Genomic and phenotypic studies among Clostridioides difficile isolates show a high prevalence of clade 2 and great diversity in clinical isolates from Mexican adults and children with healthcare-associated diarrhea.

Clostridioides difficile (C. difficile) is widely distributed in the intestinal tract of humans, animals, and in the environment. It is the most common cause of diarrhea associated with the use of antimicrobials in humans and among the most common healthcare-associated infections worldwide. Its pathogenesis is mainly due to the production of toxin A (TcdA), toxin B (TcdB), and a binary toxin (CDT), whose genetic variants may be associated with disease severity. We studied genetic diversity in 39 C. difficile isolates from adults and children attended at two Mexican hospitals, using different gene and genome typing methods and investigated their association with in vitro expression of toxins. Whole-genome sequencing in 39 toxigenic C. difficile isolates were used for multilocus sequence typing, tcdA, and tcdB typing sequence type, and phylogenetic analysis. Strains were grown in broth media, and expression of toxin genes was measured by real-time PCR and cytotoxicity in cell-culture assays. Clustering of strains by genome-wide phylogeny matched clade classification, forming different subclusters within each clade. The toxin profile tcdA+/tcdB+/cdt+ and clade 2/ST1 were the most prevalent among isolates from children and adults. Isolates presented two TcdA and three TcdB subtypes, of which TcdA2 and TcdB2 were more prevalent. Prevalent clades and toxin subtypes in strains from children differed from those in adult strains. Toxin gene expression or cytotoxicity was not associated with genotyping or toxin subtypes. In conclusion, genomic and phenotypic analysis shows high diversity among C. difficile isolates from patients with healthcare-associated diarrhea. IMPORTANCE: Clostridioides difficile is a toxin-producing bacterial pathogen recognized as the most common cause of diarrhea acquired primarily in healthcare settings. This bacterial species is diverse; its global population has been divided into five different clades using multilocus sequence typing, and strains may express different toxin subtypes that may be related to the clades and, importantly, to the severity and progression of disease. Genotyping of children strains differed from adults suggesting toxins might present a reduced toxicity. We studied extensively cytotoxicity, expression of toxins, whole genome phylogeny, and toxin typing in clinical C. difficile isolates. Most isolates presented a tcdA+/ tcdB+/cdt+ pattern, with high diversity in cytotoxicity and clade 2/ST1 was the most prevalent. However, they all had the same TcdA2/TcdB2 toxin subtype. Advances in genomics and bioinformatics tools offer the opportunity to understand the virulence of C. difficile better and find markers for better clinical use.

Candida parapsilosis: A systematic review to inform the World Health Organization fungal priority pathogens list.

Candida parapsilosis is globally distributed and recognised for causing an increasing proportion of invasive Candida infections. It is associated with high crude mortality in all age groups. It has been particularly associated with nosocomial outbreaks, particularly in association with the use of invasive medical devices such as central venous catheters. Candida parapsilosis is one of the pathogens considered in the WHO priority pathogens list, and this review was conducted to inform the ranking of the pathogen in the list. In this systematic review, we searched PubMed and Web of Science to find studies between 2011 and 2021 reporting on the following criteria for C. parapsilosis infections: mortality, morbidity (hospitalisation and disability), drug resistance, preventability, yearly incidence, and distribution/emergence. We identified 336 potentially relevant papers, of which 51 were included in the analyses. The included studies confirmed high mortality rates, ranging from 17.5% to 46.8%. Data on disability and sequelae were sparse. Many reports highlighted concerns with azole resistance, with resistance rates of >10% described in some regions. Annual incidence rates were relatively poorly described, although there was clear evidence that the proportion of candidaemia cases caused by C. parapsilosis increased over time. While this review summarises current data on C.parapsilosis, there remains an urgent need for ongoing research and surveillance to fully understand and manage this increasingly important pathogen.

Association of Frailty With Risk of Incident Hospital-Treated Infections in Middle-Aged and Older Adults: A Large-Scale Prospective Cohort Study.

BACKGROUND: Although frailty is associated with a range of adverse health outcomes, its association with the risk of hospital-treated infections is uncertain. METHODS: A total of 416 220 participants from the UK Biobank were included in this prospective cohort study. Fried phenotype was adopted to evaluate frailty, which included 5 aspects (gait speed, physical activity, grip strength, exhaustion, and weight). More than 800 infectious diseases were identified based on electronic health records. Cox proportional models were used to estimate the associations. RESULTS: During a median 12.3 years (interquartile range 11.4-13.2) of follow-up (4 747 345 person-years), there occurred 77 988 (18.7%) hospital-treated infections cases. In the fully adjusted model, compared with participants with nonfrail, the hazard ratios (HRs) (95% confidence intervals [CIs]) of those with prefrail and frail for overall hospital-treated infections were 1.22 (1.20, 1.24) and 1.78 (1.72-1.84), respectively. The attributable risk proportion of prefrail and frail were 18.03% and 43.82%. Similarly, compared to those without frailty, the HRs (95% CIs) of those with frailty for bacterial infections were 1.76 (1.70-1.83), for viral infections were 1.62 (1.44-1.82), and for fungal infections were 1.75 (1.47-2.08). No association was found between frailty and parasitic infections (HR: 1.17; 95% CI: 0.62-2.20). CONCLUSIONS: Frailty was significantly associated with a higher risk of hospital-treated infections, except for parasitic infections. Studies evaluating the effectiveness of implementing frailty assessments are needed to confirm our results.

Characterization and genetic analysis of extensively drug-resistant hospital acquired Pseudomonas aeruginosa isolates.

BACKGROUND: The incidence of hospital-acquired infections in extensively drug-resistant Pseudomonas aeruginosa (XDR-PA) has been increasing worldwide and is frequently associated with an increase in mortality and morbidity rates. The aim of this study was to characterize clinical XDR-PA isolates recovered during six months at three different hospitals in Egypt. RESULTS: Seventy hospital-acquired clinical isolates of P. aeruginosa were classified into multidrug-resistant (MDR), extensively drug-resistant (XDR) and pandrug-resistant (PDR), according to their antimicrobial resistance profile. In addition, the possession of genes associated with mobile genetic elements and genes encoding antimicrobial resistance determinants among isolates were detected using polymerase chain reaction. As a result, a significant percentage of the isolates (75.7%) were XDR, while 18.5% were MDR, however only 5.7% of the isolates were non-MDR. The phenotypic detection of carbapenemases, extended-spectrum ß-lactamases (ESBLs) and metallo ß-lactamase (MBL) enzymes showed that 73.6% of XDR-PA isolates were carbapenemases producers, whereas 75.5% and 88.7% of XDR-PA isolates produced ESBLs and MBL respectively. In addition, PCR screening showed that oxa gene was the most frequently detected gene of carbapenemases (91.4%), while aac(6')-lb gene was mostly detected (84.3%) among the screened aminoglycosides-resistance genes. Furthermore, the molecular detection of the colistin resistance gene showed that 12.9% of isolates harbored mcr-1 gene. Concerning mobile genetic element markers (intI, traA, tnp513, and merA), intI was the highest detected gene as it was amplified in 67 isolates (95.7%). Finally, phylogenetic and molecular typing of the isolates via ERIC-PCR analysis revealed 10 different ERIC fingerprints. CONCLUSION: The present study revealed a high prevalence of XDR-PA in hospital settings which were resistant to a variety of antibiotics due to several mechanisms. In addition, 98% of the XDR-PA clinical isolates contained at least one gene associated with movable genetic elements, which could have aided the evolution of these XDR-PA strains. To reduce spread of drug resistance, judicious use of antimicrobial agents and strict infection control measures are therefore essential.

Comparing automated surveillance systems for detection of pathogen-related clusters in healthcare settings.

BACKGROUND: Detection of pathogen-related clusters within a hospital is key to early intervention to prevent onward transmission. Various automated surveillance methods for outbreak detection have been implemented in hospital settings. However, direct comparison is difficult due to heterogenicity of data sources and methodologies. In the hospital setting, we assess the performance of three different methods for identifying microbiological clusters when applied to various pathogens with distinct occurrence patterns. METHODS: In this retrospective cohort study we use WHONET-SaTScan, CLAR (CLuster AleRt system) and our currently used percentile-based system (P75) for the means of cluster detection. The three methods are applied to the same data curated from 1st January 2014 to 31st December 2021 from a tertiary care hospital. We show the results for the following case studies: the introduction of a new pathogen with subsequent endemicity, an endemic species, rising levels of an endemic organism, and a sporadically occurring species. RESULTS: All three cluster detection methods showed congruence only in endemic organisms. However, there was a paucity of alerts from WHONET-SaTScan (n = 9) compared to CLAR (n = 319) and the P75 system (n = 472). WHONET-SaTScan did not pick up smaller variations in baseline numbers of endemic organisms as well as sporadic organisms as compared to CLAR and the P75 system. CLAR and the P75 system revealed congruence in alerts for both endemic and sporadic organisms. CONCLUSIONS: Use of statistically based automated cluster alert systems (such as CLAR and WHONET-Satscan) are comparable to rule-based alert systems only for endemic pathogens. For sporadic pathogens WHONET-SaTScan returned fewer alerts compared to rule-based alert systems. Further work is required regarding clinical relevance, timelines of cluster alerts and implementation.

Plasmid genomic epidemiology of carbapenem-hydrolysing class D ß-lactamase (CDHL)-producing Enterobacterales in Canada, 2010-2021.

Carbapenems are last-resort antibiotics for treatment of infections caused by multidrug-resistant Enterobacterales, but carbapenem resistance is a rising global threat due to the acquisition of carbapenemase genes. Oxacillinase-48 (bla OXA-48)-type carbapenemases are increasing in abundance in Canada and elsewhere; these genes are frequently found on mobile genetic elements and are associated with specific transposons. This means that alongside clonal dissemination, bla OXA-48-type genes can spread through plasmid-mediated horizontal gene transfer. We applied whole genome sequencing to characterize 249 bla OXA-48-type-producing Enterobacterales isolates collected by the Canadian Nosocomial Infection Surveillance Program from 2010 to 2021. Using a combination of short- and long-read sequencing, we obtained 70 complete and circular bla OXA-48-type-encoding plasmids. Using MOB-suite, four major plasmids clustered were identified, and we further estimated a plasmid cluster for 91.9 % (147/160) of incomplete bla OXA-48-type-encoding contigs. We identified different patterns of carbapenemase mobilization across Canada, including horizontal transmission of bla OXA-181/IncX3 plasmids (75/249, 30.1 %) and bla OXA-48/IncL/M plasmids (47/249, 18.9 %), and both horizontal transmission and clonal transmission of bla OXA-232 for Klebsiella pneumoniae ST231 on ColE2-type/ColKP3 plasmids (25/249, 10.0 %). Our findings highlight the diversity of OXA-48-type plasmids and indicate that multiple plasmid clusters and clonal transmission have contributed to bla OXA-48-type spread and persistence in Canada.

Temporal analysis of prevalence and antibiotic-resistance patterns in Stenotrophomonas maltophilia clinical isolates in a 19-year retrospective study.

Stenotrophomonas maltophilia is a nonfermenting gram-negative bacterium associated with multiple nosocomial outbreaks. Antibiotic resistance increases healthcare costs, disease severity, and mortality. Multidrug-resistant infections (such as S. maltophilia infection) are difficult to treat with conventional antimicrobials. This study aimed to investigate the isolation rates, and resistance trends of S. maltophilia infections over the past 19 years, and provide future projections until 2030. In total, 4466 patients with S. maltophilia infection were identified. The adult and main surgical intensive care unit (ICU) had the highest numbers of patients (32.2%), followed by the cardiology department (29.8%), and the paediatric ICU (10%). The prevalence of S. maltophilia isolation increased from 7% [95% confidence interval (CI) 6.3-7.7%] in 2004-2007 to 15% [95% CI 10.7-19.9%] in 2020-2022. Most S. maltophilia isolates were resistant to ceftazidime (72.5%), levofloxacin (56%), and trimethoprim-sulfamethoxazole (14.05%), according to our study. A consistent and significant difference was found between S. maltophilia-positive ICU patients and non-ICU patients (P = 0.0017) during the three-year pandemic of COVID-19 (2019-2021). The prevalence of S. maltophilia isolates is expected to reach 15.08% [95% CI 12.58-17.59%] by 2030. Swift global action is needed to address this growing issue; healthcare authorities must set priorities and monitor infection escalations and treatment shortages.

Healthcare-associated infections and antimicrobial use in acute care hospitals: a point prevalence survey in Lombardy, Italy, in 2022.

BACKGROUND: Healthcare-Associated Infections (HAIs) are a global public health issue, representing a significant burden of disease that leads to prolonged hospital stays, inappropriate use of antimicrobial drugs, intricately linked to the development of resistant microorganisms, and higher costs for healthcare systems. The study aimed to measure the prevalence of HAIs, the use of antimicrobials, and assess healthcare- and patient-related risk factors, to help identify key intervention points for effectively reducing the burden of HAIs. METHODS: A total of 28 acute care hospitals in the Lombardy region, Northern Italy, participated in the third European Point Prevalence Survey (PPS-3) coordinated by ECDC for the surveillance of HAIs in acute care hospitals (Protocol 6.0). RESULTS: HAIs were detected in 1,259 (10.1%, 95% CI 9.6-10.7%) out of 12,412 enrolled patients. 1,385 HAIs were reported (1.1 HAIs per patient on average). The most common types of HAIs were bloodstream infections (262 cases, 18.9%), urinary tract infections (237, 17.1%), SARS-CoV-2 infections (236, 17.0%), pneumonia and lower respiratory tract infections (231, 16.7%), and surgical site infections (152, 11.0%). Excluding SARS-CoV-2 infections, the overall prevalence of HAIs was 8.4% (95% CI 7.9-8.9%). HAIs were significantly more frequent in patients hospitalized in smaller hospitals and in intensive care units (ICUs), among males, advanced age, severe clinical condition and in patients using invasive medical devices. Overall, 5,225 patients (42.1%, 95% CI 41.3-43.0%) received systemic antimicrobial therapy. According to the WHO's AWaRe classification, the Access group accounted for 32.7% of total antibiotic consumption, while Watch and Reserve classes accounted for 57.0% and 5.9% respectively. From a microbiological perspective, investigations were conducted on only 64% of the HAIs, showing, however, a significant pattern of antibiotic resistance. CONCLUSIONS: The PPS-3 in Lombardy, involving data collection on HAIs and antimicrobial use in acute care hospitals, highlights the crucial need for a structured framework serving both as a valuable benchmark for individual hospitals and as a foundation to effectively channel interventions to the most critical areas, prioritizing future regional health policies to reduce the burden of HAIs.

Whole-genome sequencing analysis of multidrug-resistant Serratia marcescens isolates in an intensive care unit in Brazil.

INTRODUCTION: Serratia marcescens is an opportunistic pathogen found ubiquitously in the environment and associated with a wide range of nosocomial infections. This multidrug-resistant bacterium has been a cause of concern for hospitals and healthcare facilities due to its ability to spread rapidly and cause outbreaks. Next generation sequencing genotyping of bacterial isolates has proven to be a valuable tool for tracking the spread and transmission of nosocomial infections. This has allowed for the identification of outbreaks and transmission chains, as well as determining whether cases are due to endogenous or exogenous sources. Evidence of nosocomial transmission has been gathered through genotyping methods. The aim of this study was to investigate the genetic diversity of carbapenemase-producing S. marcescens in an outbreak at a public hospital in Cuiaba, MT, Brazil. METHODOLOGY: Ten isolates of S. marcenses were sequenced and antibiotic resistance profiles analyzed over 12 days. RESULTS: The isolates were clonal and multidrug resistant. Gentamycin and tigecycline had sensitivity in 90% and 80% isolates, respectively. Genomic analysis identified several genes that encode ß-lactamases, aminoglycoside-modifying enzymes, efflux pumps, and other virulence factors. CONCLUSIONS: Systematic surveillance is crucial in monitoring the evolution of S. marcescens genotypes, as it can lead to early detection and prevention of outbreaks.

Investigation of multiple nosocomial infections using a semi-Markov multi-state model.

BACKGROUND: The prevalence of multiple nosocomial infections (MNIs) is on the rise, however, there remains a limited comprehension regarding the associated risk factors, cumulative risk, probability of occurrence, and impact on length of stay (LOS). METHOD: This multicenter study includes all hospitalized patients from 2020 to July 2023 in two sub-hospitals of a tertiary hospital in Guangming District, Shenzhen. The semi-Markov multi-state model (MSM) was utilized to analyze risk factors and cumulative risk of MNI, predict its occurrence probability, and calculate the extra LOS of nosocomial infection (NI). RESULTS: The risk factors for MNI include age, community infection at admission, surgery, and combined use of antibiotics. However, the cumulative risk of MNI is lower than that of single nosocomial infection (SNI). MNI is most likely to occur within 14 days after admission. Additionally, SNI prolongs LOS by an average of 7.48 days (95% Confidence Interval, CI: 6.06-8.68 days), while MNI prolongs LOS by an average of 15.94 days (95% CI: 14.03-18.17 days). Furthermore, the more sites of infection there are, the longer the extra LOS will be. CONCLUSION: The longer LOS and increased treatment difficulty of MNI result in a heavier disease burden for patients, necessitating targeted prevention and control measures.

Association of institutional masking policies with healthcare-associated SARS-CoV-2 infections in Swiss acute care hospitals during the BA.4/5 wave (CH-SUR study): a retrospective observational study.

BACKGROUND: In the initial phase of the SARS-CoV-2 pandemic, masking has been widely accepted in healthcare institutions to mitigate the risk of healthcare-associated infection. Evidence, however, is still scant and the role of masks in preventing healthcare-associated SARS-CoV-2 acquisition remains unclear.We investigated the association of variation in institutional mask policies with healthcare-associated SARS-CoV-2 infections in acute care hospitals in Switzerland during the BA.4/5 2022 wave. METHODS: SARS-CoV-2 infections in hospitalized patients between June 1 and September 5, 2022, were obtained from the "Hospital-based surveillance of COVID-19 in Switzerland"-database and classified as healthcare- or community-associated based on time of disease onset. Institutions provided information regarding institutional masking policies for healthcare workers and other prevention policies. The percentage of healthcare-associated SARS-CoV-2 infections was calculated per institution and per type of mask policy. The association of healthcare-associated SARS-CoV-2 infections with mask policies was tested using a negative binominal mixed-effect model. RESULTS: We included 2'980 SARS-CoV-2 infections from 13 institutions, 444 (15%) were classified as healthcare-associated. Between June 20 and June 30, 2022, six (46%) institutions switched to a more stringent mask policy. The percentage of healthcare-associated infections subsequently declined in institutions with policy switch but not in the others. In particular, the switch from situative masking (standard precautions) to general masking of HCW in contact with patients was followed by a strong reduction of healthcare-associated infections (rate ratio 0.39, 95% CI 0.30-0.49). In contrast, when compared across hospitals, the percentage of health-care associated infections was not related to mask policies. CONCLUSIONS: Our findings suggest switching to a more stringent mask policy may be beneficial during increases of healthcare-associated SARS-CoV-2 infections at an institutional level.

Nosocomial outbreak caused by disinfectant-resistant Serratia marcescens in an adult intensive care unit, Hungary, February to March 2022.

In 2022, an outbreak with severe bloodstream infections caused by Serratia marcescens occurred in an adult intensive care unit (ICU) in Hungary. Eight cases, five of whom died, were detected. Initial control measures could not stop the outbreak. We conducted a matched case-control study. In univariable analysis, the cases were more likely to be located around one sink in the ICU and had more medical procedures and medications than the controls, however, the multivariable analysis was not conclusive. Isolates from blood cultures of the cases and the ICU environment were closely related by whole genome sequencing and resistant or tolerant against the quaternary ammonium compound surface disinfectant used in the ICU. Thus, S. marcescens was able to survive in the environment despite regular cleaning and disinfection. The hospital replaced the disinfectant with another one, tightened the cleaning protocol and strengthened hand hygiene compliance among the healthcare workers. Together, these control measures have proved effective to prevent new cases. Our results highlight the importance of multidisciplinary outbreak investigations, including environmental sampling, molecular typing and testing for disinfectant resistance.

Clinical risk factors and outcomes of carbapenem-resistant Escherichia coli nosocomial infections in a Chinese teaching hospital: a retrospective study from 2013 to 2020.

The emergence of carbapenem-resistant Escherichia coli strains poses a considerable challenge to global public health, and little is known about carbapenemase-producing E. coli strains in Tianjin, China. This study aimed to investigate the risk factors for infections with carbapenem-resistant E. coli (CREC) strains. This retrospective case-control study was conducted at a tertiary teaching hospital. A total of 134 CREC clinical isolates were collected from the General Hospital of Tianjin Medical University between 2013 and 2020. The control group was selected at a ratio of 1:1 from patients with nosocomial carbapenem-susceptible E. coli infection. Risk factors for nosocomial CREC infection and clinical outcomes were analyzed using univariate and multivariate analyses. Multivariate analysis revealed that cephalosporin exposure (odd ratio OR = 2.01), carbapenem exposure (OR = 1.96), glucocorticoid exposure (OR = 32.45), and surgical history (OR = 3.26) were independent risk factors for CREC infection. The in-hospital mortality rate in the CREC group was 29.1%, and age >65 years (OR = 3.19), carbapenem exposure (OR = 3.54), and central venous catheter insertion (OR = 4.19) were independent risk factors for in-hospital mortality in patients with CREC infections. Several factors were identified in the development of nosocomial CREC infections. The CREC isolates were resistant to most antibiotics. Reducing CREC mortality requires a comprehensive consideration of appropriate antibiotic use, underlying diseases, and invasive procedures.IMPORTANCEEscherichia coli is an opportunistic pathogen that causes severe hospital-acquired infections. The spread of carbapenem-resistant E. coli is a global threat to public health, and only a few antibiotics are effective against these infections. Consequently, these infections are usually associated with poor prognosis and high mortality. Therefore, understanding the risk factors associated with the causes and outcomes of these infections is crucial to reduce their incidence and initiate appropriate therapies. In our study, several factors were found to be involved in nosocomial carbapenem-resistant E. coli (CREC) infections, and CREC isolates were resistant to most antibiotics. Reducing CREC mortality needs a comprehensive consideration of whether antibiotics are used appropriately, underlying diseases, and invasive interventions. These findings provide valuable evidence for the development of anti-infective therapy, infection prevention, and control of CREC-positive infections.

Risk factors for multidrug-resistant and extensively drug-resistant Acinetobacter baumannii infection of patients admitted in intensive care unit: a systematic review and meta-analysis.

BACKGROUND: Multidrug-resistant (MDR) and extensively drug-resistant (XDR) Acinetobacter baumannii infections pose challenges for clinical treatment and cause high mortality, particularly in intensive care units (ICUs). AIM: To systematically summarize and analyse the risk factors for MDR/XDR A. baumannii-infected patients admitted to ICUs. METHODS: PubMed, Embase, Web of Science, and the Cochrane Library were searched for eligible original studies published in English before October 2023. Meta-analysis was conducted where appropriate, with mean differences (MDs) and odds ratios (ORs) calculated for continuous and nominal scaled data. The quality of included studies was assessed using the Newcastle-Ottawa Scale (NOS). FINDINGS: Ten studies reporting 1199 ICU patients (604 from general ICUs, 435 from neonatal ICUs, and 160 from paediatric ICUs) from eight countries were included in our analysis. Risk factors associated with MDR A. baumannii infection among patients admitted to general ICUs included high Acute Physiology And Clinical Health II (APACHE Ⅱ) score (mean difference (MD): 7.52; 95% confidence interval (CI): 3.24-11.80; P = 0.0006), invasive procedures (odds ratio (OR): 3.47; 95% CI: 1.70-7.10; P = 0.0006), longer ICU stay (MD: 3.40; 95% CI: 2.94-3.86; P < 0.00001), and use of antibiotics (OR: 2.69; 95% CI: 1.22-5.94; P = 0.01). In the sub-group analysis, longer neonatal ICU stay (MD: 16.88; 95% CI: 9.79-23.97; P < 0.00001) was associated with XDR A. baumannii infection. CONCLUSION: Close attention should be paid to patients with longer ICU stays, undergoing invasive procedures, using antibiotics, and with high APACHE Ⅱ scores to reduce the risk of MDR and XDR A. baumannii infections.

Genomic diversity and antimicrobial resistance in clinical Klebsiella pneumoniae isolates from tertiary hospitals in Southern Ghana.

OBJECTIVES: Comprehensive data on the genomic epidemiology of hospital-associated Klebsiella pneumoniae in Ghana are scarce. This study investigated the genomic diversity, antimicrobial resistance patterns, and clonal relationships of 103 clinical K. pneumoniae isolates from five tertiary hospitals in Southern Ghana-predominantly from paediatric patients aged under 5 years (67/103; 65%), with the majority collected from urine (32/103; 31%) and blood (25/103; 24%) cultures. METHODS: We generated hybrid Nanopore-Illumina assemblies and employed Pathogenwatch for genotyping via Kaptive [capsular (K) locus and lipopolysaccharide (O) antigens] and Kleborate (antimicrobial resistance and hypervirulence) and determined clonal relationships using core-genome MLST (cgMLST). RESULTS: Of 44 distinct STs detected, ST133 was the most common, comprising 23% of isolates (n = 23/103). KL116 (28/103; 27%) and O1 (66/103; 64%) were the most prevalent K-locus and O-antigen types. Single-linkage clustering highlighted the global spread of MDR clones such as ST15, ST307, ST17, ST11, ST101 and ST48, with minimal allele differences (1-5) from publicly available genomes worldwide. Conversely, 17 isolates constituted novel clonal groups and lacked close relatives among publicly available genomes, displaying unique genetic diversity within our study population. A significant proportion of isolates (88/103; 85%) carried resistance genes for ≥3 antibiotic classes, with the blaCTX-M-15 gene present in 78% (n = 80/103). Carbapenem resistance, predominantly due to blaOXA-181 and blaNDM-1 genes, was found in 10% (n = 10/103) of the isolates. CONCLUSIONS: Our findings reveal a complex genomic landscape of K. pneumoniae in Southern Ghana, underscoring the critical need for ongoing genomic surveillance to manage the substantial burden of antimicrobial resistance.

Molecular surveillance of carbapenem-resistant Enterobacterales in two nearby tertiary hospitals to identify regional spread of high-risk clones in Germany, 2019-2020.

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

Risk factors for in-hospital acquisition of carbapenem-resistant Enterobacterales in patients with severe burns.

BACKGROUND: Although patients with severe burns are prone to severe infections with antibiotic-resistant bacteria and inevitably have some risk factors for carbapenem-resistant Enterobacterales (CRE) acquisition, risk factors for CRE infection or colonization in these patients have not been investigated. AIM: To identify the independent risk factors for CRE acquisition in patients with severe burns. METHODS: Patients admitted to the burn intensive care unit (BICU) for acute burn care were categorized based on culture results during BICU care into the CRE group and non-CRE group, which included the carbapenem-susceptible Enterobacterales (CSE) and control groups. Clinical and microbiological factors were compared between the CRE and non-CRE groups, and between the CRE and CSE groups to identify independent risk factors for in-hospital CRE acquisition. FINDINGS: Among the included 489 patients, 101 (20.7%) and 388 (79.3%) patients were classified in the CRE and non-CRE groups, respectively. The non-CRE group included 91 (18.6%) and 297 (60.7%) patients in the CSE and control groups, respectively. In multivariate analysis between the CRE and non-CRE groups, exposure to other CRE-acquired patients (P = 0.018), abbreviated burn severity index score ≥9 (P = 0.012), and mechanical ventilation (P < 0.001) were associated with CRE acquisition. In multivariate analysis between the CRE and CSE groups, exposure to other CRE-acquired patients was associated with CRE acquisition (P = 0.048). CONCLUSION: Considering the limitation of controlling the burn severity in hospitalized patients, enhanced infection control measures for preventing in-hospital CRE transmission among patients with severe burns should be emphasized.

Ventilator-Associated Pneumonia, Ventilator-Associated Events, and Nosocomial Respiratory Viral Infections on the Leeside of the Pandemic.

The COVID-19 pandemic has had an unprecedented impact on population health and hospital operations. Over 7 million patients have been hospitalized for COVID-19 thus far in the United States alone. Mortality rates for hospitalized patients during the first wave of the pandemic were > 30%, but as we enter the fifth year of the pandemic hospitalizations have fallen and mortality rates for hospitalized patients with COVID-19 have plummeted to 5% or less. These gains reflect lessons learned about how to optimize respiratory support for different kinds of patients, targeted use of therapeutics for patients with different manifestations of COVID-19 including immunosuppressants and antivirals as appropriate, and high levels of population immunity acquired through vaccines and natural infections. At the same time, the pandemic has helped highlight some longstanding sources of harm for hospitalized patients including hospital-acquired pneumonia, ventilator-associated events (VAEs), and hospital-acquired respiratory viral infections. We are, thankfully, on the leeside of the pandemic at present; but the large increases in ventilator-associated pneumonia (VAP), VAEs, bacterial superinfections, and nosocomial respiratory viral infections associated with the pandemic beg the question of how best to prevent these complications moving forward. This paper reviews the burden of hospitalization for COVID-19, the intersection between COVID-19 and both VAP and VAEs, the frequency and impact of hospital-acquired respiratory viral infections, new recommendations on how best to prevent VAP and VAEs, and current insights into effective strategies to prevent nosocomial spread of respiratory viruses.