Draft Genome Sequence of Carbapenem-Resistant Klebsiella pneumoniae XPY20 Collected from a Bloodstream Infection Patient

ABSTRACT Bloodstream infections caused by carbapenem-resistant Klebsiella pneumoniae (CRKP) strains have been a severe problem with high clinical costs and high mortality rates. The bla KPC-2-producing CRKP strain XPY20 was collected from the blood of a patient. The genome characteristics and antimicrobial resistance mechanisms were determined using next-generation sequencing.

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Disease Severity Is an Independent Risk Factor of Mortality and Outcomes in Critically Ill Patients With Carbapenem-resistant Klebsiella Pneumoniae Bloodstream Infections: a 5-year Retrospective Analysis

10.21203/rs.3.rs-658252/v1 ◽

2021 ◽

Author(s):

Yuzhen Qiu ◽

Wen Xu ◽

Yunqi Dai ◽

Ruoming Tan ◽

Jialin Liu ◽

...

Keyword(s):

Risk Factors ◽

Septic Shock ◽

Klebsiella Pneumoniae ◽

Critically Ill Patients ◽

Bloodstream Infections ◽

Polymyxin B ◽

Mortality Rates ◽

Carbapenem Resistant ◽

All Cause Mortality ◽

Independent Risk Factors

Abstract Background: Carbapenem-resistant Klebsiella pneumoniae bloodstream infections (CRKP-BSIs) are associated with high morbidity and mortality rates, especially in critically ill patients. Comprehensive mortality risk analyses and therapeutic assessment in real-world practice are beneficial to guide individual treatment.Methods: We retrospectively analyzed 87 patients with CRKP-BSIs (between July 2016 and June 2020) to identify the independent risk factors for 28-day all-cause mortality. The therapeutic efficacies of tigecycline-and polymyxin B-based therapies were analyzed.Results: The 28-day all-cause mortality and in-hospital mortality rates were 52.87% and 67.82%, respectively, arising predominantly from intra-abdominal (56.32%) and respiratory tract infections (21.84%). A multivariate analysis showed that 28-day all-cause mortality was independently associated with the patient’s APACHE II score (p = 0.002) and presence of septic shock at BSI onset (p = 0.006). All-cause mortality was not significantly different between patients receiving tigecycline- or polymyxin B-based therapy (55.81% vs. 53.85%, p = 0.873), and between subgroups mortality rates were also similar. Conclusions: Critical illness indicators (APACHE II scores and presence of septic shock at BSI onset) were independent risk factors for 28-day all-cause mortality. There was no significant difference between tigecycline- and polymyxin B-based therapy outcomes. Prompt and appropriate infection control should be implemented to prevent CRKP infections.

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Combination Regimens for Treatment of Carbapenem-Resistant Klebsiella pneumoniae Bloodstream Infections

Antimicrobial Agents and Chemotherapy ◽

10.1128/aac.03007-15 ◽

2016 ◽

Vol 60 (6) ◽

pp. 3601-3607 ◽

Cited By ~ 47

Author(s):

A. Gomez-Simmonds ◽

B. Nelson ◽

D. P. Eiras ◽

A. Loo ◽

S. G. Jenkins ◽

...

Keyword(s):

Combination Therapy ◽

Klebsiella Pneumoniae ◽

Active Agent ◽

Bloodstream Infections ◽

Individual Treatment ◽

Beta Lactam ◽

Content Type ◽

Carbapenem Resistant ◽

Extended Spectrum

Previous studies reported decreased mortality in patients with carbapenemase-producingKlebsiella pneumoniaebloodstream infections (BSIs) treated with combination therapy but included carbapenem-susceptible and -intermediate isolates, as per revised CLSI breakpoints. Here, we assessed outcomes in patients with BSIs caused by phenotypically carbapenem-resistantK. pneumoniae(CRKP) according to the number ofin vitroactive agents received and whether an extended-spectrum beta-lactam (BL) antibiotic, including meropenem, or an extended-spectrum cephalosporin was administered. We retrospectively reviewed CRKP BSIs at two New York City hospitals from 2006 to 2013, where all isolates had meropenem or imipenem MICs of ≥4 μg/ml. Univariate and multivariable models were created to identify factors associated with mortality. Of 141 CRKP BSI episodes, 23% were treated with a single active agent (SAA), 26% were treated with an SAA plus BL, 28% were treated with multiple active agents (MAA), and 23% were treated with MAA plus BL. Ninety percent of isolates had meropenem MICs of ≥16 μg/ml. Thirty-day mortality was 33% overall and did not significantly differ across the four treatment groups in a multivariable model (P= 0.4); mortality was significantly associated with a Pitt bacteremia score of ≥4 (odds ratio [OR], 7.7; 95% confidence interval [CI], 3.2 to 18.1;P= 0.1), and immunosuppression was protective (OR, 0.4; 95% CI, 0.2 to 1.0;P= 0.04). Individual treatment characteristics were also not significantly associated with outcome, including use of SAAs versus MAA (26% versus 38%,P= 0.1) or BL versus no BL (26% versus 39%,P= 0.1). In summary, in patients with CRKP BSIs caused by isolates with high carbapenem MICs, the role of combination therapy remains unclear, highlighting the need for prospective studies to identify optimal treatment regimens.

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Draft Genome Sequence of a Polymyxin-Resistant Klebsiella pneumoniae Clinical Strain Carrying mcr-8.1 and blaNDM-5

Microbiology Resource Announcements ◽

10.1128/mra.01224-20 ◽

2021 ◽

Vol 10 (12) ◽

Author(s):

Na Pei ◽

Zijuan Jian ◽

Yirui Liu ◽

Tianzhu Liang ◽

Wenen Liu ◽

...

Keyword(s):

Klebsiella Pneumoniae ◽

Global Health ◽

Genome Sequence ◽

Draft Genome ◽

Draft Genome Sequence ◽

Clinical Strain ◽

Content Type ◽

Major Threat ◽

Carbapenem Resistant

ABSTRACT Carbapenem-resistant Klebsiella pneumoniae (CRKP) is a major threat to global health. Here, we report the draft genome sequence of a Klebsiella pneumoniae clinical strain carrying mcr-8.1 and blaNDM-5.

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Population Structure of Klebsiella pneumoniae Causing Bloodstream Infections at a New York City Tertiary Care Hospital: Diversification of Multidrug-Resistant Isolates

Journal of Clinical Microbiology ◽

10.1128/jcm.03455-14 ◽

2015 ◽

Vol 53 (7) ◽

pp. 2060-2067 ◽

Cited By ~ 40

Author(s):

Angela Gomez-Simmonds ◽

Michelle Greenman ◽

Sean B. Sullivan ◽

Joshua P. Tanner ◽

Madeleine G. Sowash ◽

...

Keyword(s):

New York ◽

New York City ◽

Klebsiella Pneumoniae ◽

York City ◽

Tertiary Care Hospital ◽

Tertiary Care ◽

Bloodstream Infections ◽

Mortality Rates ◽

Care Hospital ◽

Content Type

Despite the growing importance of carbapenem-resistantKlebsiella pneumoniae(CRKP), the clonal relationships between CRKP and antibiotic-susceptible isolates remain unclear. We compared the genetic diversity and clinical features of CRKP, third-generation and/or fourth-generation cephalosporin-resistant (Ceph-R)K. pneumoniae, and susceptibleK. pneumoniaeisolates causing bloodstream infections at a tertiary care hospital in New York City between January 2012 and July 2013. Drug susceptibilities were determined with the Vitek 2 system. Isolates underwent multilocus sequence typing and PCR sequencing of thewziandblaKPCgenes. Clinical and microbiological data were extracted from patient records and correlated with molecular data. Among 223 patients, we identified 272 isolates. Of these, 194 were susceptible, 30 Ceph-R, and 48 CRKP, belonging to 144 sequence types (STs). Susceptible (127 STs) and Ceph-R (20 STs) isolates were highly diverse. ST258 dominated CRKP strains (12 STs, with 63% ST258). There was minimal overlap in STs between resistance groups. TheblaKPC-3gene (30%) was restricted to ST258/wzi154, whereasblaKPC-2(70%) was observed for severalwziallele types. CRKP infections occurred more frequently among solid organ transplant (31%) and dialysis (17%) patients. Mortality rates were high overall (28%) and highest among CRKP-infected patients (59%). In multivariable analyses, advanced age, comorbidities, and disease severity were significant predictors of 30-day mortality rates, whereas theK. pneumoniaesusceptibility phenotype was not. Among CRKP infections, we observed a borderline significant association of increased mortality rates with ST258 and thewzi154 allele. Although the clonal spread of ST258 continues to contribute substantially to the dissemination of CRKP, non-ST258 strains appear to be evolving. Further investigations into the mechanisms promoting CRKP diversification and the effects of clonal backgrounds on outcomes are warranted.

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Effect of Resistance Mechanisms on the Inoculum Effect of Carbapenem in Klebsiella pneumoniae Isolates with Borderline Carbapenem Resistance

Antimicrobial Agents and Chemotherapy ◽

10.1128/aac.00533-15 ◽

2015 ◽

Vol 59 (8) ◽

pp. 5014-5017 ◽

Cited By ~ 21

Author(s):

Amos Adler ◽

Ma'ayan Ben-Dalak ◽

Ina Chmelnitsky ◽

Yehuda Carmeli

Keyword(s):

Klebsiella Pneumoniae ◽

Therapeutic Efficacy ◽

Carbapenem Resistance ◽

Bactericidal Effect ◽

Resistance Mechanisms ◽

Content Type ◽

Carbapenem Resistant ◽

Inoculum Effect

ABSTRACTWe aimed to examine the effects of resistance mechanisms on several resistance phenotypes among carbapenem-resistantKlebsiella pneumoniaeisolates with borderline carbapenem MICs. We compared carbapenemase-negativeK. pneumoniaewith carbapenemase-producingK. pneumoniae(CPKP) isolates with similar MICs. CPKP isolates exhibited a marked inoculum effect and were more resistant to the bactericidal effect of meropenem. This suggests that MIC measurements alone may not be sufficient in predicting the therapeutic efficacy of carbapenems against CPKP.

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A Nationwide Screen of Carbapenem-Resistant Klebsiella pneumoniae Reveals an Isolate with Enhanced Virulence and Clinically Undetected Colistin Heteroresistance

Antimicrobial Agents and Chemotherapy ◽

10.1128/aac.00107-19 ◽

2019 ◽

Vol 63 (5) ◽

Cited By ~ 7

Author(s):

Jessie E. Wozniak ◽

Victor I. Band ◽

Andrew B. Conley ◽

Lavanya Rishishwar ◽

Eileen M. Burd ◽

...

Keyword(s):

Multidrug Resistance ◽

Klebsiella Pneumoniae ◽

Resistance Genes ◽

Resistance Mechanisms ◽

Gene Encoding ◽

Content Type ◽

Carbapenem Resistant

ABSTRACT The convergence of hypervirulence and multidrug resistance in Klebsiella pneumoniae is a significant concern. Here, we report the first screen for hypermucoviscosity, a trait associated with increased virulence, using a U.S. surveillance collection of carbapenem-resistant (CR) K. pneumoniae isolates. We identified one hypermucoviscous isolate, which carried a gene encoding the KPC-3 carbapenemase, among numerous resistance genes. The strain further exhibited colistin heteroresistance undetected by diagnostics. This convergence of diverse resistance mechanisms and increased virulence underscores the need for enhanced K. pneumoniae surveillance.

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Roles of ramR and tet(A) Mutations in Conferring Tigecycline Resistance in Carbapenem-Resistant Klebsiella pneumoniae Clinical Isolates

Antimicrobial Agents and Chemotherapy ◽

10.1128/aac.00391-17 ◽

2017 ◽

Vol 61 (8) ◽

Cited By ~ 17

Author(s):

Sheng-Kang Chiu ◽

Li-Yueh Huang ◽

Hsi Chen ◽

Yu-Kuo Tsai ◽

Ci-Hong Liou ◽

...

Keyword(s):

Klebsiella Pneumoniae ◽

Synergistic Effects ◽

Fold Increase ◽

Amplicon Sequencing ◽

Resistance Mechanisms ◽

Content Type ◽

Carbapenem Resistant ◽

A Site

ABSTRACT Tigecycline is regarded as a last-resort treatment for carbapenem-resistant Klebsiella pneumoniae (CRKP) infections, but increasing numbers of tigecycline-resistant K. pneumoniae isolates have been reported. The tigecycline resistance mechanisms in CRKP are undetermined. This study aimed to elucidate the mechanisms underlying tigecycline resistance in 16 tigecycline- and carbapenem-resistant K. pneumoniae (TCRKP) isolates. Mutations in tigecycline resistance determinant genes [ramR, acrR, oqxR, tet(A), tet(L), tet(X), tet(M), rpsJ] were assessed by PCR amplicon sequencing, and mutations in ramR and tet(A) exhibited high prevalences individually (81%) and in combination (63%). Eight functional ramR mutation profiles reducing tigecycline sensitivity were verified by plasmid complementation of wild-type and mutant ramR. Using a site-specific mutant, the most frequent RamR mutation, A19V (60%), had no significant effect on tigecycline susceptibility or the upregulation of ramA and acrA. Two tet(A) variants with double frameshift mutations, type 1 and type 2, were identified; type 2 tet(A) is novel. A parent strain transformed with a plasmid carrying type 1 or type 2 tet(A) increased the tigecycline MIC by 8-fold or 4-fold, respectively. Synergistic effects were observed in strains harboring no ramR gene and a mutated tet(A), with an 8-fold increase in the tigecycline MIC compared with that in strains harboring only mutated tet(A) being seen. Overall, mutations in the ramR and tet(A) efflux genes constituted the major tigecycline resistance mechanisms among the studied TCRKP isolates. The identification of strains exhibiting the combination of a ramR deficiency and widespread mutated tet(A) is concerning due to the possible dissemination of increased tigecycline resistance in K. pneumoniae.

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Ertapenem-Containing Double-Carbapenem Therapy for Treatment of Infections Caused by Carbapenem-Resistant Klebsiella pneumoniae

Antimicrobial Agents and Chemotherapy ◽

10.1128/aac.01569-15 ◽

2015 ◽

Vol 60 (1) ◽

pp. 669-673 ◽

Cited By ~ 33

Author(s):

Jessica B. Cprek ◽

Jason C. Gallagher

Keyword(s):

Urinary Tract ◽

Klebsiella Pneumoniae ◽

Clinical Success ◽

Treatment Options ◽

Bloodstream Infections ◽

Content Type ◽

Skin Structure ◽

Carbapenem Resistant ◽

Tract Infections ◽

Intraabdominal Infections

ABSTRACTWe describe outcomes of patients with infections with carbapenem-resistantKlebsiella pneumoniae(CRKP) who received ertapenem-containing double-carbapenem therapy (ECDCT). Clinical success was observed in 7/18 (39%) patients overall: bloodstream infections, 3/7 (43%); pneumonia, 1/5 (20%); intraabdominal infections, 0/2 (0%); urinary tract infections, 2/3 (67%); and a skin and skin structure infection, 1/1 (100%). Microbiologic success was observed in 11/14 (79%) evaluable patients; 5/18 (28%) patients died. ECDCT may be effective for CRKP infections with limited treatment options.

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Draft Genome Sequence of an NDM-1- and KPC-2-Coproducing Hypervirulent Carbapenem-Resistant Klebsiella pneumoniae Strain Isolated from Burn Wound Infections

Genome Announcements ◽

10.1128/genomea.00192-18 ◽

2018 ◽

Vol 6 (13) ◽

Cited By ~ 10

Author(s):

Dan-Dan Wei ◽

La-Gen Wan ◽

Yang Liu

Keyword(s):

Klebsiella Pneumoniae ◽

Genome Sequence ◽

Burn Injury ◽

Draft Genome ◽

Draft Genome Sequence ◽

Wound Infections ◽

Burn Wound ◽

Content Type ◽

Republic Of China ◽

Carbapenem Resistant

ABSTRACT We report here the draft genome sequence of an NDM-1- and KPC-2-coproducing hypervirulent carbapenem-resistant Klebsiella pneumoniae strain, isolated from a 58-year-old male in the People’s Republic of China with a burn injury.

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Colistin Resistance Mechanisms in Klebsiella pneumoniae Strains from Taiwan

Antimicrobial Agents and Chemotherapy ◽

10.1128/aac.04763-14 ◽

2015 ◽

Vol 59 (5) ◽

pp. 2909-2913 ◽

Cited By ~ 70

Author(s):

Yi-Hsiang Cheng ◽

Tzu-Lung Lin ◽

Yi-Jiun Pan ◽

Yu-Ping Wang ◽

Yi-Tsung Lin ◽

...

Keyword(s):

Amino Acid ◽

Klebsiella Pneumoniae ◽

Resistance Mechanisms ◽

Single Amino Acid ◽

Colistin Resistance ◽

Amino Acid Mutation ◽

Content Type ◽

Carbapenem Resistant ◽

Resistant Strains ◽

Sequence Types

ABSTRACTColistin is one of the antibiotics of last resort for the treatment of carbapenem-resistantKlebsiella pneumoniaeinfection. This study showed that capsular type K64 (50%) and ST11 (53.9%) are the prevalent capsular and sequence types in the colistin-resistant strains in Taiwan. The interruption of transcripts (38.5%) and amino acid mutation (15.4%) inmgrBare the major mechanisms contributing to colistin resistance. In addition, novel single amino acid changes in MgrB (Stop48Tyr) and PhoQ (Leu26Pro) were observed to contribute to colistin resistance.

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