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PubMed2005

Chinchilla and murine models of upper respiratory tract infections with respiratory syncytial virus.

Respiratory syncytial virus (RSV) is a major cause of lower respiratory tract infections in infants and the elderly. While the primary infection is the most serious, reinfection of the upper airway throughout life is the rule. Although relatively little is known about either RSV infection of the upper respiratory tract or host mucosal immunity to RSV, recent literature suggests that RSV is the predominant viral pathogen predisposing to bacterial otitis media (OM). Herein, we describe mouse and chinchilla models of RSV infection of the nasopharynx and Eustachian tube. Both rodent hosts were susceptible to RSV infection of the upper airway following intranasal challenge; however, the chinchilla proved to be more permissive than the mouse. The chinchilla model will likely be extremely useful to test the role of RSV in bacterial OM and the efficacy of RSV vaccine candidates designed to provide mucosal and cytotoxic T-lymphocyte immunity. Ultimately, we hope to investigate the relative ability of these candidates to potentially protect against viral predisposal to bacterial OM.

Animals↗
PubMed2002

The continuing challenge of lower respiratory tract infections.

Lower respiratory tract infections have been a major cause of morbidity and mortality among humans since the dawn of history. The initial hope that the era of antibiotics would remove this scourge has been replaced by the more realistic view that although antimicrobial agents represent a major therapeutic advance, they have not yet solved all of the problems of lower respiratory tract infections. The pneumococcus, for example, causes mortality in a certain number of patients despite antimicrobial therapy. An even greater challenge is being imposed by the emergence of antimicrobial resistance among important bacterial pathogens, especially Streptococcus pneumoniae.

Centers for Disease Control and Prevention, U.S.↗
PubMed1995

Role of inflammation in respiratory tract infections.

In respiratory tract infections, leukocytes are recruited to the lungs, where they help remove invading organisms through phagocytic clearance. In some instances, however, the normal inflammatory response may be as destructive as it is defensive. The neutrophils secrete a proteolytic enzyme, neutrophil elastase, which has emerged as a major culprit in the pathogenesis of inflammatory airway disease. This enzyme has been found to strip the bronchial epithelium, reduce ciliary beating, and stimulate excess mucus secretion, leading to mucus retention, bacterial proliferation, and recurrent infections. Neutrophil elastase also stimulates epithelial cell interleukin-8 secretion and produces other chemoattractant cleavage products that lead to further neutrophil recruitment. It also impairs host defenses by damaging the major opsonophagocytic receptor on the neutrophil and by weakening the efficacy of immunoglobulins. For this reason, an important goal in the treatment of respiratory tract infections should be to prevent or shorten the duration of neutrophil elastase release. A number of different approaches have been proposed or attempted in an effort to modulate the proteinase burden. These include direct inhibition of elastase and interference with the recruitment, adherence, and degranulation of neutrophils. An even more fundamental approach would start in the bone marrow, where attempts might be made to modulate or modify neutrophil precursors so as to limit the destructive potential of the mature neutrophils.

Bone Marrow Cells↗
PubMed2000

[Serological screening examinations of atypical pathogens (Mycoplasma pneumoniae, Chlamydia pneumoniae) in respiratory tract infection].

Lower respiratory tract infections are a heterogeneous group of disorders induced by plenty of pathogens. Atypical bacteria play an important role in the respiratory tract pathology. In our study 90 patients with acute infection of the respiratory tract were examined in serological screening test for Mycoplasma pneumonia and Chlamydia pneumoniae. It was confirmed that in 21 patients with community acquired pneumonia Mycoplasma pneumonia antibodies were detected in 38% and Chlamydia pneumoniae in 10%. In our opinion this screening serological tests are useful for early diagnosis of atypical bacterial infections of the respiratory tract.

Acute Disease↗
PubMedDate not supplied

[Reduced natural killer function in children with recurrent respiratory tract infections].

Respiratory infections are the major cause of disease in childhood in the industrialized areas of the world. This essentially depends on two factors: immunological immaturity and immunological naivety. In most cases a virus has been considered the causative agent in respiratory infection. A defect in immune responses has been described in children with recurrent respiratory infections and in particular a decrease in CD4/CD8 T lymphocyte ratio or in IL-2 and IFN-gamma production. Our results show that Natural Killer (NK) cell activity is defective in children with recurrent respiratory infections. That is particularly noteworthy since NK cells play an important role in host defense against viral infections. At present it is difficult to understand whether the NK defect is a primary defect or it is secondary to viral infections. Further studies will help to clarify whether NK decreased activity depends on a cell damage directly caused by virus or it depends on the decreased levels of cytokines.

Adolescent↗
PubMed1991

The scope of lower respiratory tract infection.

Lower respiratory tract infections (LRTI) are commonly classified as either bronchitis or pneumonia, and these infections are associated with an extremely high morbidity in the community, as well as a high mortality in those patients that require hospitalisation. Therefore, such infections place a huge burden, both economically and as a user of health services, on the entire health care system. The antibiotic treatment of community-acquired pneumonia caused by gram-negative organisms or staphylococci is controversial, and these organisms may cause one-third of the cases of community-acquired pneumonia. Nosocomial pneumonia is caused even more often by gram-negative bacteria, and as such the development of rational and effective antibiotic therapy to cover these organisms is very important.

Anti-Bacterial Agents↗
PubMed1990

Upper respiratory tract infections.

Upper respiratory tract infections are among the most common acute infections in humans. This review discusses the clinically important aspects of the epidemiology, etiology, clinical presentation, diagnosis, management, complications, and prevention of the common cold, pharyngitis, otitis media, and sinusitis. Most episodes of the common cold and pharyngitis are of viral origin, and curative therapy is not available. Streptococcal pharyngitis, acute otitis media, and sinusitis are secondary to bacterial infections, and antibiotic therapy is important.

Anti-Bacterial Agents↗
PubMed1998

Potential infectious disease complications of upper respiratory tract infections.

Upper respiratory tract infections (URTIs), particularly otitis media and sinusitis, are prevalent among children. With recurrent URTIs there is an increased likelihood of sequelae. Suppurative complications associated with URTIs, although rare, must be treated rapidly to prevent serious morbidity and mortality. Further, increase in antimicrobial resistance may be accompanied by an increased risk for complications because infecting pathogens may be more difficult to eradicate.

Child↗
PubMed2002

Clinical and economic implications of antimicrobial resistance for the management of community-acquired respiratory tract infections.

Lower respiratory tract infections (RTIs), particularly community-acquired pneumonia (CAP), account for over 50 million deaths annually worldwide. They place an extensive clinical and financial burden on healthcare authorities. Upper RTIs, usually mild and non-life threatening, also incur significant healthcare costs. The rising prevalence of resistance of the major causative agents of CAP (Streptococcus pneumoniae, Haemophilus influenzae and Moraxella catarrhalis) to beta-lactam antimicrobials and newer macrolides has necessitated new strategies for appropriate antimicrobial usage. A successful clinical outcome will depend on the patient, choice of drug, and the epidemiology and resistance of the pathogen. Treatment failure will result in increased costs, particularly if hospitalization is required. Pharmacokinetic and pharmacodynamic parameters are being used increasingly to predict maximally effective therapy and optimal bacterial eradication, thus limiting the development of resistance. Antimicrobial susceptibility criteria by MIC should be dictated by the type and location of the infection. Modifying the current MIC breakpoints for penicillin so that more pneumococcal pneumonia isolates are reported appropriately as being susceptible may lead to a decrease in the use of broad-spectrum antimicrobial therapy and its associated increased costs, in favour of more narrow-spectrum therapy. Targeting the pathogen with the most effective antimicrobial in an appropriately selected patient should optimize clinical and microbiological success and, consequently, maximize response rates and economic outcomes. In addition, research efforts need to concentrate on developing new agents with low propensity to select for or induce resistance.

Community-Acquired Infections↗
PubMed1995

Mechanisms of airway narrowing and hyperresponsiveness in viral respiratory tract infections.

Viral respiratory tract infections are associated with an acute increase in airway responsiveness in normal subjects and patients with asthma. Airway responsiveness is also increased at least transiently in animals during acute viral infections. In this article, we discuss possible mechanisms whereby viral infections can increase airway responsiveness, emphasizing the effects of viral-induced airway epithelial damage during acute lytic infection and the mechanical consequences of airway inflammation and edema, both internal and external to the smooth muscle layer. We also describe possible mechanisms by which acute lytic viral infections could induce chronic sequelae in atopic individuals and contribute to the development of persistence of asthma. Finally, results of recent studies from our laboratory that document adenoviral genome in lungs of patients with chronic obstructive pulmonary disease (COPD) and long-term persistence of respiratory syncytial viral genome and protein in an animal model are discussed in terms of the possible role of latent and persistent viral infections in the pathogenesis of asthma and COPD.

Animals↗
PubMed2001

The management of upper respiratory tract infections.

Upper respiratory tract infections are the commonest reason for consultation in primary care. Group A beta-haemolytic Streptococcus (GABHS), the most important bacterial pathogen in this condition, can be cultured from about 30% of patients, more so in children than adults. Clinical features that are predictive of positive GABHS culture are absence of cough, fever, cervical adenopathy, tonsillar enlargement and tonsillar exudate. Use of a sore throat score can help in the detection of streptococcal throat infection. Symptomatic therapies which are useful include anticholinergic, antihistamine, decongestant, humified hot air and Vitamin C. Antibiotics are universally over-prescribed in this condition as a result of high patient expectation and faulty clinical decision making. Oral Penicillin V for 10 days is the drug of choice. Effective intervention to reduce inappropriate antibiotic prescription probably require a multifaceted approach targeted at both the patients and the prescribers.

Adult↗
PubMed2006

[Definition of low respiratory tract infections].

Lower respiratory tract infection is easily suggested on clinical signs (cough and sputum) associated with fever. To discriminate between pneumonia and acute bronchitis is crucial because of the mortality associated with pneumonia and of its specific management. Chest X-ray is a key exam for the diagnosis and should be performed on the basis of validated clinical signs that are however of weak diagnostic value. Clinical as well as radiological signs cannot be reliably used to identify the causative germ. Sputum examination, the search for pneumococcal and legionella urinary antigens are of good diagnostic value. An associated COPD may lead to an acute respiratory failure. Acute exacerbation of chronic bronchitis results from various causes but infection is involved in about 50% of the cases, mostly viral and most often due to a rhinovirus. Viral infection can be associated to bacterial infection and the most frequently isolated germs are Streptococcus pneumoniae, Haemophilus influenzae, and B. catarrhalis. Severity assessment relies on the value of basal FEV1 that is often non available. Therefore Afssaps suggests using a dyspnea index to assess exacerbation severity.

Adult↗
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↗
PubMed1995

Intermittent treatment with inhaled steroids for deterioration of asthma due to upper respiratory tract infections.

Upper respiratory tract infection (URTI) is a common cause of deterioration of asthma in children. We investigated if inhaled steroids (budesonide), started early after URTI, could reduce asthma. Thirty-one children, 3-10 years of age, with deterioration during URTI participated. The study design was double-blind, crossover and placebo-controlled. Peak-expiratory flow (PEF) and symptom scores were recorded. Four treatment periods of 9 days, two with budesonide and two with placebo, were planned. Treatment was started at the first sign of URTI. Budesonide/placebo was given by Turbuhaler at 0.2 mg qid for 3 days, tid for 3 and bid for the last 3 days. Twenty-two children completed 67 periods. Eleven visited the emergency room, only three during budesonide therapy. Five received oral steroids and two where admitted to hospital, all receiving placebo. Symptom scores were not significantly lower during budesonide treatment. PEF, both morning and evening, was significantly higher during budesonide than placebo (p = 0.015 and p = 0.022). Inhaled budesonide can attenuate exacerbation of URTI-induced asthma.

Administration, Inhalation↗
PubMed2001

Elevated levels of myeloperoxidase, pro-inflammatory cytokines and chemokines in naturally acquired upper respiratory tract infections.

Upper respiratory tract infections (URTIs) are characterised by a neutrophilic mucosal infiltration. The purpose of this study was to investigate the time course of release of the cytokines/chemokines interleukins (IL) IL-1beta, IL-1ra, tumour necrosis factor-alpha (TNF-alpha), IL-6, IL-8, interferon-gamma (IFN-gamma) and monocyte chemotactic protein (MCP-1), soluble intercellular adhesion molecule-1 (sICAM-1), myeloperoxidase (MPO) and bradykinin in nasal secretions of patients with a naturally acquired URTI. A total of 117 healthy adult volunteers were recruited for baseline nasal lavages, 39 of whom developed URTI symptoms within 6 months and returned to our centre within 48 h. Lavages were performed daily during the symptomatic period and 3 weeks thereafter, with symptoms no longer present. Compared to baseline, significantly elevated concentrations of total protein, bradykinin, IL-1beta, TNF-alpha, IL-6, IL-8, MCP-1, IFN-gamma, MPO and sICAM-1 were detected in nasal lavage fluids of symptomatic patients, whereas IL-1ra remained unaltered. All studied variables reached baseline 3 weeks after the URTI. Naturally acquired URTI represent a limited, neutrophilic inflammatory reaction, orchestrated by the release of pro-inflammatory cytokines and chemokines.

Adult↗
PubMed1993

Importance of beta-lactamase stability in treating today's respiratory tract infections.

In respiratory tract infections Streptococcus pneumoniae, Moraxella catarrhalis, Haemophilus influenzae and Klebsiella spp. are the most frequently encountered bacterial pathogens. Resistance of clinical S. pneumoniae isolates is known to be independent of beta-lactamase production, whereas resistance of the other species mentioned is due to beta-lactamase production. With respect to M. catarrhalis the first beta-lactamase-producing (bla+) isolate was detected in clinical specimens in 1976 and now, 70-90% of all clinical isolates are bla+. The enzymes BRO-1 and BRO-2 are transposon-mediated thus explaining their rapid spread; they hydrolyze penicillin compounds very rapidly and, to a lesser extent, the older cephalosporins. Resistance in clinical H. influenzae isolates is mainly due to the prevalence of the most widespread transposon-mediated beta-lactamase, TEM-1, which has a substrate profile resembling that of the BRO enzymes. Bla+ H. influenzae isolates make up to 6% of the total in Northern Europe, in Southern Europe up to 55% and in many African countries more than 80%. More than 95% of Klebsiella spp. isolates possess a chromosomally encoded penicillinase and to a varying extent a plasmid-mediated enzyme in addition. Recently, reports from several countries have pointed to the clinical relevance of 'extended-spectrum enzymes' derived by point mutation from the 'classical' TEM-1 or TEM-2 enzymes. These new enzymes (TEM-3 to TEM-21) exhibit a broadened substrate profile, inactivating even the oxyiminocephalosporins. The most stable compounds are ceftibuten and cefetamet. With respect to the future, these enzymes may spread between species due to their location on transposons.(ABSTRACT TRUNCATED AT 250 WORDS)

Bacteria↗
PubMed1998

The pattern of micro-organisms and the efficacy of new macrolide in acute lower respiratory tract infections.

Lower respiratory tract infection (LRTI) is one of the major health problems in developing countries such as Indonesia. According to the National Household Health Survey conducted by the Ministry of Health in 1992, LRTIs still rank fourth as the main cause of death in Indonesia. The problem of LRTIs could be simply managed as long as the causative organism can be identified and the proper antibiotic known. In some occasions, it is not quite so easy to identify the causative micro-organism, especially in lower tract infections. There are several methods of obtaining specimens from LRTIs for cultures. The easiest, most simple way is to collect expectorated sputum. Unfortunately, because of the high rate of contamination by upper respiratory tract flora, this method is not reliable. Recognizing the difficulties with routine expectorated sputum cultures, two alternative approaches have been suggested. One approach is to bypass potential expectorated sputum 'contaminants' in the oropharynx by transtracheal aspiration or transthoracic aspiration. The second approach is to modify the usual technique of processing expectorated sputum by either washing techniques or by quantitative cultures. Azithromycin and clarithromycin are chemically related to macrolide erithromycin. Both antibiotics retain the traditional macrolide spectrum of activity against gram-positive and atypical pneumonia pathogens, while demonstrating improved activity against gram-negative bacteria. The American Thoracic Society (ATS) recommended the use of macrolide for outpatients with community-acquired pneumonia, without comorbidity and 60 years of age or younger. A total of 34 outpatients with acute LRTIs were open-comparative, randomly allocated to treatment with the new macrolide in Persahabatan Hospital, Jakarta, 1996. The purposes of this study were: (i) to identify the causative micro-organisms; and (ii) to evaluate the clinical efficacy of the new macrolide in these infections. Azithromycin 500 mg was given orally once a day for 3 days and was administered 1 h before or 2 h after every meal. Clarithromycin 500 mg was given orally every 12 h for 10 days. The diagnosis of the patients were: 16 with pneumonia, 10 with acute bronchitis and 8 with acute exacerbation of chronic bronchitis. In this study of 34 patients, the sputum specimens were washed with N acetylcysteine before culture and we could only detect micro-organisms in one patient. Before treatment, we found 47 strains in 33 (97.05%) patients and after treatment we found five strains. From serological examination, only four (11.76%) atypical bacterial were detected. The most frequently found microorganisms were 23 strains of Klebsiella pneumoniae (40.42%), 10 of Streptococcus alpha haemolyticus (21.26%), five of Streptococcus pneumoniae (10.63%) and five of Staphylococcus aureus (10.63%). The atypical bacterial were: two Legionella pneumophila, one Mycoplasma pneumoniae and one Chlamydia pneumoniae. The clinical efficacy of new macrolides were 100% and the bacteriological responses with eradication of 94.12% vs 70.59% of isolates in the azithromycin and clarithromycin groups are shown in Table 1. There were no adverse reactions detected in the two treatment groups until the end of the study.

Administration, Oral↗