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Background Infections caused by carbapenemase-producing Enterobacteriaceae (CPE) have continually grown as a global public health threat, with significant mortality rates observed across the world. We examined the clinical data from patients with CPE infections and their outcomes, concentrating on Klebsiella pneumoniae isolates. We analysed the clinical information, performed antimicrobial susceptibility testing, and conducted molecular epidemiological and genomic analyses on the isolates to identify patterns in the data. Methods The clinical characteristics of 33 hospitalised patients with confirmed CPE, including patient-related factors associated with the development of CPE infections, were examined. Patients were divided according to whether they were “colonised” or “infected” with CPE and by the timing and frequency of their rectal swab collections, from which 45 swabs were randomly selected for analysis. CPE isolates were purified, and antimicrobial susceptibility tests performed. Whole genome sequences of these isolates were determined and analysed to compute bacterial multilocus sequence types and plasmid replicon types, infer phylogenetic relationships, and identify antimicrobial resistance and virulence genes. Results Altogether, 88.9% (40/45) of the CPE isolates were K. pneumoniae . The most abundant carbapenemase gene family in the K. pneumoniae isolates (33/39) was bla OXA-232 , with bla NDM-1 additionally identified in 19 of them. All CPE isolates carrying either bla OXA-232 or bla NDM-1 were resistant to meropenem, but only 40 from 45 were susceptible to colistin. Among the CPE-infected patients ( n  = 18) and CPE-colonised patients who developed CPE infections during the study ( n  = 3), all but one received standard colistin-based combination therapy. Phylogenetic analysis revealed the polyclonal spread of carbapenemase-producing K. pneumoniae (CPKP) within the patient population, with the following two major subclades identified: ST16 ( n  = 15) and ST231 ( n  = 14). CPKP-ST231 had the highest virulence score of 4 and was associated with primary bacteraemia. The siderophores yersiniabactin and aerobactin, considered to be important virulence factors, were only identified in the CPKP-ST231 genomes. Conclusions This study has revealed the genomic features of colonising CPE isolates, focusing on antimicrobial resistance and virulence determinants. This type of multi-layered analysis can be further exploited in Thailand and elsewhere to modify the regimes used for empirical antibiotic treatment and improve the management strategies for CPE infections in hospitalised patients.

BackgroundThe challenging disinfection process for the elevator mechanism on duodenoscopes and linear echoendoscopes has been identified as a source of clinically significant bacterial transmission. Despite increased awareness, there continues to be a lack of definitive guidelines for bacterial culturing protocols for elevator-containing endoscopes.AimsTo compare two different prospective bacterial surveillance protocols for duodenoscopes and linear echoendoscopes with regard to accuracy, efficiency, and cost.MethodsConsecutive duodenoscopes and linear echoendoscopes used at a single tertiary care center were reprocessed following hospital and manufacturer guidelines, dried using an automatic endoscope-drying machine, and hung overnight in an upright position. Following reprocessing, culture samples were sequentially obtained from each endoscope using two methods, first, the brush protocol followed immediately by the swab protocol.ResultsA total of 532 primary cultures were collected from 17 duodenoscopes and eight linear echoendoscopes. Of these, 266 cultures gathered using the brush protocol were negative, while 266 cultures gathered using the swab protocol resulted in three positive cultures (1.1%). Positive cultures showed Enterobacter cloacae and Klebsiella pneumoniae from one duodenoscope and two linear echoendoscopes. Yearly, the brush protocol amounts to approximately 520 nursing hours, and the swab protocol takes an estimated 42 nursing hours. Annually, the swab protocol could save over $26,500 and 478 nursing hours.ConclusionsThe proposed swab protocol was superior to the brush protocol when evaluating the presence of residual bacteria on elevator-containing endoscopes following reprocessing and saves cost and nursing hours.

Klebsiella pneumoniae is a leading cause of antimicrobial-resistant (AMR) healthcare-associated infections, neonatal sepsis and community-acquired liver abscess, and is associated with chronic intestinal diseases. Its diversity and complex population structure pose challenges for analysis and interpretation of K. pneumoniae genome data. Here we introduce Kleborate, a tool for analysing genomes of K. pneumoniae and its associated species complex, which consolidates interrogation of key features of proven clinical importance. Kleborate provides a framework to support genomic surveillance and epidemiology in research, clinical and public health settings. To demonstrate its utility we apply Kleborate to analyse publicly available Klebsiella genomes, including clinical isolates from a pan-European study of carbapenemase-producing Klebsiella , highlighting global trends in AMR and virulence as examples of what could be achieved by applying this genomic framework within more systematic genomic surveillance efforts. We also demonstrate the application of Kleborate to detect and type K. pneumoniae from gut metagenomes. Klebsiella pneumoniae is a pathogen of increasing public health concern and antimicrobial resistance is becoming more prevalent. Here, the authors describe a K. pneumoniae genotyping tool, Kleborate, that can be used to identify lineages and detect antimicrobial resistance and virulence loci.

Background Data about the burden of extended-spectrum beta-lactamase (ESBL)-producing microorganisms in Africa are limited. Our study aimed to estimate the prevalence of human faecal ESBL carriage in the community of an informal urban settlement in Dar es Salaam (Tanzania, East Africa) by using environmental contamination of household latrines with ESBL as a surrogate marker. Methods Within the context of a large survey in February 2014 assessing 636 randomly selected household latrines for faecal contamination by the detection of growth of E. coli and total faecal coliform bacteria, a randomly selected subset of the samples were screened for ESBL. Results Seventy latrines were screened for ESBL. An average of 11.4 persons (SD ±6.5) were sharing one latrine. Only three (4.3%) latrines had hand-washing facilities and 50 showed faeces on the floor. ESBL-producing Enterobacteriaceae were confirmed in 17 (24.3%) of the 70 latrine samples: 16 E. coli and 1 Klebsiella pneumoniae. Five ESBL E. coli strains were detected on door handles. The most prevalent ESBL type was CTX-M-1 group (76.5%). Pulsed-field gel electrophoresis typing of a subset of ESBL-producing E. coli isolates revealed both diverse singular types and a cluster of 3 identical isolates. There was no significant difference of the latrine and household characteristics between the group with ESBL ( n  = 17) and the group with non-ESBL E. coli ( n  = 53) ( p  > 0.05). Conclusions Almost a quarter of private and shared latrines in an informal urban settlement in Tanzania are contaminated with ESBL-producing microorganisms, suggesting a high prevalence of human ESBL faecal carriage in the community. Shared latrines may serve as a reservoir for transmission in urban community settings in Tanzania.

A 30-year-old bombing victim with a fracture-related pandrug-resistant Klebsiella pneumoniae infection after long-term (>700 days) antibiotic therapy is treated with a pre-adapted bacteriophage along with meropenem and colistin, followed by ceftazidime/avibactam. This salvage therapy results in objective clinical, microbiological and radiological improvement of the patient’s wounds and overall condition. In support, the bacteriophage and antibiotic combination is highly effective against the patient’s K. pneumoniae strain in vitro, in 7-day mature biofilms and in suspensions. In this case study of a patient with fracture-related pandrug-resistant Klebsiella pneumoniae infection after long-term antibiotic therapy, the authors use a combination therapy of pre-adapted bacteriophage and antibiotics resulting in clinical, microbiological and radiological improvement.

Carbapenem-resistant Klebsiella pneumoniae (CRKP) are of particular concern due to the spread of antibiotic resistance genes associated with mobile genetic elements. In this study, we collected 687 carbapenem-resistant strains recovered among clinical samples from 41 hospitals in nine Southern European countries (2016-2018). We identified 11 major clonal lineages, with most isolates belonging to the high-risk clones ST258/512, ST101, ST11, and ST307. bla KPC-like was the most prevalent carbapenemase-encoding gene (46%), with bla OXA-48 present in 39% of isolates. Through the combination and comparison of this EURECA collection with the previous EuSCAPE collection (2013-2014), we investigated the spread of high-risk clones circulating in Europe exhibiting regional differences. We particularly found bla KPC-like ST258/512 in Greece, Italy, and Spain, bla OXA-48 ST101 in Serbia and Romania, bla NDM ST11 in Greece, and bla OXA-48-like ST14 in Türkiye. Genomic surveillance across Europe thus provides crucial insights for local risk mapping and informs necessary adaptions for implementation of control strategies. Klebsiella pneumoniae is an opportunistic pathogen of increasing concern due to the spread of carbapenem resistance. In this study, the authors sequence carbapenem-resistant strains from a hospital surveillance network in southern Europe, describe evolution of high-risk clones, and identify locally important lineages.

Hypervirulent Klebsiella pneumoniae strains often cause life-threatening community-acquired infections in young and healthy hosts, but are usually sensitive to antibiotics. In this study, we investigated a fatal outbreak of ventilator-associated pneumonia caused by a new emerging hypervirulent K pneumoniae strain. The outbreak occurred in the integrated intensive care unit of a new branch of the Second Affiliated Hospital of Zhejiang University (Hangzhou, China). We collected 21 carbapenem-resistant K pneumoniae strains from five patients and characterised these strains for their antimicrobial susceptibility, multilocus sequence types, and genetic relatedness using VITEK-2 compact system, multilocus sequence typing, and whole genome sequencing. We selected one representative isolate from each patient to establish the virulence potential using a human neutrophil assay and Galleria mellonella model and to establish the genetic basis of their hypervirulence phenotype. All five patients had undergone surgery for multiple trauma and subsequently received mechanical ventilation. The patients were aged 53–73 years and were admitted to the intensive care unit between late February and April, 2016. They all had severe pneumonia, carbapenem-resistant K pneumoniae infections, and poor responses to antibiotic treatment and died due to severe lung infection, multiorgan failure, or septic shock. All five representative carbapenem-resistant K pneumoniae strains belonged to the ST11 type, which is the most prevalent carbapenem-resistant K pneumoniae type in China, and originated from the same clone. The strains were positive on the string test, had survival of about 80% after 1 h incubation in human neutrophils, and killed 100% of wax moth larvae (G mellonella) inoculated with 1 × 106 colony-forming units of the specimens within 24 h, suggesting that they were hypervirulent K pneumoniae. Genomic analyses showed that the emergence of these ST11 carbapenem-resistant hypervirulent K pneumoniae strains was due to the acquisition of a roughly 170 kbp pLVPK-like virulence plasmid by classic ST11 carbapenem-resistant K pneumoniae strains. We also detected these strains in specimens collected in other regions of China. The ST11 carbapenem-resistant hypervirulent K pneumoniae strains pose a substantial threat to human health because they are simultaneously hypervirulent, multidrug resistant, and highly transmissible. Control measures should be implemented to prevent further dissemination of such organisms in the hospital setting and the community. Chinese National Key Basic Research and Development Program and Collaborative Research Fund of Hong Kong Research Grant Council.

We aimed to clarify the epidemiologic and clinical importance of evolutionary events that occurred in carbapenem-resistant Klebsiella pneumoniae (CRKP). We collected 203 CRKP causing bloodstream infections in a tertiary hospital in China during 2013-2017. We detected a subclonal shift in the dominant clone sequence type (ST) 11 CRKP in which the previously prevalent capsular loci (KL) 47 had been replaced by KL64 since 2016. Patients infected with ST11-KL64 CRKP had a significantly higher 30-day mortality rate than other CRKP-infected patients. Enhanced virulence was further evidenced by phenotypic tests. Phylogenetic reconstruction demonstrated that ST11-KL64 is derived from an ST11-KL47-like ancestor through recombination. We identified a pLVPK-like virulence plasmid carrying rmpA and peg-344 in ST11-KL64 exclusively from 2016 onward. The pLVPK-like-positive ST11-KL64 isolates exhibited enhanced environmental survival. Retrospective screening of a national collection identified ST11-KL64 in multiple regions. Targeted surveillance of this high-risk CRKP clone is urgently needed.

Among the most urgent public health threats is the worldwide emergence of carbapenem-resistant Enterobacteriaceae 1 – 4 , which are resistant to the antibiotic class of ‘last resort’. In the United States and Europe, carbapenem-resistant strains of the Klebsiella pneumoniae ST258 (ref. 5 ) sequence type are dominant, endemic 6 – 8 and associated with high mortality 6 , 9 , 10 . We report the global evolution of pathogenicity in carbapenem-resistant K. pneumoniae , resulting in the repeated convergence of virulence and carbapenem resistance in the United States and Europe, dating back to as early as 2009. We demonstrate that K. pneumoniae can enhance its pathogenicity by adopting two opposing infection programs through easily acquired gain- and loss-of-function mutations. Single-nucleotide polymorphisms in the capsule biosynthesis gene wzc lead to hypercapsule production, which confers phagocytosis resistance, enhanced dissemination and increased mortality in animal models. In contrast, mutations disrupting capsule biosynthesis genes impair capsule production, which enhances epithelial cell invasion, in vitro biofilm formation and persistence in urinary tract infections. These two types of capsule mutants have emerged repeatedly and independently in Europe and the United States, with hypercapsule mutants associated with bloodstream infections and capsule-deficient mutants associated with urinary tract infections. In the latter case, drug-tolerant K. pneumoniae can persist to yield potentially untreatable, persistent infection. Mutations in Klebsiella pneumoniae that lead to gain or loss of capsule production affect pathogenicity and associate with bloodstream or urinary tract infections, respectively.

Background. Klebsiella pneumoniae is an opportunistic pathogen and leading cause of hospital-associated infections. Intensive care unit (ICU) patients are particularly at risk. Klebsiella pneumoniae is part of the healthy human microbiome, providing a potential reservoir for infection. However, the frequency of gut colonization and its contribution to infections are not well characterized. Methods. We conducted a 1-year prospective cohort study in which 498 ICU patients were screened for rectal and throat carriage of K. pneumoniae shortly after admission. Klebsiella pneumoniae isolated from screening swabs and clinical diagnostic samples were characterized using whole genome sequencing and combined with epidemiological data to identify likely transmission events. Results. Klebsiella pneumoniae carriage frequencies were estimated at 6% (95% confidence interval [CI], 3%–8%) among ICU patients admitted direct from the community, and 19% (95% CI, 14%–51%) among those with recent healthcare contact. Gut colonization on admission was significantly associated with subsequent infection (infection risk 16% vs 3%, odds ratio [OR] = 6.9, P < .001), and genome data indicated matching carriage and infection isolates in 80% of isolate pairs. Five likely transmission chains were identified, responsible for 12% of K. pneumoniae infections in ICU. In sum, 49% of K. pneumoniae infections were caused by the patients' own unique strain, and 48% of screened patients with infections were positive for prior colonization. Conclusions. These data confirm K. pneumoniae colonization is a significant risk factor for infection in ICU, and indicate ∼50% of K. pneumoniae infections result from patients' own microbiota. Screening for colonization on admission could limit risk of infection in the colonized patient and others.