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Infants asymptomatically excrete Clostridioides difficile during their first year of life, suggesting that they may represent a source of infection for adults who acquire community-associated C. difficile infection (CA-CDI). The genetic relationship of C. difficile strains from asymptomatic infants and adults with CA-CDI is not well defined.
In this study, 50 infants were recruited at birth, and stool samples were collected at routine well-child visits. Adult stool samples collected during the same period and geographical area from patients who were diagnosed with CA-CDI were selected for comparison. C. difficile was cultivated and probed by PCR for toxin genes and were typed by PCR fluorescent ribotyping. Isolates from adults and infants with shared ribotypes were subjected to whole-genome sequencing (WGS).
Of these 50 infants, 36 were positive for C. difficile at least once in their first year of life, with a peak incidence at 6 months. Among 180 infant stool samples, 48 were positive. Of 48 isolates from positive stools, 29 were toxigenic by polymerase chain reaction (PCR) and 8 of 48 stool samples were positive for toxin by enzyme immunoassays (EIAs). Ribotypes F106 and F014-020 were present in both colonized infants and adults with CA-CDI. WGS identified 1 adult–infant pair that differed by 5 single-nucleotide polymorphisms (SNPs). Also, 4 additional adult–infant clusters differed by ≤16 SNPs.
Infants that are colonized with C. difficile share ribotypes with adults from the same geographical region with CA-CDI. Selected isolates in the 2 populations show a genetic relationship by WGS.
To assess variability in antimicrobial use and associations with infection testing in pediatric ventilator-associated events (VAEs).
Descriptive retrospective cohort with nested case-control study.
Pediatric intensive care units (PICUs), cardiac intensive care units (CICUs), and neonatal intensive care units (NICUs) in 6 US hospitals.
Children≤18 years ventilated for≥1 calendar day.
We identified patients with pediatric ventilator-associated conditions (VACs), pediatric VACs with antimicrobial use for≥4 days (AVACs), and possible ventilator-associated pneumonia (PVAP, defined as pediatric AVAC with a positive respiratory diagnostic test) according to previously proposed criteria.
Among 9,025 ventilated children, we identified 192 VAC cases, 43 in CICUs, 70 in PICUs, and 79 in NICUs. AVAC criteria were met in 79 VAC cases (41%) (58% CICU; 51% PICU; and 23% NICU), and varied by hospital (CICU, 20–67%; PICU, 0–70%; and NICU, 0–43%). Type and duration of AVAC antimicrobials varied by ICU type. AVAC cases in CICUs and PICUs received broad-spectrum antimicrobials more often than those in NICUs. Among AVAC cases, 39% had respiratory infection diagnostic testing performed; PVAP was identified in 15 VAC cases. Also, among AVAC cases, 73% had no associated positive respiratory or nonrespiratory diagnostic test.
Antimicrobial use is common in pediatric VAC, with variability in spectrum and duration of antimicrobials within hospitals and across ICU types, while PVAP is uncommon. Prolonged antimicrobial use despite low rates of PVAP or positive laboratory testing for infection suggests that AVAC may provide a lever for antimicrobial stewardship programs to improve utilization.
Adult ventilator-associated event (VAE) definitions include ventilator-associated conditions (VAC) and subcategories for infection-related ventilator-associated complications (IVAC) and possible ventilator-associated pneumonia (PVAP). We explored these definitions for children.
Pediatric, cardiac, or neonatal intensive care units (ICUs) in 6 US hospitals
Patients ≤18 years old ventilated for ≥1 day
We identified patients with pediatric VAC based on previously proposed criteria. We applied adult temperature, white blood cell count, antibiotic, and culture criteria for IVAC and PVAP to these patients. We matched pediatric VAC patients with controls and evaluated associations with adverse outcomes using Cox proportional hazards models.
In total, 233 pediatric VACs (12,167 ventilation episodes) were identified. In the cardiac ICU (CICU), 62.5% of VACs met adult IVAC criteria; in the pediatric ICU (PICU), 54.2% of VACs met adult IVAC criteria; and in the neonatal ICU (NICU), 20.2% of VACs met adult IVAC criteria. Most patients had abnormal white blood cell counts and temperatures; we therefore recommend simplifying surveillance by focusing on “pediatric VAC with antimicrobial use” (pediatric AVAC). Pediatric AVAC with a positive respiratory diagnostic test (“pediatric PVAP”) occurred in 8.9% of VACs in the CICU, 13.3% of VACs in the PICU, and 4.3% of VACs in the NICU. Hospital mortality was increased, and hospital and ICU length of stay and duration of ventilation were prolonged among all pediatric VAE subsets compared with controls.
We propose pediatric AVAC for surveillance related to antimicrobial use, with pediatric PVAP as a subset of AVAC. Studies on generalizability and responsiveness of these metrics to quality improvement initiatives are needed, as are studies to determine whether lower pediatric VAE rates are associated with improvements in other outcomes.
To determine the frequency of false-positive Clostridium difficile toxin enzyme immunoassay (EIA) results in hospitalized children and to examine potential reasons for this false positivity.
Two tertiary care pediatric hospitals.
As part of a natural history study, prospectively collected EIA-positive stools were cultured for toxigenic C. difficile, and characteristics of children with false-positive and true-positive EIA results were compared. EIA-positive/culture-negative samples were recultured after dilution and enrichment steps, were evaluated for presence of the tcdB gene by polymerase chain reaction (PCR), and were further cultured for Clostridium sordellii, a cause of false-positive EIA toxin assays.
Of 112 EIA-positive stools cultured, 72 grew toxigenic C. difficile and 40 did not, indicating a positive predictive value of 64% in this population. The estimated prevalence of C. difficile infection (CDI) in the study sites among children tested for this pathogen was 5%–7%. Children with false-positive EIA results were significantly younger than those with true-positive tests but did not differ in other characteristics. No false-positive specimens yielded C. difficile when cultured after enrichment or serial dilution, 1 specimen was positive for tcdB by PCR, and none grew C. sordellii.
Approximately one-third of EIA tests used to evaluate pediatric inpatients for CDI were falsely positive. This finding was likely due to the low prevalence of CDI in pediatric hospitals, which diminishes the test's positive predictive value. These data raise concerns about the use of EIA assays to diagnosis CDI in children.
We sought to determine the frequency of horizontal transmission of antibiotic-resistant gram-negative bacilli (ARGNB) in a pediatric intensive care unit during a nonoutbreak period. Among 5,300 admissions over 39 consecutive months, 13 ARGNB clusters involving 35 children were identified by pulsed-filed gel electrophoresis analysis, which suggests that person-to-person transmission was uncommon.
To determine the cause of fever in critically ill children and to identify opportunities for reducing antibiotic use in this population.
Prospective case series.
A tertiary-care medical-surgical pediatric intensive care unit (PICU).
Children admitted to the PICU who experienced fever (axillary temperature >38.3°C).
Consecutive children who were febrile at any point in their PICU stay were investigated over two winter seasons. Etiology of the fever was determined by physical examination and routine microbiology and radiographic tests. Three subgroups were reviewed to approximate the number of antibiotic-days that could have been reduced; namely, those with an indeterminate source, those with a documented viral infection, and those receiving a prolonged course of antibiotics. A set of standards reflecting common antibiotic use then was applied to these three patient groups.
Of 211 subjects, the majority (83.3%) had either a definitive or suspected focus for their fever, and nearly all of these patients were judged to have an infectious etiology. The study population received a total of 2,036 antibiotic-days. Despite the high incidence of infectious causes of fever in our subjects, however, approximately 15% of total antibiotic-days could have been reduced by applying common-use standards.
Fever in the PICU was usually of defined focus and infectious in origin. However, among febrile patients in the PICU, substantial opportunity exists for reduction of antibiotic use. Trials determining the safety of antibiotic reduction in this population should be pursued vigorously.
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