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PubMed2001

Responsible prescribing for upper respiratory tract infections.

Upper respiratory tract infections (URTIs) are responsible for a large amount of community antibacterial use worldwide. Recent systematic reviews have demonstrated that most URTIs resolve naturally, even when bacteria are the cause. The high consumer expectation for antibacterials in URTIs requires intervention by the general practitioner and a number of useful strategies have been developed. Generic strategies, including eliciting patient expectations, avoiding the term 'just a virus', providing a value-for-money consultation, providing verbal and written information, empowering patients, conditional prescribing, directed education campaigns, and emphasis on symptomatic treatments, should be used as well as discussion of alternative medicines when relevant. The various conditions have differing rates of bacterial infection and require different approaches. For acute rhinitis, laryngitis and tracheitis, viruses are the only cause and, therefore, antibacterials are never required. In acute sore throat (pharyngitis) Streptococcus pyogenes is the only important bacterial cause. A scoring system can help to increase the likelihood of distinguishing a streptococcal as opposed to viral infection, or alternatively patients should be given antibacterials only if certain conditions are fulfilled. Strategies for treating acute otitis media vary in different countries. Most favour the strategy of prescribing antibacterials only when certain criteria are fulfilled, delaying antibacterial prescribing for at least 24 hours. In otitis media with effusion, on the other hand, there is no primary role for antibacterials, as the condition resolves naturally in almost all patients aged >3 months. Detailed strategies for acute sinusitis have not been worked out but restricting antibacterial prescribing to certain clinical complexes is currently recommended by several authorities because of the high natural resolution rate.

Anti-Bacterial Agents↗
PubMed2005

Expression of programmed death-1 ligand (PD-L) 1, PD-L2, B7-H3, and inducible costimulator ligand on human respiratory tract epithelial cells and regulation by respiratory syncytial virus and type 1 and 2 cytokines.

BACKGROUND: Respiratory syncytial virus (RSV) is associated with wheezing illness, and infections can occur repeatedly throughout life. We hypothesized that RSV infection of respiratory tract epithelial cells up-regulates B7 molecules that regulate memory immune responses and that type 1 and 2 cytokines differentially modulate this induction. METHODS: We used flow-cytometric analysis to investigate programmed death-1 ligand (PD-L) 1, PD-L2, B7-H3, and inducible costimulatory ligand (ICOS-L) expression on tracheal (NCI-H292), bronchial (BEAS-2B), and alveolar (A549) epithelial cells; regulation of this expression by RSV, interferon (IFN)- gamma , and interleukin (IL)-4; and the effects of IFN-gamma and IL-4 on RSV-induced expression of these molecules. RESULTS: B7-H3 was strongly expressed, PD-L1 and ICOS-L were moderately expressed, and PD-L2 was weakly expressed on unstimulated tracheal, bronchial, and alveolar epithelial cells. RSV infection up-regulated PD-L1, PD-L2, and B7-H3 expression on all cells and ICOS-L expression on bronchial and alveolar epithelial cells. IL-4 treatment alone had no effect, whereas IFN-gamma treatment alone increased PD-L1 and PD-L2 expression on all cells and decreased B7-H3 expression on bronchial and alveolar epithelial cells. On RSV-infected alevolar epithelial cells, IFN-gamma treatment increased PD-L1 and PD-L2 expression and decreased B7-H3 and ICOS-L expression, and IL-4 treatment increased PD-L2 and B7-H3 expression and decreased ICOS-L expression. CONCLUSIONS: Respiratory tract epithelial cells express a wide range of B7 molecules. RSV infection increases their expression, and this expression is differentially regulated by IFN-gamma and IL-4. These processes may be involved in decreasing T cell antiviral immune responses to RSV and in RSV-associated wheezing.

Antigens, CD↗
PubMed2003

Worldwide trends in antimicrobial resistance among common respiratory tract pathogens in children.

BACKGROUND: Respiratory tract infections among children are a common reason for health care provider visits and the primary reason for antimicrobial prescribing in this population. The increased prevalence of resistance among Streptococcus pneumoniae and Haemophilus influenzae pathogens poses a serious challenge in the successful treatment of respiratory tract infections caused by these pathogens. METHODS: This paper reviews worldwide trends in antimicrobial resistance among common respiratory tract pathogens, highlighting data obtained from the pediatric population where available. RESULTS: S. pneumoniae resistance to beta-lactams is mediated through alterations in the penicillin-binding proteins and macrolide resistance to acquisition of efflux or methylation genes. The mechanisms of resistance to the fluoroquinolones include target enzyme alterations via genetic mutations and transport out of the bacterial cell via an efflux pump. Beta-lactamase production is the primary mechanism of resistance to penicillins among H. influenzae isolates. Although S. pneumoniae with reduced susceptibility to penicillin was first documented > 30 years ago, resistance has increased at an alarming rate worldwide in the past decade. According to recent surveillance data, the worldwide prevalence of S. pneumoniae with reduced susceptibility to penicillin is 18.2%. Beta-lactamase production among H. influenzae ranges from approximately 4% in Russia to 26% in the United States and to 31% in France. The prevalence of beta-lactamase-negative, ampicillin-resistant H. influenzae remains very low (< 1%) worldwide, except in Japan, where the incidence is higher. In general, the highest rates of resistance are observed in isolates obtained from children, and risk factors for infection with a resistant pathogen include young age, the site of infection, day-care center attendance and recent antimicrobial use. CONCLUSIONS: Increased prevalence of antimicrobial resistance among respiratory tract pathogens isolated from children and adults is evident worldwide. Treatment of infections caused by S. pneumoniae and H. influenzae with older agents or ineffective dosing regimens may not eradicate infections and may contribute to the spread of resistance. These observations confirm the need for appropriate antimicrobial use to halt or at least limit the spread of resistance.

Bacterial Infections↗
PubMed2004

Mechanisms of resistance among respiratory tract pathogens.

Antimicrobial resistance among respiratory tract pathogens represents a significant health care threat. Identifying the antimicrobial agents that remain effective in the presence of resistance, and knowing why, requires a thorough understanding of the mechanisms of action of the various agents as well as the mechanisms of resistance demonstrated among respiratory tract pathogens. The primary goal of antimicrobial therapy is to eradicate the pathogen, via killing or inhibiting bacteria, from the site of infection; the defenses of the body are required for killing any remaining bacteria. Targeting a cellular process or function specific to bacteria and not to the host limits the toxicity to patients. Currently, there are four general cellular targets to which antimicrobials are targeted: cell wall formation and maintenance, protein synthesis, DNA replication, and folic acid metabolism. Resistance mechanisms among respiratory tract pathogens have been demonstrated for all four targets. In general, the mechanisms of resistance used by these pathogens fall into one of three categories: enzymatic inactivation of the antimicrobial, prevention of intracellular accumulation, and modification of the target site to which agents bind to exert an antimicrobial effect. Resistance to some agents can be overcome by modifying the dosage regimens (e.g., using high-dose therapy) or inhibiting the resistance mechanism (e.g., b-lactamase inhibitors), whereas other mechanisms of resistance can only be overcome by using an agent from a different class. Understanding the mechanisms of action of the various agents and the mechanisms of resistance used by respiratory tract pathogens can help clinicians identify the agents that will increase the likelihood of achieving optimal outcomes.

Anti-Bacterial Agents↗
PubMed1992

Lower respiratory tract infection in hospitalized children due to respiratory syncytial (RS) virus during a suspected epidemic period of RS virus in Delhi.

A study of 131 children below 5 years of age seeking hospitalization due to lower respiratory tract infections (LRTI), comprising 56 cases of bronchiolitis, 61 cases of bronchopneumonia, and 14 cases of other lower respiratory tract diseases showed significant occurrence of bronchiolitis in younger age groups (chi 2 = 79.21; P less than 0.001). Employing two rapid techniques, viz. immunofluorescent antibody technique (IFAT) and enzyme immunoassay (EIA) along with tissue culture, Respiratory Syncytial (RS) virus could be detected in higher percentage of bronchiolitis cases (54 per cent by both culture and IFAT, 70 per cent by EIA) compared to bronchopneumonia (36 per cent by both culture and IFAT, 49 per cent by EIA) and other LRTI cases (14 per cent each by culture, IFAT and EIA). The detection rate of RS virus was higher in the age group 0-6 months compared to the remaining age groups combined (7-60 months) in bronchiolitis cases irrespective of the technique employed while no such difference could be noted in bronchopneumonia. Eighteen (90 per cent) out of 20 specimens positive for RS virus by EIA, but negative by culture were found to be true positives as revealed by blocking test. In comparison to culture, sensitivities of IFAT, EIA, and EIA (by blocking test) were found to be 89, 94, and 94 per cent, respectively, while specificities of these techniques were found to be 92, 74, and 76 per cent, respectively. Higher detection rate of RS virus in the present study compared to earlier ones from India is attributed to application of EIA as well as selection of LRTI cases during a period of suspected epidemic of RS virus.

Age Factors↗
PubMed2002

A preventive measure for otitis media in children with upper respiratory tract infections.

Recurrent upper respiratory tract infections (URTI) are very common in patients of all ages. Rhinitis, bronchitis, chronic sinusitis and otitis appear to be the prevalent forms of recurrent respiratory infections in the paediatric population. The aim of treatment is so the solution of the respiratory pathology and the also the prevention of their complications. Antibacterial therapy is still the classical treatment approach in patients both with respiratory tract infections and with otitis media, despite the fact that antibacterials have several well known drawbacks, especially when used to treat recurrent infections. Eighty-four paediatric patients of both sexes (range: 4-14 years) with otitis were enrolled in the study. Patients were included if they had a >2 years' history of recurrent or chronic respiratory infections, and/or had experienced at least three episodes requiring medical consultations and/or treatment during the winter prior to the study. The young patients were randomised to receive Immucytal (group A) or placebo (group B) treatment according to the following protocol: (1) starting therapy (1 month): one tablet daily in the morning 4 days per week for 3 consecutive weeks; (2) maintenance period (5 months): one tablet daily in the morning 4 days per week for 1 week every month. Placebo and Immucytal tablets were identical in shape and size, in order to maintain double-blind conditions. Patients of group A with recurrent URTI had a significantly decreased incidence of ENT infections, fever and shorter duration of illness, decreased requirement for ancillary medications and fewer work-days lost. The reduction in the incidence of infectious episodes became significant vs. placebo. A significantly improved outcome vs. placebo was also observed on the incidence of fever, frequency and duration of infectious episodes, ancillary therapies. Immucytal treatment was associated with significant changes in both immunological and auditory function parameters. Serum concentrations of immunoglobulins were significantly increased in Immucytal. For both evaluations, a significant difference between treatment groups was found (P>0.001). Preventive strategies, such as ribosomal immunotherapy, may represent a valid alternative approach.

Administration, Oral↗
PubMed2002

Current issues on resistance, treatment guidelines, and the appropriate use of fluoroquinolones for respiratory tract infections.

BACKGROUND: Community-acquired respiratory tract infections comprise a large percentage of diseases treated by primary care physicians, and rates of antimicrobial use for respiratory tract infections are increasing. The fluoroquinolones comprise a drug class with broad-spectrum activity against many of the key pathogens associated with community-acquired respiratory tract infections, including Streptococcus pneumoniae, and other significant pathogens, such as Staphylococcus aureus and Pseudomonas aeruginosa. While fluoroquinolones have gained popularity, the settings for their appropriate use in treating respiratory tract infections remain unclear. OBJECTIVE: In this article, the mechanisms of fluoroquinolone resistance in S. pneumoniae, treatment guidelines, and the mode of spread of resistance are reviewed. METHODS: The authors conducted a MEDLINE search for articles published from 1990 to the present. Search terms included Streptococcus pneumoniae, fluoroquinolones, and resistance. Articles were selected for inclusion based on their relevance to the objective of this review. RESULTS: Although 3 sets of treatment guidelines for community-acquired pneumonia (CAP) currently exist in the United States, a consensus for the role of fluoroquinolones in the outpatient management of CAP has not been achieved. Factors mitigating for restraint in the outpatient use of fluoroquinolones include concern for the spread of resistance to "innocent-bystander" organisms, such as S. aureus and P. aeruginosa, as well as possible inappropriate "trickle-down" use for other, less severe respiratory syndromes, such as bronchitis. CONCLUSION: Although the fluoroquinolones are potent agents against respiratory pathogens and have a clearly defined role in the treatment of hospitalized patients with CAP, their optimal role in the outpatient management of respiratory tract infections remains controversial.

Anti-Infective Agents↗
PubMed2005

Antimicrobial peptides and surfactant proteins in ruminant respiratory tract disease.

In ruminants, respiratory disease is multifactorial and a leading cause of morbidity and mortality. Pulmonary innate immunity is the first line of defense for the respiratory tract. Alteration of regulation, expression, and function of these factors may be important to disease development and resolution. Many antimicrobial peptides and surfactant proteins are constitutively expressed in the respiratory tract and expression levels are regulated. Beta-defensins are cationic peptides with broad antimicrobial activity against bacterial, viral and fungal pathogens. Beta-defensins are primarily expressed in mucosal epithelia (and in some species leukocytes); where they may also participate in chemotaxis, wound repair and adaptive immune responses. Surfactant proteins A and D are secreted pulmonary surfactant proteins that have antimicrobial and immune regulatory activity. Anionic peptide is a constitutively expressed, aspartate-rich peptide that has antimicrobial activity and is most prominent during reparative epithelial hyperplasia. Regulation of these immune defense components by stress, pathogens, and inflammatory cytokines may play a role in the susceptibility to, severity and resolution of respiratory infection. The expression patterns of these molecules can be specific for host-species, class of pathogen and stage of infection. Understanding the regulation of antimicrobial peptide/protein expression will further enhance the potential for novel prophylactic and therapeutic modalities to minimize the impact of respiratory disease.

Animals↗
PubMed2000

Rapid detection of respiratory viruses by centrifugation enhanced cultures from children with acute lower respiratory tract infections.

BACKGROUND: Acute respiratory tract infection (ARI) is the major cause of morbidity and mortality in young children in developing countries. Information on viral aetiology in ARI in India is very limited. OBJECTIVE: The aim of the study was to define the role of viruses in acute lower respiratory tract infections (ALRTI) in children in India using centrifugation enhanced cultures followed by indirect immunofluorescence (IIF). STUDY DESIGN: Nasopharyngeal aspirates (NPAs) were collected from children from September 1995 to April 1997, attending paediatric clinic of All India Institute of Medical Sciences (AIIMS) with symptoms of ALRTI. Virus isolation was done by centrifugation enhanced cultures using HEp-2, LLC-MK2 and MDCK cells. The viruses were identified at 24-48 h post inoculation by IIF staining using monoclonal antibodies to respiratory syncytial virus (RSV), parainfluenza virus (PIV), influenza virus and adenovirus. RESULTS: Of 200 NPA samples, 89 (44.5%) were positive for one or more viral pathogens. RSV was detected in 34 (17%) of all ALRTI cases followed by influenza viruses in 29 (14.5%), PIVs in 23 (11.5%) and adenoviruses in three (1.5%). In 79 children with bronchiolitis, RSV was most frequently isolated (25%) pathogen, while in bronchopneumonia cases (101) the most common viral pathogen was influenza virus (17%). In eight cases (4%) of ALRTI dual infections were detected. In 100 NPA specimens IIF staining on direct cell smears was carried out and viruses were detected in only 17%. RSV and influenza virus infection peaked from September to December, where as PIV infections were more frequent from January to April. CONCLUSION: Respiratory viruses accounted for 44.5% of cases of ALRTI in India and the results of viral aetiology could be given in 24-48 h using centrifugation enhanced cultures. RSV was the most common viral agent associated with ALRTI in children under 5 years of age with greater association with bronchiolitis.

Adenoviruses, Human↗
PubMed2002

Antimicrobial therapy of upper respiratory tract infections in children.

Respiratory tract infections still represent a serious medical problem, mainly in people with different dysfunctions of the immune system. That kind of infections frequently occurs in the children and in the elderly. The aim of the present work was to estimate paediatrician's preferences in antibiotics prescription and therapy effectiveness in cases of ambulatory bacterial upper respiratory tract infections in children. Paediatricians working in the Lublin area were asked to fill in an inquiry that estimated their preferences to the prescription of antibiotics in children. Additionally, the microbiological examinations were performed determining the treatment effectivity. The inquiry was filled by 47 persons. The most frequently prescribed antibiotic was cefuroxime (93.6%), and the macrolids were prescribed rarely. During infection state, the predominant strain isolated was S. aureus (70.5%) and S. pyogenes (14.7%). After treatment, there was a significant increase in C. albicans isolation (44.1%) and H. influenzae (20.5%). There was a significant fall in isolation of S. pyogenes and S. aureus. Antibiotic prescription without earlier determination of susceptibility to antimicrobial agents had an influence on the appearance of postantimicrobial candidiosis, establishment of carrier state and increasing resistance among bacteria.

Anti-Bacterial Agents↗
PubMed1997

[Effects of selenium supplement on acute lower respiratory tract infection caused by respiratory syncytial virus].

An intervention study was conducted in 75 young children under one year hospitalized with pneumonia or bronchiolitis caused by respiratory syncytial virus (RSV) to evaluate therapeutic effectiveness of selenium (Se) supplement on acute respiratory lower tract infection caused by RSV with randomly controlled and double-masked method. Trial subjects were divided into two groups, one with 37 children in routine treatment and the other with 38 children in routine treatment plus Se supplement. The control group derived from 35 normal children during their physical check-up in the out-patient department. Sodium selenite was supplemented orally with 1 mg on the second day of hospitalization. Results showed that days needed for their relief of symptoms and signs were fewer in Se supplement group than that in controls and recovery in indicators of cell immune was better in the former than that in the latter. Levels of Se and glutathione peroxidase in plasma and white cells could be increased by Se supplement. It suggests that Se supplement can promote recovery from RSV infection.

Bronchiolitis, Viral↗
PubMed1988

The release of leukotrienes in the respiratory tract during infection with respiratory syncytial virus: role in obstructive airway disease.

Samples of nasopharyngeal secretions from a group of 73 infants with bronchiolitis or upper respiratory illness alone during infection with respiratory syncytial virus were analyzed for leukotriene C4 (LTC4) content using a reverse-phase high-pressure liquid chromatography assay with confirmation by radioimmunoassay. Titers of respiratory syncytial virus (RSV)-specific IgE in nasopharyngeal secretion (NPS) specimens were determined using an enzyme-linked immunosorbent assay. The highest concentrations of LTC4 were found in the first 3 to 8 days after the onset of illness, and LTC4 was detectable in progressively lower concentrations in samples obtained up to 28 days after the onset of illness. LTC4 was detected in samples of NPS obtained in the acute phase of illness from 67% of infants with bronchiolitis due to RSV and in 33% of samples of NPS obtained during the same interval from infants with upper respiratory illness alone (p less than 0.025). Concentrations of LTC4 in children with bronchiolitis were 5-fold higher (1271 pg/ml) than the mean concentration of LTC4 in children with upper respiratory illness (224 pg/ml, p less than 0.02). LTC4 was detected in 83% of the children developing an RSV-IgE response and in 24% of subjects not developing an RSV-IgE response (p less than 0.001). Quantities of LTC4 measured in NPS were directly correlated with the magnitude of the RSV-IgE response in secretions (r = 0.33, p less than 0.02). These studies lend support to previous investigations suggesting that severe bronchiolitis due to RSV results from IgE-mediated hypersensitivity reactions to viral antigens, with release of chemical mediators of airway obstruction.(ABSTRACT TRUNCATED AT 250 WORDS)

Aging↗