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Initial Pseudomonas aeruginosa infection in patients with cystic fibrosis: characteristics of eradicated and persistent isolates.

Abstract

Despite intensive eradication therapy, some CF patients with early Pseudomonas aeruginosa infection rapidly develop a chronic infection. To elucidate factors associated with this persistence, bacterial characteristics of early P. aeruginosa isolates were analysed that were either eradicated rapidly or persisted despite multiple antimicrobial treatments.

Eighty-six early infection episodes were studied. First P. aeruginosa isolates from patients with eradication (36) or persistent infection (16) were included; isolates from patients with intermittent infection (34) were omitted from the study. Virulence assays, antimicrobial resistance, cytotoxicity and mutation frequencies were analysed in vitro. P. aeruginosa was genotyped by SNP-array. Transcriptomic profiles of two eradicated and two persistent strains were compared.

Nineteen per cent of patients developed persistent infection; 42% achieved eradication. Secretion of virulence factors and mutation frequencies were highly variable among both eradicated and persistent isolates and were not different between the groups. Cytotoxicity was present in 57% of eradicated vs. 100% of persistent isolates (p <0.01). None of the isolates were resistant to antibiotics. The isolates were genotypically highly diverse. Multivariate analysis showed that in vitro determined bacterial characteristics could not predict persistence after first P. aeruginosa infection. Preliminary transcriptomic data showed increased expression of some genes related to a metabolic pathway. The early onset of chronic infection was not associated with (in vitro determined) bacterial characteristics only. Although the persistent isolates were more often cytotoxic, for the individual patient it was not possible to predict the risk of persistence based on bacterial characteristics.

Unknown factors such as host-pathogen and pathogen-pathogen interactions should be further explored.

Therapeutic Options for Acute Cough Due to Upper Respiratory Infections in Children.

Cough due to upper respiratory tract infections (URIs) is one of the most frequent complaints encountered by pediatric health-care providers, and one of the most disruptive symptoms for children and families.

Despite the frequency of URIs, there is limited evidence to support the few therapeutic agents currently available in the United States (US) to treat acute cough due to URI. Published, well-designed, contemporary research supporting the efficacy of narcotics (codeine, hydrocodone) and US Food and Drug Administration (FDA)-approved over-the-counter (OTC) oral antitussives and expectorants (dextromethorphan, diphenhydramine, chlophedianol, and guaifenesin) is absent for URI-associated pediatric cough. Alternatively, honey and topically applied vapor rubs may be effective antitussives.

Somatoform respiratory disorders in children and adolescents-proposals for a practical approach to definition and classification.

Somatoform respiratory disorders represent conditions with dysfunctional breathing unexplained by structural abnormalities. This heterogeneous group includes disorders with neural dysregulation of respiration (vocal cord dysfunction) or with dysregulation of the respiratory pattern (hyperventilation, sighing dyspnea), psychogenic disorders such as unjustified anxiety of suffocation, and stereotype conditions such as throat clearing or habit cough.

Many symptoms are nonspecific and largely overlap with respiratory disease symptoms of somatic etiology. Most patients will present in a nonspecialized clinical setting. This article provides symptom-based criteria for the definition of somatoform respiratory disorders and their differentiation from somatic disease. Emphasis is put on clinical criteria which can be easily integrated in a routine setting. Owing to the multifaceted etiology of somatoform respiratory disorders therapeutic approaches integrating somatic medicine, respiratory therapy and psychology are crucial.

The introduction of defined clinical criteria may facilitate the discrimination of somatoform respiratory disorders from somatic disorders in routine patient encounters and avoid therapeutic detours. Pediatr Pulmonol. © 2011 Wiley-Liss, Inc.

Adenovirus.

Adenoviruses (AdV) are DNA viruses that typically cause mild infections involving the upper or lower respiratory tract, gastrointestinal (GI) tract, or conjunctiva. Rare manifestations of AdV infections include hemorrhagic cystitis, hepatitis, hemorrhagic colitis, pancreatitis, nephritis, or encephalitis. Adenovirus infections are more common in young children, owing to lack of humoral immunity. Epidemics of AdV infections may occur in healthy children or adults in closed or crowded settings (particularly military recruits).

The disease is more severe, and dissemination is more likely in patients with impaired immunity (eg, organ transplant recipients, human immunodeficiency virus infection, congenital immunodeficiency syndromes). Fatality rates for untreated severe AdV pneumonia or disseminated disease may exceed 50%. More than 50 serotypes of AdV have been identified. Different serotypes display different tissue trophisms and correlate with clinical manifestations of infection. The predominant serotypes differ among countries or regions and change over time. Transmission of novel strains between countries or across continents and replacement of dominant serotypes by new strains may occur.

Treatment of AdV infections is controversial because prospective, randomized therapeutic trials have not been done. Cidofovir is considered the drug of choice for severe AdV infections, but not all patients require treatment. Vaccines have been shown to be highly efficacious in reducing the risk of respiratory AdV infection but are currently not available.

Progress in the development of human parainfluenza virus vaccines.

In children under 5 years of age, human parainfluenza viruses (HPIVs) as a group are the second most common etiology of acute respiratory illness leading to hospitalization, surpassed only by respiratory syncytial virus but ahead of influenza viruses. Using reverse genetics systems for HPIV serotypes 1, 2 and 3 (HPIV1, 2 and 3), several live-attenuated HPIVs have been generated and evaluated as intranasal vaccines in adults and in children.

Two vaccines against HPIV3 were found to be well tolerated, infectious and immunogenic in Phase I trials in HPIV3-seronegative infants and children and should progress to proof-of-concept trials. Vaccines against HPIV1 and HPIV2 are less advanced and have just entered pediatric trials.

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