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The emission of glyphosate and antibiotic residues from human activities threatens the diversity and functioning of the microbial community. This study examines the impact of a glyphosate-based herbicide (GBH) and common antibiotics on Gram-negative bacteria within the ESKAPEE group (Enterococcus faecium, Staphylococcus aureus, Klebsiella pneumoniae, Acinetobacter baumannii, Pseudomonas aeruginosa, Enterobacter spp. and Escherichia coli). Ten strains, including type and multidrug-resistant strains for each species were analysed and eight antibiotics (cefotaxime, meropenem, aztreonam, ciprofloxacin, gentamicin, tigecycline, sulfamethoxazole-trimethoprim, and colistin) were combined with the GBH. While most combinations yielded additive or indifferent effects in 70 associations, antagonistic effects were observed with ciprofloxacin and gentamicin in five strains. GBH notably decreased the minimum inhibitory concentration of colistin in eight strains and displayed synergistic activity with meropenem against metallo-β-lactamase (MBL)-producing strains. Investigation into the effect of GBH properties on outer membrane permeability involved exposing strains to a combination of this GBH and vancomycin. Results indicated that GBH rendered strains sensitive to vancomycin, which is typically ineffective against Gram-negative bacteria. Furthermore, we examined the impact of GBH in combination with three carbapenem agents on 14 strains exhibiting varying carbapenem-resistance mechanisms to assess its effect on carbapenemase activity. The GBH efficiently inhibited MBL activity, demonstrating similar effects to EDTA (ethylenediaminetetraacetic acid). Chelating effect of GBH may have multifaceted impacts on bacterial cells, potentially by increasing outer membrane permeability and inactivating metalloenzyme activity. [ABSTRACT FROM AUTHOR]

Background: Carbapenem-resistant Acinetobacter baumannii (CRAB) frequently causes both healthcare-associated infections and nosocomial outbreaks in burn medicine/plastic surgery and beyond. Owing to the high antibiotic resistance, infections are difficult to treat, and patient outcomes are often compromised. The environmental persistence capability of CRAB favors its transmission in hospitals. A comprehensive analysis and understanding of CRAB epidemiology and microbiology are essential for guiding management. Methods: A three-year retrospective cohort study (2020–2022) was conducted in a German tertiary burn and plastic surgery center. In addition to epidemiological analyses, microbiological and molecular techniques, including whole-genome sequencing, were applied for the comprehensive examination of isolates from CRAB-positive patients. Results: During the study period, eight CRAB cases were found, corresponding to an overall incidence of 0.2 CRAB cases per 100 cases and an incidence density of 0.35 CRAB cases per 1000 patient-days. Six cases (75%) were treated in the burn intensive care unit, and four cases (50%) acquired CRAB in the hospital. Molecular analyses comprising 74 isolates supported the epidemiologic assumption that hospital acquisitions occurred within two separate clusters. In one of these clusters, environmental CRAB contamination of anesthesia equipment may have enabled transmission. Furthermore, molecular diversity of CRAB isolates within patients was observed. Conclusions: CRAB can pose a challenge in terms of infection prevention and control, especially if cases are clustered in time and space on a ward. Our study demonstrates that high-resolution phylogenetic analysis of several bacterial isolates from single patients can greatly aid in understanding transmission chains and helps to take precision control measures. [ABSTRACT FROM AUTHOR]

Objectives Temocillin, a carbapenem-sparing β-lactam antibiotic, is commonly used at the standard 4 g/day dosage for treating complicated urinary tract infections (cUTIs). However, pharmacokinetic/pharmacodynamic (PK/PD) data supporting this regimen is limited. This study evaluated the plasma pharmacokinetics (PK) and PTA of temocillin in non-critically ill cUTI patients with varying degrees of renal insufficiency (RI). Methods In this single-centre clinical study, 22 cUTI patients received a fixed 4 g/day (2 g q12h, intravenously) temocillin dose, irrespective of renal function (no RI: n  = 5, mild RI: n  = 8, moderate RI: n  = 9). Plasma samples were collected post-dosing for LC-MS analysis of total and unbound temocillin levels. Monte Carlo simulations were performed based on the established PK/PD target of ≥35% f T > MIC (minimal inhibitory concentration). Results Among patients, the highest plasma drug exposure and PK/PD target attainment were observed in those with moderate RI (median AUC0–12h = 1143 h.mg/L and % f T > MIC = 68%), followed by mild RI patients (median AUC0–12h = 918 h.mg/L and % f T > MIC = 34%), and the lowest in those with healthy kidney function (median AUC0–12h = 692 h.mg/L and % f T > MIC = 26%). Simulations indicated that the 4 g/day temocillin dose achieves 90% PTA only for glomerular filtration rate < 60 mL/min and MIC ≤ 8 mg/L. Conclusion The standard temocillin dose may need to be increased from 4 to 6 g/day to treat non-critically ill cUTI patients, in line with recent EUCAST recommendations. For patients with moderate RI, who experience higher exposure due to reduced renal drug clearance, 4 g/day temocillin remains appropriate. [ABSTRACT FROM AUTHOR]

Background Carbapenem-resistant Enterobacterales (CRE) bloodstream infections (BSIs) are a major threat to patients. To date, data on risk factors have been limited, with low internal and external validity. In this multicentre study, risk factors for CRE BSI were determined by comparison with two control groups: patients with carbapenem-susceptible Enterobacterales (CSE) BSI, and patients without Enterobacterales infection (uninfected patients). Methods A multicentre, case-control-control study was nested in a European prospective cohort study on CRE (EURECA). CRE BSI:CSE BSI matching was 1:1, CRE BSI:Uninfected patients matching was 1:3, based on hospital, ward and length of stay. Conditional logistic regression was applied. Results From March 2016 to November 2018, 73 CRE BSIs, 73 CSE BSIs and 219 uninfected patients were included from 18 European hospitals. For CRE versus CSE BSI, previous CRE colonization/infection [incidence rate ratio (IRR) 7.32; 95% CI 1.65–32.38) increased the risk. For CRE versus uninfected controls, independent risk factors included: older age (IRR 1.03; 95% CI 1.01–1.06), patient referral (long-term care facility: IRR 7.19; 95% CI 1.51–34.24; acute care hospital: IRR 5.26; 95% CI 1.61–17.11), previous colonization/infection with other MDR organisms (MDROs) (IRR 9.71; 95% CI 2.33–40.56), haemodialysis (IRR 8.59; 95% CI 1.82–40.53), invasive procedures (IRR 5.66; 95% CI 2.11–15.16), and β-lactam/β-lactamase inhibitor combinations (IRR 3.92; 95% CI 1.68–9.13) or third/fourth generation cephalosporin (IRR 2.75; 95% CI 1.06–7.11) exposure within 3 months before enrolment. Conclusions Evidence of previous CRE colonization/infection was a major risk factor for carbapenem resistance among Enterobacterales BSI. Compared with uninfected patients, evidence of previous MDRO colonization/infection and healthcare exposure were important risk factors for CRE BSI. Targeted screening, infection prevention and antimicrobial stewardship should focus on these high-risk patients. [ABSTRACT FROM AUTHOR]

Background People with cystic fibrosis (pwCF) are particularly susceptible to respiratory infections, including those caused by multidrug-resistant (MDR) pathogens. Ceftolozane/tazobactam (C/T) is an antibacterial agent combination active against MDR gram-negative bacteria that has shown promising results in isolates from pwCF. This subanalysis is the first extensive observation of real-world C/T use in pwCF. Methods The multicenter observational CONDUCT study included consecutive patients, some with cystic fibrosis, who received ≥1 dose of C/T at 28 centers throughout France. Patients were treated according to hospital standards and followed up until the end of C/T treatment (EOT). Results Among 260 patients who had received ≥1 dose of C/T, 63 were pwCF, including 12 with previous lung transplant. The median age was 34 years and 55.6% of patients were female. Pseudomonas aeruginosa was the most frequently isolated pathogen (n = 40/41 [97.6%]). Most tested P aeruginosa strains (n = 65/73 [91.5%]) and all other isolated strains (Escherichia coli , Citrobacter koseri , Proteus mirabilis , and Serratia marcescens) were susceptible to C/T. Most patients completed the treatment duration, including those with historical β-lactam hypersensitivity. Reasons for stopping treatment were planned EOT and improvement in condition; overall, 88.9% of patients (n = 56/63) experienced improvement in condition. No new safety signals were identified. Mean forced expiratory volume in 1 second improved from 1.33 L to 1.47 L before and after C/T treatment, respectively (n = 52; P =.057). Conclusions C/T treatment was well tolerated and effective in pwCF, including those with previous β-lactam hypersensitivity. [ABSTRACT FROM AUTHOR]

Introduction: Bloodstream infections caused by AmpC-producing Enterobacterales pose treatment challenges due to the risk of AmpC overproduction and treatment failure. Current guidelines recommend carbapenems or cefepime as optimal therapy. We aimed to evaluate empiric and definitive non-carbapenem regimens for these infections. Methods: In a retrospective study from June 2014 to March 2023, adult bacteremic patients with Enterobacter cloacae complex strains and Morganella morganii were evaluated. Demographic, clinical and lab data and outcomes were assessed. Results: The cohort comprised 120 bacteremic patients, 17 receiving empiric carbapenem and 103 non-carbapenem regimens. Both groups had similar Charlson and Norton scores and previous antimicrobial exposure. The most common sources of bacteremia were urinary, abdominal and central-line-associated sources. Empiric non-carbapenem regimens (primarily piperacillin–tazobactam and cephalosporins) were not associated with recurrent bacteremia or 30-day mortality. Definitive regimens included mainly carbapenems (n = 41) and ciprofloxacin (n = 46). Beta-lactams were administered to 25 patients. Recurrent bacteremia and 30-day mortality rates were similar among treatment groups. Ciprofloxacin showed comparable outcomes to carbapenems, however, severity of illness among these patients was lower. Conclusions: Empiric and definitive non-carbapenem regimens for bacteremia with AmpC-producing organisms were not associated with treatment failure or increased 30-day mortality. Ciprofloxacin appears promising for selected, stable patients, potentially enabling early discharge. [ABSTRACT FROM AUTHOR]

Background: Antimicrobial stewardship (AMS) for ventilator-associated pneumonia (VAP) or ventilated hospital-acquired pneumonia (vHAP) in extended-spectrum β-lactamase-producing Enterobacterales (ESBL-E) carriers is challenging. BioFire® FilmArray® Pneumonia plus Panel (mPCR) can detect bacteria and antibiotic resistance genes, including blaCTX-M, the most common ESBL-encoding gene. Methods: This monocentric, prospective study was conducted on a group of ESBL-E carriers from March 2020 to August 2022. The primary objective was to evaluate the concordance between the results of mPCR and conventional culture performed on respiratory samples of ESBL-E carriers to investigate suspected VAP/vHAP. The secondary objective was to appraise the impact of performing or not mPCR on initial antibiotic therapy adequacy in ESBL-E carriers with confirmed VAP/vHAP. Results: Over the study period, 294 patients with ESBL-E carriage were admitted to the ICU, of who 168 (57%) were mechanically ventilated. (i) Diagnostic performance of mPCR was evaluated in suspected 41 episodes of VAP/vHAP: blaCTX-M gene was detected in 15/41 (37%) episodes, where 9/15 (60%) were confirmed ESBL-E-induced pneumonia. The culture and blaCTX-M were concordant in 35/41 (85%) episodes, and in all episodes where blaCTX-M was negative (n = 26), the culture never detected ESBL-E. (ii) The impact of mPCR on initial antibiotic therapy adequacy was assessed in 95 episodes of confirmed VAP/vHAP (22 episodes were tested with mPCR and 73 without); 47 (49%) episodes were ESBL-E-induced, and 24 (25%) were carbapenem-resistant bacteria-induced. The use of mPCR was significantly associated with higher prescription of adequate empirical antibiotic therapy in the multivariable logistic regression (adjusted odds ratio (aOR) (95% CI) of 7.5 (2.1–35.9), p = 0.004), propensity-weighting (aOR of 5.9 (1.6–22.1), p = 0.008), and matching-cohort models (aOR of 5.8 (1.5–22.1), p = 0.01). Conclusion: mPCR blaCTX-M showed an excellent diagnostic value to rule out the diagnosis of ESBL-E related pneumonia in ESBL-E carriers with suspected VAP/vHAP. In addition, in patients with confirmed VAP/vHAP, a mPCR-based antibiotic therapy was associated with an increased prescription of adequate empirical antibiotic therapy. Performing mPCR on respiratory samples seems to be a promising tool in ESBL-E carriers with suspected vHAP/VAP. However, if mPCR is used in very low pre-test clinical probability of pneumonia, due to the high sensitivity and the rate of overdiagnosed pneumonia, the risk of overconsumption of carbapenem may prevail. Further studies are warranted. [ABSTRACT FROM AUTHOR]

This study was carried out to investigate the biofilm formation capacity of carbapenem resistant P. aeruginosa strains isolated from cattle carcasses by using qualitative and quantitative methods, and also to determine the presence of major carbapenemase and quorum sensing genes. In the study, 13 P. aeruginosa strains, each isolated from a different cattle carcass surface and confirmed by molecular methods, were used as materials. Determination of carbapenem resistance was carried out by disk diffusion method. The presence of blaKPC, blaOXA-48, blaNDM, blaVIM, and blaIMP genes was investigated by PCR. Biofilm production was determined by qualitative and quantitative methods. In order to detect quorum sensing systems, the presence of lasI, lasR, rhlI, and rhlR genes was investigated by PCR. In the study, all P. aeruginosa strains were found to be resistant to at least one of the carbapenems tested. Carbapenemase genes could not be detected in any isolate. All isolates showing carbapenem resistance were found to be quantitatively strong biofilm producers. According to PCR analyses, 12 of the 13 isolates analyzed (92.3%) were found to contain all lasI, lasR, rhlI and rhlR genes. It was determined that one isolate (7.69%) contained only lasR and rhlR genes. With this study, it was determined that carbapenem resistance and biofilm production in P. aeruginosa strains of animal origin are related. [ABSTRACT FROM AUTHOR]

To assess the effectiveness of colistin (administered as colistimethate sodium-CMS) and polymyxin B (PMB) for the treatment of bloodstream infections (BSIs) caused by carbapenem-resistant Klebsiella pneumoniae (CRKP). This retrospective cohort included hospitalized adult patients with CRKP BSIs from a single tertiary-care hospital. A univariate analysis comparing CMS and PMB groups was carried out and an inverse-probability propensity score (IPPS) was created. An IPPS-adjusted Cox regression model for 30-day mortality was performed including covariates potentially associated with mortality. A total of 100 patients with CRKP BSI (87 were KPC-producing isolates) were included. The 30-day mortality was 42.0 %:17/46 (38.8 %) and 25/54 (44.6 %) patients of CMS and PMB groups, respectively, P = 0.54 (incidence rate, 18.9 and 21.7/1000 patients-day in CMS and PMB groups, respectively, P = 0.62). No statistically significant difference in 30-day mortality rate was observed in a model adjusted for Pitt bacteremia score, high-risk primary site and IPPS, which included age, intensive care unit admission, minimal inhibitory concentration, previous colonization by CRKP, diabetes mellitus, malignancy, neutropenia, meropenem use before BSI, adjuvant therapy with meropenem and amikacin, and time to start polymyxin. Acute kidney injury (AKI) occurred in 52.0 % of patients, with no significant differences between groups (47.8 % and 57.4 % for CMS and PMB, respectively, P = 0.83). In-hospital mortality was 47,7 % and 50.0 % in CMS and PMB groups, respectively, P = 0.82. There was no difference in 30-day mortality and AKI rates among patients with CRKP BSI treated with PMB or CMS. [ABSTRACT FROM AUTHOR]

Resistance to last-resort antibiotics is a global threat to public health. Therefore, surveillance and monitoring systems for antimicrobial resistance should be established on a national and international scale. For the development of a One Health surveillance system, we collected exemplary data on carbapenem and colistin-resistant bacterial isolates from human, animal, food, and environmental sources. We pooled secondary data from routine screenings, hospital outbreak investigations, and studies on antimicrobial resistance. For a joint One Health evaluation, this study incorporates epidemiological metadata with phenotypic resistance information and molecular data on the isolate level. To harmonise the heterogeneous original information for the intended use, we developed a generic strategy. By defining and categorising variables, followed by plausibility checks, we created a catalogue for prospective data collections and applied it to our dataset, enabling us to perform preliminary descriptive statistical analyses. This study shows the complexity of data management using heterogeneous secondary data pools and gives an insight into the early stages of the development of an AMR surveillance programme using secondary data. [ABSTRACT FROM AUTHOR]

Purpose: The World Health Organization has identified Klebsiella pneumoniae (KP) as a significant threat to global public health. The rising threat of carbapenem-resistant Klebsiella pneumoniae (CRKP) leads to prolonged hospital stays and higher medical costs, necessitating faster diagnostic methods. Traditional antibiotic susceptibility testing (AST) methods demand at least 4 days, requiring 3 days on average for culturing and isolating the bacteria and identifying the species using matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF MS), plus an extra day for interpreting AST results. This lengthy process makes traditional methods too slow for urgent clinical situations requiring rapid decision-making, potentially hindering prompt treatment decisions, especially for fast-spreading infections such as those caused by CRKP. This research leverages a cutting-edge diagnostic method that utilizes an artificial intelligence-clinical decision support system (AI-CDSS). It incorporates machine learning algorithms for the swift and precise detection of carbapenem-resistant and colistin-resistant strains. Patients and Methods: We selected 4307 KP samples out of a total of 52,827 bacterial samples due to concerns about multi-drug resistance using MALDI-TOF MS and Vitek-2 systems for AST. It involved thorough data preprocessing, feature extraction, and machine learning model training fine-tuned with GridSearchCV and 5-fold cross-validation, resulting in high predictive accuracy, as demonstrated by the receiver operating characteristic and area under the curve (AUC) scores, laying the groundwork for our AI-CDSS. Results: MALDI-TOF MS analysis revealed distinct intensity profiles differentiating CRKP and susceptible strains, as well as colistin-resistant Klebsiella pneumoniae (CoRKP) and susceptible strains. The Random Forest Classifier demonstrated superior discriminatory power, with an AUC of 0.96 for detecting CRKP and 0.98 for detecting CoRKP. Conclusion: Integrating MALDI-TOF MS with machine learning in an AI-CDSS has greatly expedited the detection of KP resistance by approximately 1 day. This system offers timely guidance, potentially enhancing clinical decision-making and improving treatment outcomes for KP infections. [ABSTRACT FROM AUTHOR]

Abstract Background Carbapenem-resistant Acinetobacter baumannii (CRAB) frequently causes both healthcare-associated infections and nosocomial outbreaks in burn medicine/plastic surgery and beyond. Owing to the high antibiotic resistance, infections are difficult to treat, and patient outcomes are often compromised. The environmental persistence capability of CRAB favors its transmission in hospitals. A comprehensive analysis and understanding of CRAB epidemiology and microbiology are essential for guiding management. Methods A three-year retrospective cohort study (2020–2022) was conducted in a German tertiary burn and plastic surgery center. In addition to epidemiological analyses, microbiological and molecular techniques, including whole-genome sequencing, were applied for the comprehensive examination of isolates from CRAB-positive patients. Results During the study period, eight CRAB cases were found, corresponding to an overall incidence of 0.2 CRAB cases per 100 cases and an incidence density of 0.35 CRAB cases per 1000 patient-days. Six cases (75%) were treated in the burn intensive care unit, and four cases (50%) acquired CRAB in the hospital. Molecular analyses comprising 74 isolates supported the epidemiologic assumption that hospital acquisitions occurred within two separate clusters. In one of these clusters, environmental CRAB contamination of anesthesia equipment may have enabled transmission. Furthermore, molecular diversity of CRAB isolates within patients was observed. Conclusions CRAB can pose a challenge in terms of infection prevention and control, especially if cases are clustered in time and space on a ward. Our study demonstrates that high-resolution phylogenetic analysis of several bacterial isolates from single patients can greatly aid in understanding transmission chains and helps to take precision control measures.

Background: Pre-extensively drug-resistant tuberculosis (pre-XDR-TB), defined as multidrug-resistant TB (MDR-TB) with additional resistance to any fluoroquinolone (FQ) is difficult to treat. We assessed whether the use of new or repurposed drugs (bedaquiline, delamanid, linezolid, carbapenem, clofazimine, pretomanid) mitigated treatment failure of pre-XDR-TB. Methods: MDR-TB patients managed in the Taiwan MDR-TB consortium between July 2009–December 2019 were eligible. Treatment outcomes at 30 months were assessed. Logistic regression models were constructed to investigate factors associated with treatment outcomes. Results: 109 patients with FQ-resistant MDR-TB and 218 patients with FQ-susceptible MDR-TB were included. 60 (55.1%) patients with FQ-resistant MDR-TB and 63 (28.9%) patients with FQ-susceptible MDR-TB have been treated with new or repurposed drugs (p

Abstract Background Antimicrobial stewardship (AMS) for ventilator-associated pneumonia (VAP) or ventilated hospital-acquired pneumonia (vHAP) in extended-spectrum β-lactamase-producing Enterobacterales (ESBL-E) carriers is challenging. BioFire® FilmArray® Pneumonia plus Panel (mPCR) can detect bacteria and antibiotic resistance genes, including bla CTX-M, the most common ESBL-encoding gene. Methods This monocentric, prospective study was conducted on a group of ESBL-E carriers from March 2020 to August 2022. The primary objective was to evaluate the concordance between the results of mPCR and conventional culture performed on respiratory samples of ESBL-E carriers to investigate suspected VAP/vHAP. The secondary objective was to appraise the impact of performing or not mPCR on initial antibiotic therapy adequacy in ESBL-E carriers with confirmed VAP/vHAP. Results Over the study period, 294 patients with ESBL-E carriage were admitted to the ICU, of who 168 (57%) were mechanically ventilated. (i) Diagnostic performance of mPCR was evaluated in suspected 41 episodes of VAP/vHAP: bla CTX-M gene was detected in 15/41 (37%) episodes, where 9/15 (60%) were confirmed ESBL-E-induced pneumonia. The culture and bla CTX-M were concordant in 35/41 (85%) episodes, and in all episodes where bla CTX-M was negative (n = 26), the culture never detected ESBL-E. (ii) The impact of mPCR on initial antibiotic therapy adequacy was assessed in 95 episodes of confirmed VAP/vHAP (22 episodes were tested with mPCR and 73 without); 47 (49%) episodes were ESBL-E-induced, and 24 (25%) were carbapenem-resistant bacteria-induced. The use of mPCR was significantly associated with higher prescription of adequate empirical antibiotic therapy in the multivariable logistic regression (adjusted odds ratio (aOR) (95% CI) of 7.5 (2.1–35.9), p = 0.004), propensity-weighting (aOR of 5.9 (1.6–22.1), p = 0.008), and matching-cohort models (aOR of 5.8 (1.5–22.1), p = 0.01). Conclusion mPCR bla CTX-M showed an excellent diagnostic value to rule out the diagnosis of ESBL-E related pneumonia in ESBL-E carriers with suspected VAP/vHAP. In addition, in patients with confirmed VAP/vHAP, a mPCR-based antibiotic therapy was associated with an increased prescription of adequate empirical antibiotic therapy. Performing mPCR on respiratory samples seems to be a promising tool in ESBL-E carriers with suspected vHAP/VAP. However, if mPCR is used in very low pre-test clinical probability of pneumonia, due to the high sensitivity and the rate of overdiagnosed pneumonia, the risk of overconsumption of carbapenem may prevail. Further studies are warranted.

Specific data concerning the efficacy of alternative antibiotics for carbapenems against complicated urinary tract infections (cUTIs) attributed to antimicrobial-resistant (AMR) uropathogens are lacking. This study aimed to assess the efficacy of carbapenems and non-carbapenem antibiotics in the clinical outcomes of cUTIs caused by AMR uropathogens. In this systematic review and meta-analysis, databases, including MEDLINE/PubMed, the Cochrane Library, Embase and ClinicalTrials.gov , were searched. The study eligibility criteria were research articles conducted as randomised controlled trials that evaluated the composite outcomes of cUTIs. Participants were adult patients with cUTIs caused by gram-negative uropathogens resistant to third-generation cephalosporins. The intervention involved a non-carbapenem class of antimicrobial agents with in vitro activities against gram-negative uropathogens resistant to third-generation cephalosporins. Two independent researchers assessed the risk-of-bias using the second version of the Cochrane risk-of-bias tool for randomised trials. The treatment effects on each outcome were estimated as a risk ratio (RR) with a 95 % confidence interval (CI) using the random-effects model. Heterogeneity was assessed using the Cochrane Q-test and I2 statistics. Through database searches, 955 articles were retrieved. After screening the titles and abstracts, 52 articles were screened in full text. Finally, 12 studies met the inclusion criteria. No significant differences in efficacy were observed between alternative antibiotics and carbapenems (composite outcome, RR, 0.96; 95 % CI, 0.63–1.49; I2 = 21 %; low certainty of evidence). Alternative antibiotics had clinical efficacy similar to that of carbapenems for treating patients with cUTI caused by gram-negative uropathogens resistant to third-generation cephalosporins. [ABSTRACT FROM AUTHOR]

During nationwide Fantimicrobial surveillance (Korea Global Antimicrobial Resistance Surveillance System [Kor-GLASS]), the recent emergence of non-oxacillinase (OXA)-23 production by carbapenem-resistant Acinetobacter baumannii (CRAB) isolates was noted. In this study, we evaluated resistance mechanisms other than OXA-23 production to elucidate the shift in considerable CRAB clones. The presence of OXA carbapenemase genes, such as blaOXA-23, blaOXA-24, blaOXA-58, and blaOXA-51-ISAba1, was determined by PCR. Other carbapenemase genes, such as blaIMP, blaVIM, blaNDM, blaKPC, blaGES, and blaOXA-48 , were determined using sequencing. Strains lacking carbapenemase genes were subjected to whole genome sequencing, and resistance genes were analyzed using ResFinder. Four CRAB strains were collected through a Kor-GLASS study in 2022, in which OXA-23 production was not identified. The carbapenemase genotypes of the four CRAB strains lacking blaOXA-23 were blaOXA-51-ISAba1, blaOXA-66/ACD25, blaOXA-182, and blaNDM-1. To the best of our knowledge, this is the f irst study to identify CRAB producing New Delhi metallo-β-lactamase (NDM)-1 in Korea. In conclusion, domestic CRAB resistance mechanisms may undergo subtle changes. Continuous observations are required to monitor the emergence of new clones.

Introduction: Carbapenem-resistant Enterobacteriaceae (CRE) epidemiology among liver transplant (LT) recipients is variable. We studied the impact of CRE colonization and infection on LT recipients’ outcomes. Methods: This observational cohort study included consecutive adult LT recipients between January 2019 and December 2020 at Curry Cabral Hospital, Lisbon, Portugal. Primary exposures were CRE colonization (rectal swabs under a screening program) and infection within 1 year of index LT. Primary endpoint was graft failure within 1 year of the index LT. Results: Among 209 patients, the median (interquartile range [IQR]) age was 57 (47–64) years and 155 (74.2%) were male. CRE colonization was identified in 28 (13.4%) patients during the first year posttransplant (median [IQR] number of rectal swabs per patient of 4 [2–7]). CRE resistance genes identified were OXA48 in 8 (3.6%) patients, KPC in 19 (67.9%) patients, and VIM in 1 (3.6%) patient. Any bacterial/fungal and CRE infections were diagnosed in 88 (42.1%) and 6 (2.9%) patients, respectively, during the first year posttransplant. After adjusting for confounders, neither CRE colonization (aOR [95% CI] = 1.83 [0.71–4.70]; p = 0.21) nor infection (aOR [95% CI] = 1.35 [0.17–11.06]; p = 0.78) was associated with graft failure within 1 year of index LT. Discussion/Conclusion: Under a screening program, CRE colonization and infection prevalence was low and neither was associated with graft failure.

Objectives: Antibiotic-resistant Klebsiella pneumoniae is a human pathogen of major global concern due to its ability to cause multiple severe diseases that are often difficult to treat therapeutically. This study aimed to investigate the resistome of local clinical K. pneumoniae isolates. Methods: Herein, we used a whole genome sequencing approach and bioinformatics tools to reconstruct the resistome of 10 clinical K. pneumoniae isolates and one clinical isolate of the closely related Klebsiella quasipneumoniae obtained from patients from three major hospitals in Trinidad, West Indies. Results: The results of the study revealed the presence of a complex antibiotic-resistant armoury among the local isolates with multiple resistance mechanisms involving (i) inactivation of antibiotics, (ii) efflux pumps, (iii) antibiotic target alteration, protection, and replacement against antibiotics, and (iv) altered porin protein that reduced the permeability to antibiotics. Several resistance genes such as blaCTX-M-15, blaTEM-1B, blaSHV-28, blaKPC-2, oqxA, sul1, tetD, aac(6′)-Ib-cr5, aph(6)-Id, and fosA6, which are known to confer resistance to antibiotics used to treat K. pneumoniae infections. In most cases, the resistance genes were flanked by mobile elements, including insertion sequences and transposons, which facilitate the spread of these genetic features among related organisms. Conclusion: This is the first comprehensive study to thoroughly investigate the resistome of clinical K. pneumoniae isolates and K. quasipneumoniae from Trinidad, West Indies. These findings suggest that monitoring K. pneumoniae and its genome-wide antibiotic resistance features in clinical strains would be of critical importance for guiding antibiotic stewardship programs and improving regional disease management systems for this pathogen.

Abstract Background Detection of carbapenem-resistant Pseudomonas aeruginosa (CR-PA) in humans is important to prevent transmission. However, the most optimal culture method to detect CR-PA is unknown. This systematic review aims to determine which culture method is most sensitive and which culture methods are used to detect CR-PA in humans. Second, to establish the most feasible culture method taking into account the turnaround time (TAT), and third, to provide an overview of the sampling sites used to detect carriage. Methods We systematically searched the electronic databases Embase, Medline Ovid, Cochrane, Scopus, CINAHL, and Web of Science until January 27, 2023. All diagnostic accuracy studies comparing two or more culture methods to detect CR-PA and recent outbreak or surveillance reports on CR-PA carriage or infection in humans, which describe culture methods and their results, were eligible for inclusion. We used QUADAS-2 guideline for diagnostic accuracy studies and the STROBE or ORION guideline for outbreak-surveillance studies to assess the risk of bias. Results Six diagnostic accuracy studies were included. An enrichment broth was found to increase the detection of CR-PA. Using an enrichment broth extended the TAT by 18–24 h, yet selective media could reduce the TAT by 24 h compared to routine media. In total, 124 outbreak-surveillance studies were included, of which 17 studies with surveillance samples and 116 studies with clinical samples. In outbreak-surveillance studies with surveillance samples, perianal, rectal swabs or stools were the most common sampling site/specimen (13/17, 76%). A large variety was observed in whether and which kind of enrichment broth and selective media were used. Conclusions We found a benefit of using an enrichment step prior to inoculation of the material onto selective media for the detection of CR-PA. More research is needed to determine the most sensitive sampling site and culture method. Trail registration: This study was registered in the PROSPERO International prospective register of systematic reviews (registration number: CRD42020207390, http://www.crd.york.ac.uk/PROSPERO/display_record.asp?ID=CRD42020207390 ).

Acinetobacter baumannii is a non-fermentative Gram-negative bacterium that can cause nosocomial infections in critically ill patients. Carbapenem-resistant A. baumannii (CRAB) has spread rapidly in clinical settings and has become a key concern. The main objective of this study was to identify the distribution of integrons and biofilm-formation-related virulence genes in CRAB isolates. A total of 269 A. baumannii isolates (219 isolates of CRAB and 50 isolates of carbapenem-sensitive A. baumannii (CSAB)) were collected. Carbapenemase genes (blaKPC, blaVIM, blaIMP, blaNDM, and blaOXA-23-like) and biofilm-formation-related virulence genes (abal, bfms, bap, and cusE) were screened with PCR. Class 1 integron was screened with PCR, and common promoters and gene cassette arrays were determined with restriction pattern analysis combined with primer walking sequencing. Whole-genome sequencing was conducted, and data were analyzed for a blaOXA-23-like-negative isolate. All 219 CRAB isolates were negative for blaKPC, blaVIM, blaIMP, and blaNDM, while blaOXA-23-like was detected in 218 isolates. The detection rates for abal, bfms, bap, and cusE in 219 CRAB were 93.15%, 63.93%, 88.13%, and 77.63%, respectively. Class 1 integron was detected in 75 CRAB (34.25%) and in 3 CSAB. The single gene cassette array aacA4-catB8-aadA1 with relatively strong PcH2 promoter was detected in class 1 integrons. The blaOXA-23-like-negative CRAB isolate was revealed to be a new sequence type (Oxford 3272, Pasteur 2520) carrying blaOXA-72, blaOXA-259, and blaADC-26. In conclusion, blaOXA-23-like was the main reason for CRAB’s resistance to carbapenems. A new (Oxford 3272, Pasteur 2520) CRAB sequence type carrying the blaOXA-72, blaOXA-259, and blaADC-26 was reported.

Abstract Background The study aims were to evaluate the species distribution and antimicrobial resistance profile of Gram-negative pathogens isolated from specimens of intra-abdominal infections (IAI), urinary tract infections (UTI), respiratory tract infections (RTI), and blood stream infections (BSI) in emergency departments (EDs) in China. Methods From 2016 to 2019, 656 isolates were collected from 18 hospitals across China. Minimum inhibitory concentrations were determined by CLSI broth microdilution and interpreted according to CLSI M100 (2021) guidelines. In addition, organ-specific weighted incidence antibiograms (OSWIAs) were constructed. Results Escherichia coli (E. coli) and Klebsiella pneumoniae (K. pneumoniae) were the most common pathogens isolated from BSI, IAI and UTI, accounting for 80% of the Gram-negative clinical isolates, while Pseudomonas aeruginosa (P. aeruginosa) was mainly isolated from RTI. E. coli showed

Background: Acinetobacter baumannii, a common carbapenem-resistant gram-negative bacillus, usually causes nosocomial infections. Colistin has been used for carbapenem-resistant A. baumannii (CRAB) infections; however, only a few studies have evaluated colistin as a treatment option compared to appropriate controls. We investigated the effectiveness of colistin monotherapy in treating CRAB pneumonia compared to those treated without an active drug. Methods: Adult patients (≥ 18 years) with CRAB isolated from respiratory specimens were screened from September 2017 to August 2022. Only patients with pneumonia treated with colistin monotherapy (colistin group) were included and compared to those without any active antibiotics (no active antibiotics [NAA] group). The primary and secondary outcomes were 30-day all-cause mortality and acute kidney injury within 30 days. The inverse probability of the treatment-weighted Cox proportional hazard model was used to compare mortality between groups. Results: Among the 826 adult patients with CRAB in their respiratory specimens, 45 and 123 patients were included in the colistin and NAA groups, respectively. Most of the CRAB pneumonia (91.1%) cases were hospital-acquired pneumonia. The 30-day all-cause mortality rates in the colistin and NAA groups were 58.3% and 56.1%, respectively, and no difference was observed after adjustments (adjusted hazard ratio, 0.74; 95% CI, 0.47–1.17). The incidence of acute kidney injury was higher in the colistin group (65.3%) compared to the NAA group (39.0%) (P = 0.143). Conclusions: Colistin monotherapy did not significantly improve treatment outcomes for CRAB pneumonia. The development and evaluation of new antimicrobials for CRAB pneumonia should be advocated in clinical practice.

Il Kwon Bae, Jun Sung Hong Department of Companion Animal Health and Science, Silla University, Busan, South KoreaCorrespondence: Jun Sung Hong, Department of Companion Animal Health and Science, Silla University, 140 Baegyang-Daero (Blvd), 700beon-Gil Road, Sasang-Gu, Busan, 46958, South Korea, Email jumphong2@nate.comBackground: Clinical isolates of Acinetobacter species in South Korea are continuously exhibiting high rates of antimicrobial resistance to carbapenems, indicating that there are public health concerns among both healthcare-associated infections and community-associated infections. The aim of this study was to describe the prevalence and characteristics of carbapenem-resistant Acinetobacter isolates originating from community hospitals.Materials and Methods: A total of 817 non-duplicated Acinetobacter species were isolated from December 2022 to July 2023 at long-term care facilities and general hospitals in 16 regions geographically distributed throughout South Korea. Bacterial identification and antimicrobial susceptibility testing were performed using the VITEK-2 system. The bacteria were identified as Acinetobacter baumannii by blaOXA-51 PCR and as non-baumannii Acinetobacter species by rpoB sequence analysis. The carbapenem resistance genes (OXA-23, OXA-48, OXA-58, IMP, VIM, NDM, GES, and KPC) were identified via PCR and sequencing. The genetic relatedness of carbapenem-resistant A. baumannii (CRAB) isolates was assessed by multilocus sequence typing.Results: A total of 659 A. baumannii and 158 non-baumannii Acinetobacter isolates, comprising 19 different species, were identified in all 16 regions. The carbapenem resistance rate was 87.4% (n=576) for the A. baumannii isolates, and all the strains produced blaOXA-23. For non-baumannii Acinetobacter, the rate of carbapenem resistance was 8.9% (n=14); this resistance was primarily caused by blaOXA-23 (n=9), followed by blaNDM-1 (n=3) and blaVIM-2 (n=2). Of the 576 CRAB isolates, clonal complex 92 (CC92) was the predominant genotypes, followed by sequence type 229 (ST229), ST373, ST397, ST447, and ST620.Conclusion: Our results showed the distribution of Acinetobacter species and showed that CC92 CRAB clinical isolates with widespread production of blaOXA-23 were predominant in community hospitals. Our findings suggest that there is a need for urgent and effective methods to reduce carbapenem resistance in A. baumannii in South Korea.Keywords: Acinetobacter, carbapenem, carbapenemase, OXA-23, CC92, community hospitals

Aim: This study aimed to detect the carbapenem resistance of the Klebsiella pneumoniae strains, isolated from clinical specimens with genotypic and phenotypic methods. Material and Methods: A total of 87 Klebsiella pneumoniae strains whose carbapenem resistance was determined by disc diffusion method were included in the study. Carbapenemase was investigated using the combined disk method and polymerase chain reaction (PCR). Results: The evaluation of the PCR results demonstrated that OXA was detected in 60 (68.9%) samples, NDM was detected in 20 (22.9%), OXA + NDM in 5 (5.7%), and KPC was detected in 1 (1.1%) out of 87 clinical samples. Carbapenemase was not detected in one specimen with the PCR method. The results were found compatible with the combined disc test results for all isolates which were detected as only OXA, NDM, and KPC type carbapenemase positive. In 5 (5.7%) strains in which the co-existence of NDM and OXA type carbapenemases was detected by PCR, the combined disc method detected only OXA type carbapenemase. Conclusion: The combined disk method is inadequate in the presence of strains that have multiple carbapenemases, and also have OXA which is the most frequently detected carbapenemase in our hospital. EUCAST recommends verification by other methods in the presence of OXA-48. Genotypic methods can be used for confirmation testing. The detections of strains with NDM, multiple carbapenemases, and the first detection of KPC were striking in the study. Monitoring the spread of these strains in the hospital will be necessary for infection control.

Abstract Proteus mirabilis is a commensal bacterium dwelling in the gastrointestinal (GI) tract of humans and animals. Although New Delhi metallo-β-lactamase 1 (NDM-1) producing P. mirabilis is emerging as a threat, its epidemiology in our society remains largely unknown. LHPm1, the first P. mirabilis isolate harboring NDM-1, was detected from a companion dog that resides with a human owner. The whole-genome study revealed 20 different antimicrobial resistance (AMR) genes against various classes of antimicrobial agents, which corresponded to the MIC results. Genomic regions, including MDR genes, were identified with multiple variations and visualized in a comparative manner. In the whole-genome epidemiological analysis, multiple phylogroups were identified, revealing the genetic relationship of LHPm1 with other P. mirabilis strains carrying various AMR genes. These genetic findings offer comprehensive insights into NDM-1-producing P. mirabilis, underscoring the need for urgent control measures and surveillance programs using a “one health approach”.

Background: Detection of carbapenem-resistant Pseudomonas aeruginosa (CR-PA) in humans is important to prevent transmission. However, the most optimal culture method to detect CR-PA is unknown. This systematic review aims to determine which culture method is most sensitive and which culture methods are used to detect CR-PA in humans. Second, to establish the most feasible culture method taking into account the turnaround time (TAT), and third, to provide an overview of the sampling sites used to detect carriage. Methods: We systematically searched the electronic databases Embase, Medline Ovid, Cochrane, Scopus, CINAHL, and Web of Science until January 27, 2023. All diagnostic accuracy studies comparing two or more culture methods to detect CR-PA and recent outbreak or surveillance reports on CR-PA carriage or infection in humans, which describe culture methods and their results, were eligible for inclusion. We used QUADAS-2 guideline for diagnostic accuracy studies and the STROBE or ORION guideline for outbreak-surveillance studies to assess the risk of bias. Results: Six diagnostic accuracy studies were included. An enrichment broth was found to increase the detection of CR-PA. Using an enrichment broth extended the TAT by 18–24 h, yet selective media could reduce the TAT by 24 h compared to routine media. In total, 124 outbreak-surveillance studies were included, of which 17 studies with surveillance samples and 116 studies with clinical samples. In outbreak-surveillance studies with surveillance samples, perianal, rectal swabs or stools were the most common sampling site/specimen (13/17, 76%). A large variety was observed in whether and which kind of enrichment broth and selective media were used. Conclusions: We found a benefit of using an enrichment step prior to inoculation of the material onto selective media for the detection of CR-PA. More research is needed to determine the most sensitive sampling site and culture method. Trail registration: This study was registered in the PROSPERO International prospective register of systematic reviews (registration number: CRD42020207390, http://www.crd.york.ac.uk/PROSPERO/display_record.asp?ID=CRD42020207390). [ABSTRACT FROM AUTHOR]

Objectives To assess risk factors for carbapenem-resistant Pseudomonas aeruginosa (CR) and extended-β-lactam-resistant P. aeruginosa (EBR) infection/colonization, and to develop and compare tools for predicting isolation of CR and EBR from clinical cultures. Methods This retrospective study analysed hospitalized patients with positive P. aeruginosa cultures between 2015 and 2021. Two case–control analyses were performed to identify risk factors and develop scoring tools for distinguishing patients with CR versus carbapenem-susceptible (CS) P. aeruginosa and EBR versus CS P. aeruginosa. The performance of institutionally derived scores, externally derived scores and the presence/absence of key risk factors to predict CR and EBR were then compared. Results A total of 2379 patients were included. Of these, 8.3% had a positive culture for CR, 5.0% for EBR and 86.7% for CS P. aeruginosa. There was substantial overlap in risk factors for CR and EBR. Institutional risk scores demonstrated modestly higher area under the ROC curve values than external scores for predicting CR (0.67 versus 0.58) and EBR (0.76 versus 0.70). Assessing the presence/absence of ≥1 of the two strongest predictors (prior carbapenem use or CR isolation within 90 days) was slightly inferior to scoring tools for predicting CR, and comparable for predicting EBR. Conclusions Clinicians concerned about CR in P. aeruginosa should consider the likelihood of EBR when making treatment decisions. A simple approach of assessing recent history of CR isolation or carbapenem usage performed similarly to more complex scoring tools and offers a more pragmatic way of identifying patients who require coverage for resistant P. aeruginosa. [ABSTRACT FROM AUTHOR]

Carbapenems are antibiotics used for serious infections. The consumption of carbapenems has increased worldwide due to increasing microbial resistance. To investigate the effects of a carbapenem-restricted antimicrobial stewardship programme (ASP) on changes in the resistance profiles of infectious agents, the amount of antibiotics used, length of stay in the intensive care unit (ICU), mortality, and costs. Patients hospitalized in ICU between July 1st, 2020 and May 1st, 2021 were divided into two periods: the carbapenem-non-restricted period (CNRP); and the carbapenem-restricted period (CRP) in which alternative antibiotics to carbapenems were preferred during infection. The defined daily dose (DDD) per 100 patient-day methodology was used to calculate the antibiotic consumption. Of the 572 patients included in the study, 62.2% were male, and mean age was 70.5 years. In the blood culture the most frequently Gram-negative agent was Acinetobacter baumannii (25%). A. baumannii bloodstream infections with multidrug-resistant and extensively drug resistant micro-organisms were significantly different between the two periods (CNRP: 95.6% (N = 22), CRP: 66.6% (N = 8); P = 0.04). There was a gradual decrease in the incidence density and rate of nosocomial infection (P = 0.06), and a significant decrease in meropenem consumption between the two periods (CNRP vs CRP: 21.19 vs 6.37 DDD per 100 patient-days respectively; P = 0.007). ASP yielded US$8,600 of antibiotic cost savings and a total of 14% patient cost savings (P < 0.05) per patient. Combining an effective ASP with a comprehensive infection control programme may mitigate the emergence of antimicrobial-resistant bacteria. [ABSTRACT FROM AUTHOR]

The escalating threat of multidrug-resistant organisms necessitates constant exploration for novel antimicrobial agents. Eravacycline has emerged as a promising solution due to its unique chemical structure, which enhances potency and expands its spectrum of activity. This review provides a thorough examination of eravacycline, encompassing its in vitro activity against Gram-positive and Gram-negative aerobes, carbapenem-non-susceptible organisms, anaerobes, and other bacterial strains. Additionally, it evaluates evidence from clinical studies to establish its clinical effect and safety. Eravacycline, a synthetic fluorocycline, belongs to the tetracyclines class. Similar to other tetracycline, eravacycline exerts its antibacterial action by reversibly binding to the bacterial ribosomal 30S subunit. Eravacycline demonstrates potent in vitro activity against many Gram-positive and Gram-negative aerobes, anaerobes, and multidrug-resistant organisms. Randomized controlled trials and its associated meta-analysis affirm eravacycline's efficacy in treating complicated intra-abdominal infections. Moreover, real-world studies showcase eravacycline's adaptability and effectiveness in diverse clinical conditions, emphasizing its utility beyond labeled indications. Despite common gastrointestinal adverse events, eravacycline maintains an overall favorable safety profile, reinforcing its status as a tolerable antibiotic. However, ongoing research is essential for refining eravacycline's role, exploring combination therapy, and assessing its performance against biofilms, in combating challenging bacterial infections. [ABSTRACT FROM AUTHOR]

Background Antimicrobial stewardship programs can optimize antimicrobial use and have been federally mandated in all hospitals. However, best stewardship practices in immunocompromised patients with cancer are not well established. Methods An antimicrobial time out, in the form of an email, was sent to physicians caring for hospitalized patients reaching 5 days of therapy for targeted antimicrobials (daptomycin, linezolid, tigecycline, vancomycin, imipenem/cilastatin, meropenem) in a comprehensive cancer center. Physicians were to discontinue the antimicrobial if unnecessary or document a rationale for continuation. This is a quasi-experimental, interrupted time series analysis assessing antimicrobial use during the following times: period 1 (before time-out: January 2007-June 2010) and period 2 (after time-out: July 2010-March/2015). The primary antimicrobial consumption metric was mean duration of therapy. Days of therapy per 1000 patient-days were also assessed. Results Implementation of the time-out was associated with a significant decrease in mean duration of therapy for the following antimicrobials; daptomycin: −0.89 days (95% confidence interval [CI], −1.38 to −.41); linezolid: −0.89 days (95% CI, −1.27 to −.52); meropenem: −0.97 days (95% CI, −1.39 to −.56); tigecycline: −1.41 days (95% CI, −2.19 to −.63); P <.001 for each comparison. Days of therapy/1000 patient-days decreased significantly for meropenem (−43.49; 95% CI, −58.61 to −28.37; P <.001), tigecycline (−35.47; 95% CI, −44.94 to −26.00; P <.001), and daptomycin (−9.47; 95% CI, −15.25 to −3.68; P =.002). Discussion A passive day 5 time-out was associated with reduction in targeted antibiotic use in a cancer center and could potentially be successfully adopted to several settings and electronic health records. [ABSTRACT FROM AUTHOR]

Background In vitro–in vivo discordance in β-lactams' activities against metallo-ß-lactamase (MBL)-producing Enterobacterales has been described. We aimed to assess whether this discordance is attributed to the supra-physiologic zinc concentration in in vitro testing media. Methods A clinical and microbiological observational study of patients with bloodstream infections due to New Delhi metallo-ß-lactamase-producing Klebsiella pneumoniae was performed. Outcomes of patients treated empirically with non-MBL-active β-lactam therapy (carbapenems and ceftazidime/avibactam) and MBL-active β-lactam therapy (ceftazidime/avibactam + aztreonam) were documented. The patients' isolates were used to induce septicemia in mice, and survival upon meropenem treatment was recorded. Meropenem minimum inhibitory concentrations (MICs) were determined in standard media and in the presence of physiological zinc concentrations. Results Twenty-nine patients receiving empiric non-MBL-active β-lactams (median duration, 4 days) were compared with 29 receiving MBL-active β-lactams. The 14-day mortality rates were 21% and 14%, respectively. In the murine septicemia model, meropenem treatment resulted in protection from mortality (P <.0001). Meropenem MICs in the physiologic zinc concentration broth were 1- to >16-fold lower vs MICs in zinc-unadjusted broth (≥64 mg/L). Conclusions Our data provide foundational support to establish pharmacokinetic/pharmacodynamic relationships using MICs derived in physiologic zinc concentration, which may better predict β-lactam therapy outcome. [ABSTRACT FROM AUTHOR]

Acinetobacter baumannii , a common carbapenem-resistant gram-negative bacillus, usually causes nosocomial infections. Colistin has been used for carbapenem-resistant A. baumannii (CRAB) infections; however, only a few studies have evaluated colistin as a treatment option compared to appropriate controls. We investigated the effectiveness of colistin monotherapy in treating CRAB pneumonia compared to those treated without an active drug. Adult patients (≥ 18 years) with CRAB isolated from respiratory specimens were screened from September 2017 to August 2022. Only patients with pneumonia treated with colistin monotherapy (colistin group) were included and compared to those without any active antibiotics (no active antibiotics [NAA] group). The primary and secondary outcomes were 30-day all-cause mortality and acute kidney injury within 30 days. The inverse probability of the treatment-weighted Cox proportional hazard model was used to compare mortality between groups. Among the 826 adult patients with CRAB in their respiratory specimens, 45 and 123 patients were included in the colistin and NAA groups, respectively. Most of the CRAB pneumonia (91.1%) cases were hospital-acquired pneumonia. The 30-day all-cause mortality rates in the colistin and NAA groups were 58.3% and 56.1%, respectively, and no difference was observed after adjustments (adjusted hazard ratio, 0.74; 95% CI, 0.47–1.17). The incidence of acute kidney injury was higher in the colistin group (65.3%) compared to the NAA group (39.0%) (P = 0.143). Colistin monotherapy did not significantly improve treatment outcomes for CRAB pneumonia. The development and evaluation of new antimicrobials for CRAB pneumonia should be advocated in clinical practice. [ABSTRACT FROM AUTHOR]

Purpose of Review: Antimicrobial resistance is a growing threat to public health, leading to millions of antibiotic-resistant infections and thousands of deaths annually in the USA. One concerning issue is the rise of extended-spectrum beta-lactamase (ESBL)–producing Enterobacterales. Current treatments often involve intravenous carbapenems, leading to prolonged hospital stays and financial burdens. Recent Findings: To address this, new oral penem agents, tebipenem and sulopenem, are being investigated. They are administered as prodrugs, enhancing bioavailability before becoming active in the gastrointestinal tract, potentially treating multidrug-resistant infections in outpatient settings. Despite promise in clinical trials, challenges exist, such as tebipenem's renal excretion, requiring dose adjustments for kidney dysfunction. Additionally, sulopenem failed noninferiority margins in trials, and neither drug has established susceptibility testing standards. Summary: Tebipenem and sulopenem offer potential oral solutions for antimicrobial resistance, especially in urinary tract infections, but further research is needed for optimal dosing and susceptibility testing. [ABSTRACT FROM AUTHOR]

Aims Carbapenem-resistant Escherichia coli has been categorized as a pathogen of critical priority by the World Health Organization as it is highly infectious with high mortality and morbidity rates and widespread transmission potential. Carbapenem resistance is primarily mediated by carbapenemase-encoding genes and, additionally, through intrinsic factors. In India, over the years, carbapenemase-encoding genes have been reported from diverse clinically significant pathogens. The present study identifies E. coli of clinical origin that harbours bla OXA-144. Methods and results The study isolate was obtained from a tertiary referral hospital in northeast India. Carbapenemase production was investigated through culture on chromogenic agar and Rapidec Carba NP test as per manufacturer's instructions. Susceptibility of the isolate was performed by the Kirby–Bauer disc diffusion method and agar dilution method following CLSI guidelines. PCR targeting carbapenemase-encoding genes was performed, followed by transformation and conjugation experiments. Whole-genome sequencing of the isolate was done through the Illumina sequencing platform and the data were analysed using the Centre for Genomic Epidemiology database. BJD_EC180 is 6 919 180 bp in length and consists of six rRNA operons, 111 tRNA, and 6849 predicted protein-coding sequences. BJD_EC180 belonged to ST2437 and harboured the carbapenemase-encoding gene bla OXA-144 with ISAba1 upstream, along with multiple antibiotic resistance genes conferring clinical resistance towards beta-lactams, aminoglycosides, amphenicols, sulphonamides, tetracyclines, trimethoprim, and rifampin. Conclusions Carbapenem-resistant E. coli harbouring bla OXA-144 associated with insertion sequence pose a serious health threat as their mobilization into carbapenem non-susceptible strains that will contribute to the resistance burden and therefore, needs urgent monitoring. [ABSTRACT FROM AUTHOR]

Objectives Recently, reports on antimicrobial-resistant Bacteroides and Prevotella isolates have increased in the Netherlands. This urged the need for a surveillance study on the antimicrobial susceptibility profile of Bacteroides , Phocaeicola , Parabacteroides and Prevotella isolates consecutively isolated from human clinical specimens at eight different Dutch laboratories. Methods Each laboratory collected 20–25 Bacteroides (including Phocaeicola and Parabacteroides) and 10–15 Prevotella isolates for 3 months. At the national reference laboratory, the MICs of amoxicillin, amoxicillin/clavulanic acid, piperacillin/tazobactam, meropenem, imipenem, metronidazole, clindamycin, tetracycline and moxifloxacin were determined using agar dilution. Isolates with a high MIC of metronidazole or a carbapenem, or harbouring cfiA , were subjected to WGS. Results Bacteroides thetaiotaomicron/faecis isolates had the highest MIC90 values, whereas Bacteroides fragilis had the lowest MIC90 values for amoxicillin/clavulanic acid, piperacillin/tazobactam, meropenem, imipenem and moxifloxacin. The antimicrobial profiles of the different Prevotella species were similar, except for amoxicillin, for which the MIC50 ranged from 0.125 to 16 mg/L for Prevotella bivia and Prevotella buccae , respectively. Three isolates with high metronidazole MICs were sequenced, of which one Bacteroides thetaiotaomicron isolate harboured a plasmid-located nimE gene and a Prevotella melaninogenica isolate harboured a nimA gene chromosomally. Five Bacteroides isolates harboured a cfiA gene and three had an IS element upstream, resulting in high MICs of carbapenems. The other two isolates harboured no IS element upstream of the cfiA gene and had low MICs of carbapenems. Conclusions Variations in resistance between species were observed. To combat emerging resistance in anaerobes, monitoring resistance and conducting surveillance are essential. [ABSTRACT FROM AUTHOR]

The objective was to determine the presence of carbapenem resistance genes and plasmid resistance to colistin (mcr-1) in bacteria isolated from Musca domestica in a garbage dump near a hospital in Lima, Peru. Bacteria with phenotypic resistance to carbapenemics were isolated on CHROMagar mSuperCARBATM medium and colistin resistance profiling was performed using the colistin disk elution method. Detection of blaKPC, blaNDM, blaIMP, blaOXA-48, blaVIM and mcr-1 genes was performed by conventional PCR. The antimicrobial susceptibility profile was determined using the automated MicroScan system. We found that 31/38 strains had phenotypic resistance to carbapenemics and 26/38 strains had phenotypic resistance to colistin with a minimum inhibitory concentration = 4 µg/ml. Finally, we identified seven bacterial strains with carbapenem resistance genes (OXA-48 and KPC) and one bacterial strain with plasmid resistance to colistin (mcr-1). One Escherichia coli strain had three resistance genes: KPC, OXA-48 and mcr-1. [ABSTRACT FROM AUTHOR]

To date, three carbapenem resistance mechanisms have been identified: carbapenemase released from the pathogen, changes in the expression of the outer membrane OprD porin, and overexpression of the efflux pump MexAB-OprM. Twelve carbapenemase-negative carbapenem-resistant Pseudomonas aeruginosa strains, isolated from patients hospitalized at the University Hospital of Larissa, Central Greece, during 2023, which belonged to various sequence types (STs), were selected and were studied focusing on the characterization of their β-lactamases, on changes to OprD and its regulator MexT proteins, and on alterations to the MexAB-OprM regulator proteins encoded by the mexR, nalC, and nalD genes. Whole genome sequencing analysis revealed the presence of β-lactamase encoding genes, with blaPAO present in all isolates. Additionally, seven different genes of the oxacillinase family (blaOXA-35, blaOXA-50, blaOXA-395, blaOXA-396, blaOXA-486, blaOXA-488, blaOXA-494) were identified, with each strain harboring one to three of these. Regarding the OprD, five strains had truncated structures, at Loop 2, Loop 3, Loop 4, and Loop 9, while the remaining strains carried previously reported amino acid changes. Further, an additional strain had a truncated MexR; whereas, two other strains had totally modified NalC sequences. The active form of MexT, responsible for the downregulation of OprD production, as the intact sequence of the NalD protein, was found in all the strains studied. It is concluded that the truncated OprD, MexR, and NalC proteins, detected in eight strains, probably led to inactive proteins, contributing to carbapenem resistance. However, four strains carried known modifications in OprD, MexR, and NalC, as previously reported in both susceptible and resistant strains, a finding that indicates the complexity of carbapenem resistance in P. aeruginosa. [ABSTRACT FROM AUTHOR]

ABSTRACT Delayed time to antimicrobial susceptibility results can impact patients’ outcomes. Our study evaluated the impact of susceptibility turnaround time (TAT) and inadequate empiric antibacterial therapy (IET) in patients with bloodstream infections (BSI) caused by Enterobacterales (ENT) species on in-hospital mortality and length of stay (LOS). This retrospective, multicenter investigation which included 29,570 blood ENT-positive admissions across 161 US healthcare facilities evaluated the association between antimicrobial susceptibility testing (AST) TAT, carbapenem susceptibility, and empiric therapy on post-BSI in-hospital mortality and LOS following an ENT BSI event in adult patients. After adjusting for outcomes covariates, post-BSI in-hospital mortality was significantly higher for patients in the IET vs adequate empiric therapy (AET) group [odds ratio (OR): 1.61 (95% CI: 1.32, 1.98); P < 0.0001], and when AST TAT was >63 h [OR:1.48 (95% CI: 1.16, 1.90); P = 0.0017]. Patients with carbapenem non-susceptible (carb-NS) ENT BSI had significantly higher LOS (16.6 days, 95% CI: 15.6, 17.8) compared to carbapenem susceptible (carb-S, 12.2 days, 95% CI: 11.8, 12.6), (P < 0.0001). Extended AST TAT was significantly associated with longer LOS for TAT of 57–65 h and >65 h (P = 0.005 and P< 0.0001, respectively) compared to TAT ≤42 h (reference). Inadequate empiric therapy (IET), carb-NS, and delayed AST TAT are significantly associated with adverse hospital outcomes in ENT BSI. Workflows that accelerate AST TAT for ENT BSIs and facilitate timely and adequate therapy may reduce post-BSI in-hospital mortality rate and LOS.IMPORTANCEFor patients diagnosed with bloodstream infections (BSI) caused by Enterobacterales (ENT), delayed time to antimicrobial susceptibility (AST) results can significantly impact in-hospital mortality and hospital length of stay. However, this relationship between time elapsed from blood culture collection to AST results has only been assessed, to date, in a limited number of publications. Our study focuses on this important gap using retrospective data from 29,570 blood ENT-positive admissions across 161 healthcare facilities in the US as we believe that a thorough understanding of the dynamic between AST turnaround time, adequacy of empiric therapy, post-BSI event mortality, and hospital length of stay will help guide effective clinical management and optimize outcomes of patients with ENT infections.

Objectives: The rise in Carbapenem-resistant Enterobacterales (CRE) is perturbing. To curb the menace of CRE, a comprehensive understanding of its prevalence and epidemiology is crucial. As varying reports abound, the true prevalence of CRE in Nigeria remains unknown. Here, we conducted a systematic review and meta-analysis following standard guidelines to assess the situation of CRE in Nigeria. Methods: We searched electronic databases including Pubmed, ScienceDirect, Scopus, Web of Science, and Google Scholar for articles providing information on CRE in Nigeria. The data gathered were analyzed using OpenMeta Analyst and Comprehensive Meta-Analysis software. The random-effect model was employed to calculate pooled resistance to carbapenem antibiotics. Results: From 321 retrieved records, 57 were finally included. The studies were predominantly from the South-West region (n = 19). Escherichia coli and Klebsiella pneumoniae were the most frequently tested Enterobacterales among the included studies. The pooled prevalence estimate for imipenem resistance among CRE was 11.2 % (95 % CI: 7.9–15.7). Meropenem resistance had an estimate of 13.5 % (95 % CI: 9.1–19.6), whereas ertapenem and doripenem were estimated at 17.0 % (95 % CI: 9.9–27.7) and 37.9 % (95 % CI: 15.0–67.8), respectively. High heterogeneity (I2>85 %, p

Background: Evaluating the selective pressure of antimicrobials on bacteria is important for promoting antimicrobial stewardship programs (ASPs). The aim of this study was to assess the selective pressure of antimicrobials by evaluating their use (carbapenem [CBP] and CBP-sparing therapy) over time and the detection status of CBP-resistant organisms using multicenter data. Methods: Among the facilities whose data were registered in the Japan Surveillance for Infection Prevention and Healthcare Epidemiology from 2017 to 2020, those that had data on the use of CBP and CBP-sparing therapy (fluoroquinolones [FQs], cefmetazole [CMZ], piperacillin–tazobactam [PIP/TAZ], ampicillin–sulbactam [ABPC/SBT], ceftriaxone/cefotaxime [CTRX/CTX], CAZ (ceftazidime), cefepime [CFPM], and aminoglycosides [AGs]) as well as on CBP-resistant Enterobacterales (CRE) and CBP-resistant Pseudomonas aeruginosa (CRPA) detection were included. Alcohol-based hand rubbing (ABHR) usage was also analyzed. Regression analyses, including multivariable regression analysis, were performed to evaluate trends. The association of antimicrobial use density (AUD) with CRE and CRPA detection rates was evaluated. Results: In 28 facilities nationwide, CBP, FQ, CAZ, AG, and PIP/TAZ use decreased over the 3-year period, whereas the use of CMZ, ABPC/SBT, CTRX/CTX, CFPM, and ABHR as well as the rates of CRE and CRPA detection increased. The average AUD did not significantly correlate with CRE and CRPA detection rates. The multivariable regression analysis did not reveal any significant correlation between each AUD or ABHR and CRE or CRPA detection. Conclusion: CBP and ABHR use showed a decreasing and an increasing trend, respectively, while CRPA and CRE detection rates exhibited a gradual increase. The considerably low CRE and CRPA detection rates suggest that slight differences in numbers may have been observed as excessive trend changes. Further investigation is warranted to evaluate selective pressure while considering the characteristics of ASP and the mechanisms underlying resistance.

ABSTRACT Whether empirical therapy with carbapenems positively affects the outcomes of critically ill patients with bacterial infections remains unclear. This study aimed to investigate whether the use of carbapenems as the initial antimicrobial administration reduces mortality and whether the duration of carbapenem use affects the detection of multidrug-resistant (MDR) pathogens. This was a post hoc analysis of data acquired from Japanese participating sites from a multicenter, prospective observational study [Determinants of Antimicrobial Use and De-escalation in Critical Care (DIANA study)]. A total of 268 adult patients with clinically suspected or confirmed bacterial infections from 31 Japanese intensive care units (ICUs) were analyzed. The patients were divided into two groups: patients who were administered carbapenems as initial antimicrobials (initial carbapenem group, n = 99) and those who were not administered carbapenems (initial non-carbapenem group, n = 169). The primary outcomes were mortality at day 28 and detection of MDR pathogens. Multivariate logistic regression analysis revealed that mortality at day 28 did not differ between the two groups [18 (18%) vs 27 (16%), respectively; odds ratio: 1.25 (95% confidence interval (CI): 0.59–2.65), P = 0.564]. The subdistribution hazard ratio for detecting MDR pathogens on day 28 per additional day of carbapenem use is 1.08 (95% CI: 1.05–1.13, P < 0.001 using the Fine-Gray model with death regarded as a competing event). In conclusion, in-hospital mortality was similar between the groups, and a longer duration of carbapenem use as the initial antimicrobial therapy resulted in a higher risk of detection of new MDR pathogens.IMPORTANCEWe found no statistical difference in mortality with the empirical use of carbapenems as initial antimicrobial therapy among critically ill patients with bacterial infections. Our study revealed a lower proportion of inappropriate initial antimicrobial administrations than those reported in previous studies. This result suggests the importance of appropriate risk assessment for the involvement of multidrug-resistant (MDR) pathogens and the selection of suitable antibiotics based on risk. To the best of our knowledge, this study is the first to demonstrate that a longer duration of carbapenem use as initial therapy is associated with a higher risk of subsequent detection of MDR pathogens. This finding underscores the importance of efforts to minimize the duration of carbapenem use as initial antimicrobial therapy when it is necessary.

Factor V (FV) deficiency is a coagulation disorder (congenital or acquired). Unlike congenital FV deficiency, mixing tests for prothrombin time and activated partial thromboplastin time are not corrected in acquired FV cases. A 79-year-old male was admitted to the intensive care unit after an emergency operation due to gastric ulcer perforation. While receiving antibiotic treatment for septic shock, the coagulation profile began to show prolongation of prothrombin time and activated partial thromboplastin time. FV deficiency (< 1%) following meropenem administration was diagnosed. The patient did not show spontaneous bleeding or bleeding tendency. With fresh frozen plasma transfusion, steroid administration, and discontinuation of meropenem, the blood coagulation profile test result was normalized 20 days after diagnosis. His follow-up FV level increased to 78.7%. Although abnormalities in coagulation profiles are common in sepsis patients, in our patient, timely recognition and hematological consultation allowed early diagnosis and proper management of FV deficiency.

Background and aim: Colistin and carbapenem-resistant Pseudomonas and Acinetobacter isolates can cause severe infections. We aimed to determine the prevalence of colistin and carbapenem resistance in Pseudomonas and Acinetobacter nosocomial isolates and investigate the underlying mechanisms. Methods: The antimicrobial susceptibility of Pseudomonas and Acinetobacter isolates was tested through disk diffusion method, while colistin resistance was tested by agar dilution method. Extended spectrum-β-lactamases (ESβLs) production was tested using the combined disk method, and carbapenemase production was tested phenotypically (using modified carbapenem inactivation method (mCIM) and Imipenem/EDTA combined disc diffusion test). Genotypic analysis detected carbapenemase genes. Colistin-resistant isolates were investigated for efflux pump mechanisms using the carbonyl cyanide 3-chlorophenylhydrazone (CCCP). Results: Fifty Pseudomonas and thirty Acinetobacter isolates were isolated from the collected samples. Approximately, 44% of Pseudomonas and 43.3% of Acinetobacter isolates produced ESβLs. Carbapenemase production was found in 38% of Pseudomonas and 40% of Acinetobacter isolates while 28% and 23.3% produced metallo-β-Lactamases (MβLs). Colistin resistance was detected in 14% of Pseudomonas and 10% of Acinetobacter isolates. CCCP reduced colistin MIC by ≥8 folds in 85.7% and 100% of colistin-resistant Pseudomonas and Acinetobacter isolates, respectively. The carbapenemase genes bla NDM, bla VIM-2 and bla IMP-1 were found in 33.3%, 16.7% and 6.7% of Pseudomonas isolates, and in 25%, 15% and 5% of Acinetobacter isolates, respectively. Conclusion: Pseudomonas and Acinetobacter isolates showed resistance to multiple antibiotics. Carbapenemase production shows challenges for effective treatment. Efflux pump inhibitors exhibited potential in reversing colistin resistance emphasizing the need to avoid unnecessary clinical use of colistin.

The occurrence of multidrug-resistant Acinetobacter baumannii (MDRA) has increased rapidly and is associated with severe nosocomial infections. MDRA has emerged in the hospital setting and has evolved into extensively drug-resistant A. baumannii (XDRA). A clinical XDRA isolate obtained from a hospitalised patient in 2016 was evaluated for antibiotic susceptibility and whole-genome sequence. The XDRA isolate was resistant to β-lactams, including broad-spectrum cephalosporins and carbapenems, and to aminoglycosides, fosfomycin, fluoroquinolones, tetracyclines, tigecycline, and trimethoprim-sulfamethoxazole. The isolate harboured abaF, ant(3″)-II-c, aph(3″)-Ib, aph(6)-Id, armA, blaADC-73, blaTEM-1, blaOXA-66, blaOXA-23, mphE, msrE and tet(B). Quinolone resistance was associated with mutations gyrA S81L and parC S84L. Tigecycline resistance was associated with a mutation in adeS. The isolate belonged to Oxford and Pasteur scheme sequence type 1050 and 2, respectively, and harboured a conjugative plasmid containing the aminoglycoside resistance transposon TnaphA6. Our study demonstrates that the isolate is closely related to a recent MDRA identified in Australia and the USA, in which a similar conjugative plasmid is not observed. Although the MDRA in Australia caused an outbreak, our hospital's surveillance protocol managed to prevent a further outbreak. Our finding suggests that this XDRA isolate is of concern in hospital and community care settings. The gpi allele could be a marker for discriminating this isolate from clonal complex 92 isolates.

Background: Extended spectrum beta-lactamase (ESBL) producing E. coli is implicated in high rate of human infections globally. Uprising of carbapenem and colistin resistance further hinders the treatment potentials of these infections. Aim: This study was conducted to assess the phenotypic and genotypic characterization of carbapenem and colistin resistance between ESBL producing E. coli isolates obtained from chicken respiratory tract in El-Sharkia government, Egypt. Methods: Lung samples, 250, from 50 chicken farms were processed for isolation, identification and serotyping of E. coli. Antimicrobial resistance was detected by disk diffusion. ESBL phenotypic occurrence was also examined by double disc synergy. PCR/sequencing were used to investigate ESBL (β-lactamase (bla)- TEM, bla SHV, and bla CTX-M ), colistin (mcr-1), and carbapenem (bla NDM, bla VIM and bla KPC) resistant genes. Results: The results displayed that 140/250 (56%) were detected to be E. coli. All E. coli isolates had an elevated multi-antimicrobial resistance (MAR) index value (>0.2) and 65.7 % were proven to produce ESBL. Among 92 ESBL phenotypes 55 (59.7%), 32 (34.7%), 18 (19.6%), and 37 (40.2%) isolates harbor bla TEM-3, bla SHV-4, bla CTX-M-1, bla CTX-M-14 respectively. The bla NDM-1 gene was detected in all 40/50 carbapenem resistant phenotypes that represents 28.5% of all E. coli and 43.4% of ESBL isolates. The bla VIM and bla KPC were not found in any E. coli isolate. In addition, mobilized colistin resistance (mcr)-1 gene exhibited high prevalence; 64 (69.5%) among ESBL isolates. Conclusion: The reported high frequency of ESBL-producers especially carbapenem and colistin-resistant E. coli would account for a public health threat in the society. [Open Vet J 2024; 14(1.000): 459-469]

ABSTRACTThis study investigated resistance evolution mechanisms of conjugated plasmids and bacterial hosts under different concentrations of antibiotic pressure. Ancestral strain ECNX52 was constructed by introducing the blaNDM-5-carrying IncX3 plasmid into E. coli C600, and was subjected to laboratory evolution under different concentrations of meropenem pressure. Minimal inhibitory concentrations and conjugation frequency were determined. Fitness of these strains was assessed. Whole genome sequencing and transcriptional changes were performed. Ancestral host or plasmids were recombined with evolved hosts or plasmids to verify plasmid or host factors in resistance evolution. Role of the repA mutation on plasmid copy number was determined. Two out of the four clones (EM2N1 and EM2N3) exhibited four-fold increase in MIC when exposed to a continuous pressure of 2 μg/mL MEM (1/32 MIC), by down regulating expression of outer membrane protein ompF. Besides, all four clones displayed four-fold increase in MIC and higher conjugation frequency when subjected to a continuous pressure of 4 μg/mL MEM (1/16 MIC), attributing to increasing plasmid copy number generated by repA D140Y (GAT→TAT) mutation. Bacterial hosts and conjugative plasmids can undergo resistance evolution under certain concentrations of antimicrobial pressure by reducing the expression of outer membrane proteins or increasing plasmid copy numbers.

Background: An outbreak of multidrug-resistant Klebsiella pneumoniae, Escherichia coli, and Enterobacter cloacae infections in a neonatal ward within a tertiary hospital in South Africa resulted in the mortality of 10 patients within six months. In this work, the genomic epidemiology of and the molecular factors mediating this outbreak were investigated. Methods: Bacterial cultures obtained from clinical samples collected from the infected neonates underwent phenotypic and molecular analyses to determine their species, sensitivity to antibiotics, production of carbapenemases, complete resistance genes profile, clonality, epidemiology, and evolutionary relationships. Mobile genetic elements flanking the resistance genes and facilitating their spread were also characterized. Results: The outbreak was centered in two major wards and affected mainly neonates between September 2019 and March 2020. Most isolates (n = 27 isolates) were K. pneumoniae while both E. coli and E. cloacae had three isolates each. Notably, 33/34 isolates were multidrug resistant (MDR), with 30 being resistant to at least four drug classes. All the isolates were carbapenemase-positive, but four blaOXA-48 isolates were susceptible to carbapenems. BlaNDM-1 (n = 13) and blaOXA-48/181 (n = 15) were respectively found on IS91 and IS6-like IS26 composite transposons in the isolates alongside several other resistance genes. The repertoire of resistance and virulence genes, insertion sequences, and plasmid replicon types in the strains explains their virulence, resistance, and quick dissemination among the neonates. Conclusions: The outbreak of fatal MDR infections in the neonatal wards were mediated by clonal (vertical) and horizontal (plasmid-mediated) spread of resistant and virulent strains (and genes) that have been also circulating locally and globally. [ABSTRACT FROM AUTHOR]

Background Previous studies identified a rapid decrease in valproate serum concentrations when coadministered with a carbapenem; however, the specific consequences and subsequent therapy adjustments are not well described. We aimed to investigate the clinical and therapeutic implications of the carbapenem-valproate drug-drug interaction. Methods This retrospective analysis included data from 2 large academic medical centers during January 2017 to June 2022. The primary outcome was incidence of seizures or behavioral events stratified by valproate indication. All adult patient encounters with concomitant administration of any carbapenem antimicrobial and valproate were included. Patients without prolonged exposure to valproate prior to hospitalization, without valproate levels pre– and post–carbapenem administration, with an admitting diagnosis of seizure, with exposure to other agents that decrease valproate concentrations, or who had a seizure during the hospitalization prior to carbapenem exposure were excluded. Results Two hundred fifty-eight episodes of concomitant use among 78 unique adult patients were included. Valproate was used for seizure control in 41 patients (52.6%) and for mood-related disorders in 37 (47.4%). In those prescribed valproate for its antiepileptic properties, seizures occurred following carbapenem administration in 46.3% of encounters. In those taking valproate for mood-related disorders, 50.8% met the primary endpoint of behavioral disturbance. Conclusions Our study demonstrates significant clinical implications of the carbapenem-valproate interaction. Clinicians should be aware of this interaction and consider alternative antimicrobial and/or antiepileptic agents whenever possible. Adding or increasing doses of antiepileptic agents and/or consultation with a neurologist prior to concomitant use should be considered when this combination cannot be avoided. [ABSTRACT FROM AUTHOR]

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

Objectives Treatment options for urinary tract infections (UTIs) caused by ESBL-producing Enterobacterales are limited. Moreover, evidence to support therapeutic decisions is lacking. This study assessed current treatment strategies and patient and pathogen characteristics in relation to clinical and microbiological outcomes. Methods Patients with UTI caused by ESBL-producing Enterobacterales were prospectively recruited by investigators at 15 infectious disease hospital departments. Data were collected on patient characteristics, treatments, clinical and microbiological cure 10–14 days after the end of treatment, and relapse within 3 months. Bacterial isolates were subjected to MIC determination and WGS. Results In total, 235 patients (107 febrile UTI, 128 lower UTI) caused by Escherichia coli (n = 223) and Klebsiella spp. (n = 12) were included. Clinical and microbiological cure rates were 83% and 64% in febrile UTI, and 79% and 65% in lower UTI. Great variability in treatments was observed, especially in oral therapy for febrile UTI. No difference was seen in clinical outcomes with piperacillin/tazobactam (n = 28) compared with carbapenems (n = 41). Pivmecillinam was frequently used in lower UTI (n = 62), and was also associated with high clinical cure rates when used as initial therapy (10/10) or follow-up (7/8) for febrile UTI. Recurrent infection, diabetes mellitus and urogenital disease were associated (P < 0.05) with clinical failure and relapse. In E. coli , ST131 was significantly associated with relapse, and haemolysin with microbiological failure or relapse. Conclusions Antibiotic treatments were highly variable. Patient and pathogen factors were identified as potential determinants of disease presentation and outcomes and may prove useful to guide individualized treatment and follow-up. [ABSTRACT FROM AUTHOR]