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Context: The Advisory Committee on Immunization Practices (ACIP) recommends annual influenza vaccination for children with certain chronic medical conditions to prevent serious complications of influenza infection. Little is known about the relative contribution of each of these chronic medical conditions to the development of serious influenza-associated complications., Objective: To identify chronic medical conditions that are associated with respiratory failure in children hospitalized with community-acquired laboratory-confirmed influenza., Design, Setting, and Patients: A retrospective cohort study of patients aged 21 years or younger hospitalized at The Children's Hospital of Philadelphia with community-acquired laboratory-confirmed influenza during 4 consecutive influenza seasons (June 2000 through May 2004). We examined 9 ACIP-designated high-risk chronic medical conditions and 3 additional chronic medical conditions (neurological and neuromuscular disease [NNMD], gastroesophageal reflux disease [GERD], and history of prematurity) that in recent studies have been associated with influenza hospitalization and severe influenza-related complications., Main Outcome Measures: Rate and odds ratio (OR) of respiratory failure, defined as need for mechanical ventilation., Results: Of 745 children hospitalized with community-acquired laboratory-confirmed influenza, 322 (43%) had 1 or more ACIP-designated high-risk chronic medical conditions. Neurological and neuromuscular disease, GERD, and history of prematurity were present in 12%, 14%, and 3%, of children, respectively. Thirty-two children (4.3%) developed respiratory failure. In multivariate logistic regression analyses, conditions associated with respiratory failure included NNMD (OR, 6.0; 95% confidence interval [CI], 2.7-13.5), chronic pulmonary disease other than asthma (OR, 4.8; 95% CI, 1.5-15.1), and cardiac disease (OR, 4.0; 95% CI, 1.6-10.2). The predicted probabilities of respiratory failure derived from the multivariate model were 12% (95% CI, 7%-20%), 9% (95% CI, 3%-23%), and 8% (95% CI, 4%-18%) for children with NNMD, chronic pulmonary disease, and cardiac disease, respectively., Conclusions: These results support the ACIP's recent decision to add NNMD to the list of conditions for which annual influenza vaccine is recommended in children. Neurologists and primary care pediatricians should be alerted to the increased risk of respiratory failure and the importance of influenza vaccination in children with NNMD.

Background: Candida species are the fourth most common cause of bloodstream infection and are the leading cause of invasive fungal infection among hospitalized patients in the United States. However, the frequency and outcomes attributable to the infection are uncertain. This retrospective study set out to estimate the incidence of candidemia in hospitalized adults and children in the United States and to determine attributable mortality, length of hospital stay, and hospital charges related to candidemia., Methods: We used the Nationwide Inpatient Sample 2000 for adult patients and the Kids' Inpatient Database 2000 for pediatric patients. We matched candidemia-exposed and candidemia-unexposed patients by the propensity scores for the probability of candidemia exposure, which were derived from patient characteristics. Attributable outcomes were calculated as the differences in estimates of outcomes between propensity score-matched patients with and without candidemia., Results: In the United States in 2000, candidemia was diagnosed in an estimated 1118 hospital admissions of pediatric patients and 8949 hospital admissions of adult patients, yielding a frequency of 43 cases per 100,000 pediatric admissions (95% confidence interval [CI], 35-52 cases per 100,000 pediatric admissions) and 30 cases per 100,000 adult admissions (95% CI, 26-34 cases per 100,000 adult admissions). In pediatric patients, candidemia was associated with a 10.0% increase in mortality (95% CI, 6.2%-13.8%), a mean 21.1-day increase in length of stay (95% CI, 14.4-27.8 days), and a mean increase in total per-patient hospital charges of 92,266 dollars (95% CI, 65,058 dollars-119,474 dollars). In adult patients, candidemia was associated with a 14.5% increase in mortality (95% CI, 12.1%-16.9%), a mean 10.1-day increase in length of stay (95% CI, 8.9-11.3 days), and a mean increase in hospital charges of 39,331 dollars (95% CI, 33,604 dollars-45,602 dollars)., Conclusion: The impact of candidemia on excess mortality, increased length of stay, and the burden of cost of hospitalization underscores the need for improved means of prevention and treatment of candidemia in adults and children.

Health care-acquired are a major risk for hospitalized children. Similar to adult patients, children are vulnerable to infections related to medical devices. Children also are at significant risk of nosocomial transmission of common pediatric viral illness, such as respiratory syncytial virus and varicella. In addition, pediatric patients have unique or incompletely developed immune system.

Background: Zygomycosis is an increasingly emerging life-threatening infection. There is no single comprehensive literature review that describes the epidemiology and outcome of this disease., Methods: We reviewed reports of zygomycosis in the English-language literature since 1885 and analyzed 929 eligible cases. We included in the database only those cases for which the underlying condition, the pattern of infection, the surgical and antifungal treatments, and survival were described., Results: The mean age of patients was 38.8 years; 65% were male. The prevalence and overall mortality were 36% and 44%, respectively, for diabetes; 19% and 35%, respectively, for no underlying condition; and 17% and 66%, respectively, for malignancy. The most common types of infection were sinus (39%), pulmonary (24%), and cutaneous (19%). Dissemination developed in 23% of cases. Mortality varied with the site of infection: 96% of patients with disseminated disease died, 85% with gastrointestinal infection died, and 76% with pulmonary infection died. The majority of patients with malignancy (92 [60%] of 154) had pulmonary disease, whereas the majority of patients with diabetes (222 [66%] of 337) had sinus disease. Rhinocerebral disease was seen more frequently in patients with diabetes (145 [33%] of 337), compared with patients with malignancy (6 [4%] of 154). Hematogenous dissemination to skin was rare; however, 78 (44%) of 176 cutaneous infections were complicated by deep extension or dissemination. Survival was 3% (8 of 241 patients) for cases that were not treated, 61% (324 of 532) for cases treated with amphotericin B deoxycholate, 57% (51 of 90) for cases treated with surgery alone, and 70% (328 of 470) for cases treated with antifungal therapy and surgery. By multivariate analysis, infection due to Cunninghamella species and disseminated disease were independently associated with increased rates of death (odds ratios, 2.78 and 11.2, respectively)., Conclusions: Outcome from zygomycosis varies as a function of the underlying condition, site of infection, and use of antifungal therapy.

We performed a retrospective cohort study of hospitalized children with positive blood cultures for Candida species. Independent risk factors for mortality by multivariable analysis were location in the pediatric intensive care unit at the time of infection (hazard ratio, 6.3; 95% confidence interval, 1.6-24.3) and the presence of an arterial catheter (hazard ratio, 2.4; 95% confidence interval, 1.1-5.8). Our findings help identify a group of pediatric patients that should be targeted for future interventions to prevent and treat candidemia.

Invasive fungal infections have increased in frequency and severity over the past two decades as a result of an increasing number of immunocompromised patients. This new age of opportunistic fungal infections extends to pediatric patients. The last decade has seen the development of several new antifungal agents for the treatment of these infections. However, there is a paucity of data on the treatment of invasive fungal infections in children. This review provides a brief overview of the current state of antifungal therapy for children, discussing the important antifungal classes and the differences in mechanisms of action and resistance, pharmacology, and efficacy and safety data in pediatric patients outside the neonatal period.

Candida species are the most common cause of fungal infections in hospitalized patients. Recent studies have reported a relative reduction in the rates of infection caused by Candida albicans and a shift toward non-albicans Candida spp. Data on the distribution and susceptibility of Candida spp. from children's hospitals are limited. Clinical isolates of Candida were collected from 4 US children's hospitals in 2003. Broth dilution MICs for amphotericin B, fluconazole, voriconazole, caspofungin, posaconazole, and ravuconazole were performed according to National Committee for Clinical Laboratory Standards-approved methodology. A total of 179 clinical isolates were identified and included. Of 179, 77 (43%) were C. albicans. Candida parapsilosis isolates were the second most frequently identified (57/175, 32%), followed by Candida glabrata, Candida tropicalis, and Candida lusitaniae (approximately 8% each). Caspofungin was the most active agent in vitro against all Candida spp. Fluconazole resistance was seen among C. glabrata, C. tropicalis, and Candida krusei isolates. Newer azoles had improved activity against fluconazole-resistant isolates of Candida. Among isolates of C. parapsilosis, nearly 20% were resistant to amphotericin B. The current study highlights the emergence of C. parapsilosis as a distinct pediatric pathogen with clinical and therapeutic implications. Furthermore, our current susceptibility data include newer antifungal agents that appear to be quite active in vitro and may provide new therapeutic options for the treatment of serious yeast infections in children.

Management of device-related infections includes device removal for some catheter-related bloodstream infections and all ventriculoperitoneal shunt-related infections. The isolation of certain organisms (eg, Staphylococcus aureus, Candida spp) in children with central catheters should prompt consideration of disseminated infection. Future research may determine the impact of increasing catheter use in non-intensive care hospital settings and in home care. New technologies, such as antimicrobial-impregnated central venous catheters and ventricular shunts, show promise in reducing the infection rates of these devices.

Background: Differentiating Lyme meningitis from enteroviral meningitis remains difficult because both occur mostly in the summer and early fall. This distinction is clinically important because pathogen-specific diagnostic test results are not available immediately and only patients with Lyme meningitis require parenteral antibiotic therapy., Objectives: The objective of this study was to identify clinical and laboratory features that might help clinicians distinguish patients with Lyme meningitis from those with enteroviral meningitis., Methods: This cross-sectional study compared patients diagnosed with Lyme or enteroviral meningitis evaluated at a large children's hospital between January 1, 1999 and September 20, 2002., Results: Twenty-four patients with Lyme meningitis and 151 patients with enteroviral meningitis had median ages of 10.5 and 5.5 years, respectively (P < 0.0001). There was an equal proportion of boys with Lyme (63%) and enteroviral meningitis (62%; P = 1.0). The duration of symptoms before evaluation was longer for patients with Lyme meningitis (12 days) than with enteroviral meningitis (1 day; P < 0.0001). Cranial neuropathy was a presenting feature in 71% of children with Lyme meningitis. Cranial neuropathy, erythema migrans rash or papilledema occurred in 88% of patients with Lyme meningitis; no patients with enteroviral meningitis exhibited any of these findings (P < 0.0001). Lyme meningitis was unlikely when cerebrospinal fluid neutrophils exceeded 10% (negative predictive value, 99%)., Conclusions: We identified several clinical and laboratory features that may permit early differentiation of Lyme from enteroviral meningitis. These results may assist clinicians with decisions regarding additional testing and empiric antibiotic therapy.

Background: The importance of infections due to extended-spectrum beta -lactamase-producing Escherichia coli and Klebsiella species (ESBL-EK) has been increasingly recognized in recent years. ESBL-EK infections are of clinical concern, because few antimicrobials are available as therapeutic options. Increased reliance on carbapenems has led to increasing carbapenem resistance. Efforts to maintain current therapeutic options for ESBL-EK infections are essential., Methods: We conducted a case-control study to identify risk factors for multidrug resistance (MDR) among ESBL-EK. All patients at our institution who had an inpatient clinical culture result positive for an ESBL-EK during the period of 1 June 1997 through 31 December 2002 were eligible for inclusion. An MDR ESBL-EK was defined as ESBL-EK demonstrating resistance to trimethoprim-sulfamethoxazole, aminoglycosides, and quinolones. All available ESBL-EK isolates were characterized by pulsed-field gel electrophoresis (PFGE)., Results: Of 361 total ESBL-EK isolates, 68 (18.8%) were MDR. During the study period, the prevalence of MDR among ESBL-EK isolates increased from 12.5% to 26.9%. The only independent risk factor for MDR ESBL-EK was the infecting organism (i.e., Klebsiella pneumoniae; adjusted odds ratio, 11.7; 95% confidence interval, 4.77-28.51; P < .001). Prior antibiotic use was not independently associated with MDR ESBL-EK. PFGE patterns from K. pneumoniae isolates indicated close genetic relatedness among a substantial proportion of isolates., Conclusions: The emergence of MDR among ESBL-EK has important implications for the future ability to treat these infections. The strong association between the species of infecting organism and MDR suggests that the epidemiology in K. pneumoniae may be unique. PFGE results suggest that horizontal spread is important in the emergence of MDR ESBL-EK.

In this retrospective case series, we describe the clinical features and microbiology of 16 previously healthy children with suppurative intracranial complications of sinusitis. Most cases were male adolescents who presented with vomiting in addition to typical sinusitis symptoms. Neurologic signs were often absent. Streptococcus milleri group organisms, along with anaerobes, were common pathogens.

Objective: The increasing prevalence of infections caused by extended-spectrum beta-lactamase-producing Escherichia coli and Klebsiella species (ESBL-EK) has become a growing concern in the hospitalized patient population. Previous studies on risk factors for infection with ESBL-EK have mainly focused on adult populations, and these findings may not be relevant among the pediatric population that experiences a unique set of health care exposures and underlying conditions. The objective of this study was to define the risk factors and outcomes associated with ESBL-EK bloodstream infections in children., Methods: We conducted a nested case-control study using data from the Children's Hospital of Philadelphia from May 1, 1999, to September 30, 2003. Eligible patients were identified from the hospital database of microbiology laboratory records. All patients with ESBL-EK bloodstream infections were compared to a random sample of patients with non-ESBL-EK bloodstream infections. Risk factors analyzed included prior antimicrobial use, comorbid conditions, and demographic characteristics. Pulsed-field gel electrophoresis was performed to determine genetic relatedness of the ESBL-EK isolates., Results: Thirty-five cases and 105 control subjects were included in the study. The median age among the cases was 2 years (interquartile range: 0-11), compared with 1 year (interquartile range: 0-8) among control subjects. Patients with ESBL-EK infections were 5.8 times (95% confidence interval: 1.9-17.7) more likely to have had exposure to an extended-spectrum cephalosporin in the 30 days before infection than those with non-ESBL-EK infections. Other independent predictors of ESBL-EK infection were being female, infection with a Klebsiella species, and steroid use in the 30 days before infection. All ESBL-EK isolates were susceptible to carbapenem antibiotics. Pulsed-field gel electrophoresis analysis revealed that the ESBL-EK isolates were polyclonal. Although a substantially higher proportion of children with ESBL-EK died (in-hospital mortality: 36% vs 13%), this difference was not statistically significant., Conclusions: Receipt of extended-spectrum cephalosporins in the 30 days before infection by an Escherichia coli or Klebsiella species is significantly associated with having an ESBL-EK infection in hospitalized children. Curtailed use of cephalosporins among high-risk groups may reduce the occurrence of ESBL-EK infections. Future studies on identifying high-risk children and investigating the impact of curtailed third-generation cephalosporin use to limit additional emergence of ESBL-EK infections should be undertaken.

The capacity of live or inactivated respiratory syncytial virus (RSV) to induce B-cell memory in respiratory-associated lymphoid tissues of mice was examined. Eight weeks after primary inoculation with either live or inactivated RSV, adult BALB/c mice were challenged with 4x10(5) PFU of RSV. Protection from viral shedding and mucosal production of RSV-specific antibodies were examined at various time points after challenge. We found that primary immunization with live, but not inactivated, RSV induced complete and durable protection upon challenge within the upper and lower respiratory tract. Also, primary immunization with live, but not inactivated, RSV enhanced the production of mucosal RSV-specific immunoglobulin A (IgA) upon challenge. Secondary mucosal IgA responses were characterized by (i) the early production of mucosal IgA by B cells that reside in organized nasal-associated lymphoid tissues, cervical lymph nodes, and bronchial lymph nodes, and (ii) the subsequent production of RSV-specific IgA by mucosal effector tissues, such as the tracheal lamina propria and lung. These findings suggest that primary infection of mice with live RSV might induce mucosal IgA-committed memory B cells. A greater understanding of the characteristics of RSA-specific mucosal memory B cells may facilitate the development of an RSV vaccine.

Objective: To determine the risk factors for disseminated infection in hospitalized children with candidemia., Methods: We performed a nested case-control study within a cohort of hospitalized children with candidemia. The cohort was defined by all patients with positive blood cultures for Candida species in a large, urban, academic, tertiary care children's hospital from 1998 to 2001. Cases were patients with clinical, microbiologic or radiographic evidence of disseminated candidiasis. Controls were patients with no evidence of disseminated candidiasis., Results: Among 168 total children with candidemia, the median age was 3.5 years (interquartile range, 0.6-14.3). There were 189 episodes of candidemia. Candida species included:Candida albicans (41%), Candida parapsilosis (24%), Candida glabrata (13%) and Candida tropicalis (9%). The most common underlying diagnoses were oncologic (24%), gastrointestinal (15%) and cardiac (10%) diseases. Eighty-nine patients (53%) were admitted to an intensive care unit, 46 (27%) to a general pediatric or surgical ward and 33 (20%) to the oncology ward. Of the 168 patients with candidemia, 153 were included in the analysis of risk factors for disseminated candidiasis. Of 153 (17%) patients, 26 had evidence of organ dissemination. Organ involvement was most commonly identified in the lung (58%), followed by the liver (23%), kidney (16%), brain (12%), spleen (8%), eye (8%) and heart (8%). Eight of the 26 patients had evidence of dissemination to more than 1 organ. Independent risk factors for disseminated candidiasis were persistently positive blood cultures for Candida (>3 days) with a central venous catheter in place (odds ratio, 3.0; 95% confidence interval, 1.2, 7.8; P = 0.02) and immunosuppression (odds ratio, 2.9; 95% confidence interval, 1.2, 7.0; P = 0.02)., Conclusions: Prolonged duration of candidemia with a central venous catheter in place and immunosuppression were independent risk factors for disseminated candidiasis in children with candidemia. Furthermore review of the epidemiology of candidemia at our institution revealed a heterogeneous population of children at risk for candidemia and a predominance of non-albicans species as the cause of these infections. Future studies are needed to determine the extent of evaluation needed for detecting dissemination among children with candidemia and to explore interventions for its prevention.

Rabbit serum samples from eleven different research facilities were evaluated for the presence of immunoglobulin G against Pasteurella multocida by using an enzyme-linked immunosorbent assay (ELISA). Each facility which submitted serum samples also provided a brief history of each rabbit colony tested. Rabbits from colonies reported to have endemic P. multocida or of undetermined status had 83 (58.9%) of 141 rabbits that were positive. Colonies reported to be free from P. multocida had 110 (92.4%) of 119 rabbits that were negative by ELISA. The ELISA test described here showed a high degree of agreement (92-94%) with two other P. multocida ELISAs at different diagnostic facilities. This study confirms that an ELISA testing for serum antibodies against the P. multocida is a reliable diagnostic tool to screen colonies for P. multocida.

Few published reports exist describing morbidity and mortality in domestic zebra finch colonies maintained in a laboratory animal setting. A retrospective study of clinical disease and mortality in quarantined adult zebra finches was performed. Animals were observed during the 2 week quarantine period and for at least 1 month afterwards (42 days). Signs of disease, including feather and beak abnormalities, oculonasal discharge, increased respiratory rate or stridor, abdominal enlargement, pasty vent, diarrhea, lameness and pectoral muscle loss, were evaluated in our colony during this time. History, physical examination, laboratory testing and postmortem evaluation were used to determine causes of clinical disease. Common clinical findings in sick finches included sudden death, ruffled feathers, increased respiratory rate or gape mouthed breathing, pasty vent or frank diarrhea, and beak discoloration. Organisms frequently isolated were Staphylococcus spp., E. coli, Enterobacter spp., and Coccidia spp. Of the finches that died while in the colony (29.5%), 23.0% died in the first week after arrival. Pathogens frequently isolated from tissues cultured at necropsy included: E. coli, Staphylococcus aureus, Enterobacter spp., and Candida albicans. When observed, pathological lesions consisted of air sacculitis, fibrinopurulent polyserositis and ventriculitis.