Antimicrobial resistance and AmpC production in ESBL-producing Klebsiella pneumoniae and Klebsiella quasipneumoniae: A retrospective study in Japanese clinical isolates.

INTRODUCTION: The study of Klebsiella quasipneumoniae, Klebsiella variicola, and AmpC production in extended-spectrum ß-lactamase (ESBL)-producing Klebsiella in Japan is limited, and existing data are insufficient. This study aims to characterize Klebsiella species, determine AmpC production rates, and analyze antimicrobial resistance patterns in ESBL-producing Klebsiella isolates in Japan. METHODS: A total of 139 clinical isolates of ESBL-producing Klebsiella were collected in Japan, along with their corresponding antimicrobial susceptibility profiles. The isolates were identified using a web-based tool. ESBL genes within the isolates were identified using multiplex PCR. Screening for AmpC-producing isolates was performed using cefoxitin disks, followed by multiplex PCR to detect the presence of AmpC genes. Antimicrobial resistance patterns were analyzed across the predominant ESBL genotypes. RESULTS: The web-based tool identified 135 isolates (97.1%) as Klebsiella pneumoniae and 4 (2.9%) as K. quasipneumoniae subsp. similipneumoniae, with no instances of K. variicola detected. Among K. pneumoniae, the CTX-M-1 group emerged as the predominant genotype (83/135, 61.5%), followed by K. quasipneumoniae subsp. similipneumoniae (3/4, 75.0%). The CTX-M-9 group was the second most prevalent genotype in K. pneumoniae (45/135, 33.3%). The high resistance rates were observed for quinolones (ranging from 46.7% to 63.0%) and trimethoprim/sulfamethoxazole (78.5%). The CTX-M-1 group exhibited higher resistance to ciprofloxacin (66/83, 79.5%) compared to the CTX-M-9 group (18/45, 40.0%), a trend also observed for levofloxacin and trimethoprim/sulfamethoxazole. Among the 16 isolates that tested positive during AmpC screening, only one K. pneumoniae isolates (0.7%) were confirmed to carry the AmpC gene. CONCLUSION: Klebsiella pneumoniae with the CTX-M-1 group is the most common ESBL-producing Klebsiella in Japan and showed a low proportion of AmpC production. These isolates are resistant to quinolones and trimethoprim/sulfamethoxazole, highlighting the challenge of managing this pathogen. The findings underscore the importance of broader research and continuous monitoring to address the resistance patterns of ESBL-producing Klebsiella.

Longitudinal analysis within one hospital in sub-Saharan Africa over 20 years reveals repeated replacements of dominant clones of Klebsiella pneumoniae and stresses the importance to include temporal patterns for vaccine design considerations.

BACKGROUND: Infections caused by multidrug-resistant gram-negative bacteria present a severe threat to global public health. The WHO defines drug-resistant Klebsiella pneumoniae as a priority pathogen for which alternative treatments are needed given the limited treatment options and the rapid acquisition of novel resistance mechanisms by this species. Longitudinal descriptions of genomic epidemiology of Klebsiella pneumoniae can inform management strategies but data from sub-Saharan Africa are lacking. METHODS: We present a longitudinal analysis of all invasive K. pneumoniae isolates from a single hospital in Blantyre, Malawi, southern Africa, from 1998 to 2020, combining clinical data with genome sequence analysis of the isolates. RESULTS: We show that after a dramatic increase in the number of infections from 2016 K. pneumoniae becomes hyperendemic, driven by an increase in neonatal infections. Genomic data show repeated waves of clonal expansion of different, often ward-restricted, lineages, suggestive of hospital-associated transmission. We describe temporal trends in resistance and surface antigens, of relevance for vaccine development. CONCLUSIONS: Our data highlight a clear need for new interventions to prevent rather than treat K. pneumoniae infections in our setting. Whilst one option may be a vaccine, the majority of cases could be avoided by an increased focus on and investment in infection prevention and control measures, which would reduce all healthcare-associated infections and not just one.

Infection with the multidrug-resistant Klebsiella pneumoniae New Delhi metallo-B-lactamase strain in patients with COVID-19: Nec Hercules contra plures?

Background: During the coronavirus disease 2019 (COVID-19) pandemic, in patients treated for SARS-CoV-2 infection, infections with the Klebsiella pneumoniae bacteria producing New Delhi metallo-B-lactamase (NDM) carbapenemase in the USA, Brazil, Mexico, and Italy were observed, especially in intensive care units (ICUs). This study aimed to assess the impact of Klebsiella pneumoniae NDM infection and other bacterial infections on mortality in patients treated in ICUs due to COVID-19. Methods: The 160 patients who qualified for the study were hospitalized in ICUs due to COVID-19. Three groups were distinguished: patients with COVID-19 infection only (N = 72), patients with COVID-19 infection and infection caused by Klebsiella pneumoniae NDM (N = 30), and patients with COVID-19 infection and infection of bacterial etiology other than Klebsiella pneumoniae NDM (N = 58). Mortality in the groups and chosen demographic data; biochemical parameters analyzed on days 1, 3, 5, and 7; comorbidities; and ICU scores were analyzed. Results: Bacterial infection, including with Klebsiella pneumoniae NDM type, did not elevate mortality rates. In the group of patients who survived the acute phase of COVID-19 the prolonged survival time was demonstrated: the median overall survival time was 13 days in the NDM bacterial infection group, 14 days in the other bacterial infection group, and 7 days in the COVID-19 only group. Comparing the COVID-19 with NDM infection and COVID-19 only groups, the adjusted model estimated a statistically significant hazard ratio of 0.28 (p = 0.002). Multivariate analysis revealed that age, APACHE II score, and CRP were predictors of mortality in all the patient groups. Conclusion: In patients treated for SARS-CoV-2 infection acquiring a bacterial infection due to prolonged hospitalization associated with the treatment of COVID-19 did not elevate mortality rates. The data suggests that in severe COVID-19 patients who survived beyond the first week of hospitalization, bacterial infections, particularly Klebsiella pneumoniae NDM, do not significantly impact mortality. Multivariate analysis revealed that age, APACHE II score, and CRP were predictors of mortality in all the patient groups.

[Carbapenemase Genes, Virulence Genes, and Molecular Epidemiology of Carbapenem-Resistant Klebsiella pneumoniae Derived From Bloodstream Infections]. / è¡€æµæ„ŸæŸ“ç¢³é’éœ‰çƒ¯è€è¯è‚ºç‚Žå ‹é›·ä¼¯èŒçš„è€è¯åŸºå› å’Œæ¯’åŠ›åŸºå› åŠåˆ†å­æµè¡Œç— å­¦ç ”ç©¶.

Objective: To investigate the clinical characteristics and molecular epidemiology of carbapenem-resistant Klebsiella pneumoniae (CRKP) isolated from patients with bloodstream infections in a large tertiary-care general hospital in Southwest China. Methods: A total of 131 strains of non-repeating CRKP were collected from the blood cultures of patients who had bloodstream infections in 2015-2019. The strains were identified by VITEK-2, a fully automated microbial analyzer, and matrix-assisted laser desorption ionization-time of flight (MALDI-TOF) mass spectrometry. The minimum inhibitory concentration (MIC) was determined by microbroth dilution method. The common carbapenemase resistant genes and virulence factors were identified by PCR. Homology analysis was performed by multilocus sequencing typing. Whole genome sequencing was performed to analyze the genomic characteristics of CRKP without carbapenemase. Results: The 131 strains of CRKP showed resistance to common antibiotics, except for polymyxin B (1.6% resistance rate) and tigacycline (8.0% resistance rate). A total of 105 (80.2%) CRKP strains carried the Klebsiella pneumoniae carbapenemase (KPC) resistance gene, 15 (11.4%) strains carried the New Delhi Metallo-ß-lactamase (NDM) gene, and 4 (3.1%) isolates carried both KPC and NDM genes. Sequence typing (ST) 11 (74.0%) was the dominant sequence type. High detection rates for mrkD (96.2%), fimH (98.5%), entB (100%), and other virulence genes were reported. One hypervirulent CRKP strain was detected. The seven strains of CRKP that did not produce carbapenemase were shown to carry ESBL or AmpC genes and had anomalies in membrane porins OMPK35 and OMPK36, according to whole genome sequencing. Conclusion: In a large-scale tertiary-care general hospital, CRKP mainly carries the KPC gene, has a high drug resistance rate to a variety of antibiotics, and possesses multiple virulence genes. Attention should be paid to CRKP strains with high virulence.

Detection of blaKPC gene among carbapenemase producing Klebsiella pneumoniae isolated from different clinical specimens at tertiary care hospital of Nepal.

BACKGROUND: Klebsiella pneumoniae infections have become a major cause of hospital acquired infection worldwide with the increased rate of acquisition of resistance to antibiotics. Carbapenem resistance mainly among Gram negative is an ongoing problem which causes serious outbreaks dramatically limiting treatment options. This prospective cross-sectional study was designed to detect blaKPC gene from carbapenem resistant K. pneumoniae. MATERIALS AND METHODS: A totally of 1118 different clinical specimens were screened and confirmed for KPC producing K. pneumoniae phenotypically using Meropenem (10 µg) disc. The blaKPC gene was amplified from the isolates of K. pneumoniae to detect the presence of this gene. RESULT: Of the total samples processed, 18.6% (n = 36) were K. pneumoniae and among 36 K. pneumoniae, 61.1% (n = 22/36) were meropenem resistant. This study demonstrated the higher level of MDR 91.7% (n = 33) and KPC production 47.2% (n = 17) among K. pneumoniae isolates. The blaKPC gene was detected in 8.3% (n = 3) of meropenem resistant isolates. CONCLUSION: Since the study demonstrates the higher level of MDR and KPC producing K. pneumoniae isolates that has challenged the use of antimicrobial agents, continuous microbiology, and molecular surveillance to assist early detection and minimize the further dissemination of blaKPC should be initiated. We anticipate that the findings of this study will be useful in understanding the prevalence of KPC-producing K. pneumoniae in Nepal.

Molecular Epidemiology of Carbapenem-Resistant Klebsiella aerogenes in Japan.

Information regarding Klebsiella aerogenes haboring carbapenemase in Japan is limited. A comprehensive nationwide survey was conducted from September 2014 to December 2022, and 67 non-duplicate strains of carbapenem-resistant K. aerogenes were isolated from 57 healthcare facilities in Japan. Through genetic testing and whole-genome sequencing, six strains were found to possess carbapenemases, including imipenemase (IMP)-1, IMP-6, New Delhi metallo-ß-lactamase (NDM)-1, and NDM-5. The strain harboring blaNDM-5 was the novel strain ST709, which belongs to the clonal complex of the predominant ST4 in China. The novel integron containing blaIMP-1 featured the oxacillinase-101 gene, which is a previously unreported structure, with an IncN4 plasmid type. However, integrons found in the strains possessing blaIMP-6, which were the most commonly identified, matched those reported domestically in Klebsiella pneumoniae, suggesting the prevalence of identical integrons. Transposons containing blaNDM are similar or identical to the transposon structure of K. aerogenes harboring blaNDM-5 previously reported in Japan, suggesting that the same type of transposon could have been transmitted to K. aerogenes in Japan. This investigation analyzed mobile genetic elements, such as integrons and transposons, to understand the spread of carbapenemases, highlighting the growing challenge of carbapenem-resistant Enterobacterales in Japan and underscoring the critical need for ongoing surveillance to control these pathogens.

Phenotypic and molecular characterization of ß-lactamase-producing Klebsiella species among children discharged from hospital in Western Kenya.

BACKGROUND: The emergence and spread of ß-lactamase-producing Klebsiella spp. has been associated with a substantial healthcare burden resulting in therapeutic failures. We sought to describe the proportion of phenotypic resistance to commonly used antibiotics, characterize ß-lactamase genes among isolates with antimicrobial resistance (AMR), and assess the correlates of phenotypic AMR in Klebsiella spp. isolated from stool or rectal swab samples collected from children being discharged from hospital. METHODS: We conducted a cross-sectional study involving 245 children aged 1-59 months who were being discharged from hospitals in western Kenya between June 2016 and November 2019. Whole stool or rectal swab samples were collected and Klebsiella spp. isolated by standard microbiological culture. ß-lactamase genes were detected by PCR whilst phenotypic antimicrobial susceptibility was determined using the disc diffusion technique following standard microbiology protocols. Descriptive analyses were used to characterize phenotypic AMR and carriage of ß-lactamase-producing genes. The modified Poisson regression models were used to assess correlates of phenotypic beta-lactam resistance. RESULTS: The prevalence of ß-lactamase carriage among Klebsiella spp. isolates at hospital discharge was 62.9% (154/245). Antibiotic use during hospitalization (adjusted prevalence ratio [aPR] = 4.51; 95%CI: 1.79-11.4, p < 0.001), longer duration of hospitalization (aPR = 1.42; 95%CI: 1.14-1.77, p < 0.002), and access to treated water (aPR = 1.38; 95%CI: 1.12-1.71, p < 0.003), were significant predictors of phenotypically determined ß-lactamase. All the 154 ß-lactamase-producing Klebsiella spp. isolates had at least one genetic marker of ß-lactam/third-generation cephalosporin resistance. The most prevalent genes were blaCTX-M 142/154 (92.2%,) and blaSHV 142/154 (92.2%,) followed by blaTEM 88/154 (57.1%,) and blaOXA 48/154 (31.2%,) respectively. CONCLUSION: Carriage of ß-lactamase producing Klebsiella spp. in stool is common among children discharged from hospital in western Kenya and is associated with longer duration of hospitalization, antibiotic use, and access to treated water. The findings emphasize the need for continued monitoring of antimicrobial susceptibility patterns to inform the development and implementation of appropriate treatment guidelines. In addition, we recommend measures beyond antimicrobial stewardship and infection control within hospitals, improved sanitation, and access to safe drinking water to mitigate the spread of ß-lactamase-producing Klebsiella pathogens in these and similar settings.

Emergence of OXA-48-producing Klebsiella pneumoniae in Lithuania, 2023: a multi-cluster, multi-hospital outbreak.

In 2023, an increase of OXA-48-producing Klebsiella pneumoniae was noticed by the Lithuanian National Public Health Surveillance Laboratory. Whole genome sequencing (WGS) of 106 OXA-48-producing K. pneumoniae isolates revealed three distinct clusters of carbapenemase-producing K. pneumoniae high-risk clones, including sequence type (ST) 45 (n = 35 isolates), ST392 (n = 32) and ST395 (n = 28), involving six, six and nine hospitals in different regions, respectively. These results enabled targeted investigation and control, and underscore the value of national WGS-based surveillance for antimicrobial resistance.

Occurrence, antibiotic resistance profiles and associated risk factors of Klebsiella pneumoniae in poultry farms in selected districts of Somalia Reginal State, Ethiopia.

BACKGROUND: Klebsiella pneumoniae is an opportunistic infection that causes production losses and death in the chicken industry. A cross-sectional study was conducted on exotic chicken breeds reared at the Jigjiga poultry farm from November 2022 to May 2023 to estimate the occurrence, associated risk factors, and antimicrobial susceptibility profiles of Klebsiella pneumoniae. The chickens were selected using systematic random sampling techniques. A total of 384 cloacal swabs were collected aseptically and transported to the laboratory for analysis. For statistical analysis, STATA® version 14.0 statistical software was used. RESULTS: From 384 examined faecal samples, 258 (67.2%) prevalences of Klebsiella pneumoniae were found. Furthermore, the association of the study's risk factors with the prevalence of Klebsiella pneumoniae was explored, and no statistically significant association was identified between sex and age. Nonetheless, relative prevalence at the age level was higher in chickens aged 12 months (67.6%) and Sasso breeds (90.0%). Similarly, male chickens and those raised for meat and egg production had a high prevalence rate of 72.5 and 75.8%, respectively. A total of 30 isolated Klebsiella pneumoniae colonies were tested in vitro for antibiotic sensitivity for six drugs, and it was shown that Klebsiella pneumoniae is moderately sensitive to Penicillin G (43.3%) while having higher resistance to Oxytetracycline (80.0%). CONCLUSIONS: The current findings revealed that the research area had the highest prevalence of Klebsiella pneumoniae, and the isolates were resistant to commonly used drugs in the study area. Thus, a long-term intervention plan, thorough research to determine a nationwide status, as well as further multi-drug resistance patterns and molecular characterization, were urged.

Thrombocytopenia in Klebsiella pneumoniae liver abscess: a retrospective study on its correlation with disease severity and potential causes.

Objective: Thrombocytopenia is commonly associated with infectious diseases and serves as an indicator of disease severity. However, reports on its manifestation in conjunction with Klebsiella pneumoniae liver abscess (KPLA) are scarce. The present study sought to elucidate the correlation between thrombocytopenia and KPLA severity and delve into the etiological factors contributing to the incidence of thrombocytopenia. Materials and methods: A retrospective analysis of the clinical data from patients with KPLA admitted between June 2012 and June 2023 was performed. Baseline characteristics, biochemical assessments, therapeutic interventions, complications, and clinical outcomes were compared between patients with and without thrombocytopenia. To investigate the potential etiologies underlying thrombocytopenia, the association between platelet count reduction and thrombophlebitis was examined, with a particular focus on platelet consumption. Furthermore, bone marrow aspiration results were evaluated to assess platelet production anomalies. Results: A total of 361 KPLA patients were included in the study, among whom 60 (17%) had concurrent thrombocytopenia. Those in the thrombocytopenia group exhibited significantly higher rates of thrombophlebitis (p = 0.042), extrahepatic metastatic infection (p = 0.01), septic shock (p = 0.024), admissions to the intensive care unit (p = 0.002), and in-hospital mortality (p = 0.045). Multivariate analysis revealed that thrombocytopenia (odds ratio, 2.125; 95% confidence interval, 1.114-4.056; p = 0.022) was independently associated with thrombophlebitis. Among the thrombocytopenic patients, eight underwent bone marrow aspiration, and six (75%) had impaired medullar platelet production. After treatment, 88.6% of thrombocytopenic patients (n = 47) demonstrated recovery in their platelet counts with a median recovery time of five days (interquartile range, 3-6 days). Conclusions: Thrombocytopenia in patients with KPLA is indicative of increased disease severity. The underlying etiologies for thrombocytopenia may include impaired platelet production within the bone marrow and augmented peripheral platelet consumption as evidenced by the presence of thrombophlebitis.

Extended-spectrum beta-lactamases in clinical isolates of Escherichia coli and Klebsiella pneumoniae recovered from patients at the Tamale Teaching Hospital, Ghana.

INTRODUCTION: Extended-spectrum beta-lactamase (ESBL)-producing Escherichia coli and Klebsiella pneumoniae are pathogens of significant public health interest for which new antibiotics are urgently needed. AIM: To determine the prevalence of ESBLs in E. coli and K. pneumoniae isolates from patients attending the Tamale Teaching Hospital (TTH) in Ghana. METHODOLOGY: The study was a cross-sectional study involving convenience sampling of E. coli and K. pneumoniae isolates from consenting patients' clinical specimens, between April and June 2015. Antimicrobial susceptibility test was performed, and ESBL-producer phenotypes were further screened for BlaTEM, BlaSHV, and BlaCTX-M genes. Patients' clinical data were additionally collected using a structured questionnaire. RESULTS: Of the 150 non-duplicate E. coli and K. pneumoniae isolates identified, 140 were confirmed as E. coli (84%, n = 117) and K. pneumoniae (16%, n = 23). Of these, sixty-two (44%) [E. coli (84%; n = 52); K. pneumoniae (16%; n = 10)] phenotypically expressed ESBLs. The proportion of ESBL-producing isolates was higher in adults (15-65 years) than in neonates (< 28 days) (p = 0.14). Most of the isolates showed a high percentage resistance to ampicillin (96%) and tetracycline (89%), but a relatively lower resistance to amikacin (36%). No isolate was resistant to meropenem. More ESBL producers were multidrug resistant compared to non-ESBL-producers [23% (14/62) versus 18% (14/78); p = 0.573]. Overall, 74% (n = 46) of the ESBL genotypes expressed BlaCTX-M-1 genes, followed by 63% (n = 39) BlaTEM, and 16% (n = 10) BlaSHV. The study showed a high prevalence of ESBL-positive E. coli and K. pneumoniae, mostly CTX-M-1 producers at TTH. CONCLUSION: Routine laboratory ESBL screening is warranted to inform patient management.

Surveillance and Resistance of Community-Onset Extended-Spectrum ß-Lactamase-Producing Escherichia coli and Klebsiella pneumonia in Oral and Maxillofacial Surgery Site Infections.

Background: The prevalence of community-onset infections of extended spectrum ß-lactamase (ESBL)-producing strains has increased globally, yet surveillance and resistance in patients with oral and maxillofacial surgery site infections is less investigated. Patients and Methods: A retrospective cohort study was performed to investigate risk factors and resistance of ESBL-producing Escherichia coli (ESBL-EC) and ESBL-producing Klebsiella pneumonia (ESBL-KP) among community-onset patients with oral and maxillofacial surgery during January 2010 to December 2016. Demographic features, predisposing factors, clinical outcomes, and antibiotic agent costs were analyzed. Antimicrobial susceptibility testing of nine antimicrobial agents against ESBL-KP and ESBL-EC were measured. Results: Among 2,183 cultures from infection sites in patients with oral and maxillofacial surgery site (45 cases [2.06%]) were confirmed with community-onset ESBL-KP (24; 1.10%) or ESBL-EC (21; 0.96%) infection. Multivariable analysis showed the independent risk factors for ESBL-producing bacterial infection were prior history of hospitalization (adjusted odds ratio [aOR], 10.984; 95% confidence interval [CI], 5.965-59.879; p = 0.025) and malignant condition (aOR, 3.373; 95% CI 2.947-7.634; p = 0.024). Based on antimicrobial susceptibility testing, 57.8% ESBL-KP and ESBL-EC were found receiving inappropriate antimicrobial therapy, and antibiotic agent costs were higher than non-ESBL-producing bacterial infections ($493.8 ± $367.3 vs. $304.1 ± $334.7; p = 0.031). Conclusions: Infections caused by ESBL-KP and ESBL-EC among patients in sites with oral and maxillofacial surgery are associated with prior history of hospitalization and malignant conditions. Prompt detection and appropriate antibiotic administration for community-onset infections of ESBLs are necessary for such populations.

Prevalence of AmpC beta-lactamase and extended spectrum beta-lactamase co-producer in Escherichia coli and Klebsiella species in a teaching hospital.

INTRODUCTION: Beta-lactamase producing bacterial infection has been on surge due to selection pressure and injudicious antibiotics usage. Organisms that co-produced more than one beta lactamase enzyme posed diagnostic challenges which may result in inadequate treatment. To date, there is no standardised guideline offering phenotypic detection of AmpC ß-lactamase. The purpose of this study was to determine the prevalence of ESBLs, AmpC ß-lactamase and co-producer organisms in a teaching hospital. MATERIALS AND METHODS: Three hundred and four isolates of E. coli and Klebsiella sp. had been selected via convenient sampling. These isolates were identified using conventional laboratory methods and their antimicrobial susceptibilities were determined using disc diffusion method. Those isolates were then proceeded with ESBL confirmatory test, cloxacillin-containing Muller Hinton confirmatory test, modified double disk synergy test and AmpC disk test. RESULTS: Out of 304 isolates, 159 isolates were E. coli and 145 were Klebsiella sp. The prevalence of organisms which co-produced AmpC ß-lactamase and ESBL enzymes were 3.0%. Besides that, 39 cefoxitin resistant and three cefoxitin susceptible isolates (13.8%) were proven to produce AmpC ß-lactamase through AmpC disk test. Through the CLSI confirmatory test, 252 (82.9%) isolates were identified as ESBLs producers and the prevalence increased slightly when cloxacillin-containing Muller Hinton were used. Only three ESBLs positive organisms were positive for modified double disk synergy test. CONCLUSION: Distinguishing between AmpC ß-lactamase and ESBL-producing organisms has epidemiological significance as well as therapeutic importance. Moreover, AmpC ß-lactamase and ESBLs co-producing organisms can lead to false negative ESBL confirmatory test. Therefore, knowing the local prevalence can guide the clinician in navigating the treatment.

Expansion and transmission dynamics of high risk carbapenem-resistant Klebsiella pneumoniae subclones in China: An epidemiological, spatial, genomic analysis.

AIMS: Carbapenem-resistant Klebsiella pneumonia (CRKP) is a global threat that varies by region. The global distribution, evolution, and clinical implications of the ST11 CRKP clone remain obscure. METHODS: We conducted a multicenter molecular epidemiological survey using isolates obtained from 28 provinces and municipalities across China between 2011 and 2021. We integrated sequences from public databases and performed genetic epidemiology analysis of ST11 CRKP. RESULTS: Among ST11 CRKP, KL64 serotypes exhibited considerable expansion, increasing from 1.54% to 46.08% between 2011 and 2021. Combining our data with public databases, the phylogenetic and phylogeography analyses indicated that ST11 CRKP appeared in the Americas in 1996 and spread worldwide, with key clones progressing from China's southeastern coast to the inland by 2010. Global phylogenetic analysis showed that ST11 KL64 CRKP has evolved to a virulent, resistant clade with notable regional spread. Single-nucleotide polymorphism (SNP) analysis identified BMPPS (bmr3, mltC, pyrB, ppsC, and sdaC) as a key marker for this clade. The BMPPS SNP clade is associated with high mortality and has strong anti-phagocytic and competitive traits in vitro. CONCLUSIONS: The high-risk ST11 KL64 CRKP subclone showed strong expansion potential and survival advantages, probably owing to genetic factors.

Antimicrobial Resistance as Risk Factor for Recurrent Bacteremia after Staphylococcus aureus, Escherichia coli, or Klebsiella spp. Community-Onset Bacteremia.

We investigated links between antimicrobial resistance in community-onset bacteremia and 1-year bacteremia recurrence by using the clinical data warehouse of Europe's largest university hospital group in France. We included adult patients hospitalized with an incident community-onset Staphylococcus aureus, Escherichia coli, or Klebsiella spp. bacteremia during 2017-2019. We assessed risk factors of 1-year recurrence using Fine-Gray regression models. Of the 3,617 patients included, 291 (8.0%) had >1 recurrence episode. Third-generation cephalosporin (3GC)-resistance was significantly associated with increased recurrence risk after incident Klebsiella spp. (hazard ratio 3.91 [95% CI 2.32-6.59]) or E. coli (hazard ratio 2.35 [95% CI 1.50-3.68]) bacteremia. Methicillin resistance in S. aureus bacteremia had no effect on recurrence risk. Although several underlying conditions and infection sources increased recurrence risk, 3GC-resistant Klebsiella spp. was associated with the greatest increase. These results demonstrate a new facet to illness induced by 3GC-resistant Klebsiella spp. and E. coli in the community setting.

Risk of death in Klebsiella pneumoniae bloodstream infections is associated with specific phylogenetic lineages.

BACKGROUND: Klebsiella pneumoniae species complex (KpSC) bloodstream infections (BSIs) are associated with considerable morbidity and mortality, particularly in elderly and multimorbid patients. Multidrug-resistant (MDR) strains have been associated with poorer outcome. However, the clinical impact of KpSC phylogenetic lineages on BSI outcome is unclear. METHODS: In an 18-month nationwide Norwegian prospective study of KpSC BSI episodes in adults, we used whole-genome sequencing to describe the molecular epidemiology of KpSC, and multivariable Cox regression analysis including clinical data to determine adjusted hazard ratios (aHR) for death associated with specific genomic lineages. FINDINGS: We included 1078 BSI episodes and 1082 bacterial isolates from 1055 patients. The overall 30-day case-fatality rate (CFR) was 12.5%. Median patient age was 73.4, 61.7% of patients were male. Median Charlson comorbidity score was 3. Klebsiella pneumoniae sensu stricto (Kp) (79.3%, n = 858/1082) and K. variicola (15.7%, n = 170/1082) were the dominating phylogroups. Global MDR-associated Kp clonal groups (CGs) were prevalent (25.0%, n = 270/1082) but 78.9% (n = 213/270) were not MDR, and 53.7% (n = 145/270) were community acquired. The major findings were increased risk for death within 30 days in monomicrobial BSIs caused by K. variicola (CFR 16.9%, n = 21; aHR 1.86, CI 1.10-3.17, p = 0.02), and global MDR-associated Kp CGs (CFR 17.0%, n = 36; aHR 1.52, CI 0.98-2.38, p = 0.06) compared to Kp CGs not associated with MDR (CFR 10.1%, n = 46). CONCLUSION: Bacterial traits, beyond antimicrobial resistance, have a major impact on the clinical outcome of KpSC BSIs. The global spread of MDR-associated Kp CGs is driven by other mechanisms than antibiotic selection alone. Further insights into virulence determinants, and their association with phylogenetic lineages are needed to better understand the epidemiology of KpSC infection and clinical outcome.

Klebsiella pneumoniae sequence type 147: a high-risk clone increasingly associated with plasmids carrying both resistance and virulence elements.

Introduction. The first hybrid resistance/virulence plasmid, combining elements from virulence plasmids described in hypervirulent types of Klebsiella pneumoniae with those from conjugative resistance plasmids, was described in an isolate of sequence type (ST) 147 from 2016. Subsequently, this type has been increasingly associated with these plasmids.Hypothesis or gap statement. The extent of carriage of hybrid virulence/resistance plasmids in nosocomial isolates of K. pneumoniae requires further investigation.Aim. To describe the occurrence of virulence/resistance plasmids among isolates of K. pneumoniae received by the UK reference laboratory, particularly among representatives of ST147, and to compare their sequences.Methodology. Isolates received by the laboratory during 2022 and the first half of 2023 (n=1278) were screened for virulence plasmids by PCR detection of rmpA/rmpA2 and typed by variable-number tandem repeat analysis. Twenty-nine representatives of ST147 (including a single-locus variant) from seven hospital laboratories were subjected to long-read nanopore sequencing using high-accuracy q20 chemistry to provide complete assemblies.Results. rmpA/rmpA2 were detected in 110 isolates, of which 59 belonged to hypervirulent K1-ST23, K2-ST86 and K2-ST65/375. Of the remainder, representatives of ST147 formed the largest group, with 22 rmpA/rmpA2-positive representatives (out of 47 isolates). Representatives were from 19 hospital laboratories, with rmpA/rmpA2-positive isolates from 10. Nanopore sequencing of 29 representatives of ST147 divided them into those with no virulence plasmid (n=12), those with non-New Delhi metallo-ß-lactamase (NDM) virulence plasmids (n=6) and those carrying bla NDM-5 (n=9) or bla NDM-1 (n=2) virulence plasmids. These plasmids were of IncFIB(pNDM-Mar)/IncHI1B(pNDM-MAR) replicon types. Most of the non-NDM virulence plasmids were highly similar to the originally described KpvST147L_NDM plasmid. Those carrying bla NDM-5 were highly similar to one another and to previously described plasmids in ST383 and carried an extensive array of resistance genes. Comparison of the fully assembled chromosomes indicated multiple introductions of ST147 in UK hospitals.Conclusion. This study highlights the high proportion of representatives of ST147 that carry IncFIB(pNDM-Mar)/IncHI1B(pNDM-MAR) hybrid resistance virulence plasmids. It is important to be aware of the high probability that representatives of this type carry these plasmids combining resistance and virulence determinants and of the consequent increased risk to patients.

Genomic analysis of extensively drug resistant (XDR) Klebsiella pneumoniae high-risk clone ST14 co-harboring blaNDM and blaOXA-48 recovered from Saudi Arabia.

BACKGROUND: This study presents a comprehensive genomic analysis of NDM and OXA-48-producing Klebsiella pneumoniae in the Western region of Saudi Arabia, traversed by tens of millions of Muslims from various countries annually. This significant influx of visitors invariably leads to the spread and diversity of MDR bacteria. METHODS: Genome sequencing was performed using MiSeq system of 29 CPKP isolates that were NDM and OXA-48-positive isolated from nosocomial infections and demonstrated resistance to most antibiotics, including carbapenems. RESULTS: WGS analysis showed that 12 (41.3%) isolates co-harbored blaOXA-48,blaCTX-M-15 and blaNDM genes. Notably, 16 (55.1%) isolates were identified as high-risk clone ST14, with 50% of these isolates co-harbored blaOXA-48, blaNDM and blaCTX-M-15 genes. All ST14 isolates were identified as capsular genotype KL2 and O1/O2v1 antigen with yersiniabactin locus ypt 14 carried by ICEKp5. The two isolates were identified as ST2096/KL64 hypervirulent K. pneumoniae (hvKp) clone harboring several virulence factors, including the regulator of the mucoid phenotype rmpA2 and aerobactin (iuc-1). Interestingly, two of the hvKp ST383/KL30 isolates were resistant to all tested antimicrobials except colistin and tigecycline, and simultaneously carried numerous ESBLs and carbapenemase genes. These isolates also harbor several virulence factors such as rmpA1, rmpA2, carried on KpVP-1, and aerobactin (iuc-1). CONCLUSION: this study provides insights into the spread and prevalence of high-risk clones of CPKP in the Western region of Saudi Arabia. The ST14 high-risk clone appears to be the predominant CPKP clone in this region, posing a significant threat to public health. This study also reports the presence of two globally disseminated hypervirulent K. pneumoniae (hvKp) clones, namely ST2096 and ST383. Therefore, it is essential to improve surveillance and implement strict infection control measures in this region, which receives a substantial number of visitors to effectively monitor and reduce the spread of high-risk clones of antimicrobial-resistant bacteria, including CPKP.

An Intra-Hospital Spread of Colistin-Resistant K. pneumoniae Isolates-Epidemiological, Clinical, and Genetic Analysis.

Background and Objective: Klebsiella pneumoniae appears to be a significant problem due to its ability to accumulate antibiotic-resistance genes. After 2013, alarming colistin resistance rates among carbapenem-resistant K. pneumoniae have been reported in the Balkans. The study aims to perform an epidemiological, clinical, and genetic analysis of a local outbreak of COLr CR-Kp. Material and Methods: All carbapenem-resistant and colistin-resistant K. pneumoniae isolates observed among patients in the ICU unit of Military Medical Academy, Sofia, from 1 January to 31 October 2023, were included. The results were analyzed according to the EUCAST criteria. All isolates were screened for blaVIM, blaIMP, blaKPC, blaNDM, and blaOXA-48. Genetic similarity was determined using the Dice coefficient as a similarity measure and the unweighted pair group method with arithmetic mean (UPGMA). mgrB genes and plasmid-mediated colistin resistance determinants (mcr-1, mcr-2, mcr-3, mcr-4, and mcr-5) were investigated. Results: There was a total of 379 multidrug-resistant K. pneumoniae isolates, 88% of which were carbapenem-resistant. Of these, there were nine (2.7%) colistin-resistant isolates in six patients. A time and space cluster for five patients was found. Epidemiology typing showed that two isolates belonged to clone A (pts. 1, 5) and the rest to clone B (pts. 2-4) with 69% similarity. Clone A isolates were coproducers of blaNDM-like and blaOXA-48-like and had mgrB-mediated colistin resistance (40%). Clone B isolates had only blaOXA-48-like and intact mgrB genes. All isolates were negative for mcr-1, -2, -3, -4, and -5 genes. Conclusions: The study describes a within-hospital spread of two clones of COLr CR-Kp with a 60% mortality rate. Clone A isolates were coproducers of NDM-like and OXA-48-like enzymes and had mgrB-mediated colistin resistance. Clone B isolates had only OXA-48-like enzymes and intact mgrB genes. No plasmid-mediated resistance was found. The extremely high mortality rate and limited treatment options warrant strict measures to prevent outbreaks.

Comparative genomics of an extensively drug resistant strain Klebsiella pneumoniae IITR008 with international high-risk clonal lineage ST147 isolated from river water.

Carbapenem resistant Klebsiella pneumoniae causing severe infection resulting in morbidity and mortality have become a global health concern. K. pneumoniae with sequence type ST147 is an international high-risk clonal lineage, genomic studies have been done on K. pneumoniae ST147 isolated from clinical origin but genomic data for environmental K. pneumoniae ST147 is very scarce. Herein, K. pneumoniae IITR008, an extensively drug resistant and potentially hypervirulent bacterium, was isolated from Triveni Sangam, the confluence of three rivers where religious congregations are organized. Phenotypic, genomic and comparative genomic analysis of strain IITR008 was performed. Antibiotic susceptibility profiling revealed resistance to 9 different classes of antibiotics including ß-lactams, ß-lactam combination agents, carbapenem, aminoglycoside, macrolide, quinolones, cephams, phenicol, and folate pathway antagonists and was found to be susceptible to only tetracycline. The strain IITR008 possesses hypervirulence genes namely, iutA and iroN in addition to numerous virulence factors coding for adherence, regulation, iron uptake, secretion system and toxin. Both the IITR008 chromosome and plasmid pIITR008_75 possess a plethora of clinically relevant antibiotic-resistant genes (ARGs) including blaCTX-M-15, blaTEM-1, and blaSHV-11, corroborating the phenotypic resistance. Comparative genomic analysis with other ST147 K. pneumoniae provided insights on the phylogenetic clustering of IITR008 with a clinical strain isolated from a patient in Czech with recent travel history in India and other clinical strains isolated from India and Pakistan. According to the 'One Health' perspective, surveillance of antibiotic resistance in the environment is crucial to impede its accelerated development in diverse ecological niches.