Susceptibility Testing Data Research Articles

Antibiotic Susceptibility among Infective Endocarditis Population: Syndromic Antibiogram Evaluation at Indonesian National Cardiovascular Center

Infective Endocarditis (IE) is a life-threatening disease with a high mortality rate (25%). Laboratory approaches to support the diagnosis of IE especially blood and/or cardiac vegetation culture, are crucial for providing definitive therapy. However, negative culture is frequently observed, therefore empirical use of antibiotics seems unavoidable and may lead to increasing antimicrobial resistance. This study aims to observe the prevalence of antibiotic susceptibility among the IE population using the WISCA approach. This retrospective study observed medical record data of all inpatients diagnosed with IE according to ICD-10 at Cardiovascular Center Harapan Kita Hospital (NCCHK) between January 2018 and December 2022. Patient data were combined with bacterial identification and antibiotic susceptibility test data from the laboratory information system, and evaluated based on period (year). A total of 67,858 inpatients and 1.1% (n=772) were diagnosed with IE. Successful culture growth (blood and/or cardiac vegetation specimen) was between 36.8% and 70% annually. Streptococcus viridans group (82/237, 34.6%) and Coagulase-negative Staphylococci (57/237, 24.1%) were dominantly observed among the IE population. Low susceptibility among Penicillin (34.3%) towards Gram-positive bacteria, as first-line treatment option in IE. Meanwhile, high susceptibility range was observed in Ceftriaxone (95.7%), Gentamicin (80.4%), Rifampicin (84.4%), and Vancomycin (98.7%) as second-line treatment in IE. Despite the low prevalence, the occurrence of antimicrobial resistance in IE has become a priority concern. Continuing the syndromic antibiogram is mandatory to assist the trend of empirical antibiotic usage and refine the established local treatment guidelines.

Prevalence and distribution of carbapenem-resistant Enterobacterales in companion animals: A nationwide study in the United States using commercial laboratory data.

Carbapenem-resistant Enterobacterales (CRE) are a concern in both human and animal medicine globally. Despite extensive research in humans, limited data exist on CRE in companion animals, with a lack of nationwide prevalence estimates. To assess the occurrence and trends of CRE in cats and dogs across the United States by analyzing 4 years of commercial antimicrobial susceptibility testing (AST) data. Between 2019 and 2022, 477 426 ASTs were conducted on Enterobacterales isolates against imipenem. Isolates were derived from 379 598 dogs and 97 828 cats. Animal origin was not disclosed. In this retrospective study, antimicrobial susceptibility test data from IDEXX Laboratories were analyzed. Analysis included resistance estimations to imipenem stratified by sampling site, an assessment of resistance patterns over time and location, and the application of space-time cluster analysis to identify potential outbreaks. Antibiograms were produced for carbapenem-resistant isolates. Susceptibility to imipenem was high, at 98.86%. Temporal analysis indicated stability in susceptibility, with an unexplained reduction in susceptible isolates in June 2019. Spatial analysis identified 2 high-risk clusters along the Western Coast (relative risk [RR]: 23.26; P < .001) and in Texas (RR: 10.72; P < .001) in that month. Three other clusters were found, in Missouri (RR: 39.55; P = .038), Florida (RR: 4.53; P < .001), and New York (RR: 9.20; P < .001). CRE are present at a low prevalence in dogs and cats across the United States. Variations in prevalence across patient-level and environmental factors highlight the need for tailored stewardship programs.

Prolonged treatment of dermatophytosis caused by Trichophyton indotinea with terbinafine or itraconazole impacts better outcomes irrespective of mutation in the squalene epoxidase gene.

Over the past decades, the increasing incidence of recurrent dermatophytosis associated with terbinafine-resistant Trichophyton has posed a serious challenge in management of dermatophytosis. Independent reports of failure of treatment and high minimum inhibitory concentrations (MIC) of antifungals are available, but data correlating MIC and clinical outcomes is still sparse. Therefore, the present study was conducted to evaluate the outcomes of systemic treatment of dermatophytosis and its correlation with MIC of the etiological agents isolated from such patients. Retrospective analysis of 587 consecutive patients with dermatophytosis was done from March 2017 to March 2019. Demographic and clinical details of the patients were noted, along with the results of direct microscopy and fungal culture. The isolates were identified by sequencing the internal transcribed spacer region of rDNA. Antifungal susceptibility testing was performed following the CLSI M38 protocol. Mutation in the squalene epoxidase (SE) gene was detected by DNA sequencing and ARMS-PCR. Based on the culture-positivity and prescribed systemic antifungal, patients were categorised into Group I culture-positive cases treated with systemic terbinafine and Group II culture-positive cases treated with systemic itraconazole, each for a total period of 12 weeks. In the present study, 477 (81.39%) were culture-positive; however, 12 weeks follow-up was available for 294 patients (Group I-157 and Group II-137) who were included for statistical analysis. In both groups [Group I-37/63 (51.4%) and Group II-14/54 (58.3%)], a better cure rate was observed if the initiation of therapy was performed within <6 months of illness. Treatment outcome revealed that if therapy was extended for 8-12 weeks, the odds of cure rate are significantly better (p < .001) with either itraconazole (Odd Ratio-15.5) or terbinafine (Odd Ratio-4.34). Higher MICs for terbinafine were noted in 41 cases (cured-18 and uncured-23) in Group I and 39 cases (cured-16 and uncured-23) in Group II. From cured (Group I-17/18; 94.4% and Group II-14/16; 87.5%) and uncured (Group I-20/23; 86.9% and Group II-21/23; 91.3%) cases had F397L mutation in the SE gene. No significant difference in cure rate was observed in patients with Trichophyton spp. having terbinafine MIC ≥ 1or <1 μg/mL (Group I-p = .712 and Group II-p = .69). This study revealed that prolonging terbinafine or itraconazole therapy for beyond 8 weeks rather than the standard 4 weeks significantly increases the cure rate. Moreover, no correlation has been observed between antifungal susceptibility and clinical outcomes. The MIC remains the primary parameter for defining antifungal activity and predicting the potency of antifungal agents against specific fungi. However, predicting therapeutic success based solely on the MIC of a fungal strain is not always reliable, as studies have shown a poor correlation between invitro data and invivo outcomes. To address this issue, further correlation of antifungal susceptibility testing (AFST) data with clinical outcomes and therapeutic drug monitoring is needed. It also highlights that initiation of the treatment within <6 months of illness increases cure rates and reduces recurrence. Extensive research is warranted to establish a better treatment regime for dermatophytosis.

The rv2820c K114N mutation is related with capreomycin tolerance

As one of the factors affecting the treatment outcomes, drug tolerance in mycobacteriosis has not been paid due attention. Genome-wide association studies on 607 Mycobacterium tuberculosis clinical isolates with phenotypic drug susceptibility test data revealed that a K114N mutation on the rv2820c gene was highly enriched in capreomycin-resistant isolates (32/213, 15.02%). However, the mutation was also observed in capreomycin-sensitive isolates (10/394, 2.53%). In most cases (31/42, 73.81%), the rv2820c K114N mutation occurred in isolates with the known capreomycin resistance conferring mutation rrs A1401G. In contrast, the general frequency of the rv2820c K114N mutation was low in 7061 genomes downloaded from the National Center for Biotechnology Information database. To determine the impact of this mutation on the antimycobacterial activity of capreomycin, the intact rv2820c gene and the rv2820c K114N mutant were over-expressed in Mycobacterium smegmatis (Ms), and the results of susceptibility tests showed that the rv2820c K114N mutation did not affect the minimum inhibition concentration (MIC) of capreomycin. Subsequently, the data of time-kill assays showed that, it took only 2 h of capreomycin treatment (40 μg/ml, 5 × MIC) to kill 99.9% bacterial cells of Ms MC2155 pMV261::rv2820cH37Rv, while it took 6 h to achieve that for Ms MC2155 pMV261::rv2820cK114N. Taken together, these data suggested that the rv2820c K114N mutation is related with capreomycin tolerance, which merits further investigation.

A five-year retrospective antibiogram review in the paediatric burns unit at a tertiary South African Hospital

BackgroundThere is a global concern regarding increasing colonization and/or infection of paediatric burns patients with multi-drug-resistant organisms, especially in Africa. Surveillance of antimicrobial resistant patterns enables clinicians to opt for the most appropriate empiric antimicrobial agent according to the unit’s susceptibility profile. ObjectiveThis study sought to compile unit-specific antibiograms comparing the organism prevalence and their antimicrobial resistance trends in the paediatric burns unit, Chris Hani Baragwanath Academic Hospital (CHBAH) from January 2015 to December 2019. MethodsA retrospective, laboratory-based review was conducted of bacterial and fungal isolates including antimicrobial susceptibility testing (AST) data from blood cultures and tissue samples. Enterobacterales, non-fermenters, gram-positive organisms, and yeasts were analysed as a percentage of total positive blood cultures comparing 2015–2017 to 2018–2019 data. Analysis of antimicrobial resistance trends was performed for extended-spectrum beta-lactamases (ESBLs), carbapenem-resistant Enterobacterales (CRE), extensively-drug-resistant (XDR) Acinetobacter baumannii, and meticillin-resistant Staphylococcus aureus (MRSA) for the years 2015, 2017, and 2019. ResultsA total of 1243 blood culture isolates were studied with A.baumannii (208/1243;17 %), coagulase negative staphylococci (141/1243; 11 %) and Candida auris (53/1243; 4 %) representing the predominant gram-negative bacteria, gram-positive bacteria, and yeast, respectively. A significant decrease in ESBLs (p = 0.00) was noted with a rise in CREs (p = 0.00) during the study period. Majority of the A. baumannii were XDR (≥77 %) despite an appreciable decrease. A notable decrease in MRSA (p = 0.00) isolates was observed. Pseudomonas aeruginosa (72/275; 26 %) was the leading organism recovered from a total of 275 tissue isolates. ConclusionThe results of this study encourage review of the current antimicrobial choices in the unit for empiric antibacterial cover. Due to the low numbers of yeasts, we cannot comment on the institution of early antifungal strategies. We support reinforced infection prevention and control practices as well as antimicrobial stewardship initiatives.

Practice of standardization of CLSI M45 A3 antimicrobial susceptibility testing of Infrequently Isolated or Fastidious Bacteria strains isolated from blood specimens in Guangdong Province 2017-2021.

The concentration of antimicrobial agents in environments like water and food has increased rapidly, which led to a rapid increase in antimicrobial resistance levels in the environment. Monitoring of bacterial resistance levels is considered as a necessary means to control the bacterial resistance. Reference standards are critical for antimicrobial susceptibility testing. CLSI M45 A3 standard defines pathogenic microorganisms that cause infections less frequently than those covered by CLSI M02, M07, and M100 as Infrequently Isolated or Fastidious Bacteria and specifies antimicrobial susceptibility testing methods. Our study investigated the epidemiology and antimicrobial susceptibility testing data of Infrequently Isolated or Fastidious Bacteria strains isolated from blood specimens in 70 hospitals in Guangdong Province between 2017 and 2021. We defined testing methods other than those specified in CLSI M45 A3 as "Non-Standardized." The proportion of standardized antimicrobial susceptibility testing for penicillin increased significantly (Corynebacterium spp. 17.4% vs. 50.0% p < 0.05; Micrococcus spp. 50.0% vs. 77.8% p < 0.05; Abiotrophia spp. and Granulicatella spp. 21.4% vs. 90.9% p < 0.001), while for cefotaxime (Corynebacterium spp. 0.0% vs. 45.2% p < 0.05; Abiotrophia spp. and Granulicatella spp. 0.0% vs. 14.3% p = 0.515) and vancomycin increased finitely. Non-standardized methods were used for all other antimicrobials. Due to limitations in the economic and medical environment, some clinical laboratories are unable to fully comply with CLSI M45 A3 standard. We recommend that CLSI should add breakpoints for disk diffusion method to improve the standardization of antimicrobial susceptibility testing.

Clinicomycological Study of Dermatophyte Infections in Patients Attending Dermatology Outpatient Department in a Tertiary Care Hospital

Context: Dermatophytosis is a fungal disease characterized by the infection of skin, hair, and nails. There is an upsurge of complicated superficial dermatophytosis and an increase in the incidence of chronic, relapsing, recurrent cases in India that are also often unresponsive to conventional doses of drugs. Aims: The aim of this study was to study the prevalence of dermatophyte species in the particular study area and it is susceptibility to itraconazole, terbinafine, and fluconazole. Settings and Design: All dermatophytes isolates obtained were subjected to 10% KOH mount, fungal culture, and antifungal sensitivity testing for fluconazole, itraconazole, and terbinafine. Materials and Methods: Newly diagnosed cases of dermatophytosis without treatment for the past 3 months were included in the study. KOH preparation was observed and subjected to fungal culture. Then, the susceptibility of the dermatophytes to oral antifungals (itraconazole, terbinafine, and fluconazole) was done. Results: Out of 28 patients with tinea, 14 males and 12 females were tested KOH positive. Out of them, 23 patients showed positive for dermatophyte growth. In them, 15 isolates were Trichophyton mentagrophytes and 8 isolates were Trichophyton rubrum. Antifungal drug susceptibility testing data indicated that, for the two species, MIC of itraconazole ranged between 0.03 and 16 μg/ml, terbinafine between 0.03 and 16 μg/ml, and fluconazole between 0.25 and 64 μg/ml. Conclusions: The study provided information regarding the prevalent species of dermatophyte in our study area and it is high sensitivity to itraconazole compared to terbinafine and the lowest for fluconazole. This gives us guidance as to which antifungal to use empirically in our clinical practice to treat tinea infection.

Antimicrobial and Diagnostic Stewardship of the Novel β-Lactam/β-Lactamase Inhibitors for Infections Due to Carbapenem-Resistant Enterobacterales Species and Pseudomonas aeruginosa.

Carbapenem-resistant Gram-negative bacterial infections are a major public health threat due to the limited therapeutic options available. The introduction of the new β-lactam/β-lactamase inhibitors (BL/BLIs) has, however, altered the treatment options for such pathogens. Thus, four new BL/BLI combinations-namely, ceftazidime/avibactam, meropenem/vaborbactam, imipenem/relebactam, and ceftolozane/tazobactam-have been approved for infections attributed to carbapenem-resistant Enterobacterales species and Pseudomonas aeruginosa. Nevertheless, although these antimicrobials are increasingly being used in place of other drugs such as polymyxins, their optimal clinical use is still challenging. Furthermore, there is evidence that resistance to these agents might be increasing, so urgent measures should be taken to ensure their continued effectiveness. Therefore, clinical laboratories play an important role in the judicious use of these new antimicrobial combinations by detecting and characterizing carbapenem resistance, resolving the presence and type of carbapenemase production, and accurately determining the minimum inhibitor concentrations (MICs) for BL/BLIs. These three targets must be met to ensure optimal BL/BLIs use and prevent unnecessary exposure that could lead to the development of resistance. At the same time, laboratories must ensure that results are interpreted in a timely manner to avoid delays in appropriate treatment that might be detrimental to patient safety. Thus, we herein present an overview of the indications and current applications of the new antimicrobial combinations and explore the diagnostic limitations regarding both carbapenem resistance detection and the interpretation of MIC results. Moreover, we suggest the use of alternative narrower-spectrum antibiotics based on susceptibility testing and present data regarding the effect of synergies between BL/BLIs and other antimicrobials. Finally, in order to address the absence of a standardized approach to using the novel BL/BLIs, we propose a diagnostic and therapeutic algorithm, which can be modified based on local epidemiological criteria. This framework could also be expanded to incorporate other new antimicrobials, such as cefiderocol, or currently unavailable BL/BLIs such as aztreonam/avibactam and cefepime/taniborbactam.

Antimicrobial susceptibility testing data analysis over 3 years at the Yaoundé General Hospital, Cameroon.

Antimicrobial resistance (AMR) is a major health concern with high rates in low-income countries. Bacteriology laboratories sustain the fight against AMR by providing antibiotic susceptibility testing (AST) results to ensure appropriate therapies. These laboratories generate a lot of data, which are usually used for prospective interventions. Our study conducted in a lower-middle-income hospital setting aimed to describe the profile of bacteria isolated from the specimens received over 3 years, assess their susceptibility profile and identify potential gaps or area of improvement from the analysis of our data. Monthly data were retrieved from registers for all specimens received between January 2020 until December 2022. Data were compiled and analysed using the R and WHONET software. Out of 3582 specimens received, 797 were culture positive (22.3%). Escherichia coli and Klebsiella pneumoniae were frequently isolated (30.5% and 24.2%, respectively). AST results analysis showed high resistance of Gram-negative bacteria to penams and cephems, whereas low resistance was observed to carbapenems. Susceptibility to antibiotics based on the AWaRe antibiotic classification was variable. The bacteriological profile in the various types of specimen was established and rational information to design a therapeutic protocol adapted to our hospital setting was obtained. AST results may not only be used for prospective guidance for treatment, but rather cumulative data analysis can contribute to design effective antibiotic prescriptions and improve general practices at the laboratory. This is, however, dependent on a good record-keeping, standardization of practices and collaboration between clinicians and laboratory scientists.

Assessing stakeholders' opinions on sharing antimicrobial susceptibility testing data from animals is key to developing a centralized database and dashboard tool.

To present, analyze, and discuss stakeholders' opinions regarding sharing antimicrobial susceptibility testing (AST) data from animals into a centralized database and dashboard tool that would collect, aggregate, store, and analyze this type of data from veterinary diagnostic laboratories (VDLs) across the country. 1 in-person focus group (9 participants), 9 virtual focus groups (49 participants), and online pre- and postmeeting surveys (76 and 35 participants, respectively). Focus groups and surveys were conducted to assess the opinions of veterinarians, producers, researchers, diagnosticians, and government officials. A strong majority of stakeholders recognize AMR as a serious concern for both human and animal health and see several benefits in establishing a centralized AMR database; however, several concerns were raised associated with data confidentiality, security, curation, and harmonization. In the interest of alleviating those concerns, among other items, stakeholders suggested education and training of data users, providers, and the public in addition to assuring strong data confidentiality protections. Stakeholder engagement is a critical component of all stages of development, implementation, and utilization of an AMR database and dashboard tool that could be used to inform antimicrobial stewardship in veterinary medicine. This assessment of stakeholders' needs and concerns can be used to help guide future recommendations for data legal protections as well as a data confidentiality and security framework. Maintaining open communication on data usage, storage, and security as well as involvement and education of data providers, users, and the public will remain key to enabling development of an AMR database and dashboard tool for domesticated animals.

Predicting Antibiotic Tolerance in hvKP and cKP Respiratory Infections Through Biofilm Formation Analysis and Its Resistance Implications.

Respiratory infections are a major global health concern, with Klebsiella pneumoniae standing out due to its evolving antibiotic resistance. This study compares the resistance profiles of hypervirulent Klebsiella pneumoniae (hvKP) and classical Klebsiella pneumoniae (cKP), aiming to shed light on their clinical implications. We analyzed 86 cases, comprising 42 hvKP and 44 cKP strains, using comprehensive antimicrobial susceptibility testing and clinical data evaluation to assess antibiotic tolerance and resistance mechanisms. Our findings reveal distinct resistance patterns between hvKP and cKP, highlighting the role of chromosomal mutations and plasmid-mediated gene transfer in conferring antibiotic resistance. Notably, hvKP strains exhibited unique resistance trends, including the production of extended-spectrum β-lactamases (ESBLs) and carbapenemases, differing from those of cKP. This research underscores the importance of continuous surveillance and the development of targeted therapies against antibiotic-resistant Klebsiella pneumoniae. It emphasizes the critical need for judicious antibiotic use and novel therapeutic approaches to combat respiratory infections caused by these increasingly resistant pathogens.

Navigating the network: a narrative overview of AMR surveillance and data flow in the United States.

The antimicrobial resistance (AMR) surveillance landscape in the United States consists of a data flow that starts in the clinical setting and is maintained by a network of national and state public health laboratories. These organizations are well established, with robust methodologies to test and confirm antimicrobial susceptibility. Still, the bridge that guides the flow of data is often one directional and caught in a constant state of rush hour that can only be refined with improvements to infrastructure and automation in the data flow. Moreover, there is an absence of information in the literature explaining the processes clinical laboratories use to coalesce and share susceptibility test data for AMR surveillance, further complicated by variability in testing procedures. This knowledge gap limits our understanding of what is needed to improve and streamline data sharing from clinical to public health laboratories. Successful models of AMR surveillance display attributes like 2-way communication between clinical and public health laboratories, centralized databases, standardized data, and the use of electronic health records or data systems, highlighting areas of opportunity and improvement. This article explores the roles and processes of the organizations involved in AMR surveillance in the United States and identifies current knowledge gaps and opportunities to improve communication between them through standardization, communication, and modernization of data flow.

Biofilms in mycobacterial infection

The ability to form biofilms in lung tissue destruction cavities has been described for both the causative agent of tuberculosis (Mycobacterium tuberculosis) and for non-tuberculous mycobacteria. This process is associated with the chronic infection. It is assumed that a change in the biology of the pathogen inside the biofilm (formation of an antibiotic-resistant phenotype) makes ineffective standard chemotherapy regimens, which based on the susceptibility test data of mycobacteria in the “free state”. This review describes the biology of mycobacterial biofilms and the main approaches to combat them. Available information suggests that control of mycobacterial biofilm formation is one potential strategy to improve the effectiveness of treatment for tuberculosis and mycobacteriosis.

Effective Stakeholder Engagement for Collation, Analysis and Expansion of Antimicrobial Resistance (AMR) Data: A CAPTURA Experience.

An effective implementation of antimicrobial resistance (AMR) surveillance projects requires sustainable and multidisciplinary engagement with stakeholders from various backgrounds, interests and aims. The "Capturing Data on Antimicrobial resistance Patterns and Trends in Use in Regions of Asia" (CAPTURA) project, funded by the Fleming Fund, initially targeted 12 countries in South Asia (SA) and Southeast Asia (SEA) to "expand the volume of historical and current data on AMR and antimicrobial usage" and support local agencies through capacity building activities. In this article, we focus on early stakeholder engagement activities and present overall statistics on AMR data collated from 72 laboratories across seven countries. This included 2.3 million records of antimicrobial susceptibility testing (AST) data, which were curated, analyzed, and shared back to the facilities for informed decision making. Approximately 98% of the data collated by CAPTURA originated from laboratories based in SA countries. Furthermore, country-wide data were analyzed to identify commonly reported pathogens in each country, followed by descriptions of AST practices and multidrug-resistant (MDR) pathogens. Overall, we found meager adherence to standard guidelines to perform and record AST results, and a significant number of MDR pathogens were reported. We conclude that close collaboration with the existing national mechanisms for identifying AMR data sources was crucial for the project's success. Although we show a vast retrospective dataset on AMR is available for data sharing in Asia, there remain critical gaps in data generation/management practice and analysis capacity for AMR data at most facilities.

Direct Detection of Fluoroquinolone Resistance in Sputum Samples from Tuberculosis Patients by High Resolution Melt Curve Analysis.

Multidrug-resistant tuberculosis (MDR-TB) requires treatment with fluoroquinolone (FLQ) drugs, however, the excessive use of FLQ has led to the rise of extensively drug-resistant TB. In 2019, ~ 20% of total MDR-TB cases were estimated to be resistant to FLQ drugs. In the present study, we developed and evaluated the utility of high-resolution melt curve analysis (HRM) for the rapid detection of FLQ-resistant Mycobacterium tuberculosis for the first time directly from sputum samples. A reference plasmid library was generated for the most frequently observed mutations of gyrA gene and was used to discriminate between mutant and wild-type samples in the FLQ-HRM assay. The developed assay was evaluated on n = 25 MDR M. tuberculosis clinical isolates followed by validation on archived sputum DNA (n = 88) using DNA sequencing as a gold standard. The FLQ-HRM assay showed a 100% sensitivity [95% Confidence Interval (CI): 71.5 to 100] and specificity (95% CI: 39.7 to 100) in smear-positive category, and a sensitivity of 88.9% (95% CI: 77.3 to 95.8) with 84.2% (95% CI: 60.4 to 96.6) specificity in smear-negative category. The assay showed a high level of concordance of ~ 90% (κ = 0.74) with DNA sequencing, however, we were limited by the absence of phenotypic drug susceptibility testing data. In conclusion, HRM is a rapid, cost-effective (INR150/USD1.83) and closed-tube method for direct detection of FLQ resistance in sputum samples including direct smear-negative samples.

Antimicrobial Susceptibility Patterns Among a Large, Nationwide Cohort of Chryseobacterium Species Clinical Isolates

Abstract Background Chryseobacterium species are ubiquitous in nature that can be found in soil, water, sinks, and medical devices. They have been implicated in various infections including ventilator-associated pneumonia, catheter-related bloodstream infections (CRBSI), skin and soft tissue infections, and meningitis. C. indologenes has been shown to possess an extended-spectrum beta-lactamase (ESBL) and metallo-β-lactamase (MBL) that render it resistant to most antibiotics. Antimicrobial susceptibility testing (AST) data are required to help clinicians choose effective empiric antibiotics and to investigate potential resistance mechanisms. Methods Chryseobacterium spp. identification was determined prior to submission by client laboratories or performed in our laboratory by MALDI-TOF (Bruker Biotyper) or 16S rRNA gene sequencing. AST was performed on Chryseobacterium species isolates received from across the United States between April 2004 and December 2018. AST was performed using custom-made broth microdilution panels, and minimal inhibitory concentrations (MICs) were interpreted using CLSI M100 MIC breakpoints for non-Enterobacterales organisms. Isolates from a range of clinical specimens including blood, respiratory, wound, tissue, bone, and body fluids were included. Quality control was performed using Escherichia coli ATCC 25922 and Pseudomonas aeruginosa ATCC 27853. Results were included only if the QC values were within range. The MIC50, MIC90, and MIC ranges for antimicrobials for frequently tested Chryseobacterium species were determined. Results AST was completed for 245 Chryseobacterium species clinical isolates, and the most frequently tested species were C. gleum/ indologenes (n = 78), C. hominis (n = 25), C. taklimakanense (n = 14), C. anthropi/ haifense (n = 12), C. arthrospharae (n = 12), C. bernardetii/jejuense (n = 3), C. pallidum (n = 3), and C. solincola/treverense (n = 3). 84 isolates were unable to be identified to species level, and were grouped as “Chryseobacterium spp.” Regarding susceptibility, across all Chryseobacterium species, the antibiotics with the most activity included minocycline (97.8%), trimethoprim-sulfamethoxazole (TMP-SMX; 95.5%), levofloxacin (92.3%), and ciprofloxacin (82.8%). Comparing the β-lactams, piperacillin-tazobactam had the most activity (59.7%), whereas ceftazidime (42.2%), cefepime (44.3%), meropenem (41.2%), and imipenem (46.3%) had similar low activity. The highest resistance rates were found for tobramycin (96%), aztreonam (94.6%), and gentamicin (62.7%). Among the Chryseobacterium isolates, certain species were found to be largely pan-susceptible, including C. anthropic/haifense, C. hominis, and C. taklimakanense. Conclusions Chryseobacterium species display significant resistance against β-lactam antibiotics, which are often used for empiric therapy. Minocycline, TMP-SMX, and fluoroquinolones have the most activity against Chryseobacterium species clinical isolates.

Comparison of carbapenem-susceptible and carbapenem-resistant Enterobacterales at nine sites in the USA, 2013-2016: a resource for antimicrobial resistance investigators.

Carbapenem-resistant Enterobacterales (CRE) are an urgent public health threat. Genomic sequencing is an important tool for investigating CRE. Through the Division of Healthcare Quality Promotion Sentinel Surveillance system, we collected CRE and carbapenem-susceptible Enterobacterales (CSE) from nine clinical laboratories in the USA from 2013 to 2016 and analysed both phenotypic and genomic sequencing data for 680 isolates. We describe the molecular epidemiology and antimicrobial susceptibility testing (AST) data of this collection of isolates. We also performed a phenotype-genotype correlation for the carbapenems and evaluated the presence of virulence genes in Klebsiella pneumoniae complex isolates. These AST and genomic sequencing data can be used to compare and contrast CRE and CSE at these sites and serve as a resource for the antimicrobial resistance research community.

Nocardia species distribution and antimicrobial susceptibility within Australia.

Nocardia is a ubiquitous saprophyte capable of causing human disease. Disease is primarily respiratory or cutaneous, usually acquired via inhalation or inoculation. Under the influence of environmental and host factors, Nocardia incidence and species distribution demonstrate geographical variation. To examine for differences in Nocardia incidence within Western Australia (WA) and analyse species distribution in the context of prior published studies. To analyse antibiogram data from a nationwide passive antimicrobial resistance surveillance program. Retrospective extraction of laboratory data for Western Australian Nocardia isolates over a 21-year period. Analysis of Nocardia antimicrobial susceptibility testing data submitted to the Australian Passive Antimicrobial Resistance Surveillance (APAS) program between 2005 and 2022. Nine hundred sixty WA isolates were identified, giving an annual incidence of 3.03 per 100 000 population with apparent latitudinal variation. The four most common species identified within WA and amongst APAS isolates were N. nova, N. cyriacigeorgica, N. brasiliensis and N. farcinica. APAS data demonstrated that all species exhibited high rates of susceptibility to linezolid (100%) and trimethoprim-sulfamethoxazole (98%). Amikacin (>90% susceptibility for all species except N. transvalensis) was the next most active parenteral agent, superior to both carbapenems and third-generation cephalosporins. Susceptibility to oral antimicrobials (other than linezolid) demonstrated significant interspecies variation. We demonstrate geographical variation in the distribution of Nocardia incidence. Four species predominate in the Australian setting, and nationwide data confirm a high in vitro susceptibility to trimethoprim-sulphamethoxazole and linezolid, justifying their ongoing role as part of first-line empiric therapy.

An accurate and interpretable model for antimicrobial resistance in pathogenic Escherichia coli from livestock and companion animal species.

Understanding the microbial genomic contributors to antimicrobial resistance (AMR) is essential for early detection of emerging AMR infections, a pressing global health threat in human and veterinary medicine. Here we used whole genome sequencing and antibiotic susceptibility test data from 980 disease causing Escherichia coli isolated from companion and farm animals to model AMR genotypes and phenotypes for 24 antibiotics. We determined the strength of genotype-to-phenotype relationships for 197 AMR genes with elastic net logistic regression. Model predictors were designed to evaluate different potential modes of AMR genotype translation into resistance phenotypes. Our results show a model that considers the presence of individual AMR genes and total number of AMR genes present from a set of genes known to confer resistance was able to accurately predict isolate resistance on average (mean F1 score = 98.0%, SD = 2.3%, mean accuracy = 98.2%, SD = 2.7%). However, fitted models sometimes varied for antibiotics in the same class and for the same antibiotic across animal hosts, suggesting heterogeneity in the genetic determinants of AMR resistance. We conclude that an interpretable AMR prediction model can be used to accurately predict resistance phenotypes across multiple host species and reveal testable hypotheses about how the mechanism of resistance may vary across antibiotics within the same class and across animal hosts for the same antibiotic.

Benefits and challenges of creating veterinary antibiograms for empiric antimicrobial selection in support of antimicrobial stewardship and advancement of one-health goals.

Antibiograms are important tools for antimicrobial stewardship that are often underutilized in veterinary medicine. Antibiograms summarize cumulative antimicrobial susceptibility testing (AST) data for specific pathogens over a defined time period; in veterinary medicine, they are often stratified by host species and site of infection. They can aid practitioners with empiric therapy choices and assessment of antimicrobial resistance trends within a population in support of one-health goals for antimicrobial stewardship. For optimal application, consideration must be given to the number of isolates used, the timeframe of sample collection, laboratory analytical methodology, and the patient population contributing to the data (eg, treatment history, geographic region, and production type). There are several limitations to veterinary antibiograms, including a lack of breakpoint availability for bacterial species, a lack of standardization of laboratory methodology and technology for culture and AST, and a lack of funding to staff veterinary diagnostic laboratories at a level that supports antibiogram development and education. It is vital that veterinarians who use antibiograms understand how to apply them in practice and receive relevant information pertaining to the data to utilize the most appropriate antibiogram for their patients. This paper explores the benefits and challenges of developing and using veterinary antibiograms and proposes strategies to enhance their applicability and accuracy. Further detail regarding the application of veterinary antibiograms by privately practicing clinicians is addressed in the companion Currents in One Health article by Lorenz et al (JAVMA, September 2023).