Use of antibiotics in paediatric long-term care facilities.

BACKGROUND: Adult long-term care (LTC) facilities have high rates of antibiotic use, raising concerns about antimicrobial resistance. Few studies have examined antibiotic use in paediatric LTC facilities. AIM: To describe antibiotic use in three paediatric LTC facilities and to describe the factors associated with use. METHODS: A retrospective cohort study was conducted from September 2012 to December 2015 in three paediatric LTC facilities. Medical records were reviewed for demographics, healthcare-associated infections (HAIs), antimicrobial use and diagnostic testing. Logistic regression was used to identify predictors for antibiotic use. The association between susceptibility testing results and appropriate antibiotic coverage was determined using Chi-squared test. FINDINGS: Fifty-eight percent (413/717) of residents had at least one HAI, and 79% (325/413) of these residents were treated with at least one antibiotic course, totalling 2.75 antibiotic courses per 1000 resident-days. Length of enrolment greater than one year, having a neurological disorder, having a tracheostomy, and being hospitalized at least once during the study period were significantly associated with receiving antibiotics when controlling for facility (all P < 0.001). Diagnostic testing was performed for 40% of antibiotic-treated HAIs. Eighty-six percent of antibiotic courses for identified bacterial pathogens (201/233) provided appropriate coverage. Access to susceptibility testing was not associated with appropriate antibiotic choice (P = 0.26). CONCLUSION: Use of antibiotics in paediatric LTC facilities is widespread. There is further need to assess antibiotic use in paediatric LTC facilities. Evaluation of the adverse outcomes associated with inappropriate antibiotic use, including the prevalence of resistant organisms in paediatric LTC facilities, is critical.

Identifying variations in adherence to the CDC sexually transmitted disease treatment guidelines of Neisseria gonorrhoeae.

OBJECTIVE: Neisseria gonorrhoeae is identified as a national challenge due to emerging antimicrobial resistance. The Centers for Disease Control and Prevention (CDC) sexually transmitted diseases (STD) Treatment guidelines are updated to address emerging concerns. The aims of this study were 1) to determine the proportion of cases that were adherent to two aspects of the treatment guidelines: antimicrobial treatment and follow-up recommendations and 2) to evaluate differences in adherence based on clinical location. STUDY DESIGN: A retrospective review of medical records was performed for the first positive N. gonorrhoeae tests identified in subjects between May 2011 and December 2013 at a large urban academic medical centre. We hypothesised that provider adherence to STD treatment and prevention guidelines was better at STD specialised clinics than non-specialised settings. METHODS: Adherence to CDC STD treatment guidelines was determined for both treatment and prevention management. Demographic, testing differences, and appropriate treatment and follow-up between speciality and non-speciality clinics were evaluated using chi-squared, Fisher's exact, and Student's t-test, when appropriate. RESULTS: During the study period, 542/714 positive tests were analysed. Healthcare provider adherence to antimicrobial management guidelines was 82% during the study period. Adherence to the guidelines was 76% and 88% for the 2010 and 2012 time periods, respectively. Non-adherence to recommendations included lack of dual therapy for N. gonorrhoeae in speciality clinics and incorrect dose in non-speciality clinics. Appropriate preventive follow-up was identified in only 31% of cases. Both speciality clinics and non-speciality clinics had errors related to partner therapy. CONCLUSIONS: Providers in speciality clinics were more adherent to the guidelines compared with providers at other clinical sites. Significant lack of adherence was identified in the follow-up management of N. gonorrhoeae. Evaluation of treatment errors may help improve medical management of N. gonorrhoeae.

Novel inter-hemispheric white matter connectivity in the BTBR mouse model of autism.

Alterations in the volume, density, connectivity and functional activation of white matter tracts are reported in some individuals with autism and may contribute to their abnormal behaviors. The BTBR (BTBR T+tf/J) inbred strain of mouse, is used to model facets of autism because they develop low social behaviors, stereotypical and immune changes similar to those found in people with autism. Previously, it was thought a total absence of corpus callosal interhemispheric connective tissues in the BTBR mice may underlie their abnormal behaviors. However, postnatal lesions of the corpus callosum do not precipitate social behavioral problems in other strains of mice suggesting a flaw in this theory. In this study we used digital pathological methods to compare subcortical white matter connective tracts in the BTBR strain of mice with those found in the C57Bl/6 mouse and those reported in a standardized mouse brain atlas. We report, for the first time, a novel connective subcortical interhemispheric bridge of tissue in the posterior, but not anterior, cerebrum of the BTBR mouse. These novel connective tissues are comprised of myelinated fibers, with reduced myelin basic protein levels (MBP) compared to levels in the C57Bl/6 mouse. We used electrophysiological analysis and found increased inter-hemispheric connectivity in the posterior hemispheres of the BTBR strain compared with the anterior hemispheres. The conduction velocity was slower than that reported in normal mice. This study shows there is novel abnormal interhemispheric connectivity in the BTBR strain of mice, which may contribute to their behavioral abnormalities.

Developmental PCB exposure induces hypothyroxinemia and sex-specific effects on cerebellum glial protein levels in rats.

Polychlorinated biphenyls (PCBs) are persistent lipophilic environmental contaminants which are found in fatty tissues of humans and wild-life alike. Maternal transfer of PCBs to offspring is easily achieved across the placenta and via lactation. In male rats, perinatal PCB exposure induces behavioral abnormalities, in addition to hypothyroxinemia and white matter changes. There are sex differences in white matter volume synthesis and density in adult and aged rodents. Yet whether PCB exposure effects on white matter are sex-specific is unclear, because the previous studies were conducted in male offspring. Furthermore, although hypothyroxinemia induced by PCB exposure is thought to trigger white matter changes, PCBs also affect interleukin-6 (IL-6) expression, and IL-6 regulates white matter growth. We hypothesized that perinatal PCB exposure would have sex-specific effects on white matter development associated with altered IL-6 levels. We found that female offspring had higher levels of myelin basic protein (MBP) than males did, at postnatal day (PND) 7, 18 and 21. PCB exposure induced hypothyroxinemia in males and females at PND7, 14, 21, and 42. PCB exposure also increased MBP and reduced glial fibrillary acidic protein (GFAP) levels in males at PND21, but had the opposite effect in females. In addition, at PND14 and 21, PCB exposure elevated IL-6 levels in male offspring only. The induction of sex-specific changes in white matter proteins, in the absence of sex differences in thyroxine levels after PCB exposure, suggests that serum thyroxine levels do not directly contribute to the white matter alterations. Instead, IL-6 may contribute to increased MBP levels in males, whereas in females estromimetic and thyromimetic PCB metabolites may affect white matter development. This data adds to an increasing body of literature showing that perinatal insults induce sex-specific effects in offspring.

Medical education through community experience: community projects at the University of South Dakota School of Medicine.

Community projects are a requirement of third-year medical students at three South Dakota clinical campuses. Students identify a community issue, design and implement either a service or research project, and present the project to faculty and peers. Topics include cardiovascular and other disease risk factors, nutrition education, firearm safety and many others. These projects answer a need to advance an understanding of population health, promote community involvement among student physicians, and improve the health of the community.

Lymphocyte diversity in a 9-year-old boy with idiopathic CD4+ T cell lymphocytopenia.

Since CD4+ lymphocytopenia can be caused by disturbed thymic T-cell maturation, we investigated the T-cell subsets of a 9-year-old boy fulfilling the diagnostic criteria for CD4+ lymphocytopenia in a follow-up period of 4 years. We found (I) reduced CD45RA expression, (II) enhanced CD45RO expression and (III) a significant increase in gamma delta TCR-bearing T cells. An accelerated apoptosis (11%) was observed in the CD45RO+, but not CD45RA+ subset. These findings provide evidence that a disturbed thymic T-cell maturation process might play a role in the pathogenesis of CD4+ lymphocytopenia.

Nosocomial rotavirus in a pediatric hospital.

We describe a nosocomial rotavirus outbreak among pediatric cardiology patients and the impact of a prospective, laboratory-based surveillance program for rotavirus in our university-affiliated, quartenary-care pediatric hospital in New York City. Improved compliance with infection control and case-finding among patients and healthcare workers halted the outbreak.

Generation of humanized mice susceptible to peptide-induced inflammatory heart disease.

BACKGROUND: Dilated cardiomyopathy (DCM) is a major cause of sudden cardiac death. In certain mouse major histocompatibility complex (MHC) backgrounds, myocarditis and inflammatory cardiomyopathy can be triggered by immunization with heart muscle-specific proteins. Similarly, chronic heart disease in humans has been linked to certain HLA alleles, such as HLA-DQ6. However, there is no experimental evidence showing that human MHC class II molecules and peptides derived from human proteins are involved in the pathogenesis of myocarditis and DCM. METHODS AND RESULTS: We generated double CD4- and CD8-deficient mice transgenic for human CD4 (hCD4) and human HLA-DQ6 to specifically reconstitute the human CD4/DQ6 arm of the immune system in mice. Transgenic hCD4 and HLA-DQ6 expression rendered genetically resistant C57BL/6 mice susceptible to the induction of autoimmune myocarditis induced by immunization with cardiac myosin. Moreover, we identified heart-specific peptides derived from both mouse and human alpha-myosin heavy chains capable of inducing inflammatory heart disease in hCD4 and HLA-DQ6 double transgenic mice but not in hCD4 single transgenic littermates. The autoimmune inflammatory heart disease induced by the human heart muscle-specific peptide in hCD4 and HLA-DQ6 double transgenic mice shared functional and phenotypic features with the disease occurring in disease-susceptible nontransgenic mice. CONCLUSIONS: Our data provide the first genetic and functional evidence that human MHC class II molecules and a human alpha-myosin heavy chain-derived peptide can cause inflammatory heart disease and suggest that human inflammatory cardiomyopathy can be caused by organ-specific autoimmunity. The humanized mice generated in this study will be an ideal animal model to further elucidate the pathogenesis of inflammatory heart disease and facilitate the development of rational treatment strategies.

Diagnosis of pediatric tuberculosis in the modern era.

BACKGROUND: Correctly diagnosing tuberculosis (TB) in children is critical to provide appropriate treatment and to detect undiagnosed source cases. However, diagnosing TB in children may be difficult. OBJECTIVE: We sought to determine whether Amplicor, a Food and Drug Administration-approved polymerase chain reaction (PCR) assay used to detect Mycobacterium tuberculosis in sputum and computerized tomography (CT) would facilitate the diagnosis of TB in children. We also examined the applicability of the Centers for Disease Control and Prevention clinical case definition for TB. SETTING: A university-affiliated pediatric hospital in New York City. SUBJECTS: From March, 1995, to November, 1997, 27 children < 15 years of age (mean age, 3.9 years) were evaluated for suspected TB. RESULTS: M. tuberculosis was cultured from 5 of 76 (6.6%) gastric aspirate specimens, and PCR detected M. tuberculosis DNA in 3 (4.1%) of these specimens. There was poor correlation between culture and PCR because 6 specimens were discordant. CT scans were diagnostic of mediastinal or hilar adenopathy in 6 children with equivocal or negative chest radiographs and confirmed adenopathy in 8 others. Six children received alternative diagnoses. CONCLUSIONS: We conclude that the commercially available PCR technology had very limited utility in detecting M. tuberculosis from gastric aspirates, but CT scans were useful in assessing pediatric patients with suspected TB.

Chlamydia infections and heart disease linked through antigenic mimicry.

Chlamydia infections are epidemiologically linked to human heart disease. A peptide from the murine heart muscle-specific alpha myosin heavy chain that has sequence homology to the 60-kilodalton cysteine-rich outer membrane proteins of Chlamydia pneumoniae, C. psittaci, and C. trachomatis was shown to induce autoimmune inflammatory heart disease in mice. Injection of the homologous Chlamydia peptides into mice also induced perivascular inflammation, fibrotic changes, and blood vessel occlusion in the heart, as well as triggering T and B cell reactivity to the homologous endogenous heart muscle-specific peptide. Chlamydia DNA functioned as an adjuvant in the triggering of peptide-induced inflammatory heart disease. Infection with C. trachomatis led to the production of autoantibodies to heart muscle-specific epitopes. Thus, Chlamydia-mediated heart disease is induced by antigenic mimicry of a heart muscle-specific protein.

Ureteral obstruction secondary to indinavir in the pediatric HIV population.

Indinavir sulfate is a protease inhibitor used in the treatment of the human immunodeficiency virus (HIV). This case report describes the radiographic and urologic manifestations of indinavir urolithiasis in two pediatric patients with acquired immunodeficiency syndrome (AIDS). Management involves aggressive hydration and surgical intervention when indicated.

Genital chlamydial disease in an urban, primarily Hispanic, family planning clinic.

BACKGROUND AND OBJECTIVES: Although chlamydia is a well-studied disease, little is known about the rates of genital chlamydial disease among female Hispanics in urban family planning clinics. GOALS: To determine the prevalence of women with chlamydia in two clinic populations during 1994. We also sought to describe previously identified and novel risk factors for chlamydial disease in this unique population. STUDY DESIGN: We conducted a retrospective case-control analysis in two community clinics in the Washington Heights section of New York City. RESULTS: In 1994, 4,190 screening tests were done for Chlamydia trachomatis in these clinics, and the prevalence of positive tests was 5.4% (227/4,190). The mean age of the women screened was 19.2 years and most were of Hispanic origin (76%), students (51%), and received Medicaid (61%). Risk factors found to be associated with C. trachomatis infection included young age; earlier age at first coitus; pregnancy at the time of chlamydia screening; concurrent gonorrheal infection; and the clinical findings of cervical abnormalities, vaginal discharge, and adnexal tenderness. Hormonal contraception appeared to be protective against chlamydial infection (odds ratio, 0.36%; confidence interval, 0.17-0.77). CONCLUSION: Sexually transmitted diseases were common in our population because 5.4% of the women screened had chlamydial infection and 1.5% had concurrent gonorrheal infection. Our study confirmed risk factors established in other populations. These data support the need for enhanced screening efforts for chlamydia to decrease the prevalence of disease in our population.

PIP: The prevalence of and risk factors associated with chlamydia infection were investigated retrospectively among 4190 US women under 30 years (mean age, 19.2 years) who were patients at two young adult family planning clinics in New York City, New York. Immigrants from the Dominican Republic comprise the largest segment of the population served by these clinics. 76% of study participants were Hispanic, 61% were Medicaid recipients, and 51% were students. 227 women (5.4%) were positive for Chlamydia trachomatis. 7 women (3.5%) with chlamydia had concurrent gonorrhea. Compared with their counterparts with a negative chlamydia test, women with chlamydia were younger (mean age, 19.4 vs. 18.8 years) and had a lower mean age at first coitus (16 vs. 15 years). Use of barrier methods of contraception alone conferred no more protection against chlamydia than contraceptive nonuse, presumably because of inconsistent or improper use. However, women who used both a barrier and hormonal method were less than half as likely to be infected with chlamydia than those using no protection. 39% of women diagnosed with chlamydia had no cervical or vaginal abnormalities, while 20% of women with a negative chlamydia test had physical examination findings suggestive of genital infection. Regression analysis identified three factors significantly associated with chlamydia infection: positive pregnancy test at the time of the first clinic visit, vaginal discharge on pelvic examination, and self-reported drug use. The positive predictive value of diagnosing an infection increased from 50% using the clinical impressions of the providers to 61% with this model.

iNOS expression and nitrotyrosine formation in the myocardium in response to inflammation is controlled by the interferon regulatory transcription factor 1.

BACKGROUND: Production of NO by inducible NO synthase (iNOS) has been implicated in the pathology of spontaneous and antigen-induced autoimmune diseases, and iNOS is expressed in the myocardium of patients with heart failure. It is not clear whether inflammatory murine autoimmune heart disease, an experimental model for human postviral heart disease, is characterized by increased iNOS expression within the heart and whether iNOS and NO are essential in the pathogenesis of autoimmune myocarditis. METHODS AND RESULTS: In the murine model of cardiac myosin-induced myocarditis, we demonstrate that iNOS expression was elicited in inflammatory macrophages and in distinct cardiomyocytes. Autoimmune heart disease was accompanied by formation of the NO reaction product nitrotyrosine in inflammatory macrophages as well as in cardiomyocytes. iNOS expression and nitrotyrosine formation were strictly dependent on myocardial inflammation. Focal myocarditis was sufficient to induce nitrotyrosine formation throughout the whole heart muscle. Mice defective for the interferon regulatory transcription factor-1 (IRF-1(-/-)) after gene targeting failed to induce iNOS expression and nitrotyrosine formation in the heart but developed cardiac myosin-induced myocarditis at prevalence and severity similar to those of heterozygous littermates (IRF-1(+/-)). CONCLUSIONS: These data provide the first in vivo evidence that iNOS expression and NO synthesis in macrophages and distinct cardiomyocytes are elicited in experimental murine inflammatory heart disease. The transcription factor IRF-1 controls iNOS expression and NO synthesis in disease. Because autoimmune myocarditis can develop in animals lacking IRF-1, these mice will be useful to elucidate the link between iNOS expression in inflammatory heart disease and the development of dilated cardiomyopathy and heart failure.

Essential role of the thymus to reconstitute naive (CD45RA+) T-helper cells after human allogeneic bone marrow transplantation.

To contribute to the understanding of the role of the thymus in humans in the reconstitution of naive (CD45RA+) T cells after bone marrow transplantation (BMT), we compared T-cell regeneration in a unique situation, namely a thymectomized cancer patient (15 years old), with that of thymus-bearing patients after allogeneic BMT. These cases shared features of transplantation (total body irradiation, HLA-matched donors, and graft-versus-host disease prophylaxis with cyclosporine A) and all had an uncomplicated post-transplantation course. As shown by fluorescence-activated cell sorting analyses, the thymectomized host failed to reconstitute CD45RA+ T-helper cells even 24 months after BMT (11% CD45RA+ of CD4+ cells). In this patient, preferentially CD45RO+ cells contributed to the recovery of CD4+ cells (206 of 261/microL at 6 months and 463 of 558/microL at 24 months after BMT, CD45RA+ of CD4+ cells), whereas CD45RA+ cells remained low (<60/microL). In contrast, nine thymus-bearing hosts (5 children and 4 adults) examined between 6 and 24 months after BMT effectively reconstituted CD4+/CD45RA+ cells according to their normal age-related range (> or = 28% in adults and > or = 50% in children). Five of these were analyzed sequentially at 6 and 9 months after BMT. Within this period, CD45RA+ cells increasingly contributed to the recovery of CD4+ cells (median, +21%), even when total CD4+ cells decreased. With respect to T-cytotoxic/suppressor cells, the thymectomized host retained the capacity to recover CD45RA+ cells (137 of 333/microL at 6 months and 596 of 1,046/microL at 24 months after BMT, CD45RA+ of CD8+ cells), a proportion similar to that seen in thymus-bearing hosts. These findings suggest that a thymus-independent pathway exists to regenerate CD45RA+ T-cytotoxic/suppressor cells, but residual thymus is essential to reconstitute naive (CD45RA+) T-helper cells after BMT in humans.

Induction of autoimmune myocarditis in interleukin-2-deficient mice.

BACKGROUND: Interleukin (IL)-2 is an important growth and survival factor for T cells and plays a crucial role in inflammation. Myosin-induced myocarditis is strictly dependent on activated T cells and is a model for postinfectious inflammatory heart disease in humans. To explore the role of IL-2 in myocarditis, we injected mice genetically deficient for IL-2 with cardiac myosin. Because it is conceivable that the lack of IL-2 either promotes or ameliorates the disease, we selected mouse strains that differ in their susceptibility to cardiac myosin-induced myocarditis. METHODS AND RESULTS: Mice from a susceptible strain (C3H) that were rendered IL-2 deficient by gene targeting (IL-2-/- mice) and littermate controls were immunized twice with purified cardiac myosin at a 7-day interval. Three weeks after the first immunization, hearts were obtained for histopathological and immunohistochemical analysis. Sera were tested for autoantibodies to the cardiac myosin isoform by enzyme-linked immunosorbent assay. The majority of C3H IL-2-/- mice developed severe myocarditis accompanied by high-titer myosin autoantibodies. In C57BL/6 mice, which develop only little myocarditis on myosin immunization, lack of IL-2 did not increase susceptibility to the disease. Moreover, the composition of the inflammatory infiltrate in C3H IL-2-/- mice was virtually identical to that seen in the wild-type strain. CONCLUSIONS: Our data provide the first genetic evidence that in cardiac myosin-immunized mice, IL-2 has no essential role for the development of autoimmune heart disease and the generation of myosin autoantibodies.