Carbapenem-resistant Enterobacteriaceae Research Articles

Incidence of hospital-acquired infections due to carbapenem-resistant Enterobacterales and Pseudomonas aeruginosa in critically ill patients in Italy: a multicentre prospective cohort study

BackgroundCarbapenem-Resistant Gram-Negative Bacteria, including Carbapenem-Resistant Enterobacterales (CRE) and Carbapenem-Resistant Pseudomonas aeruginosa (CRPA), are common causes of infections in intensive care units (ICUs) in Italy.ObjectiveThis prospective observational study evaluated the epidemiology, management, microbiological characterization, and outcomes of hospital-acquired CRE or CRPA infections treated in selected ICUs in Italy.MethodsThe study included patients with hospital-acquired infections due to CRE and CRPA treated in 20 ICUs from June 2021 to February 2023. The primary endpoint was the 1-year incidence of CRE/CRPA infections. Secondary endpoints included the rate of CRE/CRPA infections, mortality in ICU, infection outcome, and microbiological characterization.ResultsAmong 13,088 patients admitted over the 12-month study period across each of the 20 ICUs, 283 had CRE infections, and 138 had CRPA infections. The incidence of CRE and CRPA infections was 3.57 per 1000 patient days and 1.74 per 1000 patient days, respectively. The proportion of CRE and CRPA infections over the total number of infections due to Enterobacterales and Pseudomonas aeruginosa was 19.2% and 26.8%, respectively. Among 158 patients included in the full analysis, 98 (62%) had CRE infections and 60 (38%) had CRPA infections. Ventilator-associated pneumonia and bloodstream infections were the most common infections, occurring in 53.8 and 34.2% of cases. Empirical therapy targeting gram-negative pathogens resulted inappropriate in 59.2% of analysed patients (77/130). The overall crude mortality in ICU rate was 30.4%, with a higher rate in CRE patients (36.7%) than in CRPA patients (20.0%). Clinical success, including microbiological eradication, was achieved in 50.6% of cases. Klebsiella pneumoniae was observed as the predominant CRE species, and all CRE isolates, including metallo-β-lactamases-producing CRE (MBL-CRE), were susceptible to Aztreonam-Avibactam.ConclusionsThese results highlight the high prevalence of CRE/CRPA infections in Italian ICUs and emphasize the need for enhanced prevention and surveillance strategies.

EVALUATION OF THE APPLICABILITY OF THE O.K.N.V.I. RESIST-5 AND THE KPC&MBL&0XA-48 DISK TESTS IN A ROUTINE MICROBIOLOGY LABORATORY

Background: The global spread of carbapenemase-producing Enterobacterales (CPE) and the increasing emergence of clinical Enterobacterales harboring multiple carbapenemases of different molecular classes have prioritized the use of rapid molecular detection methods in routine microbiology laboratories. The aim of this study was to evaluate the applicability of the immunochromatographic O. K.N.V.I. RESIST-5 and the KPC&MBL&0XA-48 disc tests in a clinical microbiology laboratory. Material and methods: The tests were performed with 50 CPE belonging to 8 species and producing 7 molecularly characterized carbapenemases. Six of these isolates carried two different carbapenemases. To assess the specificity of the assays, 18 non-carbapenemase-producing but carbapenem-resistant Enterobacterales (non-CP CRE) were also included. Both tests were performed from a common overnight culture on Mueller-Hinton agar with inoculum harvested around an ertapenem disk. Results: The O.K.N.V.I. RESIST-5 correctly detected all 56 carbapenemases, including KPC-2 in Klebsiella pneumoniae; OX-48 in Serratia marcescens, Citrobacter freundii, Enterobacter hormaechei and K. pneumoniae; NDM-1 in Escherichia coli, Morganella morganii, E. hormaechei, C. freundii, S. marcescens and K. pneumoniae; VIM-1 in Proteus mirabilis; VIM-4 in C. freundii and S. marcescens; VIM-86 with and without NDM-1 in Providencia stuartii, and NDM-5 with and without OXA-232 in K. pneumoniae. The KPC&MBL&0XA-48 disc tests correctly confirmed KPC, OX-48-like and most MBL except VIM in P. mirabilis. Furthermore, the combination disc tests failed to detect OXA-48-like in pairs with MBL in K. pneumoniae. Conclusions:The O.K.N.V.I. RESIST-5 multiplex lateral assay is an excellent test for rapid diagnostic of CPE in routine microbiology laboratories. It is easy to handle and provides results with 100% sensitivity and specificity when an inoculum around ertapenem disc from routine antibiogram was used.

Characterization of the Prevalence and Antibiotic Resistance of Staphylococcus Species in an Exercise Facility in Central Kentucky, USA

The spread of methicillin-resistant Staphylococcus aureus (MRSA) in community settings, including fitness/exercise centers, remains relevant for public health. MRSA, a cause of severe infections in some, can be transmitted through shared equipment and skin contact. Understanding its prevalence and the frequency of antibiotic resistance in such environments can be useful for informing hygiene and intervention strategies. For investigating, multiple environmental swabs were collected from 14 different sites within a fitness facility, including equipment and locker rooms. Samples were collected for characterizing the prevalence of staphylococci (including MRSA), E. coli, and carbapenem-resistant Enterobacterales (CRE). Isolated colonies were identified biochemically and evaluated for antibiotic resistance. Logistic regression was applied to assess risk across different surfaces. Among 42 samples, the highest prevalence of Staphylococcus spp. was on locker room surfaces. S. aureus was prevalent on locker room floors and benches. Non-S. aureus species, such as S. saprophyticus and S. haemolyticus, were common. Resistance to oxacillin and penicillin was widespread, particularly among non-S. aureus species. E. coli was detected once, and CRE was not detected. Fitness center surfaces can harbor staphylococci, including MRSA. The results obtained corroborate other studies finding notable antibiotic resistance among staphylococci from fitness center surfaces. Hygiene improvements, including personal hygiene actions, are essential for reducing transmission risks.

Genomic Characterization of Carbapenemase-Producing Enterobacteriaceae from Clinical and Epidemiological Human Samples

Background/Objectives: Infections caused by multidrug-resistant (MDR)bacteria pose a significant public health threat by worsening patient outcomes, contributing to hospital outbreaks, and increasing health and economic burdens. Advanced genomic tools enhance the detection of resistance genes, virulence factors, and high-risk clones, thus improving the management of MDR infections. In the Autonomous Community of Aragon, the diversity and incidence of carbapenemase-producing Enterobacteriaceae (CPE) have increased during the last years. This study analyses CPE trends at a tertiary hospital in Spain from 2021 to 2023, aiming to optimize personalized medicine. Methods: CPE isolates were the first isolate per patient, year, species, and carbapenemase from January 2021 to December 2023. Additional metadata were collected from the laboratory’s information system. Antibiotic susceptibility testing was performed by broth microdilution. Whole-genome sequencing (WGS) was performed using Illumina short reads. De novo assembly was used to generate draft genomes in order to determine their complete taxonomic classification, resistome, plasmidome, sequence type (ST), core–genome multilocus sequence typing (cgMLST), and phylogenetic relationships using a suite of bioinformatics tools and in-house scripts. Results: Between 2021 and 2023, 0.4% out of 38,145 Enterobacteriaceae isolates were CPE. The CPE rate tripled in 2022 and doubled again in 2023. The most common species was Klebsiella pneumoniae (51.8%) and the most common carbapenemase was blaOXA-48. WGS revealed concordant species identification and the carbapenemase distribution in detail. Resistance rates to critical antibiotics, such as carbapenems, were variable, but in most cases were above 70%. Genetic diversity was observed in WGS and phylogenetic analyses, with plasmids often mediating carbapenemase dissemination. Conclusions: The increasing rate of CPE in healthcare settings highlights a critical public health challenge, with limited treatment options. Genomic characterization is essential to understanding resistance mechanisms, aiding therapy, limiting outbreaks, and improving precision medicine.

High Frequency of Detection of NDM‐Producing Enterobacterales Among Companion Animals Hospitalized in an Italian Veterinary Teaching Hospital

Carbapenems are considered one of the most important last‐resort classes of antibiotics, and the spread of carbapenem‐resistant Enterobacterales (CRE) is a serious concern worldwide. From a One Health point of view, reports on CRE in companion animals are increasing, requiring attention regarding their role in maintenance and direct transmission to humans. The aim of this study was to assess the frequency of detection at admission and the in‐hospital acquisition of CRE from perirectal swabs in dogs and cats hospitalized in an Italian Veterinary Teaching Hospital (VTH). Of the 150 patients sampled, 11.3% (n = 17) were CRE carriers at admission, 25.6% (n = 34) acquired CRE in their commensal microbiota during their hospital stay, and 2% (n = 3) developed an infection caused by CRE. Genotypical analysis showed that in 100% (78/78) of the CRE isolates (44 Escherichia coli, 33 Klebsiella pneumoniae, and 1 Klebsiella aerogenes) carbapenem resistance was conferred by the carbapenemase gene blaNDM, suggesting an endemic presence of such gene within the hospital. Co‐occurrent β‐lactamase‐encoding genes were found in most of the isolates. Risk factors associated with CRE acquisition were length of hospitalization (p = 0.0002) and treatment with piperacillin–tazobactam (PTZ; p = 0.0380), indicating potential cross‐selection of CRE. These results reinforce the suspicion that companion animals could silently contribute to the maintenance and dissemination of CRE in the local community, posing a threat to global health.

An Observational Study to Determine the Prevalence of COVID-19 Among Hospitalized Patients With Multidrug-Resistant Enterobacterales Infections and Clinical Outcomes, 10 US Sites, 2020--2022.

We investigated hospitalized carbapenem-resistant Enterobacterales (CRE) and extended-spectrum β-lactamase-producing Enterobacterales (ESBL-E) cases with and without COVID-19, as identified through Emerging Infections Program surveillance in 10 sites from 2020 to 2022. We defined a CRE case as the first isolation of Escherichia coli, Enterobacter cloacae complex, Klebsiella aerogenes, K oxytoca, K pneumoniae, or K variicola resistant to any carbapenem. We defined an ESBL-E case as the first isolation of E coli, K pneumoniae, or K oxytoca resistant to any third-generation cephalosporin and nonresistant to all carbapenems tested. Specimens were drawn from a normally sterile site or urine among hospitalized residents of the surveillance area in a 30-day period. We defined COVID-19 as a positive SARS-CoV-2 test result (SC2+) within 14 days before CRE or ESBL-E specimen collection and performed multivariable logistic regression analyses. Of 1595 CRE and 1866 ESBL-E hospitalized cases, 38 (2.4%) and 60 (3.2%), respectively, had a SC2+. Among these cases, a SC2+ was associated with intensive care unit admission (adjusted odds ratio [aOR], 1.69 [95% CI, 1.14-2.50]; aOR, 1.48 [95% CI, 1.03-2.12]) and 30-day mortality (aOR, 1.79 [95% CI, 1.22-2.64]; aOR, 1.94 [95% CI, 1.39-2.70]). CRE and ESBL-E infections among hospitalized patients with preceding COVID-19 were uncommon but had worse outcomes when compared with cases without COVID-19. COVID-19 prevention in patients at risk of CRE and ESBL-E infections is needed, as well as continued infection control measures and antibiotic stewardship for patients with COVID-19.

Predictive Application Value of Metagenomic Next-Generation Sequencing in the Resistance of Carbapenem-Resistant Enterobacteriaceae.

Objective: Although metagenomic next-generation sequencing (mNGS) technology has achieved notable outcomes in pathogen detection, there remains a gap in the research regarding its application in predicting the antibiotic resistance of pathogenic bacteria. This study aims to analyze the clinical application value of mNGS in predicting the resistance of carbapenem-resistant Enterobacteriaceae (CRE), as well as the relevant influencing factors, thereby providing valuable insights for clinical antimicrobial therapy. Methods: Nonduplicate isolates of Enterobacterales bacteria collected from Liaocheng People's Hospital from April 2023 to June 2024 were selected, and CRE bacteria were screened. mNGS was used to detect resistance genes, and the results were compared with those of polymerase chain reaction (PCR) to evaluate the specificity and sensitivity of gene detection. Furthermore, the performance of mNGS in identifying pathogenic microorganisms and predicting antibiotic resistance was assessed by comparing the sequencing results with those of antimicrobial susceptibility testing (AST). Results: A total of 46 isolates were confirmed as CRE through traditional AST and were further identified using the Vitek MS and Vitek 2 systems. The results indicated 27 isolates of Klebsiella pneumoniae, 14 isolates of Escherichia coli, 2 isolates of Enterobacter hormaechei, 2 isolates of Enterobacter cloacae, and 1 isolate of Citrobacter freundii. These isolates were subjected to both mNGS and PCR for detection. The calculation of the area under the receiver operating characteristic (ROC) curve demonstrated the reliability of mNGS in detecting resistance genes. Conclusion: mNGS demonstrated high sensitivity in predicting the presence of carbapenemase resistance genes in CRE, showing potential in early indication of isolate resistance information, thereby facilitating timely guidance for clinical treatment strategies.

Investigating Gram-negative bacilli isolates’ sensitivity to ceftazidime/avibactam

ABSTRACT Background: Multidrug resistant (MDR) Gram negative organisms are becoming increasingly common. Carbapenem resistant Enterobacterales (CRE) pose a major threat and necessitate the development of new antibiotics. MDR and carbapenem resistant infections, which are common in intensive care units and hospitals, lead to increased morbidity, mortality, prolonged hospital stays, and higher healthcare costs. New antimicrobials such as ceftazidime avibactam offer potential alternatives to conventional treatments such as tigecycline and colistin, which have significant side effects and limitations. Aim: This study focuses on the antibiotic susceptibility of ceftazidime/ avibactam to Gram negative bacilli found in a large number of clinical samples collected from a tertiary care facility in Netaji Subhas Medical University and Hospital, Bihta, India. Methodology: The study included 81 Gram negative bacteria isolated from patient samples. Based on the Clinical Laboratory Standards Institute guidelines mentioned in the Kirby Bauer disc diffusion method. Result and Conclusion: the results showed that ceftazidime avibactam inhibited 89.9% of the Enterobacteriaceae isolates, which was higher than the 80.3% of amikacin and the 85.1% of meropenem. Ceftazidime avibactam was effective against CRE isolates in 69.9% of cases and against MDR isolates in urine in 94% of cases, which was higher than the 40% of ceftriaxone and 94% of nitrofurantoin. The results show that ceftazidime avibactam can cure MDR and CRE infections, especially urinary tract infections, better than conventional antibiotics, which is a great help in the fight against increasing antibiotic resistance.

Epidemiology and Resistance Profiles of Bacteria Isolated from Blood Samples in Septic Patients at Emergency Department Admission: A 6-year Single Center Retrospective Analysis from Northern Italy.

This study aimed to investigate the microbiological and clinical heterogeneity of community-onset bloodstream infections (BSIs) and identify features to support targeted empirical antibiotic therapy in the Emergency Department (ED). Clinical and microbiological data from 992 BSI cases (1,135 isolates) diagnosed within 24 hours of ED admission at IRCCS Humanitas Research Hospital, Milan, Italy (January 2015-June 2022), were analyzed. Drug resistance was interpreted using EUCAST-2023. Clinical features included age, sex, comorbidities (e.g., cancer, diabetes), infection source, presence of central venous catheters (CVC), ongoing therapies, and sepsis severity. Microbiological data included pathogen identification and antimicrobial susceptibility. Antibiotic-susceptible Escherichia coli (29.5%) was the most common isolate, including extended-spectrum beta-lactamase (ESBL)-producing strains (11.3%), followed by methicillin-susceptible Staphylococcus aureus (MSSA, 8.4%). BSIs due to E. coli were more frequent in patients >60 years (43.9% vs. 27.3%, p<0.001) and associated with ESBL production (OR=2.202, p=0.031) and urosepsis (OR=1.688, p=0.006). Younger patients (≤60 years) had more S. aureus-associated BSIs (22.4% vs. 10.8%, p<0.001) and methicillin resistance (7.9% vs. 3.6%, p=0.021). Carbapenem-resistant Enterobacterales were rare (2.1%-2.8%), predominantly involving Klebsiella pneumoniae. Onco-hematological patients had a lower multidrug-resistance prevalence (9.5% vs. 21.1%, p<0.001). Community-onset BSIs demonstrated substantial prevalence of resistant pathogens, including ESBL and MRSA, emphasizing the need for robust surveillance systems. Age is a critical factor in guiding empirical antibiotic therapy in the ED.

Outbreak of carbapenem resistant Klebsiella pneumoniae in a neurorehabilitation unit: genomic epidemiology reveals complex transmission pattern in a tertiary care hospital.

Infections by Carbapenem-Resistant Enterobacterales in hospitals represent a severe threat but little is known on outbreaks in rehabilitation wards caused by Klebsiella pneumoniae producing Klebsiella pneumoniae Carbapenemase (KPC-Kp). We report an outbreak by KPC-Kp, in a Neurorehabilitation Unit in Italy, analysed through Whole-Genome Sequencing (WGS) for transmission routes reconstruction to improve management of KPC-Kp infections in rehabilitation units. We investigated cases and KPC-Kp isolates collected from February to October 2022 from hospital surveillance. Carbapenem resistance was identified with disk diffusion and minimal inhibitory concentration tests, carbapenemase production through immunochromatographic lateral flow assays. All isolates were genotyped through WGS to highlight possible phylogenetic relationships. The most likely transmission networks of KPC-Kp, were reconstructed with Bayesian discrete-time stochastic models. 19 patients were colonized by KPC-Kp. Two isolates belonged to sporadic STs (ST348 and ST219) while 9/19 and 8/19 isolates belonged to ST307 and ST716, respectively. Among ST307 isolates, we identified two genomically distinct clusters of five and two cases. All ST716 isolates were highly similar. Genotyping and the reconstruction of transmission networks of KPC-Kp based on genomic data identified seven independent introductions into the Neurorehabilitation Unit rather than a single outbreak as initially hypothesized before genomic investigation. Three of the seven introductions generated chains of secondary infections, while the remaining four remained single cases. The outbreak root-causes were identified in temporary staff shortage and insufficient microbiological surveillance. Measures were adopted accordingly and the outbreak ended. The study highlights the critical role of genomic epidemiology in hospital outbreaks.

Carbapenem-Resistant Gram-Negative Bacterial Infections at a Tertiary Health Care Center in Nepal: An Observational Study

Introduction: Carbapenems are last-resort antibiotics and are considered the drugs of choice for infections caused by multi-drug-resistant bacteria. During the last several years, there has been an alarming global increase in the detection and spread of Carbapenem-resistant organisms among gram-negative bacteria. Therefore, the main objective of this study is to determine Carbapenem-resistant gram-negative bacterial infections.Methodology: A descriptive cross-sectional study was performed. Ethical approval was granted by the Institutional Review Committee (Reference number: CMC-IRC/080/081-071). A total of 3149 non-repeated, different clinical specimens were collected, from November 2023 to February 2024, processed aseptically under the standard protocol of the American Society for Microbiology (ASM), and screened according to the Antibiotic sensitivity pattern. The analysis of the results was performed using Microsoft Excel and manual calculations.Results: Out of 3149 samples, 361 had culture-positive. Among 361 isolates, 316 were Gram-negative bacteria, among the specimens, 83 (26.26%) were identified as Carbapenem-resistant gram negative bacteria. Within this group, Acinetobacter baumannii was present in 37 (44.57%) cases, followed by Escherichia coli with 20 (24.09%), Klebsiella pneumoniae with 19 (22.89%), Stenotrophomonas maltophilia with 3 (4.81%), and Pseudomonas aeruginosa and Klebsiella aerogenes, each with 2 (2.40%) cases. The most effective antibiotics against Carbapenem-resistant Enterobacteriaceae included Colistin and Fosfomycin, whereas Carbapenem-resistant non-fermenter included Colistin and Tigecycline.Conclusions: Among Carbapenem-resistant Organisms, Acinetobacter baumannii was most prevalent. The results revealed a significant proportion of infections resistant to commonly used antibiotics, highlighting an alarming trend in antibiotic resistance.

Clinical Predispositions, Features, and Outcomes of Infections with Carbapenem-resistant Enterobacterales among Critical Care Patients.

Carbapenem-resistant Enterobacterales (CRE) infections pose a significant global public health threat. We aimed to assess the risk variables, clinical characteristics, and outcomes of CRE-caused infections in criticalcare patients. This prospective study enrolled 181 adult patients infected with Enterobacterales in the intensive care unit (ICU). Patients underwent clinical assessment and monitoring throughout their ICU stay. Carbapenem resistance was identified through antibiotic susceptibility testing and multiplex molecular detection of carbapenemase-encoding genes. The mean age of patients was 67.99 ± 12.89 years, with 71.3% being males. Of 181 patients, 111 (61.3%) were found to have CRE infections, including 39 Klebsiella pneumoniae and 31 Escherichia coli isolates. The CRE isolates showed the predominance of the OXA-48 (74.8%), followed by the NewDelhi Metallobetalactamase (NDM) carbapenemase genes (20.7%). The risk factors associated with CRE infection included high sequential organ failure assessment (SOFA) score, prolonged length of stay (LOS) in ICU, prior use of broad-spectrum antimicrobials, hemodialysis, plasma exchange, and prolonged mechanical ventilation. Carbapenem-resistant Enterobacterales infections significantly required longer LOS, more need for mechanical ventilation, and exhibited lower rates of bacterial elimination than carbapenem-susceptible Enterobacterales (CSE) infections. The type of resistance gene did not significantly influence the mortality rate among CRE patients. The successful treatment of OXA-48-positive CRE showed a strong correlation with tigecycline and colistin antibiotics. Carbapenem-resistant Enterobacterales infection in ICU patients was associated with adverse outcomes. Identification of high-risk patients is essential for early diagnosis and appropriate management. Therefore, it is crucial to improve infection control methods and implement antimicrobial stewardship to avoid spreading infections. Shoala ARK, Nassar Y, El-Kholy AA, Soliman NS, Abdel-Fattah A, El-Ghawaby H. Clinical Predispositions, Features, and Outcomes of Infections with Carbapenem-resistant Enterobacterales among Critical Care Patients. Indian J Crit Care Med 2025;29(1):36-44.

Tracing the transmission of carbapenem-resistant Enterobacterales at the patient: ward environmental nexus

IntroductionColonisation and infection with Carbapenem-resistant Enterobacterales (CRE) in healthcare settings poses significant risks, especially for vulnerable patients. Genomic analysis can be used to trace transmission routes, supporting antimicrobial stewardship and informing infection control strategies. Here we used genomic analysis to track the movement and transmission of CREs within clinical and environmental samples.Methods25 isolates were cultured from clinical patient samples or swabs, that tested positive for OXA-48-like variants using the NG-Test® CARBA-5 test and whole genome sequenced (WGS) using Oxford Nanopore Technologies (ONT). 158 swabs and 52 wastewater samples were collected from the ward environment. 60 isolates (matching clinical isolate genera; Klebsiella, Enterobacter, Citrobacter and Escherichia) were isolated from the environmental samples using selective agar. Metagenomic sequencing was undertaken on 36 environmental wastewater and swab samples.Results21/25 (84%) clinical isolates had > 1 blaOXA gene and 19/25 (76%) harboured > 1 blaNDM gene. Enterobacterales were most commonly isolated from environmental wastewater samples 27/52 (51.9%), then stick swabs 5/43 (11.6%) and sponge swabs 5/115 (4.3%). 11/60 (18%) environmental isolates harboured > 1 blaOXA gene and 1.9% (1/60) harboured blaNDM-1. blaOXA genes were found in 2/36 (5.5%) metagenomic environmental samples.ConclusionsPotential for putative patient-patient and patient-ward transmission was shown. Metagenomic sampling needs optimization to improve sensitivity.

Efficiency of combination therapy versus monotherapy for the treatment of infections due to carbapenem-resistant Gram-negative bacteria: a systematic review and meta-analysis

BackgroundFor resistant Gram-positive bacteria, evidence suggests that combination therapy is more effective. However, for resistant Gram-negative bacteria, no consensus has been reached. This study aims to comprehensively summarize the evidence and evaluate the impact of combination versus monotherapy on infections caused by carbapenem-resistant Gram-negative bacteria (CRGNB).MethodsA systematic search was conducted in PubMed, Cochrane library, Web of Science, and Embase up to June 15, 2024, to identify relevant studies. This study included comparisons of monotherapy and combination therapy for treating infections caused by CRGNB. Topical antibiotics (i.e., inhalational or intratracheal administration) and monotherapy with sulbactam/relebactam was excluded. The primary outcome was mortality, and the secondary outcomes were clinical success and microbiological eradication. Pooled odds ratios (OR) and 95% confidence intervals (CI) were calculated in order to systematically assess effect of treatment on mortality, clinical success and microbiological eradication. Subgroup analyses, publication bias tests, and sensitivity analyses were also performed.ResultsA total of 62 studies, including 8342 participants, were analyzed, comprising 7 randomized controlled trials and 55 non-randomized studies. Monotherapy was associated with higher mortality (OR = 1.29, 95%CI: 1.11–1.51), lower clinical success (OR = 0.74, 95%CI: 0.56–0.98), and lower microbiological eradication (OR = 0.71, 95%CI: 0.55–0.91) compared to combination therapy for CRGNB infections. Specifically, patients with carbapenem-resistant Enterobacteriaceae (CRE) infections receiving monotherapy had higher mortality (OR = 1.50, 95%CI: 1.15–1.95), comparable clinical success (OR = 0.57,95%CI: 0.28–1.16), and lower microbiological eradication (OR = 0.48,95%CI:0.25–0.91) than those receiving combination therapy. For carbapenem-resistant Acinetobacter baumannii (CRAB) infections, no significant differences were observed in mortality (OR = 1.15.95%CI: 0.90–1.47), clinical success (OR = 0.95,95%CI: 0.74–1.24) and microbiological eradication (OR = 0.78,95%CI: 0.54–1.12).ConclusionsMonotherapy or combination therapy is controversial. The systematic review and meta-analysis suggested that monotherapy is associated with higher mortality, lower clinical success, and lower microbiological eradication for treating infection caused by CRGNB. The available evidence suggests that treatment should be selected based on the specific bacteria and antibiotic used. Monotherapy for CRE infections may lead to adverse outcomes. For CRAB infections, no significant differences were found between combination therapy and monotherapy.Systematic review registrationPROSPERO CRD42022331861.

Susceptibility of various Gram-negative bacteria to antibacterial agents: SMART in China 2019–2020

BackgroundThe Study for Monitoring Antimicrobial Resistance Trends (SMART) is an international surveillance program longitudinally monitoring aerobic and facultative Gram-negative bacteria (GNB) involvement in infections and their antimicrobial resistance profiles. Here the incidence and resistance patterns of Chinese GNB isolates from bloodstream infections (BSI), intraabdominal infections (IAI), respiratory tract infections (RTI) and urinary tract infections (UTI) to commonly used antibacterial agents has been updated. 4,975 GNB isolates collected from 22 hospitals across 7 regions of China from 2019 to 2020 were analyzed. Antimicrobial minimum inhibitory concentrations were assessed using broth microdilution, and susceptibility interpretations followed the breakpoints of European Committee on Antimicrobial Susceptibility Testing 2022 or Clinical and Laboratory Standards Institute.ResultsThis study affirmed that Escherichia coli (Ec) was the most commonly identified GNB (32.1%) and then Klebsiella pneumoniae (Kp) (25.3%), Pseudomonas aeruginosa (Pa) (13.9%) and Acinetobacter baumannii (10.5%). The detection rates of carbapenem-resistant (CR) Enterobacterales varied across major infection sites, ranging from 10.3% in UTI to 18.9% in RTI. Specifically, the detection rates of CR-Kp and CR-Pa ranged from 16.2% in IAI to 35.8% in UTI and from 16.1% in UTI to 38.0% in RTI, respectively. Extended-spectrum β-lactamases (ESBL)-producing Ec and Kp bacteria exhibited over 91.7% susceptibility to carbapenems and at least 87.8% susceptibility to amikacin and colistin, but showed lower susceptibility to piperacillin/tazobactam (57.5–86.2%), levofloxacin (10.8–39.7%) and aztreonam (15.3–27.6%) across different infection sources. Amikacin showed higher efficacy against CR strains compared to other commonly used antibacterial drugs, with 80.0% susceptibility against CR-Ec and 82.3% susceptibility against CR-Pa, while only 36.3% susceptibility was observed against CR-Kp.ConclusionsThe study found varying incidences of CR isolates in Chinese hospitals. Treatment options remained limited due to resistance to multiple antibacterial agents. Carbapenems demonstrated effective antimicrobial in vitro activity against ESBL-producing Enterobacterales found in BSI, IAI, UTI and RTI, outperforming broad-spectrum cephalosporins and other β-lactamase inhibitors.

Seven versus 14 days of antimicrobial therapy for severe multidrug-resistant Gram-negative bacterial infections in intensive care unit patients (OPTIMISE): a randomised, open-label, non-inferiority clinical trial

BackgroundShorter courses of antimicrobial therapy have been shown to be non-inferior to longer durations for the management of several infections. However, data on critically ill patients with severe infections by multidrug-resistant Gram-negative bacteria (MDR-GNB) are scarce. In the duratiOn of theraPy in severe infecTIons by MultIdrug-reSistant gram-nEgative bacteria (OPTIMISE) trial, we assessed the non-inferiority of 7-day versus 14-day antimicrobial therapy for patients with intensive care unit (ICU)-acquired severe infections by MDR-GNB.MethodsThis was a randomised multicenter, open-label, parallel controlled, non-inferiority trial. Adult patients with severe infections by MDR-GNB initiated ≥ 48 h of ICU admission were eligible if they were hemodynamically stable and without fever > 48 h on the 7th day of appropriate antimicrobial therapy. Patients were 1:1 randomised to discontinue antimicrobial therapy on the 7th (± 1) day or to continue for a total of 14 (± 1) days. The primary outcome was clinical failure, defined as death or relapse of infection within 28 days of randomisation. An upper edge of the two-tailed 95% confidence interval (CI) of the delta between the clinical failure rate in the 7- and the 14-day lower than 10% in both intention-to-treat (ITT) and per protocol (PP) analyses was set as the non-inferiority criteria.ResultsA total of 106 patients composed the ITT population: 59 and 47 allocated to 7- and 14-day groups, respectively. The PP population included 75 patients: 47 and 28 in the 7- and 14-day groups, respectively. Clinical failure occurred in 42.4% and 44.7% of the ITT population in 7- and 14-day groups, respectively, (risk difference (RD) − 2.3, 95%CI − 21.3 to 16.7), and in 46.8% and 50.0% of the PP population in 7- and 14-day groups, respectively (RD − 3.2, 95%CI − 26.6 to 20.2). Most infections were of the respiratory tract (73/68.9%) and caused by carbapenem-resistant Enterobacterales (42/39.6%). The study was interrupted before reaching planned sample size due to low recruitment rate.ConclusionThe OPTIMISE trial could not determine the non-inferiority of 7-day compared to 14-day therapy for severe infections caused by MDR-GNB due to early termination related to the low recruitment rate.Trial registration: NCT05210387 on January 13, 2022.

Temporal trends in antimicrobial resistance of medically important pathogens on Curaçao

BackgroundThe Caribbean lacks recent comprehensive antimicrobial resistance data to inform clinicians and decision-makers. This study aims to provide a snapshot of susceptibility trends for pathogens on Curaçao, an island in the southern Caribbean.MethodsWe analyzed susceptibility data of bacterial pathogens isolated from samples submitted from patients attending general practitioners, outpatient clinics and those who were hospitalized between January 2018 and December 2023. Samples originating from blood, urine, genital tract, soft tissue, and lungs were included. Susceptibility testing was performed by VITEK2 according using the European Committee on Antimicrobial Susceptibility Testing criteria.ResultsIn total, 13,528 patients contributed to 22,876 first isolates. Of all infections in adults with Staphylococcus aureus, 14% (95% confidence interval 10–18%) were methicillin-resistant S. aureus (MRSA) in blood, and up to 27% (20–35%) in soft-tissue cultures. For Escherichia coli and Klebsiella pneumoniae, resistance levels were up to 27% (95% CI 22–32%) for cefuroxime and up to 18% (95% CI 18–28%) for third-generation cephalosporins. The addition of gentamicin to empirical therapy with cefuroxime increased coverage only moderately, especially in K. pneumoniae (16%, 95% CI 12–20%). Resistance to amoxicillin-clavulanic acid was up to 47% (95% CI 43–50%), to ciprofloxacin 34% (95% CI 31–37%) and to cotrimoxazole 37% (95% CI 34–39) in urine cultures from outpatients. In contrast, low levels of carbapenem resistant Enterobacterales and Pseudomonas aeruginosa were observed.ConclusionsAntimicrobial resistance is high and widespread across several important antibiotic classes. The widespread occurrence of MRSA and resistance to third-generation cephalosporins highlights the importance of identifying risk factors, enabling more effective guidance for antimicrobial stewardship.

Epidemiological and genetic characteristics of clinical carbapenemase-producing Enterobacterales isolates from Batna hospitals in Algeria

BackgroundCarbapenemase-producing Enterobacterales isolates are associated with significant mortality and have emerged as a major problem in healthcare settings worldwide.ObjectiveOur aim was to investigate the epidemiological and genotypic characteristics of carbapenemase-positive Enterobacterales isolates from patients hospitalised in three hospitals in the city of Batna, Algeria.MethodsBetween 2016 and 2019, a total of 5,316 clinical isolates were obtained. The collected isolates were identified using the VITEK-2 system. Demographic and microbiological data were collected as well as the antimicrobial susceptibility testing, phenotypic and molecular characterisation of carbapenemase and mcr-1 genes were performed.ResultsOut of the 5,316 isolates, 201 were carbapenem-resistant Enterobacterales isolates and 179 of them (89.05%) were positive for the production of carbapenemase, of which Klebsiella pneumoniae, Escherichia coli and Enterobacter cloacae were the most common. The blaOXA−48−like gene alone was detected in 147 isolates (82.12%) moreover, the blaNDM gene was detected in ten isolates (5.59%). Dual and triple combinations of carbapenemase genes were also observed here for the first time in Algeria: blaVIM and blaOXA−48−like; blaKPC, blaVIM and blaOXA−48−like; blaVIM and blaNDM; blaKPC, blaNDM and blaVIM; blaNDM and blaOXA−48−like genes. In addition, resistance to both colistin and carbapenem antibiotics was detected in eight isolates, however none of them was positive for the mcr-1 gene.ConclusionThis is the first study reporting the detection of carbapenemase genes in Klebsiella aerogenes, Enterobacter sakazakii, Raoultella ornithinolytica, Serratia ficaria, and Serratia marcescens and specific carbapenemase gene combinations in Algeria. The present study revealed that blaOXA−48−like were found to be the predominant carbapenemase genes in Batna hospitals.

High-Risk Lineages of Hybrid Plasmids Carrying Virulence and Carbapenemase Genes

Background/Objectives: Carbapenem-resistant Enterobacterales (CRE) are a global health threat due to their high morbidity and mortality rates and limited treatment options. This study examines the plasmid-mediated transmission of virulence and antibiotic resistance determinants in carbapenem-resistant Klebsiella pneumoniae (Kpn) and Escherichia coli (E. coli) isolated from Russian hospitals. Methods: We performed short- and long-read whole-genome sequencing of 53 clinical isolates (48 Kpn and 5 E. coli) attributed to 15 genetic lineages and collected from 21 hospitals across nine Russian cities between 2016 and 2022. Results: The plasmid analysis identified 18 clusters that showed high concordance with replicon typing, with all clusters having a major replicon type. The majority of plasmids in the IncHI1B(pNDM-MAR)/IncFIB(pNDM-Mar)-like cluster (79.16%) carried both antibiotic resistance genes (e.g., blaNDM-1 and blaOXA-48) and virulence factors (VFs) such as siderophore genes. We hypothesized that hybrid plasmids could play a critical role in the dissemination of antibiotic resistance genes and VFs. Comparative analyses with global plasmid databases revealed high-risk lineages of hybrid plasmids that are predominantly spread throughout Russia at present. Conclusions: Our findings underscore the importance of monitoring plasmid backbones for clinical management, surveillance, and infection control activities.

Carbapenem-Resistant E. coli Adherence to Magnetic Nanoparticles.

Carbapenem-resistant Enterobacterales (CRE) is an emerging global concern. Specifically, carbapenemase-producing (CP) E. coli strains in CRE have recently been found in clinical, environmental, and food samples worldwide, causing many hospitalizations and deaths. Their rapid identification and characterization are paramount in control, management options, and treatment choices. Thus, this study aimed to characterize the cell surface properties of carbapenem-resistant (R) E. coli isolates and their interaction with glycan-coated magnetic nanoparticles (gMNPs) compared with carbapenem-susceptible (S) E coli. This study used two groups of bacteria: The first group included E. coli (R) isolates harboring carbapenemases and had no antibiotic exposure. Their initial gMNP-cell binding capacity, with cell surface characteristics, was assessed. In the second group, one of the E. coli (R) isolates and E. coli (S) had long-term serial antibiotic exposure, which we used to observe their cell surface characteristics and gMNP interactions. Initially, cell surface characteristics (cell morphology and cell surface charge) of the E. coli isolates were evaluated using confocal laser scanning microscope (LSCM) and a Zetasizer, respectively. The interaction of gMNPs with the E. coli isolates was assessed through LSCM and transmission electron microscope (TEM). Further, the gMNP-cell attachment was quantified as a concentration factor (CF) through the standard plating method. The results showed that the CF values of all E. coli (R) were significantly different from those of E. coli (S), which could be due to the differences in cell characteristics. The E. coli (R) isolates displayed heterogeneous cell shapes (rod and round cells) and lower negative zeta potential (cell surface charge) values compared to E. coli (S). Further, this research identified the differences in the cell surface characteristics of E. coli (S) under carbapenem exposure, compared to unexposed E. coli (S) that impact their attachment capacity. The gMNPs captured more E. coli (S) cells compared to carbapenem-exposed E. coli (S) and all E. coli (R) isolates. This study clearly found that differences in cell surface characteristics impact their interaction with magnetic nanoparticles. The gained insights aid in further understanding adhesion mechanisms to develop or improve bacterial isolation techniques and diagnostic and treatment methods for CRE.