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Objective: The aim of this study was to evaluate the antibiotic resistance of microorganisms isolated in cases of culture-positive nosocomial late-onset neonatal sepsis in the neonatal intensive care unit. Materials and Methods: Infants admitted to our neonatal intensive care unit between October 2015 and June 2022 were retrospectively screened. A total of 458 different cultures from 386 sepsis incidents in 250 infants were analyzed. Results: Over an 8-year period, 407 cases of culture-positive nosocomial late-onset neonatal sepsis were reviewed in a total of 4244 infants. Twenty-one cases were excluded due to insufficient data. The incidence of culture-positive nosocomial sepsis was 6.3%. Coagulase-negative Staphylococcus and Staphylococcus aureus were the most common gram-positive bacteria found in cultures. Resistance to ampicillin and cephalosporin treatments was high, while resistance to vancomycin, teicoplanin, and linezolid was low. Klebsiella spp. were the most frequent gram-negative bacteria isolated in cultures and showed high resistance to non-carbapenembased regimens. The only fungal microorganisms isolated in cultures were Candida spp., which had a high mortality rate despite their low resistance profile. The mortality rate due to nosocomial sepsis was 19.6%. Conclusion: Our study demonstrated that microorganisms and their antibiotic resistance profiles changed over time in the newborn intensive care unit. Gram-negative pathogens exhibited high antibiotic resistance, while fungi had high mortality rates. It is essential to adjust empirical antibiotic regimens for nosocomial sepsis based on thorough surveillance. [ABSTRACT FROM AUTHOR]

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]

Introduction: The study of Klebsiella quasipneumoniae, Klebsiella variicola, and AmpC production in extended-spectrum β-lactamase (ESBL)-producing Klebsiella in Japan is limited, and existing data are insufficient. This study aims to characterize Klebsiella species, determine AmpC production rates, and analyze antimicrobial resistance patterns in ESBL-producing Klebsiella isolates in Japan. Methods: A total of 139 clinical isolates of ESBL-producing Klebsiella were collected in Japan, along with their corresponding antimicrobial susceptibility profiles. The isolates were identified using a web-based tool. ESBL genes within the isolates were identified using multiplex PCR. Screening for AmpC-producing isolates was performed using cefoxitin disks, followed by multiplex PCR to detect the presence of AmpC genes. Antimicrobial resistance patterns were analyzed across the predominant ESBL genotypes. Results: The web-based tool identified 135 isolates (97.1%) as Klebsiella pneumoniae and 4 (2.9%) as K. quasipneumoniae subsp. similipneumoniae, with no instances of K. variicola detected. Among K. pneumoniae, the CTX-M-1 group emerged as the predominant genotype (83/135, 61.5%), followed by K. quasipneumoniae subsp. similipneumoniae (3/4, 75.0%). The CTX-M-9 group was the second most prevalent genotype in K. pneumoniae (45/135, 33.3%). The high resistance rates were observed for quinolones (ranging from 46.7% to 63.0%) and trimethoprim/sulfamethoxazole (78.5%). The CTX-M-1 group exhibited higher resistance to ciprofloxacin (66/83, 79.5%) compared to the CTX-M-9 group (18/45, 40.0%), a trend also observed for levofloxacin and trimethoprim/sulfamethoxazole. Among the 16 isolates that tested positive during AmpC screening, only one K. pneumoniae isolates (0.7%) were confirmed to carry the AmpC gene. Conclusion: Klebsiella pneumoniae with the CTX-M-1 group is the most common ESBL-producing Klebsiella in Japan and showed a low proportion of AmpC production. These isolates are resistant to quinolones and trimethoprim/sulfamethoxazole, highlighting the challenge of managing this pathogen. The findings underscore the importance of broader research and continuous monitoring to address the resistance patterns of ESBL-producing Klebsiella. [ABSTRACT FROM AUTHOR]

Background Investigations into antibiotics for extended-spectrum β-lactamase-producing Enterobacterales (ESBL-E) bloodstream infections (BSIs) have focused on bla CTX-M genes. Patient outcomes from non–CTX-M-producing ESBL-E BSIs and optimal treatment are unknown. Methods A multicenter observational study investigating 500 consecutive patients with ceftriaxone-resistant Enterobacterales BSIs during 2018–2022 was conducted. Broth microdilution and whole-genome sequencing confirmed antibiotic susceptibilities and ESBL gene presence, respectively. Inverse probability weighting (IPW) using propensity scores ensured patients with non–CTX-M and CTX-M ESBL-E BSIs were similar before outcome evaluation. Results 396 patients (79.2%) were confirmed to have an ESBL-E BSI. ESBL gene family prevalence was as follows: bla CTX-M (n = 370), bla SHV (n = 16), bla OXY (n = 12), and bla VEB (n = 5). ESBL gene identification was not limited to Escherichia coli and Klebsiella species. In the IPW cohort, there was no difference in 30-day mortality or ESBL-E infection recurrence between the non–CTX-M and CTX-M groups (odds ratio [OR], 0.99; 95% confidence interval [CI],.87–1.11; P =.83 and OR, 1.10; 95% CI,.85–1.42; P =.47, respectively). In an exploratory analysis limited to the non–CTX-M group, 86% of the 21 patients who received meropenem were alive on day 30; none of the 5 patients who received piperacillin-tazobactam were alive on day 30. Conclusions Our findings suggest that non–CTX-M and CTX-M ESBL-E BSIs are equally concerning and associated with similar clinical outcomes. Meropenem may be associated with improved survival in patients with non–CTX-M ESBL-E BSIs, underscoring the potential benefit of comprehensive molecular diagnostics to enable early antibiotic optimization for ESBL-E BSIs beyond just bla CTX-M genes. [ABSTRACT FROM AUTHOR]

We investigated links between antimicrobial resistance in community-onset bacteremia and 1-year bacteremia recurrence by using the clinical data warehouse of Europe's largest university hospital group in France. We included adult patients hospitalized with an incident community-onset Staphylococcus aureus, Escherichia coli, or Klebsiella spp. bacteremia during 2017-2019. We assessed risk factors of 1-year recurrence using Fine-Gray regression models. Of the 3,617 patients included, 291 (8.0%) had >1 recurrence episode. Third-generation cephalosporin (3GC)-resistance was significantly associated with increased recurrence risk after incident Klebsiella spp. (hazard ratio 3.91 [95% CI 2.32-6.59]) or E. coli (hazard ratio 2.35 [95% CI 1.50-3.68]) bacteremia. Methicillin resistance in S. aureus bacteremia had no effect on recurrence risk. Although several underlying conditions and infection sources increased recurrence risk, 3GC-resistant Klebsiella spp. was associated with the greatest increase. These results demonstrate a new facet to illness induced by 3GC-resistant Klebsiella spp. and E. coli in the community setting. [ABSTRACT FROM AUTHOR]

Introduction: Urinary tract infection (UTI) is among the common bacterial infections in pediatric patients. These infections are more common in girls over one year old. This study aimed to investigate the bacterial distribution and drug resistance status in urine cultures of pediatric patients in our center. Materials and Methods: Urine culture results of patients who were presented to the outpatient clinics or were admitted to the Sivas Cumhuriyet University hospital between January 2017 and December 2022 were included in the study. The hospital automation system, patient files, and laboratory information management system were examined retrospectively. Statistical analysis was performed using the SPSS 22.0 software. A P-value of <0.05 was deemed significant. Results: Significant growth was observed in the urine cultures of a total of 1287 pediatric patients, 889 (69.1%) girls and 398 boys (30.9%). The patients included in the study were between the ages of 0-17, and children aged 1-6 (37.6%) were diagnosed with UTI more frequently than other ages. The most common UTI agent in the pediatric age group was Escherichia coli (56.6%). The first agent isolated in girls and boys is E.coli. Additionally, the prevalence of K. pneumoniae, P. mirabilis and K. oxytoca bacteria was higher in boys (p < 0.05). E. coli isolates showed minimal resistance to such as amikacin (0.6%), fosfomycin (1.0%), nitrofurantoin (1.4%), ertapenem (2.4%), imipenem (0.7%) and meropenem (0.9%). Conclusion: In this study, low resistance levels were detected for amikacin, fosfomycin, nitrofurantoin and carbapenem group antibiotics, which are important alternatives in the empirical treatment of UTI. On the other hand, due to the high resistance levels detected, it is thought that more caution should be exercised in the empirical use of amoxicillin-clavulanate, trimethoprimsulfamethoxazole and cefixime. If these antibiotics are to be preferred, waiting for the antibiogram results is an appropriate approach. [ABSTRACT FROM AUTHOR]

Introduction: Urinary tract infection (UTI) is among the common bacterial infections in pediatric patients. These infections are more common in girls over one year old. This study aimed to investigate the bacterial distribution and drug resistance status in urine cultures of pediatric patients in our center. Materials and Methods: Urine culture results of patients who were presented to the outpatient clinics or were admitted to the Sivas Cumhuriyet University hospital between January 2017 and December 2022 were included in the study. The hospital automation system, patient files, and laboratory information management system were examined retrospectively. Statistical analysis was performed using the SPSS 22.0 software. A P-value of <0.05 was deemed significant. Results: Significant growth was observed in the urine cultures of a total of 1287 pediatric patients, 889 (69.1%) girls and 398 boys (30.9%). The patients included in the study were between the ages of 0-17, and children aged 1-6 (37.6%) were diagnosed with UTI more frequently than other ages. The most common UTI agent in the pediatric age group was Escherichia coli (56.6%). The first agent isolated in girls and boys is E.coli. Additionally, the prevalence of K. pneumoniae, P. mirabilis and K. oxytoca bacteria was higher in boys (p < 0.05). E. coli isolates showed minimal resistance to such as amikacin (0.6%), fosfomycin (1.0%), nitrofurantoin (1.4%), ertapenem (2.4%), imipenem (0.7%) and meropenem (0.9%). Conclusion: In this study, low resistance levels were detected for amikacin, fosfomycin, nitrofurantoin and carbapenem group antibiotics, which are important alternatives in the empirical treatment of UTI. On the other hand, due to the high resistance levels detected, it is thought that more caution should be exercised in the empirical use of amoxicillin-clavulanate, trimethoprimsulfamethoxazole and cefixime. If these antibiotics are to be preferred, waiting for the antibiogram results is an appropriate approach. [ABSTRACT FROM AUTHOR]

Carbapenemase‐producing gram‐negative bacteria (CP‐GNB) infections threaten public health with high mortality, morbidity and treatment costs. Although frequencies remain low in Australia (total number of CP‐GNB infections reported was 907 in 2022), blaIMP‐4 has established low levels of endemicity in many states. Imipenemase metallo‐β‐lactamase types alone accounted for more than half of all carbapenemases in carbapenemase‐producing Enterobacterales isolates in Australia, particularly in Enterobacter cloacae complex. New Delhi metallo‐β‐lactamase constitutes almost 25% of all carbapenemases in Australia and was identified predominantly in Escherichia coli. The OXA‐48‐like carbapenemases include almost 10% of all carbapenemases and are mainly seen in Klebsiella pneumoniae and E. coli. Although K. pneumoniae carbapenemase‐type carbapenemases are rare in Australia, some local outbreaks have occurred. Most carbapenem‐resistant (CR) Pseudomonas aeruginosa strains in Australia do not produce carbapenemases. Finally, OXA‐23‐like carbapenemases are overwhelmingly positive in CR‐Acinetobacter baumannii strains in Australia. Treatment of CR‐GNB infections challenges physicians. Of 10 new antibiotics active against at least some CR‐GNB infections that are approved by the US Food and Drug Administration, just three are approved for use in Australia. In this context, there is still an unmet need for novel antibacterials that can be used for the treatment of CR‐GNB infections in Australia, as well as a pressing requirement for new mechanisms to 'de‐link' antibiotic sales from their availability. In this narrative review, we aim to overview the epidemiology and clinical significance of carbapenem resistance in Australia as it pertains to Enterobacterales, P. aeruginosa and A. baumannii. [ABSTRACT FROM AUTHOR]

Purpose To characterize the susceptibilities of positive bacterial cultures and the appropriateness of empiric antimicrobial regimens for patients admitted from post–acute care facilities (PACFs). Methods This was a retrospective quality improvement study. The study included patients admitted from a PACF to one of 2 tertiary care teaching hospitals within the University of Pennsylvania Health System, located in Philadelphia, PA, from August 2020 to December 2021. Patients were included if they had at least one positive culture within 72 hours of admission. Results A total of 167 patients and 230 isolates from the study period were evaluated. The majority of positive cultures were from a urinary source (114 of 230, 49.6%). Nineteen patients (11.4%) had a history of multidrug-resistant organisms. The most common empiric antibiotics used were vancomycin (61.7%) and cefepime (59.3%). Sixty-one patients (36.5%) received inappropriate empiric therapy based on the culture results. When comparing our hospitals' general antibiogram to that of only PACF patients, Escherichia coli and Klebsiella pneumoniae had at least a 20% difference in susceptibility to levofloxacin, ceftriaxone, and cefepime. Extended-spectrum β-lactamase resistance was also higher in the PACF cohort (odds ratio, 2.09; 95% confidence interval, 1.4-3.1). Conclusion Clinically significant differences in antimicrobial susceptibility were found among patients admitted from PACFs compared to our health system's general antibiogram. The increased resistance rates identified in this study support the need for hospitals to evaluate this at-risk patient population, which may drive changes to empiric antibiotic prescribing practices. [ABSTRACT FROM AUTHOR]

Background: Antimicrobial resistance research in uncomplicated urinary tract infection typically focuses on the main causative pathogen, Escherichia coli; however, little is known about the antimicrobial resistance burden of Klebsiella species, which can also cause uncomplicated urinary tract infections. This retrospective cohort study assessed the prevalence and geographic distribution of antimicrobial resistance among Klebsiella species and antimicrobial resistance trends for K. pneumoniae in the United States (2011–2019). Methods: K. pneumoniae and K. oxytoca urine isolates (30-day, non-duplicate) among female outpatients (aged ≥ 12 years) with presumed uUTI at 304 centers in the United States were classified by resistance phenotype(s): not susceptible to nitrofurantoin, trimethoprim/sulfamethoxazole, or fluoroquinolone, extended-spectrum β-lactamase-positive/not susceptible; and multidrug-resistant based on ≥ 2 and ≥ 3 resistance phenotypes. Antimicrobial resistance prevalence by census division and age, as well as antimicrobial resistance trends over time for Klebsiella species, were assessed using generalized estimating equations. Results: 270,552 Klebsiella species isolates were evaluated (250,719 K. pneumoniae; 19,833 K. oxytoca). The most frequent resistance phenotypes in 2019 were nitrofurantoin not susceptible (Klebsiella species: 54.0%; K. pneumoniae: 57.3%; K. oxytoca: 15.1%) and trimethoprim/sulfamethoxazole not susceptible (Klebsiella species: 10.4%; K. pneumoniae: 10.6%; K. oxytoca: 8.6%). Extended-spectrum β-lactamase-positive/not susceptible prevalence was 5.4%, 5.3%, and 6.8%, respectively. K. pneumoniae resistance phenotype prevalence varied (p < 0.0001) geographically and by age, and increased over time (except for the nitrofurantoin not susceptible phenotype, which was stable and > 50% throughout). Conclusions: There is a high antimicrobial resistance prevalence and increasing antimicrobial resistance trends among K. pneumoniae isolates from female outpatients in the United States with presumed uncomplicated urinary tract infection. Awareness of K. pneumoniae antimicrobial resistance helps to optimize empiric uncomplicated urinary tract infection treatment. [ABSTRACT FROM AUTHOR]

Background: An increasing number of drugs are used each year in the treatment of small pets (cats and dogs), including medicines (cephalosporins and fluoroquinolones) used in human therapy. Aim: The purpose of this study was to isolate and explore the antibiotic resistance of opportunistic Enterobacteriaceae (Escherichia coli, Klebsiella, Proteus, Ci trobacter, Enterobacter) from cats and dogs, and to isolate resistance genes in the microorganisms. Methods: In 2021, 808 samples of biological material from small domestic animals were collected in veterinary clinics in Kostanay. From these, 210 microorganisms were isolated and identified. Results: A large majority of the strains sampled belonged to E. coli-149 (70.9%), Enterobacter-11 (5.2%), Klebsiella-28 (13.3%), Proteus-12 (5.7%) and 10 Citrobacter isolates (4.8%). In all isolates identified, antibiotic resistance/sensitivity was determined by disc-diffusion method to ampicillin, cefoxitin, gentamicin, levomycetin, tetracycline, ciprofloxacin, norfloxacin, ofloxacin, cefoperazone, cefpodoxime, streptomycin, kanamycin, doxycycline, gemifloxacin, nalidixic acid, furazolidone, furadonine, amoxicillin, and enrofloxacin. Conclusion: The study has demonstrated that the greatest number of Enterobacteriaceae were sensitive to the action of meropenem, which belongs to the group of beta-lactam antibiotics; resistance was demonstrated against tetracycline, doxycycline, ampicillin, amoxicillin, ofloxacin, and cefpodoxime. The most common genes encoding antimicrobial resistance were as follows: BlaTEM and OXA in 41 and 28 isolates, respectively, encoding resistance to beta-lactams; StrA and StrB in 45 and 48 isolates encoding aminoglycosides; and tetA and tetB in 43 and 28 isolates encoding tetracyclines. Obtained data demonstrate that uncontrolled and frequent use of beta-lactam and tetracycline antibacterials, in cats and dogs, results in the spread of genotypic resistance among micro-organisms of the family Enterobacteriaceae. [ABSTRACT FROM AUTHOR]

This document is a correction notice for an article titled "Review and analysis of the overlapping threats of carbapenem and polymyxin resistant E. Coli and Klebsiella in Africa" published in the journal Antimicrobial Resistance & Infection Control. The correction notes errors in Table 2 and Additional File 1, which have been corrected in the notice. The article discusses the susceptibility and resistance of E. Coli and Klebsiella to carbapenem and polymyxin antibiotics in various African nations. The document provides a table showing reported carbapenem or polymyxin susceptibility in African nations, with the number of reported cases for each country. It is mentioned that reports on susceptibility were not found for certain countries. The document also includes supplementary material and a note from the publisher emphasizing their neutrality. [Extracted from the article]

Background The clinical and microbial factors associated with Klebsiella pneumoniae bloodstream infections (BSIs) are not well characterized. Prior studies have focused on highly resistant or hypervirulent isolates, limiting our understanding of K. pneumoniae strains that commonly cause BSI. We performed a record review and whole-genome sequencing to investigate the clinical characteristics, bacterial diversity, determinants of antimicrobial resistance, and risk factors for in-hospital death in a cohort of patients with K. pneumoniae BSI. Methods We identified 562 patients at Massachusetts General Hospital with K. pneumoniae BSIs between 2016 and 2022. We collected data on comorbid conditions, infection source, clinical outcomes, and antibiotic resistance and performed whole-genome sequencing on 108 sequential BSI isolates from 2021 to 2022. Results Intra-abdominal infection was the most common source of infection accounting for 34% of all BSIs. A respiratory tract source accounted for 6% of BSIs but was associated with a higher in-hospital mortality rate (adjusted odds ratio, 5.4 [95% confidence interval, 2.2–12.8]; P <.001 for comparison with other sources). Resistance to the first antibiotic prescribed was also associated with a higher risk of death (adjusted odds ratio, 5.2 [95% confidence interval, 2.2–12.4]; P <.001). BSI isolates were genetically diverse, and no clusters of epidemiologically and genetically linked cases were observed. Virulence factors associated with invasiveness were observed at a low prevalence, although an unexpected association between O-antigen type and the source of infection was found. Conclusions These observations demonstrate the versatility of K. pneumoniae as an opportunistic pathogen and highlight the need for new approaches for surveillance and the rapid identification of patients with invasive antimicrobial-resistant K. pneumoniae infection. [ABSTRACT FROM AUTHOR]

Background and Aim: Since first reported in 2015, the mobile colistin resistance (mcr-1) gene has been found in increasing numbers worldwide. However, only a few studies have been carried out in Morocco. Herein, we aimed to investigate the prevalence of colistin resistance and mcr-like genes among Enterobacteriaceae clinical isolates from the North-West of Morocco. Materials and Methods: The prevalence of colistin resistance was investigated among 338 Enterobacteriaceae clinical isolates. These isolates were collected from Tangier and Tetouan cities between December 2020 and May 2021. The isolates included Escherichia coli (E. coli), Klebsiella pneumoniae (K. pneumoniae), Enterobacterspp, Citrobacter freundii (C. freundii), and Proteus mirabilis (P. mirabilis). Antibacterial susceptibility tests were performed using disc diffusion assay and minimal inhibitory concentrations (MIC). All isolates that were found resistant to colistin were subjected to PCR and sequencing techniques to screen them for the presence of mcr-like genes (mcr-1 to mcr-5). Results: 22.78% of isolates were multidrug-resistant (MDR), among which 57.14% of P. mirabilis isolates, 30% of Enterobacter spp isolates, 22.22% of K. pneumoniae isolates, and 22.05% of E. coli isolates. Colistin resistance was found in 51 of 338 isolates, including 33 E. coli, 11 K. pneumoniae, and 7 P. mirabilis. The mcr-1 gene was detected in 3 E. coli isolates. Mcr-2 to mcr-5 genes were absent in this study. Sequencing of PCR amplicons revealed 99–100% similarity to mcr-1 gene. Conclusion: This is the first study conducted in Morocco to investigate the prevalence of colistin resistance among clinical isolates, and it has revealed the first three mcr-1 genes circulating in Morocco. This could lead to the dissemination of these genes throughout Morocco. [ABSTRACT FROM AUTHOR]

Extensively drug-resistant (XDR), multidrug-resistant (MDR) and pandrug-resistant (PDR) Gram-negative microorganisms (GNBs) are considered a significant global threat. β-lactam and aminoglycoside combinations and imipenem:cyclodextrin inclusion complexes were studied for the treatment of lethal GNBs. This is because of the broad empiric coverage of the two drugs and their possession of different spectra of activity. Two cyclodextrins (β- and hydroxy propyl β-cyclodextrins) were utilized for inclusion complex formation with imipenem using the physical and kneading methods. In silico investigation using the molecular docking and Fourier-infrared spectroscopy (FTIR) were employed to estimate binding constant and confirm complex formation, respectively. The in vitro effects of amikacin and imipenem combination in comparison to the effect of imipenem-β- and hydroxy propyl β-cyclodextrin (CD) complexes against Klebsiella spp. and Acinetobacter baumannii were studied. The isolated microorganisms' antimicrobial responsiveness to various antibiotics (19 antibiotics) was evaluated. It was found that piperacillin/tazobactam and gentamycin (resistance rates were 33.3% and 34%, respectively) were the most effective antimicrobials. The in vitro studies have been performed by the checkerboard technique and time-killing assay. The studied combination of amikacin and imipenem showed a substantial drop in bacterial count (p < 0.05). The in vitro studies demonstrated a synergism for the investigated combination. Conventional PCR was used in molecular studies to identify the resistance genes bla IMP and aac (6′)-Ib. The blaIMP and aac (6′)-Ib were recorded in 38.2% and 3.6% of the studied isolates, respectively. The in vitro studies showed synergistic effects among the tested antibiotics with FICIs of ≤0.5. Finally, the study compared the reduction in bacterial count between the tested antibiotic combinations and imipenem:CD physical and kneaded mixtures. Imipenem:CD inclusion complexes demonstrated a significant bacterial count reduction over the antibiotic combination. These results highlight the emerging role of CDs as safe biofunctional excipients in the combat against superbug bacterial resistance. [ABSTRACT FROM AUTHOR]

Urinary tract infections (UTIs) are highly prevalent bacterial infections that pose significant health risks. Specific probiotic strains have been recommended for UTI control and management of antibiotic resistance. Otherwise, para- probiotics, defined as inactivated probiotic cells, offer potential advantages by minimizing risks associated with live microorganisms. However, the effectiveness of heat-killed probiotic strains against UTIs remains uncertain. Additionally, lactoferrin (LF), an iron-binding glycoprotein, exhibits immunomodulatory, antimicrobial, and anti-inflammatory prop-erties. Recently, we had developed recombinant LF-expression probiotics, which can display considerate antibacterial activities against select food-borne pathogens in vitro. Thus, the present study aimed to evaluate the antibacterial activities of heat-killed natural and recombinant LF-expressing probiotics against UTIs in vitro and in vivo. Firstly, using in vitro assays, we assessed the antibacterial activity of heat-killed natural and recombinant LF-expressing probiotics against uropathogenic Escherichia coli and Klebsiella pneumoniae. Among the tested probiotics, 10 heat-killed LF-expressing strains displayed superior antibacterial efficacy compared to 12 natural probiotics. Based on their potent in vitro activity, selected probiotics were formulated into three probiotic mixtures: viable probiotic mixture (LAB), heat-killed probiotic mixture (HK-LAB), and heat-killed LF-expressing probiotic mixture (HK-LAB/LF). To further evaluate the therapeutic potential of these probiotic mixtures in vivo, we established a murine model of UTIs by intraurethral administration of E. coli to 40 female C57BL/6JNarl mice on day 0. Subsequently, mice received oral gavage of placebo, LAB, HK-LAB, or HK- LAB/LF for 21 consecutive days (n = 8 per group). An additional control group (n = 8) received ampicillin treatment for 7 days. To assess protective effects against re-infection or UTI relapse, all mice were challenged with E. coli on day 22 and E. coli plus K. pneumoniae on day 25. Results from the murine UTI model demonstrated that placebo administration did not reduce bacteriuria throughout the experiment. Conversely, supplementation with ampicillin, HK-LAB/LF, HK-LAB, or LAB significantly (p < 0.05) reduced daily bacteriuria by 10³ to 104-fold on days 1, 3, 5, and 14, respectively. Furthermore, all four therapeutic treatments improved the bacteriological cure rate (BCR) with varying levels of efficacy. For the 7-day treatment course, the BCR was 25% (placebo), 62.5% (ampicillin), 37.5% (LAB), 37.5% (HK-LAB), and 62.5% (HK-LAB/LF). For the 21-day treatment course, the BCR was 25% (placebo), 75% (ampicillin), 37.5% (LAB), 37.5% (HK-LAB), and 75% (HK-LAB/LF). Notably, HK-LAB and HK-LAB/LF demonstrated superior therapeutic efficacy compared to viable LAB in treating UTIs. Overall, regarding BCR, the three probiotic mixtures can provide benefits against UTI in mice, but ampicillin therapy remains the most efficient among the four treatments. Furthermore, there was no significant difference between pre- and post-challenge courses for the two instances of re-challenging uropathogens in all mice groups, as bacteriuria levels remained below 103 CFU/mL, implying that adaptive responses of mice may help reduce the risk of recurrent UTIs. In conclusion, our results provide new evidence that oral administration of heat-killed probiotic mixtures can confer significant therapeutic efficacy against UTIs in a murine model. [ABSTRACT FROM AUTHOR]

Background: The burden of Klebsiella drug resistance to antimicrobials is a major public health concern worldwide; particularly the problem is severe in developing countries including Ethiopia. Therefore, the aim of this systematic review and meta-analysis is to establish the pooled estimate of Klebsiella drug resistance; and antimicrobial-specific resistance pattern among Klebsiella clinical isoaltes in Ethiopia. Methods: Articles were searched from PubMed, Google Scholar, and Science direct and grey literature from 2009 to 2019. Four authors have independently extracted data on the prevalence and antimicrobial resistance pattern of the isolates. Statistical analysis was conducted by using Open meta-analyst (version 3.13) and Comprehensive meta-analysis (version 3.3). The main outcome measures were the overall Klebsiella resistance; and drug-specific resistance patterns. A random-effects model was used to determine the pooled resistance prevalence with 95% confidence interval (CI), and significant heterogeneity was considered at p < 0.1; and I2 > 50% using DerSimonian and Laird method. In addition, subgroup analyses were conducted to improve the outcome. Result: We obtained 174 potentially relevant studies through searching electronic databases, and finally, 35 eligible studies were included for meta-analysis. A total of 13,269 study samples participated, from which 1017 Klebsiella species were isolated. The overall Klebsiella resistance in Ethiopia was found to stand at 53.75% (95% CI: 48.35—58.94%). Based on the subgroup analyses; the highest (64.39%); and lowest (46.16%) values were seen in Southern Nations, Nationalities, and Peoples of Ethiopia; and Tigray regions respectively; and the highest Klebsiella resistance was reported to ampicillin (90.56%), followed by amoxicillin (76.01%) and trimethoprim-sulfamethoxazole (66.91%). A relatively low level of resistance rate was observed to amikacin (16.74%) and cefoxitin (29.73%). Conclusion: The pooled Klebsiella resistance was found to be considerably high (53.75%) to most of the essential antibiotics in Ethiopia. Klebsiella was highly resistant to ampicillin and amoxicillin but relatively lower to amikacin. Therefore, appropriate interventional strategies need to be taken to address the emerging resistance of Klebsiella species. [ABSTRACT FROM AUTHOR]

Emergence of antimicrobial resistance in animal husbandry is of utmost concern as it has resulted in therapeutic failure and nowadays it is one of the latest challenges faced by scientific community across the world. Extensive use of antibiotics without performing antibiotic susceptibility testing may lead to development of multidrug resistant (MDR) organisms. This study was undertaken to assess the AMR pattern and their correlation with plasmid profiling in ESBL producing Klebsiella spp. from bovine origin. Total 160 samples (80 mastitic milk and 80 diarrhoeic faeces) were collected from 2 district of Eastern Plain Zone of Uttar Pradesh (India) and 63 (39.37%) isolates were confirmed as Klebsiella spp. by conventional methods (cultural characteristics on selective media & biochemical tests). Antimicrobial susceptibility testing of confirmed isolates revealed 82.0%-94.0% resistance to 3rd & 4th generation cephalosporin, 100% to ampicillin and all isolates were found 100% sensitive to aminoglycosides, chloramphenicol and polypeptides class of antibiotics. Total 49 (77.8%) isolates were confirmed as ESBL producers using DDST and ESBL E-strip test, out of which 45 (71.43%) isolates revealed the presence of bla-CTX-M gp genes by PCR analysis. On plasmid profiling, total 82.82% isolates revealed the presence of plasmid with molecular weight between 2.5 kb to >10 kb and number 1-2. These high molecular weight plasmids are mostly situated on conjugative plasmid, which are horizontally transferred from one species to another in highly populous country like India. [ABSTRACT FROM AUTHOR]

Background Antimicrobial resistance (AMR) data in the pediatric population are limited, particularly in developing countries. This study assessed the AMR profile and key resistance phenotypes and genotypes for Gram-negative bacteria (GNB) isolates collected as part of the Antimicrobial Testing Leadership and Surveillance program from pediatric patients in Latin America, Africa-Middle East, and Asia in 2016–2020 versus 2011–2015. Methods Minimum inhibitory concentrations by broth microdilution methodology were interpreted per the Clinical and Laboratory Standards Institute. European Committee on Antimicrobial Susceptibility Testing breakpoints were used for interpreting colistin activity. β-lactamase genes were screened by polymerase chain reaction and sequencing. Results For Acinetobacter baumannii , low susceptibility (<60.0%) was observed for all antimicrobials, except colistin (≥92.9%), across regions and year periods. Ceftazidime-avibactam, amikacin, colistin, and meropenem were mostly active (78.6%–100.0%) against Enterobacter cloacae , Escherichia coli , and Klebsiella pneumoniae. For Pseudomonas aeruginosa , susceptibility to ceftazidime-avibactam, amikacin, and colistin was ≥85.9%. Among resistance phenotypes, carbapenem-resistant (CR, ≥44.8%) and difficult-to-treat resistant (DTR, ≥37.1%) rates were the highest in A. baumannii. A consistent increase in CR and DTR K. pneumoniae was noted across regions over time. Extended-spectrum β-lactamases (ESBL)-producing K. pneumoniae (32.6%–55.6%) were more frequent than ESBL-producing E. coli (25.3%–37.1%). CTX-M was the dominant ESBL among Enterobacterales. NDM-positive Enterobacterales species and VIM-positive P. aeruginosa were identified across regions. Conclusions This study identified high susceptibility to few agents for key GNB in pediatric patients. Continued surveillance of resistance phenotypes and genotypes at regional levels may help to guide appropriate treatment decisions. [ABSTRACT FROM AUTHOR]

Introduction: Neonatal sepsis is a clinical syndrome characterized by non-specific signs and symptoms caused by various pathogens. The diagnosis is based on a combination of clinical and laboratory findings. Gram-positive and Gram-negative bacteria are the predominant etiologic agents. In our study,we aimed to evaluate the types of microorganisms grown in neonatal blood cultures and antimicrobial susceptibilities of Gram-negative agents. Materials and Methods: We retrospectively analyzed 2566 blood culture results. Samples from blood culture bottles with growth were passaged on blood agar. The growing colonies were identified by MALDİ-TOF MS. Antibiotic susceptibility tests were performed on a fully automated device. The results were evaluated according to EUCAST standards. Results: Growth was detected in 12.1% of the samples. 59.5% of the patients with growth were male. 66% of the patients were at term and 53.7% had early-onset sepsis. 74.6% of the cases were cesarean section and 59.5% were above 2500 grams. Coagulase-negative staphylococci (CNS) were the most common organisms grown in early and late-onset sepsis. 73.9% CNS, 9% Gram-negative enteric and nonfermentary bacilli, 2.9% Gram-positive bacilli and 0.1% fungi were grown. 40% of S.aureus were methicillin resistant. The most antimicrobial-resistant Gram-negative agent was Klebsiella spp. Klebsiella spp. isolates were resistant to amikacin 9%, ampicillin 100%, cefepime 72.7%, ceftazidime 81.8%, gentamicin 81.8%, meropenem 9.1%. Extended spectrum beta lactamase was positive in 90.9%. Acinetobacter spp. isolates were resistant to amikacin 42.8%, ampicillin 42.8%, gentamicin 42.8%, meropenem 42.8%. Conclusion: Microorganism species and antibiotic susceptibilities in intensive care units vary over time and between clinics. Broad-spectrum antimicrobials started early with suspicion of sepsis without culture confirmation can be replaced with agentspecific narrow-spectrum antimicrobials when growth is detected in culture,monotherapy can be switched or treatment can be terminated early. This may contribute to the prevention of resistance development. [ABSTRACT FROM AUTHOR]

Background. Various antibiotics are prescribed empirically by physicians to cope with infections in renal disease patients. A urinary tract infection (UTI) is often caused by biofilm-forming multidrug-resistant (MDR) uropathogens. This study aimed to analyze the antibiogram of UTI strains from renal disease patients and the biofilm-forming ability of those strains. Methods. 102 patients clinically diagnosed with a UTI and renal disease were recruited into the study from August 2017 to January 2018. Clean-catch midstream urine samples were processed for the isolation and identification of the bacteria following standard methodologies. The antibiogram of the isolates (n = 106) was produced by the Kirby–Bauer disc diffusion method. Detection of biofilm formation was performed in tissue culture plates. Results. The incidence of a UTI in renal disease was 19.1%. Most patients were diagnosed with chronic kidney disease (18.63%), nephrotic syndrome (16.67%), and nephrolithiasis (14.71%). The commonest uropathogens were Escherichia coli (52.8%), Klebsiella pneumoniae (16%), and Enterococcus spp. (15.0%). Ceftriaxone was the most common antibiotic prescribed empirically (37%), whereas nitrofurantoin was the most prescribed antibiotic as adjusted therapy (36.1%). Among the first- and second-line antibiotics, most Gram-negative bacteria were sensitive to amikacin (70.7%), meropenem (70.7%), cefoperazone-sulbactam (70.0%), piperacillin-tazobactam (67.2%), gentamicin (66.7%), and nitrofurantoin (66.7%). Most Gram-positive bacteria were sensitive to doxycycline (90.0%), nitrofurantoin (72.2%), gentamicin (66.7%), and tetracycline (62.5%). All MDR Gram-negative uropathogens were susceptible to colistin sulfate and polymyxin B. Among the 106 isolates, 74.5% produced biofilms and 70.8% were MDR. In 67.0% of cases, including both MDR and biofilm-producing bacteria, the empirical therapy needed adjustment. Conclusions. Aminoglycoside, carbapenem, beta-lactam combination agents, and nitrofuran group of antibiotics may be the optimal first-line empirical therapies for uropathogens in hospitalized renal disease patients. Regular surveillance of resistance patterns and the study of biofilm formation in uropathogens must be performed to ensure effective management of the patients. [ABSTRACT FROM AUTHOR]

Background and Aim: Antimicrobial resistance (AMR) is a serious global threat and the World Health Organization (WHO) declared AMR is one of 10 public health threatsfacing humanity. An increase in Carbapenem resistance is the major problem that hinders patient treatment. Various genes are responsible for carbapenem resistance but the gene bla-NDM can inactivate various carbapenem antibiotics namely meropenem and imipenem etc. Therefore, this study aimed to observe the prevalence of the bla-NDM gene in the carbapenem-resistant Klebsiella spp. isolates. Materials and Methods: The isolates of multidrug-resistant Klebsiella spp. were collected from the central diagnostic laboratory, Sree Balaji Medical College and Hospital, India after obtaining ethical clearance. The isolates were screened for carbapenem resistance using the Rapidec Carba NP method. The presence of bla-NDM was confirmed using the conventional PCR technique. Results & Conclusion: Most of the isolates showed resistance to ampicillin, gentamycin, cefazolin, imipenem, and meropenem. 45% of the isolates of K. pneumonia showed resistance to the carbapenem group of antibiotics and 20% of the K. oxytoca showed carbapenem resistance. Among the carbapenem-resistant 23.75% of K. pneumonia showed the presence of the bla-NDM gene and 6.6% of K. oxytoca showed the presence of the bla-NDM gene. Continuous increase in carbapenem drug-resistant organisms is worrisome and the judicious usage of antibiotics should be practiced. [ABSTRACT FROM AUTHOR]

Introduction: Hemodialysis patients are at risk of infections. This study examines the spectrum of infections and antibiotic resistance patterns. Methods: We retrospectively reviewed the records of 586 hemodialysis patients from May 2018 to April 2020 in a tertiary care hospital in North India. Results: The study identified 99 episodes of confirmed infections. Urinary tract infections were the most common type of infections (55.5%), followed by catheter-related bloodstream infections (CRBSI) (definitive 21.2%). Other infections were pneumonia (8.1%), tuberculosis (6.1%), skin and soft tissue infection (4.0%), dengue fever (3.03%), and empyema thoracis (1.0%). Overall, Escherichia coli (33.3%) was the most common organism isolated. The most frequent uropathogens recovered were Escherichia coli (54%). In confirmed CRBSI, P. aeruginosa (23.8%) and MSSA (23.8%) were the most common pathogen isolated. K. pneumonia (37.5%) was the most common pathogen in pneumonia. Uropathogens showed the highest resistance to fluoroquinolones (93.3%-100%). Pathogens isolated in CRBSI showed maximum resistance to ciprofloxacin (100%). In pneumonia, the highest resistance was seen to third-generation cephalosporins (75%-100%). Conclusion: Though the bacterial spectrum remains the same over time, antibiotic resistance is changing in uropathogens. There is a trend of predominance of Gram-negative bacterial infections in CRBSI. Tuberculosis incidence rate was much higher than the general population. There is a need for nationwide and worldwide continuous surveillance. [ABSTRACT FROM AUTHOR]

Antimicrobial resistance (AMR) is a global public health threat. Quality data on AMR are needed to tackle the rise of multidrug-resistant clones. These data are rare in low-income countries, especially in sub-Saharan Africa. In this study, we investigated the rise of extended-spectrum β-lactamase–producing (ESBL) Enterobacteriaceae in Bangui, Central African Republic. We collected 278 fecal samples from 0–5-year-old children admitted to the Pediatric University Hospital Complex in Bangui from July to September 2021. Enterobacteriaceae were isolated and identified, and their susceptibility to 19 antibiotics was tested. We recovered one and two Enterobacteriaceae species from 208 and 29 samples, respectively. One clone of each species from each sample was further characterized, for a total of 266 isolates. Escherichia coli predominated, followed by Klebsiella. AMR was frequent, with 98.5% (262/266) of the isolates resistant to at least one antibiotic. Additionally, 89.5% (238/266) of the isolates were multidrug resistant, with resistance being frequent against all tested antibiotics except carbapenems and tigecycline, for which no resistance was found. Importantly, 71.2% (198/278) of the children carried at least one ESBL species, and 85.3% (227/266) of the isolates displayed this phenotype. This study confirms the rise of ESBL Enterobacteriaceae in Bangui and stresses the need for action to preserve the efficacy of antibiotics, as crucial for the treatment of bacterial infections. [ABSTRACT FROM AUTHOR]

Background: Antibiotic resistance has become an enduring threat to human health. This has prompted extensive research to identify the determinants responsible in a bid to fight the spread of resistance and also develop new antibiotics. However, routine procedures focus on identifying genetic determinants of resistance only on phenotypically resistant isolates. We aimed to characterise plasmid mediated resistance determinants in key Enterobacteriaceae isolates with differential phenotypic susceptibility profiles and evaluated the contribution of resistance genes on phenotypic expression of susceptibility. Methods: The study was carried out on 200 Enterobacteriaceae isolates belonging to the genera E. coli, Salmonella, and Klebsiella; 100 resistant and 100 susceptible to quinolones, aminoglycosides, and ESBL-producing as determined by disk diffusion. Reduced susceptibility in susceptible isolates was determined as an increased MIC by broth microdilution. Plasmid-borne resistance genes were sought in all isolates by endpoint PCR. We performed correlations tests to determine the relationship between the occurrence of resistance genes and increased MIC in susceptible isolates. We then used the notion of penetrance to show adequacy between resistance gene carriage and phenotypic resistance as well as diagnostic odds ratio to evaluate how predictable phenotypic susceptibility profile could determine the presence of resistant genes in the isolates. Results: Reduced susceptibility was detected in 30% (9/30) ESBL negative, 50% (20/40) quinolone-susceptible and 53.33% (16/30) aminoglycoside-susceptible isolates. Plasmid-borne resistance genes were detected in 50% (15/30) of ESBL negative, 65% (26/40) quinolone susceptible and 66.67% (20/30) aminoglycoside susceptible isolates. Reduced susceptibility increased the risk of susceptible isolates carrying resistance genes (ORs 4.125, 8.36, and 8.89 respectively for ESBL, quinolone, and aminoglycoside resistance genes). Resistance gene carriage correlated significantly to reduced susceptibility for quinolone and aminoglycoside resistance genes (0.002 and 0.015 at CI95). Gene carriage correlated with phenotypic resistance at an estimated 64.28% for ESBL, 56.90% for quinolone, and 58.33% for aminoglycoside resistance genes. Conclusions: A high carriage of plasmid-mediated genes for ESBL, quinolone, and aminoglycoside resistance was found among the Enterobacteriaceae tested. However, gene carriage was not always correlated with phenotypic expression. This allows us to suggest that assessing genetic determinants of resistance should not be based on AST profile only. Further studies, including assessing the role of chromosomal determinants will shed light on other factors that undermine antimicrobial susceptibility locally. [ABSTRACT FROM AUTHOR]

Objectives: Ventilator-associated pneumonia (VAP) is a widely recognized and potentially fatal healthcarerelated infection that occurs in all high-dependency units. Mechanically ventilated patients are at an elevated risk of developing VAP, which has a high death and morbidity rate. The prevalence of VAP varies greatly depending on the location and diagnostic approach. Radiological and clinical markers impact VAP diagnosis accuracy. Reliable sampling and confirmation of microbes are highly recommended. The purpose of this study was to document the incidence, patient distribution, bacteriological profile, and antibiotic susceptibility pattern of VAP patients. Material and Methods: A prospective observational study was done between January 2016 and December 2019. Critically, ill patients on mechanical ventilation for more than 48 hours were included in the study. Based on the initial baseline, positive end-expiratory pressure, and fraction of inspired oxygenwere followed by three-tier VAP criteria as per NSHN guidelines. Results: Out of 1220 VAP-suspected patients (mechanically ventilated), 49 patients developed hospital-acquired VAP. The incidence of VAP significantly reduced from 10.7 to 1.4 VAP/1000 ventilator days with continuous intervention and auditing over some time. Elderly males aged 51–66 years were found to be in higher risk groups. Klebsiella pneumoniae and Pseudomonas aeruginosa were found to be the most common pathogen. The majority of Enterobacterales (79%) were found to be resistant to third-generation cephalosporin, 69% were resistant toward fluoroquinolone and cotrimoxazole, followed by 55% resistance to beta-lactam and beta-lactamase inhibitor combination. Conclusion: Targeted strategies with implementable policies, such as the care bundle approach, will reduce the in-patient days. It might improve patient outcomes and reduce the incidence of VAP. [ABSTRACT FROM AUTHOR]

Introduction: Antimicrobial resistance (AMR) is a major public health concern. The spread of AMR-encoding genes between enterobacteria, especially in Klebsiella pneumoniae strains, lead to failure in the treatment of most individuals. The aim of this study was to characterize multidrug resistant (MDR) clinical K. pneumoniae isolates that produce extended-spectrum ß-lactamases (ESBLs) from Algeria. Methodology: The isolates were identified using biochemical tests, and the identification was confirmed by mass spectrometry using VITEK® MS (BioMerieux, Marcy l'Etoile, France). Antibiotic susceptibility testing was assessed by the disk diffusion method. Molecular characterization was performed by whole genome sequencing (WGS) using Illumina technology. Sequenced raw reads were processed using bioinformatics parameters: FastQC, ARIBA, and Shovill-Spades. Multilocus sequence typing (MLST) was used to estimate the evolutionary relationship between isolate strains. Results: Molecular analysis resulted in the first detection of blaNDM-5 encoding K. pneumoniae in Algeria. Other resistance genes were blaTEM, blaSHV, blaCTX-M, aac(6')-Ib-cr, qnrB1, qnrB4, qnrB19, qnrS1, gyrA and parC variants. Conclusions: Our data demonstrated a very high level of resistance in clinical K. pneumoniae strains which were resistant to most common antibiotic families. This was the first detection of K. pneumoniae with the blaNDM-5 gene in Algeria. Surveillance of antibiotic use and measures for control should be implemented to reduce occurrence of AMR in clinical bacteria. [ABSTRACT FROM AUTHOR]

Background: One of the most typical illnesses seen in clinical practise is urinary tract infection (UTI). 50% to 60% of adult women may encounter a urinary tract infection at some point in their lives, making it one of the most prevalent bacterial illnesses in women. Due to their anatomical characteristics, such as a narrow urethra, as well as other variables like pregnancy, the use of diaphragms, and sexual activity, women are more likely to acquire UTI. Objectives: 1. To isolate and identify the uropathogens from the urine samples. 2. To detect the antimicrobial resistance of uropathogens to fluoroquinolones. Material & Methods: Study Design: Descriptive Cross-sectional study. Study area: Department of Obstetrics & Gynecology, Murshidabad Medical college and Hospital, Berhampore, West Bengal. Study Period: Jan 2022 - Dec. 2022. Study population: Urine culture sensitivity reports were analyzed of patients who were suspected to be having urinary tract infection. Sample size: Study consisted a total of 300 subjects. Sampling Technique: Simple Random technique. Results: The resistant pattern of E.coli and Klebsiella to the 4 fluroquinolones, highest resistance is seen to ciprofloxacin followed by norfloxacin. In this study the most sensitive drug was Amikacin, followed by Pippericillin/Tazobactum and imipenem. In this study the drug with maximum resistance was cotrimoxazole. Amoxycillin and quinolones followed the list. Conclusion: We need to take a number of steps to address the significant worldwide opposition issue we are facing. These include (i) using fewer antibiotics to lessen the pressure for resistance to develop. (ii) increasing our understanding of the mechanisms by which bacteria acquire resistance and how they reduce the ensuing fitness costs. [ABSTRACT FROM AUTHOR]

Background Patients with bacteremia due to carbapenem-resistant Enterobacterales (CRE) experience delays until appropriate therapy and high mortality rates. Rapid molecular diagnostics for carbapenemases and new β-lactam/β-lactamase inhibitors may improve outcomes. Methods We conducted an observational study of patients with CRE bacteremia from 2016 to 2018 at 8 New York and New Jersey medical centers and assessed center-specific clinical microbiology practices. We compared time to receipt of active antimicrobial therapy and mortality between patients whose positive blood cultures underwent rapid molecular testing for the Klebsiella pneumoniae carbapenemase (KPC) gene (bla KPC) and patients whose cultures did not undergo this test. CRE isolates underwent antimicrobial susceptibility testing by broth microdilution and carbapenemase profiling by whole-genome sequencing. We also assessed outcomes when ceftazidime-avibactam and polymyxins were used as targeted therapies. Results Of 137 patients with CRE bacteremia, 89 (65%) had a KPC-producing organism. Patients whose blood cultures underwent bla KPC PCR testing (n = 51) had shorter time until receipt of active therapy (median: 24 vs 50 hours; P =.009) compared with other patients (n = 86) and decreased 14-day (16% vs 37%; P =.007) and 30-day (24% vs 47%; P =.007) mortality. bla KPC PCR testing was associated with decreased 30-day mortality (adjusted odds ratio:.37; 95% CI:.16–.84) in an adjusted model. The 30-day mortality rate was 10% with ceftazidime-avibactam monotherapy and 31% with polymyxin monotherapy (P =.08). Conclusions In a KPC-endemic area, bla KPC PCR testing of positive blood cultures was associated with decreased time until appropriate therapy and decreased mortality for CRE bacteremia, and ceftazidime-avibactam is a reasonable first-line therapy for these infections. [ABSTRACT FROM AUTHOR]

Wastewater-based surveillance enabled the first detection of the mobile colistin resistance gene mcr-10 in Italy. This plasmid-borne resistance gene was found in strains of Klebsiella quasipneumoniae isolated from samples of human raw sewage collected over several months. Although the isolates were phenotypically susceptible to colistin, the emergence of mcr-10 is concerning due to the highly variable expression of the gene and the potential for horizontal transfer to other species. In addition, the strains also carried an extended-spectrum β-lactamase gene and were phenotypically resistant to several beta-lactams. This study highlights the value of wastewater-based surveillance as an effective tool to monitor the emergence of antimicrobial resistance in strains circulating in the community and the environment. [ABSTRACT FROM AUTHOR]

Simple Summary: The increasing incidence of multidrug-resistant microbes is a major problem in human and veterinary medicine. In our study we assessed the prevalence and antibiotic resistance of Klebsiella spp. strains isolated from turkey broilers and breeders. The obtained results show that isolates have become more susceptible to most of the popular antimicrobials. One of the important problems in poultry production is bacterial infections and increasing resistance to antibiotics. The increasing incidence of multidrug-resistant bacteria is a major challenge for physicians and veterinarians and considerably limits treatment options. This study was undertaken in order to assess the prevalence and antibiotic resistance of Klebsiella spp. strains isolated from turkeys sampled from 2019 to 2022 in Poland. The material for study consisted of clinical samples taken during routine monitoring and microbiological identification testing at commercial poultry farms. From all 507 isolates of Klebsiella, 95% were identified by MALDI-TOF (Matrix-Assisted Laser Desorption - Ionisation-Time of Flight) as Klebsiella pneumonia, 2% were Klebsiella oxytoca, 2% Klebsiella variicola, or unidentified (1%). All isolated Klebsiella strains were tested for antimicrobial susceptibility by disk diffusion. The results of our study indicated that colistin, neomycin, florfenicol and amoxicillin/clavulanic acid were the most effective against the Klebsiella spp. isolated from turkeys. In addition, the results show a decrease in the number of multi-resistant Klebsiella spp. strains between 2019 and 2021. [ABSTRACT FROM AUTHOR]

Objectives: Protegrins are a family of natural peptides from the innate immune system of vertebrates, with broad-spectrum antimicrobial activity. However, the toxicity and haemolysis of protegrin-1 (PG-1) at low concentrations renders it useless for therapeutic application. We rationally designed PLP-3, a novel synthetic PG-1-like peptide, comprising key activity features of protegrins in a constrained bicyclic structure. Our main objective was to investigate PLP-3's activity against MDR strains of Acinetobacter baumannii, Pseudomonas aeruginosa and Klebsiella pneumoniae and to analyse its haemolysis and cytotoxicity.Methods: Peptide synthesis was performed via solid phase and intramolecular ligation in solution, and the correct folding of the peptide was verified by circular dichroism. Antimicrobial activity was performed through broth microdilution. The test panel contained 45 bacterial strains belonging to A. baumannii, P. aeruginosa and K. pneumoniae (15 strains per species) comprising colistin-resistant and MDR strains. Cytotoxicity was assessed by XTT cell viability assays using HeLa and A549 cells and haemolysis of human erythrocytes.Results: PLP-3 was successfully synthesized, and its antiparallel β-sheet conformation was confirmed. Antimicrobial activity screening showed MIC90 values of 2 mg/L for A. baumannii, 16 mg/L for K. pneumoniae and 8 mg/L for P. aeruginosa. The haemolysis IC50 value was 48.53 mg/L. Cytotoxicity against human HeLa and A549 cells showed values of ca. 200 mg/L in both cell lines resulting in a 100-fold selectivity window for bacterial over human cells.Conclusions: PLP-3 has potent antimicrobial activity, especially against A. baumannii, while maintaining low haemolysis and toxicity against human cell lines at antimicrobial concentrations. These characteristics make PLP-3 a promising peptide with an interesting therapeutic window. [ABSTRACT FROM AUTHOR]

Objective: Osteoradionecrosis of the jaw (ORNJ) is one of the most common and serious complications after radiotherapy of head and neck malignancies due to the high incidence of nasopharyngeal cancer in Southern China. Clinicians lack understanding and consensus on anti‐infective treatment in ORNJ lesions. This research aims to provide evidence for rational use of antibiotics by reviewing the bacterial spectrums and antimicrobial susceptibility test of ORNJ patients. Methods: We collected patient who was diagnosed with ORNJ from November 2012 to June 2019 in our hospital. Exudate or bone unexposed wound surface sampling, agar plates culturing, and susceptibility testing were analyzed. Descriptive statistics were used for data presentation. Results: A total of 219 samples were collected in our retrospective study. The most common cultured bacteria were Klebsiella pneumoniae (15.10%), Pseudomonas aeruginosa (13.54%), and Staphylococcus aureus (10.94%). Methicillin‐resistant Staphylococcus aureus (MRSA) accounted for 5.21% in the whole positive samples. Ticarcillin, Ofloxacin, Vancomycin, Tigecycline, and Meropenem were more susceptible than other antibiotics to treat uncontrollable infection. Conclusions: Our research provided objective evidence for understanding the types of local bacterial flora and drug susceptibility in ORNJ lesions and gave a guiding reference for empirical antibiotics medication. [ABSTRACT FROM AUTHOR]

Background. Multidrug-resistant (MDR) clones of Klebsiella pneumoniae (Kpn) have been increasingly documented in community-acquired and nosocomial infections all around the globe. Extended-spectrum β-lactamases (ESBLs) are a rapidly evolving group of β-lactamase enzymes derived from SHV genes by mutations. This research work aimed to investigate and analyze the widespread prevalence of Kpn antibiotic resistance in different areas of the southern part of Bangladesh. Methods. This particular study was executed and implemented by using 501 clinical samples or isolates from two different hospitals in Chattogram. The disk diffusion method was used to detect Kpn's sensitivity to 16 antibiotics in a drug susceptibility test. By using the PCR technique, the widespread prevalence of antibiotic-resistant gene blaSHV-11 was studied. Sequencing along with phylogenetic analysis was utilized to verify isolates with the blaSHV-11 gene. Results. Almost all of the Kpn isolates were spotted to be antibiotic-resistant. These Kpn isolates were resistant to β-lactams, aminoglycosides, and quinolones at high levels. The spatial analysis displayed that infections involving Kpn were more common in the urban areas (70%) than in the rural areas (30%). Neonates had substantially higher levels (p < 0.001) of resistance to multidrug than other age groups. Cefepime was identified as the most frequent antibiotic-resistant to all age groups (56.68%). The highest numbers of resistant isolates (36.92%) were found in urine samples. The ESBL gene blaSHV-11 was found in 38% isolates. Conclusion. The significant frequency of MDR Kpn harboring β-lactamases and AMR genes strongly suggests the requirement to develop effective antimicrobial resistance control and prevention measures in Bangladesh. [ABSTRACT FROM AUTHOR]

Background. Antibiotic resistance is a global public health problem, leading to high mortality and treatment costs. To achieve more efficient treatment protocols and better patient recovery, the distribution and drug resistance of pathogens in our hospital were investigated, allowing significant clinical guidance for the use of antimicrobials. Methods. In this retrospective study (2017–2019), 3482 positive samples were isolated from 43,981 specimens in 2017; 3750 positive specimens were isolated from 42,923 specimens in 2018; and 3839 positive pathogens were isolated from 46,341 specimens in 2019. These samples were from various parts of the patients, including the respiratory tract, urine, blood, wound secretions, bile, and puncture fluids. The distribution and antibiotic resistance of these isolated pathogens from the whole hospital were analyzed. Results. The results from pathogen isolation showed that Escherichia coli (12.8%), Staphylococcus aureus (11%), Klebsiella pneumoniae (10.8%), Pseudomonas aeruginosa (10.7%), and Acinetobacter baumannii (6.4%) represented the five main pathogenic bacteria in our hospital. Pseudomonas aeruginosa (16.2% and 17.5%) occupied the largest proportion in the central intensive care unit (central ICU) and respiratory intensive care unit (RICU), while Acinetobacter baumannii (15.4%) was the most common pathogen in the emergency intensive care unit (EICU). The resistance rate of Escherichia coli to trimethoprim and minocycline was 100%, and the sensitivity rate to ertapenem, furantoin, and amikacin was above 90%. The resistance rate of Pseudomonas aeruginosa to all antibiotics, such as piperacillin and ciprofloxacin, was under 40%. The sensitivity rate of Acinetobacter baumannii to tigecycline and minocycline was less than 30%, and the resistance rate to many drugs such as piperacillin, ceftazidime, and imipenem was above 60%. Extended-spectrum β-lactamases (ESBLs)-producing Klebsiella pneumoniae (ESBLs-KPN) and carbapenem-resistant Klebsiella pneumoniae (CRE-KPN), ESBLs-producing Escherichia coli (ESBLs-ECO) and carbapenem-resistant Escherichia coli (CRE-ECO), multidrug-resistant Acinetobacter baumannii (MDR-AB), multidrug-resistant Pseudomonas aeruginosa (MDR-PAE), and methicillin-resistant Staphylococcus aureus (MRSA) are all important multidrug-resistant bacteria found in our hospital. The resistance rate of ESBLs-producing Enterobacteriaceae to ceftriaxone and amcarcillin-sulbactam was above 95%. CRE Enterobacteriaceae bacteria showed the highest resistance to amcarcillin-sulbactam (97.1%), and the resistance rates of MDR-AB to cefotaxime, cefepime, and aztreonam were 100%. The resistance rates of MDR-PAE to ceftazidime, imipenem, and levofloxacin were 100%, and the sensitivity rate to polymyxin B was above 98%. The resistance rate of MRSA to oxacillin was 100%, and the sensitivity rate to linezolid and vancomycin was 100%. Conclusion. The distribution of pathogenic bacteria in different hospital departments and sample sources was markedly different. Therefore, targeted prevention and control of key pathogenic bacteria in different hospital departments is necessary, and understanding both drug resistance and multiple drug resistance of the main pathogenic bacteria may provide guidance for the rational use of antibiotics in the clinic. [ABSTRACT FROM AUTHOR]

Background: Infections caused by Klebsiella oxytoca are the second most common cause of Klebsiella infections in humans. Most studies have focused on K. oxytoca outbreaks and few have examined the broader clinical context of K. oxytoca.Methods: Here, we collected all clinical isolates identified as K. oxytoca in a hospital microbiological diagnostic lab across a 15-month period (n = 239). Whole genome sequencing was performed on a subset of 92 isolates (all invasive, third-generation cephalosporin resistant (3GCR) and non-urinary isolates collected > 48 h after admission), including long-read sequencing on a further six isolates with extended-spectrum beta-lactamase or carbapenemase genes.Results: The majority of isolates were sensitive to antimicrobials, however 22 isolates were 3GCR, of which five were also carbapenem resistant. Genomic analyses showed those identified as K. oxytoca by the clinical laboratory actually encompassed four distinct species (K. oxytoca, Klebsiella michiganensis, Klebsiella grimontii and Klebsiella pasteurii), referred to as the K. oxytoca species complex (KoSC). There was significant diversity within the population, with only 10/67 multi-locus sequence types (STs) represented by more than one isolate. Strain transmission was rare, with only one likely event identified. Six isolates had extended spectrum beta-lactamase (blaSHV-12 and/or blaCTX-M-9) or carbapenemase (blaIMP-4) genes. One pair of K. michiganensis and K. pasteurii genomes carried identical blaIMP-4 IncL/M plasmids, indicative of plasmid transmission.Conclusion: Whilst antimicrobial resistance was rare, the resistance plasmids were similar to those found in other Enterobacterales, demonstrating that KoSC has access to the same plasmid reservoir and thus there is potential for multi-drug resistance. Further genomic studies are required to improve our understanding of the KoSC population and facilitate investigation into the attributes of successful nosocomial isolates. [ABSTRACT FROM AUTHOR]

Objectives: To investigate the in vitro activity of fosfomycin, colistin and combinations thereof against planktonic and biofilm cultures of Gram-negative pathogens, mostly showing MDR phenotypes, at concentrations achievable via inhalation of aerosolized drugs.Methods: Activity against planktonic cultures was tested by the chequerboard assay with 130 strains, including 52 Pseudomonas aeruginosa, 47 Klebsiella pneumoniae, 19 Escherichia coli, 7 Stenotrophomonas maltophilia and 5 Acinetobacter baumannii. Activity against biofilm cultures was tested by biofilm chequerboard and quantitative antibiofilm assays with a subset of 20 strains. In addition, 10 of these strains were tested in mutant prevention concentration (MPC) assays.Results: Against planktonic cultures, synergism between fosfomycin and colistin was detected with a minority (10%) of strains (eight K. pneumoniae and five P. aeruginosa), while antagonism was never observed. Synergism between fosfomycin and colistin against biofilms was observed with the majority of tested strains (16/20 in biofilm chequerboard assays, and 18/20 in the quantitative antibiofilm assays), including representatives of each species and regardless of their resistance genotype or phenotype. Furthermore, combination of fosfomycin and colistin was found to significantly reduce the MPC of individual drugs.Conclusions: Fosfomycin and colistin in combination, at concentrations achievable via inhalation of nebulized drugs, showed notable synergy against MDR Gram-negative pathogens grown in biofilm, and were able to reduce the emergence of fosfomycin- and colistin-resistant subpopulations. [ABSTRACT FROM AUTHOR]

Aims: Klebsiella pneumoniae is an important cause of nosocomial infections. The present study sought to detect resistance status and the frequency of multidrug-resistant (MDR), extensively drug-resistant (XDR), and pandrug-resistant (PDR) K. pneumoniae strains isolated from hospitalized patients. Materials and Methods: Confirmation of K. pneumoniae isolates was performed by polymerase chain reaction (PCR) for rpoB fragment. Drug susceptibility was done by disk diffusion method based on the Clinical and Laboratory Standards Institute. According to the susceptibility pattern, the strains were categorized as MDR, XDR, and PDR. Results: On the basis of PCR results, rpoB gene was identified in all 100 K. pneumoniae isolates. Most K. pneumoniae strains showed a high percentage of resistance against ampicillin-sulbactam (93%). On the other hand, tigecycline and fosfomycin were active against 100% and 90% isolates, respectively. The multiple resistance analysis of the strains showed that 58% and 13% of isolates were identified as MDR and XDR, respectively. Overall, no PDR isolate was detected in any tested strains. Conclusion: Our results demonstrated that the vast majority of K. pneumoniae strains indicated the MDR phenotype including a high resistance rate to common antibiotics. Therefore, it is suggested to implement antimicrobial susceptibility testing before prescribing, to assist in selecting the most effective agents within the antimicrobial categories for the treatment of infections with multiple antibiotic-resistant K. pneumoniae strains in hospitalized patients. [ABSTRACT FROM AUTHOR]

Background: The high prevalence of carbapenem-resistant Klebsiella imposes optimizing antibiotic consumption. We aimed to evaluate the impact of antibiotic stewardship program on carbapenem consumption and the Klebsiella resistance. Method: We retrospectively evaluated critically ill patients with isolated Klebsiella species from Elaraby hospital, Egypt during the period from April 2017 to January 2019. We collected data related to carbapenems consumption and Klebsiella clinical isolates with their antimicrobial susceptibility. Based on susceptibility, Klebsiella isolates were classified into sensitive, extended spectrum beta-lactamase (ESBL) producer, and carbapenem-resistant Klebsiella (CRK), respectively. Our primary outcome was the change in carbapenems consumption after implementing the program, while the secondary outcomes were the changes in the incidence of CRK. Results: The study included 205 patients with isolated Klebsiella species during the study period. The antibiotic stewardship program started in March 2018. Out of the 205 patients, 61 patients (29.8%) represented the pre-intervention sample, and 144 patients (70.2%) represented the post-intervention sample. Applying the antibiotic stewardship program was associated with a significant decrease in the carbapenems consumption from 38.9 to 26.6 defined daily dose/1000 patient-days (p = 0.02). The incidence of CRK was decreased from 85.25% of total Klebsiella isolates to 48.6% (p < 0.001). Klebsiella species were more likely to be in a lower category of resistance after applying the program with an odds ratio of 6.3 (2.88–13.73) using ordinal logistic regression. Conclusion: Applying the antibiotic stewardship program could reduce the unnecessary carbapenems use in the ICU with a subsequent decrease in the emergence of the Klebsiella- resistant strains. [ABSTRACT FROM AUTHOR]

Objectives: To characterize a clinical Klebsiella pneumoniae isolate from China co-harbouring tet(X4), blaOXA-181 and the aerobactin operon on an IncFIBk-FII-X3-ColKP3 hybrid plasmid.Methods: A tigecycline-resistant strain was recovered from the intestinal sample of a patient. It was subjected to antimicrobial susceptibility testing, conjugation assay, virulence testing, WGS, bioinformatics analysis, plasmid stability testing and fitness cost testing.Results: The strain K. pneumoniae T877 was resistant to tigecycline, intermediate to piperacillin/tazobactam and ertapenem, and positive for tet(X), blaOXA-181 and the virulence-associated operon iutAiucABCD, which were located on the same plasmid, named pKPT877-hybrid. It was 99.96% identical to the IncFIBk-FII plasmid pSCH6109-Vir (accession number CP050860) from K. pneumoniae strain SCH6109 at 96% coverage with the absence of a 50 kb region on pKPT877-hybrid; this region was highly homologous to the 51 kb IncX3-ColKP3-type, blaOXA-181-carrying plasmid pOXA181-191773 (accession number CP080367). Plasmid pKPT877-hybrid was conjugatively transferable to the ST11 K. pneumoniae strains FJ8 and KP04. pKPT877-hybrid did not have a significant impact on the fitness cost and could be maintained stably in T877.Conclusions: We report for the first time (to the best of our knowledge) the co-transfer of last-line antibiotic resistance determinants [tet(X4) and blaOXA-181] and the aerobactin operon (iutAiucABCD) by a mobile IncFIBk-FII-X3-ColKP3 hybrid plasmid, which can be stably maintained in K. pneumoniae strains, even in the absence of antibiotic selective pressure. Once the plasmid transfers to a K. pneumoniae with porin deficiency, the strain might have high levels of resistance to carbapenems and tigecycline, which are the last line of defence against infections. Heightened and continuous efforts are needed to control its dissemination. [ABSTRACT FROM AUTHOR]

This study characterized quinolone (Q) resistance determinants in a series of Klebsiella pneumoniae (n = 26) and Escherichia coli (n = 19) isolates of human and animal origin. The presence of plasmid-mediated quinolone resistance (PMQR) and carabpenemase genes was examined by PCR. The quinolone resistance-determining regions (QRDRs) of gyrA and parC genes were sequenced. Thirty-three isolates had ciprofloxacin MIC≥8 mg/l. About 34.6% and 10.5% of K. pneumoniae and E. coli isolates were ESBL producers respectively. The PMQR genes were detected in 77% (n = 35) of isolates. The oqxAB was the most prevalent PMQR gene being identified in all K. pneumoniae isolates, followed by aac(6ʹ)-Ib-cr (34.6%), qnrS (23%) and qnrB (7.7%). The most frequently detected gene among E. coli isolates was qnrS (36.8%) followed by aac(6′)-Ib-cr (10.5%) and qepA (5.2%). All Q resistant isolates harbored amino acid substitutions in both GyrA and ParC QRDRs. High prevalence of PMQR genes among food-producing animal isolates is an issue of great concern. [ABSTRACT FROM AUTHOR]

Background: Increased use of colistin in healthcare necessitates studies on the trend of colistin resistance and the underlying mechanisms.Objectives: To understand the susceptibility trend and molecular mechanisms of colistin resistance in neonatal isolates over a 12 year period.Methods: Colistin susceptibility, mRNA expression, whole genome sequence and mutational analysis was performed. Phylogenomic comparison with a global collection of colistin-resistant Klebsiella pneumoniae strains (n = 70) was done.Results: Of 319 Enterobacterales (K. pneumoniae and Escherichia coli) studied, colistin resistance was found in 9 K. pneumoniae (2.8%). The transmissible colistin resistance gene, mcr, was absent. Colistin-resistant K. pneumoniae belonged to diverse sequence types (ST14/37/101/147/716) and exhibited multiple mechanisms of colistin resistance including overexpression of the two-component systems (TCS) (phoP/Q, pmrA/B), and AcrAB-TolC pump and its regulators. Mutations in TCS, mgrB, pumps, repressors, and lipopolysaccharide-modifying genes were detected. Phylogenomic comparison revealed that this global collection of colistin-resistant K. pneumoniae was diverse, with the presence of epidemic and international clones. Mutations in mgrB and TCS noted in global strains were comparable to the study strains. Co-occurrence of carbapenem resistance (n = 61, 87%) was observed in global strains. Co-existence of dual carbapenemases (blaNDM-5 with blaOXA-48/181) in multiple lineages within different replicons was found in neonatal colistin-resistant study isolates only.Conclusions: Colistin resistance both in study and global strains is multifaceted and attributed to mutations in chromosomal genes leading to lipopolysaccharide modification or efflux of colistin through pumps. With no transmissible mcr, prevalence of colistin-resistant strains was low in this unit. Colistin-resistant strains with dual carbapenemases causing sepsis are alarming as they are practically untreatable. [ABSTRACT FROM AUTHOR]

Mobile phones have become an indispensable part of human lives for communication, education, and entertainment activities. This study aims to evaluate the diversity pattern of bacterial contaminants on mobiles and to check antibiotic resistance profiles in 105 samples. The study revealed a contamination of 51% in men and 49% in women, the highest in the 21- to 30-year age group, evidencing the extreme use of mobiles by teenagers. The study observed Gram-negative bacteria (63%) versus Gram-positive bacteria (37%). Overall, Gram-negative bacterial isolates showed the highest sensitivity to antibiotic nitrofurantoin (90%) and the lowest in ampicillin (35%). Gram positive has highest incidence of sensitivity towards tigecycline (100%) and lowest in cefoxitin (20%). ESβL producers were found to be 21.0% and highest being in Klebsiella oxytoca (35%) followed by Klebsiella pneumonia (31%). Staphylococcus pseudintermedius and Staphylococcus capitis have been identified on the mobile phones for the very first time. Interestingly, some soil microbes were also isolated and unfortunately found to have some antibiotic resistance like Raoultella ornithinolytica and Sphingomonas paucimobilis. The results revealed that mobiles were contaminated with multidrug-resistant (MDR) pathogens, and this study also showed that few of the saprophytic soil strains have antibiotic resistance, which can be an alarming situation that needs to be addressed. [ABSTRACT FROM AUTHOR]

Background: The emergence and spread of Extended-spectrum β-lactamases (ESBLs) in Enterobacteriaceae through the plasmid-mediated exchange have become a major threat to public health by complicating the treatment of severe infections in both animals and humans. Therefore, the current study focused on evaluating the manifestation of ESBLs production from the fecal isolates of E. coli, Shigella spp, Salmonella spp, and Klebsiella spps in commercial poultry production systems of Kiambu County, Kenya. Materials and methods: Out of 591 isolates identified as E. coli, Shigella spp, Salmonella spp, and Klebsiella spps from 437 fecal samples, only 78 were phenotypically suggestive to be ESBL producers. The possible ESBL producers were screened for the presence of blaTEM, blaCTX-M, blaOXA, and blaSHV using the PCR technique. These isolates were also screened for carriage of the QnrS gene that confers resistance to the fluoroquinolone class of drugs. Results: The most detected ESBL gene from the isolates was blaOXA (n = 20; 26%), followed by blaTEM (n = 16, 21%), with the majority of them detected in E. coli. The blaCTX-M was identified in all the 4 enteric's bacteria-type isolates tested. Three E. coli and Salmonella spp respectively were found to harbor all the 5 antimicrobial resistance (AMR) gene types. The blaTEM, blaOXA, blaSHV, and QnrS genes were not detected from Klebsiella and Shigella spps. Additionally, most of the AMR gene co-carriage was detected in both E. coli and Salmonella spps as follows blaTEM + blaOXA (n = 4); blaTEM + QnrS (n = 3); blaTEM + blaOXA + QnrS (n = 3), concurrently. Conclusion: Our findings highlight the significance of commercial poultry production in disseminating transferable antibiotic resistance genes that act as potential sources of extensive drug resistance in livestock, humans, and the environment, leaving limited therapeutic options in infection management. [ABSTRACT FROM AUTHOR]

Bacterial resistance to colistin has prompted the search for alternative strategies to enhance antibacterial potential. Combination therapy remains one of the viable strategies in antibacterial therapy and has been proven to be effective in reducing the risk of resistance. In this study, the potential of orientin for enhancing the antibacterial activity of colistin was assessed against Klebsiella pneumoniae and Pseudomonas aeruginosa in vitro. The involvement of oxidative stress in such enhancement was also assessed. The minimum inhibitory concentrations (MICs) of colistin and orientin were 16 μg/mL and 64 μg/mL against K. pneumoniae and 64 μg/mL and 256 μg/mL against P. aeruginosa respectively. For the combination therapy, orientin potentiates the antibacterial effect of colistin with a friction inhibitory concentration index (FICI) of 0.37 and 0.31 against K. pneumoniae and P. aeruginosa, respectively. This observation suggests a synergistic interaction, with the MIC of colistin being reduced by 3- and 4-fold in the presence of orientin against K. pneumoniae and P. aeruginosa, respectively. Additionally, treatment with the combination of colistin and orientin induced oxidative stress against both organisms through increased cellular levels of superoxide anion radicals with concomitant increase in NAD+/NADH and ADP/ATP ratios. These findings suggest that orientin enhanced colistin in the killing of the test bacteria and the cotreatment of colistin and orientin induced oxidative stress, through reactive oxygen species generation, which consequently facilitated bacterial lethality without causing drug-drug interactions. Although, the data presented in this study has supported the capability of orientin for strengthening antibacterial activity of colistin toward the fight against drug-resistant Gram-negative bacteria, studies focusing on the exact target and mechanism of action of orientin are underway. [ABSTRACT FROM AUTHOR]

Aim. This study aimed to provide profiles of microorganisms isolated from bile and antibiotic susceptibility patterns of biliary tract infections (BTIs) in our center. Methods. A total of 277 patients diagnosed with BTIs at the Second Affiliated Hospital of Harbin Medical University from 2011 to 2018 were included in this study. Medical records were reviewed to obtain clinical and demographic data. Bile specimens were prepared through endoscopic retrograde cholangiopancreatography (ERCP), percutaneous transhepatic cholangiodrainage (PTCD), and percutaneous transhepatic gallbladder drainage (PTGD) under aseptic conditions. In those with positive bile culture results, blood cultures were concurrently conducted. The concordance of the results between bile culture and blood culture were also analysed. Results. Two hundred and sixty-seven bile cultures were positive, while 280 strains of micro-organisms were isolated. Among these, 76.8% were Gram-negative, 22.5% were Gram-positive and 0.7% were fungi. The most common microorganisms were Escherichia coli, Klebsiella pneumoniae, and Enterococcus faecalis. Gram-negative bacteria we tested were highly sensitive to ertapenem, imipenem, tigecycline, and amikacin. Gram-positive bacteria we tested were highly sensitive to tigecycline, teicoplanin, linezolid, vancomycin, and chloramphenicol. For the 44 patients with positive bile cultures, a blood culture was also performed. Among them, 29 cases yielded positive blood culture results. Among those cases with positive blood culture, 48.3% showed complete agreement with bile culture, 3.4% showed partial agreement, and 48.3% showed disagreement. The most common microorganisms in blood culture were the same as in bile culture. Additionally, the proportion of Staphylococcus epidermidis was significantly higher in blood culture (P < 0.05). Conclusion. Our study provided a comprehensive analysis of the bacteria distribution and drug resistance profiles in patients with BTIs in northern China. Further studies should be conducted to validate our findings. [ABSTRACT FROM AUTHOR]

The present study was intended to isolate extended-spectrum beta-lactamase (ESBL) producing Klebsiella spp. from chevon samples (n = 150) collected various retail chevon markets in and around Anand (Gujarat) to check their prevalence and evaluate the hygienic level. The isolates obtained were also subjected to anti-microbial susceptibility testing. According to Clinical and Laboratory Standards Institute (CLSI) guidelines, Bacterial isolation, identification, and anti-microbial susceptibility tests were performed. Out of 150 samples, Klebsiella spp. were recovered from 85 chevon samples with an overall prevalence of 56.67%. The highest prevalence was observed in the intestine (76.67%), while the lowest was observed in muscle samples (36.67%) with intermediate prevalence in other samples like heart, liver, and water. Amongst Klebsiella spp. isolates, 100 % antibiotic resistance was detected towards ampicillin and ceftazidime, followed by cefepime (64%) and ceftazidime/clavulinic acid (63%); whereas higher sensitivity was detected towards amoxicillin/clavulanic acid (89.41%) followed by gentamicin (70.58%) and amikacin (61.17%). The high prevalence of ELBS producing Klebsiella spp. with greater anti-microbial resistance suggest the judicious use of antibiotics and the need to track and monitor the spread of ESBL producing strains in food-producing animals to safeguard public health. [ABSTRACT FROM AUTHOR]

Background: The genus Providencia, earlier considered a rare pathogen, is now increasingly recognized as a notorious opportunistic pathogen capable of causing serious nosocomial infections, mainly urinary tract infections (UTIs). Treating these infections is an onerous task given the resistance seen in clinical strains to many currently available antimicrobials. The objective of the present study is to provide an overall view into the prevalence of Providencia spp. causing UTIs, their antibiotic susceptibility pattern, and respective clinical outcomes. Materials and methods: This is a retrospective observational study carried out in a tertiary care teaching referral hospital located in Jaipur, India from March 2021 to May 2021. All Providencia spp. strains isolated from urine samples were included in the study. Data were entered in Microsoft Office Excel worksheet. Results are presented in numbers and percentages. Results: Out of 1,261 urine samples processed in the laboratory during the study period, 426 were culture positive and the majority were gram-negative isolates and included Escherichia coli (46.0%) and Klebsiella spp. (28.0%). Providencia spp. was the fourth most common gram-negative pathogen (6.0%). The median age of patients was 65 years. The male:female ratio was 3:2 and maximum patients belonged to the 30-60-year age-group. Diabetes was the commonest associated comorbidity. All patients had an indwelling urinary catheter. Three (20.0%) patients succumbed to infections. Conclusion: Providencia is an opportunistic pathogen that cannot be neglected due to escalating antibiotic resistance. Effective infection control and antibiotic stewardship policies are required to prevent the development of further antibiotic resistance. [ABSTRACT FROM AUTHOR]

What is Known and Objective: Antibiograms gives an overview of the cumulative susceptibility of formal antibiotics to bacterial isolates, which reflects the portion of each bacterium susceptible to a given antibiotic formulation by using antimicrobial susceptibility testing. The objective of this study is to gather and analyse data from drug utilization evaluation (DUE) studies and antimicrobial susceptibility tests in order to create an antibiogram toolkit that will help clinicians to select appropriate antimicrobial agents for initial empirical antibiotic therapy at point of care settings and avoid irrational use of antibiotics. Methods: A prospective interventional study was conducted at tertiary care hospital, biological samples of infectious patients were collected from various wards as per Clinical & Laboratory Standards Institute CLSI M39‐A4 guidelines. Antimicrobial susceptibility results were analysed using WHONET software. Antibiotic stewardship committee was formed and involved in monitoring the usage of antibiotics, measuring outcomes, collecting feedback and finding the scope for improving the application of antibiogram toolkit in the hospital. Antibiotic usage tracking method was followed to know the level of adherence to the prescribing guidelines by the health care professionals. Results and Discussion: A total of 157 samples were obtained from various wards of the hospital. In that, Escherichia coli, Staphylococcus aureus and Klebsiella Pneumoniae were isolated in significant numbers. Antibacterial susceptibility results were collected, an initial antibiogram was developed for 18 antibacterial agents with respect to 3 gram‐positive (+) and 1 gram‐negative (−) organisms. 90% of prescribers mentioned that the antibiogram was useful, and 76% of them adhered to the guidelines. 26% were not adhered due to the patient‐related factors. What is New and Conclusion: In our study, we have used qualitative and quantitative evaluation of drug utilization (DUE) reports to understand the existing prescribing pattern of antibiotics and setting target organisms and antibacterials to develop the hospital antibiogram. Combining DUE studies and antibiogram development was helpful in implementing effective antibiotic policies for the hospital. Further, this study pattern will be continued on a yearly basis and focused on developing cumulative antibiograms to understand the changes in resistance pattern of antimicrobials and utilization of antibiotics in the hospital. [ABSTRACT FROM AUTHOR]

β‐Lactams are the most commonly used antibiotics in intensive care units (ICUs). As critically ill patients often experience pharmacokinetic aberrations, and rates of antimicrobial resistance vary between hospital settings, reliance on tertiary sources or package labeling to guide empiric dosing often results in suboptimal β‐lactam exposure. The primary objective was to identify β‐lactam regimens capable of achieving ≥90% cumulative fraction of response (CFR) against 7 Gram‐negative pathogens within 4 ICUs at our institution. Unit‐specific minimal inhibitory concentration (MIC) distribution data was used in combination with published pharmacokinetic parameters in critically ill patients to perform Monte Carlo simulations. The percentage of time for which the unbound concentration of antibiotic remained above the MIC (%ƒT > MIC) was used as the pharmacodynamic target: 70%ƒT >MIC for cefepime, 40%ƒT > MIC for meropenem, and 50%ƒT > MIC for piperacillin/tazobactam. Regimens were modeled to determine the likelihood of achieving ≥90% CFR. Overall, intermittently dosed cefepime, meropenem, and piperacillin/tazobactam failed to achieve ≥90% CFR for every organism. Cefepime 2 g intermittent bolus every 8 hours failed to achieve ≥90% CFR for Klebsiella pneumoniae or Enterobacter cloacae despite susceptibility rates exceeding 90%. Piperacillin/tazobactam 4.5 g prolonged infusion (PI) every 6 hours achieved <85% CFR for Pseudomonas aeruginosa and <50% CFR for Acinetobacter baumannii in every ICU. Meropenem 2 g PI every 8 hours and meropenem 2 g PI every 6 hours were the only regimens capable of achieving ≥90% CFR for P aeruginosa in all units. Use of Monte Carlo simulations, with incorporation of local MIC distribution data, provides a mechanism to effectively predict optimal agent and dose selection within specific hospital systems, thereby enhancing pharmacokinetic/pharmacodynamic optimization and improving clinical efficacy. [ABSTRACT FROM AUTHOR]