Sepsis in neonates due to imipenem-resistant Klebsiella pneumoniae producing NDM-1 in India

Roy, Subhasree; Viswanathan, Rajlakshmi; Singh, Amit Kumar; Das, Parijat; Basu, Sulagna

doi:10.1093/jac/dkr068

Cited by 50 publications

(40 citation statements)

References 7 publications

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“…It appears that a majority of the cases that include clinical outcomes have predominantly been treated successfully, most often with colistin-and/or amikacin-based regimens (26)(27)(28)(29)(30)(31)(32)(33)(34)(35)(36)(37)(38)(39). It is likely that this collection of largely positive case reports is a result of publication bias and should be interpreted cautiously, since a small number of clinical failures with these same regimens have also been reported (6)(7)(8)40).…”

Section: Discussionmentioning

confidence: 99%

In VivoEfficacy of Human Simulated Regimens of Carbapenems and Comparator Agents against NDM-1-Producing Enterobacteriaceae

Wiskirchen

Nordmann

Crandon

et al. 2014

Antimicrob Agents Chemother

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e Doripenem and ertapenem have demonstrated efficacy against several NDM-1-producing isolates in vivo, despite having high MICs. In this study, we sought to further characterize the efficacy profiles of humanized regimens of standard (500 mg given every 8 h) and high-dose, prolonged infusion of doripenem (2 g given every 8 h, 4-h infusion) and 1 g of ertapenem given intravenously every 24 h and the comparator regimens of ceftazidime at 2 g given every 8 h (2-h infusion), levofloxacin at 500 mg every 24 h, and aztreonam at 2 g every 6 h (1-h infusion) against a wider range of isolates in a murine thigh infection model. An isogenic wild-type strain and NDM-1-producing Klebsiella pneumoniae and eight clinical NDM-1-producing members of the family Enterobacteriaceae were tested in immunocompetent-and neutropenic-mouse models. The wild-type strain was susceptible to all of the agents, while the isogenic NDM-1-producing strain was resistant to ceftazidime, doripenem, and ertapenem. Clinical NDM-1-producing strains were resistant to nearly all five of the agents (two were susceptible to levofloxacin). In immunocompetent mice, all of the agents produced >1-log 10 CFU reductions of the isogenic wild-type and NDM-1-producing strains after 24 h. Minimal efficacy of ceftazidime, aztreonam, and levofloxacin against the clinical NDM-1-producing strains was observed. However, despite in vitro resistance, >1-log 10 CFU reductions of six of eight clinical strains were achieved with high-dose, prolonged infusion of doripenem and ertapenem. Slight enhancements of doripenem activity over the standard doses were obtained with high-dose, prolonged infusion for three of the four isolates tested. Similar efficacy observations were noted in neutropenic mice. These data suggest that carbapenems are a viable treatment option for infections caused by NDM-1-producing Enterobacteriaceae. New Delhi metallo-␤-lactamase (NDM-1) is a novel carbapenemase that was first identified in a Klebsiella pneumoniae isolate in India in 2008 (1). Since then, it has disseminated at a high rate among Enterobacteriaceae isolates both within the Indian subcontinent and worldwide (2-4). The treatment options for infections caused by NDM-1-producing isolates are extremely limited, as these enzymes are known to hydrolyze penicillins, cephalosporins, and carbapenems while typically retaining susceptibility to only colistin and tigecycline (2), neither of which has been shown to be a dependable option on the basis of in vitro time-kill data and case reports (5-8). Aztreonam is not readily inactivated by metallo-␤-lactamases, including NDM-1, and may represent another potential option for therapy (1, 9). However, NDM-1-producing strains often coproduce other ␤-lactamases, such as CTX-M-and CMY-type enzymes, that possess the ability to hydrolyze aztreonam, further limiting the utility of all ␤-lactam antibiotics (1). Furthermore, in vivo efficacy data evaluating potential treatment options for NDM-1-producing isolates are sparse and clinical experience in treating inf...

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Section: Discussionmentioning

confidence: 99%

In VivoEfficacy of Human Simulated Regimens of Carbapenems and Comparator Agents against NDM-1-Producing Enterobacteriaceae

Wiskirchen

Nordmann

Crandon

et al. 2014

Antimicrob Agents Chemother

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“…Since then, infections associated with NDM-1-positive strains have been reported worldwide, including in India, the United Kingdom, the United States, Canada, Australia, France, Holland, China, Pakistan, Italy, Japan, and Spain (4). The majority of these reported cases were strains isolated from adult patients (5). Here, we report an outbreak of NDM-1-producing K. pneumoniae in the neonatal ward of a tertiary teaching hospital in mainland China.…”

mentioning

confidence: 99%

Outbreak of NDM-1-Producing Klebsiella pneumoniae Causing Neonatal Infection in a Teaching Hospital in Mainland China

Zhang

Wang

et al. 2015

Antimicrob Agents Chemother

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The emergence and spread of bacteria carrying the bla NDM-1 gene has become a worldwide concern. Here, we report eight cases of Klebsiella pneumoniae with bla NDM-1 in the neonatal ward of a teaching hospital in mainland China. Multilocus sequence typing showed that seven isolates were clonally related and confirmed them as sequence type 17 (ST17). One isolate belonged to ST433. These findings suggest continuous spread of bla NDM-1 in mainland China and emphasize the need for intensive surveillance and precautions.

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“…Multidrug resistant gram-negative organisms form a big threat to the preterm, low birth weight and immuocompromised newborns. Klebsiella species are the most commonly implicated pathogen in neonatal sepsis outbreaks followed by Escherichia coli (Szilagyi et al, 2010, Roy et al, 2011. However, Enterobacter species outbreaks have also been reported (Ostwal et al,2014).…”

Section: Resultsmentioning

confidence: 99%

“…2015). Carbapenem-resistant Klebsiella pneumoniae is associated with high morbidity and mortality (Roy et al, 2011, Jin et al, 2015. The Klebsiella species, in addition to its virulence and ability to acquire antibiotic resistance determinants are able to survive on skin and watery surfaces and resist desiccation which adds to its pathogenicity.…”

Section: Introductionmentioning

confidence: 99%

Outbreak of Carbapenemase-Producing Klebsiella pneumoniae Blood Stream Infections in Neonatal Intensive Care Unit

Kaur¹,

Sheemar²,

Chand³

et al. 2016

Int.J.Curr.Microbiol.App.Sci

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Sepsis in neonates due to imipenem-resistant Klebsiella pneumoniae producing NDM-1 in India

Cited by 50 publications

References 7 publications

In VivoEfficacy of Human Simulated Regimens of Carbapenems and Comparator Agents against NDM-1-Producing Enterobacteriaceae

In VivoEfficacy of Human Simulated Regimens of Carbapenems and Comparator Agents against NDM-1-Producing Enterobacteriaceae

Outbreak of NDM-1-Producing Klebsiella pneumoniae Causing Neonatal Infection in a Teaching Hospital in Mainland China

Outbreak of Carbapenemase-Producing Klebsiella pneumoniae Blood Stream Infections in Neonatal Intensive Care Unit

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