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Pertussis in young infants is a unique, severe, afebrile, cough illness that is frequently fatal.All pertussis cases ≤120 days of age admitted to a pediatric intensive care unit in California between October 1, 2013, and April 25, 2015, were evaluated.Of 100 pertussis patients ≤120 days of age admitted to pediatric intensive care unit, there were 5 deaths. The white blood cell counts in the fatal cases were significantly higher than in the nonfatal cases. Thirty-four percent of patients were intubated, 18% received inotropic and/or vasoactive support, 22% received steroid, 4% received extracorporal membrane oxygenation, and 3% underwent exchange blood transfusion. The median age at the time of illness onset in the patients who died was 23 days.These data, as well as data from previous California studies, suggest updated strategies for the management of severe pertussis. These include perform serial white blood cell counts, treat all presumptive cases with azithromycin, evaluate for pulmonary hypertension, intubate and administer oxygen for apneic episodes and administer inotropic/vasoactive agents for cardiogenic shock. Do not administer steroids or nitric oxide. Criteria for exchange blood transfusion therapy for leukocytosis with lymphocytosis are suggested.

Fever and neutropenia (FN) is one of the most common, life-threatening, and costly complications of treatment for childhood cancer [1–3]. Although initial blood cultures identify bloodstream infections (BSI) in 10–20% of children with FN, the majority of episodes do not have an identified infectious etiology, and fever persists despite antibiotic therapy in up to 40% of cases [4–7]. Although blood cultures are frequently repeated in children with persistent FN, it is unclear how often this strategy identifies additional BSI, and how management is altered based on subsequent blood cultures. Potential harms of excessive blood culture collection include iatrogenic blood loss, which may increase transfusion requirements, and false positive results, which lead to additional laboratory testing, unnecessary antibiotic therapy, and increased costs [8–10]. The optimal approach to repeating blood cultures during persistent FN was identified as an important research gap in recent pediatric FN guidelines [11]. Prior studies examining the yield of subsequent blood cultures in patients with FN have demonstrated varying rates of new BSI. In an adult hematopoietic stem cell transplant (HSCT) cohort, 1 (0.9%) of 109 patients who had blood cultures collected after day 1 of FN had a new pathogen identified by follow-up culture [12]. In a study of children with FN whose initial cultures were negative, new BSI were identified via subsequent cultures in 24 (10%) of 220 episodes [13]. Because secondary infections may occur during treatment for the initial infection, it is also important to evaluate the yield of subsequent blood cultures in children whose initial cultures are positive [6, 14]. Subsequent blood culture yield should also be evaluated in pediatric HSCT recipients, a group with high incidence of persistent FN and high risk for BSI [4, 15]. At our center, blood cultures are repeated every 24 hours in the setting of ongoing FN. We evaluated the diagnostic yield of subsequent cultures in order to better characterize the utility of this approach in children with persistent FN, including those with previous positive cultures and HSCT recipients.

Background Coccidioidomycosis is a spectrum of diseases caused by the dimorphic fungi Coccidioides. Current regimens for severe or disseminated disease include fluconazole, itraconazole, or amphotericin; newer triazoles (ie, voriconazole, posaconazole) have been demonstrated to be useful in refractory disease. Previous reported experience with combination triazole and caspofungin therapy has been very limited; however, the utility of this combination for treatment of other invasive fungal diseases suggests potential benefit in refractory coccidioidomycosis. Methods We conducted a retrospective review of 9 pediatric patients treated with combination voriconazole and caspofungin (V/C) salvage therapy for refractory coccidioidomycosis at two children's hospitals between January 2000 and June 2012. Results Nine children with refractory coccidioidomycosis were treated with V/C salvage therapy after failing conventional therapy consisting of a triazole, amphotericin B, or a combination of both. Eight of the 9 patients are currently in remission; 1 patient with central nervous system involvement continues to progress. Conclusions We report our positive clinical experience treating medically refractory coccidioidomycosis in the pediatric population with concurrent voriconazole and caspofungin therapy. Additional in vitro and in vivo evaluations are warranted to support the role of V/C salvage therapy for refractory coccidioidomycosis.

© 2015 Wolters Kluwer Health, Inc. All rights reserved. BACKGROUND:: Without prophylaxis, Pneumocystis jiroveci pneumonia (PCP) develops in 5-15% of pediatric hematopoietic stem cell transplant (HCT) patients with mortality above 50%. Trimethoprim-sulfamethoxazole (TMP-SMZ) is standard PCP prophylaxis; pentamidine is frequently used as second-line prophylaxis due to TMP-SMZ’s potential for cytopenias. Monthly IV pentamidine has variable efficacy with PCP infection rates of 0-10% in pediatric patients, and higher breakthrough rates in those

The complexity of congenital cardiac defects and the aggressive medical management required to support patients through their recovery place children at high risk for surgical site infection (SSI).We conducted a retrospective review of children undergoing cardiothoracic surgery at a tertiary care referral center between January 1, 2000, and June 30, 2001. Preoperative, intraoperative, and postoperative data were assessed by multivariate analysis.Of 726 surgical procedures performed in 626 patients, SSIs occurred after 46 procedures performed in 46 patients (6.3%). Infections were superficial (n = 22; 47.8%), deep tissue (n = 7; 15.2%), or organ space (n = 17; 37.0%), including 5 episodes of mediastinitis. Median time to SSI was 10 days; 36% of the infections were identified after discharge. On multivariate analysis, children with SSIs were more likely to have been30 days old (odds ratio [OR], 2.9; 95% confidence interval [CI], 1.2-70), to have a perioperative medical device, and to use parenteral nutrition (OR, 3.3; 95% CI, 1.4-7.9). Multiple severity of illness scores, the Risk Adjustment for Congenital Heart Surgery (RACHS-1) category, and longer duration of postoperative antimicrobials were not associated with SSI.The use of perioperative medical interventions increases the risk of SSI in young children after cardiac surgery. Prolonged postoperative courses of antimicrobials should be avoided in the absence of documented infection.

VZV is an important cause of morbidity and mortality among patients after hematopoietic SCT (HSCT). There is controversy surrounding the use of the live attenuated varicella vaccine (LAVV) in this population due to concerns that the immunization may cause VZ-related disease. The Blood and Marrow Transplant (BMT) group at the University of California, San Francisco (UCSF) Children's Hospital has been recommending the LAVV for immunocompetent HSCT patients since 1995. We retrospectively examined the incidence of post-immunization complications attributable to the LAVV in pediatric patients after HSCT. We also reported seroconversion rates when possible. Among 68 recipients of the LAVV after HSCT, 3 (4.4%; 95% confidence interval (CI)=1.0-12.7%) experienced mild-to-moderate symptoms potentially attributable to vaccination, and there were no severe reactions. Among 28 patients analyzed for seroconversion, 18 (64.3%; 95% CI=45.8-79.4%) seroconverted, 3 (10.7%; 95% CI 2.9-28.0%) possibly seroconverted and 7 (25.0%; 95% CI=12.4-43.6%) failed to seroconvert. It appears safe to administer the LAVV to immunocompetent patients after HSCT. Prospective studies are needed to more accurately determine rates of vaccine complications, efficacy and immunologic responses to vaccination.

We present three cases ofVLBW infants with Candida albicans fungemia who had brainmicroabscesses (

Summary Two cases of invasive fungal sinusitis are presented which occurred in immunocompromised pediatric patients and were successfully resolved. The management of these cases can provide important recommendations in regards to identification and interventions, both medical and surgical, as well as the timing of treatment.

The current dosage of zidovudine for children is 180 mg/m2 every 6 h. To investigate whether a lower dosage was equally effective, human immunodeficiency virus (HIV)-infected children (3 months to 12 years) with mild to moderate symptoms were randomly assigned to receive either high-dose (180 mg/m2/dose) or low-dose (90 mg/m2/dose) zidovudine (double-blind). Treatments were compared with respect to neuropsychologic function, survival, clinical and laboratory evidence of disease progression, and safety and tolerance. Four hundred twenty-six HIV-infected children were enrolled; median time for receipt of study drug was 35 months. Zidovudine in either dose was well tolerated, with no difference in efficacy or tolerance by treatment group using any clinical or laboratory parameter. In children with mild to moderate disease, a reduction of zidovudine to 90 mg/m2/dose will result in substantial cost savings and should be the recommended dose.

We report 3 children who, after undergoing hematopoietic stem cell transplant, developed herpes simplex virus (HSV) stomatitis while receiving weekly cidofovir as preemptive treatment for cytomegalovirus infection. All patients responded well to treatment with either acyclovir or ganciclovir. Despite the in vitro susceptibility of HSV to cidofovir, once-weekly treatment with this agent may not be adequate prophylaxis in pediatric patients.

Community-associated methicillin-resistant Staphylococcus aureus (CA-MRSA) has caused a nationwide epidemic of skin and soft-tissue infections in ambulatory pediatrics. Antibiotic treatment recommendations suggest incorporating local epidemiology for the prevalence of CA-MRSA. We sought to identify the antibiotic strategy with the highest probability of activity and to identify threshold values for epidemiologic variables including bacterial prevalence and antibiotic resistance.We used decision analysis to evaluate 3 empiric antibiotic strategies: clindamycin, trimethoprim/sulfamethoxazole (T/S), and cephalexin. We calculated the probability of activity against the bacteria causing the infection (CA-MRSA, methicillin-sensitive S. aureus and group A Streptococcus [GAS]) by incorporating estimates of prevalence and antibiotic resistance to determine the optimal strategy. Sensitivity analysis was used to identify thresholds for prevalence and antibiotic resistance where 2 strategies were equal.Clindamycin (0.95) and T/S (0.89) had substantially higher probability of activity than cephalexin (0.28) using baseline estimates for bacterial prevalence and antibiotic resistance. Cephalexin was the optimal antibiotic only when CA-MRSA prevalence was10%. The probability of activity for clindamycin and T/S was highly sensitive to changes in the values for bacterial prevalence (both CA-MRSA and GAS) and CA-MRSA resistance to clindamycin.Empiric treatment of skin and soft-tissue infections with either clindamycin or T/S maximizes the probability that the antibiotic will be active when CA-MRSA prevalence is10%. Deciding between T/S and clindamycin requires consideration of antibiotic resistance and prevalence of GAS. This model can be customized to local communities and illustrates the importance of ongoing epidemiologic surveillance in primary care settings.

Forty-two infants of HIV-seropositive women were evaluated to determine the value of polymerase chain reaction (PCR) in the early detection of HIV infection. All infants less than 6 months old had a simultaneous PCR and culture for HIV. There was an 88% concordance between the two techniques. PCR results showed an excellent correlation with clinical outcome; no PCR-negative patient has subsequently been found to be infected. Occasional false-positive or equivocal PCR results did occur. There was one false-negative culture. PCR is a rapid and sensitive diagnostic test for the early diagnosis of HIV infection in infants at risk, but at present it should be performed in conjunction with other diagnostic tests and good clinical follow-up.

To diagnose infection with the human immunodeficiency virus (HIV) soon after birth in infants born to HIV type 1-infected women, we developed antiviral IgA Western blot and dot blot assays with recombinant HIV-1 proteins. Thirty-three infants born to HIV-1-seropositive mothers and nine infants born to HIV-1-seronegative intravenous drug-abusing mothers were followed prospectively. Infection was documented by positive virus culture. Results with the polymerase chain reaction were used for comparison. Twelve infants were found infected with HIV-1; the earliest age at which cultures became positive ranged from birth to 31 weeks of age. Of the 12 culture-positive infants, 10 had anti-HIV IgA antibodies detectable initially between birth (cord blood) and 27 weeks of age. Anti-HIV IgA was not present in the uninfected infants or in the control subjects, either by Western blot or dot blot assays. Testing for anti-HIV IgA antibodies with recombinant HIV-1 proteins is an effective method for detecting viral infection in newborn and young infants.

CD8 cells from human immunodeficiency virus (HIV)-infected adults and children can show cytotoxic as well as noncytotoxic activity against viral replication. The noncytotoxic anti-HIV response, measured by suppression of acute viral infection of CD4 cells, has also been observed in uninfected adults who have a history of exposure to HIV. This CD8 cell antiviral activity was found to be detectable as well in approximately 50% of uninfected children born of infected mothers. The findings could reflect a protective response of the children to HIV after being exposed to the virus.

Background Direct fluorescent antibody (DFA) testing of nasopharyngeal wash specimens is a rapid and reliable means of diagnosing respiratory viral infection. The utility of DFA testing in the evaluation of febrile children without respiratory symptoms has not been critically evaluated. It is not known whether clinical or demographic factors apart from respiratory symptoms are associated with a positive DFA or whether a positive DFA is more likely to be associated with lower or upper respiratory tract symptoms (RTS). Methods This is a retrospective case-series of 756 consecutive nasopharyngeal specimens with respiratory DFA testing performed at the University of California San Francisco from November 1, 2002 through October 31, 2003. Results No RTS was a statistically significant predictor of negative DFA [odds ratio (OR), 0.03; 95% confidence interval (CI), 0.004-0.2; P = 0.001] compared with lower RTS. Male subjects were more likely than female subjects to have a positive DFA (OR 1.8; 95% CI 1.1-2.8; P = 0.02). Specimens collected from April to October were less likely to have a positive DFA (OR 0.4; 95% CI 0.2-0.7; P = 0.001). Specimens collected at the time of hospital admission and during a hospitalization were less likely to have a positive DFA (OR 0.5; 95% CI 0.3-0.9; P = 0.01 and OR, 0.07; 95% CI 0.02-0.2; P = 0.001, respectively) compared with specimens collected in the outpatient setting. Conclusion The yield of testing children without respiratory tract illness is extremely low.

RISK OF INFECTION, AND ANTIBIOTIC PROPHYLAXIS, are topics that have been debated for decades by those involved in the care of children undergoing cardiac surgery. In this review we attempt to analyse what is known and what has been postulated about this subject. Suggestions regarding the best strategies for treatment have been formulated, based on published reports, as well as current practices worldwide.

In a recent Oregon case, the state successfully sued for custody of an infant to prevent his human immunodeficiency virus (HIV)‐infected mother from breastfeeding him and to require antiretroviral prophylaxis. As more HIV-infected women give birth, pediatricians may increasingly face dilemmas when parents reject medical recommendations to forgo breastfeeding and to administer antiretroviral prophylaxis to the infant. Such disagreements create ethical dilemmas because pediatricians have an obligation to both protect the infant and respect parental decision making. Pediatricians need to balance these obligations in deciding whether to ask the courts to intervene on the infant’s behalf. To that end, we analyze the legal and ethical issues that arise when an HIV-infected mother refuses interventions to reduce neonatal transmission of HIV to her infant, provide an approach for addressing these disagreements, and present illustrative scenarios in which pediatricians should, may, and should not seek a court order to intervene. Arch Pediatr Adolesc Med. 2001;155:927-933

To assess the risk of transmission of hepatitis C virus from mother to infant during pregnancy or at delivery, we measured the antibody to hepatitis C virus (anti-HCV) by an enzyme-linked immunosorbent assay (ELISA) and a recombinant immunoblot assay (RIBA) in serum from 43 infants whose mothers took illicit drugs intravenously. Passively transmitted maternal anti-HCV was detected in 17 (40%) of the 43 infants tested with the ELISA during the first 4 postnatal months. Ten of these initially seropositive infants were followed to 15 months of age or beyond; anti-HCV cleared from nine infants and persisted in one. Among 24 initially seronegative infants, three (12.5%) showed persistent anti-HCV at 6, 11, and 18 months of age, respectively. The remaining two infants were initially tested with ELISA at 6 and 15 months of age; both were transiently seropositive, but anti-HCV disappeared by 12 and 24 months of age, respectively. Among the 17 infants with maternal antibody, nine with ELISA reactions greater than 2.5 optical density units were reactive by RIBA: the eight with weaker reactivity by ELISA were nonreactive by RIBA. When serum samples from the four infants who showed persistent reactivity by ELISA were tested with RIBA, one, reacted to both antigens displayed by RIBA (C-100 and 5-1-1), one reacted to the 5-1-1 antigen only, and two were nonreactive. Serum transaminase values were elevated in three of these four infants; all four were also infected with human immunodeficiency virus. The results indicate that vertically transmitted hepatitis C virus may be a cause of hepatitis in infants, especially those coinfected with human immunodeficiency virus. Neonates at risk of hepatitis C virus infection should be monitored beyond 12 months of age. The interpretation of tests for anti-HCV antibody during infancy requires further investigation.

Objective To assess the utility of a panviral DNA microarray platform (Virochip) in the detection of viruses associated with pediatric respiratory tract infections (RTIs). Study design The Virochip was compared with conventional direct fluorescent antibody (DFA)- and polymerase chain reaction (PCR)-based testing for the detection of respiratory viruses in 278 consecutive nasopharyngeal aspirate samples from 222 children. Results The Virochip was superior in performance to DFA, showing a 19% increase in the detection of 7 respiratory viruses included in standard DFA panels, and was similar to virus-specific PCR (sensitivity, 85% to 90%; specificity, ≥99%; positive predictive value, 94% to 96%; negative predictive value, 97% to 98%) in the detection of respiratory syncytial virus, influenza A, and rhinoviruses/enteroviruses. The Virochip also detected viruses not routinely tested for or missed by DFA and PCR, as well as double infections and infections in critically ill patients that DFA failed to detect. Conclusions Given its favorable sensitivity and specificity profile and expanded spectrum for detection, microarray-based viral testing holds promise for clinical diagnosis of pediatric RTIs.

The major limitation of mismatched bone marrow transplantation is fatal graft versus host disease (GVHD). We processed haplotype-identical parental marrow with soybean agglutinin (SBA), sheep erythrocytes (SRBC), and neuraminidase-treated SRBC (N-SRBC) to enrich for marrow stem cells and remove mature T cells. Nine patients with severe combined immunodeficiency disease (SCID) who lacked histocompatible donors received these SBA-negative, SRBC-negative, N-SRBC-negative marrow transplants (0.5-5.0 X 10(8) cells/kg). Seven of the nine patients (78%) had documented T-lymphocyte engraftment based on HLA typing and/or chromosomal analysis. Six patients showed evidence of B-cell immunity on the basis of increased immunoglobulin levels, isohemagglutinins, and/or HLA-DR typing of non-T cells. Three patients received marrow ablative chemotherapy pretransplant for maternal-fetal GVHD; neutrophil engraftment occurred between 9 and 17 days posttransplantation, erythrocytes engrafted within 3-4 weeks of transplantation, and platelet recovery was seen between day 17 and day 49 following the transplants. No immunosuppression was given prophylactically posttransplant. Three patients had no GVHD, two had transient rash and/or fever, and two developed mild focal (stage I) chronic cutaneous GVHD. Of the seven who engrafted, five (71%) are alive and clinically well without GVHD 18-35 months posttransplant. These data demonstrate that SBA- and SRBC/N-SRBC-treated haploidentical marrow transplantation results in functional lymphocyte engraftment in SCID without significant GVHD, and can be used for some patients who otherwise would have no hope for survival.

Immune globulin preparations clearly provide safe and effective passive prophylaxis in a variety of viral infections: hepatitis A, hepatitis B, primary varicella zoster, measles, rubella, and rabies. When available, specific preparations (HBIG, VZIG, RIG) should be used. The use of CMVIG remains controversial at this time. Only recently have immunoglobulins been used for therapy of viral infections; however, their use in Kawasaki disease, AIDS, and echovirus in patients with hypogammaglobulinemia appears promising.

To determine the usefulness of DNA amplification by polymerase chain reaction for the early identification of human immunodeficiency virus type 1 (HIV-1) infection in infants and children, we compared the polymerase chain reaction and concurrent viral cultures of peripheral blood mononuclear cells from 25 high-risk subjects aged 5 weeks to 8 years. In two separate primer pairs, HIV-1 proviral DNA gag sequences were successfully identified in cell lysates from seven patients, including two infants with previously indeterminate HIV-1 status on the basis of serologic and culture results. In the remaining 18 patients the polymerase chain reaction was negative for HIV-1. Simultaneously grown HIV-1 cultures concurred with polymerase chain reaction results for all patients. In an 18-month-old infant who had had a single HIV-1 positive culture at 1 month of age with four subsequent negative cultures, both polymerase chain reaction and HIV-1 culture were negative. Our data demonstrate the clinical applicability of polymerase chain reaction on crude cell lysates for the rapid, early, definitive detection of HIV-1 infection in high-risk infants and children.

TRIALS WITH PNEUMOCOCCAL POLYSACCHARIDE vaccine have shown that patients with sickle cell disease who are immunized at or after 2 years of age have a good antibody response and fewer pneumoeoccal infections than unimmunized controls? However, the duration of the increased antibody levels has not been studied. The effect of booster immunization has been evaluated at 1 to 1 89 years after the original dose in a population of normal adults. Adverse local reactions were frequent, but no significant increase in antibody titers occurred, 2 We undertook this study in patients with sickle cell disease to determine (1) the duration of the antibody response 8 to 9 years after primary immunization, (2) the incidence of systemi c and severe local reactions with booster immunizations, and (3) the serologic response to booster immunization.

An infant who received multiple transfusions during the first few days of life for rhesus disease became ill with recurrent infections when 6 months old. Hepatitis, thrush, Candida dermatitis, otitis media, and disseminated Mycobacterium avium intracellulare infection occurred by 14 months of age. Immunological studies showed raised immunoglobulin levels, decreased mononuclear-cell responses to allogeneic cells and mitogen, and a decreased helper/suppressor cell ratio. It was determined that one of the blood donors, who was well at the time of blood donation, had died 17 months after with multiple opportunistic infections and acquired immunodeficiency. The clinical and laboratory findings in our patient suggest that he acquired a transmissible infectious agent from a blood transfusion, resulting in acquired immunodeficiency, and that this agent was not cytomegalovirus, Epstein-Barr virus, or hepatitis B virus.

We evaluated 16 children at high risk for AIDS because of mothers infected with HIV. Two children were persistently seropositive and had laboratory and clinical evidence of HIV infection but had no detectable infectious HIV in their peripheral blood mononuclear cells (PBMC). Seven children, all of whom had clinical and laboratory evidence of HIV infection, were seropositive and virus culture-positive. One child who died at 10 months of age of candida septicemia was HIV antibody-negative but HIV was grown from cultures of his PBMC. Six children had no serologic or virologic evidence of HIV infection; of these, four who were asymptomatic with normal laboratory studies were HIV antibody-positive up to 12 months of age but became antibody-negative by 15 months of age. These observations indicate that: (1) as many as 60% of infants of infected mothers may be infected with HIV; (2) maternal antibody can result in a false-positive or false-negative diagnosis of HIV infection in infants exposed in utero or perinatally, and (3) the use of viral cultures for HIV is valuable for the early diagnosis of maternally transmitted HIV infection.

The limitation of mismatched BMT is fatal graft vs. host disease (GVHD). We processed haplotype mismatched parental marrow with SBA to enrich for stem cells and reduce GVHD and successfully treated 6 patients with severe combined immune deficiency disease. HLA chimerism was found within 3 weeks post BMT. All the patients demonstrate T cell and 2 have evidence of B cell engraftment. T cell numbers and responses to phytohemagglutinin (PHA) and alloantigen pre and post BMT are: In #2,5,6 who required pre BMT immunosuppression for maternal GVHD, neutrophil, RBC, and platelet engraftment occurred by days 11,26,32 respectively. No immunosuppression was given post BMT. 2 patients had no GVHD, 3 had transient rash/fever, and only 1 developed persistent rash. Patients are now 3 to 17mo. post BMT. These results demonstrate that treated mismatched BMT can result in engraftment without significant GVHD and can be used for patients who otherwise have limited hope for survival.