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Antimicrobial resistance (AMR) is a current public health issue globally. To counter this phenomenon and prioritize AMR in the health sector, the World Health Organization (WHO) published a list of bacterial pathogens against which the development of new antimicrobial agents is urgently needed, designating the ESKAPE pathogens (i.e., Enterococcus faecium, Staphylococcus aureus, Klebsiella pneumoniae, Acinetobacter baumannii, Pseudomonas aeruginosa, and Enterobacter species) with a ‘priority status’. Moreover, the One Health High Level Expert Panel (OHHLEP) states that human health is closely linked to animal and environmental health, thus promoting a holistic One Health approach in order to be prepared to address possible emerging health threats from the human–animal–environment interface. Wild birds may host and spread pathogens, integrating the epidemiology of infectious diseases. The aim of this study was to examine the role of wild birds as a source of ESKAPE bacteria and other antibiotic-resistant enterobacterales. A total of fifty strains within the ESKAPE group were detected in 40/163 cloacal samples of examined birds (24.5%). Additionally, different strains of enterobacterales were detected in 88/163 cloacal samples (53.9%). Isolated strains exhibited antimicrobial resistance, including towards critically important antibiotics (e.g., third, fourth, fifth generation cephalosporins, fluoroquinolones) for human medicine. Our results confirm that wild birds are potential reservoirs of several pathogens and antimicrobial-resistant bacteria and that they could be involved in the dissemination of those bacteria across different environments, with resulting public health concerns.

Antimicrobial resistance is increased by international mobility. We present data about intestinal colonization of travelers departing from a middle-income country. Travelers were recruited from 2015 to 2019, collected an anal stool specimen and answered a questionnaire before and after travel. Enterobacterales isolates were investigated for antimicrobial resistance; extended-spectrum beta-lactamase (ESBL) and carbapenemase production; plasmid-encoded cephalosporinases (pAmpC), plasmid-mediated quinolone resistance (PMQR) and mcr genes by PCR and sequencing; and association with travel related variables. Among 210 travelers, 26 (12%) carried multidrug-resistant Enterobacterales (MDR-E) and 18 (9%) ESBL-producing Enterobacterales (ESBL-E) before travel, with an increased prevalence from 1% to 11% over the study years. Acquisition of MDR-E and ESBL-E occurred in 59 (32%) and 43 (22%) travelers, respectively, mostly blaCTX-M-15 carrying Escherichia coli. One traveler acquired one isolate carrying blaOXA-181 gene, and two others, isolates carrying mcr-1. PMQR were detected in 14 isolates of returning travelers. The risk of MDR-E acquisition was higher in Southeast Asia and the Indian subcontinent, and after using antimicrobial agents. We describe an increasing pre-travel prevalence of ESBL-E colonization in subjects departing from this middle-income country over time. Travel to known risk areas and use of antimicrobial agents during travel were associated with acquisition of MDR-E. Travel advice is critical to mitigating this risk, as colonization by MDR-E may raise the chances of antimicrobial-resistant infections.

Background: The intestinal tract is a host to a high number of diverse bacteria, and the presence of multidrug-resistant (MDR) Enterobacterales strains acts as a reservoir and a source of infection. The interactions between the intestinal microbiome and colonizer Enterobacterales strains influence long-lasting colonization. Aims: In this narrative review, we summarize available data about the intestinal colonization of MDR Enterobacterales strains and correlations between colonization and the intestinal microbiome. Results: Several endogenous and exogenous factors influence the intestinal colonization of MDR Enterobacterales strains. On the gut microbiome level, the intestinal microbial community is composed of the Lachnospiraceae family (e.g., Lachnoclostridium, Agathobacter, Roseburia, Tyzzerella), which indicates a protective role against colonizer MDR Enterobacterales strains; by contrast, a high abundance of Enterobacterales correlates with the colonization of MDR Enterobacterales strains. In specific patient groups, striking differences in microbiome composition can be detected. Among hematopoietic stem-cell-transplanted patients colonized by extended-spectrum beta-lactamase (ESBL)-producing Enterobacterales, a greater abundance of Bifidobacterium, Blautia, Clostridium, Coprococcus, L-Ruminococcus, Mogibacteriaceae, Peptostreptococceae and Oscillospira was observed compared to patients not colonized by ESBL-producing strains, who had a greater abundance of Actinomycetales. In liver transplant patients, a reduction in the alpha-diversity of the intestinal microbiome in fecal samples correlates with the carriage of MDR Enterobacterales. Conclusions: Intestinal colonization with MDR Enterobacterales is a multifactorial process that involves the MDR strain (e.g., its plasmids, fimbria), host and mucosal factors (e.g., IgA and defensin) and exogenous factors (e.g., use of antibiotics, hospitalization). On the gut microbiome level, the Lachnospiraceae family is dominant among intestines not colonized by MDR strains, but a high abundance of Enterobacterales was correlated with colonization with MDR Enterobacterales strains.

Duodenoscopy-associated infections occur worldwide despite strict adherence to reprocessing standards. The exact scope of the problem remains unknown because a standardized sampling protocol and uniform sampling techniques are lacking. The currently available multi-society protocol for microbial culturing by the Centers for Disease Control and Prevention, the United States Food and Drug Administration (FDA) and the American Society for Microbiology, published in 2018 is too laborious for broad clinical implementation. A more practical sampling protocol would result in increased accessibility and widespread implementation. This will aid to reduce the prevalence of duodenoscope contamination. To reduce the risk of duodenoscopy-associated pathogen transmission the FDA advised four supplemental reprocessing measures. These measures include double high-level disinfection, microbiological culturing and quarantine, ethylene oxide gas sterilization and liquid chemical sterilization. When the supplemental measures were advised in 2015 data evaluating their efficacy were sparse. Over the past five years data regarding the supplemental measures have become available that place the efficacy of the supplemental measures into context. As expected the advised supplemental measures have resulted in increased costs and reprocessing time. Unfortunately, it has also become clear that the efficacy of the supplemental measures falls short and that duodenoscope contamination remains a problem. There is a lot of research into new reprocessing methods and technical applications trying to solve the problem of duodenoscope contamination. Several promising developments such as single-use duodenoscopes, electrolyzed acidic water, and vaporized hydrogen peroxide plasma are already applied in a clinical setting.

Infections caused by multidrug-resistant (MDR) and extensively drug-resistant (XDR) Gram-negative bacteria (GNB), including carbapenem-resistant (CR) Enterobacterales (CRE; harboring mainly bla KPC , bla NDM , and bla OXA-48 -like genes), CR- or MDR/XDR- Pseudomonas aeruginosa (production of VIM, IMP, or NDM carbapenemases combined with porin alteration), and Acinetobacter baumannii complex (producing mainly OXA-23, OXA-58-like carbapenemases), have gradually worsened and become a major challenge to public health because of limited antibiotic choice and high case-fatality rates. Diverse MDR/XDR-GNB isolates have been predominantly cultured from inpatients and hospital equipment/settings, but CRE has also been identified in community settings and long-term care facilities. Several CRE outbreaks cost hospitals and healthcare institutions huge economic burdens for disinfection and containment of their disseminations. Parenteral polymyxin B/E has been observed to have a poor pharmacokinetic profile for the treatment of CR- and XDR-GNB. It has been determined that tigecycline is suitable for the treatment of bloodstream infections owing to GNB, with a minimum inhibitory concentration of ≤ 0.5 mg/L. Ceftazidime-avibactam is a last-resort antibiotic against GNB of Ambler class A/C/D enzyme-producers and a majority of CR- P. aeruginosa isolates. Furthermore, ceftolozane-tazobactam is shown to exhibit excellent in vitro activity against CR- and XDR- P. aeruginosa isolates. Several pharmaceuticals have devoted to exploring novel antibiotics to combat these troublesome XDR-GNBs. Nevertheless, only few antibiotics are shown to be effective in vitro against CR/XDR- A. baumannii complex isolates. In this era of antibiotic pipelines, strict implementation of antibiotic stewardship is as important as in-time isolation cohorts in limiting the spread of CR/XDR-GNB and alleviating the worsening trends of resistance.

PurposeMultidrug-resistant Gram-negative bacteria (MDR-GNB) have become a major global public health threat. Ceftazidime–avibactam (CAZ–AVI) is a newer combination of β-lactam/β-lactamase inhibitor, with activity against carbapenem-resistant Enterobacterales (CRE) and carbapenem-resistant Pseudomonas aeruginosa (CRPA). The aim of this review is to describe the recent real-world experience of CAZ–AVI for the infections due to MDR-GNB.MethodsWe searched PubMed, Embase and Google Scholar for clinical application in CAZ-AVI for MDR-GNB infections. Reference lists were reviewed and synthesized for narrative review.ResultsMDRGNB infections are associated with higher mortality significantly comparing to drug-susceptible bacterial infections. Fortunately, CAZ–AVI shows significant benefits for infections due to KPC or OXA-48 CRE, comparing to colistin, carbapenem, aminoglycoside and other older agents, even in those with immunocompromised status. The efficacy of CAZ–AVI varies in different infection sites due to CRE, which is lower in pneumonia. Early use is associated with improved clinical outcomes. Noteworthy, when adopted as salvage therapy, CAZ–AVI is still superior to other GNB active antibiotics. CAZ–AVI plus aztreonam is recommended as the first line of MBL-CRE infections. However, for infections caused by KPC- and OXA-48-producing isolates, further investigations are needed to demonstrate the benefit of combination therapy. Besides CRE, CAZ-AVI is also active to MDR-PA. However, the development of resistance in CRE and MDR-PA against CAZ–AVI is alarming, and more investigations and studies are needed to prevent, diagnose, and treat infections due to CAZ–AVI-resistant pathogens.ConclusionsCAZ-AVI appears to be a valuable therapeutic option in MDR-GNB infections. Using CAZ-AVI appropriately to improve efficacy and decrease the emergence of resistance is important.

The effectiveness of contact isolation for decreasing the spread of extended-spectrum β-lactamase-producing Enterobacterales (ESBL-E) has been questioned. The aim of this study was to establish the benefits of contact isolation over standard precautions for reducing the incidence density of ESBL-E colonisation and infection in adult medical and surgical wards with an active surveillance culture programme. We did a cluster-randomised crossover trial in adult wards in four European university hospitals. Medical, surgical, or combined medical–surgical wards without critical care were randomised to continue standard precautions alone or implement contact isolation alongside standard precautions for 12 months, followed by a 1 month washout period and 12 months of the alternate strategy. Randomisation was done via a computer-generated sequence, with a block size of two consecutive wards. Only laboratory technicians and data analysts were masked to allocation. Patients were screened for ESBL-E carriage within 3 days of admission, once a week thereafter, and on discharge. The primary outcome was the incidence density of ESBL-E, defined as the acquisition rate per 1000 patient-days at risk at the ward level and assessed in the per-protocol population, which included all patients screened at least twice with a length of stay of more than 1 week for each intervention period. No specific safety measures were assessed given the minimal risk of adverse events. The trial is registered, ISRCTN57648070. We enrolled 20 wards from four hospitals in Germany (eight wards), the Netherlands (four wards), Spain (four wards), and Switzerland (four wards). Between Jan 6, 2014, and Aug 31, 2016, 38 357 patients were admitted to these wards. Among 15 184 patients with a length of stay of more than 1 week, 11 368 patients (75%) were screened at least twice. The incidence density of ward-acquired ESBL-E was 6·0 events per 1000 patient-days at risk (95% CI 5·4–6·7) during periods of contact isolation and 6·1 (5·5–6·7) during periods of standard precautions (p=0·9710). Multivariable analysis adjusted for length of stay, percentage of patients screened, and prevalence in first screening cultures yielded an incidence rate ratio of 0·99 (95% CI 0·80–1·22; p=0·9177) for care under contact isolation compared with standard precautions. Contact isolation showed no benefit when added to standard precautions for controlling the spread of ESBL-E on non-critical care wards with extensive surveillance screening. European Commission.

Gastrointestinal carriage of antimicrobial-resistant bacteria, especially carbapenemase-producing Enterobacterales (CPE), presents a critical public health threat globally. However, in many resource-constrained countries, epidemiological data on CPE is limited. Here, we assessed gastrointestinal carriage and associated factors of CPE among inpatient and outpatient children (≤ 5 years). This hospital-based cross-sectional study was conducted at Thika Level 5 Hospital in Kenya from February to June 2023. In total, 540 participants were recruited from outpatient (270) and inpatient (270) children, excluding those admitted for < 48 h and outpatients with ≤ 3 months hospitalization history. Demographic data were collected using a questionnaire, and stool or swab samples were cultured following standard microbiology methods. Automated platforms were used for isolates identification and antimicrobial susceptibility testing. Gastrointestinal carriage rate of CPE was 9.6%, 95% confidence interval (CI): 6.39–13.79% (26/270) among the inpatients and 5.9%, 95% CI: 3.42–9.45% (16/270) among the outpatients. The carbapenemase-producing Enterobacterales were predominated by multidrug-resistant Escherichia coli from inpatients (22/22, 100%) and outpatients (8/10, 80%). The colonization rate was higher among inpatients who were presenting with chills (aOR = 10.57, p  = 0.008). We report a high gastrointestinal carriage of CPE among children (≤ 5 years). Strict adherence to colonization screening, and antimicrobial stewardship policies are critical to control CPE dissemination in the current study area and beyond.

Elderly people confined to chronic care facilities face an increased risk of acquiring infections by multidrug-resistant organisms (MDROs). This review presents the current knowledge of the prevalence and risk factors for colonization by MDROs in long-term care facilities (LTCF), thereby providing a useful reference to establish objectives for implementing successful antimicrobial stewardship programs (ASPs). We searched in PubMed and Scopus for studies examining the prevalence of MDROs and/or risk factors for the acquisition of MDROs in LTCF. One hundred and thirty-four studies published from 1987 to 2020 were included. The prevalence of MDROs in LTCF varies between the different continents, where Asia reported the highest prevalence of extended-spectrum ß-lactamase (ESBL) Enterobacterales (71.6%), carbapenem resistant (CR) Enterobacterales (6.9%) and methicillin-resistant Staphylococcus aureus (MRSA) (25.6%) and North America the highest prevalence to MDR Pseudomonas aeruginosa (5.4%), MDR Acinetobacter baumannii (15.0%), vancomycin-resistant Enterococcus spp. (VRE) (4.0%), and Clostridioides difficile (26.1%). Furthermore, MDRO prevalence has experienced changes over time, with increases in MDR P. aeruginosa and extended spectrum ß-lactamase producing Enterobacterales observed starting in 2015 and decreases of CR Enterobacterales, MDR A. baumannii, VRE, MRSA and C. difficile. Several risk factors have been found, such as male sex, chronic wounds, the use of medical devices, and previous antibiotic use. The last of these aspects represents one of the most important modifiable factors for reducing colonization with MDROs through implementing ASPs in LTCF.

Background This study aimed to investigate the epidemiology, microbiology, and risk factors associated with mortality and multi-drug resistance bacterial bloodstream infections (BSIs) among adult cancer patients in Shiraz, Iran. We also report a four-year trend of antimicrobial resistance patterns of BSIs. Methods We conducted a retrospective study at a referral oncology hospital from July 2015 to August 2019, which included all adults with confirmed BSI. Results 2393 blood cultures tested during the four-year study period; 414 positive cultures were included. The mean age of our patients was 47.57 ± 17.46 years old. Central Line-Associated BSI (CLABSI) was more common in solid tumors than patients with hematological malignancies. Gram-negative (GN) bacteria were more detected (63.3%, 262) than gram-positive bacteria (36.7%, 152). Escherichia coli was the most common gram-negative organism (123/262, 47%), followed by Pseudomonas spp. (82/262, 31%) and Klebsiella pneumoniae (38/262, 14.5%). Coagulase-negative staphylococci (CoNS) was the most frequently isolated pathogen among gram-positive bacteria (83/152, 54.6%). Acinetobacter spp. , Pseudomonas spp ., E. coli , and K. pneumoniae were the most common Extended-Spectrum Beta-Lactamase (ESBL) producers (100, 96.2, 66.7%, and 60.7, respectively). Acinetobacter spp., Pseudomonas spp., Enterobacter spp., E. coli , and K. pneumoniae were the most common carbapenem-resistant (CR) isolates (77.8, 70.7, 33.3, 24.4, and 13.2%, respectively). Out of 257 Enterobacterales and non-fermenter gram-negative BSIs, 39.3% (101/257) were carbapenem-resistant. Although the incidence of multi-drug resistance (MDR) gram-negative BSI increased annually during 2015–2018, the mortality rate of gram-negative BSI remains unchanged at about 20% ( p -value = 0.55); however, the mortality rate was significantly greater (35.4%) in those with resistant gram-positive BSI (p-value = 0.001). The overall mortality rate was 21.5%. Early (7-day mortality) and late mortality rate (30-day mortality) were 10 and 3.4%, respectively. Conclusions The emergence of MDR gram-negative BSI is a significant healthcare problem in oncology centers. The high proportion of the most frequently isolated pathogens were CR and ESBL-producing Enterobacterales and Pseudomonas spp. We have few effective choices against MDRGN BSI, especially in high-risk cancer patients, which necessitate newer treatment options.