Congenital Cytomegalovirus Testing Outcomes From the ValEAR Trial.

OBJECTIVE: To determine the positivity rate of congenital cytomegalovirus (cCMV) testing among universal, hearing-targeted CMV testing (HT-cCMV) and delayed targeted dried blood spot (DBS) testing newborn screening programs, and to examine the characteristics of successful HT-cCMV testing programs. STUDY DESIGN: Prospective survey of birth hospitals performing early CMV testing. SETTING: Multiple institutions. METHODS: Birth hospitals participating in the National Institutes of Health ValEAR clinical trial were surveyed to determine the rates of cCMV positivity associated with 3 different testing approaches: universal testing, HT-cCMV, and DBS testing. A mixed methods model was created to determine associations between successful HT-cCMV screening and specific screening protocols. RESULTS: Eighty-two birth hospitals were surveyed from February 2019 to December 2021. Seven thousand six hundred seventy infants underwent universal screening, 9017 infants HT-cCMV and 535 infants delayed DBS testing. The rates of cCMV positivity were 0.5%, 1.5%, and 7.3%, respectively. The positivity rate for universal CMV screening was less during the COVID-19 pandemic than that reported prior to the pandemic. There were no statistically significant drops in positivity for any approach during the pandemic. For HT-cCMV testing, unique order sets and rigorous posttesting protocols were associated with successful screening programs. CONCLUSION: Rates of cCMV positivity differed among the 3 approaches. The rates are comparable to cohort studies reported in the literature. Universal CMV prevalence decreased during the pandemic but not significantly. Institutions with specific order set for CMV testing where the primary care physician orders the test and the nurse facilitates the testing process exhibited higher rates of HT-cCMV testing.

Epidemiology of Deep Surgical Site Infections After Pediatric Spinal Fusion Surgery.

STUDY DESIGN: Single-institution, retrospective case series. OBJECTIVE: To determine whether the microbiology of deep surgical site infections (SSIs) after spinal fusion surgery for deformity has changed over the last decade at our institution. SUMMARY OF BACKGROUND DATA: SSI after pediatric spinal deformity surgery results in significantly increased patient morbidity and health care costs. Although risk factors are multifactorial, prophylactic and treatment antibiotic coverage is based in part on historical epidemiologic data, which may evolve over time. METHODS: This study represents a retrospective review of clinical and microbiology records of patients less than 21 years old who underwent spinal deformity surgery at a single institution between 2000 and 2012. Patients were included who underwent index surgery at our institution and developed a deep SSI. Patients with growth-preserving spine constructs were excluded. RESULTS: The overall incidence of deep SSI was 3.6% (39/1094). The incidence of deep SSI following primary surgery was 3.3% (34/1034) and 8.3% (5/60) following revision surgery. The incidence of deep SSI varied by primary diagnosis: idiopathic (1.0%), neuromuscular (14.3%), syndromic (5.3%), congenital (5.7%), and kyphosis (0.0%). The most common inciting pathogens were Staphylococcus epidermidis (26%), methicillin-sensitive Staphylococcus aureus (MSSA, 18%), Propionibacterium acnes (P. acnes; 18%), and Escherichia coli (18%). Sixteen of the 18 (89%) gram-negative infections occurred in neuromuscular patients (P = 0.006). Between 2000 and 2006 and between 2007 and 2012, MSSA occurred in 2/18 (11%) and 5/21 (24%) of cases (P = 0.41), methicillin-resistant S. aureus occurred in 1/18 (6%) and 3/21 (14%) (P = 0.61), and P. acnes occurred in 3/18 (17%) and 4/21 (19%) (P = 1.0). CONCLUSION: The epidemiology of deep SSI following spinal fusion for deformity in pediatric patients at our institution has not changed significantly during 13 years. Prophylactic antibiotic coverage for both gram-positive and gram-negative organisms may be indicated for patients with primary neuromuscular diagnoses. LEVEL OF EVIDENCE: 4.

Pharmacokinetics and pharmacodynamics of linezolid in children with cystic fibrosis.

UNLABELLED: Alternative antimicrobial regimens are needed for treatment of methicillin-resistant Staphylococcus aureus (MRSA)-associated pulmonary exacerbations in children with cystic fibrosis (CF). There are no published pharmacokinetic (PK) and pharmacodynamic (PD) data for linezolid in children with CF. OBJECTIVES: (1) To determine the PK and PD profile of linezolid among children with CF; (2) to characterize the effect of linezolid on MRSA infection; (3) to determine the effect of age and CF transmembrane regulator (CFTR) gene mutations on drug clearance. HYPOTHESES: Linezolid clearance is enhanced in children with CF requiring a higher dosage regimen. Age and CFTR gene mutations affect drug clearance. METHODS: This was a retrospective cohort study; medical records of children with MRSA-associated pulmonary exacerbations treated with linezolid (10 mg/kg/dose IV every 8h) were reviewed. Linezolid peak and trough concentrations in serum were determined by high performance liquid chromatography, PK profiles determined using standard noncompartmental method, and PD indices were evaluated. RESULTS: 10 children (mean +/- SD, 10.2 +/- 5.5 years) received 14 courses of linezolid at 10 +/- 0.4 mg/kg/dose every 8h for 15.4 +/- 3.2 days. Seven had homozygous DeltaF508 CFTR mutation. Peak and trough linezolid concentrations varied widely (range, 8.4-20.5 and 0.1-11.5 mcg/mL respectively). The PK profile of children <10 years differed significantly from older patients (>or=10 years). The PK indices of children with homozygous DeltaF508 differed marginally from those with heterozygous CFTR mutations, but there were too few subjects to allow separation of age and CFTR mutations effect. No patient achieved the target PD ratio of AUC/MIC >80. MRSA persisted in sputum or throat culture after treatment with linezolid. CONCLUSIONS: Additional PK and PD data are needed to optimize linezolid therapy in children with cystic fibrosis; it is likely that higher doses will be needed.

Evaluation of LBM415 (NVP PDF-713), a novel peptide deformylase inhibitor, for treatment of experimental Mycoplasma pneumoniae pneumonia.

Mycoplasma pneumoniae is a major cause of community-acquired pneumonia. We evaluated the efficacy of LBM415, a novel peptide deformylase inhibitor antimicrobial agent, for the treatment of M. pneumoniae pneumonia in a mouse model. Eight-week-old BALB/c mice were intranasally inoculated once with 10(7) CFU of M. pneumoniae. Groups of mice were treated with LBM415 (50 mg/kg of body weight) or placebo subcutaneously daily for 13 days, starting 24 h after inoculation. Groups of mice were evaluated at the baseline; at days of treatment 1, 3, 6, and 13; and at 7 days after treatment. The MIC of LBM415 against M. pneumoniae was <0.005 microg/ml. LBM415-treated mice had significantly lower bronchoalveolar lavage fluid M. pneumoniae concentrations than placebo-treated mice on days 6 and 13 of treatment. Compared with placebo treatment, therapy with LBM415 significantly decreased lung histopathology scores at days 3, 6, and 13 of treatment and at 7 days after treatment. Airway obstruction was significantly lower in LBM415-treated mice than in placebo-treated mice on days 1, 3, and 6 of treatment and after 7 days of therapy, while airway hyperresponsiveness was significantly lower only on day 3 of therapy. The bronchoalveolar lavage fluid concentrations of tumor necrosis factor alpha, gamma interferon (IFN-gamma), interleukin-6 (IL-6), IL-12, KC (functional IL-8), monocyte chemotactic protein 1, macrophage inflammatory protein 1alpha, monokine induced by IFN-gamma, and IFN-inducible protein 10 were significantly reduced in LBM415-treated mice compared with the levels in placebo-treated mice. There were no differences in the bronchoalveolar lavage fluid concentrations of granulocyte-macrophage colony-stimulating factor, IL-1beta, IL-2, IL-4, IL-5, and IL-10 between the two groups of mice. LBM415 therapy had beneficial microbiologic, histologic, respiratory, and immunologic effects on acute murine M. pneumoniae pneumonia.