Severe Sepsis Facilitates Intestinal Colonization by Extended-Spectrum-β-Lactamase-Producing Klebsiella pneumoniae and Transfer of the SHV-18 Resistance Gene to Escherichia coli during Antimicrobial Treatment

ABSTRACTInfections caused by multidrug-resistant pathogens are frequent and life threatening in critically ill patients. To investigate whether severe sepsis affects gut colonization by resistant pathogens and genetic exchange between opportunistic pathogens, we tested the intestinal-colonization ability of an extended-spectrum beta-lactamase-producingKlebsiella pneumoniaestrain carrying the SHV-18 resistance gene and the transfer ability of the resistance gene to endogenousEscherichia coliunder ceftriaxone treatment in rats with burn injury only or severe sepsis induced by burns plus endotoxin exposure. Without ceftriaxone treatment, theK. pneumoniaestrain colonized the intestine in both septic and burned rats for a short time, with clearance occurring earlier in burn-only rats but never in sham burn rats. In both burned and septic rats, the colonization level of the challenge strain dropped at the beginning and then later increased during ceftriaxone treatment, after which it declined gradually. This pattern coincided with the change in resistance ofK. pneumoniaeto ceftriaxone during and after ceftriaxone treatment. Compared with burn-only injury, severe sepsis had a more significant effect on the change in antimicrobial resistance to ceftriaxone. Only in septic rats was the resistance gene successfully transferred from the challenge strain to endogenousE. coliduring ceftriaxone treatment; the gene persisted for at least 4 weeks after ceftriaxone treatment. We concluded that severe sepsis can facilitate intestinal colonization by an exogenous resistant pathogen and the transfer of the resistance gene to a potential endogenous pathogen during antimicrobial treatment.

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Carbapenem Therapy for Bacteremia Due to Extended-Spectrum-β-Lactamase-Producing Escherichia coli or Klebsiella pneumoniae: Implications of Ertapenem Susceptibility

Antimicrobial Agents and Chemotherapy ◽

10.1128/aac.06301-11 ◽

2012 ◽

Vol 56 (6) ◽

pp. 2888-2893 ◽

Cited By ~ 24

Author(s):

Nan-Yao Lee ◽

Ching-Chi Lee ◽

Wei-Han Huang ◽

Ko-Chung Tsui ◽

Po-Ren Hsueh ◽

...

Keyword(s):

Risk Factors ◽

Escherichia Coli ◽

Klebsiella Pneumoniae ◽

Content Type ◽

Extended Spectrum Beta Lactamase ◽

E Coli ◽

Medical Centers ◽

Extended Spectrum ◽

Appropriate Therapy ◽

Related Mortality

ABSTRACTA retrospective study was conducted at two medical centers in Taiwan to evaluate the clinical characteristics, outcomes, and risk factors for mortality among patients treated with a carbapenem for bacteremia caused by extended-spectrum-beta-lactamase (ESBL)-producing organisms. A total of 251 patients with bacteremia caused by ESBL-producingEscherichia coliandKlebsiella pneumoniaeisolates treated by a carbapenem were identified. Among these ESBL-producing isolates, rates of susceptibility to ertapenem (MICs ≤ 0.25 μg/ml) were 83.8% and 76.4%, respectively; those to meropenem were 100% and 99.3%, respectively; and those to imipenem were 100% and 97.9%, respectively. There were no significant differences in the critical illness rate (P= 0.1) or sepsis-related mortality rate (P= 0.2) for patients with bacteremia caused by ESBL-producingK. pneumoniae(140 isolates, 55.8%) andE. coli(111 isolates, 44.2%). Multivariate analysis of variables related to sepsis-related mortality revealed that the presence of severe sepsis (odds ratio [OR], 15.9; 95% confidence interval [CI], 5.84 to 43.34;P< 0.001), hospital-onset bacteremia (OR, 4.65; 95% CI, 1.42 to 15.24;P= 0.01), and ertapenem-nonsusceptible isolates (OR, 5.12; 95% CI, 2.04 to 12.88;P= 0.001) were independent risk factors. The patients receiving inappropriate therapy had a higher sepsis-related mortality than those with appropriate therapy (P= 0.002), irrespective of ertapenem, imipenem, or meropenem therapy. Infections due to the ertapenem-susceptible isolates (MICs ≤ 0.25 μg/ml) were associated with a more favorable outcome than those due to ertapenem-nonsusceptible isolates (MICs > 0.25 μg/ml), if treated by a carbapenem. However, the mortality for patients with bacteremic episodes due to isolates with MICs of ≤0.5 μg/ml was similar to the mortality for those whose isolates had MICs of >0.5 μg/ml (P= 0.8). Such a finding supports the rationale of the current CLSI 2011 criteria for carbapenems forEnterobacteriaceae.

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Escherichia coli and Klebsiella pneumoniae Producing CTX-M Cephalosporinase from Swine Finishing Barns and Their Association with Antimicrobial Use

Applied and Environmental Microbiology ◽

10.1128/aem.03169-12 ◽

2012 ◽

Vol 79 (3) ◽

pp. 1052-1054 ◽

Cited By ~ 9

Author(s):

Dixie F. Mollenkopf ◽

Jennifer M. Mirecki ◽

Joshua B. Daniels ◽

Julie A. Funk ◽

Steven C. Henry ◽

...

Keyword(s):

Escherichia Coli ◽

Klebsiella Pneumoniae ◽

Antimicrobial Use ◽

Fecal Samples ◽

Content Type ◽

Extended Spectrum ◽

Lactamase Gene

ABSTRACTWe report the recovery ofEscherichia coliorKlebsiella pneumoniaecontaining the extended-spectrum β-lactamase geneblaCTX-Mfrom 24 of 1,495 (1.6%) swine fecal samples in 8 of 50 (16%) finishing barns located in 5 U.S. states. We did not detect an association between antimicrobial use and recovery ofblaCTX-M.

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Genome-Wide Screening for Enteric Colonization Factors in Carbapenem-Resistant ST258 Klebsiella pneumoniae

mBio ◽

10.1128/mbio.02663-18 ◽

2019 ◽

Vol 10 (2) ◽

Cited By ~ 7

Author(s):

Hea-Jin Jung ◽

Eric R. Littmann ◽

Ruth Seok ◽

Ingrid M. Leiner ◽

Ying Taur ◽

...

Keyword(s):

Klebsiella Pneumoniae ◽

Genetic Factors ◽

Intestinal Lumen ◽

Intestinal Colonization ◽

Antibiotic Resistant ◽

Content Type ◽

Carbapenem Resistant ◽

Gut Colonization ◽

Colonization Factors

ABSTRACT A diverse, antibiotic-naive microbiota prevents highly antibiotic-resistant microbes, including carbapenem-resistant Klebsiella pneumoniae (CR-Kp), from achieving dense colonization of the intestinal lumen. Antibiotic-mediated destruction of the microbiota leads to expansion of CR-Kp in the gut, markedly increasing the risk of bacteremia in vulnerable patients. While preventing dense colonization represents a rational approach to reduce intra- and interpatient dissemination of CR-Kp, little is known about pathogen-associated factors that enable dense growth and persistence in the intestinal lumen. To identify genetic factors essential for dense colonization of the gut by CR-Kp, we constructed a highly saturated transposon mutant library with >150,000 unique mutations in an ST258 strain of CR-Kp and screened for in vitro growth and in vivo intestinal colonization in antibiotic-treated mice. Stochastic and partially reversible fluctuations in the representation of different mutations during dense colonization revealed the dynamic nature of intestinal microbial populations. We identified genes that are crucial for early and late stages of dense gut colonization and confirmed their role by testing isogenic mutants in in vivo competition assays with wild-type CR-Kp. Screening of the transposon library also identified mutations that enhanced in vivo CR-Kp growth. These newly identified colonization factors may provide novel therapeutic opportunities to reduce intestinal colonization by CR-Kp. IMPORTANCE Klebsiella pneumoniae is a common cause of bloodstream infections in immunocompromised and hospitalized patients, and over the last 2 decades, some strains have acquired resistance to nearly all available antibiotics, including broad-spectrum carbapenems. The U.S. Centers for Disease Control and Prevention has listed carbapenem-resistant K. pneumoniae (CR-Kp) as an urgent public health threat. Dense colonization of the intestine by CR-Kp and other antibiotic-resistant bacteria is associated with an increased risk of bacteremia. Reducing the density of gut colonization by CR-Kp is likely to reduce their transmission from patient to patient in health care facilities as well as systemic infections. How CR-Kp expands and persists in the gut lumen, however, is poorly understood. Herein, we generated a highly saturated mutant library in a multidrug-resistant K. pneumoniae strain and identified genetic factors that are associated with dense gut colonization by K. pneumoniae. This study sheds light on host colonization by K. pneumoniae and identifies potential colonization factors that contribute to high-density persistence of K. pneumoniae in the intestine.

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Tigecycline DisplaysIn VivoBactericidal Activity against Extended-Spectrum-β-Lactamase-Producing Enterobacteriaceae after 72-Hour Exposure Period

Antimicrobial Agents and Chemotherapy ◽

10.1128/aac.01824-12 ◽

2012 ◽

Vol 57 (1) ◽

pp. 640-642 ◽

Cited By ~ 9

Author(s):

Pamela R. Tessier ◽

David P. Nicolau

Keyword(s):

Escherichia Coli ◽

Klebsiella Pneumoniae ◽

Clinical Outcomes ◽

Bactericidal Activity ◽

Exposure Period ◽

Content Type ◽

Density Reduction ◽

Extended Spectrum ◽

Level Of Activity

ABSTRACTProgressively enhanced activity of a humanized tigecycline (TGC) regimen was noted over 3 days against an extended-spectrum-β-lactamase (ESBL)-producingEscherichia coliisolate and an ESBL-producingKlebsiella pneumoniaeisolate. Bacterial density reduction approximated 3 log10approaching bactericidal activity at 72 h. This level of activity has not been previously noted for compounds such as tetracyclines, normally considered bacteriostatic antimicrobials. Extended regimen studiesin vivomay aid in better delineation of antimicrobial effects, producing improved correlation with clinical outcomes.

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Mutations in blaKPC-3 That Confer Ceftazidime-Avibactam Resistance Encode Novel KPC-3 Variants That Function as Extended-Spectrum β-Lactamases

Antimicrobial Agents and Chemotherapy ◽

10.1128/aac.02534-16 ◽

2017 ◽

Vol 61 (5) ◽

Cited By ~ 73

Author(s):

Ghady Haidar ◽

Cornelius J. Clancy ◽

Ryan K. Shields ◽

Binghua Hao ◽

Shaoji Cheng ◽

...

Keyword(s):

Escherichia Coli ◽

Klebsiella Pneumoniae ◽

Site Directed Mutagenesis ◽

Directed Mutagenesis ◽

Content Type ◽

Extended Spectrum

ABSTRACT We identified four bla KPC-3 mutations in ceftazidime-avibactam-resistant clinical Klebsiella pneumoniae isolates, corresponding to D179Y, T243M, D179Y/T243M, and EL165-166 KPC-3 variants. Using site-directed mutagenesis and transforming vectors into Escherichia coli, we conclusively demonstrated that mutant bla KPC-3 encoded enzymes that functioned as extended-spectrum β-lactamases; mutations directly conferred higher MICs of ceftazidime-avibactam and decreased the MICs of carbapenems and other β-lactams. Impact was strongest for the D179Y mutant, highlighting the importance of the KPC Ω-loop.

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Decreased Susceptibility to Noncarbapenem Antimicrobials in Extended-Spectrum-β-Lactamase-Producing Escherichia coli and Klebsiella pneumoniae Isolates in Toronto, Canada

Antimicrobial Agents and Chemotherapy ◽

10.1128/aac.00260-12 ◽

2012 ◽

Vol 56 (7) ◽

pp. 3977-3980 ◽

Cited By ~ 17

Author(s):

Christopher F. Lowe ◽

Allison McGeer ◽

Matthew P. Muller ◽

Kevin Katz

Keyword(s):

Escherichia Coli ◽

Klebsiella Pneumoniae ◽

Retrospective Review ◽

Content Type ◽

E Coli ◽

Extended Spectrum ◽

Susceptibility Profiles

ABSTRACTRetrospective review from 11 Canadian hospitals showed increasing incidence of extended-spectrum β-lactamase (ESBL)-producingEscherichia coliandKlebsiella pneumoniaefrom 0.12 per 1,000 inpatient days during 2005 to 0.47 per 1,000 inpatient days during 2009. By 2009, susceptibility rates of ESBL-positiveE. coli/K. pneumoniaewere as follows: ciprofloxacin, 12.8%/9.0%; TMP/SMX, 32.9%/12.2%; and nitrofurantoin, 83.8%/10.3%. Nosocomial and nonnosocomial ESBL-producingE. coliisolates had similar susceptibility profiles, while nonnosocomial ESBL-producingK. pneumoniaewas associated with decreased ciprofloxacin (P= 0.03) and nitrofurantoin (P< 0.001) susceptibilities.

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Extended-Spectrum-β-Lactamase-Producing Escherichia coli as Intestinal Colonizers in the German Community

Antimicrobial Agents and Chemotherapy ◽

10.1128/aac.01993-13 ◽

2013 ◽

Vol 58 (2) ◽

pp. 1228-1230 ◽

Cited By ~ 97

Author(s):

Giuseppe Valenza ◽

Silke Nickel ◽

Yvonne Pfeifer ◽

Christoph Eller ◽

Elzbieta Krupa ◽

...

Keyword(s):

Escherichia Coli ◽

Age Groups ◽

Resistant Bacteria ◽

Intestinal Colonization ◽

Content Type ◽

Extended Spectrum ◽

Study Participants ◽

Esbl Producers

ABSTRACTWe determined the presence of extended-spectrum-β-lactamase (ESBL)-producingEscherichia coliamong 3,344 study participants from the German community. Intestinal colonization was detected in 211 persons (6.3%), without significant differences among the different age groups. The majority (95.2%) of isolates harbored CTX-M-type ESBL, with CTX-M-15 (46%) and CTX-M-1 (24.2%) as the most common types. The finding of ESBL producers and one isolate additionally producing carbapenemase OXA-244 indicates a risk of dissemination of resistant bacteria outside the hospitals.

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Changing Epidemiology of Extended-Spectrum β-Lactamases in Argentina: Emergence of CTX-M-15

Antimicrobial Agents and Chemotherapy ◽

10.1128/aac.00745-12 ◽

2012 ◽

Vol 56 (11) ◽

pp. 6003-6005 ◽

Cited By ~ 35

Author(s):

S. Sennati ◽

G. Santella ◽

J. Di Conza ◽

L. Pallecchi ◽

M. Pino ◽

...

Keyword(s):

Escherichia Coli ◽

Klebsiella Pneumoniae ◽

Molecular Epidemiology ◽

Content Type ◽

Extended Spectrum ◽

Multicenter Survey

ABSTRACTA multicenter survey, carried out in 2010 in Argentina, showed an increased prevalence of extended-spectrum β-lactamase (ESBL)-producing enterobacteria, with some changes in the molecular epidemiology of circulating ESBLs. While enzymes of the CTX-M-2 group remain endemic, the emergence of CTX-M-15 and of enzymes of the CTX-M-8 and CTX-M-9 groups was observed. The CTX-M-15-positive isolates represented 40% of CTX-M producers and included representatives ofEscherichia coliST131 andKlebsiella pneumoniaeST11.

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Activity of NXL104 in Combination with β-Lactams against Genetically Characterized Escherichia coli and Klebsiella pneumoniae Isolates Producing Class A Extended-Spectrum β-Lactamases and Class C β-Lactamases

Antimicrobial Agents and Chemotherapy ◽

10.1128/aac.01722-10 ◽

2011 ◽

Vol 55 (5) ◽

pp. 2434-2437 ◽

Cited By ~ 65

Author(s):

P. R. S. Lagacé-Wiens ◽

F. Tailor ◽

P. Simner ◽

M. DeCorby ◽

J. A. Karlowsky ◽

...

Keyword(s):

Escherichia Coli ◽

Klebsiella Pneumoniae ◽

The Novel ◽

Content Type ◽

E Coli ◽

Class A ◽

Extended Spectrum ◽

Class C ◽

Lactamase Inhibitor

ABSTRACTThe novel non-β-lactam β-lactamase inhibitor NXL104, in combination with cefepime, ceftazidime, ceftriaxone, amdinocillin, and meropenem, was tested against 190 extended-spectrum β-lactamase (ESBL)-producingEscherichia coliandKlebsiella pneumoniaeisolates, 94 AmpC-hyperproducingE. coliisolates, and 8 AmpC/ESBL-coexpressingE. coliisolates. NXL104 restored 100% susceptibility to the partner cephalosporins for all isolates tested. Amdinocillin and meropenem MICs were modestly improved (2 to 32 times lower) by NXL104. These results suggest that NXL104 may be useful in combination with β-lactams for the treatment of infections caused by ESBL- and AmpC-producingEnterobacteriaceae.

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Acquisition of Extended-Spectrum β-Lactamases by Escherichia coli and Klebsiella pneumoniae in Gut Microbiota of Pilgrims during the Hajj Pilgrimage of 2013

Antimicrobial Agents and Chemotherapy ◽

10.1128/aac.02396-15 ◽

2016 ◽

Vol 60 (5) ◽

pp. 3222-3226 ◽

Cited By ~ 20

Author(s):

Thongpan Leangapichart ◽

Ndèye Méry Dia ◽

Abiola Olumuyiwa Olaitan ◽

Philippe Gautret ◽

Philippe Brouqui ◽

...

Keyword(s):

Escherichia Coli ◽

Klebsiella Pneumoniae ◽

Gut Microbiota ◽

Detection Rate ◽

M Gene ◽

Content Type ◽

E Coli ◽

Extended Spectrum

ABSTRACTWe reported the acquisition of extended-spectrum-β-lactamase (ESBL)-producing bacteria in rectal samples of 129 pilgrims during the 2013 Hajj (pilgrimage to Makkah). When returning from the Hajj, there was a significant increase in the number of pilgrims carryingE. coliresistant to ceftriaxone (P= 0.008). The CTX-M gene was detected in rectal samples, with the detection rate increasing from 10.08% to 32.56% of samples after the Hajj (P< 0.001).

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