retrospective study (2022-2022) included patients within a large healthcare system presenting to outpatient clinics (n=120) and affiliated Urgent Care Centers (n=24) across Connecticut. Patient encounters were identified via CABP ICD-10 codes and IDSA relevant patient comorbidities (chronic heart, lung, liver, or renal disease; diabetes; alcoholism; malignancy; asplenia) were extracted from patient problem lists. Primary outcome was to describe the proportion of patients receiving concordant therapy (antibiotic choice and prescription of monotherapy or combination therapy depending on presence of comorbidity) per IDSA guideline and local antibiogram. Results Patient characteristics are listed in Table 1. Overall guideline concordance rate was 36.6% (1,468/4,011 antibiotic orders). Among orders in patients with comorbidities (n=2,212), a large proportion received discordant therapy (n=1,417; 64.1%) via monotherapy particularly doxycycline (DOX) or azithromycin (AZM). Among appropriate combination therapy orders (n=370) in patients with comorbidities, the most common pairings were amoxicillin-clavulanate plus AZM (160/370; 43.2%) followed by amoxicillin-clavulanate plus DOX (86/370; 23.2%). 10.5% (232/2,212) received a guideline concordant respiratory fluoroquinolone monotherapy. Among antibiotic orders in patients with no comorbidity (n=1,799), 1,126 (62.6%), orders were discordant largely due to inappropriate monotherapies (742/1,126; 65.9%) in particular AZM monotherapy (352/1,126; 31.3%) despite local pneumococcal resistance rates &amp;gt;25%. Conclusion Guideline concordance was low, primarily due to lack of combination therapy in patients with comorbidities, as well as use of AZM monotherapy despite high resistance rates. Overall, these data will be instrumental in our current efforts to initiate an outpatient ASP and deploy interventions to improve care across the continuum of care. Disclosures Tomefa E. Asempa, PharmD, FDA/CDER: Grant/Research Support|Paratek: Grant/Research Support|Shionogi: Grant/Research Support|Spero: Grant/Research Support|VenatoRx: Grant/Research Support David P. Nicolau, PharmD, CARB-X: Grant/Research Support|Innoviva: Grant/Research Support|Innoviva: Honoraria|Merck: Advisor/Consultant|Merck: Grant/Research Support|Merck: Honoraria|Pfizer: Advisor/Consultant|Pfizer: Grant/Research Support|Pfizer: Honoraria|Shionogi: Advisor/Consultant|Shionogi: Grant/Research Support|Shionogi: Honoraria|Venatorx: Grant/Research Support

Serotyping and antimicrobial resistance of Actinobacillus pleuropneumoniae isolates from fattening pigs in Poland from 2019 to 2024

BackgroundActinobacillus pleuropneumoniae is a prevalent respiratory pathogen causing substantial economic losses in swine production worldwide. The bacterium's ability to rapidly develop antimicrobial resistance (AMR) poses a significant challenge to effective treatment and control. In Poland, limited data on A. pleuropneumoniae serotype distribution and AMR patterns hinder evidence-based treatment strategies. This study examined the serotype diversity and AMR patterns of A. pleuropneumoniae isolates from porcine pleuropneumonia outbreaks in northeastern Poland between 2019 and 2024, providing crucial information for regional veterinary practices and antimicrobial stewardship efforts.ResultsAnalysis of 119 isolates from 67 farms demonstrated the predominance of serotype 2 (65.5%), followed by serogroups 3, 6, 8 (18.5%) and 1, 9, 11 (15.1%). This distribution differs from recent trends in other European countries, suggesting regional epidemiological variations. High resistance rates were observed for tylosin (55.5%), gentamicin (36.1%), doxycycline (32.8%), and sulfamethoxazole/trimethoprim (26.1%). Multidrug resistance fluctuated between 14.3% and 21.9% over the study period, with no clear linear trend. From 2022 onwards, strains exhibiting resistance to seven or more antimicrobials, including cephalosporins, emerged, marking a significant shift in resistance profiles. Temporal analysis revealed diverse resistance patterns, with significant increases in some antimicrobials (e.g., sulfamethoxazole/trimethoprim, p = 0.001) and stability in others (e.g., tetracycline, p = 0.890). Notably, several antimicrobials, including florfenicol and colistin, maintained 100% efficacy against all isolates throughout the study period.ConclusionsThe findings highlight the dynamic nature of AMR development in A. pleuropneumoniae and underscore the need for ongoing surveillance in the region. The emergence of highly resistant strains, particularly those resistant to cephalosporins, raises concerns about future treatment options. These results can guide evidence-based treatment strategies and enhance antimicrobial stewardship efforts in regional swine production. Furthermore, the study emphasizes the importance of local AMR data in guiding antimicrobial use policies and the need for a coordinated approach to combat AMR in veterinary medicine.

P-1667. Effect of Penicillin Allergy on Common Urinary Tract Pathogens within a Community Health-System Antibiogram

Abstract Background A penicillin allergy label promotes use of broad-spectrum and alternative antibiotics, which can cause an increase in resistance. Urinary tract infections are commonly encountered in health systems and few studies have shown how a documented penicillin allergy affects resistance on a yearly antibiogram for these isolates. Urinary Antibiogram for Penicillin and Non-penicillin Allergic PatientsTable 1lists Gram negative isolates for penicillin and non-penicillin allergic patients and Table 2 lists the Gram positive isolates Methods This was a retrospective, observational chart review of patients admitted in 2022 within a two-hospital community health-system. Using a query language server and third-party software, patients with a first positive bacterial culture were compared with those with a penicillin allergy to create distinct antibiograms. Data collected included culture site and organism, antibiotic susceptibility, and presence of an infectious diseases (ID) consultation. The primary outcome was percentage of susceptible and non-susceptible isolates of E. coli, P. mirabilis, K. pneumoniae, P. aeruginosa, and E. faecalis in penicillin allergic and non-penicillin allergic patients. A secondary outcome was to determine if ID consultation was different between subgroups. Chi-squared and student's t-test were used for categorical and continuous variables, respectively. Results Of 3,757 patients meeting inclusion criteria, 12.8% (n=484) were penicillin allergic with results in Table 1&amp;2. E. coli had a significantly lower susceptibility rate for ciprofloxacin (p &amp;lt; 0.001), levofloxacin (p &amp;lt; 0.001), and trim/sulfa (p=0.002) in penicillin allergic patients. P. mirabilis had a significantly lower susceptibility rate for cefepime (p=0.015), gentamicin (p=0.006), levofloxacin (p=0.025), ciprofloxacin (p=0.023), and pip/tazo (p=0.012). K. pneumoniae showed higher susceptibility rates for multiple antibiotics in the penicillin allergic group. P. aeruginosa and E. faecalis did not show any statistically significant differences. There was ID consultation on 137/484 (28.3%) of penicillin allergic patients and 899/3273 (27.5%) of non-penicillin allergic patients, which was not statistically different (p=0.7719). Conclusion Labeled penicillin allergic patients demonstrated increased resistance in E. coli and P. mirabilis, while K. pneumoniae had higher resistance rates in non-allergic patients. Both groups had similarly high rates of ID consultation. Disclosures Christopher M. Bland, PharmD, FCCP, FIDSA, BCPS, Merck: Honoraria|Nestle/Seres: Honoraria|Shionogi: Advisor/Consultant|Shionogi: Honoraria Bruce M. Jones, Pharm.D., FIDSA, BCPS, AbbVie: Advisor/Consultant|AbbVie: Honoraria|Ferring: Honoraria|Innoviva: Honoraria|Paratek: Honoraria

P-869. Comparison of β-lactams Antibiotics Resistance of Viridans Streptococci in Bacteremic Children and Adults with Malignancy

Abstract Background Viridans streptococcus bacteremia (VSB) is an important complication after receiving chemotherapy in patients with malignancy. The increase in antibiotic resistance treating patients with VSB has been a major concern especially in children. Methods This is a retrospective study to evaluate patients with malignancy diagnosed with VSB at Niigata University Hospital in Japan between January 2009 and May 2023. Clinical characteristics of the patients, and antibiotic susceptibility of viridans streptococci were evaluated. We used the Mann-Whitney test for numerical variables and the χ2 test, or Fisher’s exact test for categorical variables. Results A total of 85 episodes (29 in children, 56 in adults) of VSB were identified during the study period. Acute myeloid leukemia was the most common diagnosis in both children (41%) and adults (61%). The susceptibility rate was significantly lower in children than adults; penicillin (45% vs. 79%, p =. 001), cefepime (52% vs. 91%, p &amp;lt; .001), and meropenem (55% vs. 89%, p &amp;lt; .001). Vancomycin was 100% susceptible in both groups. Based on the susceptibility results, the rate of appropriate initial antimicrobial coverage by empiric therapy was lower in children (59%) than in adults (91%) (p &amp;lt; .001). Severe complications included 2 meningitis cases in children, and a septic shock case in adults, 2 pediatric cases were treated with non-susceptible antibiotics at the onset of fever. No mortality was observed. The median number of previous febrile neutropenia episodes was higher in children (2, IQR 1-4) than adults (1, IQR 0-2) (p &amp;lt; .001). Additionally, the median duration of neutropenia at the onset was longer in children (6.5 days, IQR 4-11days) than adults (5 days, IQR 3-7days) (p = .03). No difference in β-lactam antibiotics use at the onset (7% vs. 0%, p = .11), or β-lactam exposure within 30 days of onset (41% vs. 41%, p = .98) was observed between child and adults. Conclusion We demonstrated a high rate of β-lactam antibiotics resistance to viridans streptococci in patients with malignancy, especially in children. The frequent antimicrobial exposure in children might be related to such high resistance. Vancomycin may need to be included in an empiric therapy in the setting where β-lactam antibiotics resistance of viridans streptococci is high. Disclosures All Authors: No reported disclosures

387. High Rates of Bacteremia and Fluoroquinolone Resistance during an Outbreak of Shigellosis among People Experiencing Homelessness and Opioid Use Disorder in Philadelphia, PA

Abstract Background In October 2023, the city of Philadelphia, PA reported a dramatic rise in shigellosis cases from Shigella flexneri, leading to widespread diarrheal illness and many hospitalizations. Notable qualities of this outbreak included high antibiotic resistance, high rates of bacteremia in hospitalized patients, a death due to invasive shigellosis, and extensive housing insecurity and opioid use disorder (OUD) among those affected. Rates of antibiotic susceptibility and resistance among tested isolates of Shigella flexneri. Methods All patients hospitalized at Temple University Health Systems (TUHS) with confirmed shigellosis between October 2023 and April 2024 were included in the study. Diagnosis was made via stool culture, blood culture, and/or polymerase chain reaction (PCR) stool pathogen panel. Charts were reviewed for patient age, sex, housing status, history of OUD, stool and blood culture data, stool pathogen panel data, antibiotic susceptibility data, and any death due to shigellosis. Hospitalizations and Bacteremia Over Time Number of patients hospitalized and number of patients with documented Shigella flexneri bacteremia per month during an outbreak of shigellosis. Results Sixty-seven patients were hospitalized at TUHS from October 2023 to April 2024 with confirmed shigellosis. The average age of patients was 43 and 60% were male. Bacteremia was documented in 21 patients (31.3%). Among cultured isolates, 0% were ampicillin or ciprofloxacin susceptible, 2.1% were levofloxacin susceptible, 4.8% were ceftriaxone susceptible, and 89.6% were trimethoprim-sulfamethoxazole (TMP-SMX) susceptible. One patient died from shigellosis, a 1.5% mortality rate in hospitalized patients. Housing insecurity was documented for 67% of patients, and 68.7% of patients had OUD. Conclusion This shigellosis outbreak in Philadelphia saw an unprecedented rate of bacteremia among hospitalized patients. Cultured isolates were highly beta-lactam and fluoroquinolone resistant. TMP-SMX was the only oral antibiotic with reliable susceptibility. Most hospitalized patients had housing insecurity and OUD. Due to the fecal-oral route of infection, outbreak containment challenges reflect the insufficient sanitation facilities for people experiencing homelessness. Disclosures Sara K. Schultz, MD FACP FIDSA, AbbVie: Advisor/Consultant

P-861. CTX-M-15-producing H30 ST131 Escherichia coli contributes to carbapenem use for E. coli bloodstream infections in the United States

Abstract Background Drug-resistant E. coli is a leading cause of antimicrobial resistance-associated deaths globally. Specifically, resistance to ceftriaxone (CRO-R) is increasing in E. coli. High-risk clonal group ST131 and its pandemic H30 subclone are of high concern yet studies characterizing these infections are limited. We evaluated baseline characteristics and clinical outcomes associated with H30 ST131, non-H30 ST131 and non-ST131 E. coli bloodstream infections (BSI). Methods Patients with monomicrobial carbapenem-susceptible E. coli BSI that were matched 1:1 by study site (CRO-R and CRO-susceptible community-acquired and hospital onset cases) were prospectively enrolled from 14 United States hospitals between November 12, 2020 to April 28, 2021 in the multicenter Study of Highly Resistant E. coli (SHREC). Isolates underwent whole genome sequencing. The primary outcome was a 30-day Desirability of Outcome Ranking (DOOR) after index culture including clinical response to treatment and all-cause mortality. Results There were 92 (33%) H30 ST131, 29 (10%) non-H30 ST131, and 161 (57%) non-ST131 isolates in 282 E. coli BSI (Table 1). Most ceftriaxone resistance was conferred by CTX-M-15 produced by H30 ST131 isolates (Figure 1, Table 1). H30 ST131 BSI patients were older (median age [IQR] 70.5 [63,76] vs. 67 [56,77] vs 65 [51,74] years, p = 0.017), had higher Charlson comorbidity indices (3 [2,5] vs. 2 [1,4] vs. 2 [1,4], p=0.009), and were more often admitted from long-term care facilities (18/92 [20%] vs. 3/29 [10%] vs. 7/161 [4%], p = 0.003) compared to non-H30 ST131 and non-ST131 BSI patients. Among H30 ST131 isolates, high rates of antibiotic resistance were observed to cephalosporins and fluoroquinolones, resulting in significantly more carbapenem use compared with non-H30 ST131 and non-ST131 isolates (75/92 [82%] vs. 14/29 [48%] vs. 50/161 [31%], p &amp;lt; 0.001) (Figure 2). 30-day DOOR and hospital length of stay did not differ between groups (Table 2). Conclusion Compared with non-H30 ST131 and non-ST131 E. coli BSI, H30 ST131 E. coli BSI have a unique epidemiology with more healthcare exposures, comorbidities and antibiotic resistance and are more likely to be treated with carbapenems, though no significant difference in clinical outcomes was observed. Disclosures Yohei Doi, MD, PHD, AbbVie: Honoraria|Entasis: Grant/Research Support|Gilead: Advisor/Consultant|GSK: Advisor/Consultant|Meiji Seika: Advisor/Consultant|Moderna: Advisor/Consultant|Pfizer: Advisor/Consultant|Shionogi: Advisor/Consultant|Shionogi: Honoraria Elie Saade, MD, MPH, FIDSA, Janssen Global Services: Advisor/Consultant|Janssen Global Services: Advisor/Consultant|Janssen Research and Development: Advisor/Consultant|Janssen Research and Development: Advisor/Consultant Loren G. Miller, MD MPH, Armata: Grant/Research Support|Contrafect: Grant/Research Support|GSK: Grant/Research Support|Merck: Grant/Research Support|Paratek: Grant/Research Support Michael J. Satlin, MD, AbbVie: DSMB participant|bioMerieux: Grant/Research Support|Merck: Grant/Research Support|Selux Diagnostics: Grant/Research Support|SNIPRBiome: Grant/Research Support W. Charles Huskins, MD, MSc, ADMA Biologics: Advisor/Consultant|Bristol Myers Squibb: Stocks/Bonds (Public Company)|Pfizer: Advisor/Consultant|Pfizer: Stocks/Bonds (Public Company)|Zimmer Biomet: Stocks/Bonds (Public Company) Carol Hill, PhD, Glaxo SmithKline: Retirement Health, Cash Balance Plan|Glaxo SmithKline: Stocks/Bonds (Public Company) Robin Patel, MD, a patent on Bordetella pertussis/parapertussis PCR issued, a patent on a device/method for sonication with royalties paid by Samsung to Mayo Clinic, a: See above|MicuRx Pharmaceuticals and BIOFIRE: Grant/Research Support|PhAST, Day Zero Diagnostics, Abbott Laboratories, Sysmex, DEEPULL DIAGNOSTICS, S.L., Netflix, Oxford Nanopore Technologies and CARB-X: Advisor/Consultant|Up-to-Date and the Infectious Diseases Board Review Course.: Honoraria Vance G. Fowler, MD, MHS, Affinergy: Advisor/Consultant|ArcBio: Stocks/Bonds (Private Company)|Armata: Advisor/Consultant|Astra Zeneca: Advisor/Consultant|Astra Zeneca: Grant/Research Support|Basilea: Advisor/Consultant|Basilea: Grant/Research Support|ContraFect: Advisor/Consultant|ContraFect: Grant/Research Support|Debiopharm: Advisor/Consultant|Destiny: Advisor/Consultant|EDE: Grant/Research Support|Genentech: Advisor/Consultant|Genentech: Grant/Research Support|GSK: Advisor/Consultant|Janssen: Advisor/Consultant|Karius: Grant/Research Support|MedImmune: Grant/Research Support|Merck: Grant/Research Support|sepsis diagnostics: Patent pending|UptoDate: Royalties|Valanbuio: Stocks/Bonds (Private Company)|Valanbuio: Stocks/Bonds (Private Company) David van Duin, MD, PhD, Merck: Advisor/Consultant|Merck: Grant/Research Support|Pfizer: Advisor/Consultant|Qpex: Advisor/Consultant|Roche: Advisor/Consultant|Shionogi: Advisor/Consultant|Shionogi: Grant/Research Support

P-2099. A Novel Anaerobic Activity Index to define the “anti-anaerobic” spectrum of antimicrobials

Abstract Background While necessary for the treatment of anaerobic infections, use of antibiotics with anaerobic activity may be associated with poor patient outcomes including graft-versus host disease after bone marrow transplant and mortality in critically ill patients. However, we lack a uniform method to assess the relative anaerobic activity of antibiotics and have poor definitions of what it means for antimicrobials to be “anti-anaerobic”. Methods A PubMed search using terms “microbial sensitivity test”, “anti-bacterial agents” and “bacteria, anaerobic” yielded 575 papers published between January 2013-2024 (Figure 1). Papers with &amp;lt; 100 isolates, non-human isolates, or without antimicrobial susceptibility testing (AST) were excluded. AST for an average of 17,709 anaerobic clinical isolates per antimicrobial from 56 publications were summarized. Anaerobes were categorized into 11 groups based on the literature (Table 1). For 16 commonly used antibiotics, values of 0, 1, or 2 were awarded for each group of anaerobes for average published susceptibility of ≤ 10%, 11-89.4%, and ≥ 89.5%, respectively, and tallied to create a composite score (0-22, Score A). Three alternative scores were created based on different susceptibility cutoffs (Scores B-D; Table 2).Table 1:Groups of anaerobes for which antimicrobial susceptibility was scored Results In Anaerobic Activity Index Score A, scores ranged from 11 for moxifloxacin to 22 for tigecycline, meropenem, and imipenem (Table 2). Anaerobic Activity Index scores were plotted against the Antibiotic Spectrum Coverage (ASC), a previously published antibiotic “broad” spectrum score (Figure 2). Varying susceptibility thresholds affected estimated anaerobic activity for some antibiotics, including clindamycin and vancomycin, but overall, there was good agreement across all scores (A-D). Moxifloxacin had the lowest overall scores due to high rates of resistance across all groups of anaerobes. Conclusion Antibiotic broad-spectrum scores have been proposed, but no valid score exists and no score assessing anaerobic activity has been developed. An Anaerobic Activity Index may improve the definition of “anti-anaerobic” antimicrobials for clinical care and research. Further studies are needed to validate this index as a potential tool to evaluate the effect of anaerobic antibiotic exposure on clinical outcomes. Disclosures Vincent B. Young, MD, PhD, Aimmune: Honoraria|American Society for Microbiology: Board Member|Debiopharm: Advisor/Consultant|Peggy Lillis Foundation: Board Member|University of Oklahoma COBRE: Advisor/Consultant|Vedanta: Advisor/Consultant|Vedanta Bioscience: Advisor/Consultant|Vedanta Bioscience: Grant/Research Support David van Duin, MD, PhD, Merck: Advisor/Consultant|Merck: Grant/Research Support|Pfizer: Advisor/Consultant|Qpex: Advisor/Consultant|Roche: Advisor/Consultant|Shionogi: Advisor/Consultant|Shionogi: Grant/Research Support

P-1689. Impact of Antibiotic Usage on Antimicrobial Resistance Rates among Gram-Negatives at a COVID-Care Facility

Abstract Background Antimicrobial resistance is directly associated with antimicrobial use and abuse, becoming an important public health problem in modern practice. Unchecked prescriptions, noncompliance with antimicrobial stewardship programs, pandemics, and outbreaks contribute to this issue. This study aims to analyze the antimicrobial resistance patterns over the years in a tertiary-level facility compared to antibiotic usage. E. coli antimicrobial resistance rates and antibiotic usage Methods A retrospective single-center study from 2019 to 2022 was conducted at the Intensive Care Unit of Hospital San Jose, Monterrey, Mexico. Antibiotic usage was calculated using a defined daily dose (DDD) in g/100 beds for Cefepime, Ceftazidime, Ceftriaxone, Ertapenem, Levofloxacin, Meropenem, and Piperacillin/tazobactam. Antimicrobial resistance rates to these antibiotics by Escherichia coli, Klebsiella pneumoniae, and Pseudomonas aeruginosa isolates from ICU were calculated and compared against antibiotic usage over the years. P. aeruginosa antimicrobial resistance rates and antibiotic usage Results During COVID-19 pandemic in 2020, there was an increased resistance rate of E. coli to cephalosporins (ceftriaxone 80%, ceftazidime 80% and cefepime 80%) in comparison to 2019 and the following years. Klebsiella pneumoniae had a similar behavior, with high resistance rates to cephalosporins (60% each). Pseudomonas aeruginosa isolates also presented a higher resistance rate in 2020 to cefepime (49.6%), ceftazidime (41.6%), meropenem(57.4%) and piperacillin-tazobactam(31.2%) during 2020. During the same year, high DDDs were observed for ceftriaxone (53.3) and meropenem (32.79). Nonetheless, resistance rates to meropenem by P. aeruginosa in 2019 and 2020 (60, 57.4%), E. coli (5.6, 4.4%) and K. pneumoniae (26.3, 7.4%) were not influenced by overuse of meropenem, neither during COVID-19 or the following years. K. pneumoniae antimicrobial resistance rates and antibiotic usage Conclusion Besides overuse of Beta-lactam antibiotics such as ceftriaxone and meropenem during the COVID-19 pandemic, surpassing importantly recommended DDDs by the WHO, resistance rates to these antibiotics in the following years was not affected. Multidisciplinary teams including an infectious disease specialist were fundamental for antimicrobial stewardship during the pandemic, positively impacting resistance rates of Gram-negatives. Disclosures All Authors: No reported disclosures

Examining the Biophysical Properties of the Inner Membrane of Gram-Negative ESKAPE Pathogens.

The World Health Organization has identified multidrug-resistant bacteria as a serious global health threat. Gram-negative bacteria are particularly prone to antibiotic resistance, and their high rate of antibiotic resistance has been suggested to be related to the complex structure of their cell membrane. The outer membrane of Gram-negative bacteria contains lipopolysaccharides that protect the bacteria against threats such as antibiotics, while the inner membrane houses 20-30% of the bacterial cellular proteins. Given the cell membrane's critical role in bacterial survival, antibiotics targeting the cell membrane have been proposed to combat bacterial infections. However, a deeper understanding of the biophysical properties of the bacterial cell membrane is crucial to developing effective and specific antibiotics. In this study, Martini coarse-grain molecular dynamics simulations were used to investigate the interplay between membrane composition and biophysical properties of the inner membrane across four pathogenic bacterial species: Klebsiella pneumoniae, Pseudomonas aeruginosa, Enterobacter cloacae, and Escherichia coli. The simulations indicate the impact of species-specific membrane composition on the overall membrane properties. Specifically, the cardiolipin concentration in the inner membrane is a key factor influencing the membrane features. Model membranes with varying concentrations of bacterial lipids (phosphatidylglycerol, phosphatidylethanolamine, and cardiolipin) further support the significant role of cardiolipin in determining the membrane biophysical properties. The bacterial inner membrane models developed in this work pave the way for future simulations of bacterial membrane proteins and for simulations investigating novel strategies aimed at disrupting the bacterial membrane to treat antibiotic-resistant infections.