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Antimicrobial resistance is a global issue, and implementation of antimicrobial stewardship programs in outpatient settings is crucial. Japan has also focused on outpatient oral antimicrobial stewardship programs and difficulties in standardizing prescriptions have led to overprescription in primary emergency medical centers. There is a lack of research investigating the antibiotic prescription status of pediatric primary emergency medical centers and the benchmark prescription rates in pediatric outpatient settings. We conducted a multi-center, cross-sectional study of seven pediatric primary emergency medical centers located in five prefectures of Japan. We retrospectively extracted data from health claims or directly obtained them from charts at each institution and evaluated trends in the antibiotic prescription rate based on the AWaRe classification between April 2016 and December 2019. Our study included 383,525 encounters, with the most common infectious disease diagnosis being acute upper respiratory tract infection in 93,449 cases (24.4 %). The antibiotic prescription rate during the study period was 7.4 %, representing a decrease of 46 %, from 10.2 % in 2016 to 5.5 % in 2019. The percentage of prescriptions in the Access group increased at all institutions; however, it exceeded 60 % in only three facilities in 2019. The percentage of third-generation cephalosporins varied among facilities, ranging from 1.7 % to 59.4 %, as of 2019. For pediatric primary emergency medical centers where antimicrobial stewardship programs are implemented, we suggest 5 % as a reasonable benchmark level for the antibiotic prescription rate. Prescribing the antibiotics in the Access groups less frequently remains a domestic challenge in Japan. [ABSTRACT FROM AUTHOR]

Antimicrobial resistance (AMR) poses a serious threat to the clinical management of typhoid fever. AMR in Salmonella Typhi (S. Typhi) is commonly associated with the H58 lineage, a lineage that arose comparatively recently before becoming globally disseminated. To better understand when and how H58 emerged and became dominant, we performed detailed phylogenetic analyses on contemporary genome sequences from S. Typhi isolated in the period spanning the emergence. Our dataset, which contains the earliest described H58 S. Typhi organism, indicates that ancestral H58 organisms were already multi-drug resistant (MDR). These organisms emerged spontaneously in India in 1987 and became radially distributed throughout South Asia and then globally in the ensuing years. These early organisms were associated with a single long branch, possessing mutations associated with increased bile tolerance, suggesting that the first H58 organism was generated during chronic carriage. The subsequent use of fluoroquinolones led to several independent mutations in gyrA. The ability of H58 to acquire and maintain AMR genes continues to pose a threat, as extensively drug-resistant (XDR; MDR plus resistance to ciprofloxacin and third generation cephalosporins) variants, have emerged recently in this lineage. Understanding where and how H58 S. Typhi originated and became successful is key to understand how AMR drives successful lineages of bacterial pathogens. Additionally, these data can inform optimal targeting of typhoid conjugate vaccines (TCVs) for reducing the potential for emergence and the impact of new drug-resistant variants. Emphasis should also be placed upon the prospective identification and treatment of chronic carriers to prevent the emergence of new drug resistant variants with the ability to spread efficiently. A phylogenetic analysis of Salmonella Typhi isolated from returning travelers to the United Kingdom between 1980 and 1995 suggests that H58 emerged from a chronic carrier in India in 1987 before spreading globally and was already multidrug resistant. [ABSTRACT FROM AUTHOR]

The article discusses the growing threat of multidrug-resistant Gram-negative infections. Topics discussed include the rapid evolution of bacterial resistance mechanisms, the pharmaceutical industry's challenges in developing effective antibiotics, and a poignant case study of fatal antibiotic-resistant E. coli in a child.

Purpose Multidrug-resistant (MDR) infections are challenging to treat due to underlying patient conditions, pathogen characteristics, and high antibiotic resistance rates. As newer antibiotic therapies come to market, limited data exist about their real-world utilization. Methods This was a national retrospective cohort study of ceftazidime/avibactam (approved in 2015) utilization among inpatients from the Veterans Affairs (VA) Healthcare System, from 2015 through 2021. Joinpoint regression was used to estimate time trends in utilization. Results Ceftazidime/avibactam use increased by 52.3% each year (days of therapy per 1,000 bed days; 95% confidence interval, 12.4%-106.4%). We identified 1,048 unique predominantly male (98.3%) and white (66.2%; Black, 27.7%) patients treated with ceftazidime/avibactam, with a mean (SD) age of 71.5 (11.9) years. The most commonly isolated organisms were Pseudomonas aeruginosa (36.3%; carbapenem resistant, 80.6%; MDR, 65.0%) and Klebsiella species (34.1%; carbapenem resistant, 78.4%; extended-spectrum cephalosporin resistant, 90.7%). Common comorbid conditions included hypertension (74.8%), nervous system disorders (60.2%), diabetes mellitus (48.7%), and cancer (45.1%). Median time to ceftazidime/avibactam initiation from admission was 6 days, with a median of 3 changes in therapy before ceftazidime/avibactam initiation and a subsequent median length of inpatient stay of 14 days (median of 8 days of ceftazidime/avibactam therapy). Treatment heterogeneity was high, both before ceftazidime/avibactam initiation (89.6%) and during ceftazidime/avibactam treatment (85.6%), and common concomitant antibiotics included vancomycin (41.4%), meropenem (24.1%), cefepime (15.2%), and piperacillin/tazobactam (15.2%). The inpatient mortality rate was 23.6%, and 20.8% of patients had a subsequent admission with ceftazidime/avibactam treatment. Conclusion Utilization of ceftazidime/avibactam increased from 2015 to 2021 in the national VA Healthcare System. Ceftazidime/avibactam was utilized in complex, difficult-to-treat patients, with substantial treatment heterogeneity and variation in the causative organism and culture sites. [ABSTRACT FROM AUTHOR]

Purpose Cefdinir and cephalexin are cephalosporin antibiotics commonly used in the treatment of urinary tract infections (UTIs). Their efficacy depends on achieving sufficient time with concentrations exceeding the minimum inhibitory concentration (MIC). Despite being frequently prescribed for UTIs, cefdinir has markedly lower urine penetration compared to cephalexin. It is possible that differences in pharmacokinetics could result in dissimilar efficacy between these agents; however, comparative studies of cephalosporins in UTIs are lacking. Methods This was a retrospective comparative study of patients discharged from emergency departments within a community health system with a diagnosis of acute cystitis who were prescribed cefdinir or cephalexin. Treatment failure rates at 7 and 14 days were compared between the 2 agents using a χ 2 or Fisher's exact test, as appropriate. Results There were no differences in overall treatment failure between the cefdinir and cephalexin groups. Treatment failure at 7 days occurred in 11.6% (n = 14) of patients in the cefdinir group and 8.3% (n = 10) of patients in the cephalexin group (P = 0.389). Treatment failure at 14 days was higher for cefdinir at 20.7% (n = 25) than for cephalexin at 11.8% (n = 14), but this difference was not statistically significant (P = 0.053). There were no differences in the rate of treatment failure in subgroup analyses of uncomplicated or complicated UTIs. Conclusion The results of this study suggest that cefdinir and cephalexin have comparable efficacy for the treatment of lower UTIs. While there was a numerically higher rate of treatment failure with cefdinir, there were no significant differences in treatment failure between the agents. [ABSTRACT FROM AUTHOR]

Salmonella Typhimurium is a zoonotic pathogen that poses a major threat to public health. This generalist serotype can be found in many hosts and the environment where varying selection pressures may result in the accumulation of antimicrobial resistance determinants. However, the transmission of this serotype between food-producing hosts, specifically between poultry layer flocks and nearby dairy herds, was never demonstrated. We investigated an outbreak at a dairy in Israel to determine the role of nearby poultry houses to be sources of infection. The 2-month outbreak resulted in a 47% mortality rate among 15 calves born in that period. Routine treatment of fluid therapy, a nonsteroidal anti-inflammatory, and cefquinome was ineffective, and control was achieved by the introduction of vaccination of dry cows against Salmonella (Bovivac S, MSD Animal Health) and a strict colostrum regime. Whole genome sequencing and antimicrobial sensitivity tests were performed on S. Typhimurium strains isolated from the dairy (n = 4) and strains recovered from poultry layer farms (n = 10). We identified acquired antimicrobial-resistant genes, including the blaCTX-M-55 gene, conferring resistance to extended-spectrum cephalosporins, which was exclusive to dairy isolates. Genetic similarity with less than five single nucleotide polymorphism differences between dairy and poultry strains suggested a transmission link. This investigation highlights the severe impact of S. Typhimurium on dairy farms and the transmission risk from nearby poultry farms. The accumulation of potentially transferable genes conferring resistance to critically important antimicrobials underscores the increased public health risk associated with S. Typhimurium circulation between animal hosts. [ABSTRACT FROM AUTHOR]

Antibiotics are often used to treat severe Vibrio infections, with third-generation cephalosporins and tetracyclines combined or fluoroquinolones alone being recommended by the US Centers for Disease Control and Prevention. Increases in antibiotic resistance of both environmental and clinical vibrios are of concern; however, limited longitudinal data have been generated among environmental isolates to inform how resistance patterns may be changing over time. Hence, we evaluated long-term trends in antibiotic resistance of vibrios isolated from Chesapeake Bay waters (Maryland) across two 3-year sampling periods (2009-2012 and 2019-2022). Vibrio parahaemolyticus (n = 134) and Vibrio vulnificus (n = 94) toxR-confirmed isolates were randomly selected from both sampling periods and tested for antimicrobial susceptibility against eight antibiotics using the Kirby-Bauer disk diffusion method. A high percentage (94%-96%) of V. parahaemolyticus isolates from both sampling periods were resistant to ampicillin and only 2%-6% of these isolates expressed intermediate resistance or resistance to third-generation cephalosporins, amikacin, tetracycline, and trimethoprim-sulfamethoxazole. Even lower percentages of resistant V. vulnificus isolates were observed and those were mostly recovered from 2009 to 2012, however, the presence of multiple virulence factors was observed. The frequency of multi-drug resistance was relatively low (6%-8%) but included resistance against antibiotics used to treat severe vibriosis in adults and children. All isolates were susceptible to ciprofloxacin, a fluoroquinolone, indicating its sustained efficacy as a first-line agent in the treatment of severe vibriosis. Overall, our data indicate that antibiotic resistance patterns among V. parahaemolyticus and V. vulnificus recovered from the lower Chesapeake Bay have remained relatively stable since 2009. [ABSTRACT FROM AUTHOR]

Urinary tract infection (UTI) is considered as one of the highly prevalent infections worldwide. Regarding its prevalence, UTI is more common in women. The outcome of the research is expected to predict the severity of the urinary tract infection. The study of prevalence and antibiotic susceptibility helps to provide data on the occurrence of uropathogens in different age groups and helps to treat the infection with effective antibiotics to prevent further progression of infection. The study has been carried out to identify and investigate the prevalence of uropathogens and to determine their antibiotic susceptibility potential. Overall, 713 urine samples were collected, MacConkey agar, Blood agar, CLED agar and LuriaBertani agar were used for isolation of uropathogens by calibrated loop streak method and incubated at 37°C. Antibiotic susceptibility was carried out using the Kirby Disc diffusion method. A total of 665 showed positive bacteriuria. E. coli (37.3%) and K. pneumoniae (32.03%) were the most common uropathogens followed by E. fergusonii (17.9%), P. aeruginosa (8.4%), and A. baumannii (4.4%). The study found that above 70% of antibiotic susceptibility was observed in fluoroquinolones followed by imipenem, while all isolates showed high resistance to ampicillin. The organisms E. coli, E. fergusonii, and P. aeruginosa exhibited the least susceptibility (>50%) for third-generation cephalosporins. P. aeruginosa and A. baumannii showed no susceptibility to nitrofurantoin, whereas other isolates were least susceptible. The study concludes that K. pneumoniae and E. coli were highly prevalent within the study group and that fluoroquinolone and imipenem can be effective for treatment. [ABSTRACT FROM AUTHOR]

Non-diphtheritic Corynebacteria (NDC), originally considered contaminants in clinical samples, have now emerged as nosocomial pathogens, emphasising the importance of their identification and prompt reporting. 120 non-diphtheritic corynebacteria isolated from pus were chosen for examination. A battery of tests identified isolates and minimum inhibitory concentration (MIC) was detected by broth microdilution and interpreted as per Clinical & Laboratory Standards Institute (CLSI) and British Society for Antimicrobial Chemotherapy (BSAC) guidelines. C. amycolatum 28 (31%), followed by C. striatum 18 (20.5%) was the predominant isolate. Cephalosporins were least effective followed by Gentamycin. However, all isolates were sensitive to Vancomycin and Linezolid. Our research highlights the necessity of implementing clinical antimicrobial therapy protocols for Corynebacterium spp. Empirical treatment with vancomycin or linezolid is recommended until in vitro susceptibility results become accessible. [ABSTRACT FROM AUTHOR]

Acid dissociation constants of three cephalosporin antibiotics (cefapirin, ceftiofur, and cefotaxime) were calculated by a newly developed methodology. Plane-wave DFT calculations were performed to determine the pKa values, and by choosing the appropriate cell sizes, accurate values could be calculated. Some characteristic points were found which helped us to find correlations among the structural and physic-chemical parameters, and correlation factors were defined as well. This present study can be a base for further approaches to determining acid dissociation constants of cephalosporin molecules. [ABSTRACT FROM AUTHOR]

A study published in the Journal of Antimicrobial Chemotherapy examined the development of resistance to ertapenem and meropenem among a type of bacteria called Enterobacterales. The researchers found that resistance to ertapenem occurred more easily than resistance to meropenem. They also observed that using ertapenem could potentially lead to resistance to meropenem. These findings emphasize the need to monitor and manage the use of carbapenem antibiotics to prevent resistance. Another study compared the effects of ertapenem and meropenem on carbapenem-resistant Enterobacteriaceae isolates. The study found that ertapenem isolates showed greater reductions in susceptibility compared to meropenem isolates. The authors suggest that this may support the use of meropenem over ertapenem in hospitals for treating these infections, but more research is needed. The study was funded internally and the authors have no conflicts of interest. [Extracted from the article]

Background: In 2012, Botswana introduced 13-valent pneumococcal conjugate vaccine (PCV-13) to its childhood immunization program in a 3+0 schedule, achieving coverage rates of above 90% by 2014. In other settings, PCV introduction has been followed by an increase in carriage or disease caused by non-vaccine serotypes, including some serotypes with a high prevalence of antibiotic resistance. Methods: We characterized the serotype epidemiology and antibiotic resistance of pneumococcal isolates cultured from nasopharyngeal samples collected from infants (≤12 months) in southeastern Botswana between 2016 and 2019. Capsular serotyping was performed using the Quellung reaction. E-tests were used to determine minimum inhibitory concentrations for common antibiotics. Results: We cultured 264 pneumococcal isolates from samples collected from 150 infants. At the time of sample collection, 81% of infants had received at least one dose of PCV-13 and 53% had completed the three-dose series. PCV-13 serotypes accounted for 27% of isolates, with the most prevalent vaccine serotypes being 19F (n = 20, 8%), 19A (n = 16, 6%), and 6A (n = 10, 4%). The most frequently identified non-vaccine serotypes were 23B (n = 29, 11%), 21 (n = 12, 5%), and 16F (n = 11, 4%). Only three (1%) pneumococcal isolates were resistant to amoxicillin; however, we observed an increasing prevalence of penicillin resistance using the meningitis breakpoint (2016: 41%, 2019: 71%; Cochran-Armitage test for trend, p = 0.0003) and non-susceptibility to trimethoprim-sulfamethoxazole (2016: 55%, 2019: 79%; p = 0.04). Three (1%) isolates were multi-drug resistant. Conclusions: PCV-13 serotypes accounted for a substantial proportion of isolates colonizing infants in Botswana during a four-year period starting four years after vaccine introduction. A low prevalence of amoxicillin resistance supports its continued use as the first-line agent for non-meningeal pneumococcal infections. The observed increase in penicillin resistance at the meningitis breakpoint and the low prevalence of resistance to ceftriaxone supports use of third-generation cephalosporins for empirical treatment of suspected bacterial meningitis. [ABSTRACT FROM AUTHOR]

Cluster regularly interspaced short palindromic repeats and CRISPR associated protein 9 (CRISPR-Cas9) is a promising tool for antimicrobial re-sensitization by inactivating antimicrobial resistance (AMR) genes of bacteria. Here, we programmed CRISPR-Cas9 with common spacers to target predominant blaCTX-M variants in group 1 and group 9 and their promoter in an Escherichia coli model. The CRISPR-Cas9 was delivered by non-replicative phagemid particles from a two-step process, including insertion of spacer in CRISPR and construction of phagemid vector. Spacers targeting blaCTX-M promoters and internal sequences of blaCTX-M group 1 (blaCTX-M-15 and -55) and group 9 (blaCTX-M-14, -27, -65, and -90) were cloned into pCRISPR and phagemid pRC319 for spacer evaluation and phagemid particle production. Re-sensitization and plasmid clearance were mediated by the spacers targeting internal sequences of each group, resulting in 3 log10 to 4 log10 reduction of the ratio of resistant cells, but not by those targeting the promoters. The CRISPR-Cas9 delivered by modified ΦRC319 particles were capable of re-sensitizing E. coli K-12 carrying either blaCTX-M group 1 or group 9 in a dose-dependent manner from 0.1 to 100 multiplicity of infection (MOI). In conclusion, CRISPR-Cas9 system programmed with well-designed spacers targeting multiple variants of AMR gene along with a phage-based delivery system could eliminate the widespread blaCTX-M genes for efficacy restoration of available third-generation cephalosporins by reversal of resistance in bacteria. [ABSTRACT FROM AUTHOR]

Carbapenems are widely used for empiric treatment of healthcare-associated central nervous system (CNS) infections. We investigated the feasibility of a carbapenem-sparing strategy, utilising a third-generation cephalosporin (ceftriaxone or cefotaxime) (combined with vancomycin) for the empirical treatment of healthcare-associated CNS infections in Eastern Denmark. The departments of neurosurgery and neuro-intensive care at Copenhagen University Hospital Rigshospitalet. First, we analysed local microbiological data (1st January 2020–31st August 2022) to identify microorganisms non-susceptible to third-generation cephalosporin. Subsequently, we assessed all carbapenem prescriptions over a three-month period for their indication and justification. In total, 25,247 bacterial cultures were identified, of which 2,563 CNS-related, were included in the analysis. The positivity rate was 10.5% (n = 257/2439) for cerebrospinal-fluid samples and 75.8% (n = 95/124) for brain parenchyma. CNS samples from five individual patients revealed bacteria non-susceptible to third generation cephalosporins (Enterobacter spp. (n = 3), Pseudomonas spp. (n = 2), Klebsiella spp. (n = 2), Citrobacter freundii (n = 1)). All five patients had been hospitalised for ≥10days at the time-point of antibiotic therapy. Out of 11,626 sets of blood cultures, a total of 10 individual patients had Gram-negative blood-stream infections with resistance to ceftriaxone and piperacillin/tazobactam. 140 days-of-therapy (32%) with carbapenem in 18 patients (36%) were definitively or possibly indicated according to guidelines, none were indicated for healthcare-associated CNS-infections. An empiric treatment strategy relying on a third-generation cephalosporin appears suitable for healthcare-associated CNS infections at our tertiary hospital, serving a population of 2.6 million. However, in patients with prolonged hospitalization (≥10 days), immunosuppression, prior broad-spectrum antibiotic use, or history of resistant Gram-negative bacteria, empirical prescription of carbapenem may be needed. [ABSTRACT FROM AUTHOR]

While a tailored antibiotic treatment plan is often straightforward, what we often observe in daily clinical practice is a highly variable approach when defining empirical therapy. Specifically, a debate exists on preference to spare the new β-lactams and β-lactamase inhibitors (BL-BLIs) or to apply a carbapenem-sparing strategy first. To investigate, we designed a web survey aimed at investigating the variables considered relevant to empirically choosing one antibiotic over the other. Submitted to Italian infectious diseases and intensive care physicians through the support of Società Italiana di Malattie Infettive e Tropicali (SIMIT), Società Italiana di Terapia Antinfettiva (SITA) and Società Italiana Anestesia, Analgesia, Rianimazione e Terapia Intensiva (SIAARTI). We found that demographic characteristics were irrelevant when deciding for empirical therapy. Clinical and anamnestic data were most meaningful. Significantly considered were underlying comorbidities and previous exposure to antimicrobial treatments. History of third-generation cephalosporin-resistant, carbapenem-resistant and/or metallo-β-lactamase-producing Enterobacterales rectal colonisation and/or infection were considered the most relevant by most physicians. Unexpectedly, clinicians considered less the source of infection. These results prompt the need of straightforward methods to retrieve medical histories and the magnitude of rectal colonisation data, often not routinely obtained. [ABSTRACT FROM AUTHOR]

Background: Measuring antimicrobial use is a core component of antimicrobial stewardship. Purchasing data may be easier to obtain than prescription data in some situations, but differences in clinic size, caseload and collection timeframes must be considered. Objective: Our objective was to evaluate purchases of systemic antibacterial agents by small animal veterinary facilities in 5 networks across 3 countries, using a mg/veterinarian full time equivalent (FTE)/week as the metric. Methods: Data were obtained from purchasing records of 2194 veterinary facilities from networks from the United States (US, n = 3: US‐A, 1036 facilities; US‐B, 101 facilities; US‐C, 886 facilities), Canada (n = 1: 117 facilities) and the United Kingdom (UK, n = 1: 54 facilities) during 2019‐2021. Results: In total, 20 020 269 767 mg (20.02 t) of antimicrobials were purchased. Overall differences between the UK and North America were driven by significantly higher purchases of amoxicillin‐clavulanic acid in the UK (P <.001), with substantially less purchasing of third generation cephalosporins in the UK (P <.0001). A significant association was found between FTE and purchasing, with decreased purchasing (mg/FTE/week) as facility FTE increased. Significant differences also were found among US regions. Facilities in the top 10% of total purchasing accounted for 23%‐30% of purchases, compared to only 1.6%‐3.8% for the bottom 10%. Conclusions and Clinical Importance: These data provide useful information about general purchasing trends, inter‐ and intraregional differences and differences among facility types and identify high purchasing outliers for further investigation. [ABSTRACT FROM AUTHOR]

Background: Urinary tract infection (UTI) is one of the most prevalent diseases affecting neonate to geriatric age group. Widespread use of antibiotics has led to emergence of resistant microorganisms. As the antibiogram of the microorganisms are frequently changing the present study was done to analyze recent antibiotic sensitivity pattern of uropathogens. Methods: The present study is a retrospective analysis of antibiotic susceptibility patterns of uropathogens, conducted at Department of General medicine at a tertiary care hospital, Andhrapradesh, India. Age, Gender and Co morbidities of the patients were obtained from inpatient registers of General medicine. The organism isolated and antimicrobial susceptibility profiles were collected from the Department of Microbiology. Results: 100 urine samples were collected and sent for culture and sensitivity of which organisms were isolated from 74 samples, of which 67.56% were females and 32.44% were males. The overall prevalence of UTI was found to be high in diabetics (42%). High prevalence was observed in females as compared to males (2:1). Though the overall prevalence was high in >45 years age group patients, in females high prevalence was seen among middle-aged (31 to 45 years) patients and in male high prevalence was seen among >45 years age group patients. Escherichia coli (54.05%) was the commonest isolate causing UTI followed by Klebsiella pneumoniae (27.02%). The most effective antimicrobial agents in our study were Meropenem, Amikacin, Nitrofurantoin and Cotrimoxazole whereas higher resistance was observed among Fluoroquinolone, Amoxicillin, third generation Cephalosporins. Conclusion: As drug resistance among bacterial pathogens vary time to time and by region, regular surveillance and monitoring is necessary for giving updated information to physician for most effective empirical treatment of UTIs. [ABSTRACT FROM AUTHOR]

This study aimed to clarify other diseases claimed simultaneously with acute upper respiratory infection (URI), antibiotic prescriptions, and examinations associated with infectious diseases in pediatric patients with acute URI insurance claims at otorhinolaryngology outpatient visits. Pediatric patients who visited an otolaryngology department between 2019 and 2021 and were definitively diagnosed with URI were selected using a large Japanese medical claims database. Patient backgrounds, antibiotic use, and examinations were descriptively evaluated. In total, 8010 patients were included in the analysis. The median number (interquartile range) of diseases claimed in the same month as acute URI was 4 (3–6). Only 519 (6.5 %) patients were claimed as acute URI alone. Regardless of the prescription of antibiotics, the most commonly redundantly claimed disease in these patients was allergic rhinitis, followed by acute bronchitis, acute sinusitis, and earwax impaction. The frequently prescribed antibiotics were third-generation cephalosporins, macrolides, and penicillins with extended-spectrum, including amoxicillin which was recommended by the Japanese manual; the proportion of patients with examinations was low (2.9–21.7 %). Among patients with acute URI, diagnoses requiring antibiotics were also claimed; therefore, when evaluating acute URI using the Japanese medical claims database, care must be taken in patient selection. Moreover, the implementation rate of examinations necessary for diagnosis was low, so there is an urgent need to develop an environment where examinations can be conducted in outpatient settings. [ABSTRACT FROM AUTHOR]

Background: The emergence and spread of β-lactamase-producing Klebsiella spp. has been associated with a substantial healthcare burden resulting in therapeutic failures. We sought to describe the proportion of phenotypic resistance to commonly used antibiotics, characterize β-lactamase genes among isolates with antimicrobial resistance (AMR), and assess the correlates of phenotypic AMR in Klebsiella spp. isolated from stool or rectal swab samples collected from children being discharged from hospital. Methods: We conducted a cross-sectional study involving 245 children aged 1–59 months who were being discharged from hospitals in western Kenya between June 2016 and November 2019. Whole stool or rectal swab samples were collected and Klebsiella spp. isolated by standard microbiological culture. β-lactamase genes were detected by PCR whilst phenotypic antimicrobial susceptibility was determined using the disc diffusion technique following standard microbiology protocols. Descriptive analyses were used to characterize phenotypic AMR and carriage of β-lactamase-producing genes. The modified Poisson regression models were used to assess correlates of phenotypic beta-lactam resistance. Results: The prevalence of β-lactamase carriage among Klebsiella spp. isolates at hospital discharge was 62.9% (154/245). Antibiotic use during hospitalization (adjusted prevalence ratio [aPR] = 4.51; 95%CI: 1.79–11.4, p < 0.001), longer duration of hospitalization (aPR = 1.42; 95%CI: 1.14–1.77, p < 0.002), and access to treated water (aPR = 1.38; 95%CI: 1.12–1.71, p < 0.003), were significant predictors of phenotypically determined β-lactamase. All the 154 β-lactamase-producing Klebsiella spp. isolates had at least one genetic marker of β-lactam/third-generation cephalosporin resistance. The most prevalent genes were blaCTX-M 142/154 (92.2%,) and blaSHV 142/154 (92.2%,) followed by blaTEM 88/154 (57.1%,) and blaOXA 48/154 (31.2%,) respectively. Conclusion: Carriage of β-lactamase producing Klebsiella spp. in stool is common among children discharged from hospital in western Kenya and is associated with longer duration of hospitalization, antibiotic use, and access to treated water. The findings emphasize the need for continued monitoring of antimicrobial susceptibility patterns to inform the development and implementation of appropriate treatment guidelines. In addition, we recommend measures beyond antimicrobial stewardship and infection control within hospitals, improved sanitation, and access to safe drinking water to mitigate the spread of β-lactamase-producing Klebsiella pathogens in these and similar settings. [ABSTRACT FROM AUTHOR]

Background: Vibrio furnissii is an emerging human pathogen closely related to V. fluvialis that causes acute gastroenteritis. V. furnissii infection has been reported to be rarer than V. fluvialis, but a multi-drug resistance plasmid has recently been discovered in V. furnissii. Methods: During daily monitoring at a general hospital in Beijing, China, seven V. furnissii strains were collected from patients aged over 14 years who presented with acute diarrhoea between April and October 2018. Genome analysis and comparison were performed for virulence and antimicrobial resistance genes, plasmids and transposon islands, together with phylogenetic analysis. Antimicrobial resistance to 19 antibiotics was investigated using the microbroth dilution method. Virulence phenotypes were investigated based on type VI secretion system (T6SS) expression and using a bacterial killing assay and a haemolysin assay. Results: Phylogenetic analysis based on single-nucleotide polymorphisms revealed a closer relationship between V. furnissii and V. fluvialis than between other Vibrio spp. The seven V. furnissii isolates were in different monophyletic clades in the phylogenetic tree, suggesting that the seven cases of gastroenteritis were independent. High resistance to cefazolin, tetracycline and streptomycin was found in the V. furnissii isolates at respective rates of 100.0%, 57.1% and 42.9%, and intermediate resistance to ampicillin/sulbactam and imipenem was observed at respective rates of 85.7% and 85.7%. Of the tested strains, VFBJ02 was resistant to both imipenem and meropenem, while VFBJ01, VFBJ02, VFBJ05 and VFBJ07 were multi-drug resistant. Transposon islands containing antibiotic resistance genes were found on the multi-drug resistance plasmid in VFBJ05. Such transposon islands also occurred in VFBJ07 but were located on the chromosome. The virulence-related genes T6SS, vfh, hupO, vfp and ilpA were widespread in V. furnissii. The results of the virulence phenotype assays demonstrated that our isolated V. furnissii strains encoded an activated T6SS and grew in large colonies with strong beta-haemolysis on blood agar. Conclusion: This study showed that diarrhoea associated with V. furnissii occurred sporadically and was more common than expected in the summer in Beijing, China. The antibiotic resistance of V. furnissii has unique characteristics compared with that of V. fluvialis. Fluoroquinolones and third-generation cephalosporins, such as ceftazidime and doxycycline, were effective at treating V. furnissii infection. Continua laboratory-based surveillance is needed for the prevention and control of V. furnissii infection, especially the dissemination of the antibiotic resistance genes in this pathogen. [ABSTRACT FROM AUTHOR]

Increased antimicrobial resistance (AMR) among bacteria underscores the need to strengthen AMR surveillance and promote data-based prescribing. To evaluate trends and associations between antimicrobial usage (AMU) and AMR, we explored a dataset of 34,672 bacterial isolates collected between 2015 and 2020 from clinical samples at the University Teaching Hospital (UTH) in Lusaka, Zambia. The most frequently isolated species were Escherichia coli (4,986/34,672; 14.4%), Staphylococcus aureus (3,941/34,672; 11.4%), and Klebsiella pneumoniae (3,796/34,672; 10.9%). Of the 16 drugs (eight classes) tested, only amikacin and imipenem showed good (> 50%) antimicrobial activity against both E. coli and K. pneumoniae, while nitrofurantoin was effective only in E. coli. Furthermore, 38.8% (1,934/4,980) of E. coli and 52.4% (2,079/3,791) of K. pneumoniae isolates displayed multidrug resistance (MDR) patterns on antimicrobial susceptibility tests. Among S. aureus isolates, 44.6% (973/2,181) were classified as methicillin-resistant (MRSA). Notably, all the MRSA exhibited MDR patterns. The annual hospital AMR rates varied over time, while there was a weak positive relationship (r = 0.38, 95% CI = 0.11–0.60) between the monthly use of third-generation cephalosporins (3GCs) and 3GC resistance among Enterobacterales. Overall, the results revealed high AMR rates that fluctuated over time, with a weak positive relationship between 3GC use and resistance. To our knowledge, this is the first report to evaluate the association between AMU and AMR in Zambia. Our results highlight the need to strengthen antimicrobial stewardship programs and optimize AMU in hospital settings. [ABSTRACT FROM AUTHOR]

Cefaclor is a bactericidal antibiotic recommended for treating diverse types of infections. This review aims to comprehensively assess the pharmacokinetic (PK) data on cefaclor in humans. Google Scholar, PubMed, Cochrane Library, and EBSCO databases were systematically performed to identify all the relevant studies containing at least one reported PK parameter of cefaclor. Cefaclor shows the linear PK profile as the area under the plasma concentration-time curve from 0 to t (AUC0-t) and maximum plasma concentration (Cmax) increase in a dose-dependent manner. The AUC0-t of cefaclor in the rice diet was found to be higher than that of bread food, i.e. 19.9 ± 2.6 ug/ml.hr vs 15.4 ± 4 ug/ml.hr. The AUC in paediatrics during the fed state was significantly higher compared to that in adults. Patients with renal impairments showed a Cmax 2.2 times higher than that of normal subjects. A significant increase in Cmax was depicted among individuals following a vegetarian diet in comparison with the non-vegetarian diet. Moreover, cefaclor exhibits time-dependent killing above the minimum inhibitory concentration (MIC < 2 ug), favouring its use in treating infections caused by specific pathogens. This systematic review summarises all the reported PK parameters of cefaclor in healthy and diseased subjects in the literature. This data can help practitioners in adjusting cefaclor doses among different diseases and populations to avoid drug interactions and adverse effects. [ABSTRACT FROM AUTHOR]

Background: Surgical antimicrobial prophylaxis (SAP) is the peri-operative administration of antimicrobial agents. Compliance rates vary worldwide from 15% to 84.3%, with studies in Turkey not exceeding 35%. The aim of this multicenter study was to determine the rate of appropriate antibiotic class, timing, and duration as well as discharge prescriptions in Turkey. Thus, we aimed to determine the rate of full compliance with SAP procedures in our country Patients and Methods: This multicenter, prospective, observational, descriptive study was conducted in 47 hospitals from 28 provinces in seven different regions of Turkey. Patients over 18 years of age in all surgical units between June 6, 2022, and June 10, 2022, were included in the study. Results: Of the 7,978 patients included in the study, 332 were excluded from further analyses because of pre-existing infection, and SAP compliance analyses were performed on the remaining 7,646 cases. The antibiotic most commonly used for SAP was cefazolin (n = 4,701; 61.5%), followed by third-generation cephalosporins (n = 596; 7.8%). The most common time to start SAP was within 30 minutes before surgery (n = 2,252; 32.5%), followed by 30 to 60 minutes before surgery (n = 1,638; 23.6%). Surgical antimicrobial prophylaxis duration was <24 hours in 3,516 (50.7%) patients and prolonged until discharge in 1,505 (21.7%) patients. Finally, the actual proportion of patients compliant with SAP was 19% (n = 1,452) after omitting 4,458 (58.3%) patients who were prescribed oral antibiotic agents at discharge as part of a prolonged SAP. Conclusions: Surgical antimicrobial prophylaxis compliance rates are still very low in Turkey. Prolonged duration of SAP and especially high rate of antibiotic prescription at discharge are the main reasons for non-compliance with SAP. [ABSTRACT FROM AUTHOR]

Acute bacterial upper respiratory infections are common indications for antibiotics in pediatrics, and many prescriptions may be inappropriate. Novel approaches to outpatient antimicrobial stewardship interventions are needed. This quasi-experimental study of an order set and best practice advisory alert targeting cefdinir prescriptions demonstrated an 8.4% decrease in cefdinir prescribing (P ≤.001). [ABSTRACT FROM AUTHOR]

Sepsis is a medical emergency that describes the body's systemic immunological response to an infectious process that can result in organ dysfunction and cause death. One of the causes of sepsis is Gram-negative bacteria that produce Extended Spectrum Beta Lactamase (ESBL). Beta-Lactamase production is defined as an enzyme produced by certain bacteria that is capable of hydrolyzing a broad spectrum of cephalosporins, and is effective against beta-lactam antibiotics. There is no data on the cause of sepsis caused by ESBL-producing Gram-negative bacteria at Indramayu Regional Hospital. For this reason, the aim of this study was to determine the species and percentage of ESBL producers in sepsis patients at Indramayu Regional Hospital. This research is a descriptive research. The data obtained in the research is primary data obtained from the results of culture examinations and sensitivity tests of sepsis patient specimens carried out in the Microbiology Section of the Clinical Pathology Laboratory of Indramayu Regional Hospital, in the period September-October 2023. The results of the research obtained 38 specimens from sepsis patients in the form of blood, urine and pussy. ESBL-producing bacteria were 18,4211%, non-ESBL bacteria were 13,1579%, and there was no bacterial growth as much as 68,4211%. ESBL-producing bacteria were found to be Escherechia coli from blood by 10,5263% and urine by 2,6316%, Klebsiella pneumoniae from blood by 2,6316% and pus by 2,6316%. [ABSTRACT FROM AUTHOR]

Introduction: The coronavirus disease 2019 (COVID-19) pandemic affected antibiotic usage worldwide. However, there is limited data from Serbia. Dispensing of oral antibiotics in Serbian pharmacies was analyzed to calculate monthly and yearly changes between 2018-2021, and to explore immediate and long-term effects of COVID-19 on antibiotic dispensing during this period. Methodology: The number of antibiotic packages dispensed from pharmacies during the study period was analyzed with a Chi-square test to assess the average change in annual dispensing, and an interrupted time-series analysis was used to evaluate the impact of the pandemic on antibiotic dispensing. The data from 2018-2021 were retrieved from the database of a large community pharmacy chain in Serbia. Results: The average number of antibiotic packages dispensed per day and per pharmacy was higher in 2021 compared to 2018 by one package. However, the dispensing of macrolides increased significantly; 17.7% (2018) vs. 22.5% (2021) (p < 0.05). In general, an increase in antibiotic dispensing was detected during COVID-19 for total antibiotics (16.4%), Watch antibiotics (44.8%), third-generation cephalosporins (80.4%), macrolides (45.5%) and azithromycin (83.7%). However, the immediate effect of COVID-19 was a decrease in the dispensing of Watch antibiotics, penicillin, and third-generation cephalosporins (p < 0.05); and a notable long-term COVID-19 effect was an increase in the dispensing of azithromycin (p < 0.05). Conclusions: In spite of a relatively stable trend of total antibiotic dispensing before and during COVID-19 pandemic, the use of Watch antibiotics, third-generation cephalosporins, and macrolides (particularly azithromycin) showed an increasing trend in dispensing that should be optimized. [ABSTRACT FROM AUTHOR]

Food contamination with plasmid-mediated antibiotic-resistant Escherichia coli has not been thoroughly investigated. This study aimed to clarify the prevalence of colistin-resistant AmpC/extended-spectrum β-lactamase (ESBL)-producing E. coli harbouring mcr (COL-ESBL-EC) and to determine antibiotic resistance by comparison with AmpC/ESBL-producing E. coli (ESBL-EC) and colistin-resistant E. coli harbouring mcr (COL-EC). Sixty chicken meats were tested for COL-ESBL-EC contamination. The result showed that 64 COL-ESBL-EC were isolated from 66.7% of the samples, and compared with ESBL-EC and COL-EC were isolated before. The genotypes of the COL-ESBL-EC showed blaCTX-M-55/TEM, blaCTX-M-55, blaCMY-2, and blaCTX-M-65 were predominant. The COL-ESBL-EC results showed a similar trend for blaCTX-M identification to that of ESBL-EC. The mcr was investigated, and mcr-1 was detected in COL-ESBL-EC and COL-EC. Antibiotic susceptibility testing revealed that many strains of COL-ESBL-EC and ESBL-EC were resistant to quinolones, and fosfomycin (FOS). These results suggest that COL-ESBL-EC has simultaneously acquired AmpC/ESBL-related, quinolone, and FOS resistance genes in COL-EC. [ABSTRACT FROM AUTHOR]

Salmonellosis is one of the leading causes of gastrointestinal infections in humans. In Canada, it is estimated that approximately 87,500 cases of salmonellosis occur every year in humans, resulting in 17 deaths. In the United States, it is estimated that 26,500 hospitalizations and 420 deaths occur every year. In dairy cattle, infections caused by nontyphoidal Salmonella enterica can cause mild to severe disease, including enteritis, pneumonia, and septicemia. Our study objectives were to determine the proportion of fecal samples positive for Salmonella in dairy cattle in Canada and determine the resistance pattern of these isolates. We used data collected through the Canadian Dairy Network for Antimicrobial Stewardship and Resistance (CaDNetASR). Pooled fecal samples from preweaning calves, postweaning heifers, lactating cows, and manure storage were cultured for Salmonella, and the isolates were identified using matrix-assisted laser desorption/ionization-time of flight mass spectrometry. Antimicrobial susceptibilities were determined using the minimum inhibitory concentration test, and resistance interpretation was made according to the Clinical and Laboratory Standards Institute. A 2-level, multivariable logistic regression model was built to determine the probability of recovering Salmonella from a sample, accounting for province, year, and sample source. The proportion of farms with at least one positive sample were 12% (17/140), 19% (28/144), and 17% (24/144) for the sampling years 2019, 2020, and 2021, respectively. Out of the 113 Salmonella isolates, 23 different serovars were identified. The occurrence of Salmonella appeared to be clustered by farms and provinces. The most common serovars identified were Infantis (14%) and Typhimurium (14%). Overall, 21% (24/113) of the Salmonella isolates were resistant to at least one antimicrobial. Resistance to tetracycline was commonly observed (17%); however, very limited resistance to category I antimicrobials (categorization according to Health Canada that includes third-generation cephalosporins, fluoroquinolones, polymyxins, and carbapenems) was observed, with one isolate resistant to amoxicillin and clavulanic acid. The proportion of Salmonella isolates resistant to 2 and 3 antimicrobial classes was 3.5% and 8.8%, respectively. Our study provided valuable information on the proportion of fecal samples positive for Salmonella , the serovars identified, and the associated resistance patterns across CaDNetASR herds, at regional and national levels. [ABSTRACT FROM AUTHOR]

Objectives An Escherichia coli isolate, WGS1363, showed resistance to piperacillin/tazobactam but susceptibility to cephalosporins and contained a previously unrecognized β-lactamase, CTX-M-255, as the only acquired β-lactamase. CTX-M-255 was identical to CTX-M-27 except for a G239S substitution. Here, we characterize the hydrolytic spectrum of CTX-M-255 and a previously reported β-lactamase, CTX-M-178, also containing a G239S substitution and compare it to their respective parental enzymes, CTX-M-27 and CTX-M-15. Methods All β-lactamase genes were expressed in E. coli TOP10 and MICs to representative β-lactam-antibiotics were determined. Furthermore, bla CTX-M-15,   bla CTX-M-27, bla CTX-M-178 and bla CTX-M-255 with C-terminal His-tag fusions were affinity purified for enzyme kinetic assays determining Michaelis–Menten kinetic parameters against representative β-lactam-antibiotics and IC50s of clavulanate, sulbactam, tazobactam and avibactam. Results TOP10-transformants expressing bla CTX-M-178 and bla CTX-M-255 showed resistance to penicillin/β-lactamase combinations and susceptibility to cephalothin and cefotaxime in contrast to transformants expressing bla CTX-M-15 and bla CTX-M-27. Determination of enzyme kinetic parameters showed that CTX-M-178 and CTX-M-255 both lacked hydrolytic activity against cephalosporins and showed impaired hydrolytic efficiency against penicillin antibiotics compared to their parental enzymes. Both enzymes appeared more active against piperacillin compared to benzylpenicillin and ampicillin. Compared to their parental enzymes, IC50s of β-lactamase-inhibitors were increased more than 1000-fold for CTX-M-178 and CTX-M-255. Conclusions CTX-M-178 and CTX-M-255, both containing a G239S substitution, conferred resistance to piperacillin/tazobactam and may be characterized as inhibitor-resistant CTX-M β-lactamases. Inhibitor resistance was accompanied by loss of activity against cephalosporins and monobactams. These findings add to the necessary knowledge base for predicting antibiotic susceptibility from genotypic data. [ABSTRACT FROM AUTHOR]

Enterococci are commensal members of the gastrointestinal tract and also major nosocomial pathogens. They possess both intrinsic and acquired resistance to many antibiotics, including intrinsic resistance to cephalosporins that target bacterial cell wall synthesis. These antimicrobial resistance traits make enterococcal infections challenging to treat. Moreover, prior therapy with antibiotics, including broad-spectrum cephalosporins, promotes enterococcal proliferation in the gut, resulting in dissemination to other sites of the body and subsequent infection. As a result, a better understanding of mechanisms of cephalosporin resistance is needed to enable development of new therapies to treat or prevent enterococcal infections. We previously reported that flow of metabolites through the peptidoglycan biosynthesis pathway is one determinant of enterococcal cephalosporin resistance. One factor that has been implicated in regulating flow of metabolites into cell wall biosynthesis pathways of other Gram-positive bacteria is GlmR. In enterococci, GlmR is encoded as the middle gene of a predicted 3-gene operon along with YvcJ and YvcL, whose functions are poorly understood. Here we use genetics and biochemistry to investigate the function of the enterococcal yvcJ-glmR-yvcL gene cluster. Our results reveal that YvcL is a DNA-binding protein that regulates expression of the yvcJ-glmR-yvcL operon in response to cell wall stress. YvcJ and GlmR bind UDP-GlcNAc and reciprocally regulate cephalosporin resistance in E. faecalis, and binding of UDP-GlcNAc by YvcJ appears essential for its activity. Reciprocal regulation by YvcJ/GlmR is essential for fitness during exposure to cephalosporin stress. Additionally, our results indicate that enterococcal GlmR likely acts by a different mechanism than the previously studied GlmR of Bacillus subtilis, suggesting that the YvcJ/GlmR regulatory module has evolved unique targets in different species of bacteria. Author summary: Enterococci are commensal members of the gastrointestinal tract and also major nosocomial pathogens. They possess both intrinsic and acquired resistance to many antibiotics, including intrinsic resistance to cephalosporins that target bacterial cell wall synthesis, rendering enterococcal infections challenging to treat. Moreover, prior therapy with antibiotics, including cephalosporins, is a major risk factor for subsequent acquisition of an enterococcal infection. Hence, a better understanding of mechanisms of cephalosporin resistance is needed to enable development of new therapies to treat or prevent enterococcal infections. We investigated the function of the well-conserved yvcJ-glmR-yvcL gene cluster in enterococcal cephalosporin resistance, revealing that YvcJ and GlmR reciprocally regulate cephalosporin resistance in E. faecalis, and this regulation is essential for fitness during exposure to cephalosporin stress. Additionally, our results indicate that enterococcal GlmR likely acts by a different mechanism than the previously studied GlmR of Bacillus subtilis, suggesting that the YvcJ/GlmR regulatory module has evolved unique targets in different species of bacteria. [ABSTRACT FROM AUTHOR]

The goal of this study is to investigate the origin, prevalence, and evolution of the pESI megaplasmid in Salmonella isolated from animals, foods, and humans. We queried 510,097 Salmonella genomes under the National Center for Biotechnology Information (NCBI) Pathogen Detection (PD) database for the presence of potential sequences containing the pESI plasmid in animal, food, and environmental sources. The presence of the pESI megaplasmid was confirmed by using seven plasmid-specific markers (rdA, pilL, SogS, TrbA, ipf, ipr2 and IncFIB(pN55391)). The plasmid and chromosome phylogeny of these isolates was inferred from single nucleotide polymorphisms (SNPs). Our search resolved six Salmonella clusters carrying the pESI plasmid. Four were emergent Salmonella Infantis clusters, and one each belonged to serovar Senftenberg and Alachua. The Infantis cluster with a pESI plasmid carrying blaCTX-M-65 gene was the biggest of the four emergent Infantis clusters, with over 10,000 isolates. This cluster was first detected in South America and has since spread widely in United States. Over time the composition of pESI in United States has changed with the average number of resistance genes showing a decrease from 9 in 2014 to 5 in 2022, resulting from changes in gene content in two integrons present in the plasmid. A recent and emerging cluster of Senftenberg, which carries the blaCTX-M-65 gene and is primarily associated with turkey sources, was the second largest in the United States. SNP analysis showed that this cluster likely originated in North Carolina with the recent acquisition of the pESI plasmid. A single Alachua isolate from turkey was also found to carry the pESI plasmid containing blaCTX-M-65 gene. The study of the pESI plasmid, its evolution and mechanism of spread can help us in developing appropriate strategies for the prevention and further spread of this multi-drug resistant plasmid in Salmonella in poultry and humans. [ABSTRACT FROM AUTHOR]

Background Optimization of antimicrobial stewardship is key to tackling antimicrobial resistance, which is exacerbated by overprescription of antibiotics in pediatric emergency departments (EDs). We described patterns of empiric antibiotic use in European EDs and characterized appropriateness and consistency of prescribing. Methods Between August 2016 and December 2019, febrile children attending EDs in 9 European countries with suspected infection were recruited into the PERFORM (Personalised Risk Assessment in Febrile Illness to Optimise Real-Life Management) study. Empiric systemic antibiotic use was determined in view of assigned final "bacterial" or "viral" phenotype. Antibiotics were classified according to the World Health Organization (WHO) AWaRe classification. Results Of 2130 febrile episodes (excluding children with nonbacterial/nonviral phenotypes), 1549 (72.7%) were assigned a bacterial and 581 (27.3%) a viral phenotype. A total of 1318 of 1549 episodes (85.1%) with a bacterial and 269 of 581 (46.3%) with a viral phenotype received empiric systemic antibiotics (in the first 2 days of admission). Of those, the majority (87.8% in the bacterial and 87.0% in the viral group) received parenteral antibiotics. The top 3 antibiotics prescribed were third-generation cephalosporins, penicillins, and penicillin/β-lactamase inhibitor combinations. Of those treated with empiric systemic antibiotics in the viral group, 216 of 269 (80.3%) received ≥1 antibiotic in the "Watch" category. Conclusions Differentiating bacterial from viral etiology in febrile illness on initial ED presentation remains challenging, resulting in a substantial overprescription of antibiotics. A significant proportion of patients with a viral phenotype received systemic antibiotics, predominantly classified as WHO Watch. Rapid and accurate point-of-care tests in the ED differentiating between bacterial and viral etiology could significantly improve antimicrobial stewardship. [ABSTRACT FROM AUTHOR]

[Display omitted] • A novel AuPtRh/Ti 3 C 2 MXene photocatalyst was prepared by one-step reduction method. • The formation of AuPtRh/Ti 3 C 2 MXene heterojunction helped the separation of electrons and holes. • AuPtRh/Ti 3 C 2 MXene photocatalyst exhibited excellent visible light photocatalytic performance and stability. • Possible Mechanism was proposed based on experimental analysis. The escalating prevalence of cephalosporin antibiotics in wastewater poses a serious threat to public health and environmental balance. Thus, it is crucial to develop effective methods for removing cephalosporin antibiotics from water sources. Herein, we propose the use of AuPtRh trimetallic nanoparticles supported on Ti 3 C 2 MXene as a photocatalyst for the degradation of cephalosporin antibiotics. Initially, AuPtRh nanoparticles were uniformly grown onto Ti 3 C 2 MXene sheets using one-step reduction technique. The prepared AuPtRh/Ti 3 C 2 MXene exhibited a complete degradation of cefixime and ceftriaxone sodium, while an impressive degradation efficiency of 91.58 % for cephalexin was achieved after 60 min of exposure to visible light, surpassing the performance of its individual AuPtRh nanoparticles and Ti 3 C 2 MXene. The enhanced photoactivity of AuPtRh/Ti 3 C 2 MXene was resulted from improved light absorption capacity and efficient generation, separation, and transfer of charge carriers driven by the formation of heterojunction between AuPtRh and Ti 3 C 2 MXene. Electron paramagnetic resonance and radicals trapping experiments results revealed that •O 2 – and h+ are the principal reactive species governing the degradation of cephalosporins. The photocatalyst exhibited excellent stability and could be reused four times without significant loss in efficiency. Our study highlights the potential of MXene composites for environmental remediation, offering insights into designing sustainable AuPtRh/Ti 3 C 2 MXene photocatalyst for water pollutant degradation. [ABSTRACT FROM AUTHOR]

Objective: Polypharmacy among pediatric inpatients is common and exposes children to the risk of drug-drug interactions (DDIs). This study aimed to characterize potential DDIs (pDDIs) and their associated risk factors among pediatric inpatients. Methods: A cross-sectional study was conducted over six months at the University Children's Hospital in Damascus. A total of 575 children taking two drugs or more participated. pDDIs were checked using LexiInteract® software. pDDIs within risk category B (No action needed), C (Monitor therapy), D (Modify regimen), and X (Avoid combination) were included. Logistic regression was used to identify factors associated with pDDIs. Results: At least one pDDI was detected in 49.7% of children. Overall, 744 pDDIs were identified. The majority of pDDIs were within risk category C (71.6%), followed by D (14%), B (12.8%), and X (1.6%). The most common pDDIs were: aminoglycosides - penicillins (n=56), aminoglycosides - cephalosporins (n=27), and vitamin D analogs - calcium salts (n=23). The number of prescribed drugs and nervous system drugs were significantly associated with the presence of pDDIs. Conclusion: pDDIs among pediatric inpatients were prevalent. The majority of the pDDIs were within risk category C, which necessitates therapy monitoring and necessary action to avoid adverse consequences. [ABSTRACT FROM AUTHOR]

Antibiotic resistance in animals is a significant and highly challenging threat among animals. Extended spectrum β-lactamase (ESBL) producing E. coli amongst all bacteria have been categorized by the WHO as the most critical AMR pathogen to human health and a major public health concern. In an effort to study the prevalence of ESBL producing coliforms among the ruminant species, phenotypic screening and confirmation by Kirby Bauer diffusion method followed by genotypic characterization of the isolates were carried out to ascertain the type of β-lactamase involved in conferring resistance. A total of 50 fecal swabs were collected from the cattle (n=26), buffalo (n=11), goat (n=10) and sheep (n=3) species. A total of 72 (26/50) % and 68 (34/50) % of the coliform isolates from the ruminant species were found to be phenotypically resistant to most of the β-lactam group of antibiotics and third generation cephalosporins, respectively. The isolates showing phenotypic resistance to third generation cephalosporins were genotypically confirmed by multiplex PCR to determine the types of β-lactamase coding for the resistance. The multiplex PCR for TEM, SHV and OXA type ESBLs revealed the presence of 713 and 564 bp amplicon indicating the predominance of serine β-lactamases, viz., SHV (Class A) and OXA (Class D) type ESBL in 85.7 % and 7.0 % of the coliform isolates of ruminants. This study confirms and emphasizes the prevalence of ESBL producing coliforms and the hidden threat underlying in healthy ruminant species. [ABSTRACT FROM AUTHOR]

Simple Summary: Little is known on the distribution of beta-lactam resistant Gram-negative bacteria in the gut of Madagascan animals. To increase respective knowledge, swabs from 49 animal stool droppings were collected in the Madagascan Tsimanapesotsa National Park and assessed by microbial culture, antimicrobial susceptibility testing, and sequence analysis. Third generation cephalosporine resistance, predominantly mediated by ampC-type beta-lactamases, was the most frequently observed beta-lactam resistance phenotype. Future studies should assess whether and to what extent an exchange of resistant isolates between humans and animals facilitates a local spread of resistant bacteria. Third generation cephalosporin-resistant (3GCR) Enterobacterales are known to be prevalent in Madagascar, with high colonization or infection rates in particular in Madagascan patients. Extended spectrum beta-lactamases (ESBLs) have been reported to be the predominant underlying resistance mechanism in human isolates. So far, little is known on antimicrobial resistance and its molecular determinants in Enterobacterales and other bacteria causing enteric colonization of Madagascan wild animals. To address this topic, swabs from 49 animal stool droppings were collected in the Madagascan Tsimanapesotsa National Park and assessed by cultural growth of bacterial microorganisms on elective media. In addition to 7 Acinetobacter spp., a total of 31 Enterobacterales growing on elective agar for Enterobacterales could be isolated and subjected to whole genome sequencing. Enterobacter spp. was the most frequently isolated genus, and AmpC-type beta-lactamases were the quantitatively dominating molecular resistance mechanism. In contrast, the blaCTX-M-15 gene, which has repeatedly been associated with 3GC-resistance in Madagascan Enterobacterales from humans, was detected in a single Escherichia coli isolate only. The identification of the fosfomycin-resistance gene fosA in a high proportion of isolates is concerning, as fosfomycin is increasingly used to treat infections caused by multidrug-resistant bacteria. In conclusion, the proof-of-principle assessment indicated a high colonization rate of resistant bacteria in stool droppings of Madagascan wild animals with a particular focus on 3GCR Enterobacterales. Future studies should confirm these preliminary results in a more systematic way and assess the molecular relationship of animal and human isolates to identify potential routes of transmission. [ABSTRACT FROM AUTHOR]

Multidrug-resistant Neisseria gonorrhoeae is a serious concern worldwide. Resistance to β-lactam antibiotics occurs through mutations in penicillin-binding proteins (PBPs), acquisition of β-lactamases, and alteration of antibiotic penetration. Mosaic structures of penA, which encodes PBP2, play a major role in resistance to β-lactams, especially cephalosporins. Ceftriaxone (CRO) is recognized as the only satisfiable antibiotic for the treatment of gonococcal infections; however, CRO-resistant isolates have emerged in the community. Here, we examined the affinity of β-lactam antibiotics for recombinant PBP2 in a competition assay using fluorescence-labeled penicillin. We found no or little difference in the affinities of penicillins and meropenem (MEM) for PBP2 from cefixime (CFM)-reduced-susceptible strain and cephalosporin-resistant strain. However, the affinity of cephalosporins, including CRO, for PBP2 from the cephalosporin-resistant strain was markedly lower than that for PBP2 from the CFM-reduced-susceptible-resistant strain. Notably, piperacillin (PIP) showed almost the same affinity for PBP2 from penicillin-susceptible, CFM-reduced-susceptible, and cephalosporin (including CRO)-resistant strains. Thus, PIP/tazobactam and MEM are candidate antibiotics for the treatment of CRO-resistant/multidrug-resistant N. gonorrhoeae. [ABSTRACT FROM AUTHOR]

Nontyphoid salmonella can cause severe infections in newborns and is therefore declared a pathogen of major health significance at this age. The aim of the study was molecular and antimicrobial characterization of β-lactamase-producing Salmonella Mikawasima outbreak clone on a Neonatal ward, University Hospital of Split (UHS), Croatia during the COVID-19 pandemic. From April 2020, until April 2023, 75 nonrepetitive strains of Salmonella Mikawasima were isolated from stool specimens and tested for antimicrobial resistance. All 75 isolates were resistant to ampicillin and gentamicin, while 98% of isolates were resistant to amoxicillin/clavulanic acid. A high level of resistance was observed to third-generation cephalosporins (36% to ceftriaxone and 47% to ceftazidime). Extended-spectrum β-lactamase production was phenotypically detected by double-disk synergy test in 40% of isolates. Moderate resistance to quinolones was detected; 7% of isolates were resistant to pefloxacin and ciprofloxacin. All isolates were susceptible to carbapenems, chloramphenicol, and co-trimoxazole. Fourteen representative isolates, from 2020, 2021, 2022, and 2023, were analyzed with PFGE and all of them belong to the same clone. Whole-genome sequencing (WGS) analysis of three outbreak-related strains (SM1 and SM2 from 2020 and SM3 from 2023) confirmed that these strains share the same serotype (Mikawasima), multilocus sequence typing profile (ST2030), resistance genes [blaTEM-1B,aac(6′)-Iaa, aac(6′)-Im, and aph(2′′)-Ib)] and carry incompatibility group C (IncC) plasmid. Furthermore, the gene blaSHV-2 was detected in SM1 and SM2. In summary, WGS analysis of three representative strains clearly demonstrates the persistence of β-lactamase-producing Salmonella Mikawasima in UHS during the 4-year period. [ABSTRACT FROM AUTHOR]

Amoxicillin and third-generation cephalosporins are widely used in the prevention and treatment of established infections. These broad-spectrum antibiotics are mainly excreted via urine and are considered relatively safe. However, several reports have indicated that substantial nephrotoxicity (e.g. acute interstitial nephritis and crystal nephropathy) occurs with amoxicillin and several cases of nephrotoxicity have been reported with ceftriaxone. While corticosteroids have been shown to improve kidney function in some patients with acute interstitial nephritis, close monitoring of kidney function for acute kidney injury can lead to an early diagnosis and recovery. Strategies preventing acute kidney injury can also be implemented. [ABSTRACT FROM AUTHOR]

Control measures are being introduced globally to reduce the prevalence of antibiotic resistance (ABR) in bacteria on farms. However, little is known about the current prevalence and molecular ecology of ABR in bacterial species with the potential to be key opportunistic human pathogens, such as Escherichia coli, on South American farms. Working with 30 dairy cattle farms and 40 pig farms across two provinces in central-eastern Argentina, we report a comprehensive genomic analysis of third-generation cephalosporin-resistant (3GC-R) E. coli, which were recovered from 34.8% (cattle) and 47.8% (pigs) of samples from fecally contaminated sites. Phylogenetic analysis revealed substantial diversity suggestive of long-term horizontal and vertical transmission of 3GC-R mechanisms. CTX-M-15 and CTX-M-2 were more often produced by isolates from dairy farms, while CTX-M-8 and CMY-2 and co-carriage of amoxicillin/clavulanate resistance and florfenicol resistance were more common in isolates from pig farms. This suggests different selective pressures for antibiotic use in these two animal types. We identified the β-lactamase gene blaROB, which has previously only been reported in the family Pasteurellaceae, in 3GC-R E. coli. blaROB was found alongside a novel florfenicol resistance gene, ydhC, also mobilized from a pig pathogen as part of a new composite transposon. As the first comprehensive genomic survey of 3GC-R E. coli in Argentina, these data set a baseline from which to measure the effects of interventions aimed at reducing on-farm ABR and provide an opportunity to investigate the zoonotic transmission of resistant bacteria in this region.IMPORTANCELittle is known about the ecology of critically important antibiotic resistance among bacteria with the potential to be opportunistic human pathogens (e.g., Escherichia coli) on South American farms. By studying 70 pig and dairy cattle farms in central-eastern Argentina, we identified that third-generation cephalosporin resistance (3GC-R) in E. coli was mediated by mechanisms seen more often in certain species and that 3GC-R pig E. coli were more likely to be co-resistant to florfenicol and amoxicillin/clavulanate. This suggests that on-farm antibiotic usage is key to selecting the types of E. coli present on these farms. 3GC-R E. coli and 3GC-R plasmids were diverse, suggestive of long-term circulation in this region. We identified the de novo mobilization of the resistance gene blaROB from pig pathogens into E. coli on a novel mobile genetic element, which shows the importance of surveying poorly studied regions for antibiotic resistance that might impact human health. [ABSTRACT FROM AUTHOR]

Background: Asymptomatic bacteriuria (ASB) during pregnancy can lead to symptomatic urinary tract infection (UTI), with increased fetal and maternal morbidity and mortality. We evaluated the incidence, clinical and microbiological profile, and outcome of ASB in pregnant women attending our antenatal clinic. Materials and Methods: This prospective study was conducted on 3769 pregnant women in a routine antenatal clinic at a tertiary care center. Participants were divided into two groups, ASB and non-bacteriuria. Data were collected in a standard proforma and analyzed using the software Statistical Package for the Social Sciences (SPSS) v. 20. Results: The incidence of ASB was 3.29% (124/3769). Majority of the women were in the age group of 21-30 years (78.76%, n = 89). Escherichia coli (61.06%) was the most common organism isolated. Maternal anemia (30.08% and 2.93% in the ASB and non-bacteriuria groups, respectively), low birth weight (LBW; 42.5% and 27.98% in the ASB and non-bacteriuria groups, respectively), intrauterine death (4.4% and 1.4% in the ASB and non-bacteriuria groups, respectively), and preterm delivery (37.2% and 22.31% in the ASB and non-bacteriuria groups, respectively) were were associated with ASB (P = 0.001). Conclusion: ASB was associated with maternal anemia, preterm delivery, intrauterine death, and LBW. Early detection and treatment of ASB may result in favorable maternal outcome. [ABSTRACT FROM AUTHOR]

Objectives Haemophilus parainfluenzae is an opportunistic pathogen causing respiratory tract infection and sexually transmitted diseases. The emergence of multidrug resistance in this species is particularly worrisome, especially since the recent description of CTX-M-15 ESBL-producing isolates in Spain. The aim of this study was to characterize a CTX-M-15-producing H. parainfluenzae clinical isolate, HP01, obtained from a urethral swab. Methods MICs were determined with gradient strips for this isolate. Hydrolysis assays were performed with the β LACTA test. Genomic DNA from HP01 was subjected to Illumina and Oxford Nanopore sequencing to investigate the genetic environment of bla CTX-M-15. Phylogenetic analysis was performed with available H. parainfluenzae genomes from the NCBI database, including CTX-M-15 producers. Results HP01, an XDR isolate, was resistant to penicillin, third-generation cephalosporins, fluoroquinolones, macrolides, cyclines and co-trimoxazole and susceptible only to carbapenems and rifampicin. HP01 carried bla TEM-1, bla CTX-M-15, tet (M), catS and mef (E) /mel and harboured amino acid substitutions in PBP3, PBP5, GyrA, ParC and FolA implicated in resistance. Genomic analysis revealed that bla CTX-M-15 was carried by a Tn 3 -like transposon inserted into a novel integrative and conjugative element (ICE), ICE Hpa SLS, present on the chromosome and belonging to the ICE Hin1056 family described in Haemophilus influenzae. The tet (M)-MEGA element was also detected on the chromosome. No plasmid was found. The phylogenetic analysis showed that four H. parainfluenzae producing CTX-M-15 clustered in the same clade. Conclusions Here we report the description of an XDR H. parainfluenzae producing bla CTX-M-15 isolated from a urethral swab. The bla CTX-M-15 gene was inserted into an ICE structure similar to those recently described in CTX-M-15 producers in Spain. The emergence of XDR H. parainfluenzae producing bla CTX-M-15 is a matter of great concern. Careful surveillance is required to prevent its spread. [ABSTRACT FROM AUTHOR]

Objectives: Although amoxicillin is the first‐line prophylactic drug for impacted mandibular third molar extraction, third‐generation cephalosporins are widely prescribed in Japan. The lack of real‐world evidence may be one reason for this inappropriate use. We evaluated differences in the incidence of surgical site infection between amoxicillin and third‐generation cephalosporins for impacted mandibular third molar extraction. Methods: Using the JMDC Claims Database, we identified dental visits with fully or horizontally impacted mandibular third molar extraction from April 2015 to March 2020. One‐to‐one propensity‐score matching was conducted between amoxicillin and third‐generation cephalosporin groups. The incidence of surgical site infection following extraction was compared in the matched pairs using McNemar's test. Results: We identified 109,266 dental visits, including 39,514 (36.2%) patients who received amoxicillin and 69,752 (63.8%) patients who received third‐generation cephalosporins. In the 39,514 matched pairs, the incidence of surgical site infection was 3.5% (n = 1399) for amoxicillin group and 3.7% (n = 1467) for third‐generation cephalosporin group (p = 0.003). Conclusions: Amoxicillin was associated with a lower incidence of surgical site infection after impacted mandibular third molar extraction compared with third‐generation cephalosporins. This result supports current guidelines and strengthens the importance of disseminating and implementing antimicrobial resistance control in dentistry. [ABSTRACT FROM AUTHOR]

Background: The two latest studies on prolonged versus intermittent use of β-lactam antibiotics in patients with sepsis did not reach consistent conclusions, further contributing to the controversy surrounding the effectiveness of the prolonged β-lactam antibiotics infusion strategy. We conducted a systemic review and meta-analysis to evaluate the efficacy and safety of prolonged and intermittent β-lactam infusion in adult patients with sepsis. Methods: We systematically searched PubMed, EMBASE, and Cochrane Library databases for original randomized controlled trials comparing prolonged and intermittent β-lactam infusion in sepsis patients. A random-effects model was used to evaluate mortality, clinical success, microbiological success, and adverse events. We also conducted subgroup analyses to explore the impact of various factors on the mortality rates. Relative risk (RR) and corresponding 95% confidence intervals (CIs) were used to calculate the overall effect sizes for dichotomous outcomes. This meta-analysis was registered in PROSPERO (CRD42023463905). Results: We assessed 15 studies involving 2130 patients. In our comprehensive assessment, we found a significant reduction in all-cause mortality (RR, 0.83; 95% CI 0.72–0.97; P = 0.02) and a notable improvement in clinical success (RR, 1.16; 95% CI 1.03–1.31; P = 0.02) in the prolonged infusion group compared to the intermittent infusion group, whereas microbiological success did not yield statistically significant results (RR, 1.10; 95% CI 0.98–1.23; P = 0.11). No significant differences in adverse events were observed between the two groups (RR, 0.91; 95% CI 0.64–1.29; P = 0.60). Additionally, remarkable conclusions were drawn from subgroup analyses including studies with sample sizes exceeding 20 individuals per group (RR, 0.84; 95%CI 0.72–0.98; P = 0.03), research conducted post-2010 (RR, 0.84; 95%CI 0.72–0.98; P = 0.03), cases involving infections predominantly caused by Gram-negative bacteria (RR, 0.81; 95%CI 0.68–0.96; P = 0.02), as well as the administration of a loading dose (RR, 0.84; 95% CI 0.72–0.97; P = 0.02) and the use of penicillin (RR, 0.61; 95% CI 0.38–0.98; P = 0.04). Conclusions: Compared to intermittent infusion, prolonged infusion of β-lactam antibiotics significantly decreases all-cause mortality among patients with sepsis and enhances clinical success without increasing adverse events. [ABSTRACT FROM AUTHOR]

(1) Background: Linear immunoglobulin A bullous dermatosis (LABD) is a rare autoimmune, subepidermal blistering disease, characterized by linear IgA deposits along the epidermal basement membrane. LABD is idiopathic and is associated with medication and systemic autoimmune diseases. (2) Methods: We investigated the demographic characteristics, disease course, causative agents, and associated diseases in Korean patients with LABD. The Korean Health Insurance Review and Assessment Service database was used to obtain data. We identified 670 LABD cases between 2010 and 2022. (3) Results: The annual incidence of LABD was 1.3 per 100,000 persons, with a higher prevalence in individuals ≥60 years old. The patients were treated with dapsone for 30.7 ± 56.7 days, had 1.3 ± 0.7 hospital visits, and were hospitalized for 19.8 ± 19.7 days. Risk factors, including malignancy, commonly preceded LABD. Antibiotic use, specifically vancomycin and third-generation cephalosporins, was a risk factor. The mean age of LABD diagnosis was 55.9 ± 21.7 years. (4) Conclusion: This is the first published study to assess a nationwide cohort for LABD. The incidence of LABD was higher than that in other studies. Most case reports have linked LABD with the administration of specific antibiotics; however, this study shows there were more associations with other conditions. [ABSTRACT FROM AUTHOR]

Introduction: Many studies have demonstrated significant antibiotic resistance by commonly isolated organisms. This is an eye-opener for the clinicians, who prescribe antibiotics day in and out. This situation shifts our attention towards the usage of antiseptic measures, which can at times play an important role in preventing and treating various infections. Method: This is a double-blinded randomized controlled study that compares the bundle approach to the conventional approach for the prevention of surgical site infections in patients of peritonitis undergoing midline laparotomy in emergency. The bundle approach includes three measures, namely, painting of surgical site with chlorhexidine, dabbing the wound with povidone-iodine after the closure of the rectus sheath, and application of chlorhexidine-impregnated gauze piece over the skin wound. Results: The total sample size was 64 (32 in each arm). The rate of surgical site infection was significantly lower in the test arm (21.8%) as compared to the conventional arm (46.8%). The mean length of hospital stay was shorter by one day in the test arm, although, not significant. The isolates from the peritoneal fluid culture and wound culture were mostly gram-negative organisms. Most of the organisms exhibited resistance toward third generation cephalosporins, fluoroquinolones, and aminoglycosides. Conclusion: Antibiotic resistance is a burning concern in today's world. Alternative methods of preventing infection in the form of using antiseptics should be sought. Although our study was limited to emergency cases, this bundle approach can be implemented in elective cases as well. [ABSTRACT FROM AUTHOR]

To evaluate the prevalence and quality of antimicrobial prescriptions using a Global Point Prevalence Survey (PPS) tool and help identify targets for improvement of antimicrobial prescribing and inform the development of antimicrobial stewardship activities. Antimicrobial prescriptions for inpatients staying at a hospital overnight were surveyed on one weekday in October 2018, November 2019, and November 2020. Data including basic patient information, antimicrobial drugs, quality evaluation of antimicrobial drug prescription, and the risk factors of nosocomial infection were collected from doctor network workstation. Patient information was anonymized and entered in the PPS Web application by physicians. A total of 720 patients (median age, 62 years) were surveyed. Of them, 246 (34.2%) were prescribed antimicrobials on the survey days. Hospital-wide antimicrobial use had a significantly decreasing trend (P < 0.001). The most commonly prescribed antimicrobial drugs were third-generation cephalosporins (40.5%), followed by quinolones (21.8%) and second-generation cephalosporin (12.5%). In our study, cefoperazone/sulbactam, ceftazidime, and levofloxacin were the most commonly used antimicrobials. The most common indication for antimicrobial use was pneumonia or lower respiratory tract infection (159/321, 49.5%). Antimicrobial for surgical prophylaxis represented 16.2% of the total antibiotic doses. Of those, 67.3% were administered for more than 24 h. The rate of adherence to antibiotic guidelines was 61.4%. The indications for antimicrobials were not documented in 54.5% of the prescriptions. Stop/review date was documented for 36.8% of prescriptions. The PPS tool is useful in identifying targets to enhance the quality of antimicrobial prescriptions to improve the adherence rate in hospitals. This survey can be used as a control to assess the rational application quality of antimicrobial after regular application of antimicrobial intervention. [ABSTRACT FROM AUTHOR]

For the first time since 2015, the World Health Organization's (WHO) global Antimicrobial Resistance and Use Surveillance (GLASS) featured both global reports for antimicrobial resistance (AMR) and antimicrobial consumption (AMC) data in its annual reports. In this study we investigated the relationship of AMR with AMC within participating countries reported in the GLASS 2022 report. Our analysis found a statistically significant correlation between beta-lactam/cephalosporin and fluoroquinolones consumption and AMR to these antimicrobials associated with bloodstream E. coli and Klebsiella pneumoniae among the participating countries (P<0.05). We observed that for every 1 unit increase in defined daily dose DDD of beta-lactam/cephalosporins and quinolone consumptions among the countries, increased the recoveries of bloodstream-associated beta-lactam/cephalosporins-resistant E. coli/Klebsiella spp. by 11–22% and quinolone-resistant E. coli/Klebsiella spp. by 31–40%. When we compared the antimicrobial consumptions between the antimicrobial ATC (Alphanumeric codes developed by WHO) groups and countries, we observed a statistically significant higher daily consumption of beta-lactam-penicillins (J01C, DDD difference range: 5.23–8.13) and cephalosporins (J01D, DDD difference range: 2.57–5.13) compared to other antimicrobial groups among the countries (adjusted for multiple comparisons using Tukey's method). Between the participating countries, we observed a statistically significant higher daily consumption of antimicrobial groups in Iran (DDD difference range: 3.63–4.84) and Uganda (DDD difference range: 3.79–5.01) compared to other participating countries (adjusted for multiple comparisons using Tukey's method). Understanding AMC and how it relates to AMR at the global scale is critical in the global AMR policy development and implementation of global antimicrobial stewardship. [ABSTRACT FROM AUTHOR]

OBJECTIVE To describe the clinical findings, microbiological data, treatment, and outcome of a population of cats with suspected acute pyelonephritis (APN). ANIMALS 32 client-owned cats. CLINICAL PRESENTATION AND PROCEDURES Retrospective case series from 2 veterinary teaching hospitals between January 1, 2014, and December 31, 2020. Cats were included if they had a positive bacterial urine culture and a clinical diagnosis of acute kidney injury. RESULTS Older female cats with underlying chronic kidney disease have a higher probability to develop bacterial culture–positive acute kidney injury or APN. Escherichia coli was the most commonly cultured bacterial species, and E coli isolates with susceptibility testing were resistant to amoxicillin-clavulanate but susceptible to fluoroquinolones or third-generation cephalosporins. Of the 20 cats with available follow-up information in the medical record, 14 were alive at 3 months after hospital discharge. Markers of renal function including creatinine (P = .008), BUN (P = .005), and phosphorus (P < .001) at the time of presentation were all higher in nonsurvivors compared with survivors. CLINICAL RELEVANCE The survival rate with feline APN is higher than previous reports of acute kidney injury when all etiologies are considered. Nonsurvivors had more pronounced azotemia upon initial presentation. Amoxicillin-clavulanate was a poor empirical antimicrobial in this cohort based on the microbiological data. [ABSTRACT FROM AUTHOR]