Association of Empiric Antibiotic Regimen Discordance With 30-Day Mortality in Neonatal and Pediatric Bloodstream Infection-A Global Retrospective Cohort Study.

2020

2020 Dec 21

1532-0987

<p><strong>BACKGROUND: </strong>While there have been studies in adults reporting discordant empiric antibiotic treatment associated with poor outcomes, this area is relatively unexplored in children and neonates despite evidence of increasing resistance to recommended first-line treatment regimens.</p>

<p><strong>METHODS: </strong>Patient characteristics, antibiotic treatment, microbiology, and 30-day all-cause outcome from children &lt;18 years with blood-culture-confirmed bacterial bloodstream infections (BSI) were collected anonymously using REDCap™ through the Global Antibiotic Prescribing and Resistance in Neonates and Children network from February 2016 to February 2017. Concordance of early empiric antibiotic treatment was determined using European Committee on Antimicrobial Susceptibility Testing interpretive guidelines. The relationship between concordance of empiric regimen and 30-day mortality was investigated using multivariable regression.</p>

<p><strong>RESULTS: </strong>Four hundred fifty-two children with blood-culture-positive BSI receiving early empiric antibiotics were reported by 25 hospitals in 19 countries. Sixty percent (273/452) were under the age of 2 years. S. aureus, E. coli, and Klebsiella spp. were the most common isolates, and there were 158 unique empiric regimens prescribed. Fifteen percent (69/452) of patients received a discordant regimen, and 7.7% (35/452) died. Six percent (23/383) of patients with concordant regimen died compared with 17.4% (12/69) of patients with discordant regimen. Adjusting for age, sex, presence of comorbidity, unit type, hospital-acquired infections, and Gram stain, the odds of 30-day mortality were 2.9 (95% confidence interval: 1.2-7.0; P = 0.015) for patients receiving discordant early empiric antibiotics.</p>

<p><strong>CONCLUSIONS: </strong>Odds of mortality in confirmed pediatric BSI are nearly 3-fold higher for patients receiving a discordant early empiric antibiotic regimen. The impact of improved concordance of early empiric treatment on mortality, particularly in critically ill patients, needs further evaluation.</p>

10.1097/INF.0000000000002910

Pediatr Infect Dis J

33395208

Antibiotics and Cure Rates in Childhood Febrile Urinary Tract Infections in Clinical Trials: A Systematic Review and Meta-analysis.

2018

2018 Oct 11

1179-1950

<p><strong>PURPOSE: </strong>Urinary tract infections (UTIs) are common bacterial infections among children.</p>

<p><strong>OBJECTIVE: </strong>To systematically review the antimicrobials used for febrile UTIs in paediatric clinical trials and meta-analyse the observed cure rates and reasons for treatment failure.</p>

<p><strong>MATERIALS AND METHODS: </strong>We searched Medline, Embase and Cochrane central databases between January 1, 1990, and November 24, 2016, combining MeSH and free-text terms for: "urinary tract infections", AND "therapeutics", AND "clinical trials" in children (age range 0-18&nbsp;years). Two independent reviewers assessed study quality and performed data extraction. The major outcome measures were clinical and microbiological cure rates according to different antibiotics.</p>

<p><strong>RESULTS: </strong>We identified 2762 published studies and included 30 clinical trials investigating 3913 cases of paediatric febrile urinary tract infections. Children with no underlying condition were the main population included in the trials (n = 2602; 66.5%). Cephalosporins were the most frequent antibiotics studied in trials (22/30, 73.3%). Only a few antibiotics active against resistant UTIs have been tested in randomised clinical trials, mainly aminoglycosides. The average point cure rate of all investigational drugs was estimated to 95.3% (95% CI 93.5-96.9%). Among 3002 patients for whom cure and failure rates were reported, only 3.9% (3.9%; 118/3002) were considered clinically to have treatment failure, while 135 (4.5%; 135/3002) had microbiological failure.</p>

<p><strong>CONCLUSIONS: </strong>We observed high treatment cure rates, regardless of the investigational drug chosen, the route of administration, duration and dosing. This suggests that future research should prioritise observational studies and clinical trials on children with multi-drug-resistant infections.</p>

10.1007/s40265-018-0988-1

Drugs

30311096

Urinary Tract Infection Antibiotic Trial Study Design: A Systematic Review.

2017

2017 Dec

1098-4275

<p><strong>CONTEXT: </strong>Urinary tract infections (UTIs) represent common bacterial infections in children. No guidance on the conduct of pediatric febrile UTI clinical trials (CTs) exist.</p>

<p><strong>OBJECTIVE: </strong>To assess the criteria used for patient selection and the efficacy end points in febrile pediatric UTI CTs.</p>

<p><strong>DATA SOURCES: </strong>Medline, Embase, Cochrane central databases, and clinicaltrials.gov were searched between January 1, 1990, and November 24, 2016.</p>

<p><strong>STUDY SELECTION: </strong>We combined Medical Subject Headings terms and free-text terms for "urinary tract infections" and "therapeutics" and "clinical trials" in children (0-18 years), identifying 3086 articles.</p>

<p><strong>DATA EXTRACTION: </strong>Two independent reviewers assessed study quality and performed data extraction.</p>

<p><strong>RESULTS: </strong>We included 40 CTs in which a total of 4381 cases of pediatric UTIs were investigated. Positive urine culture results and fever were the most common inclusion criteria (93% and 78%, respectively). Urine sampling method, pyuria, and colony thresholds were highly variable. Clinical and microbiological end points were assessed in 88% and 93% of the studies, respectively. Timing for end point assessment was highly variable, and only 3 studies (17%) out of the 18 performed after the Food and Drug Administration 1998 guidance publication assessed primary and secondary end points consistently with this guidance.</p>

<p><strong>LIMITATIONS: </strong>Our limitations included a mixed population of healthy children and children with an underlying condition. In 6 trials, researchers studied a subgroup of patients with afebrile UTI.</p>

<p><strong>CONCLUSIONS: </strong>We observed a wide variability in the microbiological inclusion criteria and the timing for end point assessment. The available guidance for adults appear not to be used by pediatricians and do not seem applicable to the childhood UTI. A harmonized design for pediatric UTIs CT is necessary.</p>

10.1542/peds.2017-2209

Pediatrics

29187579