Antimicrobial Susceptibility Data Research Articles

Assessing the Value of New Antimicrobials: Evaluations of Cefiderocol and Ceftazidime-Avibactam to Inform Delinked Payments by the NHS in England.

The UK has recently established subscription-payment agreements for two antimicrobials: cefiderocol and ceftazidime-avibactam. This article summarises the novel value assessments that informed this process and lessons learned for future pricing and funding decisions. The evaluations used decision modelling to predict population incremental net health effects (INHEs), informed by systematic reviews, evidence syntheses, national surveillance data and structured expert elicitation. Significant challenges faced during the development of the evaluations led to profound uncertainty in the estimates of INHEs. The value assessment required definition of the population expected to receive the new antimicrobials; estimating value within this heterogenous population; assessing comparative efficacy using antimicrobial susceptibility data due to the absence of relevant clinical data; and predicting population-level benefits despite poor data on current numbers of drug-resistant infections and uncertainties around emerging resistance. Though both antimicrobials offer the potential to treat multi-drug resistant infections, the benefits estimated were modest due to the rarity of true pan-resistance, low life expectancy of the patient population and difficulty of identifying and quantifying additional sources of value. Assessing the population INHEs of new antimicrobials was complex and resource intensive. Future evaluations should continue to assemble evidence relating to areas of expected usage, patient numbers over time and comparative effectiveness and safety. Projections of patient numbers could be greatly enhanced by the development of national level linked clinical, prescribing and laboratory data. A practical approach to synthesising these data would be to combine expert assessments of key parameters with a simple generic decision model.

High Mortality Rates and Antimicrobial Resistance in Children with Invasive Bacterial Infections in a Tertiary Care Facility in West Africa

Abstract Background Childhood data on infection mortality and antimicrobial resistance in Sub-Saharan Africa are emerging but remain limited. The University of Maryland Center for Vaccine Development (CVD) and CVD-Mali have been conducting a prospective observational study at L’Hopital Gabriel Toure (HGT), a referral hospital in Bamako, Mali, since 2002 to identify causes of invasive bacterial infections (IBI) in children. These data have been used to initiate vaccination programs to decrease the burden of Haemophilus influenzae type b and Streptococcus pneumoniae. Additional demographic and antimicrobial susceptibility data have been collected since 2021, allowing for more detailed resistance and mortality analyses. Methods All children presenting to HGT are screened. Children ages 0-15 years with temperature of at least 39 degrees Celsius and/or suspicion of IBI are eligible. Eligible children have blood cultures collected with additional site-specific cultures when focal infection is suspected. Cultures are performed using the Bactec system; when positive, Gram staining, sub-culturing, and antimicrobial susceptibility testing (by disk diffusion using standard methods) are performed. Organisms thought to be contaminants are excluded. American type culture collection strains are utilized for quality control. Results Between 1/14/2021 and 9/14/2023, 28703 patients were screened. 2156 patients were included. 212 patients (10%) had 235 pathogens isolated. Gram positive organisms were most frequently isolated (N=112), followed by Gram negative Enterobacterales (N=81), non-Enterobacterales Gram negatives (N=36), and yeast (N=6). Staphylococcus aureus was the most frequently isolated Gram positive organism (59 bloodstream isolates, 2 joint isolates, 2 subcutaneous isolates) followed by S.pneumoniae (10 bloodstream isolates, 17 cerebrospinal fluid isolates, 1 joint isolate) and Enterococcus species (16 bloodstream isolates). Klebsiella pneumoniae (28 bloodstream isolates, 2 cerebrospinal fluid isolates) and Escherichia coli (18 bloodstream isolates, 3 cerebrospinal fluid isolates, 2 subcutaneous isolates) were the most frequently isolated Gram negative Enterobacterales, with Pseudomonas species most common among non-Enterobacterales Gram negative organisms (16 bloodstream isolates, 1 cerebrospinal fluid isolate). Mortality rates in both culture-positive and culture-negative patients were high (52% and 28%, respectively), with greater than 50% of deaths occurring within 48 hours in both groups. 88% of Gram negative Enterobacterales were ceftriaxone resistant or intermediate, with 56% ciprofloxacin resistant or intermediate; 55% of isolates were resistant or intermediate to both. 71% of isolates were gentamicin resistant. Imipenem resistance remained low, with 91% of isolates retaining sensitivity. 24% of S. aureus isolates were oxacillin resistant and 34% of isolates were resistant or intermediate to trimethoprim/sulfamethoxazole. 100% of S. aureus isolates tested (14/60) retained sensitivity to clindamycin. Only 54% of pneumococcal isolates had positive oxacillin screens, implying frequent penicillin resistance, and only 60% of enterococcal species were ampicillin sensitive, although 92% retained vancomycin sensitivity. Conclusion We found higher mortality rates in our study than in similar studies; the contribution of issues such as limited access to advanced supportive care and delay in presentation is an area for further study. The high frequency of multidrug-resistant organisms is alarming, suggesting an urgent need to investigate underlying contributing factors, increase access to affordable broad-spectrum antibiotics, and create robust antimicrobial stewardship programs.

VITEK2 BASED DIAGNOSIS AND CHARACTERIZATION STAPHYLOCOCCI AERUS STRAIN CAUSING URINARY TRACT INFECATION IN FEMAL AND MALE

Background, The aim of this study was to assess the clinical presentation, risk factors, and comorbidities of the patients with Staphylococcus aureus bacteriuria, and to analyze the antimicrobial susceptibility data of S. aureus isolated from their urine samples. Methods, A total of 80 isolates of S. aureus were collected from patients with urinary tract infections (UTIs)in hospital Refai. Urinalysis was performed manually, including macroscopic examination of color and appearance, and microscopic examination for the presence of urinary pus cells, and bacteria and culture on MaCconky agar,Blood agar. Full diagnosis and susceptibility testing of S. aureus were performed by the VITEK 2 system (BioMérieux, Marcy-l'Étoile, France) using standard criteria. Results, The majority of the patients were female (50), with a mean age of 30 years and male(30) mean ageof45 years . Most of the patients were inhospatial . Seventy positive urine cultures were associated with UTI symptoms. ButTen negative urine cultures. Conclusion, Although S. aureus UTI is known to be associated with other risk factors such as urinary catheterization, long hospital stay, or complicated UTI, our results show the community-acquired presentation of UTI. Trimethoprim-sulfamethoxazole may be used as an effective treatment for UTI caused by S. aureus. S. aureus UTI could be an alarming sign of more invasive infections such as S. aureus bacteremia, though clinical evaluation and finding the source of S. aureus are crucial for effective treatment and prevention of further complications

Pertussis upsurge, age shift and vaccine escape post-COVID-19 caused by ptxP3 macrolide-resistant Bordetella pertussis MT28 clone in China

ObjectivesChina has experienced a notable upsurge in pertussis cases post-COVID-19, alongside an age shift to older children, increased vaccine escape, and a notable rise in the prevalence of macrolide-resistant Bordetella pertussis. Here, we present a genomic epidemiological investigation of these events. MethodsWe performed a retrospective observational study using culture-positive B pertussis isolated in Shanghai, China, from 2016 to 2024. We analysed strain and pertussis epidemiology dynamics by integrating whole-genome sequencing of 723 strains with antimicrobial susceptibility, transcriptomic profile, and clinical data. We compared the genome sequences of Shanghai strains with 6450 Chinese and global strains. ResultsFrom pre-COVID-19 (before December 2019) to post-COVID-19, patients shifted from predominantly infants (90%, 397/442) to a higher proportion of infections in older children (infant: 16%, 132/844), with the share of vaccinated individuals surging from 31% (107/340) to 88% (664/756). The macrolide-resistant Bordetella pertussis prevalence increased from 60% (267/447) to 98% (830/845). The emergence and expansion of a ptxP3-lineage macrolide-resistant clone, MR-MT28, which is uniquely capable of causing substantial infections among older children and vaccinated individuals, was temporally strongly associated with the pertussis upsurge and epidemiological transition. Although MR-MT28 showed increased expression of genes encoding pertussis toxin, it was associated with significantly milder clinical symptoms and a lower hospitalization rate. MR-MT28 likely originated in China around 2016, after acquiring several key mutations, including a novel prn150 allele, and has been detected across multiple regions in China. In addition, 26% (50/195) of MR-MT28 has evolved into predicted Pertactin (PRN)-deficient strains, with an IS481 insertion being the predominant mechanism. Discussion: We report that the post-COVID-19 upsurge of pertussis in China is associated with ptxP3-MR-MT28, and provide evidence that pathogen evolution is likely the primary factor driving + pertussis upsurge, age shift, and vaccine escape. MR-MT28 poses a high risk of global spread and warrants global surveillance.

Bayesian estimation of the prevalence of antimicrobial resistance: a mathematical modelling study.

Estimates of the prevalence of antimicrobial resistance (AMR) underpin effective antimicrobial stewardship, infection prevention and control, and optimal deployment of antimicrobial agents. Typically, the prevalence of AMR is determined from real-world antimicrobial susceptibility data that are time delimited, sparse, and often biased, potentially resulting in harmful and wasteful decision-making. Frequentist methods are resource intensive because they rely on large datasets. To determine whether a Bayesian approach could present a more reliable and more resource-efficient way to estimate population prevalence of AMR than traditional frequentist methods. Retrospectively collected, open-source, real-world pseudonymized healthcare data were used to develop a Bayesian approach for estimating the prevalence of AMR by combination with prior AMR information from a contextualized review of literature. Iterative random sampling and cross-validation were used to assess the predictive accuracy and potential resource efficiency of the Bayesian approach compared with a standard frequentist approach. Bayesian estimation of AMR prevalence made fewer extreme estimation errors than a frequentist estimation approach [n = 74 (6.4%) versus n = 136 (11.8%)] and required fewer observed antimicrobial susceptibility results per pathogen on average [mean = 28.8 (SD = 22.1) versus mean = 34.4 (SD = 30.1)] to avoid any extreme estimation errors in 50 iterations of the cross-validation. The Bayesian approach was maximally effective and efficient for drug-pathogen combinations where the actual prevalence of resistance was not close to 0% or 100%. Bayesian estimation of the prevalence of AMR could provide a simple, resource-efficient approach to better inform population infection management where uncertainty about AMR prevalence is high.

Evolutionary genomic analyses of canine E. coli infections identify a relic capsular locus associated with resistance to multiple classes of antimicrobials.

Much of the human genomic epidemiology data available for E. coli mechanism discovery studies has been heavily biased toward shiga-toxin producing strains from humans and livestock. E. coli occupies many niches and produces a wide variety of other significant pathotypes, including some implicated in chronic disease. We hypothesized that since dogs tend to share similar strains with their owners and are treated with similar antibiotics, their pathogenic isolates will harbor unexplored AMR mechanisms of importance to humans as well as animals. By comparing over 1,000 genomes with in vitro antimicrobial susceptibility data from sick dogs across the US and Canada, we identified a strong multidrug resistance association with an operon that appears to have once conferred a type 1 capsule production system.

Patient characteristics and antimicrobial susceptibility profiles of Escherichia coli and Klebsiella pneumoniae infections in international travellers: a GeoSentinel analysis.

Antimicrobial resistance (AMR) is a global health crisis, with Enterobacterales including Escherichia coli and Klebsiella pneumoniae playing significant roles. While international travel to low- and middle-income countries is linked to colonisation with AMR Enterobacterales, the clinical implications, particularly the risk of subsequent infection, remain unclear due to limited data. We aimed to characterise E. coli and K. pneumoniae infections in travellers and the antimicrobial susceptibility profiles of their isolates. We analysed data on E. coli and K. pneumoniae infections in travellers collected at GeoSentinel sites between 2015 and 2022, focusing on epidemiological, clinical and microbiological characteristics. We defined multi-drug resistance (MDR) as non-susceptibility to agents from at least three drug classes. Over the 8-year period, we included 655 patients (median age 41years; 74% female) from 57 sites in 27 countries, with 584 E. coli and 72K. pneumoniae infections. Common travel regions included Sub-Saharan Africa, Southeast Asia, and South-Central Asia. Urinary tract infections predominated. Almost half (45%) were hospitalised. Among infections with antimicrobial susceptibility data across three or more drug classes, 203/544 (37%) E. coli and 19/67 (28%) K. pneumoniae demonstrated MDR. Over one-third of E. coli and K. pneumoniae isolates were non-susceptible to third-generation cephalosporins and cotrimoxazole, with 38% and 28% non-susceptible to fluoroquinolones, respectively. Travellers to South-Central Asia most frequently had isolates non-susceptible to third-generation cephalosporins, fluoroquinolones and carbapenems. We observed increasing frequencies of phenotypic extended spectrum beta-lactamase and carbapenem resistance over time. E. coli and K. pneumoniae infections in travellers, particularly those to Asia, may be challenging to empirically treat. Our analysis highlights the significant health risks these infections pose to travellers and emphasises the escalating global threat of AMR. Enhanced, systematic AMR surveillance in travellers is needed, along with prospective data on infection risk post travel-related AMR organism acquisition.

Creative usage of Vivli’s Antimicrobial Resistance Surveillance Open Data through the Re-Use Data Challenge

The escalation of infections caused by drug-resistant bacteria worldwide poses a formidable challenge to global health, necessitating innovative approaches to combat this issue. In 2022, Vivli launched the Antimicrobial Resistance (AMR) Register, a platform that consolidates antimicrobial susceptibility data from pharmaceutical industry surveillance programs. This register provides a freely available and fully searchable user-friendly repository to facilitate scientific understanding of resistance patterns and support development of innovative strategies to address AMR globally. To promote the register’s utility, raise AMR awareness and encourage further re-use of the available data, Wellcome funded the Vivli AMR Surveillance Open Data Re-Use Data Challenge in 2023. This data challenge successfully fostered diverse, impactful, and innovative solutions that leveraged the AMR Register data to contribute to resolving the AMR crisis. The outcomes of the initiative underscore the importance of access to open data in stimulating collaboration and innovation in the public health domain, particularly in combatting the growing threat of drug-resistant infections.

Best Practice of Peritoneal Dialysis-Associated Gram-Negative Peritonitis in Children: Insights From the International Pediatric Peritoneal Dialysis Network Registry

Gram-negative peritonitis (GNP) is associated with significant morbidity in children receiving long-term peritoneal dialysis (PD) and current treatment recommendations are based on limited data. Analysis of 379 GNP episodes in 308 children (median age 6.9 years, interquartile range [IQR]: 3.0-13.6) from 45 centers in 28 countries reported to the International Pediatric Peritoneal Dialysis Network registry between 2011 and2023. Overall, 74% of episodes responded well to empiric therapy and full functional recovery (FFR) was achieved in 82% of cases. Invitro bacterial susceptibility to empiric antibiotics and lack of severe abdominal pain at onset were associated with a good initial response. Risk factors for failure to achieve FFR included severe abdominal pain at onset and at 60 to 72 hours from treatment initiation (odds ratio [OR]: 3.81, 95% confidence interval [CI]: 2.01-7.2 and OR: 3.94, 95% CI: 1.06-14.67, respectively), Pseudomonas spp. etiology (OR: 1.73, 95% CI: 1.71-4.21]) and invitro bacterial resistance to empiric antibiotics (OR: 2.40, 95% CI: 1.21-4.79); the risk was lower with the use of monotherapy as definitive treatment (OR: 0.40, 95% CI: 0.21-0.77). Multivariate analysis showed no benefit of dual antibiotic therapy for treatment of Pseudomonas peritonitis after adjustment for age, presenting symptomatology, 60 to 72-hour treatment response, and treatment duration. Monotherapy with cefazolin in susceptible Enterobacterales peritonitis resulted in a similar FFR rate (91% vs. 93%) as treatment with ceftazidime or cefepime monotherapy. Detailed microbiological assessment, consisting of patient-specific and center-specific antimicrobial susceptibility data, should guide empiric treatment. Treatment "deescalation" with the use of monotherapy and narrow spectrum antibiotics according to susceptibility data is not associated with inferior outcomes and should be advocated in the context of emerging bacterial resistance.

Corynebacterium diphtheriae and Corynebacterium ulcerans: development of EUCAST methods and generation of data on which to determine breakpoints.

Evidence-based clinical susceptibility breakpoints have been lacking for antimicrobial agents used for diphtheria. We aimed to evaluate broth microdilution and disc diffusion methods and create a dataset of MIC values and inhibition zone diameters (ZDs) from which breakpoints could be determined. We included 400 recent clinical isolates equally distributed by species (Corynebacterium diphtheriae and Corynebacterium ulcerans) and by national surveillance programmes (France and Germany). Non-duplicate toxigenic and non-toxigenic isolates were chosen to enable the inclusion of a diversity of susceptibility levels for the 13 agents tested. Broth microdilution and disc diffusion, using EUCAST methodology for fastidious organisms, were used. The distributions of MIC and ZD values were largely in agreement among methods and countries. Breakpoints to allow categorization of WT isolates as susceptible, i.e. susceptible (S) or susceptible, increased exposure (I) were determined for 12 agents. The data supported a breakpoint for benzylpenicillin and amoxicillin of resistant (R) > 1 mg/L since WT isolates were inhibited by 1 mg/L or less. WT isolates were categorized as I (S ≤ 0.001 mg/L) for benzylpenicillin, emphasizing the need for increased exposure, and S (S ≤ 1 mg/L) for amoxicillin. Erythromycin breakpoints were set at S ≤ 0.06 mg/L and R > 0.06 mg/L. The corresponding ZD breakpoints were determined for all agents except amoxicillin, for which categorization was based on benzylpenicillin results. This work provided a large set of antimicrobial susceptibility data for C. diphtheriae and C. ulcerans, using a harmonized methodology. The dataset allowed EUCAST and experts in the diphtheria field to develop evidence-based breakpoints in January 2023.

Predictive Modeling of Phenotypic Antimicrobial Susceptibility of Selected Beta-Lactam Antimicrobials from Beta-Lactamase Resistance Genes.

The outcome of bacterial infection management relies on prompt diagnosis and effective treatment, but conventional antimicrobial susceptibility testing can be slow and labor-intensive. Therefore, this study aims to predict phenotypic antimicrobial susceptibility of selected beta-lactam antimicrobials in the bacteria of the family Enterobacteriaceae from different beta-lactamase resistance genotypes. Using human datasets extracted from the Antimicrobial Testing Leadership and Surveillance (ATLAS) program conducted by Pfizer and retail meat datasets from the National Antimicrobial Resistance Monitoring System for Enteric Bacteria (NARMS), we used a robust or weighted least square multivariable linear regression modeling framework to explore the relationship between antimicrobial susceptibility data of beta-lactam antimicrobials and different types of beta-lactamase resistance genes. In humans, in the presence of the blaCTX-M-1, blaCTX-M-2, blaCTX-M-8/25, and blaCTX-M-9 groups, MICs of cephalosporins significantly increased by values between 0.34-3.07 μg/mL, however, the MICs of carbapenem significantly decreased by values between 0.81-0.87 μg/mL. In the presence of carbapenemase genes (blaKPC, blaNDM, blaIMP, and blaVIM), the MICs of cephalosporin antimicrobials significantly increased by values between 1.06-5.77 μg/mL, while the MICs of carbapenem antimicrobials significantly increased by values between 5.39-67.38 μg/mL. In retail meat, MIC of ceftriaxone increased significantly in the presence of blaCMY-2, blaCTX-M-1, blaCTX-M-55, blaCTX-M-65, and blaSHV-2 by 55.16 μg/mL, 222.70 μg/mL, 250.81 μg/mL, 204.89 μg/mL, and 31.51 μg/mL respectively. MIC of cefoxitin increased significantly in the presence of blaCTX-M-65 and blaTEM-1 by 1.57 μg/mL and 1.04 μg/mL respectively. In the presence of blaCMY-2, MIC of cefoxitin increased by an average of 8.66 μg/mL over 17 years. Compared to E. coli isolates, MIC of cefoxitin in Salmonella enterica isolates decreased significantly by 0.67 μg/mL. On the other hand, MIC of ceftiofur increased in the presence of blaCTX-M-1, blaCTX-M-65, blaSHV-2, and blaTEM-1 by 8.82 μg/mL, 9.11 μg/mL, 8.18 μg/mL, and 1.04 μg/mL respectively. In the presence of blaCMY-2, MIC of ceftiofur increased by an average of 10.20 μg/mL over 14 years. The ability to predict antimicrobial susceptibility of beta-lactam antimicrobials directly from beta-lactamase resistance genes may help reduce the reliance on routine phenotypic testing with higher turnaround times in diagnostic, therapeutic, and surveillance of antimicrobial-resistant bacteria of the family Enterobacteriaceae.

Microbiological Survey and Evaluation of Antimicrobial Susceptibility Patterns of Microorganisms Obtained from Suspect Cases of Canine Otitis Externa in Gran Canaria, Spain.

A retrospective study of microbiological laboratory results from 2020 to 2022, obtained from a veterinary diagnostic laboratory of the island of Gran Canaria, Spain, focused on canine otitis cases, was performed. The objective of this study was to analyze the pathogen distribution, antimicrobial susceptibility, prevalence of multidrug resistant phenotypes and the role of coinfections in otitis cases in order to provide up-to-date evidence that could support effective control strategies for this prevalent pathology. A total of 604 submissions were processed for the diagnosis of canine external otitis. Of the samples analyzed, 472 were positive for bacterial or fungal growth (78.1%; 95% CI: 74.8-81.4%). A total of 558 microbiological diagnoses were obtained, divided in 421 bacterial (75.4%; 95% CI: 71.8-79.0%) and 137 fungal (24.6%; 95% CI: 20.9-28.1%) identifications. Staphylococcus pseudintermedius, Malassezia pachydermatis and Pseudomonas aeruginosa were the most prevalent microorganisms detected in clinical cases of otitis. High level antimicrobial resistance was found for Pseudomonas aeruginosa (30.7%), Proteus mirabilis (29.4%), Staphylococcus pseudintermedius (25.1%) and Escherichia coli (19%). Multidrug-resistant phenotypes were observed in 47% of the bacteria isolated. In addition, a 26.4% prevalence of methicillin-resistant Staphylococcus pseudintermedius was detected. The high prevalence of antimicrobial resistant phenotypes in these bacteria highlights the current necessity for constant up-to-date prevalence and antimicrobial susceptibility data that can support evidence-based strategies to effectively tackle this animal and public health concern.

In vitro antimicrobial susceptibility data of global meropenem-resistant Acinetobacter baumannii isolates causing pneumonia: Data from the Antimicrobial Testing Leadership and Surveillance Program, 2014–2021, and re-estimations of susceptibility breakpoints and appropriate dosages of important antibiotics for pneumonia treatment

To evaluate the susceptibility of globally pneumonia-causing meropenem-resistant (MEM-R) Acinetobacter baumannii isolates against important antibiotics and estimate appropriate dosages of indicated antibiotics. We extracted the 2014-2021 Antimicrobial Testing of Leadership Surveillance database regarding the susceptibility of MEM-R A. baumannii isolates causing pneumonia against important antibiotics. The susceptibility and carbapenemase-encoding gene (CPEG) data of pneumonia-causing MEM-R A. baumannii isolates from patients hospitalized in intensive care units of five major regions were analyzed. The susceptibility breakpoints (SBP) recommended by the Clinical and Laboratory Standards Institute (CLSI) in 2022, other necessary criteria [SBP of MIC for colistin, 2 mg/L, in the CLSI 2018; and cefoperazone-sulbactam (CFP-SUL), 16 mg/L], and the pharmacokinetic and pharmacodynamic data of indicated antibiotics were employed. Applying the aforementioned criteria, we observed the susceptible rates of colistin, minocycline, and CFP-SUL against the pneumonia-causing MEM-R A. baumannii isolates globally (n = 2905) were 93.2%, 69.1%, and 26.3%, respectively. Minocycline was significantly more active in vitro (MIC ≤4 mg/L) against the pneumonia-causing MEM-R A. baumannii isolates collected from North and South America compared to those from other regions (>90% vs. 58-72%). Additionally, blaOXA-23 and blaOXA-72 were the predominant CPEG in pneumonia-causing MEM-R A. baumannii isolates. After deliberative estimations, dosages of 200 mg minocycline intravenously every 12 h (SBP, 8 mg/L), 100 mg tigecycline intravenously every 12 h (SBP, 1 mg/L), and 160 mg nebulized colistin methanesulphonate every 8 h (SBP, 2 mg/L) are needed for the effective treatment of pneumonia-causing MEM-R A. baumannii isolates.

Clinical and microbiological characteristics of Ruminococcus gnavus bacteremia and intra-abdominal infection

ObjectivesRuminococcus gnavus is a rare human pathogen, and clinical data on R. gnavus infection are insufficient. This retrospective study aimed to investigate the clinical characteristics of R. gnavus infections. MethodsThis study included 13 cases of bacteremia and three cases of non-bacteremia infections caused by R. gnavus. We evaluated the patient data, infection source, clinical outcomes, and antimicrobial susceptibility of R. gnavus isolates for these cases. ResultsThe median age of patients was 75 years (range 47–95), and eight patients were female. Twelve cases were presumed to have an intra-abdominal infection source, and the remaining four cases had an unknown infection source. The most common underlying conditions were immunosuppression (seven cases), solid tumors (seven cases), and history of gastrointestinal surgery (five cases). Thirteen patients exhibited gastrointestinal problems (dysfunction, bleeding, intra-abdominal infection, or inflammation). Multiple pathogens were observed in six cases, and fatal outcomes were recorded in three cases. Antimicrobial susceptibility data were available for eight isolates, all of which exhibited low minimum inhibitory concentrations to penicillin (≤0.03 μg/mL), ampicillin–sulbactam (≤0.5 μg/mL), piperacillin–tazobactam (≤4 μg/mL), and metronidazole (≤0.5–1 μg/mL). ConclusionRuminococcus gnavus is frequently associated with an intra-abdominal infection source, and treatment strategies should consider the possibility of multiple pathogens.

Salmonella enterica Serovar Dublin from Cattle in California from 1993 to 2019: Characterization and Analysis of Antimicrobial Resistance Diversity.

For this study, antimicrobial susceptibility data for Salmonella enterica subsp. enterica serovar Dublin (S. Dublin)-a well-known cattle-adapted pathogen with current concerns for multidrug resistance-were recovered from cattle at the California Animal Health and Food Safety Laboratory System (CAHFS) over the last three decades (1993-2019) and were evaluated using tools to capture diversity in antimicrobial resistance. For this purpose, minimum inhibitory concentration (MIC) testing was conducted for 247 clinical S. Dublin isolates. Antimicrobial resistance (AMR) profiles revealed a predominant core multidrug-resistant pattern in the three most common AMR profiles observed. Antimicrobial resistance richness, diversity, and similarity analysis revealed patterns for changes in AMR profiles for different age groups. Discriminant analysis using MIC log2-transformed data revealed changes in MIC for year groups, with a time-sequence pattern observed. Drivers for reduced susceptibility were observed for 3rd generation cephalosporins and quinolones observed for more recent year groups (2011-2015 and 2016-2019) when compared to older year groups (1993-1999 and 2000-2005). Together, these results highlight the changes in the diversity of AMR profiles, as well as changes in susceptibility of S. Dublin over time for critical antimicrobials of importance to both animals and humans, and support the need for continued monitoring and efforts that will support judicious use of antimicrobials, especially for these two drug classes.

Analysis of blood culture data at a university hospital: bacterial distribution and cumulative antimicrobial resistance (2016–2020)

Background: The distribution of bacteria isolated from bloodstream infections and cumulative antimicrobial susceptibility data are the basis for empirical decisions regarding antibiotics as an initial treatment. Therefore, it is important to consistently collect blood culture results of individual patients and analyze them correctly. Methods: The blood culture results of patients at Gachon University Gil Medical Center from 2016 to 2020 were analyzed retrospectively to determine the bacterial distributions and antibiotic resistance patterns. Duplicates were eliminated by including only the first isolate of each species per patient. Results: Escherichia coli (27.1%) was the most commonly isolated bacterium from blood cultures, followed by Klebsiella pneumoniae (10.1%) and Staphylococcus aureus (8.6%). The methicillin resistance rate of S. aureus was 49.2%, and the vancomycin resistance rate of Enterococcus faecium was 39.5%; with no significant changes over the study period. The cefotaxime, ciprofloxacin, and ertapenem resistance rates of E. coli were 35.0%, 46.8%, and 0.7%, respectively. Seventeen carbapenem-resistant E. coli strains were isolated, of which 11 produced carbapenemase. The cefotaxime, ciprofloxacin, and ertapenem resistance rates of K. pneumoniae were 29.5%, 31.7%, and 5.4%, respectively. Forty-eight carbapenem-resistant K. pneumoniae strains were isolated, of which 37 produced carbapenemase. The imipenem resistance rates of Acinetobacter baumannii and Pseudomonas aeruginosa were 72.3% and 23.4%, respectively. Conclusion: In the blood culture results from 2016 to 2020, the isolation frequency of E. coli, K. pneumoniae, and E. faecium showed an increasing trend, whereas that of S. aureus was stable. Over the 5 year study period, the ciprofloxacin resistance rate of E. coli and P. aeruginosa and ampicillin/sulbactam resistance rate of A. baumannii significantly increased.

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

61 Antibiotic Resistant Patterns of Bacterial Pathogens Causing Invasive Neonatal Infections in Northern Alberta

Abstract Background Antimicrobial resistance is one of the most serious global health threats facing the world today. The neonatal intensive care unit (NICU) is a clinical environment that houses newborn infants who are highly susceptible to overwhelming infection. Early and decisive treatment with powerful anti-microbials tends to be the preferred clinical choice for treating sick infants empirically. Prolonged exposure to antimicrobials can result in multi-drug resistant organisms (MDROs), which can be associated with mortality due to an increase in virulence, delay in appropriate treatment, and a lack of treatment options. An updated antibiogram is important for determining the optimal empirical antimicrobial choice for sepsis evaluations. There is currently a lack of antimicrobial susceptibility data for bacterial pathogens in the Northern Alberta region. Objectives The objective of this study is to understand the antibiotic resistance patterns among isolates responsible for bacteremia and meningitis in the NICUs in Northern Alberta through the standard antibiograms produced by microbiology laboratories. Design/Methods We conducted a retrospective study to analyze antimicrobial resistance patterns found in NICUs during 2013-2021 in Northern Alberta. Bacteria isolated from blood and cerebrospinal fluid according to commonly used antibiotics in NICUs were collated to create a provincial antibiogram. Results A total of 5562 isolates were included in this antibiogram. The most frequently isolated organisms were Escherichia coli (1521), Staphylococcus aureus (1157), members of coagulase-negative staphylococcus (534), Enterococcus faecalis (326), and Klebsiella pneumoniae (357) in neonatal populations. Among the 1157 S. aureus isolates, 24% were resistant to oxacillin (i.e., “methicillin-resistant S. aureus” or MRSA) and 1% were resistant to vancomycin (i.e., “vancomycin-resistant S. aureus” or VRSA). Of the 326 strains of Enterococcus spp., there were no vancomycin-resistant enterococci (VRE) identified. Among gram-negative isolates, 251 out of the 2690 (9.6%) were producing extended-spectrum beta-lactamase (ESBL), in which 52% and 94% were susceptible to gentamicin and amikacin respectively. Among the non-ESBL-producing isolates, E. coli (1521) and K. pneumoniae (357), 7% of the E. coli strains and 1% of the K. pneumoniae strains were resistant to gentamicin. Conclusion The provincial antibiogram is a useful clinical tool that can best inform clinicians on the appropriate choice of empirical antimicrobial agent based on commonly identified invasive pathogens in neonatal infections within Northern Alberta. Our findings on these resistant patterns can aid next steps for developing an antimicrobial stewardship program.

Resistome-based surveillance identifies ESKAPE pathogens as the predominant gram-negative organisms circulating in veterinary hospitals.

Healthcare-associated infections (HCAIs) associated with extended-spectrum cephalosporin-resistant gram-negative (ESC-R GN) bacteria are an emerging concern in veterinary hospitals, especially in companion animal intensive care units (ICUs). To understand the molecular epidemiology of ESC-R GN isolates in two veterinary hospitals (equine and small animal), a 6-month pilot study was performed during which fecal and environmental samples were obtained twice from selected patients, upon ICU admission and after 48 h of hospitalization. In total, 295 ESC-R GNs were analyzed using the Acuitas Resistome® Test (OpGen, Maryland, US), a PCR-based assay screening for 50 antimicrobial resistance gene families encoding for production of extended-spectrum beta-lactamase (ESBLs), TEM/SHV/OXA or AmpC beta-lactamases and carbapenemases. Combining organism identification and antimicrobial susceptibility data to genotyping results, unique "Acuitas profiles" were generated that can be used for fast typing the isolates and tracking transmission events. ESKAPE GN pathogens were the most prevalent ESC-R GN isolates circulating in both the small animal and equine hospitals, consisting of Enterobacter cloacae complex (21.7%), Pseudomonas aeruginosa (20%), Klebsiella pneumoniae (15.9%), and Acinetobacter baumannii complex (13.6%) followed by Escherichia coli (12.2%), most harboring a combination of genes encoding for beta-lactamases and ESBLs. Some ESKAPE genotypes showed likely intra-hospital transmission, including E. cloacae (two genotypes, one carrying SHV4, SHV5, and TEM7 and the other TEM1, TEM3, and TEM7 enzymes) in the equine and K. pneumoniae (SHV1, SHV5, and DHA1-positive) in the small animal ICUs, respectively. Furthermore, P. aeruginosa (carrying OXA-50), A. baumannii complex (OXA-51), and E. coli (CTX-M-1) genotypes were isolated across both hospitals, suggesting possible transfer mediated via movement of staff and students. Importantly, isolates carrying transmissible resistance to last-resort antimicrobials (i.e. carbapenems) were identified within the hospital environments, consisting of three environmental Acinetobacter spp. harboring blaOXA - 23 and one clinical E. coli with blaOXA - 48. We describe the widespread occurrence of ESKAPE gram-negative organisms in veterinary ICU patients and hospital environments. Findings from this project provide baseline data on the epidemiology of ESKAPE pathogens in veterinary settings, which can inform infection control policies to aid in patient management and prevent transmission of nosocomial infections associated with these pathogens.

Secondary Infections in Intensive Care Unit Patients in the COVID-19 Pandemic - Retrospective Study of the Incidence, Patterns, Risk Factors, and Outcomes

Introduction: The COVID-19 pandemic has raised significant concerns for secondary infections. In the second wave, there was an unprecedented epidemic of secondary invasive fungal infections. This study analyses the prevalence, details, risk factors, and outcomes of secondary infections in COVID-19 patients in a tertiary intensive care unit (ICU) in India. Materials and Methods: Retrospective analysis of secondary infections in ICU COVID-19 patients between April 2021 and June 2021. Demographic data, secondary bacterial and fungal infections, immunomodulator therapy, antimicrobial susceptibility data, and clinical outcomes were analyzed. Results: 71/238 (29.83%) ICU patients developed secondary bacterial and fungal infections. Mortality with secondary infections was significantly higher (80.28% [P < 0.05]), compared to an overall ICU mortality of 51.68%. In patients with secondary infections, 59.66% were referred from other hospitals after receiving initial treatment and 52.10% had received various immunomodulatory therapies. Prolonged mechanical ventilation, indwelling central venous, and urinary catheters had higher secondary infection rates and higher mortality. Gram-negative bacteria were isolated in 85.91% and 32.39% had fungal isolates. Klebsiella pneumoniae, followed by Acinetobacter baumannii, were the predominant bacteria. Candida spp., followed by Mucormycosis, were the predominant fungal pathogens. Multi-drug resistant (MDR) infections were common (73.28%). 49.3% of secondary infection patients had polymicrobial infections, including fungal infections, with a higher mortality of 82.86%. Conclusions: There was a high incidence of secondary MDR bacterial and fungal infection, including Mucormycosis, in ICU COVID-19 patients, with higher mortality. Risk factors included immunomodulators such as tocilizumab, bevacizumab, and itolizumab, steroids, invasive tubes and catheters, and prolonged ICU and hospital stay. By uniform steroids, we meant the recommended use of moderate-to-high dose steroids for all patients with severe COVID-19 pneumonia (recovery trial), invasive tubes and catheters, and prolonged ICU and hospital stay.