Comparative Effectiveness of Echinocandins vs Triazoles or Amphotericin B Formulations as Initial Directed Therapy for Invasive Candidiasis in Children and Adolescents.

2021

2021 Aug 10

2048-7207

<p><strong>BACKGROUND: </strong>Invasive candidiasis is the most common invasive fungal disease in children and adolescents, but there are limited pediatric-specific antifungal effectiveness data. We compared the effectiveness of echinocandins to triazoles or amphotericin B formulations (triazole/amphotericin B) as initial directed therapy for invasive candidiasis.</p>

<p><strong>METHODS: </strong>This multinational observational cohort study enrolled patients aged &gt;120 days and &lt;18 years with proven invasive candidiasis from January 1, 2014, to November 28, 2017, at 43 International Pediatric Fungal Network sites. Primary exposure was initial directed therapy administered at the time qualifying culture became positive for yeast. Exposure groups were categorized by receipt of an echinocandin vs receipt of triazole/amphotericin B. Primary outcome was global response at 14 days following invasive candidiasis onset, adjudicated by a centralized data review committee. Stratified Mantel-Haenszel analyses estimated risk difference between exposure groups.</p>

<p><strong>RESULTS: </strong>Seven-hundred and fifty invasive candidiasis episodes were identified. After exclusions, 541 participants (235 in the echinocandin group and 306 in the triazole/amphotericin B group) remained. Crude failure rates at 14 days for echinocandin and triazole/amphotericin B groups were 9.8% (95% confidence intervals [CI]: 6.0% to 13.6%) and 13.1% (95% CI: 9.3% to 16.8%), respectively. The adjusted 14-day risk difference between echinocandin and triazole/amphotericin B groups was -7.1% points (95% CI: -13.1% to -2.4%), favoring echinocandins. The risk difference was -0.4% (95% CI: -7.5% to 6.7%) at 30 days.</p>

<p><strong>CONCLUSIONS: </strong>In children with invasive candidiasis, initial directed therapy with an echinocandin was associated with reduced failure rate at 14 days but not 30 days. These results may support echinocandins as initial directed therapy for invasive candidiasis in children and adolescents.</p>

<p><strong>CLINICAL TRIALS REGISTRATION: </strong>NCT01869829.</p>

10.1093/jpids/piab024

J Pediatric Infect Dis Soc

34374424

Fluoroquinolone Antibiotics and Tendon Injury in Adolescents.

2021

2021 May 14

1098-4275

<p><strong>OBJECTIVES: </strong>To estimate the association between fluoroquinolone use and tendon injury in adolescents.</p>

<p><strong>METHODS: </strong>We conducted an active-comparator, new-user cohort study using population-based claims data from 2000 to 2018. We included adolescents (aged 12-18 years) with an outpatient prescription fill for an oral fluoroquinolone or comparator broad-spectrum antibiotic. The primary outcome was Achilles, quadricep, patellar, or tibial tendon rupture identified by diagnosis and procedure codes. Tendinitis was a secondary outcome. We used weighting to adjust for measured confounding and a negative control outcome to assess residual confounding.</p>

<p><strong>RESULTS: </strong>The cohort included 4.4 million adolescents with 7.6 million fills for fluoroquinolone (275 767 fills) or comparator (7 365 684) antibiotics. In the 90 days after the index antibiotic prescription, there were 842 tendon ruptures and 16 750 tendinitis diagnoses (crude rates 0.47 and 9.34 per 1000 person-years, respectively). The weighted 90-day tendon rupture risks were 13.6 per 100 000 fluoroquinolone-treated adolescents and 11.6 per 100 000 comparator-treated adolescents (fluoroquinolone-associated excess risk: 1.9 per 100 000 adolescents; 95% confidence interval -2.6 to 6.4); the corresponding number needed to treat to harm was 52 632. For tendinitis, the weighted 90-day risks were 200.8 per 100 000 fluoroquinolone-treated adolescents and 178.1 per 100 000 comparator-treated adolescents (excess risk: 22.7 per 100 000; 95% confidence interval 4.1 to 41.3); the number needed to treat to harm was 4405.</p>

<p><strong>CONCLUSIONS: </strong>The excess risk of tendon rupture associated with fluoroquinolone treatment was extremely small, and these events were rare. The excess risk of tendinitis associated with fluoroquinolone treatment was also small. Other more common potential adverse drug effects may be more important to consider for treatment decision-making, particularly in adolescents without other risk factors for tendon injury.</p>

10.1542/peds.2020-033316

Pediatrics

33990459

Outpatient Fluoroquinolone Use in Children, 2000-2018.

2020

2020 Dec 30

2048-7207

<p><strong>BACKGROUND: </strong>While fluoroquinolones are commonly used in adults, the use in children has been low. Since 2000, there were 3 US Food and Drug Administration (FDA) Boxed warnings regarding fluoroquinolones (2008, 2013, and 2016). Our objective was to describe the use of fluoroquinolones in children and assess the impact of 3 recent FDA warnings on fluoroquinolone use.</p>

<p><strong>METHODS: </strong>From 2000 to 2018, we assessed claims for all outpatient prescription fills to measure the use of systemic fluoroquinolones and other broad-spectrum antibiotics in children  less than 18 years old in the MarketScan Commercial Claims and Encounters database. We describe demographics, indication for antibiotic, and clinical characteristics. To assess the impact of FDA warnings on fill rates, we conducted an interrupted time-series analysis.</p>

<p><strong>RESULTS: </strong>The cohort included 34.6 million unique beneficiaries less than 18 years old with 441 062 fluoroquinolone fills (5.5 fills per 1000 person-years). The fluoroquinolone fill rate was highest among children &gt; 11 years old. Urinary tract infection was the most common associated diagnosis (21.8%). Since 2008, the fluoroquinolone fill rate has declined. By the end of the study period in December 2018, in the (counterfactual) absence of the FDA warnings, fluoroquinolone fill rate would have been 7.5 (95% confidence interval [CI]: 5.2-9.7); however, the corresponding rate in observed data was 2.8 (95% CI: 1.7-3.9).</p>

<p><strong>CONCLUSIONS: </strong>Fluoroquinolone use was low compared with other common broad-spectrum antibiotics and declining trends over time were associated with FDA warnings, even though these warnings were not pediatric specific. Future work should assess the adverse events at issue in these warnings in children.</p>

10.1093/jpids/piaa156

J Pediatric Infect Dis Soc

33377490

Infections after pediatric ambulatory surgery: Incidence and risk factors.

2019

150-157

2019 Feb

1559-6834

<p><strong>OBJECTIVE: </strong>To describe the epidemiology of surgical site infections (SSIs) after pediatric ambulatory surgery.</p>

<p><strong>DESIGN: </strong>Observational cohort study with 60 days follow-up after surgery.</p>

<p><strong>SETTING: </strong>The study took place in 3 ambulatory surgical facilities (ASFs) and 1 hospital-based facility in a single pediatric healthcare network.ParticipantsChildren &lt;18 years undergoing ambulatory surgery were included in the study. Of 19,777 eligible surgical encounters, 8,502 patients were enrolled.</p>

<p><strong>METHODS: </strong>Data were collected through parental interviews and from chart reviews. We assessed 2 outcomes: (1) National Healthcare Safety Network (NHSN)-defined SSI and (2) evidence of possible infection using a definition developed for this study.</p>

<p><strong>RESULTS: </strong>We identified 21 NSHN SSIs for a rate of 2.5 SSIs per 1,000 surgical encounters: 2.9 per 1,000 at the hospital-based facility and 1.6 per 1,000 at the ASFs. After restricting the search to procedures completed at both facilities and adjustment for patient demographics, there was no difference in the risk of NHSN SSI between the 2 types of facilities (odds ratio, 0.7; 95% confidence interval, 0.2-2.3). Within 60 days after surgery, 404 surgical patients had some or strong evidence of possible infection obtained from parental interview and/or chart review (rate, 48 SSIs per 1,000 surgical encounters). Of 306 cases identified through parental interviews, 176 cases (57%) did not have chart documentation. In our multivariable analysis, older age and black race were associated with a reduced risk of possible infection.</p>

<p><strong>CONCLUSIONS: </strong>The rate of NHSN-defined SSI after pediatric ambulatory surgery was low, although a substantial additional burden of infectious morbidity related to surgery might not have been captured by standard surveillance strategies and definitions.</p>

10.1017/ice.2018.211

Infect Control Hosp Epidemiol

30698133

Temporal Trends and Center Variation in Early Antibiotic Use Among Premature Infants.

2018

e180164

2018 May 18

2574-3805

<p><strong>Importance: </strong>Premature infants are frequently administered empirical antibiotic therapy at birth. Early and prolonged antibiotic exposures among infants without culture-confirmed infection have been associated with increased risk of adverse outcomes.</p>

<p><strong>Objective: </strong>To examine early antibiotic use among premature infants over time and across hospitals in the United States.</p>

<p><strong>Design, Setting, and Participants: </strong>This retrospective cohort study used a comprehensive administrative database of inpatient encounters from 297 academic and community hospitals across the United States to examine data concerning very low-birth-weight (VLBW) infants (&lt;1500 g), including extremely low-birth-weight (ELBW) infants (&lt;1000 g), who were admitted to the neonatal intensive care unit and survived for at least 1 day. Data collection took place in November 2015 and analysis took place from February 2016 to November 2016.</p>

<p><strong>Exposures: </strong>Antibiotic initiation within the first 3 days of age and subsequent antibiotic administration for more than 5 days.</p>

<p><strong>Main Outcomes and Measures: </strong>Temporal trends in early antibiotic initiation and duration from 2009 to 2015, and center variation in early antibiotic use from 2014 to 2015.</p>

<p><strong>Results: </strong>We identified 40 364 VLBW infants (20 447 female [50.7%]) who survived for at least 1 day, including 12 947 ELBW infants, from 297 centers. The majority of premature infants had early antibiotic initiation (31 715 VLBW infants [78.6%] and 11 264 ELBW infants [87.0%]), and no differences were observed over time in temporal trend analyses (P = .12 for VLBW and P = .52 for ELBW). The annual risk difference in the proportion of VLBW infants administered early antibiotic therapy ranged from -0.75% (95% CI, -1.61% to 0.11%) to -0.87% (95% CI, -2.04% to 0.30%); in ELBW infants the annual risk difference ranged from -0.34% (95% CI, -1.28% to 0.61%) to -0.38% (95% CI, -1.61% to 0.85%). There was a small but significant decrease over time in the rate of prolonged antibiotic duration for VLBW infants (P = .02), but not for ELBW infants (P = .22). The annual risk difference in the proportion of VLBW infants with prolonged antibiotic duration ranged from -0.94% (95% CI, -1.65% to -0.23%) to -1.08% (95% CI, -2.00% to -0.16%); in ELBW infants the annual risk difference ranged from -0.72% (95% CI, -1.83% to 0.39%) to -0.75% (95% CI, -1.96% to 0.46%). We also observed variation in early antibiotic exposures across centers. Sixty-nine of 113 centers (61.1%) started antibiotic therapy for more than 75% of VLBW infants, and 56 of 66 centers (84.8%) started antibiotic therapy for more than 75% of ELBW infants. The proportion of VLBW and ELBW infants administered prolonged antibiotics ranged from 0% to 80.4% and 0% to 92.0% across centers, respectively.</p>

<p><strong>Conclusions and Relevance: </strong>Most premature infants in this study received empirical early antibiotic therapy with little change over a recent 7-year period. The variability in exposure rates across centers, however, suggests that neonatal antimicrobial stewardship efforts are warranted to optimize antibiotic use for VLBW and ELBW infants.</p>

10.1001/jamanetworkopen.2018.0164

JAMA Netw Open

30646054

Comparison of Antibiotic Prescribing for Pediatric Community-Acquired Pneumonia in Children's and Non-Children's Hospitals.

2018

2018 Dec 10

2168-6211

10.1001/jamapediatrics.2018.4270

JAMA Pediatr

30534969

User Testing an Information Foraging Tool for Ambulatory Surgical Site Infection Surveillance.

2018

791-802

2018 Oct

1869-0327

<p><strong>BACKGROUND: </strong> Surveillance for surgical site infections (SSIs) after ambulatory surgery in children requires a detailed manual chart review to assess criteria defined by the National Health and Safety Network (NHSN). Electronic health records (EHRs) impose an inefficient search process where infection preventionists must manually review every postsurgical encounter (&lt; 30 days). Using text mining and business intelligence software, we developed an information foraging application, the SSI Workbench, to visually present which postsurgical encounters included SSI-related terms and synonyms, antibiotic, and culture orders.</p>

<p><strong>OBJECTIVE: </strong> This article compares the Workbench and EHR on four dimensions: (1) effectiveness, (2) efficiency, (3) workload, and (4) usability.</p>

<p><strong>METHODS: </strong> Comparative usability test of Workbench and EHR. Objective test metrics are time per case, encounters reviewed per case, time per encounter, and retrieval of information meeting NHSN definitions. Subjective measures are cognitive load using the National Aeronautics and Space Administration (NASA) Task Load Index (NASA TLX), and a questionnaire on system usability and utility.</p>

<p><strong>RESULTS: </strong> Eight infection preventionists participated in the test. There was no difference in effectiveness as subjects retrieved information from all cases, using both systems, to meet the NHSN criteria. There was no difference in efficiency in time per case between the Workbench and EHR (8.58 vs. 7.39 minutes,  = 0.36). However, with the Workbench subjects opened fewer encounters per case (3.0 vs. 7.5,  = 0.002), spent more time per encounter (2.23 vs. 0.92 minutes,  = 0.002), rated the Workbench lower in cognitive load (NASA TLX, 24 vs. 33,  = 0.02), and significantly higher in measures of usability.</p>

<p><strong>CONCLUSION: </strong> Compared with the EHR, the Workbench was more usable, short, and reduced cognitive load. In overall efficiency, the Workbench did not save time, but demonstrated a shift from between-encounter foraging to within-encounter foraging and was rated as significantly more efficient. Our results suggest that infection surveillance can be better supported by systems applying information foraging theory.</p>

10.1055/s-0038-1675179

Appl Clin Inform

30357777

Identifying surgical site infections in electronic health data using predictive models.

2018

2018 Jun 29

1527-974X

<p><strong>Objective: </strong>The objective was to prospectively derive and validate a prediction rule for detecting cases warranting investigation for surgical site infections (SSI) after ambulatory surgery.</p>

<p><strong>Methods: </strong>We analysed electronic health record (EHR) data for children who underwent ambulatory surgery at one of 4 ambulatory surgical facilities. Using regularized logistic regression and random forests, we derived SSI prediction rules using 30 months of data (derivation set) and evaluated performance with data from the subsequent 10 months (validation set). Models were developed both with and without data extracted from free text. We also evaluated the presence of an antibiotic prescription within 60 days after surgery as an independent indicator of SSI evidence. Our goal was to exceed 80% sensitivity and 10% positive predictive value (PPV).</p>

<p><strong>Results: </strong>We identified 234 surgeries with evidence of SSI among the 7910 surgeries available for analysis. We derived and validated an optimal prediction rule that included free text data using a random forest model (sensitivity = 0.9, PPV = 0.28). Presence of an antibiotic prescription had poor sensitivity (0.65) when applied to the derivation data but performed better when applied to the validation data (sensitivity = 0.84, PPV = 0.28).</p>

<p><strong>Conclusions: </strong>EHR data can facilitate SSI surveillance with adequate sensitivity and PPV.</p>

10.1093/jamia/ocy075

J Am Med Inform Assoc

29982511

Effect of the Procalcitonin Assay on Antibiotic Use in Critically Ill Children.

2018

e430e46

2018 May 15

2048-7207

<p>We retrospectively studied the effect of introducing procalcitonin into clinical practice on antibiotic use within a large academic pediatric intensive care unit. In the absence of a standardized algorithm, availability of the procalcitonin assay did not reduce the frequency of antibiotic initiations or the continuation of antibiotics for greater than 72 hours.</p>

10.1093/jpids/piy004

J Pediatric Infect Dis Soc

29529219

Association of Broad- vs Narrow-Spectrum Antibiotics With Treatment Failure, Adverse Events, and Quality of Life in Children With Acute Respiratory Tract Infections.

2017

2325-2336

2017 12 19

1538-3598

Importance: Acute respiratory tract infections account for the majority of antibiotic exposure in children, and broad-spectrum antibiotic prescribing for acute respiratory tract infections is increasing. It is not clear whether broad-spectrum treatment is associated with improved outcomes compared with narrow-spectrum treatment.

Objective: To compare the effectiveness of broad-spectrum and narrow-spectrum antibiotic treatment for acute respiratory tract infections in children.

Design, Setting, and Participants: A retrospective cohort study assessing clinical outcomes and a prospective cohort study assessing patient-centered outcomes of children between the ages of 6 months and 12 years diagnosed with an acute respiratory tract infection and prescribed an oral antibiotic between January 2015 and April 2016 in a network of 31 pediatric primary care practices in Pennsylvania and New Jersey. Stratified and propensity score-matched analyses to account for confounding by clinician and by patient-level characteristics, respectively, were implemented for both cohorts.

Exposures: Broad-spectrum antibiotics vs narrow-spectrum antibiotics.

Main Outcomes and Measures: In the retrospective cohort, the primary outcomes were treatment failure and adverse events 14 days after diagnosis. In the prospective cohort, the primary outcomes were quality of life, other patient-centered outcomes, and patient-reported adverse events.

Results: Of 30 159 children in the retrospective cohort (19 179 with acute otitis media; 6746, group A streptococcal pharyngitis; and 4234, acute sinusitis), 4307 (14%) were prescribed broad-spectrum antibiotics including amoxicillin-clavulanate, cephalosporins, and macrolides. Broad-spectrum treatment was not associated with a lower rate of treatment failure (3.4% for broad-spectrum antibiotics vs 3.1% for narrow-spectrum antibiotics; risk difference for full matched analysis, 0.3% [95% CI, -0.4% to 0.9%]). Of 2472 children enrolled in the prospective cohort (1100 with acute otitis media; 705, group A streptococcal pharyngitis; and 667, acute sinusitis), 868 (35%) were prescribed broad-spectrum antibiotics. Broad-spectrum antibiotics were associated with a slightly worse child quality of life (score of 90.2 for broad-spectrum antibiotics vs 91.5 for narrow-spectrum antibiotics; score difference for full matched analysis, -1.4% [95% CI, -2.4% to -0.4%]) but not with other patient-centered outcomes. Broad-spectrum treatment was associated with a higher risk of adverse events documented by the clinician (3.7% for broad-spectrum antibiotics vs 2.7% for narrow-spectrum antibiotics; risk difference for full matched analysis, 1.1% [95% CI, 0.4% to 1.8%]) and reported by the patient (35.6% for broad-spectrum antibiotics vs 25.1% for narrow-spectrum antibiotics; risk difference for full matched analysis, 12.2% [95% CI, 7.3% to 17.2%]).

Conclusions and Relevance: Among children with acute respiratory tract infections, broad-spectrum antibiotics were not associated with better clinical or patient-centered outcomes compared with narrow-spectrum antibiotics, and were associated with higher rates of adverse events. These data support the use of narrow-spectrum antibiotics for most children with acute respiratory tract infections.

10.1001/jama.2017.18715

JAMA

29260224