Outbreak of Klebsiella pneumoniae carbapenemase–producing K pneumoniae: A systematic review

Campos, Anaelís C.; Albiero, James; Ecker, Alessandra B.; Kuroda, Cristina Megumi; Meirelles, Lívia E.F.; Polato, Angelita; Tognim, Maria Cristina Bronharo; Wingeter, Márcia Arias; Teixeira, Jorge Juarez Vieira

doi:10.1016/j.ajic.2016.03.022

Cited by 79 publications

(60 citation statements)

References 32 publications

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“…Similar risk factors, including prolonged hospitalization, mechanical ventilation, and organ or stem-cell transplantation have been reported for KPC producers 84. Globally, KPC production is endemic to Greece, Israel, and Italy, with many more countries reporting sporadic hospital-associated outbreaks with associated mortality of up to 66.7% 85. In the United States, pockets of endemic KPC production exist, including many hospitals within New York and New Jersey, with one academic medical center in New York City reporting a rise in carbapenem-nonsusceptible K. pneumoniae from 9% in 2002 to a staggering 38% in 2008 84.…”

Section: Role In Therapysupporting

confidence: 55%

Ceftolozane/tazobactam and ceftazidime/avibactam for the treatment of complicated intra-abdominal infections

Goodlet¹,

Nicolau²,

Nailor³

2016

TCRM

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Complicated intra-abdominal infections (cIAI) represent a large proportion of all hospital admissions and are a major cause of morbidity and mortality in the intensive care unit. Rising rates of multidrug resistant organisms (MDRO), including extended-spectrum β-lactamase producing Enterobacteriaceae and carbapenem-nonsusceptible Pseudomonas spp., for which there are few remaining active antimicrobial agents, pose an increased challenge to clinicians. Patients with frequent exposures to the health care system or multiple recurrent IAIs are at increased risk for MDRO; however, treatment options have traditionally been limited, in some cases necessitating the utilization of last-line agents with unfavorable side-effect profiles. Ceftolozane/tazobactam and ceftazidime/avibactam are two new cephalosporin and β-lactamase inhibitor combinations with recent US Food and Drug Administration approvals for the treatment of cIAI in combination with metronidazole. Ceftolozane/tazobactam has demonstrated excellent in vitro activity against MDR and extensively drug-resistant Pseudomonas spp., including carbapenem-nonsusceptible strains, while ceftazidime/avibactam effectively inhibits a broad range of β-lactamases, making it an excellent option for the treatment of carbapenem-resistant Enterobacteriaceae. Both agents were shown to be noninferior to meropenem for treatment of cIAI in Phase III trials; however, reduced responses in patients with renal impairment at baseline highlight the importance of routine serum creatinine monitoring and ongoing dose adjustments. This review highlights in vitro and in vivo data of these two agents and suggests their proper place in cIAI treatment to ensure adequate therapy in our most at-risk patients while sparing unnecessary use in patients without MDRO risk factors.

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Section: Role In Therapysupporting

confidence: 55%

Ceftolozane/tazobactam and ceftazidime/avibactam for the treatment of complicated intra-abdominal infections

Goodlet¹,

Nicolau²,

Nailor³

2016

TCRM

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“…This has important clinical implications for the treatment of infections by and outbreaks of MDR (particularly carbapenem-resistant) K. pneumoniae isolates, given their increasing prevalence in hospitals (11). Many carbapenem-resistant K. pneumoniae isolates are susceptible to very few antibiotics, notably, colistin; treatment often involves combination therapy including colistin (12).…”

Section: Discussionmentioning

confidence: 99%

Mechanisms of Increased Resistance to Chlorhexidine and Cross-Resistance to Colistin following Exposure of Klebsiella pneumoniae Clinical Isolates to Chlorhexidine

Wand

Bock

Bonney

et al. 2017

Antimicrob Agents Chemother

232

218

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Klebsiella pneumoniae is an opportunistic pathogen that is often difficult to treat due to its multidrug resistance (MDR). We have previously shown that K. pneumoniae strains are able to "adapt" (become more resistant) to the widely used bisbiguanide antiseptic chlorhexidine. Here, we investigated the mechanisms responsible for and the phenotypic consequences of chlorhexidine adaptation, with particular reference to antibiotic cross-resistance. In five of six strains, adaptation to chlorhexidine also led to resistance to the last-resort antibiotic colistin. Here, we show that chlorhexidine adaptation is associated with mutations in the two-component regulator phoPQ and a putative Tet repressor gene (smvR) adjacent to the major facilitator superfamily (MFS) efflux pump gene, smvA. Upregulation of smvA (10-to 27-fold) was confirmed in smvR mutant strains, and this effect and the associated phenotype were suppressed when a wild-type copy of smvR was introduced on plasmid pACYC. Upregulation of phoPQ (5-to 15-fold) and phoPQ-regulated genes, pmrD (6-to 19-fold) and pmrK (18-to 64-fold), was confirmed in phoPQ mutant strains. In contrast, adaptation of K. pneumoniae to colistin did not result in increased chlorhexidine resistance despite the presence of mutations in phoQ and elevated phoPQ, pmrD, and pmrK transcript levels. Insertion of a plasmid containing phoPQ from chlorhexidine-adapted strains into wild-type K. pneumoniae resulted in elevated expression levels of phoPQ, pmrD, and pmrK and increased resistance to colistin, but not chlorhexidine. The potential risk of colistin resistance emerging in K. pneumoniae as a consequence of exposure to chlorhexidine has important clinical implications for infection prevention procedures.

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“…In developed countries, CPE transmission occurs almost exclusively within health care settings, with the main route of spread from patient to patient being via contaminated hands of health care workers (3,5). Risk factors for infection with CPE include intensive care unit (ICU) stay, mechanical ventilation, indwelling catheters, transplantation, septic shock, exposure to broadspectrum antimicrobial agents, inadequate initial antimicrobial therapy, and previous colonization with an isolate of CPE (2,4).…”

mentioning

confidence: 99%

In Vitro Activity of Imipenem against Carbapenemase-Positive Enterobacteriaceae Isolates Collected by the SMART Global Surveillance Program from 2008 to 2014

Karlowsky

Lob²,

Kazmierczak³

et al. 2017

J Clin Microbiol

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The Study for Monitoring Antimicrobial Resistance Trends (SMART) global surveillance program collected 103,960 isolates of Enterobacteriaceae from 2008 to 2014. From this isolate collection, all ertapenem-nonsusceptible isolates (MIC, Ն1 g/ml; n ϭ 3,428) and 9,371 isolates of Escherichia coli, Klebsiella pneumoniae, Klebsiella oxytoca, and Proteus mirabilis with an ertapenem-susceptible extended-spectrum-␤-lactamase (ESBL)-positive phenotype were assessed for the presence of common carbapenemase genes using a Check-MDR CT101 microarray (Check-Points,

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Outbreak of Klebsiella pneumoniae carbapenemase–producing K pneumoniae: A systematic review

Cited by 79 publications

References 32 publications

Ceftolozane/tazobactam and ceftazidime/avibactam for the treatment of complicated intra-abdominal infections

Ceftolozane/tazobactam and ceftazidime/avibactam for the treatment of complicated intra-abdominal infections

Mechanisms of Increased Resistance to Chlorhexidine and Cross-Resistance to Colistin following Exposure of Klebsiella pneumoniae Clinical Isolates to Chlorhexidine

In Vitro Activity of Imipenem against Carbapenemase-Positive Enterobacteriaceae Isolates Collected by the SMART Global Surveillance Program from 2008 to 2014

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