Treatment of Carbapenem-Resistant Enterobacteriaceae Infections in Children

Chiotos, Kathleen; Hayes, Molly; Gerber, Jeffrey S.; Tamma, Pranita D.

doi:10.1093/jpids/piz085

Cited by 64 publications

(85 citation statements)

References 119 publications

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“…However, avibactam is inactive against metallo-β-lactamase (MBL) producers, including NDM and IMP, and monobactam antibiotics are active against MBL producers. 25 Therefore, the synergistic effects of different carbapenemase classes may lead to higher levels of resistance to carbapenems and other antimicrobials. Due to the limited choice of antibiotics in children, the emergence of these strains brings great challenges to clinical treatment.…”

Section: Discussionmentioning

confidence: 99%

Clinical Molecular Epidemiology of Carbapenem-Resistant Klebsiella pneumoniae Among Pediatric Patients in Jiangsu Province, China

Kong¹,

Liu²,

Li³

et al. 2020

IDR

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Purpose The continuous emergence of carbapenem-resistant Klebsiella pneumoniae (CRKP) has become a serious public health problem globally, especially for children, but data on CRKP infection in pediatric patients are limited. This study aimed to identify epidemiological and molecular patterns of CRKP among pediatric patients in Jiangsu province, China. Patients and Methods CRKP were consecutively collected from the Children’s Hospital of Nanjing Medical University in China from July 2018 to May 2019. Then, CRKP strains were performed for further study: antimicrobial susceptibility testing, drug-resistance determinants screening and homology analysis. Results We collected 94 CRKP from 94 children. Overall, bla KPC-2 (79.8%) was the predominant carbapenemase gene, followed by bla NDM-1 (14.9%), bla IMP-4 (5.3%) and bla NDM-5 (4.3%). Notably, two isolates coharbored bla KPC-2 and bla IMP-4 , and two isolates coharbored bla KPC-2 and bla NDM-5 . MLST analysis revealed that 14 distinct sequence types (STs) were identified, of which ST11 was the most common sequence type identified. Moreover, two novel STs, ST4854 and ST4855, were detected in this study. PFGE revealed that a predominant cluster consisting of KPC-2-producing CRKP ST11 clone isolates was identified and was distributed mainly in the pediatric intensive care unit (PICU) and cardiac intensive care unit (CCU). Moreover, this is the first report to identify the dissemination of ST716 CRKP coproducing KPC-2 and IMP-4 clones. Conclusion Clonal dissemination of KPC-2-producing CRKP ST11 was observed in multiple departments. Moreover, two novel STs (ST4854 and ST4855) were identified, which indicates an increased diversity of CRKP strains. To our knowledge, this is the first report that identified the dissemination of Klebsiella pneumoniae coproducing KPC-2 and IMP-4 clones among children, which represents a significant health risk to pediatric patients. Active surveillance and effective control measures are urgently needed to prevent further transmission of these strains among children.

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Section: Discussionmentioning

confidence: 99%

Clinical Molecular Epidemiology of Carbapenem-Resistant Klebsiella pneumoniae Among Pediatric Patients in Jiangsu Province, China

Kong¹,

Liu²,

Li³

et al. 2020

IDR

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“…However, it is generally accepted that the first-line treatment of CR-Kp infection is based on colistin or a novel cephalosporin/β-lactamase inhibitor combination, ceftazidime-avibactam [ 39 ], which was not used in this study group. Considering the paucity of available data in pediatric population [ 40 ], the therapy used at our institution was adjusted on the basis of the severity of infection, the susceptibility profile of isolates, and pharmacokinetics to achieve adequate antibiotic serum concentrations. Treatment is a crucial part for patient prognosis, but we did not consider the antimicrobial therapy as a factor in our predictive model due to the inconsistency between the treatments in this retrospective cohort and the current standard.…”

Section: Discussionmentioning

confidence: 99%

A risk score based on pediatric sequential organ failure assessment predicts 90-day mortality in children with Klebsiella pneumoniae bloodstream infection

Liu

Chen

et al. 2020

BMC Infect Dis

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Background Klebsiella pneumoniae bloodstream infection (Kp-BSI) is a serious threat to pediatric patients. The objective of this study was to explore the risk factors, validate the prediction efficiency of pediatric Sequential Organ Failure Assessment (SOFA) and establish better early predictors of mortality in pediatric patients with Kp-BSI. Methods All children diagnosed with Kp-BSI were included in this retrospective cohort study from January 2009 to June 2019. Basic characteristics, symptoms and physical examinations, treatments, laboratory statistics, and SOFA at the onset of Kp-BSI were recorded. The Cox proportional hazard model and receiver operating characteristic curves were used to assess the association between the variables and the 90-day mortality and their predictive value. DeLong’s test of receiver operating characteristic curves and integrated discrimination improvement index were used to determine the improvement in predictive capacity of the modified SOFA models. A predictive score was developed using multivariate logistic regression. Results Of the 146 children enrolled, 33 (22.6%) patients died within 90 days. Hospitalization in the last 6 months, intra-abdominal source of infection, presence of organ failure, and altered levels of blood biomarkers, including C-reactive protein, albumin, and lactate were significant risk factors for 90-day mortality. The area under the curve (AUC) of SOFA for predicting 90-day mortality was 0.80 (95% CI 0.71–0.89). Moreover, we found that a prediction model combining SOFA with two other parameters, namely hospitalization in the last 6 months and intra-abdominal source of infection, was better at predicting mortality (AUC = 0.89, 95% CI 0.82–0.96; sensitivity = 0.86; specificity = 0.84). According to this novel risk model, we defined three statistically different groups: low-risk, medium-risk and high-risk groups, with an observed 90-day mortality of 5.4, 35.7, and 72.0%, respectively. With reference to the low-risk patients, the medium-risk and high-risk groups had a higher mortality, with hazard ratios of 8.36 (95% CI 3.60–27.83) and 20.27 (95% CI 7.47–54.95), respectively. Conclusions The modified SOFA may be better than the original score to predict 90-day mortality in pediatric patients with Kp-BSI. Future prospective studies are required to validate this novel scoring system in external cohorts.

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“…However, it is generally accepted that the rst-line treatment of CR-Kp infection is based on colistin or a novel cephalosporin/βlactamase inhibitor combination, ceftazidime-avibactam [39], which was not used in this study group. Considering the paucity of available data in pediatric population [40], the therapy used at our institution was adjusted on the basis of the severity of infection, the susceptibility pro le of isolates, and pharmacokinetics to achieve adequate antibiotic serum concentrations. Treatment is a crucial part for patient prognosis, but we did not consider the antimicrobial therapy as a factor in our predictive model due to the inconsistency between the treatments in this retrospective cohort and the current standard.…”

Section: Discussionmentioning

confidence: 99%

A risk score based on pediatric Sequential Organ Failure Assessment predicts 90-day mortality in children with Klebsiella pneumoniae bloodstream infection

Liu

Chen

et al. 2020

Preprint

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Background: Klebsiella pneumoniae bloodstream infection (Kp-BSI) is a serious threat to pediatric patients. The objective of this study was to explore the risk factors, validate the prediction efficiency of pediatric Sequential Organ Failure Assessment (SOFA) and establish better early predictors of mortality in pediatric patients with Kp-BSI. Methods: All children diagnosed with Kp-BSI were included in this retrospective cohort study from January 2009 to June 2019. Basic characteristics, symptoms and physical examinations, treatments, laboratory statistics, and SOFA at the onset of Kp-BSI were recorded. The Cox proportional hazard model and receiver operating characteristic curves were used to assess the association between the variables and the 90-day mortality and their predictive value. DeLong's test of receiver operating characteristic curves and integrated discrimination improvement index were used to determine the improvement in predictive capacity of the modified SOFA models. A predictive score was developed using multivariate logistic regression. Results: Of the 146 children enrolled, 33 (22.6%) patients died within 90 days. Hospitalization in the last six months, intra-abdominal source of infection, presence of organ failure, and altered levels of blood biomarkers, including C-reactive protein, albumin, and lactate were significant risk factors for 90-day mortality. The area under the curve (AUC) of SOFA for predicting 90-day mortality was 0.80 (95% CI 0.71–0.89). Moreover, we found that a prediction model combining SOFA with two other parameters, namely hospitalization in the last six months and intra-abdominal source of infection, was better at predicting mortality (AUC = 0.89, 95% CI 0.82–0.96; sensitivity = 0.86; specificity = 0.84). According to this novel risk model, we defined three statistically different groups: low-risk, medium-risk and high-risk groups, with an observed 90-day mortality of 5.4%, 35.7%, and 72.0%, respectively. With reference to the low-risk patients, the medium-risk and high-risk groups had a higher mortality, with hazard ratios of 8.36 (95% CI 3.60–27.83) and 20.27 (95% CI 7.47–54.95), respectively. Conclusions: The modified SOFA may be better than the original score to predict 90-day mortality in pediatric patients with Kp-BSI. Future prospective studies are required to validate this novel scoring system in external cohorts.

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Treatment of Carbapenem-Resistant Enterobacteriaceae Infections in Children

Cited by 64 publications

References 119 publications

Clinical Molecular Epidemiology of Carbapenem-Resistant Klebsiella pneumoniae Among Pediatric Patients in Jiangsu Province, China

Clinical Molecular Epidemiology of Carbapenem-Resistant Klebsiella pneumoniae Among Pediatric Patients in Jiangsu Province, China

A risk score based on pediatric sequential organ failure assessment predicts 90-day mortality in children with Klebsiella pneumoniae bloodstream infection

A risk score based on pediatric Sequential Organ Failure Assessment predicts 90-day mortality in children with Klebsiella pneumoniae bloodstream infection

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