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Carbapenem-resistant Enterobacterales (CRE) have become a global threat, with colistin being the last resort for treatment. CLSI and EUCAST recommend broth microdilution (BMD) as the reference method for colistin susceptibility testing. Nordmann and Poirel have developed a simple and rapid Polymyxin NP test as an alternative to BMD for screening of colistin-resistant Enterobacterale (CoRE) isolates. This study aimed to evaluate the performance of the colistin rapid NP (CRNP) test for the detection of colistin resistance. CRNP test was performed on thirty-one clinical Enterobacterales isolates [ Klebsiella pneumoniae (21), Enterobacter spp , (9) and Escherichia coli (1), which were resistant to Colistin by the reference BMD method. The results of the NP test were interpreted after 4hr by the change in color of NP solution (original orange to yellow as a result of bacterial growth) and compared with that of BMD. The CRNP test could accurately detect 26/31 of the colistin resistant Enterobacterale isolates, and thus had an overall categorical agreement of 83.8%. Out of thirty-one CoRE isolates, five Enterobacter spp. 5/31 (16.1%) could not be detected by the CRNP test giving a false-negative result. Excluding those five Enterobacter spp. the categorical agreement (CA) of the CRNP test with BMD was 100%. The overall very major error (VME) of the CRNP test was 16% but decreased to < 3% when Enterobacter spp. (5) were excluded. The CRNP test is technically less demanding, yields faster results compared to the reference BMD method, and has 100% agreement with reference BMD in Enterobacterales except for Enterobacter spp. [ABSTRACT FROM AUTHOR]

Identifying risk factors associated with the carriage of antimicrobial-resistant (AMR) bacteria in dogs is crucial to understanding their epidemiology and for developing and refining targeted control measures. However, relevant data is scattered and conflicting findings have been reported. This systematic review aimed to compile risk factors associated with the carriage of AMR-Enterobacterales in dogs worldwide and to identify relevant knowledge gaps for directing future research. A systematic review was conducted according to PRISMA guidelines, searching PubMed, CABi, and Scopus databases for studies reporting risk factors for acquiring AMR-Enterobacterales in dogs. After screening peer-reviewed, English-language studies by title/abstract, eligible studies were subjected to a full-text assessment, data extraction, risk-of-bias assessment, and qualitative synthesis. In the initial search, 774 articles were identified, including 274 duplicates. After screening by title/abstract, 77 articles were subjected to full-text review, from which 40 were eventually selected for data extraction, including 29 cross-sectional, six cohort, and five case-control studies. The most frequently investigated risk factors for AMR-Enterobacterales carriage in dogs were antimicrobial use (28 of 40), age (24), sex (22), hospitalization (19), and feeding raw diet (14). Of these, antimicrobial use was themost common risk factor significantly associated with AMR-Enterobacterales (19/28), followed by raw diet (9/14) and hospitalization (8/19). Our synthesis emphasized the importance of increasing awareness regarding the prudent use of critically important antimicrobials (CIAs), such as fluoroquinolones, in companion animal practices, strengthening infection prevention and control procedures in veterinary clinics and hospitals and educating caregivers about the potential risks of feeding raw diets in order to reduce the burden of AMR-bacteria in dogs. [ABSTRACT FROM AUTHOR]

This study continues surveillance of antimicrobial resistance associated with combat injuries in Ukraine. To compare species composition, antibiotic resistance profiles, and emergence of new resistance genes between 2014–2020 and 2022–2023. This was a retrospective multi-centre microbiological survey in Ukrainian hospitals. Antibiotic susceptibility, whole-genome sequencing and multi-locus sequence typing were conducted on 154 organisms obtained from 125 casualties between 2022 and 2023. The data revealed a predominance of Gram-negative bacteria, particularly Acinetobacter baumannii (35.7%), Pseudomonas aeruginosa (14.9%) and Klebsiella pneumoniae (20.7%). High levels of carbapenem resistance were observed among A. baumannii {meropenem 72.2% [39/54, 95% confidence interval (CI) 58.4–83.5]; imipenem 66.7% (36/54, 95% CI 52.5–78.9)}, K. pneumoniae [meropenem 90.6% (29/32, 95% CI 75.0–98.0); imipenem 81.2% (26/32, 95% CI 63.6–92.8)] and P. aeruginosa [meropenem 47.8% (11/23, 95% CI 26.8–69.4); imipenem 60.8% (14/23, 95% CI 38.5–80.3)] strains. A. baumannii sequence type (ST)-78 and ST-400 were prevalent from 2014 to 2020, while five strains of ST-1077 were newly identified in 2022–2023. P. aeruginosa strains showed diversity across 16 STs, with ST-773 increasing in frequency and new STs emerging, but lacking carbapenemase genes. K. pneumoniae exhibited increased genetic diversity over time, with three STs from 2014 to 2020 and six new STs, including bla NDM-1 , bla OXA-48 and bla KPC2 carriers, in 2022–2023. The prevalence of multi-drug-resistant isolates with STs associated with a high risk of global dissemination is increasing. [ABSTRACT FROM AUTHOR]

Background: Antimicrobial resistance is a major global public health challenge, particularly with the rise of carbapenem-resistant Enterobacterales (CRE) and Pseudomonas aeruginosa (CRPA). This study aimed to describe the characteristics of CRE and CRPA infections in Eastern Europe, focusing on Bulgaria, Croatia, Czechia, Greece, Hungary, Poland, Romania, Serbia, Slovakia, and Slovenia. Methods: Following MOOSE and PRISMA guidelines, a systematic literature review of articles published between 1 November 2017 and 1 November 2023 was conducted using the MEDLINE, Embase, Web of Science, CDSR, DARE, and CENTRAL databases. The search strategy used a combination of free text and subject headings to gather pertinent literature regarding the incidence and treatment patterns of CRE and CRPA infections. A total of 104 studies focusing on infections in both children and adults were included in this review. Results: This review revealed a significant prevalence of carbapenem-resistant Gram-negative isolates and underscored the effectiveness of imipenem/relebactam and ceftazidime/avibactam (CAZ/AVI) against Klebsiella pneumoniae carbapenemase-producing Enterobacterales and of ceftolozane/tazobactam, imipenem/relebactam and ceftazidime/avibactam against non-metallo-β-lactamase-producing CRPA strains. Conclusions: This study highlights the urgent need for comprehensive measures to combat the escalating threat of CRE and CRPA infections in Eastern European countries. At the same time, it shows the activity of the standard of care and new antimicrobials against carbapenem-resistant Gram-negative pathogens in Eastern Europe. Clinical real-world data on the treatment of carbapenem-resistant infections in Eastern Europe are needed. [ABSTRACT FROM AUTHOR]

Background: Acquired 16S rRNA methyltransferases (16S-RMTases) confer high-level resistance to aminoglycosides and are often associated with β-lactam and quinolone resistance determinants. Methods: Using PCR, whole-genome sequencing and conjugation experiments, we conducted a retrospective genomic surveillance study of 16S-RMTase-producing Enterobacterales, collected between 2006 and 2023, to explore transmission dynamics of methyltransferase and associated antibiotic resistance genes. Results: Among the 10,731 consecutive isolates, 150 (1.4%) from 13 species carried armA (92.7%), rmtB (4.7%), and rmtF + rmtB (2.7%) methyltransferase genes. The coexistence of extended-spectrum β-lactamase (blaCTX-M-3/15, blaSHV-12, blaSFO-1), carbapenemase (blaNDM-1/5, blaVIM-1/4/86, blaOXA-48), acquired AmpC (blaCMY-2/4/99, blaDHA-1, blaAAC-1), and plasmid-mediated quinolone resistance (qnrB, qnrS, aac(6′)-Ib-cr) genes within these isolates was also detected. Methyltransferase genes were carried by different plasmids (IncL/M, IncA/C, IncR, IncFIB, and IncFII), suggesting diverse origins and sources of acquisition. armA was co-transferred with blaCTX-M-3/15, blaNDM-1, blaVIM-4/86, blaOXA-48, blaCMY-4, aac(6′)-Ib-cr, qnrB, and qnrS, while rmtF1 was co-transferred with blaSFO-1, highlighting the multidrug-resistant nature of these plasmids. Long-read sequencing of ST6260 K. pneumoniae isolates revealed a novel resistance association, with rmtB1 and blaNDM-5 on the chromosome, blaOXA-232 on a conjugative ColKP3 plasmid, and rmtF1 with blaSFO-1 on self-transmissible IncFIB and IncFII plasmids. Conclusions: The genetic plasticity of plasmids carrying methyltransferase genes suggests their potential to acquire additional resistance genes, turning 16S-RMTase-producing Enterobacterales into a persistent public health threat. [ABSTRACT FROM AUTHOR]

The global emergence of extended-spectrum beta-lactamase (ESBL)-producing Klebsiella pneumoniae presents a significant public health threat and complicates antibiotic treatment for infections. This study aimed to determine the prevalence of ESBL-producing K. pneumoniae in a clinical setting, analyze their antimicrobial susceptibility profiles, and characterize both phenotypic and genetic determinants. A total of 507 non-duplicate clinical isolates of Enterobacterales were collected between 2019 and 2020, and third-generation cephalosporin resistance was screened by disk diffusion. Identification of K. pneumoniae was confirmed using biochemical tests and PCR with species-specific primers. Antimicrobial susceptibility testing was conducted using disk diffusion, and phenotypic ESBL production was confirmed using the combined disk method. Multiplex PCR detected ESBL genes (blaTEM, blaSHV, and blaCTX-M) and identified blaCTX-M groups. The genetic relatedness of ESBL-producing strains was assessed using the ERIC-PCR approach. Fitty-four isolates were confirmed as ESBL producers, all classified as multidrug-resistant (MDR). All ESBL-producing K. pneumoniae isolates exhibited resistance to ampicillin and cefotaxime, with high resistance rates for ciprofloxacin (98.2%), azithromycin (94.4%), piperacillin–tazobactam (88.9%), and trimethoprim (83.3%). Genotypic analysis revealed blaCTX-M was present in 94.4% of isolates, blaSHV in 87%, and blaTEM in 55.5%. The blaCTX-M-1 group was the most prevalent, accounting for 96.1% of isolates. Co-harboring of blaCTX-M, blaSHV, and blaTEM occurred in 42.6% of isolates, with co-carrying of blaCTX-M, and blaSHV was observed in 23/54 isolates. The ERIC-PCR analysis revealed 15 distinct types, indicating high genetic diversity. These findings highlight the urgent need for ongoing monitoring to control the spread of ESBL among K. pneumoniae and emphasize the importance of early detection and appropriate antibiotic selection for effectively treating infection caused by these pathogens. [ABSTRACT FROM AUTHOR]

Cefiderocol is a novel cephalosporin–siderophore conjugate antibiotic that holds promise to thwart infections caused by multi-drug-resistant gram-negative bacilli. Its antibacterial activity against normally susceptible species is not affected by most β-lactamases, including metallo-β-lactamases. Due to the siderophore-mediated entry into the cell, the activity of cefiderocol is less affected by porin loss or active efflux resistance than many other β-lactam antibiotics. The aim of this study was to assess in vitro susceptibility to the cefiderocol of carbapenemase-producing gram-negative bacilli from clinical samples of hospitalized patients. We analyzed 102 clinical strains of carbapenemase-producing Enterobacterales and non-fermentives from hospital centers in Łódź, Poland. Antimicrobial susceptibility to cefiderocol was tested by the minimum inhibitory concentration test strips and disc diffusion methods. The obtained results turned out to be ambiguous, and the area of technical uncertainty made their interpretation very difficult. The cost of therapy with this antibiotic, and difficulties in interpreting the drug susceptibility are the limitations to the use of cefiderocol. Intensive work should be carried out to finally standardize an easily accessible and reliable method for the determination of susceptibility to cefiderocol. [ABSTRACT FROM AUTHOR]

Aim: ESCPM bacteria include Enterobacter spp, Serratia, Citrobacter spp, Providencia spp, and Morganella spp. These Gram-negative bacilli harbor chromosomally encoded AmpC-type β-lactamases that cause resistance to β-lactam antibiotics, such as penicillins, β-lactam/β-lactamase inhibitors, and first-, second-, and third-generation cephalosporins. Bloodstream infections caused by ESCPM group bacteria (BSI-ESCPM) are difficult to treat. Purpose: To describe 30-day mortality and analyze potential risk factors for death in patients with BSI-ESCPM. Patients and Methods: A cohort study of patients aged ≥ 18 years with BSI-ESCPM was conducted at a University Hospital in Brazil, from January 2013 and December 2018. Potential risk factors for death within 30 days of bloodstream infection BSI diagnosis were analyzed using multivariable logistic regression. Results: Among 138 patients with BSI-ESCPM, 63.0% were males, with a median age of 61 years. Of 155 BSI-ESCPM episodes, 61.3% were hospital-acquired. Primary BSI-ESCPM associated with short-term central venous catheter (37.4%) and BSI-ESCPM secondary to respiratory infection (19.4%) occurred mainly. Mostly, Enterobacter spp. (49.7%) and Serratia spp. (29.0%) were isolated. Multidrug-resistance occurred in 27.7% of BSI-ESCPM episodes, involving Enterobacter spp. (16.1%) and Serratia spp. (7.7%) mainly. The mortality was 24.5%. Developing septic shock within 72 h of BSI-ESCPM diagnosis (OR: 70.26; 95% CI: 16.69– 295.77; P< 0.01) was risk factor for death. Conversely, combined antibiotic therapy (OR: 0.23; 95% CI: 0.05– 0.94; P:0.04), BSI-ESCPM secondary to urinary infection (OR: 0.11; 95% CI: 0.01– 0.99; P:0.05), and Enterobacter spp. BSI (OR: 0.16; 95% CI: 0.05– 0.56; P 0< 0.01) was protective factor against death. Tendency of association between inadequate antibiotic therapy and death (OR: 2.19; 95% CI: 0.51– 9.42; P:0.29) was observed. Conclusion: BSI-ESCPM is severe and has serious outcomes such as sepsis-associated deaths. Combined antibiotic therapy was a protective factor against death in patients with BSI-ESCPM. There is a suggestive association between inadequate antibiotic therapy and mortality. The ESCPM group bacteria that are considered to be at moderate to high risk of clinically significant AmpC production were not associated with death. [ABSTRACT FROM AUTHOR]

Bacterial infections are a common complication in patients with decompensated liver cirrhosis. The complex landscape of cirrhosis, characterized by immune paralysis and an exhausted response to exogenous triggers, explains the higher prevalence of such infections, particularly in advanced disease stages. In clinical practice, the onset of a bacterial infection can lead to further deterioration of hepatic and extra-hepatic function, potentially resulting in acute decompensation or acute-on-chronic liver failure. This has significant clinical implications, particularly for patients awaiting a transplant. In this review, we will discuss the latest evidence on the diagnosis and therapy of bacterial infections in patients with decompensated cirrhosis. Additionally, we will analyze the impact of bacterial infections in the context of liver transplantation, discussing debated topics such as the timing of transplantation in patients with infections, potential implications for prioritization, effects on post-operative recovery, grafts, and patient survival. [ABSTRACT FROM AUTHOR]

It is increasingly important to rapidly receive information on the antimicrobial susceptibility of bacteria due to the rise in antimicrobial resistance worldwide. However, traditional phenotypic methods are time-consuming. Thus, the objective of this study was to develop a rapid assay that can detect antibiotic-resistant bacterial isolates phenotypically in less than 2 h. The microplate assay used in this study is based on absorbance measurements of pure bacterial isolates grown in liquid media with and without antibiotics. Absorbance was measured at the beginning of the assay and after 90 min of incubation at 37 °C. Susceptibility was calculated for bacterial isolates that, in the absence of antibiotics, exhibited more than a 50% growth increase by comparing the absorbance value of the culture in the presence of an antibiotic at 90 min with its initial value. Here, we show that it is possible to phenotypically screen the antibiotic susceptibility of Enterobacterales and Acinetobacter spp. isolates to three different antibiotics in 90 min. The test demonstrated an accuracy of 98.8%, sensitivity of 97.6%, and specificity of 99.6%. The false susceptibility rates were 0.2% and false resistance rates were 1.0%. This rapid and simple absorbance test has proven suitable for the screening of antibiotic susceptibility for a large number of strains with high accuracy and sensitivity. This method can be performed without specialized and costly materials and/or equipment, which makes it highly suitable for laboratories with limited resources. [ABSTRACT FROM AUTHOR]

Objective: The objective was to compare the microbiological characteristics and treatment of early and late surgical site infections (SSIs) in instrumented spinal surgery. Methods: Those patients admitted for SSIs in a single center between January 2010 and December 2022 were included. The subjects were divided into early (eSSIs) and late (lSSIs) SSIs, and demographic, microbiological, treatment, and follow-up data were collected. Results: Instrumented spinal surgery was performed in 2136 patients. Ninety-six cases of infections were identified (prevalence = 4.5%), with 47.9% eSSIs and 52.1% lSSIs. In 58.7% of the cases, the eSSIs were monomicrobial: Staphylococcus aureus (37%) and Enterobacterales (33.3%) were the main bacteria involved. In 66% of the cases, the lSSIs, were monomicrobial: Cutibacterium acnes (30.3%) and staphylococci were predominant. Enterobacterales were isolated in more than 70% of the polymicrobial samples in both the eSSIs and lSSIs. The treatment of the eSSIs mostly consisted of lavage-debridement surgery associated with antibiotic treatment, while the treatment of the lSSIs combined hardware removal or replacement and long-duration antibiotic treatment. A negative outcome was observed in 17.1% of the eSSIs and 5.7% of the lSSIs. Enterobacterales were associated with negative outcomes of eSSIs. Conclusions: Enterobacterales were found in most of the polymicrobial infections regardless of the time of infection onset. Further large studies should be conducted to precisely determine the management and prevention regarding the increasing Gram-negative bacteria SSIs. [ABSTRACT FROM AUTHOR]

We examined the emergence and characteristics of oxacillinase-484–producing Enterobacterales in France during 2012–2023. Genomic analysis identified 2 predominant sequence types in Escherichia coli: ST410 and ST1722. Plasmid analysis revealed that blaOXA-484 genes were carried mostly on an IncX3-type plasmid associated with genetic elements including insertion sequences IS3000 and ISKpn19.

ABSTRACT: Objectives: This study was performed to investigate the activity of the novel ß-lactam/ß-lactamase inhibitor combination cefepime/enmetazobactam, against recently circulating Enterobacterales isolates from Europe from 2019 to 2021. Methods: A total of 2627 isolates were collected, and antimicrobial susceptibility was determined according to the European Committee on Antimicrobial Susceptibility Testing guidelines. Isolates with phenotypic resistance to ceftriaxone and ceftazidime (but susceptible to meropenem) and isolates nonsusceptible to meropenem were screened for the presence of ß-lactamases. Results: Overall, susceptibility to third-generation cephalosporins was 77%, and 97.3% were susceptible to meropenem. Cefepime/enmetazobactam susceptibility was 97.9% (72% of these isolates were Klebsiella pneumoniae from Italy), compared with 80.0% susceptibility to piperacillin/tazobactam and 99.4% to ceftazidime/avibactam. A total of 320 isolates (12.2%) were resistant to third-generation cephalosporins but susceptible to meropenem, and virtually all (96.3%) carried an extended-spectrum ß-lactamase with or without an AmpC and these were all susceptible to cefepime/enmetazobactam. Most meropenem-nonsusceptible isolates carried a KPC (68%), which were not inhibited by cefepime/enmetazobactam but were inhibited by ceftazidime/avibactam. Additionally, most meropenem-nonsusceptible isolates carrying OXA-48 (9/12 isolates) were susceptible to cefepime/enmetazobactam. Conclusions: Cefepime/enmetazobactam was highly active against Enterobacterales isolates, especially those resistant to third-generation cephalosporins. These data suggest that cefepime/enmetazobactam could be used as a carbapenem-sparing agent to replace piperacillin/tazobactam.

Abstract Background Infections caused by multi-drug resistant Gram-negative pathogens are associated with worse clinical outcomes in critically ill patients. We evaluated hospital outcomes based on adequacy of overall and newer antibacterial therapy for Enterobacterales (ENT) and Pseudomonas aeruginosa (PsA) in US patients. Methods Hospitalized adults ≥ 18 years old with facility-reported antibiotic susceptibility from 2018–2022 across 161 facilities in the BD Insights Research Database were identified as ENT- or PsA-positive. Generalized linear mixed models were used to evaluate the impact of inadequate empiric therapy (IET) and time to initiate newer antibacterials (ceftazidime-avibactam; ceftolozane-tazobactam; cefiderocol; meropenem-vaborbactam; eravacycline; and imipenem-cilcastatin-relebactam) on hospital mortality and post-culture length of stay (LOS). Results Among 229,320 ENT and 36,027 PsA susceptibility results, 1.7% and 16.8% were carbapenem non-susceptible (carb-NS), respectively. Median time to first susceptibility result was longer for carb-NS vs. carb susceptible in ENT (64 h vs. 48 h) and PsA (67 h vs. 60 h). For ENT, IET was associated with significantly higher mortality (odds ratio [OR],1.29 [95% CI, 1.16–1.43, P

Objective. To determine etiological structure of infections in the surgical intensive care unit (ICU), identify the most common mechanisms of antibiotic resistance of leading pathogens, and develop recommendations for optimizing antimicrobial therapy in the ICU at the present stage. Materials and Methods. A prospective observational study was conducted in the surgical ICU of the Moscow City Clinical Center "Kommunarka" from September 2022 to February 2024. The subjects of observation were 2120 patients treated in the unit. Microbiological examination of patients' biological fluids was carried out in accordance with approved methodological guidelines. The results of determining the susceptibility of isolated pathogens were interpreted based on the EUCAST v14.0 criteria. Automatic bacteriological analyzers, MALDI-TOF mass spectrometry for pathogen identification, PCR and immunochromatographic methods for determining resistance mechanisms were used. To determine the etiological structure of infections in hospitalized patients, only original isolates were considered, following the principle of "one patient – one microbe." Results. A total of 1213 bacterial and 53 fungal pathogens were isolated from 394 patients. The leading pathogens were Klebsiella pneumoniae (18.5%), Acinetobacter baumannii (13.4%), and Pseudomonas aeruginosa (9.5%). Resistance to meropenem was 83.0% for K. pneumoniae, 97.4% for A. baumannii, and 81.5% for P. aeruginosa. The highest in vitro activity against Enterobacterales was exhibited by ceftazidime-avibactam (79.2% of susceptible isolates), while against A. baumannii and P. aeruginosa, it was colistin (98.6% and 90.6% of susceptible isolates, respectively). The genetic mechanisms of carbapenem resistance in Enterobacterales were identified: production of NDM (26.3%), OXA-48 (29.6%), and KPC (44.1%) carbapenemases. Conclusions. The predominant pathogens of infections in surgical ICU patients are gram-negative bacteria with a high level of antibiotic resistance, including carbapenem-resistant Enterobacterales, whose resistance is due to the production of carbapenemases of various molecular classes. An increase in the prevalence of the serine carbapenemase KPC, previously atypical for the Russian Federation, has been noted. Currently, for infections caused by Enterobacterales producing serine carbapenemases, ceftazidime-avibactam can be recommended, and in the case of metallo-beta-lactamase production by Enterobacterales, a combination of ceftazidime-avibactam with aztreonam. For infections caused by A. baumannii and P. aeruginosa, regimens including polymyxins are indicated.

Bacterial infections are a common complication in patients with decompensated liver cirrhosis. The complex landscape of cirrhosis, characterized by immune paralysis and an exhausted response to exogenous triggers, explains the higher prevalence of such infections, particularly in advanced disease stages. In clinical practice, the onset of a bacterial infection can lead to further deterioration of hepatic and extra-hepatic function, potentially resulting in acute decompensation or acute-on-chronic liver failure. This has significant clinical implications, particularly for patients awaiting a transplant. In this review, we will discuss the latest evidence on the diagnosis and therapy of bacterial infections in patients with decompensated cirrhosis. Additionally, we will analyze the impact of bacterial infections in the context of liver transplantation, discussing debated topics such as the timing of transplantation in patients with infections, potential implications for prioritization, effects on post-operative recovery, grafts, and patient survival.

Background: The coronavirus disease 2019 (COVID-19) pandemic has contributed to the spread of antimicrobial resistance, including carbapenem-resistant Enterobacterales. Methods: This study utilized data from the Study for Monitoring Antimicrobial Resistance Trends (SMART) surveillance program in Taiwan. Enterobacterales from patients with bloodstream infections (BSIs) were collected and subjected to antimicrobial susceptibility testing and β-lactamase gene detection using a multiplex PCR assay. Statistical analysis was conducted to compare susceptibility rates and resistance genes between time periods before (2018–2019) and during the COVID-19 pandemic (2020–2021). Results: A total of 1231 Enterobacterales isolates were collected, predominantly Escherichia coli (55.6%) and Klebsiella pneumoniae (29.2%). The proportion of nosocomial BSIs increased during the COVID-19 pandemic (55.5% vs. 61.7%, p

Background: The irrational use of antibiotics has led to the emergence of multidrug-resistant pathogens. The phenomenon of minimum inhibitory concentration (MIC) creeps occurs when organisms start showing raised MIC but within susceptible range giving an indication of the prevalence of rise in resistant pathogens in an area. Aims and Objectives: The aims and objectives of the study are to observe the susceptibility pattern among uropathogens and the possibility of MIC creeps among the Escherichia coli isolates sensitive to nitrofurantoin. Materials and Methods: This retrospective study was done in a tertiary care hospital in Kolkata to observe the susceptibility pattern among uropathogens and the possibility of MIC creeps. We took the data from all inpatient department and outpatient department patients sent for urine culture and sensitivity from October 1st, 2022, to September 30th, 2023. The antimicrobial susceptibility testing and MIC were conducted by VITEK Compact 2. The MIC of nitrofurantoin, one of the most widely used antibiotics for lower urinary tract infections, was calculated to investigate the phenomenon of MIC creep. All the statistical analyses were carried out using the Excel spreadsheet and OpenEpi version 3.01 platform. Results: In our study, a total of 631 urine samples were analyzed: 368 were positive with the most common isolate being E. coli (53%) followed by Klebsiella spp. (12%). Two percent of resistance was observed for fosfomycin and 8% for nitrofurantoin. Extended spectrum beta-lactamase (ESBL) producers E. coli was 127 (35%). Overall, 23/368 samples had a MIC ≥128 for nitrofurantoin. Among the ESBL producers, 13/127 had MIC ≥128 for nitrofurantoin. Conclusion: In the present study, it was observed that E. coli showed a reduced susceptibility for nitrofurantoin indicated by a creeping increase in MIC within normal range. Trends in rising MIC can be an alarming sign for using drugs such as nitrofurantoin judiciously. Antimicrobial stewardship practice should be strongly implemented in hospitals to curb rising resistance and for better prognosis of patients having infectious diseases.

We conducted surveillance for carbapenem-resistant Enterobacterales (CRE) during 2016–2020 at 10 US sites and extended-spectrum β-lactamase–producing Enterobacterales (ESBL-E) during 2019–2020 at 6 US sites. Among 159 CRE cases in children (median age 5 years), CRE was isolated from urine for 131 (82.4%) and blood from 20 (12.6%). Annual CRE incidence rate (cases/100,000 population) was 0.47–0.87. Among 207 ESBL-E cases in children (median age 6 years), ESBL-E was isolated from urine of 196 (94.7%) and blood of 8 (3.9%). Annual ESBL-E incidence rate was 26.5 in 2019 and 19.63 in 2020. CRE and ESBL-E rates were >2-fold higher among infants than other age groups. Most CRE and ESBL-E cases were healthcare-associated community-onset (68 [43.0%] for CRE vs. 40 [23.7%] for ESBL-E) or community-associated (43 [27.2%] for CRE vs. 109 [64.5%] for ESBL-E). Programs to detect, prevent, and treat multidrug-resistant infections must include pediatric populations (particularly the youngest) and outpatient settings.

Objectives: To report trends in carbapenem resistance and difficult-to-treat resistance (DTR) among clinical isolates of Gram-negative priority pathogens collected by the ATLAS global surveillance program from 2018 to 2022. Methods: Reference broth microdilution testing was performed in a central laboratory for 79,214 Enterobacterales, 30,504 Pseudomonas aeruginosa, and 13,500 Acinetobacter baumannii-calcoaceticus complex isolates collected by a constant set of 157 medical centres in 49 countries in Asia Pacific (APAC), Europe (EUR), Latin America (LATAM), Middle East-Africa (MEA), and North America (NA) regions. MICs were interpreted by 2023 CLSI M100 breakpoints. β-lactamase genes were identified for meropenem-nonsusceptible (MIC ≥2 mg/L) Enterobacterales isolates. Results: Carbapenem-resistant Enterobacterales (CRE) detection increased (P < 0.05) in APAC, EUR, LATAM, and MEA regions and decreased in NA, while annual DTR percentages increased in all five regions. Carbapenem-resistant P. aeruginosa (CRPA; decreased in MEA region) and carbapenem-resistant A. baumannii-calcoaceticus complex (CRAB; decreased in MEA region and increased in EUR) remained relatively stable over time in all regions, although notably, annual percentages of CRAB and DTR A. baumannii-calcoaceticus complex isolates were consistently >25 percentage points lower in NA than in other regions. For all regions except NA, the majority of changes in CRE percentages could be attributed to hospital-acquired infections. Among meropenem-nonsusceptible Enterobacterales, KPC was the most frequent carbapenemase in NA and EUR each year. NDM was the most prevalent carbapenemase detected in 2022 in other global regions. Conclusion: CRE, CRPA, CRAB, and DTR rates vary among global regions over time highlighting the need for continuing surveillance to inform treatment strategies and antimicrobial stewardship.

ABSTRACT: Background: The rapid and global spread of Escherichia coli carrying mcr-type genes at the human-animal-environmental interface has become a serious global public health problem. Objective: To perform a genomic investigation of a colistin-resistant E. coli strain (14005RM) causing urinary tract infection, using a hybrid de novo assembly of Illumina/Nanopore sequence data, presenting phylogenomic insights into the relationship with mcr-1-positive strains circulating at the human-animal-environmental interface, in Brazil. Methods: Genomic DNA was sequenced using both the Illumina NexSeq and Nanopore MinION platforms. De novo hybrid assembly was performed by Unicycler. Genomic data were assessed by in silico prediction and bioinformatic tools. Results: The genome assembly size was 5 333 039 bp. The mcr-1.5-positive E. coli strain 14005RM belongs to the sequence type ST354 and presented a broad resistome (antibiotics, heavy metals, disinfectants, and glyphosate) and virulome. The mcr-1.5 gene was carried by an IncI2 plasmid (p14005RM, sizing 65,458 kb). Full genome SNP-based phylogenetic analysis reveals that mcr-1.5-producing E. coli strain 14005RM is highly related (> 98% identity) to colistin-resistant mcr-1.1-positive ST354 lineages associated with urinary tract infections in Brazil since 2015. Conclusion: Mobile colistin resistance within the Brazilian One Health microbiosphere is mediated by mcr gene variants propagated by IncX4, IncHI2, and IncI2 plasmids, circulating among global clones of E. coli.

Background: Infections caused by multi-drug resistant Gram-negative pathogens are associated with worse clinical outcomes in critically ill patients. We evaluated hospital outcomes based on adequacy of overall and newer antibacterial therapy for Enterobacterales (ENT) and Pseudomonas aeruginosa (PsA) in US patients. Methods: Hospitalized adults ≥ 18 years old with facility-reported antibiotic susceptibility from 2018–2022 across 161 facilities in the BD Insights Research Database were identified as ENT- or PsA-positive. Generalized linear mixed models were used to evaluate the impact of inadequate empiric therapy (IET) and time to initiate newer antibacterials (ceftazidime-avibactam; ceftolozane-tazobactam; cefiderocol; meropenem-vaborbactam; eravacycline; and imipenem-cilcastatin-relebactam) on hospital mortality and post-culture length of stay (LOS). Results: Among 229,320 ENT and 36,027 PsA susceptibility results, 1.7% and 16.8% were carbapenem non-susceptible (carb-NS), respectively. Median time to first susceptibility result was longer for carb-NS vs. carb susceptible in ENT (64 h vs. 48 h) and PsA (67 h vs. 60 h). For ENT, IET was associated with significantly higher mortality (odds ratio [OR],1.29 [95% CI, 1.16–1.43, P < 0.0001]) and longer hospital LOS (14.8 vs. 13.3, P < 0.0001). Delayed start to newer antibacterial therapy was associated with significantly greater hospital mortality for ENT (P = 0.0182) and PsA (P = 0.0249) and significantly longer post-culture LOS for ENT (P < 0.0001) and PsA (P < 0.0001). Conclusions: Overall, IET and delayed use of newer antibacterials are associated with significantly worse hospital outcomes. More rapid identification of high-risk patients can facilitate adequate therapy and timely use of newer antibacterials developed for resistant Gram-negative pathogens. [ABSTRACT FROM AUTHOR]

Antibiotic resistance has become a global threat as it is continuously growing due to the evolution of β‐lactamases diminishing the activity of classic β‐lactam (BL) antibiotics. Recent antibiotic discovery and development efforts have led to the availability of β‐lactamase inhibitors (BLIs) with activity against extended‐spectrum β‐lactamases as well as Klebsiella pneumoniae carbapenemase (KPC)‐producing carbapenem‐resistant organisms (CRO). Nevertheless, there is still a lack of drugs that target metallo‐β‐lactamases (MBL), which hydrolyze carbapenems efficiently, and oxacillinases (OXA) often present in carbapenem‐resistant Acinetobacter baumannii. This review aims to provide a snapshot of microbiology, pharmacology, and clinical data for currently available BL/BLI treatment options as well as agents in late stage development for CRO harboring various β‐lactamases including MBL and OXA‐enzymes. [ABSTRACT FROM AUTHOR]

The extended-spectrum β-lactamases (ESβLs) are bacterial enzymes capable of hydrolyzing penicillins, cephalosporins, and aztreonam. The prevalence of ESβL is increasing among clinically significant microorganisms worldwide, drastically reducing the therapeutic management of infectious diseases. The study aimed to determine the drug susceptibility of ESβL-positive clinical isolates acquired from patients hospitalized in Lodz, central Poland, and analyze the prevalence of specific genes, determining acquired resistance in these bacteria. The samples of ESβL-positive clinical isolates were gathered in 2022 from medical microbiological laboratories in the city of Lodz, central Poland. The strains were subjected to biochemical identification and antimicrobial susceptibility testing following EUCAST guidelines. The presence of studied genes (blaCTX-M, blaSHV, blaTEM, blaPER, blaVEB) was confirmed by PCR. Over 50% of studied isolates were resistant to gentamicin, cefepime, ceftazidime and ciprofloxacin. The most common ESβL gene was blaCTX-M. In most isolates, the resistance genes occurred simultaneously. The blaPER was not detected in any of the tested strains. ESβL-producing strains are largely susceptible to the currently available antibiotics. The observation of the coexistence of different genes in most clinical isolates is alarming. [ABSTRACT FROM AUTHOR]

Multiple drug resistance (MDR) has gained pronounced attention among Enterobacterales. The transfer of multiple antimicrobial resistance genes, frequently carried on conjugative incompatibility F (IncF) plasmids and facilitating interspecies resistance transmission, has been linked to Salmonella spp. and E. coli in broilers. In Egypt, the growing resistance is exacerbated by the limited clinical efficacy of many antimicrobials. In this study, IncF groups were screened and characterized in drug-resistant Salmonella spp. and E. coli isolated from broilers. The antimicrobial resistance profile, PCR-based replicon typing of bacterial isolates pre- and post-plasmid curing, and IncF replicon allele sequence typing were investigated. Five isolates of E. coli (5/31; 16.13%) and Salmonella spp. (5/36; 13.89%) were pan-susceptible to the examined antimicrobial agents, and 85.07% of tested isolates were MDR and extensively drug-resistant (XDR). Twelve MDR and XDR E. coli and Salmonella spp. isolates were examined for the existence of IncF replicons (FII, FIA, and FIB). They shared resistance to ampicillin, ampicillin/sulbactam, amoxicillin/clavulanate, doxycycline, cefotaxime, and colistin. All isolates carried from one to two IncF replicons. The FII-FIA-FIB+ and FII-FIA+FIB- were the predominant replicon patterns. FIB was the most frequently detected replicon after plasmid curing. Three XDR E. coli isolates that were resistant to 12–14 antimicrobials carried a newly FIB replicon allele with four nucleotide substitutions: C99→A, G112→T, C113→T, and G114→A. These findings suggest that broilers are a significant reservoir of IncF replicons with highly divergent IncF-FIB plasmid incompatibility groups circulating among XDR Enterobacterales. Supporting these data with additional comprehensive epidemiological studies involving replicons other than the IncF can provide insights for implementing efficient policies to prevent the spreading of new replicons to humans. [ABSTRACT FROM AUTHOR]

Background: The challenge of treating infections caused by multidrug-resistant Enterobacterales and Acinetobacter baumannii has significantly increased for medical professionals due to their resistance to conventional antibiotics. In such cases, colistin is employed as a final line of defense. This study was aimed to determine the in-vitro efficacy of colistin against multidrug-resistant gram-negative bacteria. Methods: The research was carried out in the bacteriology department of the Mohammed V Military Teaching Hospital in Rabat, Morocco. 321 isolates of multi-resistant Enterobacterales and Acinetobacter baumannii from various clinical samples were identified by standard microbiological protocols, and the Colistin minimum inhibitory concentrations value was determined using the microdilution method. Results: Of the 321 isolates included in the study, 76.3% were Enterobacterales and 23.6% were Acinetobacter baumannii. The minimum inhibitory analysis showed that 96.3% of the isolates were sensitive, while 3.7% were identified as resistant. The prevalence of resistance to colistin among multi-resistant Enterobacterales was 4.1%, and the MIC50 and MIC90 were 0.5 μg/ml and 1μg/ml respectively. Among the collected Acinetobacter baumannii isolates, the prevalence of colistin resistance was 2.6%, with the MIC50 and MIC90 of 0.5 μg/ml. Conclusion: The research indicates that colistin could be a viable treatment option for infections caused by multi-resistant Enterobacterales and Acinetobacter baumannii. [ABSTRACT FROM AUTHOR]

One Health surveillance involves the analysis of human, animal and environmental samples, recognising their interconnectedness in health systems. Such considerations are crucial to investigate the transmission of many pathogens, including drug-resistant bacteria and parasites. The highest rates of antimicrobial resistance (AMR)-associated deaths are observed in sub-Saharan Africa, where concurrently the waterborne parasitic disease schistosomiasis can be highly endemic in both humans and animals. Although there is growing acknowledgment of significant interactions between bacteria and parasites, knowledge of relationships between schistosomes, microbes and AMR remains inadequate. In addition, newly emergent research has revealed the previously underappreciated roles of animals and the environment in both AMR and schistosomiasis transmission. We consider shared environmental drivers and colonisation linkage in this narrative review, with a focus on extended-spectrum beta-lactamase-mediated resistance among bacteria from the Enterobacteriaceae family, which is exceedingly prevalent and responsible for a high burden of AMR-associated deaths. Then we examine novel findings from Malawi, where the landscapes of AMR and schistosomiasis are rapidly evolving, and make comparisons to other geographic areas with similar co-infection epidemiology. We identify several knowledge gaps that could be addressed in future research, including the need to characterise the impact of intestinal schistosomiasis and freshwater contact on intestinal AMR colonisation, before proposing a rationale for connecting AMR surveillance and schistosomiasis research within a One Health framework. [ABSTRACT FROM AUTHOR]

Purpose: To evaluate the benefit of targeted antibiotic prophylaxis (TAP) based on rectal swab culture in comparison with standard empiric antimicrobial prophylaxis in patients undergoing transrectal ultrasound-guided needle biopsy of the prostate (TRUS-BP), as well as to assess rate of fecal carriage of Fluoroquinolone-resistant Enterobacterales FQRE. Patients and methods: We prospectively analyzed data that randomized 157 patients within two groups: (G1) TAP according to rectal swab performed 10 days before PB; (G2): empirical antibiotic prophylaxis with ciprofloxacin. Prevalence of FQRE digestive carriage and risk factors were investigated. Incidence of infectious complications after (TRUS-BP) in each group was compared. Results: G2 included 80 patients versus 77 in G1. There was no difference between the two groups regarding age, diabetes, prostate volume, PSA, number of biopsy cores, and risk factors for FQRE. In G2, the prevalence of FQRE digestive carriage was 56.3% all related to E. coli species. In the case of digestive carriage of FQRE, TAP according to the rectal swab culture with third-generation cephalosporins was performed in 73.3%. Patients with FQRE had history of FQ use within the last 6 months in 17.8% (p = 0.03). Rate of febrile urinary tract infection after PB was 13% in G1 and 3.8% in G2 (p = 0.02). Conclusions: Incidence of FQ resistance in the intestinal flora of our local population was prevalent. Risk factor for resistance was the use of FQ within the last 6 months. TAP adapted to rectal swab, mainly with third-generation cephalosporins, significantly reduced the rate of infectious complications after (TRUS-BP). [ABSTRACT FROM AUTHOR]

Antimicrobial resistance poses a significant threat to global public health, especially for Enterobacterales. In this study, we investigated the distribution and antimicrobial resistance of Enterobacterales in children in the China Antimicrobial Surveillance Network (CHINET) in 2015–2021. In total, 81,681 strains isolated from children were collected in this period, accounting for 50.1% of Gram-negative organisms. The most frequently isolated Enterobacterales were Escherichia coli, Klebsiella spp., Salmonella spp., and Enterobacter spp. The main sources of the isolates were urine and the respiratory tract, accounting for 29.3% and 27.7% of isolates, respectively. The proportions of E. coli, Klebsiella pneumoniae, and Proteus mirabilis expressing extended-spectrum β-lactamase were 48.8%–57.6%, 49.3%–66.7%, and 23.1%–33.8%, respectively. The prevalence of carbapenem-resistant Enterobacterales was 5.7%–9.5%, which showed a decreasing trend from 2015 to 2021. The detection rates of carbapenem-resistant Klebsiella spp., carbapenem-resistant Enterobacter spp., and carbapenem-resistant E. coli were 14.1%–22.6%, 7.1%–15.7% and 2.0%–3.4%, respectively. In Enterobacterales, the resistance rates to ciprofloxacin were higher than to levofloxacin. However, the Enterobacterales strains were highly susceptible to amikacin, polymyxin B, and tigecycline. The resistance rate of Salmonella spp. to ampicillin was > 70%, whereas their resistance rate to ceftriaxone was < 30%. These findings indicate that the resistant rates of some Enterobacterales isolates in children to common antimicrobial agents show decreasing trends. Continuous monitoring of bacterial resistance should be strengthened to prevent and control the spread of drug-resistant bacteria. [ABSTRACT FROM AUTHOR]

AbstractThe bulb onion (Allium cepa) is second only to tomatoes in value of vegetable crops cultivated worldwide. Water-soaked lesions, bleaching and blight on leaves and slippery skin, sour skin, soft rot near the neck and centre rot on onion bulbs were observed in surveys of the onion fields, storage as well as fruit and vegetable markets of northwestern provinces of Iran in 2020. Thirty-four samples were collected from onion fields of East Azerbaijan, West Azerbaijan and Zanjan provinces and the central storage of Bonab city. Fifty bacterial strains were isolated from symptomatic samples. Pathogenicity of the strains was confirmed by inoculating on onion bulb cultivars Azarshahr and Ghermez Anari. Twenty-eight strains were able to induce soft rot on the inoculated sites of cut onion bulbs. Onion bulbs turned dark brown at lesion sites and became odorous over time. All pathogenic strains were Gram-negative, facultative aerobic and catalase positive. Strains mainly varied in starch and aesculin hydrolysis, potato rot and hypersensitive reaction. Pathogenic strains separated into four groups based on phenotypic assays. In the phylogenetic tree based on concatenated sequences of gyrB and infB genes, the strains were divided into four clusters containing the type strains of Enterobacter ludwigii, Klebsiella variicola, Proteus mirabilis and Pantoea agglomerans, confirming their identity as belonging to these four species. This is the first report of P. mirabilis as a plant pathogen and of K. variicola as a causal agent of onion bulb rot. Moreover, this is the first report of E. ludwigii and P. agglomerans associated with onion bulb rot in Iran. [ABSTRACT FROM AUTHOR]

Carbapenemase-producing Enterobacterales are increasingly being recognized in nosocomial infections. The performance of a flow cytometry-based rapid assay for their detection and differentiation was evaluated. This is a disruptive phenotypic technology, phenotypic and growth-independent, that searches for the lesions produced by drugs acting on cells after a short incubation time. Overall, 180 Gram-negative bacteria were studied, and results were compared with those obtained molecularly by PCR and phenotypically by 'KPC, MBL and OXA-48 Confirm Kit'. This phenotypic method was used as reference for comparison purposes. Susceptibility to carbapenems (imipenem, meropenem, and ertapenem) was determined by standard broth microdilution. Overall, 112 isolates (62.2%) were carbapenemase producers, 41 KPCs, 36 MβLs, and 31 OXA-48, and 4 strains were KPC + MβL co-producers. Sixty-eight isolates were carbapenemase-negative. The percentage of agreement, sensitivity, and specificity were calculated according to ISO 20776-2:2021. The FASTinov assay showed 97.7% agreement with the reference method for carbapenemase detection. Discrepant flow cytometry results were obtained in four isolates compared with both reference and PCR results. The sensitivity and specificity of this new technology were 95.3% and 98.5%, respectively, for KPCs, 97.6% and 99.3% for MβLs, and 96.9% and 98% for OXA-48 detection. In conclusion, we describe a rapid flow cytometry assay with high accuracy for carbapenemase detection and the differentiation of various carbapenemases, which should impact clinical microbiology laboratories and patient management. [ABSTRACT FROM AUTHOR]

In a retrospective multicenter study of 575 patients with bloodstream infections or pneumonia due to wild-type AmpC β-lactamase–producing Enterobacterales, species with low in vitro mutation rates for AmpC derepression were associated with fewer treatment failures due to AmpC overproduction (adjusted hazard ratio, 0.5 [95% CI,.2–.9]). However, compared to cefepime/carbapenems, using third-generation cephalosporins as definitive therapy remained associated with this adverse outcome (15% vs 1%). [ABSTRACT FROM AUTHOR]

Gram-negative antibiotic resistance continues to grow as a global problem due to the evolution and spread of β-lactamases. The early β-lactamase inhibitors (BLIs) are characterized by spectra limited to class A β-lactamases and ineffective against carbapenemases and most extended spectrum β-lactamases. In order to address this therapeutic need, newer BLIs were developed with the goal of treating carbapenemase producing, carbapenem resistant organisms (CRO), specifically targeting the Klebsiella pneumoniae carbapenemase (KPC). These BL/BLI combination drugs, avibactam/avibactam, meropenem/vaborbactam, and imipenem/relebactam, have proven to be indispensable tools in this effort. However, non-KPC mechanisms of resistance are rising in prevalence and increasingly challenging to treat. It is critical for clinicians to understand the unique spectra of these BL/BLIs with respect to non-KPC CRO. In Part 1of this 2-part series, we describe the non-KPC attributes of the newer BL/BLIs with a focus on utility against Enterobacterales and Pseudomonas aeruginosa. [ABSTRACT FROM AUTHOR]

Purpose: To evaluate the performance of the rapid colorimetric polymyxin B microelution (RCPEm) in determining polymyxin B resistance directly from Enterobacterales-positive blood cultures. Methods: A set volume of positive blood culture bottles (diluted 1:10) was inoculated into a glucose-broth-phenol red solution (NP solution), where a polymyxin B disk was previously eluted (final concentration of 3 µg/mL). Test was read each 1 h for up to 4 h. Color change from red/orange to yellow indicated resistant isolates. Results were compared to the reference method, broth microdilution (BMD), performed from colonies grown on solid media from the same blood culture bottle. Results: One hundred fifty-two Enterobacterales-positive blood cultures were evaluated, 22.4% (34/152) of them resistant to polymyxin B (including 6.6% with borderline MICs). When performing directly from positive blood cultures (RCPEm-BC), specificity and sensitivity were 99.1% and 94.1%, respectively. Of note, 79.4% (27/34) of truly resistant isolates required 3 h of incubation, compared to the 18 ± 2 h incubation that microtiter plates of BMD demand before reading can be performed. Conclusions: RCPEm directly from blood cultures has great potential to be part of the routine of clinical microbiology laboratories to establish polymyxin B susceptibility, impacting outcome of patients with bloodstream infections caused by carbapenem-resistant Enterobacterales. [ABSTRACT FROM AUTHOR]

Purpose: The current study evaluated the in vitro activities of ceftolozane/tazobactam (C/T), imipenem/relebactam (IMI/REL), and comparators against recent (2017–2021) clinical isolates of gram-negative bacilli from two countries in southern Europe. Methods: Nine clinical laboratories (two in Greece; seven in Italy) each collected up to 250 consecutive gram-negative isolates per year from lower respiratory tract, intraabdominal, urinary tract, and bloodstream infection samples. MICs were determined by the CLSI broth microdilution method and interpreted using 2022 EUCAST breakpoints. β-lactamase genes were identified in select β-lactam-nonsusceptible isolate subsets. Results: C/T inhibited the growth of 85–87% of Enterobacterales and 94–96% of ESBL-positive non-CRE NME (non-Morganellaceae Enterobacterales) isolates from both countries. IMI/REL inhibited 95–98% of NME, 100% of ESBL-positive non-CRE NME, and 98–99% of KPC-positive NME isolates from both countries. Country-specific differences in percent susceptible values for C/T, IMI/REL, meropenem, piperacillin/tazobactam, levofloxacin, and amikacin were more pronounced for Pseudomonas aeruginosa than Enterobacterales. C/T and IMI/REL both inhibited 84% of P. aeruginosa isolates from Greece and 91–92% of isolates from Italy. MBL rates were estimated as 4% of Enterobacterales and 10% of P. aeruginosa isolates from Greece compared to 1% of Enterobacterales and 3% of P. aeruginosa isolates from Italy. KPC rates among Enterobacterales isolates were similar in both countries (7–8%). OXA-48-like enzymes were only identified in Enterobacterales isolates from Italy (1%) while GES carbapenemase genes were only identified in P. aeruginosa isolates from Italy (2%). Conclusion: We conclude that C/T and IMI/REL may provide viable treatment options for many patients from Greece and Italy. [ABSTRACT FROM AUTHOR]

Bacterial soft rots are amongst the most economically important diseases that cause significant yield losses in various crops. A clear identification of the causal agents is required to develop management strategies. In 2022 and 2023, after the widespread occurrence of soft rot disease in sugar beet fields in the Firuzan region, Hamedan Province, Iran, the current study was conducted to identify and characterize the causal agents. A total of 38 bacterial isolates were obtained from sugar beet plants with soft rot symptoms and subjected to biochemical and phenotypical characterization and pathogenicity tests on healthy slices from potato tubers and sugar beet taproots. Twelve isolates from this study along with the type strain Pectobacterium carotovorum ICMP 5702 were selected for subsequent screening by BOX‐PCR. Six isolates were chosen for sequencing the 16SrRNA gene and phylogenetic analysis. In BLAST analyses, the pathogenic isolates S2, S9, S22, S11, S23 and 111 showed the highest similarity values (≥99%) with the reference sequences of Raoultella terrigena, Klebsiella michiganensis, Erwinia (Winslowiella) iniecta, Pantoea agglomerans and P. carotovorum, respectively. These isolates induced soft rot and maceration on plant materials from five species (bell pepper fruits, garlic cloves and slices from sugar beet taproot, potato tubers and carrot roots) 72 h after inoculation. In the greenhouse experiment, they caused soft rot symptoms in the taproots of 2‐month‐old sugar beet plants 3 weeks after inoculation. These soft rot agents had Gram‐negative, catalase‐positive and oxidase‐negative reactions, grew under both aerobic and anaerobic conditions, tolerated and grew at 37°C and 5% NaCl. In general, the results of this research showed that in addition to Pectobacterium, four other genera from the order Enterobacterales including Erwinia, Pantoea, Klebsiella and Raoultella, are amongst the causes of soft rot in sugar beet in Firuzan region of Hamedan. [ABSTRACT FROM AUTHOR]

Background: People living with HIV/AIDS (PLWHA) are prone to opportunistic bacterial infections caused by multidrug-resistant organisms. The aim of this study was to determine the susceptibility of Enterobacterales isolated from urine and stool samples of PLWA attending the BOYAMBI Hospital Center, Kinshasa, Democratic Republic of the Congo to commonly used antibiotics and to detect extended-spectrum β-lactamases (ESBLs) producers among the isolates. Methodology: A total of 163 HIV-infected patients attending the BOYAMBI Hospital, Kinshasa, DRC, were randomly selected for this study. Urine samples were collected from 108 patients, while stool samples were collected from 55 of them. Samples were cultured in MacConkey agar and identified using conventional microbiological methods. Antibiotic susceptibility on each isolate to selected antibiotics was performed by the disc diffusion method. Phenotypic detection of ESBL was done by the double-disc synergy test. Results: A total of 120 Enterobacterales were isolated from the samples of the 163 HIV-infected patients with 65 of 108 (60.2%) urine and 55 of 55 (100.0%) stool samples. Escherichia coli was the most frequent bacterial species from both urine and stool with 84 (70.0%), followed by Klebsiellaspecieswith23 (19.2%). Other bacterial pathogens were Citrobacter (n=6, 5.0%), Enterobacter (n=4, 3.3%), Proteus (n=2, 1.7%) and Morganella (n=1, 0.8%) species. Escherichia coli isolates were resistant to amoxicillin (90.5%), sulfamethoxazole-trimethoprim (81.0%), ciprofloxacin (77.4%), ceftriaxone (77.4%), ceftazidime (73.8%), amoxicillin–clavulanic acid (61.9%), imipenem (60.7%), and cefotaxime (50.0%). Klebsiella pneumoniae isolates were resistant to ceftazidime (95.7%), ceftriaxone (91.3%), imipenem (91.3%), ciprofloxacin (87%), sulfamethoxazole-trimethoprim (78.3%), cefotaxime (56.5%), and amoxicillin–clavulanic acid (52.2%). Citrobacter, Enterobacter, Morganella and Proteus species were resistant to the majority of antibiotics. The rate of ESBL production was 23.0% (28/120) with Citrobacter spp being the most frequent ESBL-producer, followed Klebsiella spp, Enterobacter spp and E. coli. Conclusion: The results obtained showed a high rate of ESBL-producing Enterobacterales isolates which were multi-drug resistant. Nitrofurantoin, gentamicin, chloramphenicol, cefixime and nalidixic acid were the most active antibiotics against the isolates. [ABSTRACT FROM AUTHOR]

Understanding the transmission dynamics of carbapenem-resistant Enterobacterales (CRE) is critical to addressing the escalating global threat of antimicrobial resistance (AMR). Although hospital transmission of CRE has been extensively studied, information on community transmission is lacking. To identify genomic clusters of CRE from two nearby institutions that may be indicative of community or inter-facility transmission. CRE isolates between January 1st, 2019 and December 31st, 2020 from two tertiary hospitals, detected in the respective routine microbiology laboratories, were collected and characterized by short-read whole-genome sequencing. A total of 272 CRE were collected, with Enterobacter cloacae complex (71/192, 37%) predominant in Heidelberg and Escherichia coli (19/80, 24%) in Mannheim. The most common carbapenem resistance gene, bla OXA-48 , was detected in 38% of CRE from both centres. Several putative transmission clusters were found, including six clusters of E. cloacae complex, five clusters of Klebsiella pneumoniae , four clusters of Citrobacter freundii , and two clusters each of Escherichia coli and K. aerogenes. No clusters involved isolates from both study centres, except for an ST22 C. freundii cluster. Globally circulating clones were identified between the two centres for ST131 E. coli , ST66 E. hormaechei , and ST22 C. freundii. This study found no widespread transmission clusters among isolates from both centres, suggesting a hospital-specific clonal structure. This suggests that CRE clusters involving both institutions may indicate emerging or circulating clones in the community, highlighting the need for intersectoral surveillance and data sharing. [ABSTRACT FROM AUTHOR]

Plasma-activated water (PAW) generated from tap water has gained attention as a disinfectant when used directly in its pure form. Little is known about the application of PAW for bacterial inactivation in aqueous environments because its use in fluids results in dilutions. We investigated the effect of PAW in aqueous suspensions simulating such dilutions, and we focused on the minimal addition of PAW volumes to bacterial aqueous suspensions still resulting in high inactivation rates. The antimicrobial effect was highly dependent on the activation of PAW. An increase in activation power from 90 to 100 W resulted in a greater microbial reduction with an identical 10 min activation time. The susceptibility to PAW dilutions was analyzed in detail regarding nine Gram-negative species out of Enterobacterales and other waterborne microorganisms as well as four Gram-positive species present in two different matrices, in saline and in tap water, at high concentrations simulating massive contamination situations. For this purpose, the PAW activation setting of 90 W and 30 min was defined in order to be able to differentiate the limitations of inactivation in individual bacterial species. The Gram-negatives in saline demonstrated susceptibility when one volume unit of PAW was added. However, twice the PAW volume was necessary for inactivation when bacteria were present in tap water. Gram-positive microorganisms were more robust, indicated by prolonged contact times before inactivation. Our results indicate that PAW can be used for bacterial decontamination processes in aqueous environments when added in surplus. Optimized activation settings such as electric power to generate PAW and the contact times to the samples increase the effect of the inactivation a wide range of bacteria, regardless of their resistance profiles. [ABSTRACT FROM AUTHOR]

Introduction: Raw diets have become popular in companion animal nutrition, but these diets may be contaminated with harmful bacteria because heat processing is not utilized to mitigate pathogens during the production process. We analyzed 24 commercially available frozen raw canine and feline diets for extended-spectrum beta-lactamase-producing Enterobacterales (ESBL-E). Methods: Samples were incubated in tryptic soy broth augmented with 50 µg/mL ampicillin to enrich for ESBL-E. ESBL-E were isolated using CHROMagar ESBL plates and isolate identification and antibiotic susceptibility testing were confirmed using the VITEK®2 instrument. Results: ESBL-E were isolated from 42% (10/24) of raw diets, with E. coli, Enterobacter cloacae complex and Klebsiella pneumoniae predominating. Most ESBL-E isolates (71%, 32/45) were multidrug-resistant. Direct plating of samples onto tryptic soy agar yielded bacterial counts >6 log10 for 2 samples from two diFFerent manufacturers. Conclusion: This preliminary study justifies further investigation into the potential contribution of raw diets to the dissemination of antibiotic resistant bacteria in companion animals and domestic living spaces. [ABSTRACT FROM AUTHOR]

The NG-Test CARBA 5 and Carbapenem-resistant K.N.I.V.O. Detection K-Set are lateral flow assays (LFAs) that rapidly detect five carbapenemases (KPC, NDM, IMP, VIM and OXA-48-like). We evaluated the effect of inoculum size on the performance of these two assays using 27 Enterobacterales isolates. Whole-genome sequencing (WGS) was used as the reference method. Using the NG-Test CARBA 5, eight Serratia spp. and six M. morganii isolates showed false-positive NDM results with a high inoculum. Using the Carbapenem-resistant K.N.I.V.O. Detection K-Set, eight M. morganii, four Serratia spp. and one K. pneumoniae isolates showed false-positive NDM and/or OXA-48-like bands at large inoculum sizes, while the other two M. morganii isolates demonstrated false-positive NDM and OXA-48-like results at all inoculum sizes. The false-positive bands varied in intensity. WGS confirmed that no carbapenemase gene was present. No protein sequence with a ≥50% identity to NDM or OXA-48-like enzymes was found. This study emphasizes the importance of assessing inoculum size in the diagnostic evaluation of LFAs. [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]

Background: Bacterial peritonitis (BP) in patients with gastrointestinal (GI) cancer has been poorly described, and its prevalence is unknown. Objectives: This study aimed to evaluate in patients with both GI cancer and ascites the prevalence of BP, associated features, mechanisms, prognosis, and the diagnostic performance of neutrophil count in ascites. Design: A retrospective, multicenter, observational study. Methods: All patients with GI cancer and ascites who underwent at least one paracentesis sample analyzed for bacteriology over a 1-year period were included. BP was defined by a positive ascites culture combined with clinical and/or biological signs compatible with infection. Secondary BP was defined as BP related to a direct intra-abdominal infectious source. Results: Five hundred fifty-seven ascites from 208 patients included were analyzed. Twenty-eight patients had at least one episode of BP and the annual prevalence rate of BP was 14%. Among the 28 patients with BP, 19 (65%) patients had proven secondary BP and 17 (59%) patients had multi-microbial BP, mainly due to Enterobacterales. A neutrophil count greater than 110/mm3 in ascites had negative and positive predictive values of 96% and 39%, respectively, for the diagnosis of BP. The median survival of patients with BP was 10 days (interquartile range 6–40) after the diagnosis. Conclusion: BP is not rare in patients with GI cancer and is associated with a poor short-term prognosis. When a patient with GI cancer is diagnosed with BP, a secondary cause should be sought. Further studies are needed to better define the best management of these patients. [ABSTRACT FROM AUTHOR]

La résistance des bactéries à Gram négatif aux antibiotiques, en particulier les β-lactamines, est désormais considérée comme un problème majeur de santé publique. Les principaux mécanismes de résistance aux β-lactamines chez les entérobactéries sont la production de β-lactamases à spectre étendu (BLSE) ou de carbapénémases, qui hydrolysent pratiquement toutes les β-lactamines. Cependant, une proportion substantielle de bacilles à Gram négatif résistants aux carbapénèmes ne produit pas de carbapénémase mais combine la surproduction d'une céphalosporinase et/ou d'une BLSE avec une très faible hydrolyse des pénèmes et une perméabilité réduite de la membrane externe. L'arrivée de nouveaux agents antibactériens actifs sur certaines de ces souches multirésistantes, comme les nouveaux inhibiteurs de β-lactamines, a marqué un tournant dans le traitement et représente un réel progrès. La connaissance approfondie des mécanismes de résistance est cruciale pour le choix de la molécule la plus efficace, et leur prescription nécessite une collaboration étroite entre microbiologistes, infectiologues, et médecins de soins intensifs. Si ces molécules sont significativement plus actives contre les souches résistantes que celles précédemment disponibles, leur spectre d'activité ne couvre pas l'ensemble des mécanismes de résistance chez les Gram négatifs, ni chez les autres espèces bactériennes potentiellement impliquées dans les infections polymicrobiennes. L'utilisation de ces nouveaux composés ne modifie pas les schémas antibiotiques en termes de durée et d'indication de l'antibiothérapie combinée, qui restent très limités. Resistance of Gram-negative bacteria to the most widely used antibiotics, particularly β-lactams, is now considered as major public health problem. The main resistance mechanisms to β-lactams in Enterobacterales are the production of extended spectrum β-lactamases (ESBL) or carbapenemases, which hydrolyze virtually all β-lactams. However, a substantial proportion of carbapenem-resistant Gram-negative bacilli do not produce carbapenemase but combine overproduction of a cephalosporinase and/or ESBL with very low penem hydrolysis and reduced outer membrane permeability. The arrival of new antibacterial agents active on some of these multidrug-resistant strains, such as new β-lactam inhibitors, has marked a turning point in treatment and represents real progress. In-depth knowledge of resistance mechanisms is crucial to the choice of the most effective molecule, and their prescription requires close collaboration between microbiologists, infectious disease specialists and intensive care physicians. While these compounds are significantly more active against resistant strains than those previously available, their spectrum of activity does not cover all resistance mechanisms in Gram-negatives, nor in other bacterial species potentially involved in polymicrobial infections. The use of these new compounds does not alter antibiotic regimens in terms of duration and indication of combined antibiotic therapy, which remain very limited. [ABSTRACT FROM AUTHOR]

Purpose: The MAST® D72C test is a phenotypical test which can detect ESBL and AmpC production in Enterobacterales. It can also identify the suspected presence of carbapenemase. The aim of the present study was to assess the sensitivity and specificity of this test and to discuss its usefulness in laboratories, especially those that use only an automated AST system. Method: The performance of the MAST® D72C test was assessed against a collection of 119 non-redundant Enterobacterales isolates characterized for their content in β-lactamases, and compared with that of the reference double disk synergy test. β-lactamase content was established from phenotypic and genotypic analyses to collect a broad diversity of resistance mechanisms and bacterial strains, including 30 ESBL-producing strains, 32 strains overproducing chromosomal AmpC, 10 strains producing plasmid-encoded AmpC, 12 carbapenemase-producing strains, 13 strains combining the production of several β-lactamases, and 22 strains that produced other β-lactamases. Results: The sensitivity and specificity for ESBL-detection were comparable with those of the synergy test, 75 versus 72.5%, and 94.9 versus 93.7%, respectively. The sensitivity and specificity for AmpC-detection were 71.7% and 100%, respectively, and sensitivity reached 78.7% if we excluded carbapenem-resistant isolates. Carbapenemase-detection sensitivity was 90%. Conclusion: These results show that the MAST® D72C test can be a useful tool for the detection of ESBL- and AmpC-production in clinical laboratories. [ABSTRACT FROM AUTHOR]

Antimicrobial resistance in uropathogens commonly causing urinary tract infections (UTIs) is a growing problem internationally. Pivmecillinam, the oral prodrug of mecillinam, has been used for over 40 years, primarily in Northern Europe and Canada. It is recommended in several countries as a first-line agent for the treatment of uncomplicated UTIs (uUTIs) and is now approved in the United States. We performed a structured literature search to review the available evidence on susceptibility of common uUTI-causing uropathogens to mecillinam. Among 38 studies included in this literature review, susceptibility rates for Escherichia coli to mecillinam—including resistant phenotypes such as extended-spectrum β-lactamase–producing E. coli —exceed 90% in most studies. High rates of susceptibility were also reported among many other uropathogens including Klebsiella spp. Enterobacter spp. and Citrobacter spp. In the current prescribing climate within the United States, pivmecillinam represents a viable first-line treatment option for patients with uUTI. [ABSTRACT FROM AUTHOR]

Background: The irrational use of antibiotics has led to the emergence of multidrug-resistant pathogens. The phenomenon of minimum inhibitory concentration (MIC) creeps occurs when organisms start showing raised MIC but within susceptible range giving an indication of the prevalence of rise in resistant pathogens in an area. Aims and Objectives: The aims and objectives of the study are to observe the susceptibility pattern among uropathogens and the possibility of MIC creeps among the Escherichia coli isolates sensitive to nitrofurantoin. Materials and Methods: This retrospective study was done in a tertiary care hospital in Kolkata to observe the susceptibility pattern among uropathogens and the possibility of MIC creeps. We took the data from all inpatient department and outpatient department patients sent for urine culture and sensitivity from October 1st, 2022, to September 30th, 2023. The antimicrobial susceptibility testing and MIC were conducted by VITEK Compact 2. The MIC of nitrofurantoin, one of the most widely used antibiotics for lower urinary tract infections, was calculated to investigate the phenomenon of MIC creep. All the statistical analyses were carried out using the Excel spreadsheet and OpenEpi version 3.01 platform. Results: In our study, a total of 631 urine samples were analyzed: 368 were positive with the most common isolate being E. coli (53%) followed by Klebsiella spp. (12%). Two percent of resistance was observed for fosfomycin and 8% for nitrofurantoin. Extended spectrum beta-lactamase (ESBL) producers E. coli was 127 (35%). Overall, 23/368 samples had a MIC ≥128 for nitrofurantoin. Among the ESBL producers, 13/127 had MIC ≥128 for nitrofurantoin. Conclusion: In the present study, it was observed that E. coli showed a reduced susceptibility for nitrofurantoin indicated by a creeping increase in MIC within normal range. Trends in rising MIC can be an alarming sign for using drugs such as nitrofurantoin judiciously. Antimicrobial stewardship practice should be strongly implemented in hospitals to curb rising resistance and for better prognosis of patients having infectious diseases. [ABSTRACT FROM AUTHOR]

Carbapenem-resistant Klebsiella pneumoniae (CR-KP) are a public health concern, causing infections with a high mortality rate, limited therapeutic options and challenging infection control strategies. In Portugal, the CR-KP rate has increased sharply, but the factors associated with this increase are poorly explored. In order to address this question, phylogenetic and resistome analysis were used to compare the draft genomes of 200 CR-KP isolates collected in 2017–2019 from five hospitals in the Lisbon region, Portugal. Most CR-KP belonged to sequence type (ST) 13 (29%), ST17 (15%), ST348 (13%), ST231 (12%) and ST147 (7%). Carbapenem resistance was conferred mostly by the presence of KPC-3 (74%) or OXA-181 (18%), which were associated with IncF/IncN and IncX plasmids, respectively. Almost all isolates were multi-drug resistant, harbouring resistance determinants to aminoglycosides, beta-lactams, trimethoprim, fosfomycin, quinolones and sulphonamides. In addition, 11% of isolates were resistant to colistin. Colonizing and infecting isolates were highly related, and most colonized patients (89%) reported a previous hospitalization. Moreover, among the 171 events of cross-dissemination identified by core genome multi-locus sequence typing data analysis (fewer than five allelic differences), 41 occurred between different hospitals and 130 occurred within the same hospital. The results suggest that CR-KP dissemination in the Lisbon region results from acquisition of carbapenemases in mobile genetic elements, influx of CR-KP into the hospitals by colonized ambulatory patients, and transmission of CR-KP within and between hospitals. Prudent use of carbapenems, patient screening at hospital entry, and improvement of infection control are needed to decrease the burden of CR-KP infection in Portugal. [ABSTRACT FROM AUTHOR]

The Infectious Diseases Society of America (IDSA) recommends a single dose of an aminoglycoside for uncomplicated cystitis caused by extended-spectrum beta-lactamase (ESBL)-producing Enterobacterales (ESBL-E) and difficult-to-treat Pseudomonas aeruginosa. However, there is very little recent clinical evidence to support this recommendation. The objective of this study was to evaluate the safety and efficacy of a single-dose aminoglycoside for cystitis caused by ESBL-E or Pseudomonas aeruginosa. This was a multicenter, retrospective, cohort study. Patients who received ≥3 days of standard of care were compared to patients who received a one-time dose of an aminoglycoside with or without a short course of effective therapy before. The primary outcome was the rate of relapse defined as requiring escalation of antibiotics or starting new antibiotic therapy within 14 days after the completion of antibiotics. A total of 66 patients were included in this study, with 33 patients in each arm. There were more males and complicated cystitis patients in the standard-of-care group. There was no difference found in the rate of relapse. The length of stay was significantly shorter in the aminoglycoside group (4.5 ± 4.4 days vs. 14.1 ± 10.1 days, p < 0.0001). A one-time dose of an aminoglycoside did not increase the risk of relapse and was associated with a shorter length of stay when used to treat cystitis caused by ESBL-E or Pseudomonas aeruginosa. [ABSTRACT FROM AUTHOR]