Dataset Information

Bloodstream infections caused by Klebsiella pneumoniae: prevalence of bla_KPC, virulence factors and their impacts on clinical outcome.

ABSTRACT:

Background

Klebsiella pneumoniae bloodstream infections (BSIs) occur with significant prevalence and high mortality worldwide. Antimicrobial resistance and virulence are two main factors participating in the pathogenicity of K. pneumoniae. Here we investigated the prevalence of bla_KPC and virulence factors in K. pneumoniae isolated from patients with BSIs and their association with clinical outcome.

Methods

The clinical data of 285 K. pneumoniae BSI cases diagnosed from January 2013 to December 2015 in a Chinese university hospital were retrospectively evaluated. The "string test" was performed to identify hypermucoviscous K. pneumoniae (HMKP). bla_KPC, rmpA, magA and serotype-specific genes were detected by PCR amplification. Finally, a Cox proportional hazards model was employed to determine the predictors of 14-day mortality.

Results

Of these isolates, the prevalence of bla_KPC and rmpA were 33.3% (95/285) and 31.6% (90/285) respectively. 69 isolates (24.2%, 69/285) were HMKP. rmpA was strongly associated with HM phenotype. The KPC-producing KP and HMKP were almost non-overlapping and only three HMKP isolates harbored bla_KPC. K1 (28, 40.6%) and K2 (22, 31.9%) were the most common serotypes in HMKP. 44.9% of HMKP BSIs had origin of biliary tract infection or liver abscess. The 14-day mortality was 100% in bla_KPC⁺/HM⁺ subgroup (3/3), followed by bla_KPC⁺/HM^- (39/92, 42.4%), bla_KPC^-/HM⁺ (5/66, 7.6%) and bla_KPC^-/HM^- (7/124, 5.6%). The 14-day cumulative survival was significantly different between bla_KPC⁺ and bla_KPC^- subgroup (Log-rank p?KPC^-/HM⁺ and bla_KPC^-/HM^- subgroup (Log-rank p?=?0.578) under the condition of comparable illness severity between bla_KPC^-/HM⁺ and bla_KPC^-/HM^- subgroup. Independent risk factors for 14-day mortality were Pitt bacteremia score (HR 1.24, CI 95% 1.13-1.36, p?KPC (HR 2.20, CI 95% 1.06-4.54, p?=?0.034).

Conclusions

Most of HMKP were antibiotic-susceptible and people infected received appropriate antimicrobial therapy, which may explain the favorable outcome of HMKP BSIs. The KPC-producing HMKP BSIs were scarce but life-threatening. bla_KPC was valuable in predicting 14-day mortality.

SUBMITTER: Xu M

PROVIDER: S-EPMC6069789 | biostudies-literature | 2018 Jul

REPOSITORIES: biostudies-literature

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Publications

Bloodstream infections caused by Klebsiella pneumoniae: prevalence of bla<sub>KPC</sub>, virulence factors and their impacts on clinical outcome.

Xu Min M Fu Yiqi Y Kong Haishen H Chen Xiao X Chen Yu Y Li Lanjuan L Yang Qing Q

BMC infectious diseases 20180731 1

<h4>Background</h4>Klebsiella pneumoniae bloodstream infections (BSIs) occur with significant prevalence and high mortality worldwide. Antimicrobial resistance and virulence are two main factors participating in the pathogenicity of K. pneumoniae. Here we investigated the prevalence of bla<sub>KPC</sub> and virulence factors in K. pneumoniae isolated from patients with BSIs and their association with clinical outcome.<h4>Methods</h4>The clinical data of 285 K. pneumoniae BSI cases diagnosed from ...[more]

PMID: 30064360

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Project description:Ceftazidime-avibactam (CZA) therapy has significantly improved survival rates for patients infected by carbapenem-resistant bacteria, including KPC producers. However, resistance to CZA is a growing concern, attributed to multiple mechanisms. In this study, we characterized four clinical CZA-resistant Klebsiella pneumoniae isolates obtained between July 2019 and December 2020. These isolates expressed novel allelic variants of blaKPC-2 resulting from changes in hotspots of the mature protein, particularly in loops surrounding the active site of KPC. Notably, KPC-80 had an K269_D270insPNK mutation near the Lys270-loop, KPC-81 had a del_I173 mutation within the Ω-loop, KPC-96 showed a Y241N substitution within the Val240-loop and KPC-97 had an V277_I278insNSEAV mutation within the Lys270-loop. Three of the four isolates exhibited low-level resistance to imipenem (4 µg/mL), while all remained susceptible to meropenem. Avibactam and relebactam effectively restored carbapenem susceptibility in resistant isolates. Cloning mutant blaKPC genes into pMBLe increased imipenem MICs in recipient Escherichia coli TOP10 for blaKPC-80, blaKPC-96, and blaKPC-97 by two dilutions; again, these MICs were restored by avibactam and relebactam. Frameshift mutations disrupted ompK35 in three isolates. Additional resistance genes, including blaTEM-1, blaOXA-18 and blaOXA-1, were also identified. Interestingly, three isolates belonged to clonal complex 11 (ST258 and ST11) and one to ST629. This study highlights the emergence of CZA resistance including unique allelic variants of blaKPC-2 and impermeability. Comprehensive epidemiological surveillance and in-depth molecular studies are imperative for understanding and monitoring these complex resistance mechanisms, crucial for effective antimicrobial treatment strategies.ImportanceThe emergence of ceftazidime-avibactam (CZA) resistance poses a significant threat to the efficacy of this life-saving therapy against carbapenem-resistant bacteria, particularly Klebsiella pneumoniae-producing KPC enzymes. This study investigates four clinical isolates exhibiting resistance to CZA, revealing novel allelic variants of the key resistance gene, blaKPC-2. The mutations identified in hotspots surrounding the active site of KPC, such as K269_D270insPNK, del_I173, Y241N and V277_I278insNSEAV, prove the adaptability of these pathogens. Intriguingly, low-level resistance to imipenem and disruptions in porin genes were observed, emphasizing the complexity of the resistance mechanisms. Interestingly, three of four isolates belonged to clonal complex 11. This research not only sheds light on the clinical significance of CZA resistance but also shows the urgency for comprehensive surveillance and molecular studies to inform effective antimicrobial treatment strategies in the face of evolving bacterial resistance.

Project description:IntroductionCeftazidime/avibactam-resistance in Klebsiella pneumoniae carbapenemase-producing Klebsiella pneumoniae (KPC-Kp) is a topic of great interest for epidemiological, diagnostic, and therapeutical reasons. However, data on its prevalence and burden on mortality in patients with bloodstream infection (BSI) are lacking. This study was aimed at identifying risk factors for mortality in patients suffering from ceftazidime/avibactam-resistant KPC-Kp BSI.MethodsAn observational retrospective study (January 2018-December 2022) was conducted at a tertiary hospital including all consecutive hospitalized adult patients with a ceftazidime/avibactam-resistant KPC-Kp BSI. Data on baseline clinical features, management, and admission outcomes were analyzed.ResultsOver the study period, among all the KPC-Kp BSI events recorded, 38 (10.5%) were caused by ceftazidime/avibactam-resistant KPC-Kp strains, 37 events being finally included. The ceftazidime/avibactam-resistant KPC-Kp strains revealed susceptibility restoration to at least one carbapenem in more than 60% of cases. In-hospital and 30-day all-cause mortality rates were 22% and 16.2%, respectively. Non-survivors suffered from more baseline comorbidities and experienced a more severe ceftazidime/avibactam-resistant KPC-Kp BSI presentation (i.e., both the Pitt Bacteremia and INCREMENT-CPE scores were significantly higher). Presenting with a higher Charlson Comorbidity Index, chronic kidney disease-KDIGO stage 3A or worse-having recently gone through renal replacement therapy, having suffered from an acute kidney injury following the ceftazidime/avibactam-resistant KPC-Kp BSI, and being admitted for cardiac surgery were the strongest predictors of mortality.ConclusionCeftazidime/avibactam resistance in KPC-Kp BSI easily emerged in our highly KPC-Kp endemic area with remarkable mortality rates. Our findings might provide physicians possibly actionable information when managing patients with a ceftazidime/avibactam-resistant KPC-Kp BSI.

Dataset Information

Bloodstream infections caused by Klebsiella pneumoniae: prevalence of bla_KPC, virulence factors and their impacts on clinical outcome.

Background

Methods

Results

Conclusions

Publications

Bloodstream infections caused by Klebsiella pneumoniae: prevalence of bla<sub>KPC</sub>, virulence factors and their impacts on clinical outcome.

Similar Datasets

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Dataset Information

Bloodstream infections caused by Klebsiella pneumoniae: prevalence of blaKPC, virulence factors and their impacts on clinical outcome.

Background

Methods

Results

Conclusions

Publications

Bloodstream infections caused by Klebsiella pneumoniae: prevalence of bla<sub>KPC</sub>, virulence factors and their impacts on clinical outcome.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets

Bloodstream infections caused by Klebsiella pneumoniae: prevalence of bla_KPC, virulence factors and their impacts on clinical outcome.