Carbapenem-Resistant Enterobacteriaceae Infections in Children

Chiotos, Kathleen; Han, Jennifer H.; Tamma, Pranita D.

doi:10.1007/s11908-015-0510-9

Cited by 63 publications

(77 citation statements)

References 100 publications

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“…23 Carbapenem-resistant Enterobacteriaceae infections are still relatively uncommon in children, with prevalence being reported less than 1% and mortality rate lower compared with adults. 24 In the multivariate analysis, previous colonization by an MDR pathogen was independently associated with an MDR-HAI. Children have been proven to show particularly high colonization rates, representing a reservoir from which bacteria can spread.…”

Section: Discussionmentioning

confidence: 97%

Healthcare-Associated Infections in Pediatric and Neonatal Intensive Care Units: Impact of Underlying Risk Factors and Antimicrobial Resistance on 30-Day Case-Fatality in Italy and Brazil

Folgori

Bernaschi

Piga

et al. 2016

Infect. Control Hosp. Epidemiol.

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objectives. To describe trends in the epidemiology of healthcare-associated Infections (HAIs) in pediatric/neonatal intensive care units (ICUs) and to evaluate risk factors and impact of multidrug resistance in children admitted to ICUs.design. Multicenter, retrospective, cohort study with a nested case-control study conducted from January 1, 2010, through December 31, 2014.setting. Three tertiary care pediatric hospitals in Italy and Brazil with a total of 103 ICU beds.patients. Inclusion criteria were admission to ICU during the study period, age at onset less than 18 years, and microbiologically confirmed HAI.results. A total of 538 HAIs in 454 children were included; 93.3% of patients had comorbidities. Bloodstream infections were the leading pattern (45.4%). The cumulative incidence of HAI was 3.6/100 ICU admissions and the crude 30-day fatality rate was 5.7/1,000 admissions. The most frequently isolated pathogens were Enterobacteriaceae, followed by Pseudomonas aeruginosa and Staphylococcus aureus. Forty-four percent of isolates were multidrug-resistant (MDR). Two multivariate logistic regressions were performed. Factors independently associated with an MDR-HAI were country, previous antibiotics, transplantation, major surgery, and colonization by an MDR strain. Factors independently associated with 30-day case fatality were country, previous transplantation, fungal infection, bloodstream infection, lower respiratory tract infection, and infection caused by MDR strains.conclusions. Infection control and prevention can limit the spread of MDR strains and improve outcomes. Targeted surveillance programs collecting neonatal and pediatric HAI/bloodstream infection data and outcomes would allow global benchmarking. The next step is to identify methods to monitor key HAIs and integrate these into affordable intervention programs. 2016;37:1302-1309 Healthcare-associated infections (HAIs) are one of the most frequent adverse events affecting children admitted to intensive care units (ICUs). Infect Control Hosp Epidemiol1,2 Exposure to invasive devices and procedures, immune suppression, and underlying conditions are considered as main determinants of patients' increased susceptibility.3,4 The impact of multidrug-resistant (MDR) organisms in pediatrics is increasing globally. [5][6][7] It is assumed that infections caused by MDR bacteria will have a worse prognosis because of the delay in the administration of appropriate therapy. However, it is difficult to estimate the clinical impact of MDR-HAI in children.Previous literature has shown conflicting results about the impact of different underlying risk factors on the clinical outcome of patients with HAI admitted to ICUs. There is no clear independent correlation between antimicrobial resistance and patients' mortality. [8][9][10][11] Clarifying the relationship between patient risk factors and pediatric HAI mortality could allow improved targeting of interventions on the patients most at risk of adverse outcome. The aims of this study were to describe trends i...

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Section: Discussionmentioning

confidence: 97%

Healthcare-Associated Infections in Pediatric and Neonatal Intensive Care Units: Impact of Underlying Risk Factors and Antimicrobial Resistance on 30-Day Case-Fatality in Italy and Brazil

Folgori

Bernaschi

Piga

et al. 2016

Infect. Control Hosp. Epidemiol.

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“…32 Unlike ESBL-producing organisms, carbapenemase-producing organisms in US children have been limited to those with previous healthcare exposure. 2,33 …”

Section: Discussionmentioning

confidence: 99%

The Prevalence and Molecular Epidemiology of Multidrug-Resistant Enterobacteriaceae Colonization in a Pediatric Intensive Care Unit

Suwantarat

Logan

Carroll

et al. 2016

Infect. Control Hosp. Epidemiol.

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OBJECTIVE To determine the prevalence and acquisition of extended-spectrum β-lactamases (ESBLs), plasmid-mediated AmpCs (pAmpCs), and carbapenemases (“MDR Enterobacteriaceae”) colonizing children admitted to a pediatric intensive care unit (PICU). DESIGN Prospective study. SETTING 40-bed PICU. METHODS Admission and weekly thereafter rectal surveillance swabs were collected on all pediatric patients during a 6-month study period. Routine phenotypic identification and antibiotic susceptibility testing were performed. Enterobacteriaceae displaying characteristic resistance profiles underwent further molecular characterization to identify genetic determinants of resistance likely to be transmitted on mobile genetic elements and to evaluate relatedness of strains including DNA microarray, multilocus sequence typing, repetitive sequence-based PCR, and hsp60 sequencing typing. Results Evaluating 854 swabs from unique children, the overall prevalence of colonization with an MDR Enterobacteriaceae upon admission to the PICU based on β-lactamase gene identification was 4.3% (n = 37), including 2.8% ESBLs (n =24), 1.3% pAmpCs (n =11), and 0.2% carbapenemases (n =2). Among 157 pediatric patients contributing 603 subsequent weekly swabs, 6 children (3.8%) acquired an incident MDR Enterobacteriaceae during their PICU stay. One child acquired a pAmpC (E. coli containing blaDHA) related to an isolate from another patient. Conclusions Approximately 4% of children admitted to a PICU were colonized with MDR Enterobacteriaceae (based on β-lactamase gene identification) and an additional 4% of children who remained in the PICU for at least 1 week acquired 1 of these organisms during their PICU stay. The acquired MDR Enterobacteriaceae were relatively heterogeneous, suggesting that a single source was not responsible for the introduction of these resistance mechanisms into the PICU setting.

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“…This case represents the first report of meropenem‐vaborbactam monotherapy in a pediatric patient for treatment of a BSI caused by KPC‐producing organism. Carbapenem‐resistant Enterobacteriaceae infections are becoming responsible for more health care–associated infections in adult patients, and they are associated with poor clinical outcomes and mortality rates of 40% to 65% . Currently, CRE infections are not as common in children, but reports of infections both in the United States and worldwide are increasing.…”

Section: Discussionmentioning

confidence: 99%

“…As the medically complex pediatric population increases, CRE may emerge as a significant nosocomial pathogen in pediatric centers in the near future. To date, CRE infections have been documented in neonatal and pediatric ICUs, as well as in children residing in long‐term care facilities and children with oncologic conditions . As such, meropenem‐vaborbactam may be a safe and effective alternative to best available therapy in the treatment of CRE infections in these pediatric populations due to the familiarity of meropenem with pediatric practitioners until additional studies can be conducted.…”

Section: Discussionmentioning

confidence: 99%

“…Carbapenem-resistant Enterobacteriaceae infections are becoming responsible for more health care-associated infections in adult patients, and they are associated with poor clinical outcomes and mortality rates of 40% to 65%. [21][22][23][24][25][26] Currently, CRE infections are not as common in children, but reports of infections both in the United States and worldwide are increasing. As the medically complex pediatric population increases, CRE may emerge as a significant nosocomial pathogen in pediatric centers in the near future.…”

Section: Discussionmentioning

confidence: 99%

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Pharmacokinetics of the Meropenem Component of Meropenem‐Vaborbactam in the Treatment of KPC‐Producing Klebsiella pneumoniae Bloodstream Infection in a Pediatric Patient

et al. 2018

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Meropenem‐vaborbactam is a new β‐lactam/β‐lactamase inhibitor combination designed to target Klebsiella pneumoniae carbapenemase (KPC)‐producing Enterobacteriaceae. Meropenem‐vaborbactam was United States Food and Drug Administration–approved for complicated urinary tract infections in patients 18 years of age or older. An understanding of the pharmacokinetics of meropenem when given in combination with vaborbactam is important to understanding the dosing of meropenem‐vaborbactam. In addition, the safety and efficacy of meropenem‐vaborbactam in a pediatric patient have yet to be described in the literature. The authors conducted a retrospective single‐patient chart review for a 4‐year‐old male patient with short bowel syndrome, colostomy and gastrojejunal tube, bronchopulmonary dysplasia, and a central line for chronic total parenteral nutrition and hydration management, complicated with multiple central line–associated bloodstream infections (BSIs). The patient was brought to our medical center with fever concerning for a BSI. On day 2, the patient was started on meropenem‐vaborbactam at a dosage of 40 mg/kg every 6 hours infused over 3 hours for KPC‐producing K. pneumoniae BSI. Meropenem serum concentrations obtained on day 5 of meropenem‐vaborbactam therapy, immediately following the completion of the infusion and 1 hour after the infusion, were 51.3 and 13.6 μg/ml, respectively. Serum concentrations correlated to a volume of distribution of 0.59 L/kg and a clearance of 13.1 ml/min/kg. Repeat blood cultures remained negative, and meropenem‐vaborbactam was continued for a total of 14 days. A meropenem‐vaborbactam regimen of 40 mg/kg every 6 hours given over 3 hours was successful in providing a target attainment of 100% for meropenem serum concentrations above the minimum inhibitory concentration for at least 40% of the dosing interval and was associated with successful bacteremia clearance in a pediatric patient.

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Carbapenem-Resistant Enterobacteriaceae Infections in Children

Cited by 63 publications

References 100 publications

Healthcare-Associated Infections in Pediatric and Neonatal Intensive Care Units: Impact of Underlying Risk Factors and Antimicrobial Resistance on 30-Day Case-Fatality in Italy and Brazil

Healthcare-Associated Infections in Pediatric and Neonatal Intensive Care Units: Impact of Underlying Risk Factors and Antimicrobial Resistance on 30-Day Case-Fatality in Italy and Brazil

The Prevalence and Molecular Epidemiology of Multidrug-Resistant Enterobacteriaceae Colonization in a Pediatric Intensive Care Unit

Pharmacokinetics of the Meropenem Component of Meropenem‐Vaborbactam in the Treatment of KPC‐Producing Klebsiella pneumoniae Bloodstream Infection in a Pediatric Patient

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