Katalin Koranyi

Serious Group A streptococcal diseases in children

The illnesses of 40 patients with diagnoses of septicemia, cellulitis with bacteremia, pneumonia empyema, and meningitis caused by Streptococcus pyogenes, Group A, are described. Twenty-five of 27 patients (93%) without underlying disease survived, whereas only seven of 13 children (54%) with underlying disease survived. Nine of the 25 patients who were otherwise normal and who survived these infections had prolonged, complicated illnesses. Four of these patients, and one who died, had septicemia without a focus of infection at the time of admission. Streptococcus pyogenes, Group A, although very sensitive to penicillin G and other antibiotics, can cause both severe and rapidly progressive disease in children.

Pharmacokinetics of azithromycin in pediatric patients with acute otitis media.

The objective of our study was to characterize the pharmacokinetics of azithromycin after the oral administration of multiple doses in suspension to children with acute otitis media. Thirteen children (ranging in age from 7.5 months to 5 years) received a single oral dose of 10 mg of azithromycin per kg of body weight on day 1 followed by single daily doses of 5 mg/kg on days 2 to 5. Each child fasted overnight before receiving the final dose on day 5. Multiple blood samples were collected after the last dose. Concentrations of azithromycin in serum were measured by a specific high-performance liquid chromatography-mass spectrometry method. The means and standard deviations for the maximum concentration of azithromycin in serum, the time to maximum concentration of azithromycin in serum, the area under the concentration-time curve (from 0 to 24 h), and the elimination half-life were 224 +/- 120 ng/ml, 1.8 +/- 0.4 h, 1,841 +/- 651 ng.h/ml, and 31.6 +/- 6.6 h, respectively. Concentrations in serum (means +/- standard deviations) at 0 h (predose) and at 24, 48, and 72 h after the final dose were 51 +/- 26, 47 +/- 21, 27 +/- 17, and 17 +/- 13 ng/ml, respectively. Thus, the once-daily administration of azithromycin resulted in sustained systemic exposure to the drug. The drug dosage regimen used in this study should lead to tissue drug concentrations exceeding the MICs for common pathogens.

Lipodystrophy in HIV-Infected Pediatric Patients Receiving Protease Inhibitors

BACKGROUND: In adults with HIV infection, lipodystrophy syndrome may develop, characterized by peripheral wasting in the extremities, central obesity, hyperlipidemia, and insulin resistance. This syndrome occurs in HIV-positive pediatric patients who take protease inhibitors (PIs). However, the full characteristics of the syndrome in this population is not fully understood. OBJECTIVE: To evaluate the association between the use of PIs and the occurrence of lipodystrophy in HIV-infected children. METHODS: Pediatric patients attending an outpatient HIV clinic between 1994 and 2000 were prospectively enrolled. All patients were between 1 and 17 years of age and had received a PI for at least 1 month. The medical records were reviewed monthly for 3 months before PI therapy was started and then monthly for 36 months. At each evaluation, serum total cholesterol, high-density lipoprotein-cholesterol, low-density lipoprotein-cholesterol, triglycerides, and blood glucose concentrations were recorded, as well as physician-documented physical examination findings including subcutaneous fat in the arms, face, and legs, and abdominal girth. Baseline clinical and laboratory data were compared with follow-up data using a paired t-test. RESULTS: Twenty-one pediatric patients received a PI. Of these, 2 developed lipodystrophy, one at 15 months and one at 18 months after PI therapy was started. Neither child had had lipodystrophy before therapy. Twelve children who were taking ritonavir or nelfinavir, including 1 who developed lipodystrophy, developed abnormally high total cholesterol and triglyceride blood concentrations. All patients receiving indinavir also experienced a substantial increase in their triglyceride concentrations at follow-up evaluations, but no significant increases in total cholesterol occurred. Blood glucose concentrations were not significantly different between baseline and follow-up examinations in our patients. CONCLUSIONS: Lipodystrophy may occur in some HIV-infected children receiving PIs, and dyslipidemias may also develop in some patients taking these drugs.

Acute Hepatitis and Bleeding Possibly Induced by Zidovudine and Ritonavir in an Infant with HIV Infection

Acute hepatitis led to abnormal coagulopathy, bleeding, and death in a nonhemophiliac infant infected with the human immunodeficiency virus, possibly due to zidovudine or ritonavir or both. Acute hepatitis during ritonavir treatment and episodes of spontaneous bleeding have been reported in patients with hemophilia. Zidovudine is associated with elevated liver enzymes, elevated bilirubin, and hepatomegaly leading to abnormal coagulopathy, bleeding, and death in adults. A temporal relationship between the start of combination antiretroviral therapy and onset of hepato‐splenomegaly and rise in liver enzymes suggests that zidovudine or ritonavir, or both, are the likely cause of this adverse event. Ritonavir is believed to cause direct hepatotoxicity, probably by inducing acute mitochondrial toxicity, and may hasten reverse transcriptase inhibitor‐induced liver toxicity. Liver function of patients receiving a combination of nucleoside reverse transcriptase inhibitor and protease inhibitors should be closely monitored.

Tuberculin skin testing and T-SPOT.TB in internationally adopted children.

Background: Diagnosis of latent tuberculosis infection is a problem in children because of lack of a diagnostic standard and potential impact of previous Bacille Calmette–Guérin vaccination and exposure to environmental mycobacteria. Effectiveness and usefulness of interferon-gamma release assays in infants and younger children have yet to be clearly demonstrated. Methods: Prospective cohort study including 109 children (4 months to 16 years) seen in an international adoption clinic at Nationwide Children’s Hospital, Columbus, OH. Children were adopted from 14 countries, mostly (72.5%) from China, Russia and Ethiopia. Correspondence between tuberculin skin test (TST) and the T-SPOT.TB assay was evaluated. Factors associated with positive results on the TST and T-SPOT.TB were determined, and the impact of age on test performance was specifically addressed. Results: TST was positive in 23.4% (25 of 107). T-SPOT.TB was positive in 4.6% (5 of 109). Overall agreement between TST and T-SPOT.TB was 71%, with prevalence-adjusted, bias-adjusted Kappa of 0.68. History of Mycobacterium tuberculosis exposure was associated with positive results on TST (odds ratio: 25.4, 95% confidence interval: 4.8–261.6, exact logistic regression) and T-SPOT.TB (odds ratio: 78.9, 95% confidence interval: 9.7–∞). All 5 children with positive T-SPOT.TB had TST induration ≥15 mm. No patient less than 1 year of age (n = 17) had positive TST or T-SPOT.TB. Positive TST was not associated with Bacille Calmette–Guérin vaccination or scar. Conclusions: TST was positive in a significant percentage of international adoptees. T-SPOT.TB was rarely positive and discordant results reflected negative T-SPOT.TB with positive TST. In this population latent tuberculosis infection may be over-estimated by TST. Regardless, in our context at the time of the study, treatment decisions were based upon TST results, not results of the T-SPOT.TB assay. Age was consistently associated with findings on TST and T-SPOT.TB with no positive result on either test for any child <1 year of age.

Bordetella parapertussis bacteremia: two case reports.

Bordetella parapertussis is widely recognized as a cause of a pertussis-like respiratory illness in children, but reports of invasive infection are rare. We review the literature and describe the clinical presentation and treatment of 2 children with B. parapertussis bacteremia, as well as the techniques used to isolate the organism.

Successful sonographically guided drainage of epidural abscess.

WEB This is a Web exclusive article. pidural abscesses are most commonly found in the older pediatric age group (12–16 years) and adults; they are relatively rare in younger children [1]. Epidural abscesses are almost always secondary to or associated with other infections such as mastoiditis, sinusitis, postoperative infection, osteomyelitis of the skull, or complications of trauma or surgery [2, 3]. Traditional management of epidural abscesses in children involves neurosurgical drainage and antibiotic therapy [3, 4]. Techniques for neurosurgical drainage include evacuation of the epidural collection through a burr hole or a craniotomy [3]. Given the availability of more powerful antibiotics, the trend toward using less invasive alternatives for evacuation of epidural abscesses [3] has grown. In that light, we report on the percutaneous drainage of an intracranial epidural abscess using sonography guidance in a 15year-old boy.

A 2-month-old with bacteremia and gastroenteritis.

A 2.5-month-old white female with no significant prenatal history presented to the emergency department (ED) with diarrhea that was frequent, foul-smelling, and nonbloody. She was born at full-term by C-section due to late decelerations and had been bottle-fed with premixed formula since birth. The patient was diagnosed by her primary care physician with bronchiolitis 4 weeks before admission, and had cough, congestion, and post-tussive emesis that were improved since then, but not completely resolved. Six days before admission, she developed diarrhea associated with nonbilious, nonbloody emesis, and fever to up to 38.8°C. At that time, she was evaluated in the ED where her white blood cell (WBC) count was 7300/mm, with a differential count of 28% neutrophils, 57% lymphocytes, and 15% monocytes. The hemoglobin was 9.2 mg/dL and platelet count was 406,000/mm. A urinalysis was normal, and a blood culture was obtained. A chest radiograph showed bilateral upper lobe atelectasis without consolidation and a normal thymic silhouette. The patient was diagnosed with viral gastroenteritis and was discharged home; however, she continued having approximately 6 loose, foul-smelling, nonbloody stools each day. Six days later, after a Gram-negative bacterium was identified in the blood culture obtained during the ED visit, the patient was directly admitted to the Infectious Diseases service. On admission, her weight was 4.79 kg (25th–50th percentile), and her height was 54.3 cm (3rd–5th percentile). Her axillary temperature was 36.6°C, heart rate was 144 beats/min, respiratory rate was 40 breaths/min, blood pressure was 80/48 mm Hg, and oxygen saturation was 98% in room air. Physical examination revealed an alert, well-developed and well-nourished, extremely pale infant in no apparent distress. She appeared well-hydrated with moist mucous membranes and negative skin turgor test; however, she had mild erythema and edema around her eyes. Breathing was slightly labored with mild subcostal retractions and bilateral wheezing. Abdomen was soft but distended with normal bowel sounds. The liver edge was palpable at 2 cm below the right costal margin and the spleen was not palpable. Her peripheral pulses were present and symmetric, but capillary refill was delayed from 3 to 5 seconds. The remainder of the physical examination was normal. The peripheral WBC count on the day of admission was 14,700/mm, with a differential count of 3% neutrophils, 8% bands, 69% lymphocytes, 12% monocytes, 3% myelocytes, 3% eosinophils, and 2% basophils. The hemoglobin was 9.1 mg/dL, hematocrit was 27.2%, and platelet count was 560/mm. Except for an albumin level of 2.4 g/dL, her metabolic panel was normal. A lumbar puncture was performed and showed no evidence of meningitis (3 WBC; glucose of 46 mg/dL and protein of 31 mg/dL). Blood culture, urine culture, and stool studies, including adenovirus 40/41 antigen, rotavirus antigen, Escherichia coli and Shiga toxin by EIA, Clostridium difficile toxin, ova and parasite and stool cultures, were obtained. Empiric therapy with piperacillin/tazobactam was initiated for broad Gram-negative coverage. A basic immunologic workup, including quantitative immunoglobulins (IgA, IgE, IgM, and IgG) as well as T-cell, B-cell, CD45 RA, and natural killer cell immunophenotyping, was normal. What is your diagnosis? For denouement see p. 215. Accepted for publication July 14, 2011. From the *Department of Pediatrics, The Ohio State University College of Medicine, 700 Children’s Dr, W4022, Columbus, OH 43205; †Department of Laboratory Medicine, The Ohio State University College of Medicine; and ‡Division of Pediatric Infectious Diseases, Center for Vaccines and Immunity, Nationwide Children’s Hospital, Columbus, OH. E-mail: Asuncion.Mejias@ nationwidechildrens.org. The authors have no funding or conflicts of interest to disclose. Copyright

Depression in Children with HIV Infection: A Case Series.

About 46,000 individuals younger than 25 years of age currently have a diagnosis of human immunodeficiency virus (HIV) or acquired immunodeficiency syndrome (AIDS). During their lifetime, approximately one-third of patients with HIV may develop depression. While antidepressants have been studied in adults with HIV, no data exist to support the use of antidepressants in children and adolescents with HIV. We report a case series of seven pediatric patients with HIV who were prescribed antidepressants. Six of seven patients had mild to moderate improvements in depressive symptoms. None of our patients experienced any suicidal ideations, and adverse events were minor. No drug-drug interactions were reported, and no significant changes in CD4 counts, CD4 percentages, or viral loads occurred during antidepressant therapy. Placebo-controlled, randomized studies are needed to confirm our results in this patient population.

Imported Pediatric Malaria

Malaria is caused by infection with the protozoan parasite species Plasmodium. Worldwide, this disease affects 207 million people and results in 627 000 deaths annually. In nonendemic regions, such as the United States, the majority of malaria cases represent imported disease from immigrants originating from or travelers returning from endemic regions. In 2011, 1920 cases of imported malaria were reported to the Centers for Disease Control, representing a 14% increase compared with 2010 and the largest number reported in the United States since 1971. Appropriate use of malaria chemoprophylaxis and early diagnosis are important outpatient considerations in reducing the incidence and morbidity associated with imported malaria. Studies have demonstrated infrequent use of pretravel consultations as well as a high rate of failure in adherence to a malaria prophylaxis regimen in travelers visiting endemic regions. Rates of pretravel visits and prophylaxis adherence are especially low in those travelling to visit friends or relatives, the most common reported purpose of travel in those with imported malaria. Additionally, the nonspecific signs and symptoms associated with malaria often lead to a misdiagnosis or delay in diagnosis increasing the risk of complications. There remains a significant opportunity for clinicians to identify those children at risk for contracting malaria as well as those presenting with clinical disease. In this case series, we present the demographic characteristics, clinical findings, and laboratory values of imported pediatric malaria cases at a large tertiary care pediatric hospital.