First Clinical Cases of OXA-48-Producing Carbapenem-Resistant Klebsiella pneumoniae in the United States: the "Menace" Arrives in the New World

ABSTRACT Heteroresistance is a form of antibiotic resistance where a bacterial strain is comprised of a minor resistant subpopulation and a majority susceptible subpopulation. We showed previously that colistin heteroresistance can mediate the failure of colistin therapy in an in vivo infection model, even for isolates designated susceptible by clinical diagnostics. We sought to characterize the extent of colistin heteroresistance among the highly drug-resistant carbapenem-resistant Enterobacterales (CRE). We screened 408 isolates for colistin heteroresistance. These isolates were collected between 2012 and 2015 in eight U.S. states as part of active surveillance for CRE. Colistin heteroresistance was detected in 10.1% (41/408) of isolates, and it was more common than conventional homogenous resistance (7.1%, 29/408). Most (93.2%, 38/41) of these heteroresistant isolates were classified as colistin susceptible by standard clinical diagnostic testing. The frequency of colistin heteroresistance was greatest in 2015, the last year of the study. This was especially true among Enterobacter isolates, of which specific species had the highest rates of heteroresistance. Among Klebsiella pneumoniae isolates, which were the majority of isolates tested, there was a closely related cluster of colistin-heteroresistant ST-258 isolates found mostly in Georgia. However, cladistic analysis revealed that, overall, there was significant diversity in the genetic backgrounds of heteroresistant K. pneumoniae isolates. These findings suggest that due to being largely undetected in the clinic, colistin heteroresistance among CRE is underappreciated in the United States. IMPORTANCE Heteroresistance is an underappreciated phenomenon that may be the cause of some unexplained antibiotic treatment failures. Misclassification of heteroresistant isolates as susceptible may lead to inappropriate therapy. Heteroresistance to colistin was more common than conventional resistance and was overwhelmingly misclassified as susceptibility by clinical diagnostic testing. Higher proportions of colistin heteroresistance observed in certain Enterobacter species and clustering among heteroresistant Klebsiella pneumoniae strains may inform colistin treatment recommendations. Overall, the rate of colistin nonsusceptibility was more than double the level detected by clinical diagnostics, suggesting that the prevalence of colistin nonsusceptibility among CRE may be higher than currently appreciated in the United States.

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IMP-Producing Carbapenem-Resistant Klebsiella pneumoniae in the United States

Journal of Clinical Microbiology ◽

10.1128/jcm.05297-11 ◽

2011 ◽

Vol 49 (12) ◽

pp. 4239-4245 ◽

Cited By ~ 42

Author(s):

B. M. Limbago ◽

J. K. Rasheed ◽

K. F. Anderson ◽

W. Zhu ◽

B. Kitchel ◽

...

Keyword(s):

United States ◽

Klebsiella Pneumoniae ◽

The United States ◽

Carbapenem Resistant

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ARGONAUT II Study of the In Vitro Activity of Plazomicin against Carbapenemase-Producing Klebsiella pneumoniae

Antimicrobial Agents and Chemotherapy ◽

10.1128/aac.00012-20 ◽

2020 ◽

Vol 64 (5) ◽

Author(s):

Michael R. Jacobs ◽

Caryn E. Good ◽

Andrea M. Hujer ◽

Ayman M. Abdelhamed ◽

Daniel D. Rhoads ◽

...

Keyword(s):

United States ◽

16S Rrna ◽

Klebsiella Pneumoniae ◽

Great Lakes ◽

The United States ◽

Great Lakes Region ◽

In Vitro Activity ◽

Content Type ◽

Carbapenem Resistant

ABSTRACT Plazomicin was tested against 697 recently acquired carbapenem-resistant Klebsiella pneumoniae isolates from the Great Lakes region of the United States. Plazomicin MIC50 and MIC90 values were 0.25 and 1 mg/liter, respectively; 680 isolates (97.6%) were susceptible (MICs of ≤2 mg/liter), 9 (1.3%) intermediate (MICs of 4 mg/liter), and 8 (1.1%) resistant (MICs of >32 mg/liter). Resistance was associated with rmtF-, rmtB-, or armA-encoded 16S rRNA methyltransferases in all except 1 isolate.

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Multiplex PCR Analysis for Rapid Detection of Klebsiella pneumoniae Carbapenem-Resistant (Sequence Type 258 [ST258] and ST11) and Hypervirulent (ST23, ST65, ST86, and ST375) Strains

Journal of Clinical Microbiology ◽

10.1128/jcm.00731-18 ◽

2018 ◽

Vol 56 (9) ◽

Cited By ~ 24

Author(s):

Fangyou Yu ◽

Jingnan Lv ◽

Siqiang Niu ◽

Hong Du ◽

Yi-Wei Tang ◽

...

Keyword(s):

United States ◽

Klebsiella Pneumoniae ◽

Multiplex Pcr ◽

Virulence Genes ◽

The United States ◽

Sequence Type ◽

Pcr Assay ◽

Content Type ◽

Carbapenem Resistant ◽

Resistant Strains

ABSTRACT Carbapenem-resistant and hypervirulent Klebsiella pneumoniae strains have emerged recently. These strains are both hypervirulent and multidrug resistant and may also be highly transmissible and able to cause severe infections in both the hospital and the community. Clinical and public health needs require a rapid and comprehensive molecular detection assay to identify and track the spread of these strains and provide timely infection control information. Here, we develop a rapid multiplex PCR assay capable of distinguishing K. pneumoniae carbapenem-resistant isolates of sequence type 258 (ST258) and ST11, and hypervirulent ST23, ST65/ST375, and ST86 clones, as well as capsular types K1, K2, K locus type 47 (KL47), and KL64, and virulence genes rmpA, rmpA2, iutA, and iroN. The assay demonstrated 100% concordance with 118 previously genotyped K. pneumoniae isolates and revealed different populations of carbapenem-resistant and hypervirulent strains in two collections in China and the United States. The results showed that carbapenem-resistant and hypervirulent K. pneumoniae strains are still rare in the United States, whereas in China, ∼50% of carbapenem-resistant strains carry rmpA/rmpA2 and iutA virulence genes, which are largely associated with the epidemic ST11 strains. Similarly, a high prevalence of hypervirulent strains was found in carbapenem-susceptible isolates in two Chinese hospitals, but these primarily belong to ST23, ST65/ST375, and ST86, which are distinct from the carbapenem-resistant strains. Taken together, our results demonstrated that this PCR assay can be a useful tool for molecular surveillance of carbapenem-resistant and hypervirulent K. pneumoniae strains.

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1199. Epidemiology of Carbapenem-Resistant Klebsiella pneumoniae: A Comparative Study Between Facilities in the United States and the Dominican Republic

Open Forum Infectious Diseases ◽

10.1093/ofid/ofy210.1032 ◽

2018 ◽

Vol 5 (suppl_1) ◽

pp. S363-S363

Author(s):

Alfredo J Mena Lora ◽

Rita Rojas Fermin ◽

Anel Guzman ◽

Scott Borgetti ◽

Susan C Bleasdale

Keyword(s):

United States ◽

Risk Factors ◽

Klebsiella Pneumoniae ◽

Dominican Republic ◽

Antibiotic Use ◽

The United States ◽

Common Source ◽

The Past ◽

Carbapenem Resistant ◽

Common Risk Factors

Abstract Background The prevalence of multi-drug-resistant organisms (MDRO) is on the rise globally. MDRO infections carry high morbidity and mortality. There is a paucity of data on Carbapenem-resistant Klebsiella pneumoniae (CRKp) in the Dominican Republic (DR). Evaluating CRKp in various settings will provide data on contrasting epidemiologic risk factors. We evaluated the epidemiology of CKRp in three contrasting settings, a 495-bed urban academic center (AC), a 151-bed urban community hospital (CH) and a 200 bed teaching hospital in the DR (DRH). Methods We performed a retrospective cohort study of patients with CRKp cultures from 2014 to 2016 from AC, CH and DRH. A comparative evaluation of the epidemiology of CRKp between the cohorts was performed. Demographics, co-morbid conditions, antibiotic sensitivity, and outcomes were compared between hospital cohorts. Results Cohort AC had 64 patients, compared with eight from CH and eight from DRH. AC (59%) and CH (62%) cohorts included more men than the DRH cohort (25%). Average age was 62, 66, and 51, respectively. History of MDRO, antibiotic use in the past 6 months and hospitalization within the past year were common risk factors (Figure 1). Diabetes and end-stage renal disease were common comorbidities at all facilities (Figure 2). Charleston Comorbidity Index (CCI) score was highest at AC (6.6) and DRH (6.4) compared with CH (4). Mortality was highest in DRH (63%, 6/8) and AC (11%, 7/64) while CH had no deaths. Urine was the most common source at AC (67%) and CH (75%) while blood was most common at DRH (62.5%). CRKp isolates were susceptible to colistin at varying rates (AC=85%, CH = 63%, DRH = 80%). Conclusion Prior antibiotic use and hospitalization were common risk factors in all settings. Mortality and CCI scores for CRKp was highest at AC and DRH, which are tertiary referral centers. CH had less overall mortality and higher rates of colistin resistance. Further studies are needed to understand these risk factors. Strengthening antimicrobial stewardship and infection control practices in the United States and abroad may help curb the spread of resistance in different clinical settings. Disclosures All authors: No reported disclosures.

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Emergence of KPC-2 and KPC-3 in Carbapenem-Resistant Klebsiella pneumoniae Strains in an Israeli Hospital

Antimicrobial Agents and Chemotherapy ◽

10.1128/aac.00299-07 ◽

2007 ◽

Vol 51 (8) ◽

pp. 3026-3029 ◽

Cited By ~ 167

Author(s):

Azita Leavitt ◽

Shiri Navon-Venezia ◽

Inna Chmelnitsky ◽

Mitchell J. Schwaber ◽

Yehuda Carmeli

Keyword(s):

United States ◽

Klebsiella Pneumoniae ◽

Medical Center ◽

Carbapenem Resistance ◽

The United States ◽

Tel Aviv ◽

Carbapenem Resistant ◽

Single Clone ◽

Rapid Dissemination ◽

Almost All

ABSTRACT Carbapenem resistance due to KPC has rarely been observed outside the United States. We noticed a sharp increase in carbapenem-resistant Klebsiella pneumoniae strains possessing KPC in Tel Aviv Medical Center from 2004 to 2006. Sixty percent of the isolates belonged to a single clone susceptible only to gentamicin and colistin and carried the bla KPC-3 gene, while almost all other clones carried the bla KPC-2 gene. This rapid dissemination of KPC outside the United States is worrisome.

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Intravenous Fosfomycin Treatment for Carbapenem-Resistant Klebsiella pneumoniae in the United States

Annals of Pharmacotherapy ◽

10.1177/1060028015598326 ◽

2015 ◽

Vol 49 (10) ◽

pp. 1177-1178 ◽

Cited By ~ 9

Author(s):

Jacques Simkins ◽

Ji Fan ◽

Jose F. Camargo ◽

Laura Aragon ◽

Corey Frederick

Keyword(s):

United States ◽

Klebsiella Pneumoniae ◽

The United States ◽

Carbapenem Resistant

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Plasmid-Mediated KPC-2 in a Klebsiella pneumoniae Isolate from China

Antimicrobial Agents and Chemotherapy ◽

10.1128/aac.01053-06 ◽

2006 ◽

Vol 51 (2) ◽

pp. 763-765 ◽

Cited By ~ 135

Author(s):

Ze-Qing Wei ◽

Xiao-Xing Du ◽

Yun-Song Yu ◽

Ping Shen ◽

Ya-Gang Chen ◽

...

Keyword(s):

United States ◽

Klebsiella Pneumoniae ◽

The United States ◽

Resistant Isolate ◽

Genetic Environment ◽

Class A ◽

Carbapenem Resistant

ABSTRACT A carbapenem-resistant isolate of Klebsiella pneumoniae producing class A carbapenemase KPC-2 was identified in Zhejiang, China. The KPC-2 gene was located on an approximately 60-kb plasmid in a genetic environment partially different from that of bla KPC-2 in the isolates from the United States and Colombia.

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First Report on a Hyperepidemic Clone of KPC-3-Producing Klebsiella pneumoniae in Israel Genetically Related to a Strain Causing Outbreaks in the United States

Antimicrobial Agents and Chemotherapy ◽

10.1128/aac.00987-08 ◽

2008 ◽

Vol 53 (2) ◽

pp. 818-820 ◽

Cited By ~ 126

Author(s):

Shiri Navon-Venezia ◽

Azita Leavitt ◽

Mitchell J. Schwaber ◽

J. Kamile Rasheed ◽

Arjun Srinivasan ◽

...

Keyword(s):

United States ◽

Klebsiella Pneumoniae ◽

The United States ◽

Drug Resistant ◽

Resistant Clone ◽

Bacterial Strains ◽

First Report ◽

Carbapenem Resistant ◽

Extensively Drug Resistant ◽

Global Spread

ABSTRACT A highly epidemic carbapenem-resistant clone of KPC-3-producing Klebsiella pneumoniae emerged in Israel in 2006, causing a nationwide outbreak. This clone was genetically related to outbreak strains from the United States isolated in 2000 but differed in KPC-carrying plasmids. The threat of the global spread of hyperepidemic, extensively drug-resistant bacterial strains should be recognized and confronted.

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