Avinash K. Shetty

Lactobacillus Sepsis Associated With Probiotic Therapy

Probiotic strains of lactobacilli are increasingly being used in clinical practice because of their many health benefits. Infections associated with probiotic strains of lactobacilli are extremely rare. We describe 2 patients who received probiotic lactobacilli and subsequently developed bacteremia and sepsis attributable to Lactobacillus species. Molecular DNA fingerprinting analysis showed that the Lactobacillus strain isolated from blood samples was indistinguishable from the probiotic strain ingested by the patients. This report indicates, for the first time, that invasive disease can be associated with probiotic lactobacilli. This report should not discourage the appropriate use of Lactobacillus or other probiotic agents but should serve as a reminder that these agents can cause invasive disease in certain populations.

Orbital cellulitis in children.

Background: To review the epidemiology and management of orbital cellulitis in children. Methods: The medical records of children ≤18 years old and hospitalized from June 1, 1992, through May 31, 2002, at the Brenner Childrens Hospital, with a discharge ICD-9 code indicating a diagnosis of orbital cellulitis and confirmed by computed tomography scan were reviewed. A literature search for additional studies for systematic review was also conducted. Results: Forty-one children with orbital cellulitis were identified. The mean age was 7.5 years (range, 10 months to 16 years), and 30 (73%) were male (male:female ratio = 2.7). All cases of orbital cellulitis were associated with sinusitis; ethmoid sinusitis was present in 40 (98%) patients. Proptosis and/or ophthalmoplegia was documented in 30 (73%), and 34 (83%) had subperiosteal and/or orbital abscesses. Twenty-nine (71%) had surgical drainage and 12 (29%) received antibiotic therapy only. The mean duration of hospitalization was 5.8 days. The mean duration of antibiotic therapy was 21 days. Conclusions: Orbital cellulitis occurs throughout childhood and in similar frequency among younger and older children. It is twice as common among males as females. Selected cases of orbital cellulitis, including many with subperiosteal abscess, can be treated successfully without surgical drainage.

Clinical Experience in Adults and Children Treated with Intravenous Peramivir for 2009 Influenza A (H1N1) Under an Emergency IND Program in the United States

Peramivir, an investigational intravenous neuraminidase inhibitor, was given to 31 hospitalized patients with severe viral pneumonia during the 2009 H1N1 influenza pandemic under the Emergency IND regulations. The drug was generally well tolerated and associated with recovery in most patientes.

Childhood sarcoidosis: A rare but fascinating disorder

Childhood sarcoidosis is a rare multisystemic granulomatous disorder of unknown etiology. In the pediatric series reported from the southeastern United States, sarcoidosis had a higher incidence among African Americans. Most reported childhood cases have occurred in patients aged 13–15 years. Macrophages bearing an increased expression of major histocompatibility class (MHC) II molecules most likely initiate the inflammatory response of sarcoidosis by presenting an unidentified antigen to CD4+ Th (helper-inducer) lymphocytes. A persistent, poorly degradable antigen driven cell-mediated immune response leads to a cytokine cascade, to granuloma formation, and eventually to fibrosis. Frequently observed immunologic features include depression of cutaneous delayed-type hypersensitivity and a heightened helper T cell type 1 (Th1) immune response at sites of disease. Circulating immune complexes, along with signs of B cell hyperactivity, may also be found. The clinical presentation can vary greatly depending upon the organs involved and age of the patient. Two distinct forms of sarcoidosis exist in children. Older children usually present with a multisystem disease similar to the adult manifestations, with frequent hilar lymphadenopathy and pulmonary infiltrations. Early-onset sarcoidosis is a unique form of the disease characterized by the triad of rash, uveitis, and arthritis in children presenting before four years of age. The diagnosis of sarcoidosis is confirmed by demonstrating a typical noncaseating granuloma on a biopsy specimen. Other granulmatous diseases should be reasonably excluded. The current therapy of choice for sarcoidosis in children with multisystem involvement is oral corticosteroids. Methotrexate given orally in low doses has been effective, safe and steroid sparing in some patients. Alternative immunosuppressive agents, such as azathioprine, cyclophosphamide, chlorambucil, and cyclosporine, have been tried in adult cases of sarcoidosis with questionable efficacy. The high toxicity profile of these agents, including an increased risk of lymphoproliferative disorders and carcinomas, has limited their use to patients with severe disease refractory to other agents. Successful steroid sparing treatment with mycophenolate mofetil was described in an adolescent with renal-limited sarcoidosis complicated by renal failure. Novel treatment strategies for sarcoidosis have been developed including the use of TNF-alpha inhibitors, such as infliximab. The long-term course and prognosis is not well established in childhood sarcoidosis, but it appears to be poorer in early-onset disease.

Validation of the Edinburgh Postnatal Depression Scale among women in a high HIV prevalence area in urban Zimbabwe

Despite the significant burden of common mental disorders (CMD) among women in sub Saharan Africa, data on postnatal depression (PND) is very limited, especially in settings with a high HIV prevalence. The Edinburgh Postnatal Depression Scale (EPDS), a widely used screening test for PND has been validated in many countries, but not in Zimbabwe. We assessed the validity of the EPDS scale among postpartum women compared with Diagnostic Manual of Mental Disorders (DSM-IV) criteria for major depression. Six trained community counselors administered the Shona version of the EPDS to a random sample of 210 postpartum HIV-infected and uninfected women attending two primary care clinics in Chitungwiza. All women were subsequently subjected to mental status examination using DSM IV criteria for major depression by 2 psychiatrists, who were blinded to the subject’s EPDS scores. Data were analyzed using receiver operating characteristic (ROC) curve analysis. Of the 210 postpartum mothers enrolled, 64 (33%) met DSM IV criteria for depression. Using a cut-off score of 11/12 on the Shona version of the EPDS for depression, the sensitivity was 88%, and specificity was 87%, with a positive predictive value of 74%, a negative predictive value of 94%, and an area under the curve of 0.82. Cronbachs alpha coefficient for the whole scale was 0.87. Conclusion: The Shona version of the EPDS is a reliable and valid tool to screen for PND among HIV-infected and un-infected women in Zimbabwe. Screening for PND should be integrated into routine antenatal and postnatal care in areas with high HIV prevalence.

Comparison of conventional viral cultures with direct fluorescent antibody stains for diagnosis of community-acquired respiratory virus infections in hospitalized children.

Objective. Because of the widespread availability of rapid viral antigen testing, many institutions never adopted a routine practice of ordering viral cultures to detect community-acquired respiratory viruses (CRVs). The ease of performing complete viral studies in our on site laboratory allowed us to assess the clinical implications of the absence of conventional culture results in previously healthy hospitalized children with CRV infections. Methods. From June 1997 through May 2000, the results of direct immunofluorescence assay (DFA) of 1069 nasopharyngeal swab (NP) specimens were compared with simultaneously inoculated conventional tube cell cultures for detection of CRVs. In addition the medical records of 140 previously healthy infants and children hospitalized for management of lower respiratory tract infections caused by culture-proved CRVs were reviewed. Results. Viruses were isolated or detected by DFA or viral culture or both in 468 (30%) of the 1557 NP samples evaluated. The most common CRV isolated was respiratory syncytial virus (49%), followed by parainfluenza viruses (15%), influenza A viruses (14%), rhinoviruses (8%), adenoviruses (4%), enteroviruses (4%) and influenza B viruses (1%). Of the 1069 NP specimens for which both viral culture and rapid antigen testing were performed, 190 specimens were DFA-positive and culture-positive, 7 specimens were DFA-positive and culture-negative, 35 specimens were DFA-negative and culture-positive and 837 specimens were DFA-negative and culture-negative. The overall sensitivity, specificity, positive predictive value and negative predictive value of DFA were 84, 99, 96 and 96%, respectively. Of the 140 hospitalized patients with culture-proved viral cultures (89 respiratory syncytial virus, 22 influenza A, 20 parainfluenza virus and 9 adenovirus), the mean duration of hospital stay was 3.6 days, and the mean time for viral cultures to become positive was 7.7 days (P < 0.001, signed rank test). One hundred twenty (86%) viral cultures did not become positive until after the patient had been discharged from the hospital. In no case was the clinical decision regarding the patient’s treatment or discharge from the hospital based on the results of viral culture. Conclusions. We conclude that positive viral cultures have no impact on clinical decision making and management of healthy children during hospitalization for illness attributable to community-acquired respiratory viruses.

Safety and trough concentrations of nevirapine prophylaxis given daily, twice weekly, or weekly in breast-feeding infants from birth to 6 months.

Despite the success of antiretroviral prophylaxis in reducing mother-to-child HIV-1 transmission, postpartum transmission through breast milk remains a problem. Antiretroviral administration to the infant during the period of breast-feeding could protect against postnatal transmission. An open-label phase 1/2 study was designed to assess the safety and trough concentrations of nevirapine (NVP) given once weekly (OW), twice weekly (TW), or once daily (OD) to HIV-exposed breast-feeding infants for 24 weeks. Following maternal dosing with 200 mg NVP orally at onset of labor, breast-feeding infants were randomized within 48 hours of birth to 1 of 3 regimens: arm 1, NVP given OW (4 mg/kg from birth to 14 days, ↑ to 8 mg/kg from 15 days to 24 weeks), arm 2, NVP given TW (4 mg/kg from birth to 14 days, ↑ to 8 mg/kg from 15 days to 24 weeks), and arm 3, NVP given OD (2 mg/kg from birth to 14 days, ↑ to 4 mg/kg from 15 days to 24 weeks). Trough NVP concentrations and clinical and laboratory abnormalities were monitored. Of the 75 infants randomized (26 to OW, 25 to TW, and 24 to OD dosing), 63 completed the 32-week follow-up visit. No severe skin, hepatic, or renal toxicity related to NVP was observed. Neutropenia occurred in 8 infants. Trough NVP levels were lower than the therapeutic target (100 ng/mL) in 48 of 75 (64.0%) samples from infants in the OW arm, 3 of 65 (4.6%) samples in the TW arm, and 0 of 72 samples in the OD arm. Median (range) trough NVP concentrations were 64 ng/mL (range: <25–1519 ng/mL) with OW dosing; 459 (range: <25–1386 ng/mL) with TW dosing; and 1348 (range: 108–4843 ng/ml) with OD dosing. Our data indicate that NVP prophylaxis for 6 months was safe and well tolerated in infants. OD NVP dosing resulted in all infants with trough concentration greater than the therapeutic target and maintenance of high drug concentrations. A phase 3 study is planned to assess the efficacy of OD infant NVP regimen to prevent breast-feeding HIV-1 transmission.

Fatal Cerebral Herniation After Lumbar Puncture in a Patient With a Normal Computed Tomography Scan

Cerebral edema and resulting elevated intracranial pressure (ICP) is a well-known complication of acute pyogenic meningitis.1,,2 A diagnostic lumbar puncture (LP) may then precipitate herniation or coning of the brain, often with fatal outcome.3–8 A computed tomography (CT) scan of the brain is therefore recommended before LP whenever raised ICP is suspected, particularly if the possibility of a mass or space-occupying lesion exists.9–11 We describe a 15-year-old adolescent with bacterial meningitis with a normal CT scan who developed signs of herniation immediately after a subsequent LP. To the best of our knowledge this is the second documented report of herniation found at postmortem examination in a child with a normal CT scan.

Cavernous sinus thrombosis complicating sinusitis.

Background Septic cavernous sinus thrombosis is a rare complication of paranasal sinusitis. Objective To familiarize the clinician with the pathogenesis, diagnosis, and appropriate management of septic cavernous sinus thrombosis. Design Case report and literature review. Setting Pediatric intensive care unit in a university hospital. Patient We present a 12-yr-old female with a 1 wk history of an upper respiratory tract infection with worsening dyspnea, cough, and swelling of the left eye progressing to adult respiratory distress syndrome. Secondary to the need for significant mechanical ventilatory support, venovenous extracorporeal membrane oxygenation was initiated. Computed tomography scan of the head and neck with contrast revealed bilateral cavernous sinus thrombosis. After broad-spectrum intravenous antibiotics and aggressive supportive care in conjunction with surgical intervention (maxillary sinus lavage and right orbital exploration) and anticoagulation therapy, the patient recovered. Blood cultures were positive for Viridans streptococcus. At discharge 3 wks later, the patient had improved, but had right-eye blindness. Conclusions The diagnosis of septic cavernous sinus thrombosis requires a high index of suspicion and confirmation by imaging; early diagnosis and surgical drainage of the underlying primary source of infection in conjunction with long-term intravenous antibiotic therapy are critical for an optimal clinical outcome.

The feasibility of preventing mother-to-child transmission of HIV using peer counselors in Zimbabwe.

BackgroundPrevention of mother-to-child transmission of HIV (PMTCT) is a major public health challenge in Zimbabwe.MethodsUsing trained peer counselors, a nevirapine (NVP)-based PMTCT program was implemented as part of routine care in urban antenatal clinics.ResultsBetween October 2002 and December 2004, a total of 19,279 women presented for antenatal care. Of these, 18,817 (98%) underwent pre-test counseling; 10,513 (56%) accepted HIV testing, of whom 1986 (19%) were HIV-infected. Overall, 9696 (92%) of women collected results and received individual post-test counseling. Only 288 men opted for HIV testing. Of the 1807 HIV-infected women who received posttest counseling, 1387 (77%) collected NVP tablet and 727 (40%) delivered at the clinics. Of the 1986 HIV-infected women, 691 (35%) received NVPsd at onset of labor, and 615 (31%) infants received NVPsd. Of the 727 HIV-infected women who delivered in the clinics, only 396 women returned to the clinic with their infants for the 6-week follow-up visit; of these mothers, 258 (59%) joined support groups and 234 (53%) opted for contraception. By the end of the study period, 209 (53%) of mother-infant pairs (n = 396) came to the clinic for at least 3 follow-up visits.ConclusionDespite considerable challenges and limited resources, it was feasible to implement a PMTCT program using peer counselors in urban clinics in Zimbabwe.