Efraim Bilavsky

The Association of Intrapartum Antibiotic Exposure With the Incidence and Antibiotic Resistance of Infantile Late-Onset Serious Bacterial Infections

Background. The widespread use of intrapartum antibiotics (IPA) has raised concerns regarding the adverse effects on the newborn. Objectives. To determine if IPA is associated with infantile late-onset serious bacterial infections (SBIs) and with antibiotic resistance. Patients and methods. From 2005 to 2009, data were prospectively collected for all infants born at our center, aged 7 to 90 days, who were hospitalized for fever. Cases included infants with culture-proven SBIs, and controls included infants without SBIs. Results. A total of 71 cases and 124 controls were included. IPA was documented in 11.3% of cases and in 7.3% of controls (P = .34). Among cases, ampicillin resistance was documented in 85% of antibiotic-exposed infants and in 63% of nonexposed infants (P = .19). Corresponding rates for first-generation cephalosporin resistance in urinary tract infection were 75% and 23.5% (P = .04). Conclusion. IPA is associated with a trend toward increased antibiotic resistance in late-onset SBIs. This should be taken into consideration in the selection of empirical therapy for febrile infants.

Compartment syndrome because of acute hemorrhagic edema of infancy: a case report and literature review.

UNLABELLEDnAcute hemorrhagic edema of infancy (AHEI) is a benign, self-limiting vasculitis that usually resolves completely without any sequelae or a need for active therapy. To our knowledge, compartment syndrome because of AHEI has not been reported. Chart data for a single case were reviewed and reported in a retrospective study. A 19-month-old male presented with petechial rash and swelling of the left lower leg. AHEI was diagnosed clinically and confirmed by skin biopsy. On the basis of the clinical appearance, compartment syndrome of the foot was suspected. Measurements of compartmental pressures in the foot were well above the commonly cited ranges and a fasciotomy was performed. Following the operation, there was a marked clinical improvement in the limb perfusion. The child was discharged on the 20th day with marked clinical improvement; both active and passive leg movements were intact. We suggest that pediatric orthopedic surgeons should be familiar with this entity and its rare complication.nnnLEVEL OF EVIDENCEnV - case report.

Haemophilus influenzae Type b Meningitis in the Short Period after Vaccination: A Reminder of the Phenomenon of Apparent Vaccine Failure

We present two cases of bacterial meningitis caused by Haemophilus influenzae type b (Hib) which developed a few days after conjugate Hib vaccination. This phenomenon of postimmunization provocative time period is reviewed and discussed. These cases serve as a reminder to clinicians of the risk, albeit rare, of invasive Hib disease in the short period after successful immunization.

Apnea induced by respiratory syncytial virus infection is not associated with viral invasion of the central nervous system.

We aimed to study whether direct central nervous system invasion is responsible for the neurologic manifestations seen in hospitalized infants with respiratory syncytial virus (RSV) infection. Cerebrospinal fluid from infants with RSV infection was tested for the detection of the following respiratory RNA viruses: RSV, influenza A and B, pandemic influenza H1N1, Parainfluenza-3, human metapneumovirus, adenovirus, parechovirus and enterovirus. All children tested negative for the presence of viral material in the cerebrospinal fluid. Our results support the notion that the mechanism of RSV-induced neurologic manifestations, including apnea, is not direct central nervous system invasion.

Severe infections in twins.

We describe 4 sets of twins 5 days to 10 weeks of age with a serious bacterial or viral infection. The issue of the occurrence of a simultaneous infection in twins and the clinical dilemma of the appropriate evaluation and treatment of an asymptomatic co-twin of infants with a serious infection is discussed.

Bilateral primary spontaneous pneumothorax: buffalo chest.

A case of bilateral primary spontaneous pneumothorax (buffalo chest) in a previously healthy man is described. The clinical presentation and treatment options are discussed.

Valganciclovir Dosing for Cytomegalovirus Prophylaxis in Pediatric Solid-organ Transplant Recipients: A Prospective Pharmacokinetic Study

Background: Valganciclovir is extensively used for prophylaxis and treatment of cytomegalovirus (CMV) infection in solid-organ transplant recipients. However, pharmacokinetic data in children are scarce, and the pediatric dosing regimen is uncertain. This study sought to prospectively evaluate the pharmacokinetic profile, the clinical efficacy and safety of oral valganciclovir in pediatric transplant recipients and compare different dosing regimens. Methods: The cohort included solid-organ transplant recipients treated with valganciclovir for CMV prophylaxis in 2014–2015 at a tertiary pediatric medical center. All received a weight-based once-daily oral dose of 17 mg/kg. Ganciclovir concentrations were measured and the area under the curve (AUC0–24) was calculated. Results: Thirteen children of median age 7.3 years (interquartile range, 2.2–11.6) were included. Median ganciclovir AUC0–24 was 21.0 mcg·h/mL (interquartile range, 17.1–39.8); 10 patients (77%) attained AUC0–24 <40 mcg·h/mL. Exposure to ganciclovir was about 2-fold lower in young children (<9 years old; P = 0.01) and children with low body surface area (BSA; <0.7 m2; P = 0.006) than in their counterparts. Significantly lower doses were recommended with our weight-based protocol than with the manufacturer-recommended BSA- and glomerular filtration rate-based protocol (P = 0.002), reaching a 3-fold difference in infants. No evidence of CMV viremia or disease was observed while prophylaxis was given. Conclusions: The weight-based regimen of 17 mg/kg/dose oral valganciclovir results in relatively low ganciclovir exposure, especially in young children with low BSA, yet showed satisfactory clinical efficacy for CMV prophylaxis. The manufacturer’s dosing recommendation appears to result in supratherapeutic ganciclovir concentrations. Further studies are needed to establish target AUCs and valganciclovir dosing for CMV prophylaxis in pediatric transplant recipients.

Positive IgM in Congenital CMV Infection

Neonatal serum detection of cytomegalovirus (CMV) immunoglobulin M (IgM) has low sensitivity in identifying congenital cytomegalovirus (cCMV). Several reports have endeavored to associate the presence/absence of IgM to disease severity. Data were collected for all infants with cCMV followed in our clinic. Infant outcome after birth was compared between infants who tested positive or negative. Sensitivity of positive IgM in diagnosing cCMV was 40.7%. The rate of symptomatic disease in those who tested positive was statistically higher (67.7%, P < .001). Odds ratio for symptomatic disease in infants with positive IgM born after a maternal primary infection was 3.47 (95% confidence interval = 1.7-7.1). Positive IgM was found in only 48.8% of symptomatic and 22.1% of asymptomatic children. Our results demonstrated a low sensitivity of IgM in diagnosing cCMV. However, while a positive IgM antibody for CMV is associated with a more symptomatic disease, it does not serve as a precise laboratory marker for a severity.

Valganciclovir Is Beneficial in Children with Congenital Cytomegalovirus and Isolated Hearing Loss

Objective To evaluate the efficacy of antiviral treatment for infants with congenital cytomegalovirus (cCMV) with isolated sensorineural hearing loss (SNHL). Study design Data were reviewed retrospectively for infants with isolated SNHL who received prolonged antiviral treatment between 2005 and 2017. Hearing status was evaluated for infants who had been followed for >1 year. Results Among 329 infants treated for cCMV, 59 (18%) were born with isolated SNHL. Hearing impairment was unilateral in 38 (64.4%) infants and bilateral in 21 (35.6%). Of the 80 affected ears at baseline, 55 (68.8%) improved, and only 2 (2.5%) deteriorated. Most of the improved ears (53/55 = 96.3%) returned to normal hearing with no deterioration observed in the ears that were unaffected at baseline. On best ear evaluation, of 21 infants who had bilateral hearing loss, 16 (76.1%) improved (93.7% regaining normal functional hearing); none deteriorated. Conclusion Infants born with isolated SNHL due to cCMV were found to benefit from prolonged antiviral treatment. These children (and ears) showed significant improvement in hearing status and no deterioration of unaffected ears at baseline. Our data serve as observational evidence of the benefits of antiviral treatment in these children. Avoiding treatment of these children due to the lack of prospective data is debatable.

WHAT IS THE APPROPRIATE VALGANCICLOVIR DOSAGE IN CHILDREN WITH SOLID ORGAN TRANSPLANT? A PROSPECTIVE PHARMACOKINETIC STUDY

Valganciclovir (VGC) is extensively used for cytomegalovirus (CMV) infection treatment and prophylaxis after solid organ transplantation (SOT). VGC dosing is problematic in children. VGC has variable absorption and is renally excreted. AUC0-24 of 40–60u2005mcg·h/L is a predictive pharmacokinetic parameter of efficacy and safety. Dosing based on manufacturer recommendations is supra-therapeutic in most cases. A few published dosing algorithms result in AUC out of range. Objective To prospectively validate a VGC administration dosing regimen and compare it to other dosing algorithms. Methods Children after SOT at Schneider Childrens Medical Center, the largest tertiary pediatric center in Israel, were prospectively studied, starting Dec 2014. The dosing regimen was derived from Seattle Childrens Hospital guidelines; 14–16u2005mg/kg/dose. For impaired renal function, stratified dose reduction was used. Blood was withdrawn at steady state: 2, 5 and 10u2005hours post dosing. Drug level was analyzed by HPLC. Results Nine children aged 52 (37–137) [median; (inter-quartile range)] months were studied. Four had renal and 5 had liver transplantation. VGL dose administered was 16.67 (16.42–17.72) mg/kg/dose. AUC was 20.56 (18.7–22.7) mcg·h/L. AUC was sub-therapeutic in 8 children. Manufacturer-recommended dose in our patients was suppose to be 43.5 (24.84–46.7) mg/kg/dose, significantly higher than in our study (p=0.004). Dosing based upon Asberg et al study (Pediatr. Transplantation 2014;18:103) –25.5 (19.38–25.5) mg/kg/dose, was significantly higher than in our study (p=0.009). Conclusions VGC dosing regimen in SOT children is still not clear. There are significant differences between dosing algorithms. More studies are needed. Recruitment of patients to our study continues.