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Gram-positive bacteria account for nearly three-quarters of all surgical site infections. Antibiotic prophylaxis against these bacteria with cephalosporins or, in select circumstances, with vancomycin is considered standard of care for prevention of surgical site infections. There is little evidence to describe the optimal dosing regimen for surgical site infection prophylaxis in infants undergoing cardiac surgery, and a great deal of institutional variability exists in dosing prophylactic antibiotics. We designed this study to describe an optimal dose regimen for cephalosporin and vancomycin based on pharmacokinetic evidence for infant open-heart surgery on cardiopulmonary bypass.Two separate cohorts of infants undergoing cardiac surgery with cardiopulmonary bypass were evaluated. Plasma concentrations of vancomycin (cohort 1, N = 10) and cefazolin (cohort 2, N = 10) were measured, and mixed-effects pharmacokinetic models were constructed for each drug. Simulations of various dosing regimens were performed to describe an appropriate dosing regimen necessary to maintain antibiotic concentrations above the susceptibility cutoff for staphylococci.Both cefazolin and vancomycin plasma concentration versus time profiles were characterized by a 2-compartment model. Subject weight was a significant covariate for V1 for vancomycin. Subject age was a significant covariate for V1 for cefazolin. Cardiopulmonary bypass did not influence concentration versus time profiles. Simulations demonstrated that a 1-hour vancomycin infusion (15 mg·kg), repeated every 12 hours and a 10-minute infusion of cefazolin (30 mg·kg), repeated every 4 hours maintained plasma concentrations above 4 μg·mL and 16 μg·mL, for vancomycin and cefazolin, respectively. Both concentrations are above the minimum inhibitory concentration 90 for most susceptible staphylococci.Prophylactic treatment of vancomycin 15 mg·kg infused1 hour with 12-hour redosing and cefazolin 30 mg·kg infused10 minutes with 4-hour redosing will maintain serum levels of each antibiotic above the susceptibility cut-offs for susceptible staphylococci in infants undergoing cardiac surgery. Cefazolin levels may be adequate for some, but not all, Gram-negative bacteria. The effect of cardiopulmonary bypass on pharmacokinetics is negligible.

The diagnosis of encephalitis is particularly challenging in immunocompromised patients. We report here a case of fatal West Nile virus encephalitis confounded by the presence of budding yeast in the cerebrospinal fluid (CSF) from a patient who had undergone heart transplantation for dilated cardiomyopathy 11 months prior to presentation of neurologic symptoms.

The incidence of pyogenic arthritis is less than that of transient synovitis and varies substantially (from 1/100,000 to 37/100,000 children) depending on the population studied. Although pyogenic arthritis occurs in all age groups, the peak incidence of disease is in children under 3 years of age. A history of trauma temporally related to the onset of arthritis caused by Staphylococcus aureus is common. Upper respiratory tract infection frequently precedes pyogenic arthritis caused by Haemophilus influenzae type b (Hib) and Kingella kingae. Gastroenteritis and aphthous stomatitis also can precede arthritis with K. kingae. Although most children have no underlying disorder, risk factors for pyogenic arthritis include immunodeficiency, hemoglobinopathy, diabetes, intravenous drug abuse, and rheumatoid arthritis.

Objective.To evaluate the impact of methicillin-resistantStaphylococcus aureuson the prevalence ofS. aureusbloodstream infection among children.Methods.Retrospective analysis of demographic data, risk factors for infection, and clinical outcomes for children (age, less than 18 years) withS. aureusbacteremia hospitalized at a children's hospital during 2001–2006.Results.We identified 164 episodes ofS. aureusbacteremia among 151 children. The prevalence of bacteremia due to methicillin-susceptibleS. aureusduring 2001–2003 was approximately the same as that during 2004–2006 (29 and 30 cases, respectively, per 10,000 hospitalized children [hereafter, “per 10,000 hospitalizations”]), but the prevalence of bacteremia due to methicillin-resistantS. aureusincreased from 4 to 11 cases, respectively, per 10,000 hospitalizations (P= .015). A total of 48% of infections involved children who hadS. aureus-positive blood cultures less than 3 days after hospital admission. Seventy-four percent of these children had a preexisting comorbidity. When the prevalence ofS. aureusbacteremia was stratified by race, sex, or age, neonates hospitalized at birth and Hispanic children had significantly reduced risks of infection. Children younger than 1 year of age (excluding neonates hospitalized at birth) had an increased prevalence of hospital-onsetS. aureusbacteremia. There was a disproportionate increase in the risk ofS. aureusbacteremia for each additional week of hospitalization among children with hospital-onsetS. aureusbacteremia. Children with methicillin-resistantS. aureusbacteremia had a longer hospital stay, were transferred to another facility at a greater rate than they were discharged home, and had a greater mortality rate, compared with children with methicillin-susceptibleS. aureusbacteremia.Conclusion.This study documents the prevalence ofS. aureusbacteremia among children with a high risk for acquiring this infection, and it describes populations of children who are at higher risk for bacteremia due to either methicillin-susceptible or methicillin-resistantS. aureus. Methods to improve prevention ofS. aureusbacteremia are needed for children with healthcare-associated risk factors forS. aureusbacteremia.

Summary A 16-year-old male with a 10-year history of recurrent left lateral neck swelling and an associated draining fistula was taken to surgery for excision of the fistula. Histologic examination of the surgical specimen demonstrated findings consistent with Actinomyces species. We suspect that this patient had a third branchial cleft fistula that was infected with Actinomyces .

Cryptosporidium is an intracellular protozoa that can cause gastroenteritis in humans. In immunocompromised hosts, infection can be severe, leading to life-threatening persistent diarrhea. There is limited experience in treating this infection in solid organ transplants. Although newer drugs active against Cryptosporidium exist, they are only licensed in the USA for treatment of immunocompetent hosts. Here we describe a seven-year-old renal transplant recipient with severe cryptosporidiosis. He had a protracted course of diarrhea of up to 2 L/day. He was successfully managed with combination antimicrobial therapy including nitazoxanide, paromomycin, and azithromycin. In conjunction with this regimen, he had a reduction in immunosuppression and complete bowel rest. His stool pattern normalized in four weeks and he has had no recurrence after six months of follow up.

Congenital cytomegalovirus (CMV) affects 0.6% to 0.7% of live births in industrialized nations. It is the leading viral causeof mental retardation and can also result in sensorineural hearing loss. Accepted treatment for patients with symptomatic congenital CMV involving the central nervous system includes intravenous ganciclovir, but the benefits of intravenous ganciclovir may wane over time. Oral therapy with valganciclovir has also been used in the treatment of congenital CMV, and the benefit of longer therapy was studied in this randomized controlled trial. A total of 40 sites participated in the study, and newborns were eligible if they had symptomatic congenital CMV disease, without or without central nervous system involvement. All patients received valganciclovir for 6 weeks, and 1 group continued the treatment for 4.5 months, whereas the rest received a placebo. Change in hearing in the better ear was measured as the primary end point. From 31 study sites, a total of 96 participants were randomized, with 47 participants receiving 6 months of treatment and 49 receiving placebo. A total of 12 stopped taking the blinded medication before the end of the study, but none did so because of adverse events. At 6 months, hearing in the better ear was similar between the 2 groups, with 2 having improvement in the 6-month group and 3 having improvement in the 6-week group, and 5 and 3, respectively, worsening (P = 0.41). At 12 months, total-ear hearing was more likely to be improved or remain normal in patients in the 6-month group than in the 6-week group (73% vs 57%, P = 0.001). The 6-month group scored better on the Bayley Scales of Infant and Toddler Development than did the 6-week group after 24 months on the receptive-communication scale (P = 0.003) and the language-composite scale (P = 0.004).Grade 3 or 4 neutropenia was not different in the 6-month versus the 6-week group (21% vs 27% after 6 months, P = 0.64).These findings suggest 6 months, compared with 6 weeks, of oral valganciclovir among infants with symptomatic congenital CMV disease modestly improved hearing, not in the short term, but in the long term. The prolonged treatment also appearedto improve developmental outcomes modestly.

Bone and joint infections are a significant cause of morbidity in infants and young children. Although many principles regarding pathogenesis, diagnosis, and treatment of infection have remained constant over the years, other aspects of this important pediatric diagnosis are continuing to evolve. This article reviews current information regarding pathogenesis, epidemiology, and microbiology of pediatric bone and joint infections and the clinical presentation, diagnosis, and treatment of these infections.

Cefepime is the only fourth-generation cephalosporin licensed for use in the United States. It is being used increasingly for treatment of infections caused by resistant gram-negative bacteria in older infants and children. Some hospitals have replaced antipseudomonal third-generation cephalosporin antibiotics (eg, ceftazidime) with cefepime because of high rates of infection caused by resistant gram-negative bacteria. Although cefepime generally is not used to treat infections in neonates, it is important for neonatologists to be familiar with the characteristics of the drug because there are a few circumstances in which cefepime may be appropriate therapy for an older infant hospitalized in a neonatal intensive care unit. It is important to understand the unique differences of the drug compared with older cephalosporins. The cephalosporin antibiotics are derivatives of cephalosporin C, a natural antibiotic derived from the fungus Emericellopsis minimum . Cephalosporins have a beta-lactam ring as their major structural component, and their spectrum of activity varies, depending on substitutions at the 3 and 7 positions of the cephalosporin nucleus. Traditionally, these antibiotics are grouped by their spectrum of activity against antimicrobial organisms (Table 1). First-generation cephalosporins are active against most gram-positive bacteria (except enterococci and Listeria ) and have limited activity against some gram-negative organisms. Second-generation cephalosporins have increased activity against gram-negative organisms. Cephamycins, which generally are classified with the second-generation cephalosporins, have enhanced activity against anaerobic bacteria. The third-generation cephalosporins have extended potency against gram-negative bacteria but are generally less active against susceptible staphylococci. Cefepime hydrochloride is a newer semisynthetic, broad-spectrum fourth-generation cephalosporin antibiotic. The other antibiotic in this class is cefpirome, which is not available for use in the United States. | | First Generation | Second Generation | Third Generation | Fourth Generation | |:----------:| ---------------- | ----------------- | ---------------- | ----------------- | | Oral | Cefadroxil | Cefaclor | Cefdinir | | | | Cephalexin | Cefprozil | Cefpodoxime | | | | Cephradine | Cefuroxime axetil | | | | | | Loracarbef | | | | Parenteral | Cefazolin | Cefamandole | Cefoperazone | Cefepime | | | Cephalothin | Cefuroxime | Cefotaxime | | | | Cephapirin | | Ceftizoxime | | | | | Cephamycins | Ceftriaxone | | | | | Cefotetan | Ceftazidime | | | | | Cefoxitin | | | Table 1. Generations of Cephalosporins Cefepime differs from the third-generation cephalosporins by having a quaternized N-methylpyrrolidine substitution at the C3 position of the cephem nucleus and an alkoxyimino group at the C7 position …

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.

Defects in IL-12 production or IL-12 responsiveness result in a vulnerability to infection with non-viral intracellular organisms, but the immunological mechanisms responsible for this susceptibility remain poorly understood. We present an immunological analysis of a patient with disseminated Salmonella enteritidis and a homozygous splice acceptor mutation in the IL-12Rβ1-chain gene. This mutation resulted in the absence of IL-12Rβ1 protein on PBMC and an inability of T cells to specifically bind IL-12 or produce IFN-γ in response to either IL-12 or IL-23. The accumulation of memory (CD45R0high) CD4 T cells that were CCR7high (putative central memory cells) was normal or increased for age. Central memory CD4 T cells of the patient and age-matched controls were similar in having a low to undetectable capacity to produce IFN-γ after polyclonal stimulation. In contrast, the patient had a substantial decrease in the number of CCR7neg/dull CD45R0high memory CD4 T cells (putative effector memory cells), and these differed from control cells in having a minimal ability to produce IFN-γ after polyclonal stimulation. Importantly, tetanus toxoid-specific IFN-γ production by PBMC from the patient was also significantly reduced compared with that in age-matched controls, indicating that signaling via the IL-12Rβ1-chain is generally necessary for the in vivo accumulation of human memory CD4 T cells with Th1 function. These results are also consistent with a model in which the IL-12Rβ1 subunit is necessary for the conversion of central memory CD4 T cells into effector memory cells.

Objective To evaluate the practice of empiric antibiotics for febrile, nonneutropenic pediatric oncology patients with a central venous catheter (CVC) in place. Study design Episodes of fever without neutropenia (absolute neutrophil count [ANC] ≥500 cells/mm 3 ) were reviewed retrospectively in pediatric oncology patients with a CVC undergoing chemotherapy. Characteristics and symptoms were compared between patients with bacteremia and patients without bacteremia. Results A total of 392 episodes of nonneutropenic fever in 138 subjects (52 females; 38%) were reviewed. In this cohort, the median age at an episode was 7 years, and the majority of patients had a diagnosis of acute leukemia (54%). Median ANC was 3100 cells/mm 3 (IQR, 1570-5980 cells/mm 3 ). Median temperature was 38.7°C (IQR, 38.3-39.2°C). Twenty-four infectious episodes (6%) occurred in 18 subjects, and 5 CVCs required removal; all patients requiring removal admitted and received antibiotics owing to chills. There were no significant difference in age, sex, or ANC between patients with bacteremia and those without bacteremia; however, mean temperature was higher in the patients with bacteremia (39.4°C vs 38.7°C; P = .003). No deaths due to sepsis occurred, and no CVCs were removed because antibiotics were not administered empirically. Conclusion Our practice of observing pediatric oncology patients undergoing chemotherapy with CVCs who are not neutropenic does not appear to lead to increased serious adverse outcomes and avoids antibiotic exposure for >90% of patients without a bacterial infection.

Cytomegalovirus (CMV) is the most common cause of congenital infection worldwide. Urine viral culture is the standard for CMV diagnosis in neonates and infants. The objectives of this study were to compare the performance of serial paired rapid shell vial cultures (SVC) and routine viral cultures (RVC), and to determine the optimal number of cultures needed to detect positive cases. From 2001 to 2011, all paired CMV SVC and RVC performed on neonates and infants less than 100 days of age were recorded. Testing episodes were defined as sets of cultures performed within 7 days of one another. A total of 1264 neonates and infants underwent 1478 testing episodes; 68 (5.4%) had at least one episode with a positive CMV culture. In episodes where CMV was detected before day 21 of life, the first specimen was positive in 100% (16/16) of cases. When testing occurred after 21 days of life, the first specimen was positive in 82.7% (43/52) of cases, requiring three cultures to reach 100% detection. The SVC was more prone to assay failure than RVC. Overall, when RVC was compared to SVC, there was 86.0% positive agreement and 99.9% negative agreement. In conclusion, three serial urine samples are necessary for detection of CMV in specimens collected between day of life 22 and 99, while one sample may be sufficient on or before day of life 21. Though SVC was more sensitive than RVC, the risk of SVC failure supports the use of multimodality testing to optimize detection.

We report on the effectiveness of intravenous ribavirin for severe adenoviral pneumonia in a 10-month-old male following orthotopic liver transplantation. On day 20 post-transplantation, he developed high fever, marked respiratory compromise, and hypoxemia. The chest radiograph showed bilateral pulmonary infiltrates. Samples of bronchoalveolar lavage fluid grew adenovirus, serotype 1. Marked clinical and radiological improvement was noted after intravenous ribavirin therapy. A prospective clinical trial is needed to determine the efficacy of ribavirin therapy for severe adenovirus disease. Pediatr Pulmonol. 2000; 29:69–73. © 2000 Wiley-Liss, Inc.

Many children hospitalized with serious bacterial infections are candidates for either home oral antibiotic therapy or outpatient parenteral antibiotic therapy. Outpatient antibiotic therapy offers the potential for excellent medical treatment, reduced costs, and improved quality of life for ill children. However, cost considerations must not override good medical judgment. Certain children simply are not candidates for outpatient therapy because of the seriousness of their infection, poor compliance, lack of intravenous access, or poor social situation. In addition, although the few published studies to date all show that outpatient antibiotic therapy is effective, there is further need for properly designed clinical trials to evaluate the efficacy and safety of outpatient antibiotic therapy for serious bacterial infections in children.

Young children, Black children, and those without private insurance were at higher risk for hospitalization., We conducted a retrospective, observational, population-based study to investigate the effect of staphylococcal infections on the hospitalization of children in California during 1985–2009. Hospitalized children with staphylococcal infections were identified through the California Office of Statewide Health Planning and Development discharge database. Infections were categorized as community onset, community onset health care–associated, or hospital onset. Infection incidence was calculated relative to all children and to those hospitalized in acute-care facilities. A total of 140,265 records were analyzed. Overall incidence increased from 49/100,000 population in 1985 to a peak of 83/100,000 in 2006 and dropped to 73/100,000 in 2009. Staphylococcal infections were associated with longer hospital stays and higher risk for death relative to all-cause hospitalizations of children. The number of methicillin-resistant Staphylococcus aureus infections increased, and the number of methicillin-susceptible S. aureus infections remained unchanged. Children

Disseminated infection due to nontuberculous Mycobacterium (NTM) species is rare in pediatrics. Here we report 6 infections affecting 5 patients at a single institution in an immunocompromised population of pediatric oncology and stem cell transplant recipients. The patients presented within a 1-year period with catheter-associated bacteremia. New pulmonary nodules were noted in 4 of the 5 patients. All of the infections were due to rapidly growing NTM. Patients were successfully treated with removal of the infected catheter and combination antibiotic therapy. There are currently no consensus guidelines for treatment of NTM infections in this population, and a therapeutic approach is presented here.

We report 4 patients who developed hyperphosphatemia while receiving liposomal amphotericin B to treat an invasive fungal infection. Resolution of the hyperphosphatemia occurred after transition to amphotericin B lipid complex. This phenomenon may occur more commonly in patients with mild to moderate renal insufficiency.

We describe a pediatric renal transplant patient with Mycobacterium bovis disease who was successfully treated using an antituberculosis regimen that included rifampin. We discuss the history of M. bovis and the diagnosis and management of M. bovis infection in renal transplant patients.

hematology/oncology patients Martina I. Lefterovaa, Jennifer I. Romerob, Kathleen Gutierrezc, Gary Dahld, and Niaz Banaeia,e,f aDepartment of Pathology, cDepartment of Pediatrics, Division of Pediatric Infectious Disease, dDepartment of Pediatrics, Division of Pediatric Hematology/Oncology, eDepartment of Medicine, Division of Infectious Diseases and Geographic Medicine, fClinical Microbiology Laboratory, Stanford University School of Medicine, Stanford, CA, USA; bcurrently at Division of Immunology and Ophthalmology, Genentech, South San Francisco, CA USA.

Objective. During the 2 decades in which effective antiviral therapies have been available for neonatal herpes simplex virus (HSV) disease, changes have been documented not only in the outcomes of infected infants, but also in the natural history of the disease itself. Numerous studies previously have reported that early institution of antiviral therapy is beneficial to the outcome of the disease. The objective of this study was to provide an update of neonatal HSV disease to identify means by which future improvements in the management of HSV-infected neonates can be made. Design/Methods. Neonates enrolled in 2 studies of parenteral acyclovir for the treatment of neonatal HSV disease provided the data source. The National Institute of Allergy and Infectious Diseases Collaborative Antiviral Study Group conducted the studies between 1981 and 1997. A total of 186 patients are summarized, all of whom were treated with acyclovir. Demographic and clinical characteristics of these patients are reported. Results. Comparisons between patients treated in the periods between 1981–1988 and 1989–1997 according to extent of disease revealed that the mean time between the onset of disease symptoms and initiation of therapy has not changed significantly from the early 1980s to the late 1990s. Of all patients evaluated, 40% had fetal scalp monitors during the delivery process. A significant minority of patients did not have skin vesicles at the time of their presentation and did not develop them during the acute HSV disease (39% of patients with disseminated disease; 32% of patients with central nervous system [CNS] disease; and 17% of patients with skin, eye, and/or mouth disease). Among patients with CNS disease, mortality was associated with prematurity. Among patients with disseminated HSV disease treated with acyclovir at 30 mg/kg/d, mortality was associated with aspartate transaminase elevations of ≥10 times the upper limit of normal at the time of initiation of acyclovir therapy. Mortality was also associated with lethargy at initiation of antiviral therapy for patients with disseminated disease. Patients' morbidity status was associated with the extent of disease (skin, eye, and/or mouth disease vs CNS vs disseminated). For those patients with CNS disease, morbidity was also associated with seizures at initiation of antiviral therapy. Conclusion. Data presented in the current comparison of neonatal HSV disease over the 2 periods (1981–1988 vs 1989–1997) demonstrate that no progress has been made in decreasing the interval between onset of HSV symptoms and initiation of antiviral therapy. Additional strides in the improvement of disease outcome may occur only if the interval between onset of symptoms and initiation of therapy is shortened. The means by which this will be accomplished lie in increased consideration of neonatal HSV infections in acutely ill infants. Specific data and recommendations to facilitate this goal are contained within.

Objective. The objective of this investigation was to establish the safety of high-dose (HD) acyclovir for the treatment of neonatal herpes simplex virus (HSV) disease. In addition, an estimate of therapeutic efficacy was sought, both with respect to mortality and to morbidity. Virologic efficacy of HD acyclovir was also assessed. Participants. Infants who were ≤28 days old and whose disease was considered to be caused by HSV were enrolled in this study. Patients with central nervous system (CNS; N = 28) or disseminated (N = 41) HSV infection were offered participation in the trial. A small number of patients with HSV disease limited to the skin, eyes, or mouth (SEM; N = 10) or whose disease was clinically consistent with HSV but who did not have virologic confirmation of infection (N = 9) also were enrolled on a compassionate basis. Only patients with virologically confirmed HSV disease were included in efficacy analyses. All enrolled patients were included in safety analyses. Methods. The study was an open-label evaluation of intravenous acyclovir at dosages higher than the 30 mg/kg/d standard dosage approved by the US Food and Drug Administration. The first 16 patients enrolled received intermediate-dose (ID) acyclovir (45 mg/kg/d), and the next 72 patients received HD acyclovir (60 mg/kg/d). Acyclovir was administered in 3 divided daily doses for 21 days. Neonates were assessed prospectively throughout treatment and at scheduled follow-up visits for the first 4 years of life. Data were compared with those of a previous National Institute of Allergy and Infectious Diseases Collaborative Antiviral Study Group trial in which patients received standard-dose (SD) acyclovir for 10 days and in which identical methods (with the exception of acyclovir dosage and duration of therapy) were used. Results. Six (21%) of 29 HD acyclovir recipients whose HSV disease remained localized to the SEM or CNS experienced neutropenia. One of the 6 had an absolute neutrophil count The survival rate for the patients with disseminated HSV disease treated with HD acyclovir was significantly higher than for those in the previous study treated with SD acyclovir, with an odds ratio (OR) of 3.3 (95% confidence interval [CI]: 1.4–7.9). For patients with CNS disease, however, survival rates were similar for the HD and SD groups. To assess the effect of HD acyclovir on survival for the entire population with neonatal HSV disease, the Cox proportional hazards regression analysis was performed with stratification for disease category (CNS versus disseminated). In performing this analysis, differences in mortality for each disease category were weighted to allow statistical comparison of the treatment dosage groups (HD, ID, and SD). This analysis indicated that the survival rate for patients treated with HD acyclovir was statistically significantly higher than for patients treated with SD acyclovir (OR: 3.3; 95% CI: 1.5–7.3). Recipients of HD acyclovir had a borderline significant decrease in morbidity compared with SD recipients, after stratification for the extent of disease (SEM vs CNS vs disseminated) and controlling for the potential confounding factors of HSV type (HSV-1 vs. HSV-2), prematurity, and disease severity (seizures). Patients treated with HD acyclovir were 6.6 times (adjusted OR; 95% CI: 0.8–113.6) as likely to be developmentally normal at 12 months of age as patients treated with SD therapy. Conclusion. These data support the use of a 21-day course of HD (60 mg/kg/d) intravenous acyclovir to treat neonatal CNS and disseminated HSV disease. Throughout the course of HD acyclovir therapy, serial ANC determination should be made at least twice weekly. Decreasing the acyclovir dosage or administering granulocyte colony-stimulating factor should be considered if the ANC remains below 500/mm3 for a prolonged period.

Infection with Nocardiaposes a diagnostic challenge in patients with chronic granulomatous disease (CGD) because the signs and symptoms are often nonspecific, delay in diagnosis is common, and invasive procedures are frequently required to obtain appropriate tissue specimens. We present the first reported case of N farcinica pneumonia in an adolescent with X-linked CGD. Differentiation of N farcinica from other members of N asteroidescomplex is important because of its propensity for causing disseminated infection and antimicrobial resistance. Physicians caring for patients with CGD should maintain a high index of suspicion for nocardiosis, especially in those receiving chronic steroid therapy. Early diagnosis remains critical for decreased morbidity and occasional mortality.

Comprehensive hospital discharge data completed by the California Office of Statewide Health Planning and Development was used to determine whether the proportion of infants

Progressive multifocal leukoencephalopathy (PML) is a rapidly progressive degenerative demyelinating disease that results from infection with JC virus. PML usually occurs in an immunocompromised individual, putatively attributable to reactivation of a latent JC virus. In childhood PML has been reported in individuals with acquired immunodeficiency syndrome (AIDS),1–3 Wiskott–Aldrich syndrome,4 and inherited immunodeficiencies.5,,6We report here a 15-year-old boy with generalized morphea, a form of limited cutaneous sclerodema, and secondary amyloidosis who developed PML. The rapid onset of his neurologic manifestations and the initial neuroimaging studies suggested acute disseminated encephalomyelitis (ADEM), and a brain biopsy was needed for the diagnosis of PML. A 15-year-old boy with scleroderma and amyloidosis was admitted for progressive ataxia, dysarthria, and weakness. His medical history was notable for generalized morphea confirmed by a skin biopsy at 3 years of age. He had severe cutaneous involvement and finger and toe contractures attributable to skin and soft tissue involvement. He was treated with prednisone andD-penicillamine for several years. All autoantibodies were negative, and immunologic work-up revealed normal complement and immunoglobulin levels but a low absolute T-cell count of 533 cells/μL. There was no evidence of active arthritis or recurrent infections. Two years before admission, he was diagnosed with secondary amyloidosis with serum amyloid A protein by liver biopsy. A concomitant skin biopsy showed no evidence of amyloid deposition and continued to be consistent with morphea. Proteinuria was noted. Prednisone was stopped, and chlorambucil (4 mg per day) was started. He responded well to the chlorambucil over the next several months with significant regression of amyloidosis-related clinical findings and marked dermatologic improvement. He was maintained on chlorambucil only. However, 2 months before admission the dosage had to be decreased from 4 mg to 3 mg daily because of leukopenia with a white …

Acute viral encephalitis and postinfectious encephalomyelitis affect both children and adults. Enteroviruses, HSV types 1 and 2, and arboviruses are the most common causes of encephalitis in the United States; however, the differential diagnosis is broad. History taking and physical examination can provide clues to the cause, but the diagnosis is usually established on the basis of CSF analysis, viral culture, MRI, and serologic testing, when indicated. In the future, PCR techniques may enhance rapidity of diagnosis. Until the specific cause is identified, empirical therapy should be given. Because complications can be severe, all patients with encephalitis should be monitored in a facility capable of providing supportive intensive care. Long-term follow-up is important to detect sequelae, particularly in patients with eastern equine or HSV encephalitis.

The Safety and Efficacy of High-Dose (HD) Acyclovir (ACV) in Neonatal Herpes Simplex Virus (HSV) Infections