Next generation sequencing improves detection of drug resistance mutations in infants after PMTCT failure.

BACKGROUND: Next generation sequencing (NGS) allows the detection of minor variant HIV drug resistance mutations (DRMs). However data from new NGS platforms after Prevention-of-Mother-to-Child-Transmission (PMTCT) regimen failure are limited. OBJECTIVE: To compare major and minor variant HIV DRMs with Illumina MiSeq and Life Technologies Ion Personal Genome Machine (PGM) in infants infected despite a PMTCT regimen. STUDY DESIGN: We conducted a cross-sectional study of NGS for detecting DRMs in infants infected despite a zidovudine (AZT) and Nevirapine (NVP) regimen, before initiation of combination antiretroviral therapy. Sequencing was performed on PCR products from plasma samples on PGM and MiSeq platforms. Bioinformatic analyses were undertaken using a codon-aware version of the Smith-Waterman mapping algorithm and a mixture multinomial error filtering statistical model. RESULTS: Of 15 infants, tested at a median age of 3.4 months after birth, 2 (13%) had non-nucleoside reverse transcriptase inhibitor (NNRTI) DRMs (K103N and Y181C) by bulk sequencing, whereas PGM detected 4 (26%) and MiSeq 5 (30%). NGS enabled the detection of additional minor variant DRMs in the infant with K103N. Coverage and instrument quality scores were higher with MiSeq, increasing the confidence of minor variant calls. CONCLUSIONS: NGS followed by bioinformatic analyses detected multiple minor variant DRMs in HIV-1 RT among infants where PMTCT failed. The high coverage of MiSeq and high read quality improved the confidence of identified DRMs and may make this platform ideal for minor variant detection.

Exploring the differential diagnosis of hemorrhagic vesicopustules in a newborn.

Hemorrhagic vesicles in a newborn present a challenging differential diagnosis including both infectious and neoplastic disorders. Patients should be evaluated in an efficient manner to arrive at the correct diagnosis as quickly as possible. We present here an interesting case that outlines the methodical workup that ultimately revealed the diagnosis of congenital Langerhans cell histiocytosis. After a diagnosis of Langerhans cell histiocytosis is made, it is important to evaluate the patient thoroughly for systemic involvement. Historically, the diagnosis of congenital self-healing Langerhans cell histiocytosis was used to delineate a benign self-limited disorder limited to the skin with spontaneous resolution during the first several months of life; this disorder may also be referred to as "self-regressive Langerhans cell histiocytosis." However, some newborns with initial skin-only Langerhans cell histiocytosis progress to have multisystem disease after spontaneous resolution has occurred. For this reason, the nomenclature is changing. We suggest using the term "skin-only Langerhans cell histiocytosis." Periodic long-term follow-up is recommended to monitor for relapse or progression to systemic disease.

Sweet syndrome in infancy.

Sweet syndrome, or acute febrile neutrophilic dermatosis, is characterized by the presence of fever, peripheral leukocytosis, painful erythematous plaques and nodules, and a predominately neutrophilic dermal infiltrate. We report a case occurring in a 10-week-old male child, with preceding upper respiratory tract, and gastrointestinal infection symptoms. Sweet syndrome occurring in an infant should prompt a work-up for immunodeficiency, as well as a review of the peripheral blood smear to rule out the rare case of malignancy.

Alternative dosage of zidovudine in infants exposed to maternal human immunodeficiency virus infection.

As part of the 076 protocol, ZDV was given to HIV-exposed neonates for the first 6 weeks of life. The dosage was 2 mg/kg every 6 hours. Frequent dosing can be a deterrent to regimen adherence. We report our experience, using 3 mg/kg every 8 hours in 155 eligible HIV-exposed neonates, none of whom became HIV infected. Maximum risk of transmission that could be missed by this cohort is approximately 2%, which is consonant with current transmission rates. ZDV at 3 mg/kg every 8 hours is noninferior to 2 mg/kg every 6 hours and easier to administer.

Congenital herpes simplex virus infection: two unique cutaneous presentations associated with probable intrauterine transmission.

Cutaneous manifestations of congenital herpes simplex virus (HSV) have been classically described as grouped vesicles on an erythematous base. We report two cases of HSV infection wherein both infants presented at birth with widespread erosions and an absence of vesicles or vesicopustules. The presence of skin lesions at birth, neurologic changes seen on radiographic imaging, and a cesarean section delivery in one case suggests intrauterine transmission in both neonates.

Hypochlorite killing of community-associated methicillin-resistant Staphylococcus aureus.

We tested in vitro hypochlorite (bleach) killing of community-associated methicillin-resistant Staphylococcus aureus isolates to determine optimal concentration and duration. For all isolates maximal killing, >3-log decrease in colony forming units (CFU), was found after 5 minutes in 2.5 microL/mL bleach. We estimate that 2.5 microL/mL bleach is approximately one-half cup of bleach in one-quarter tub of water.

Local anesthetic and stylet styles: factors associated with resident lumbar puncture success.

OBJECTIVE: To assess the effects of procedural techniques, local anesthetic use, and postgraduate training level on lumbar puncture (LP) success rates. METHODS: In this prospective observational study, medical students and residents ("trainees") reported techniques used for infant LPs in an urban teaching emergency department. Data on postgraduate year, patient position, draping, total and trainee numbers of attempts, local anesthetic use, and timing of stylet removal were collected. Logistic regression analysis was used to identify predictors of successful LP, with success defined as the trainee obtaining cerebrospinal fluid with <1000 red blood cells per mm3. RESULTS: We collected data on 428 (72%) of 594 infant LPs performed during the study period. Of 377 performed by trainees, 279 (74%) were successful. Local anesthesia was used for 280 (74%), and 225 (60%) were performed with early stylet removal. Controlling for the total number of attempts, LPs were 3 times more likely to be successful among infants >12 weeks of age than among younger infants (odds ratio [OR]: 3.1; 95% confidence interval [CI]: 1.2-8.5). Controlling for attempts and age, LPs performed with local anesthetic were twice as likely to be successful (OR: 2.2; 95% CI: 1.04-4.6). For infants < or =12 weeks of age, early stylet removal improved success rates (OR: 2.4; 95% CI: 1.1-5.2). Position, drape use, and year of training were not significant predictors of success. CONCLUSIONS: Patient age, use of local anesthetic, and trainee stylet techniques were associated with LP success rates. This offers an additional rationale for pain control. Predictors identified in this study should be considered in the training of physicians, to maximize their success with this important procedure.

Very low prevalence of endophthalmitis in very low birthweight infants who survive candidemia.

OBJECTIVE: Candida species often cause sepsis in very low birthweight (VLBW) infants, leading to formal ophthalmologic evaluation for endophthalmitis. Our experience suggests that endophthalmitis is rare in this setting, and retinal vascular compromise in extreme prematurity may decrease the risk. We studied the prevalence of endophthalmitis in surviving VLBW infants with candidemia. STUDY DESIGN: Epidemiologic data and presence of ROP and endophthalmitis were ascertained for all VLBW infants with candidemia at our institution from 1994 to 2001. RESULTS: A total of 123 infants were included. Median EGA was 25 weeks (range, 23 to 32) and median birthweight was 735 g (range, 426 to 1460). Of these 123, only one had transient retinal findings (prevalence 0.8%; 95% confidence interval 0 to 4%), which resolved during therapy. In no case was either the duration of therapy or the outcome of candidemia altered by retinal examination. CONCLUSIONS: Aggressive treatment of candidemia has made endogenous endophthalmitis rare in candidemic VLBW infants.

Facial cellulitis in childhood: a changing spectrum.

BACKGROUND: Before conjugated Haemophilus influenzae type b (Hib) vaccination, a syndrome known as buccal cellulitis, usually caused by Hib and often accompanied by bacteremia, was seen. We investigated the incidence and cause of facial cellulitis at our hospital during the 10 years before and the 10 years after introduction of the vaccine. METHODS: Records of patients discharged with a diagnosis of facial cellulitis or infections of the oral cavity were reviewed. Fisher's exact test was used to compare rates of cellulitis during the two decades. RESULTS: Trauma was the most common antecedent to facial cellulitis in both eras. Buccal cellulitis accounted for 7/25 (28%) of cases before Hib vaccination and 0/19 cases since. Pneumococcal buccal cellulitis was not seen in either decade. CONCLUSIONS: Buccal cellulitis due to Hib is a disappearing disease. Eighty-nine percent of recent inpatient cases of childhood facial cellulitis were related to trauma, tooth problems, or severe sinusitis. Facial cellulitis due to S pneumoniae is rare.