Comprehensive strategy including prophylactic mupirocin to reduce Staphylococcus aureus colonization and infection in high-risk neonates.

OBJECTIVE: To examine the use of long-term prophylactic mupirocin as part of a comprehensive strategy in reducing Staphylococcus aureus colonization and infection in a neonatal intensive care unit (NICU). STUDY DESIGN: Twice daily mupirocin was applied to all infants admitted to the NICU throughout hospitalization starting in 2004. S. aureus surveillance was implemented in 2008. The efficacy of these practices was evaluated with a retrospective review of infants admitted from 2004 to 2010 found to be colonized or infected with S. aureus. RESULT: During the study period, 66 of 6283 NICU infants had a S. aureus infection with 67% methicillin resistance. There were three distinctive S. aureus outbreaks, the first being a methicillin-resistant strain July 2004. After implementation of daily mupirocin, the outbreak was eradicated and the rate of S. aureus infection significantly decreased (1.82 to 0.40/1000 patient-days-at-risk, P=0.0049). Mupirocin was discontinued March 2005 followed by a methicillin-sensitive S. aureus outbreak November 2005. In December 2005, mupirocin was reinstituted and has continued to present day, again significantly reducing S. aureus infections (1.42 to 0.33/1000 patient-days-at-risk, P<0.0001) with zero isolates resistant to mupirocin. In the pre-mupirocin period, S. aureus colonization was upwards of 60% now with rates typically <5%. S. aureus colonization strongly predicted later invasive infection (P<0.0001). CONCLUSION: Although controversial, prophylactic mupirocin in all NICU infants has acted as a barrier to colonization and markedly decreased S. aureus infection rates over a 5-year period.

Modulation of adhesion molecules and monocyte chemoattractant protein by tumor necrosis factor-alpha and salicylic acid in primary human coronary artery endothelial cells.

Kawasaki disease (KD) is an illness characterized by vascular inflammation of coronary arteries leading to coronary aneurysms and thromboses. Infiltration of immune cells into the intima and adventitia are observed in autopsy tissues of patients with KD. Using semi-quantitative RT-PCR and cell-based ELISA, we demonstrated that tumor necrosis factor-a induced the expression of intercellular adhesion molecules-1 and E-selectin, as well as monocyte chemoattractant protein-1, in a time- and dose-dependent manner in primary human coronary artery endothelial cell cultures. This increase was inhibited by salicylic acid (NaSal), and involved the transcription factor NF-kappaB. Based on these data, we suggest a pathogenetic mechanism for KD, whereby immune cells are attracted to sites of inflammation, undergo extravasation, release enzymes that assist in vascular remodeling, thereby weakening the endothelium and hastening the process of aneurysm formation. NaSal, in addition to preventing thrombosis and lowering fever in KD, may also function in down-regulating adhesion molecules during the inflammatory stage of KD.

A revised decision analysis of strategies in the management of febrile children at risk for occult bacteremia.

Two decision analysis reports published in 1991 concluded that the strategy of routine blood culture and empiric antibiotics was the superior strategy for febrile children at risk for occult bacteremia. This report describes a decision analysis of treatment strategies for these children considering the following changes that have occurred since then: (1) Hemophilus influenzae B incidence is low because of widespread vaccine use; (2) the emergence of resistant Streptococcus pneumoniae may affect the clinical effectiveness of empiric antibiotics in the future; and (3) the negative consequences of unnecessary antibiotic treatment have yet to be well defined. A decision analysis approach, modifying the original assumptions, was carried out. Sensitivity analyses were conducted on all assumption variables. Strategies employing empiric antibiotics were found to have the best outcomes, assuming low negative treatment consequences. If a high level of negative treatment consequences is assumed, strategies using a white blood cell count (WBC) are superior. If a very high level of negative treatment consequences is assumed, the strategy of no tests and no empiric antibiotic treatment is usually superior, unless the frequency of bacteremia is 10% or higher and empiric antibiotic efficacy is high, in which case a WBC strategy is superior. This information can be used to select a treatment strategy based largely on the estimation of the negative consequences of treatment.

Gowning does not affect colonization or infection rates in a neonatal intensive care unit.

OBJECTIVE: To study the effect of gowning in a neonatal intensive care unit on colonization patterns, necrotizing enterocolitis, respiratory syncytial virus and other infections, mortality, and traffic and handwashing patterns. METHODS: Alternate 2-month gowning and no-gowning cycles were established in a 24-bed level III neonatal intensive care unit for 8 months, with respiratory site, umbilical, and stool surveillance cultures done weekly on all patients. Traffic flow and handwashing compliance were evaluated by direct observation. RESULTS: Demographic data did not differ between periods. There were no significant differences between the gowning and no-gowning periods in the rates of bacterial colonization, any type of infection, or mortality. There was no effect on traffic flow or handwashing compliance. CONCLUSION: Gowning in the neonatal intensive care unit is an unnecessary custom without benefit in neonatal colonization, infection rates, mortality, traffic patterns, and handwashing behavior.

Characterization of T cell repertoire changes in acute Kawasaki disease.

Kawasaki disease (KD) is an acute multisystem vasculitis of unknown etiology that is associated with marked activation of T cells and monocyte/macrophages. Using a quantitative polymerase chain reaction (PCR) technique, we recently found that the acute phase of KD is associated with the expansion of T cells expressing the V beta 2 and V beta 8.1 gene segments. In the present work, we used a newly developed anti-V beta 2 monoclonal antibody (mAb) and studied a new group of KD patients to extend our previous PCR results. Immunofluorescence analysis confirmed that V beta 2-bearing T cells are selectively increased in patients with acute KD. The increase occurred primarily in the CD4 T cell subset. The percentages of V beta 2+ T cells as determined by mAb reactivity and flow cytometry correlated linearly with V beta expression as quantitated by PCR. However, T cells from acute KD patients appeared to express proportionately higher levels of V beta 2 transcripts per cell as compared with healthy controls or convalescent KD patients. Sequence analysis of T cell receptor beta chain genes of V beta 2 and V beta 8.1 expressing T cells from acute KD patients showed extensive junctional region diversity. These data showing polyclonal expansion of V beta 2+ and V beta 8+ T cells in acute KD provide additional insight into the immunopathogenesis of this disease.

Immunoglobulin allotypic markers in Kawasaki disease.

We investigated the possible relationship of the distribution of immunoglobulin allotypic markers for susceptibility to Kawasaki disease in Japanese, Japanese-American, and white American populations. The kappa-chain allotype Km1 was present in 25.6% of sera from white patients with Kawasaki disease and in 14.4% of control sera (p < 0.01), and the combination of Km1 with Gm heterozygosity was present in 17.9% of white patients with Kawasaki disease and in 6.4% of control sera (p < 0.0001). In all populations studied, differences were observed between the patients with Kawasaki disease and the race-matched control subjects. The findings support the hypothesis that one or more unknown infectious agents may trigger genetically influenced immune responses that result in clinically recognizable Kawasaki disease.

Intravenous immune globulin for the prevention of nosocomial infection in low-birth-weight neonates. The Multicenter Group for the Study of Immune Globulin in Neonates.

BACKGROUND: Nosocomial infection is a major risk for premature infants with very low birth weights. One reason for their susceptibility to infection may be antibody deficiency, since there is little transfer of maternal IgG to the fetus before 32 weeks' gestation. METHODS: We conducted a multicenter, double-blind study of neonates weighing 500 to 1750 g at birth. A total of 588 neonates were randomly assigned, with stratification for birth weight, to receive periodic intravenous infusions of either immune globulin (500 mg per kilogram of body weight per day) or a placebo. Mortality, morbidity, and nosocomial infection during the next 56 days were assessed. RESULTS: The infusions were well tolerated; mild, reversible adverse reactions occurred in five infants in each group. There was a significant reduction in the risk of a first nosocomial infection in the recipients of immune globulin as compared with the placebo recipients (relative risk, 0.7; 95 percent confidence interval, 0.5 to 0.9). About 85 percent of the nosocomial infections were bacterial; the majority of these were caused by coagulase-negative staphylococci or Staphylococcus aureus. The neonates who received immune globulin had fewer mean days of hospitalization than the controls (62 vs. 68, P = 0.15); among the infants with infections, the difference in the mean length of the hospital stay was even greater (80 days vs. 101 days, P = 0.02). CONCLUSIONS: For premature infants weighing between 500 and 1750 g at birth, treatment with intravenous infusions of immune globulin is safe and reduces the risk of nosocomial infection.

Selective expansion of T cells expressing T-cell receptor variable regions V beta 2 and V beta 8 in Kawasaki disease.

Kawasaki disease (KD) is an acute vasculitis complicated by the development of coronary artery abnormalities. The etiology of KD is unknown. Based on the observation that KD is associated with marked activation of T cells and monocyte/macrophages, we hypothesized that KD may be caused by a superantigen [e.g., a bacterial toxin that stimulates T cells expressing particular T-cell receptor beta chain variable (V beta) gene segments]. Peripheral blood T cells from patients in the acute and convalescent phases of KD and from various control groups were analyzed for T-cell receptor V beta gene expression by using a quantitative PCR technique and cytofluorographic analysis with available anti-V beta monoclonal antibodies. Patients with acute KD demonstrated significantly elevated levels of circulating V beta 2+ and V beta 8.1+ T cells compared to the other control groups. none of the other 20 V beta populations analyzed by quantitative PCR were found to be significantly elevated. Using flow cytometry, we confirmed a significant elevation of T cells reactive with anti-V beta 8.1 and the lack of change in several other V beta subsets--i.e. V beta 5.1, -5.2, -6.7, and -12. During the convalescence phase of KD, there was a reduction in the abnormal levels of V beta 2+ and V beta 8.1+ T cells. These observations suggest that KD may be caused by a superantigen and may provide insight into the nature of the etiologic agent.

Hepatitis A outbreak in a neonatal intensive care unit: risk factors for transmission and evidence of prolonged viral excretion among preterm infants.

An outbreak of hepatitis A virus (HAV) infection in a neonatal intensive care unit (NICU) provided the opportunity to examine the duration of HAV excretion in infants and the mechanisms by which HAV epidemics are propagated in NICUs. The outbreak affected 13 NICU infants (20%), 22 NICU nurses (24%), 8 other staff caring for NICU infants, and 4 household contacts; 2 seropositive infants (primary cases) received blood transfusions from a donor with HAV infection. Risk factors for infection among nurses were care for a primary infant-case (relative risk [RR], 3.2), drinking beverages in the unit (odds ratio [OR], infinity), and not wearing gloves when taping an intravenous line (OR, 13.7). Among infants, risk factors were care by a nurse who cared for a primary infant-case during the same shift (RR, 6.1). Serial stool samples from infant-cases were tested for HAV antigen (HAV-Ag) by enzyme immunoassay and HAV RNA by nucleic acid amplification using the polymerase chain reaction. Infant-cases excreted HAV-Ag (n = 2) and HAV RNA (n = 3) 4-5 months after they were identified as being infected. Breaks in infection control procedures and possibly prolonged HAV shedding in infants propagated the epidemic in a critical care setting.

The impact of pediatric HIV infection on emergency services.

A thorough understanding of the spectrum and ramifications of pediatric HIV infection is important to the emergency physician. Rising reports of cases in rural populations and the vertical transmission from mother to infant are important changes in HIV epidemiology. Nearly all organ systems are either directly or indirectly involved and problems encountered, including diagnostic and therapeutic considerations by organ system, are reviewed. The role of the emergency physician in caring for HIV-infected infants and children includes recognition, timely treatment of complications, protection of self and other health care workers, and protection of the immunocompromised child.

Clinical and epidemiologic characteristics of patients referred for evaluation of possible Kawasaki disease. United States Multicenter Kawasaki Disease Study Group.

STUDY OBJECTIVES: (1) To determine those diseases that most often mimic Kawasaki disease (KD) in the United States. (2) To examine the physical findings and laboratory studies that influenced experienced clinicians to exclude the diagnosis of KD. (3) To compare epidemiologic features of patients with KD and patients referred for evaluation of possible KD in whom alternative diagnoses were established. DESIGN: Case comparison study. SETTING: Seven pediatric tertiary care centers. PATIENTS: Consecutive sample of 280 patients with KD and 42 comparison patients examined within the first 14 days after onset of fever. MEASUREMENTS AND MAIN RESULTS: (1) Infectious diseases, particularly measles and group A beta-hemolytic streptococcal infection, most closely mimicked KD and accounted for 35 (83%) of 42 patients in the comparison group. (2) The standard diagnostic clinical criteria for KD were fulfilled in 18 (46%) of 39 patients in whom other diagnoses were established. (3) Patients with KD were significantly less likely to have exudative conjunctivitis or pharyngitis, generalized adenopathy, and discrete intraoral lesions, and more likely to have a perineal distribution of their rash. The patients with KD were also more likely to have anemia and elevated erythrocyte sedimentation rate; leukocyte count less than 10 X 10(3)/mm3 and platelet count less than 200 X 10(3)/mm3 were significantly less prevalent in patients with KD. (4) Residence within 200 yards of a body of water was more common among KD patients. CONCLUSIONS: (1) Measles and streptococcal infection should be excluded in patients examined for possible KD. (2) Laboratory studies that may be useful in discriminating patients with KD from those with alternative diagnoses include hemoglobin concentration, erythrocyte sedimentation rate, and serum alanine aminotransferase activity. (3) Residence near a body of water may be a risk factor for the development of KD.

Epstein-Barr virus and other herpesvirus infections in Kawasaki syndrome.

Epstein-Barr virus (EBV), a possible cause of Kawasaki syndrome (KS), is not pathenogenically associated with KS in Hawaii. The prevalence of EBV capsid antibody in KS patients was found not to differ significantly from that in controls, and the antibody response in those infected with EBV was the same as that in other children similarly infected. No EBV was isolated from acute-phase patients. All patients with capsid antibody at the onset of KS also had Epstein-Barr nuclear antigen antibody: 36 patients developed antibody within 3 months after onset of KS; in 10, EBV infection could have been coincidental with the disease. Cytomegalovirus (CMV) was isolated from 9 patients with KS and 10 controls. A similar number of controls and patients had antibody to human herpesvirus 6 (HHV6); one patient seroconverted. None of the herpes viruses (EBV, CMV, HHV6, varicella-zoster virus, or herpes simplex virus) plays a unique or dominant role in the etiology or pathogenesis of KS in Hawaii.

Absence of significant RNA-dependent DNA polymerase activity in lymphocytes from patients with Kawasaki syndrome.

Kawasaki syndrome, an acute febrile multisystem illness of young children, is a panvasculitis with prominent rheumatic features. Arthritis and pancarditis are frequent during the acute stage; coronary artery aneurysms occur in 20% of cases and the disease is now the leading cause of acquired heart disease in childhood. A microbial aetiology is suggested by the acute febrile self-limited character of the disease, the regular occurrence of epidemic outbreaks at intervals of 2-3 years, and the virtual restriction to young children, consistent with the early acquisition of immunity. Reports of elevated DNA polymerase activity (assumed to be RNA-dependent reverse transcriptase) in cultured lymphocytes from patients with acute Kawasaki syndrome suggest that a retrovirus might be the causative agent. We have measured supernatant DNA polymerase activity in lymphocyte cultures from 49 Hawaiian patients in acute and convalescent stages of Kawasaki syndrome and have been unable to demonstrate significant reverse transcriptase activity or other evidence of involvement of a retrovirus in the aetiology of the disease.

Growth of toxic shock syndrome toxin 1-producing, tryptophan-requiring strains of Staphylococcus aureus associated with the presence of Escherichia coli.

More than 80 percent of TSST-1-positive strains of Staphylococcus aureus are tryptophan auxotrophs (Trp-). Chromosomal mapping has located the genetic determinant for TSST-1 (tst) in the trp operon for strain S411 (Trp-) and near the tyrB site for strain FRI1169 (Trp*). Auxonographic screening on tryptophan-free medium of 28 strains of S. aureus (TSST-1-positive and -negative, Trp+ and Trp-) against Escherichia coli (strains 6094, 7603, and 7877) and other strains of Enterobacteriaceae showed that Trp- S. aureus strains responded only to E. coli and tryptophan. Neither E. coli nor tryptophan inhibited TSST-1 production. Cocultivation of strain FRI1169 or S411 with E. coli strain 7877 showed that TSST-1 production by FRI1169 was not enhanced. In contrast, TSST-1 production by S411 was equal to that of S. aureus alone (less than 640 ng/mL) or enhanced (greater than 12,000 ng/mL) if the input log10 cfu of S. aureus was of equal or greater ratio to input E. coli and if the recovered S. aureus was greater than log10 5 cfu. These results suggest that nutritionally deficient toxicogenic strains of S. aureus may overcome growth limitation by coexisting in dynamic balance with strains of E. coli.

Effect of magnesium on in vitro production of toxic shock syndrome toxin 1.

Batch and chemostat culture of Staphylococcus aureus strain S411 was conducted in an investigation of the role of Mg++ in the control of production of toxic shock syndrome toxin 1 (TSST-1). Under both growth conditions, Mg++ influenced bacterial growth, and TSST-1 production was correlated with bacterial growth. The specific activity of TSST-1 (ng/mg yield, ng/mg total protein) increased with increasing concentrations of Mg++ and was maximal at physiologic levels of Mg++. No production of TSST-1 was observed under anaerobic conditions. In chemostat cultures in which valine nutrient limitation was used with various levels of tryptophan in the chemically defined medium, tryptophan concentration controlled the production of TSST-1 by strain S411, regardless of the concentration of Mg++.