Klebsiella pneumoniae infections in COVID-19 patients: a 2-month retrospective analysis in an Italian hospital.
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ABSTRACT:
SUBMITTER: Arcari G
PROVIDER: S-EPMC7691820 | biostudies-literature | 2021 Jan
REPOSITORIES: biostudies-literature
Publications
Klebsiella pneumoniae infections in COVID-19 patients: a 2-month retrospective analysis in an Italian hospital.
Arcari Gabriele G Raponi Giammarco G Sacco Federica F Bibbolino Giulia G Di Lella Federica Maria FM Alessandri Francesco F Coletti Monica M Trancassini Maria M Deales Alberto A Pugliese Francesco F Antonelli Guido G Carattoli Alessandra A
International journal of antimicrobial agents 20201127 1
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Project description:Multidrug-resistant (MDR) Klebsiella pneumoniae is one of the most important causes of nosocomial infections worldwide. After the spread of strains resistant to beta-lactams at the end of the previous century, the diffusion of isolates resistant to carbapenems and colistin is now reducing treatment options and the containment of infections. Carbapenem-resistant K. pneumoniae strains have spread rapidly among Italian hospitals, with four subclades of pandemic clonal group 258 (CG258). Here we show that a single Italian hospital has been invaded by three of these subclades within 27 months, thus replicating on a small scale the "Italian scenario." We identified a single clone responsible for an epidemic outbreak involving seven patients, and we reconstructed its star-like pattern of diffusion within the intensive care unit. This epidemiological picture was obtained through phylogenomic analysis of 16 carbapenem-resistant K. pneumoniae isolates collected in the hospital during a 27-month period, which were added to a database of 319 genomes representing the available global diversity of K. pneumoniae strains. Phenotypic and molecular assays did not reveal virulence or resistance determinants specific for the outbreak isolates. Other factors, rather than selective advantages, might have caused the outbreak. Finally, analyses allowed us to identify a major subclade of CG258 composed of strains bearing the yersiniabactin virulence factor. Our work demonstrates how the use of combined phenotypic, molecular, and whole-genome sequencing techniques can help to identify quickly and to characterize accurately the spread of MDR pathogens.
| S-EPMC4540926 | biostudies-literature
Project description:Klebsiella pneumoniae is a major cause of opportunistic healthcare-associated infections, which are increasingly complicated by the presence of extended-spectrum beta-lactamases (ESBLs) and carbapenem resistance. We conducted a year-long prospective surveillance study of K. pneumoniae clinical isolates in hospital patients. Whole-genome sequence (WGS) data reveals a diverse pathogen population, including other species within the K. pneumoniae species complex (18%). Several infections were caused by K. variicola/K. pneumoniae hybrids, one of which shows evidence of nosocomial transmission. A wide range of antimicrobial resistance (AMR) phenotypes are observed, and diverse genetic mechanisms identified (mainly plasmid-borne genes). ESBLs are correlated with presence of other acquired AMR genes (median n = 10). Bacterial genomic features associated with nosocomial onset are ESBLs (OR 2.34, p = 0.015) and rhamnose-positive capsules (OR 3.12, p < 0.001). Virulence plasmid-encoded features (aerobactin, hypermucoidy) are observed at low-prevalence (<3%), mostly in community-onset cases. WGS-confirmed nosocomial transmission is implicated in just 10% of cases, but strongly associated with ESBLs (OR 21, p < 1 × 10-11). We estimate 28% risk of onward nosocomial transmission for ESBL-positive strains vs 1.7% for ESBL-negative strains. These data indicate that K. pneumoniae infections in hospitalised patients are due largely to opportunistic infections with diverse strains, with an additional burden from nosocomially-transmitted AMR strains and community-acquired hypervirulent strains.
| S-EPMC9156735 | biostudies-literature
Project description:ObjectiveA recent alarming report from the World Health Organization highlighted the rapid global spread of a hypervirulent, carbapenem-resistant strain of Klebsiella pneumoniae. The COVID-19 pandemic frequently led to bacterial co-infections, with K. pneumoniae being a common and highly pathogenic agent. This study aimed to assess KP characteristics via whole-genome sequencing and clarify its molecular epidemiology to guide standardized clinical treatment.MethodsOur retrospective analysis of clinical data from COVID-19 patients admitted to our hospital between 7 December 2022, and 2 January 2023-following China's policies changes, which led to a significant influx of patients-identified 17 K. pneumoniae isolates from sputum samples with bacterial co-infections. These isolates underwent whole-genome sequencing for ST typing, virulence gene annotation, plasmid profiling, and antimicrobial susceptibility testing.ResultsOf the 17 K. pneumoniae isolates, 52.9% were hypermucoviscous. Whole genome sequencing identified eight sequence types (STs), with ST23/KL1 being the most prevalent at 35.3%. Virulence genes were present in 94.1% of strains, including Yersiniabactin (70.6%), Aerobactin (82.3%), and Salmochelin (88.2%). Plasmid analysis revealed common IncHI1B/FIBk or IncFIBk types. All isolates were highly sensitive to antibiotics, except for blaSHV resistance. The 17 patients had a median age of 71 years and significant comorbidities, such as hypertension (64.7%) and diabetes (41.2%).ConclusionThe ST types and virulence gene profiles indicate that most K. pneumoniae strains co-infecting COVID-19 patients are common, high-virulence strains prevalent in the Asia-Pacific region. Our findings suggest that COVID-19 may contribute to the spread of hypervirulent K. pneumoniae strains, potentially informing the ongoing WHO epidemic alert.
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Project description:The increased frequency of bacteraemias caused by pandrug-resistant Klebsiellapneumoniae (PDR-Kp) has significant implications. The aim of the present study was to identify predictors associated with mortality of PDR-Kp bacteraemias. Patients with monomicrobial bacteraemia due to PDR-Kp were included. K. pneumoniae was considered PDR if it showed resistance to all available groups of antibiotics. Primary outcome was 30-day mortality. Minimum inhibitory concentrations (MICs) of meropenem, tigecycline, fosfomycin, and ceftazidime/avibactam were determined by Etest, whereas for colistin, the broth microdilution method was applied. blaKPC, blaVIM, blaNDM, and blaOXA genes were detected by PCR. Among 115 PDR-Kp bacteraemias, the majority of infections were primary bacteraemias (53; 46.1%), followed by catheter-related (35; 30.4%). All isolates were resistant to tested antimicrobials. blaKPC was the most prevalent carbapenemase gene (98 isolates; 85.2%). Thirty-day mortality was 39.1%; among 51 patients with septic shock, 30-day mortality was 54.9%. Multivariate analysis identified the development of septic shock, Charlson comorbidity index, and bacteraemia other than primary or catheter-related as independent predictors of mortality, while a combination of at least three antimicrobials was identified as an independent predictor of survival. Mortality of PDR-Kp bloodstream infections was high. Administration of at least three antimicrobials might be beneficial for infections in critically ill patients caused by such pathogens.
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Project description:BackgroundFew small studies have described hospital-acquired infections (HAIs) occurring in patients with COVID-19.Research questionWhat characteristics in critically ill patients with COVID-19 are associated with HAIs and how are HAIs associated with outcomes in these patients?Study design and methodsMulticenter retrospective analysis of prospectively collected data including adult patients with severe COVID-19 admitted to eight Italian hub hospitals from February 20, 2020, through May 20, 2020. Descriptive statistics and univariate and multivariate Weibull regression models were used to assess incidence, microbial cause, resistance patterns, risk factors (ie, demographics, comorbidities, exposure to medication), and impact on outcomes (ie, ICU discharge, length of ICU and hospital stays, and duration of mechanical ventilation) of microbiologically confirmed HAIs.ResultsOf the 774 included patients, 359 patients (46%) demonstrated 759 HAIs (44.7 infections/1,000 ICU patient-days; 35% multidrug-resistant [MDR] bacteria). Ventilator-associated pneumonia (VAP; n = 389 [50%]), bloodstream infections (BSIs; n = 183 [34%]), and catheter-related BSIs (n = 74 [10%]) were the most frequent HAIs, with 26.0 (95% CI, 23.6-28.8) VAPs per 1,000 intubation-days, 11.7 (95% CI, 10.1-13.5) BSIs per 1,000 ICU patient-days, and 4.7 (95% CI, 3.8-5.9) catheter-related BSIs per 1,000 ICU patient-days. Gram-negative bacteria (especially Enterobacterales) and Staphylococcus aureus caused 64% and 28% of cases of VAP, respectively. Variables independently associated with infection were age, positive end expiratory pressure, and treatment with broad-spectrum antibiotics at admission. Two hundred thirty-four patients (30%) died in the ICU (15.3 deaths/1,000 ICU patient-days). Patients with HAIs complicated by septic shock showed an almost doubled mortality rate (52% vs 29%), whereas noncomplicated infections did not affect mortality. HAIs prolonged mechanical ventilation (median, 24 days [interquartile range (IQR), 14-39 days] vs 9 days [IQR, 5-13 days]; P < .001), ICU stay (24 days [IQR, 16-41 days] vs 9 days [IQR, 6-14 days]; P = .003), and hospital stay (42 days [IQR, 25-59 days] vs 23 days [IQR, 13-34 days]; P < .001).InterpretationCritically ill patients with COVID-19 are at high risk for HAIs, especially VAPs and BSIs resulting from MDR organisms. HAIs prolong mechanical ventilation and hospitalization, and HAIs complicated by septic shock almost double mortality.Trial registryClinicalTrials.gov; No.: NCT04388670; URL: www.clinicaltrials.gov.
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Project description:Background During COVID-19 outbreak, Italy was the first country in Europe to be heavily affected with an intensive care unit mortality of 26%. In order to reduce this percentage, physicians should establish clear and objective criteria to stratify COVID-19 patients at high risk of in-hospital death. Thus, the aim has been to test a large spectrum of variables ranging from clinical evaluation to laboratory biomarkers to identify which parameter would best predict all-cause in-hospital mortality in COVID-19 patients. Design observational study. Results Multivariate Cox regression analysis showed that each 5 years of increase in age corresponded to a hazard ratio (HR) of 1.28 (95% CI 1.00-1.65, P = .050); each increment of 803 ng/L of N-terminal pro-B-type natriuretic peptide (NT-proBNP) corresponded to a HR of 1.24 (95% CI 1.11-1.39, P < .001); each increment of 58 ng/L of interleukin (IL)-6 corresponded to a HR of 1.23 (95% CI 1.09-1.40, P < .001), and each increment of 250 U/L of lactate dehydrogenase (LDH) corresponded to a HR of 1.23 (95% CI 1.10-1.37, P < .001). According to the calculated cut-points for age (≥70 years), NT-proBNP (≥803 ng/L), IL-6 (≥58 ng/L) and LDH (≥371 U/L) when 2 out of these 4 were overcome, the HR was 2.96 (95% CI 1.97-4.45, P < .001). Conclusion In COVID-19 patients, besides age, the evaluation of three biochemical parameters, available in few hours after hospital admission can predict in-hospital mortality regardless of other comorbidities.
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Project description:New Delhi metallo-β-lactamase (NDM) carbapenemase has been considered a global threat due to its worldwide widespread in recent years. In Portugal, a very low number of infections with NDM-producing Enterobacterales has been reported. A total of 52 strains from 40 patients and 1 environmental sample isolated during COVID-19 pandemic were included in this study. Wholegenome sequencing (WGS) was performed on 20 carbapenemase-producing strains, including 17 NDM-1-producing Klebsiella pneumoniae ST11-KL105 lineage strains, one NDM-1-producing Escherichia coli ST58 strain and one KPC-3-producing K. pneumoniae ST147 strain, recovered from a total of 19 patients. Of interest, also one NDM-1-producing K. pneumoniae ST11-KL105 was collected from the hospital environment. Genome-wide phylogenetic analysis revealed an ongoing dissemination of NDM-1-producing K. pneumoniae ST11 strains (n = 18) with the same genetic features seen across multiple wards. Furthermore, the ST58 E. coli strain, collected from a patient rectal swab that was also colonised with a K. pneumoniae strain, also showed the IncFIA plasmid replicon and the blaNDM-1 gene (preceded by IS30 and followed by genes bleMBL, trpF, dsbC, cutA, groES and groEL). The blaNDM-1 is part of Tn125-like identical to those reported in Poland, Italy and India. The blaKPC-3 K. pneumoniae ST147-KL64 strain has the genetic environment Tn4401d isoform. In conclusion, herein we report the molecular epidemiology, resistome, virulome and mobilome of the first NDM-1 carbapenemase outbreak caused by K. pneumoniae ST11-KL105 lineage during the COVID-19 pandemic in Portugal. Moreover, the outbreak strains characterised included seventeen different patients (infected and colonised) and one environmental sample which also emphasises the role of commensal and hospital environment strains in the dissemination of the outbreak.
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Project description:Multidrug resistant (MDR) Klebsiella pneumoniae is a common cause of nosocomial infections worldwide. Recent years have seen an explosion of resistance to extended-spectrum β-lactamases (ESBLs) and emergence of carbapenem resistance. Here, we examine 198 invasive K. pneumoniae isolates collected from over a decade in Kilifi County Hospital (KCH) in Kenya. We observe a significant increase in MDR K. pneumoniae isolates, particularly to third generation cephalosporins conferred by ESBLs. Using whole-genome sequences, we describe the population structure and the distribution of antimicrobial resistance genes within it. More than half of the isolates examined in this study were ESBL-positive, encoding CTX-M-15, SHV-2, SHV-12 and SHV-27, and 79% were MDR conferring resistance to at least three antimicrobial classes. Although no isolates in our dataset were found to be resistant to carbapenems we did find a plasmid with the genetic architecture of a known New Delhi metallo-β-lactamase-1 (NDM)-carrying plasmid in 25 isolates. In the absence of carbapenem use in KCH and because of the instability of the NDM-1 gene in the plasmid, the NDM-1 gene has been lost in these isolates. Our data suggests that isolates that encode NDM-1 could be present in the population; should carbapenems be introduced as treatment in public hospitals in Kenya, resistance is likely to ensue rapidly.
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