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PubMed1997

Long term follow-up of children hospitalized with respiratory syncytial virus lower respiratory tract infection and randomly treated with ribavirin or placebo.

PURPOSE: To determine the long term effects of ribavirin therapy in children hospitalized for respiratory syncytial virus (RSV) lower respiratory tract infection. METHODS: Fifty-four of 60 children in randomized trials of ribavirin therapy were enrolled in a prospective follow-up study. Subjects were examined annually and had age-appropriate pulmonary function tests; interim histories were obtained from families and personal physicians. RESULTS: Recurrent lower respiratory tract illness was reported at least once for 79% of the ribavirin and 73% of placebo group. In the first 5 years after RSV, 54% of the ribavirin group and 50% of the placebo group reported wheezing. There were no significant differences between the groups in annual rates, timing, or severity of recurrent lower respiratory tract illness. No significant differences in pulmonary function were detected by tests of oxygen saturation, peak expiratory flow and spirometry. CONCLUSIONS: Children in the ribavirin treatment group did not have exacerbated respiratory symptoms compared with those in the control group, and their pulmonary function measurements were equal to those of the placebo-treated group, suggesting no long term adverse effect or benefit of ribavirin therapy.

Antiviral Agents↗

PubMed1991

Prospective hospital study of community acquired lower respiratory tract infection in the elderly.

A prospective study of community acquired lower respiratory tract infection in the elderly was carried out over a 15-month period. During this time 127 consecutive admissions to two acute geriatric medical wards were studied. An aetiology was established in 77 (61%) of cases. Streptococcus pneumoniae was identified in 37% of patients. Haemophilus influenzae in 18% and Branhamella catarrhalis in 10%. Infection with Mycoplasma pneumoniae was found in only one episode and no cases of Legionella pneumophilia were diagnosed. A significant number of patients had multiple bacterial pathogens isolated: 18% of all bacterial pathogens isolated were ampicillin resistant. Fourteen patients died (11%). Lower respiratory tract infection is a frequent cause of hospital admission for those aged over 65 and is often regarded as a preterminal event. Adequately treated however, mortality is no higher than in the general population. Knowledge of the likely pathogens allows early and appropriate antibiotic therapy for these patients whether at home or on admission to hospital.

Aged↗

PubMed1990

Emergence and persistence of beta-lactamase-producing bacteria in the upper respiratory tract in children treated with beta-lactam antibiotics.

PURPOSE: To assess the ecologic impact, in terms of selection of beta-lactamase-producing respiratory tract bacteria, of a single course of peroral beta-lactam antibiotics. PATIENTS AND METHODS: One-hundred fifty consecutive children with clinical signs of bacterial respiratory tract infection were randomly assigned to a seven-day course of treatment with either penicillin V, amoxicillin, or cefaclor. Bacteriologic specimens were collected before treatment, at its termination, and at follow-up four weeks later. RESULTS: All three drugs investigated caused a similar increase in beta-lactamase-producing bacteria, both in absolute and relative terms, an increase that persisted over a period of at least one month after completion of treatment. CONCLUSION: Penicillin V, amoxicillin, and cefaclor all act as selective agents for beta-lactamase-producing bacteria in the upper respiratory tract. Treatment with a peroral beta-lactam antibiotic puts patients at risk of becoming persistent carriers of beta-lactamase-producing bacteria.

Amoxicillin↗

PubMed1998

Can acute Chlamydia pneumoniae respiratory tract infection initiate chronic asthma?

BACKGROUND: Chlamydia pneumoniae infection can cause acute respiratory illnesses (including sinusitis, bronchitis, and pneumonia) that are sometimes associated with wheezing. Little is known about whether acute infection in a previously unexposed, nonasthmatic individual can produce persistent wheezing leading to a diagnosis of chronic asthma. OBJECTIVE: We sought to determine whether patients with acute C. pneumoniae respiratory tract infections would develop chronic asthma. METHODS: A consecutive series of 163 primary care outpatient adolescents and adults (average age 43, 45% male) who had acute wheezing illnesses or chronic asthma were evaluated for C. pneumoniae infection by serologic testing. A subgroup of these patients also had nasopharyngeal cultures for C. pneumoniae. RESULTS: Twenty patients (12%) were diagnosed with C. pneumoniae infection defined by serology (15), culture isolation (3), or both (2). Of these 20, 10 patients wheezed for the first time and 6 of them subsequently developed chronic asthma (5) or chronic bronchitis (1) along with a serologic profile suggesting chronic infection. The other 10 patients diagnosed with C. pneumoniae infection already had a diagnosis of chronic asthma. In these patients initial serologic findings suggested chronic rather than acute infection. CONCLUSIONS: Acute C. pneumoniae respiratory tract infections in previously unexposed, nonasthmatic individuals can result in chronic asthma. Patients previously diagnosed with chronic asthma should be evaluated for possible chronic C. pneumoniae infection.

Acute Disease↗

PubMed1989

Clinical efficacy of ciprofloxacin in lower respiratory tract infections.

The sputum pharmacokinetics and clinical efficacy of ciprofloxacin in lower respiratory tract infections is reviewed. Following intravenous administration, ciprofloxacin penetrates rapidly into bronchial tissue; the elimination half life is between 3 and 4 h and a dose dependency is seen. Following oral intake, the time to reach maximal concentrations is approximately two hours and after a dose of 750 mg the concentration may reach 1.7 mg/l in patients without cystic fibrosis and range from 0.5 to 3.4 mg/l in cystic fibrosis patients. Coadministration of ciprofloxacin increases serum levels and decreases total body clearance of theophylline. In controlled comparative clinical trials, ciprofloxacin has been found to have similar clinical efficacy as amoxycillin, ampicillin, cefalexin, doxycycline, co-trimoxazole, imipenem-cilastatin and ceftazidime for the treatment of a range of lower respiratory tract infections. Ciprofloxacin has been found to be superior in clinical efficacy to cefaclor. Experimental animal models suggest a role for ciprofloxacin in infections caused by Legionella pneumophila and Mycoplasma pneumoniae. The clinical and bacteriological efficacy of ciprofloxacin is less pronounced in lung infections caused by Pseudomonas aeruginosa, but is comparable to the combination of beta-lactams and aminoglycosides. Development of resistance is frequently observed during ciprofloxacin treatment of Ps. aeruginosa. Because of the availability of other oral and effective agents, ciprofloxacin is not recommended for empirical treatment of community acquired lower respiratory infections, but should be reserved for infections caused by multiply resistant organisms.

Ciprofloxacin↗

PubMed2004

[Moraxella catarrhalis in chronic and relapsing respiratory tract infections in children].

Examination of 700 children with chronic and relapsing respiratory tract infections showed that during the period from 1996 to 2003 Moraxella catarrhalis strains were isolated from the sputum of 5.5-9.7% of the patients. The frequency of the emergence was the third after Haemophilus influenzae and Streptococcus pneumoniae. In healthy children M. catarrhalis was isolated in 2.7% of the cases. The most frequent detection of M. catarrhalis was stated in children under 1 year (4.5%). The antibiotic susceptibility tests revealed that the majority of the M. catarrhalis isolates had beta-lactamase activity, were resistant to benzylpenicillin, ampicillin and lincomycin and highly susceptible to amoxycillin/clavulanate, macrolides, certain cephalosporins and levofloxacin. The isolates were most frequent in the patients of the rather severe contingent (congenital lung disease, alveolitis, chronic pneumonia, bronchial asthma). In such patients the bronchoobstructive syndrome was more frequent (46.6%). High frequency of the affection of the upper respiratory tracts in the examined children was stated (62.1%).

Adolescent↗

PubMed1992

[A study on in vitro antibacterial activity and clinical usefulness in respiratory tract infections of panipenem/betamipron, a newly synthesized carbapenem antibiotic].

Panipenem/betamipron (PAPM/BP) is a combination drug of PAPM, a new parenteral carbapenem antibiotic and BP, an amino acid derivative at a weight ratio of 1:1. Its in vitro antibacterial activities against clinically isolated respiratory pathogenic bacteria were determined. It was superior to imipenem (IPM) in the in vitro antibacterial activities against Haemophilus influenzae, Haemophilus parainfluenzae, Branhamella catarrhalis, Staphylococcus aureus including MRSA, Klebsiella pneumoniae, Serratia marcescens and Escherichia coli. PAPM had antibacterial activities almost equal to those of IPM against Streptococcus pneumoniae and Enterococcus spp. Against Pseudomonas aeruginosa, however, its antibacterial activity was about 1/4 that of IPM. The clinical usefulness of PAPM/BP was studied by dissolving it in a solution containing lactate and administering the solution by intravenous drip infusion to 12 cases of respiratory tract infections. Out of 11 cases with respiratory tract infections excluding cytomegalovirus pneumonia, the efficacy rate was 90.9%, with 4 cases of excellent and 6 cases of good responses. In terms of its bacteriological efficacies, eradication of pathogenic bacteria including super-infection were observed in 2 out of 4 strains, but 2 strains of P. aeruginosa remained unchanged. Six strains appeared as superinfected bacteria during and after administration of this preparation substituting original pathogens. Side-effects were not observed in the 12 cases, and in laboratory tests, slight transient increases of S-GOT and S-GPT were found in 1 case. In conclusion, PAPM/BP is a very useful parenteral antibiotic against respiratory tract infections and can be one of the drugs of the first choice.

Adult↗

PubMed1997

Effect of upper respiratory tract infection in patients with neuromuscular disease.

Respiratory muscle strength during acute upper respiratory tract infection (URI) was assessed in patients with various forms of neuromuscular disease. Vital capacity (VC), oxygen saturation, end-tidal PCO2, maximal inspiratory pressure (MIP), and maximal expiratory pressure (MEP) were determined in 25 stable patients with various forms of neuromuscular disease. Thirteen episodes of URI developed in 10 patients. Respiratory parameters were reassessed within 24-36 h following the onset of symptoms in each patient. In patients with URI, mean baseline VC, MIP, and MEP were 1.16 L +/- 0.14, 49.2 cm H2O +/- 6.8, and 35.5 cm H2O +/- 3.8 and fell to 1.01 L +/- 0.15, 37.1 cm H2O +/- 6.2, and 25.5 cm H2O +/- 3.0 during URI (p < 0.05 for each), respectively. Mean baseline PCO2 and oxygen saturation were 39.1 mm Hg +/- 1.1 and 95.1% +/- 1.0, and during URI, 43.9 mm Hg +/- 2.1 (p < 0.05) and 95.0% +/- 1.0 (NS), respectively. Five episodes of significant hypercapnia were observed in 4 patients. All parameters returned to near baseline values following recovery. We conclude that patients with various forms of neuromuscular disease develop reductions in respiratory muscle strength in association with URI. Unlike normal subjects, however, these decrements in respiratory muscle function may result in symptoms of shortness of breath, reductions in vital capacity, and acute hypercapnia in this patient population.

Acute Disease↗

PubMedDate not supplied

Lower respiratory tract infections in the pediatric patient.

Lower respiratory tract infections in children are common and vary from relatively self-limited courses to life-threatening presentations. Recognition of disease patterns as they relate to age, sex, race, season, geography, environmental, and socioeconomic conditions is crucial in determining appropriate differential diagnosis and treatment strategies. The majority of children with respiratory infections will present to the primary care provider in an office setting and less frequently may require immediate referral from home or the outpatient setting to an emergency department. For children with recurrent or chronic respiratory infections, referral to a subspecialist may also be necessary. Primary providers are key in determining the extent of diagnostic effort, interventions, referrals, repeat evaluations, and in reinforcing treatment plans with children and their families.

Adolescent↗

PubMed1977

Transitory IgA-deficiency, persistent IgE deficiency and recurrent respiratory tract infectious disease after splenectomy.

In a 14 year old boy, a ruptured spleen was removed. Two months after the splenectomy he developed recurrent infections of the respiratory tract. A deficiency of IgA and IgE in his blood serum was found. His impaired resistance to respiratory tract infections responded well to substitution therapy with IgA. Spontaneous clinical recovery occurred during 3 years after the splenectomy, and was parallelled by a slow return of IgA to normal levels, whereas the absence of IgE persisted. The identical twin brother of the patient, who had his spleen intact, had normal levels of serum IgA and did not suffer from frequent respiratory tract inflammations.

Adolescent↗

PubMed1975

Vitamin A and benzo(a)pyrene carcinogenesis in the respiratory tract of hamsters fed a semisynthetic diet.

Male Syrian golden hamsters were fed a semisynthetic diet, given 12 weekly intratracheal instillation of 3 mg benzo(a)pyrene adherent to 3 mg Fe2O3, and then given either 100, 1600, or 2400 mu-g retinyl acetate (RA) per week intragastrically in 2 divided doses. One-half of the animals in each group were housed conventionally; the other half were housed in laminar flow units. Hepatic and serum vitamin A levels were markedly increased in hamsters given 1600 or 2400 mu-g RA per week compared to controls given 100 mu-g, which is adequate for growth and maintenance. In hamsters housed conventionally, increased RA intake was associated with an increased incidence of benign respiratory tract tumors. In all groups of hamster housed in laminar flow units there was a longer period to death with respiratory tract tumor than in conventionally housed hamsters; increased RA intake was associated with a somewhat lower incidence of respiratory tract tumors. Laminar flow housing significantly reduced the incidence of respiratory tract infection in non-tumor-bearing hamsters. Squamous papillomas of the forestomach were significantly reduced in all groups of hamsters given high levels of RA, regardless of housing.

Animals↗

PubMedDate not supplied

Protective immune response to Mycoplasma gallisepticum demonstrated in respiratory-tract washings from M. gallisepticum-infected chickens.

Chickens inoculated with Mycoplasma gallisepticum (MG) produced IgA, IgM, and IgG detectable in washings from the upper respiratory tract (URTW; nasal sinuses and turbinates) and lower respiratory tract (LRTW; trachea, lungs, and air sacs). URTW and LRTW from infected chickens had significant protective effects in a MG-inoculated tracheal-ring-organ-culture system. Protective effects in vitro correlated positively with total MG-specific immunoglobulin titer, but not IgA titer, as determined by enzyme-linked immunosorbent assay. URTW and LRTW from infected chickens inhibited attachment of MG to tracheal-ring-organ cultures in a dose-dependent manner. This suggests that chickens produce a protective immune response to MG that locates in the respiratory tract and that attachment inhibition may be responsible for this protective effect.

Animals↗

PubMed2006

Frequency and predictors of colonization of the respiratory tract by VIM-2-producing Pseudomonas aeruginosa in patients of a newly established intensive care unit.

The aim of this study was to examine the frequency and predictors of colonization of the respiratory tract by metallo-beta-lactamase (MBL)-producing Gram-negative bacteria in patients admitted to a newly established intensive care unit (ICU) of a tertiary care hospital. Specimens of tracheobronchial aspirates for microbiological studies were obtained every day for the first 3 days of the ICU stay and subsequently every third day for the rest of the ICU stay. PCR analysis and nucleotide sequencing were performed to identify bacteria that had MBL genes. Thirty-five patients (20 male, 15 female) were hospitalized during the initial 3 month period of functioning of the ICU. Colonization of the lower respiratory tract by Gram-negative bacteria was found in 29 of 35 patients (83 %) during the first 6-20 days (median 13 days) following admission to the ICU (13 patients with Acinetobacter baumannii, ten with Pseudomonas aeruginosa, three with Enterobacter aerogenes, two with Klebsiella pneumoniae and one with Stenotrophomonas maltophilia). Six of 29 patients (21 %) colonized with Gram-negative bacteria had bla(VIM-2)-positive P. aeruginosa isolates; one of these patients developed clinical infection due to this micro-organism. Previous use of carbapenems (P=0.01) or other beta-lactams (P=0.03), as well as a stay in the ICU of >20 days (P<0.001), were associated with colonization with bla(VIM-2)-producing P. aeruginosa. In conclusion, colonization by Gram-negative bacteria of the respiratory tract of patients in this newly established ICU was common (83 %). Use of beta-lactams, including carbapenems, was associated with subsequent colonization of the respiratory tract with MBL-positive P. aeruginosa.

Acute Disease↗

PubMed1979

Survey of Cryptococcus neoformans in the respiratory tract of patients with bronchopulmonary disorders and in the air.

Cryptococcus neoformans was cultured from 9 (1%) of 835 clinical specimens examined from the respiratory tract of patients. These isolations came from 3 (0.4%) of the760 patients; 8 isolates were from sputum and one from urine. The fungus was not demonstrable in the air at a selected site during a 2-year study although other species of Cryptococcus, namely, C. albidus, C. ater, C. flavus, C. laurentii, C. magnus, C. terreus and C. uniguttulatus were isolated. The three C. neoformans positive patients were males, with pulmonary tuberculosis as the primary disease and history of repeated exposure to pigeon excreta in two. None of these patients manifested any overt signs and symptoms specificially attributable to cryptococcosis, nor did they receive any antifungal therapy. Repeated isolations of C. neoformans from sputum, a positive urine culture and demonstration of cryptococcal antibodies in a serum specimen, followed by negative cultures and serology, suggested that patient 1 had spontaneously recovered from an episode of benign, minimal pulmonary cryptococcosis. Patients 2 and 3 probably carried the fungus as a transient resident of the respiratory tract. The results suggest that C. neoformans is of uncommon occurrence in the respiratory tract of patients with bronchopulmonary disorders and that the isolation of the fungus from this site may not necessarily imply an etiologic relationship.

Adult↗

PubMed2004

Antibacterial resistance among children with community-acquired respiratory tract infections (PROTEKT 1999-2000).

OBJECTIVE: To determine the susceptibility of bacterial respiratory tract pathogens, isolated from children (0-12 years) as part of the global PROTEKT surveillance study (1999-2000), to a range of antibacterials, including the ketolide telithromycin. METHODS: Minimum inhibitory concentrations of the antibacterials studied were determined at a central laboratory using the NCCLS microdilution broth method. Macrolide resistance mechanisms were detected by PCR. RESULTS: Of 779 Streptococcus pneumoniae isolates worldwide, 43% were non-susceptible to penicillin (18% intermediate; 25% resistant) and 37% were resistant to erythromycin, with considerable intercountry variation. Eighteen per cent of 653 Haemophilus influenzae and >90% of 316 Moraxella catarrhalis isolates produced beta-lactamase. Of 640 Streptococcus pyogenes isolates, 10% were resistant to erythromycin, with considerable intercountry variation. All S. pneumoniae and 99.8% of H. influenzae isolates were susceptible to telithromycin using breakpoints proposed to the NCCLS (<or=1 and <or=4 mg/L, respectively). All M. catarrhalis and 97% of S. pyogenes and isolates were susceptible to <or=1 mg/L telithromycin. CONCLUSIONS: Antibacterial resistance complicates the empirical treatment of respiratory tract infections in children and requires continued monitoring. Telithromycin may be a useful therapeutic alternative as it is highly active against strains exhibiting various resistance phenotypes.

Anti-Bacterial Agents↗

PubMed2004

Augmentin (amoxicillin/clavulanate) in the treatment of community-acquired respiratory tract infection: a review of the continuing development of an innovative antimicrobial agent.

Amoxicillin/clavulanate (Augmentin) is a broad-spectrum antibacterial that has been available for clinical use in a wide range of indications for over 20 years and is now used primarily in the treatment of community-acquired respiratory tract infections. Amoxicillin/clavulanate was developed to provide a potent broad spectrum of antibacterial activity, coverage of beta-lactamase-producing pathogens and a favourable pharmacokinetic/pharmacodynamic (PK/PD) profile. These factors have contributed to the high bacteriological and clinical efficacy of amoxicillin/clavulanate in respiratory tract infection over more than 20 years. This is against a background of increasing prevalence of antimicrobial resistance, notably the continued spread of beta-lactamase-mediated resistance in Haemophilus influenzae and Moraxella catarrhalis, and penicillin, macrolide and quinolone resistance in Streptococcus pneumoniae. The low propensity of amoxicillin/clavulanate to select resistance mutations as well as a favourable PK/PD profile predictive of high bacteriological efficacy may account for the longevity of this combination in clinical use. However, in certain defined geographical areas, the emergence of S. pneumoniae strains with elevated penicillin MICs has been observed. In order to meet the need to treat drug-resistant S. pneumoniae, two new high-dose amoxicillin/clavulanate formulations have been developed. A pharmacokinetically enhanced tablet dosage form of amoxicillin/clavulanate 2000/125 mg twice daily (available as Augmentin XR in the USA), has been developed for use in adult respiratory tract infection due to drug-resistant pathogens, such as S. pneumoniae with reduced susceptibility to penicillin, as well as beta-lactamase-producing H. influenzae and M. catarrhalis. Amoxicillin/clavulanate 90/6.4 mg/kg/day in two divided doses (Augmentin ES-600) is for paediatric use in persistent or recurrent acute otitis media where there are risk factors for the involvement of beta-lactamase-producing strains or S. pneumoniae with reduced penicillin susceptibility. In addition to high efficacy, amoxicillin/clavulanate has a well known safety and tolerance profile of the two new high-dose formulations are not significantly different from those of conventional formulations. Amoxicillin/clavulanate is included in guidelines and recommendations for the treatment of bacterial sinusitis, acute otitis media, community-acquired pneumonia and acute exacerbations of chronic bronchitis. Amoxicillin/clavulanate continues to be an important agent in the treatment of community-acquired respiratory tract infections, both now and in the future.

Amoxicillin-Potassium Clavulanate Combination↗

PubMed1993

Control of the mucosal microcirculation in the upper respiratory tract.

This study was designed to investigate the regulatory mechanisms of the mucosal microvascular network in the upper respiratory tract. Tracheal mucosal circulation was observed using a specially constructed chamber that allowed direct microscopic visualization of mucosal arterioles. Solutions of increasing hypertonicity (500 and 900 mOsm) applied to the tracheal epithelium resulted in increasing dilation of the underlying mucosal arterioles (p < 0.001). N(omega)-nitro-L-arginine methyl ester (L-NAME, 1 mmol/L), a specific inhibitor of nitric oxide synthesis, added to a hypertonic solution inhibited dilation of mucosal arterioles (p < 0.001). Addition of the substrate for nitric oxide synthesis, L-arginine (0.6 mmol/L) to the hypertonic solution containing L-NAME resulted in dilation of mucosal arterioles once again. These data demonstrate that nitric oxide is a crucial mediator in the response of mucosal arterioles to the hypertonic stimulus presented to the epithelial surface of the trachea. Further elucidation of the control of the mucosal microcirculation in the upper respiratory tract could be implemented in new treatment for pathologic processes of the upper respiratory tract such as mucosal congestion and edema.

Analysis of Variance↗

PubMed1992

[Identification of strains on recurrent Haemophilus influenzae infections in patients with chronic respiratory tract infections].

Nontypable Haemophilus influenzae is one of the most important pathogenic bacteria in respiratory tract infections. H. influenzae is most frequently associated with recurrent infections in chronic respiratory tract infections (CRTIs). It is known that H. influenzae often reemerges after the antibiotic treatment has been stopped. We analyzed serotype, biotype, and the OMP patterns of H. influenzae isolates from sputum of CRTIs patients to determine whether an exacerbation is caused by an identical H. influenzae strain, or by a new H. influenzae strain. One hundred eighty nine strains of H. influenzae were obtained from 124 exacerbation from 24 patients. The first and second isolates were identical in 23 out of 33 exacerbations (< or = 15-days interval between each exacerbation) and also in 22 out of 34 exacerbations (15 < days but < or = 30-days interval between each exacerbation). This is called early recurrence. In contrast, the first and second isolates were different in 28 out of 34 exacerbations (> 30-days interval between each exacerbation). This is called late recurrence. These results suggest that early recurrence and late recurrence of recurrent H. influenzae infections occur in a different mechanism.

Adult↗