Invasive aspergillosis (IA) is associated with significant morbidity and mortality. Voriconazole remains the drug of choice for the treatment of IA in children; however, the complex kinetics of voriconazole in children make dosing challenging and therapeutic drug monitoring (TDM) essential for treatment success. The overarching goal of this review is to discuss the role of voriconazole, posaconazole, isavuconazole, liposomal amphotericin B, echinocandins, and combination antifungal therapy for the treatment of IA in children. We also provide a detailed discussion of antifungal TDM in children.

<p><strong>Importance: </strong>National guidelines recommend treating children with pyelonephritis for 7 to 14 days of antibiotic therapy, yet data are lacking to suggest a more precise treatment duration.</p>

<p><strong>Objective: </strong>To compare the clinical outcomes of children receiving a short-course vs a prolonged-course of antibiotic treatment for pyelonephritis.</p>

<p><strong>Design, Setting, and Participants: </strong>Retrospective observational study using inverse probability of treatment weighted propensity score analysis of data from 5 hospitals in Maryland between July 1, 2016, and October 1, 2018. Participants were children aged 6 months to 18 years with a urine culture growing Escherichia coli, Klebsiella species, or Proteus mirabilis with laboratory and clinical criteria for pyelonephritis.</p>

<p><strong>Exposures: </strong>Treatment of pyelonephritis with a short-course (6 to 9 days) vs a prolonged-course (10 or more days) of antibiotics.</p>

<p><strong>Main Outcomes and Measures: </strong>Composite outcome of treatment failure within 30 days of completing antibiotic therapy: (a) unanticipated emergency department or outpatient visits related to urinary tract infection symptoms, (b) hospital readmission related to UTI symptoms, (c) prolongation of the planned, initial antibiotic treatment course, or (d) death. A subsequent urinary tract infection caused by a drug-resistant bacteria within 30 days was a secondary outcome.</p>

<p><strong>Results: </strong>Of 791 children who met study eligibility criteria (mean [SD] age 9.2 [6.3] years; 672 [85.0%]) were girls, 297 patients (37.5%) were prescribed a short-course and 494 patients (62.5%) were prescribed a prolonged-course of antibiotics. The median duration of short-course therapy was 8 days (interquartile range, 7-8 days), and the median duration of prolonged-course therapy was 11 days (interquartile range, 11-12 days). Baseline characteristics were similar between the groups in the inverse probability of treatment weighted cohort. There were 79 children (10.1%) who experienced treatment failure. The odds of treatment failure were similar for patients prescribed a short-course vs a prolonged-course of antibiotics (11.2% vs 9.4%; odds ratio, 1.22; 95% CI, 0.75-1.98). There was no significant difference in the odds of a drug-resistant uropathogen for patients with a subsequent urinary tract infection within 30 days when prescribed a short-courses vs prolonged-course of antibiotics (40% vs 64%; odds ratio, 0.36; 95% CI, 0.09-1.43).</p>

<p><strong>Conclusions and Relevance: </strong>The study findings suggest that short-course antibiotic therapy may be as effective as prolonged-courses for children with pyelonephritis, and may mitigate the risk of future drug-resistant urinary tract infections. Additional studies are needed to confirm these findings.</p>

<p>In a multicenter retrospective study, we sought to determine the optimal vancomycin trough concentration that would impact the duration of methicillin-resistant Staphylococcus aureus bacteremia in children. We found that a median vancomycin trough concentration of &lt;10 µg/mL within the first 72 hours may be associated with a longer duration of bacteremia compared to a median trough concentration of ≥10 µg/mL.</p>

<p><strong>BACKGROUND: </strong>Methicillin-resistant Staphylococcus aureus (MRSA) bacteremia is associated with high rates of treatment failure in adults. The epidemiology, clinical outcomes, and risk factors for treatment failure associated with MRSA bacteremia in children are poorly understood.</p>

<p><strong>METHODS: </strong>Multicenter, retrospective cohort study of children ≤18 years hospitalized with MRSA bacteremia across 3 tertiary care children's hospitals from 2007 to 2014. Treatment failure was defined as persistent bacteremia &gt;3 days, recurrence of bacteremia within 30 days, or attributable 30-day mortality. Potential risk factors for treatment failure, including the site of infection, vancomycin trough concentration, critical illness, and need for source control, were collected via manual chart review and evaluated using multivariable logistic regression.</p>

<p><strong>RESULTS: </strong>Of 232 episodes of MRSA bacteremia, 72 (31%) experienced treatment failure and 23% developed complications, whereas 5 (2%) died within 30 days. Multivariable analysis of 174 children treated with vancomycin with steady-state vancomycin concentrations obtained found that catheter-related infections (odds ratio [OR], 0.36; 95% confidence interval [CI]: 0.13-0.94) and endovascular infections (OR, 4.35; 95% CI: 1.07-17.7) were associated with lower and higher odds of treatment failure, respectively, whereas a first vancomycin serum trough concentration &lt;10 μg/mL was not associated with treatment failure (OR, 1.34; 95% CI, 0.49-3.66). Each additional day of bacteremia was associated with a 50% (95% CI: 26%-79%) increased odds of bacteremia-related complications.</p>

<p><strong>CONCLUSIONS: </strong>Hospitalized children with MRSA bacteremia frequently suffered treatment failure and complications, but mortality was low. The odds of bacteremia-related complications increased with each additional day of bacteremia, emphasizing the importance of achieving rapid sterilization.</p>

<p><strong>BACKGROUND: </strong>In 2010, the Clinical and Laboratory Standards Institute (CLSI) revised and lowered the ceftriaxone minimum inhibitory concentration breakpoints for Enterobacteriaceae and removed the requisite extended spectrum β-lactamase phenotypic testing for organisms with elevated minimum inhibitory concentrations. The impact that these recommendations have on clinical outcomes of children have not been previously evaluated.</p>

<p><strong>METHODS: </strong>We conducted a retrospective study to compare clinical outcomes between children treated with ceftriaxone and those treated with broader spectrum β-lactams for Enterobacteriaceae bacteremia with reduced susceptibility (minimum inhibitory concentrations 4-8 µg/mL) to ceftriaxone according to the new CLSI interpretive criteria. Mortality and microbiological relapse were evaluated using a multivariable logistic regression model.</p>

<p><strong>RESULTS: </strong>There were a total of 783 unique children with Enterobacteriaceae bacteremia during the study period. Using the CLSI breakpoints before 2010, 76 children would have had clinical isolates resistant to ceftriaxone. With the revised breakpoints, 229 Enterobacteriaceae isolates would no longer be susceptible to ceftriaxone (&gt;300% increase). Of the 136 children who met eligibility criteria, 63 children received ceftriaxone and 73 children received broader spectrum β-lactams. There was no difference in 30-day mortality (odds ratio 0.81, 95% confidence interval: 0.31-2.59) or microbiological relapse (odds ratio 0.97, 95% confidence interval: 0.36-2.66) between the groups.</p>

<p><strong>CONCLUSIONS: </strong>Our findings do not support the proposed clinical benefit of more conservative CLSI breakpoints. The revised breakpoints promote increased broad-spectrum β-lactam use. The need for lowered ceftriaxone breakpoints against Enterobacteriaceae in children needs to be reevaluated in larger prospective studies.</p>