Molecular epidemiology of extended-spectrum  -lactamase-, AmpC  -lactamase- and carbapenemase-producing Escherichia coli and Klebsiella pneumoniae isolated from Canadian hospitals over a 5 year period: CANWARD 2007-11

Denisuik, Andrew; Lagacé-Wiens, Philippe; Pitout, Johann; Mulvey, Michael R.; Simner, Patricia J.; Tailor, Franil; Karlowsky, James A.; Hoban, Daryl J.; Adam, Heather J.; Zhanel, George G.

doi:10.1093/jac/dkt027

Cited by 143 publications

(112 citation statements)

References 28 publications

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“…Without the ability to detect bla TEM and bla SHV ESBL determinants, BC-GN would therefore miss a significant proportion of ESBLs if implemented in that region. Second, plasmid-mediated AmpC cephalosporinase production is also well documented in these organisms in North America (18). Unfortunately, BC-GN is not designed to detect AmpC determinants.…”

Section: Discussionmentioning

confidence: 99%

Pediatric Multicenter Evaluation of the Verigene Gram-Negative Blood Culture Test for Rapid Detection of Inpatient Bacteremia Involving Gram-Negative Organisms, Extended-Spectrum Beta-Lactamases, and Carbapenemases

et al. 2014

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We evaluated the investigational use only (IUO) version of the rapid Verigene Gram-negative blood culture test (BC-GN), a microarray that detects 9 genus/species targets (Acinetobacter spp., Citrobacter spp., Enterobacter spp., Escherichia coli/Shigella spp., Klebsiella oxytoca, Klebsiella pneumoniae, Proteus spp., Pseudomonas aeruginosa, and Serratia marcescens) and 6 antimicrobial resistance determinants (bla CTX-M , bla KPC , bla NDM , bla VIM , bla IMP , and bla OXA ) directly from positive blood cultures. BC-GN was performed on positive BacT/Alert Pediatric FAN and Bactec Peds Plus blood cultures with Gram-negative organisms at two tertiary pediatric centers. Vitek MS (bioMérieux, Durham, NC) was used to assign gold standard organism identification. The Check MDR CT-102 microarray (Check Points B.V., Wageningen, Netherlands) was used as an alternative method for detecting resistance determinants. In total, 104 organisms were isolated from 97 clinical blood cultures. BC-GN correctly detected 26/26 cultures with Acinetobacter spp., P. aeruginosa, and S. marcescens, 5/6 with Citrobacter spp., 13/14 with Enterobacter spp., 23/24 with E. coli, 2/3 with K. oxytoca, 16/17 with K. pneumoniae, and 0/1 with Proteus spp. BC-GN appropriately reported negative BC-GN results in 8/13 blood cultures that grew organisms that were not represented on the microarray but failed to detect targets in 3/5 cultures that grew multiple Gram-negative organisms. BC-GN detected 5/5 and 1/1 clinical blood cultures with bla CTX-M and bla VIM . All 6 results were corroborated by Check MDR CT-102 microarray testing. The Verigene BC-GN test has the potential to expedite therapeutic decision making in pediatric patients with Gram-negative bacteremia. Sensitivity was satisfactory but may be suboptimal in mixed Gram-negative blood cultures.

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Section: Discussionmentioning

confidence: 99%

Pediatric Multicenter Evaluation of the Verigene Gram-Negative Blood Culture Test for Rapid Detection of Inpatient Bacteremia Involving Gram-Negative Organisms, Extended-Spectrum Beta-Lactamases, and Carbapenemases

et al. 2014

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“…Infections caused by Gram-negative bacilli (GNB) are a major cause of HAI, including infections caused by Pseudomonas aeruginosa and the Enterobacteriaceae, such as Klebsiella pneumoniae and Escherichia coli (4,5). The incidence of multidrug-resistant GNB, based on the presence of extended-spectrum ␤-lactamases (ESBLs) and AmpC ␤-lactamases, is increasing globally (6)(7)(8)(9). Infections caused by these organisms are associated with a poor prognosis (10,11).…”

mentioning

confidence: 99%

Population Pharmacokinetic Assessment and Pharmacodynamic Implications of Pediatric Cefepime Dosing for Susceptible-Dose-Dependent Organisms

Shoji

Bradley

Reed

et al. 2016

Antimicrob Agents Chemother

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The Clinical and Laboratory Standards Institute (CLSI) revised cefepime (CFP) breakpoints for Enterobacteriaceae in 2014, and MICs of 4 and 8 g/ml were reclassified as susceptible-dose dependent (SDD). Pediatric dosing to provide therapeutic concentrations against SDD organisms has not been defined. CFP pharmacokinetics (PK) data from published pediatric studies were analyzed. Population PK parameters were determined using NONMEM, and Monte Carlo simulation was performed to determine an appropriate CFP dosage regimen for SDD organisms in children. A total of 664 CFP plasma concentrations from 91 neonates, infants, and children were included in this analysis. The median patient age was 1.0 month (interquartile range [IQR], 0.2 to 11.2 months). Serum creatinine (SCR) and postmenstrual age (PMA) were covariates in the final PK model. Simulations indicated that CFP dosing at 50 mg/kg every 8 h (q8h) (as 0.5-h intravenous [i.v.] infusions) will maintain free-CFP concentrations in serum of >4 and 8 g/ml for >60% of the dose interval in 87.1% and 68.6% of pediatric patients (age, >30 days), respectively, and extending the i.v. infusion duration to 3 h results in 92.3% of patients with free-CFP levels above 8 g/ml for >60% of the dose interval. CFP clearance (CL) is significantly correlated with PMA and SCR. A dose of 50 mg/kg of CFP every 8 to 12 h does not achieve adequate serum exposure for older children with serious infections caused by Gram-negative bacilli with a MIC of 8 g/ml. Prolonged i.v. infusions may be useful for this population. Health care-associated infections (HAI), such as ventilator-associated pneumonia, catheter-associated urinary tract infection, surgical site infection, and catheter-related bloodstream infection, may lead to morbidity and mortality in children (1-3). Infections caused by Gram-negative bacilli (GNB) are a major cause of HAI, including infections caused by Pseudomonas aeruginosa and the Enterobacteriaceae, such as Klebsiella pneumoniae and Escherichia coli (4, 5). The incidence of multidrug-resistant GNB, based on the presence of extended-spectrum ␤-lactamases (ESBLs) and AmpC ␤-lactamases, is increasing globally (6-9). Infections caused by these organisms are associated with a poor prognosis (10, 11). Further complicating this clinical challenge is that development of new antibiotics effective against these important pathogens has been slow (12). It is important to use existing antibiotics effectively whenever possible, using pharmacokinetics (PK) and pharmacodynamics (PD) analyses. Cefepime (CFP), a fourth-generation cephalosporin, is widely used to treat infections caused by GNB in both adult and pediatric patients (13,14). Several studies have shown the effectiveness and safety of CFP in treating urinary tract and lower respiratory infections in children (15,16). Further, CFP is also an important choice to treat multidrug-resistant GNB, such as AmpC ␤-lactamase-producing strains and several strains of ESBL-producing organisms with MICs that correspond to clinically achievable pl...

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“…coli expressing CTX-M-type enzymes containing ESBLs have been increasingly seen in the community [12,[22][23][24][25][26]. Residency of a long-term care facility has been recognized as a prominent risk factor for acquisition of ESBL infections in the community.…”

Section: Introductionmentioning

confidence: 99%

“…Residency of a long-term care facility has been recognized as a prominent risk factor for acquisition of ESBL infections in the community. Various studies have also identiied ESBL bacteremia as an independent risk factor from exposure to luoroquinolones, irst-generation cephalosporins, and inally, a previously known colonization history with an ESBL [25,27]. Patients are 57% more likely to die from bloodstream infections associated with ESBL-producing Enterobacteriaceae than those with bloodstream infections caused by a non ESBL-producing strain [26].…”

Section: Introductionmentioning

confidence: 99%

Multidrug-Resistant Gram-Negative Pneumonia and Infection in Intensive Care Unit

Rodríguez¹,

Surani²

2017

Contemporary Topics of Pneumonia

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Multidrug-resistant (MDR) pneumonia can be problematic and challenging to treat in an era of increasing resistance and limited treatment armamentarium. Multidrug-resistant pathogens are associated with increased morbidity and mortality, thus early empiric appropriate antibiotics are critical for survival. Many factors play a role in the selection, optimization, and duration of therapy that should be made on an individual basis. New technologies such as "rapid diagnostics" may provide the clinician with early phenotypic or genotypic result, thus improving early appropriate therapy. The increasing antibiotic resistance is a global threat to patients worldwide and is an economic burden. In the United States, drug-resistant bacteria cause approximately 2 million cases of illnesses and contribute to 23,000 deaths each year. The inappropriate use of antibiotics has contributed to the healthcare burden that ranges from $27 to $42 billion annually. As a result, several governmental agencies have placed forth regulatory mandates to enforce antimicrobial stewardship programs in acute care hospitals. Education will be vital across all healthcare disciplines to ultimately ensure optimal prescribing and reduce the emergence of resistance.

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Molecular epidemiology of extended-spectrum -lactamase-, AmpC -lactamase- and carbapenemase-producing Escherichia coli and Klebsiella pneumoniae isolated from Canadian hospitals over a 5 year period: CANWARD 2007-11

Cited by 143 publications

References 28 publications

Pediatric Multicenter Evaluation of the Verigene Gram-Negative Blood Culture Test for Rapid Detection of Inpatient Bacteremia Involving Gram-Negative Organisms, Extended-Spectrum Beta-Lactamases, and Carbapenemases

Pediatric Multicenter Evaluation of the Verigene Gram-Negative Blood Culture Test for Rapid Detection of Inpatient Bacteremia Involving Gram-Negative Organisms, Extended-Spectrum Beta-Lactamases, and Carbapenemases

Population Pharmacokinetic Assessment and Pharmacodynamic Implications of Pediatric Cefepime Dosing for Susceptible-Dose-Dependent Organisms

Multidrug-Resistant Gram-Negative Pneumonia and Infection in Intensive Care Unit

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