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PubMed2004

Comparative in vitro activity of telithromycin and beta-lactam antimicrobials against community-acquired bacterial respiratory tract pathogens in the United States: findings from the PROTEKT US study, 2000-2001.

BACKGROUND: Telithromycin is a new ketolide antimicrobial that was developed to provide good activity against resistant respiratory tract pathogens. PROTEKT US (Prospective Resistant Organism Tracking and Epidemiology for the Ketolide Telithromycin in the United States) is a multicenter in vitro surveillance study that was initiated in 2000 to chart the emergence and spread of antimicrobial-resistant pathogens in patients with community-acquired respiratory tract infections (CARTIs). OBJECTIVE: This article reports first-year results from PROTEKT US pertaining to the comparative in vitro activity of telithromycin and beta-lactam antimicrobials against community-acquired bacterial respiratory tract pathogens. METHODS: Data were compiled on the comparative in vitro activity of telithromycin and beta-lactams against Streptococcus pneumoniae (10,103 isolates), Streptococcus pyogenes (3918 isolates), and Haemophilus influenzae (2706 isolates). Minimum inhibitory concentrations (MICs) and susceptibilities were determined according to National Committee for Clinical Laboratory Standards methods. RESULTS: In total, 38.8% (3920/10,103) of pneumococcal isolates were not susceptible to penicillin (12.5% [1266] intermediate [MIC, > or =0.12-1.0 mg/dL], 26.3% [2654] resistant [MIC, > or =2 mg/dL]). Telithromycin was highly active against S pneumoniae (MIC required to inhibit 90% of isolates [MIC(90)], 0.5 mg/L), with 99.6% (10,062/10,103) of isolates fully susceptible (MIC, < or =1 mg/L). Based on MIC(90)s, the rank order of antimicrobial activity was telithromycin (0.5 mg/L), followed by amoxicillin/clavulanate (2 mg/L), penicillin (4 mg/L), and cefuroxime (8 mg/L). Telithromycin retained high activity (MIC(90), 1 mg/L) against penicillin-resistant penumococci that showed high levels of coresistance to beta-lactams. All isolates of S pyogenes were fully susceptible to the beta-lactams tested. Beta-lactamase production was common among H influenzae isolates (28.3% [765/2706]). Telithromycin was active against H influenzae (MIC(90), 4 mg/L), irrespective of beta-lactamase production. CONCLUSION: Overall, these findings from the first year of PROTEKT US support the potential value of telithromycin in the treatment of CARTIs.

Anti-Bacterial Agents↗
PubMed1984

Substance P-immunoreactive sensory nerves in the lower respiratory tract of various mammals including man.

The occurrence and origin of substance P (SP)-immunoreactive (IR) nerves in the lower respiratory tract was studied by means of immunohistochemistry in the guinea-pig, rat, cat and man. In addition, biopsies from human material were also analysed by radioimmunoassay. SP-IR nerves were seen in four principal locations: 1) under or within the lining epithelium, 2) around blood vessels, 3) within the bronchial smooth muscle layer, and 4) around local tracheobronchial ganglion cells. Ligation experiments combined with capsaicin pretreatments indicated that all SP-IR nerves in the respiratory tract are sensory. The trachea seems to be mainly supplied by the vagal nerves, while intrapulmonary bronchi and blood vessels receive SP-IR nerves of both vagal and non-vagal (spinal) origin. SP-IR nerves were also found in the human bronchi with principally similar location as in the guinea-pig. The levels of SP-IR in the trachea and peripheral bronchi of man were about 3-4 pmol/g, which is in the same range as the content of corresponding tissues from the guinea-pig. In conclusion, the present experimental findings of SP-IR nerves in the lower respiratory tract in both experimental animals and man support the functional evidence for the importance of SP in the vagal and non-vagal (spinal) control of bronchial smooth muscle tone and vascular permeability.

Adult↗
PubMed1982

Development of antibody-dependent cell-mediated cytotoxicity in the respiratory tract after natural infection with respiratory syncytial virus.

Antibody-dependent cell-mediated cytotoxicity (ADCC) was measured in nasopharyngeal secretions collected from 42 infants and young children at various intervals after primary or secondary infection with respiratory syncytial virus. ADCC was determined by specific immune release of 51Cr from respiratory syncytial virus-infected HEp-2 cell culture monolayers, with lymphocytes from adult volunteers as effector cells. Specific ADCC responses in nasopharyngeal secretions after primary infection were observed as early as 3 days after the onset of clinical symptoms, and peak activity was observed 14 to 29 days after the onset of illness. ADCC responses after reinfection were significantly greater in both the acute and convalescent phases (P less than 0.05) than were ADCC responses after primary infection. ADCC in secretions was mediated primarily by the immunoglobulin G isotype of respiratory syncytial virus antibody.

Acute Disease↗
PubMed1985

Collagenase in the lower respiratory tract of patients with adult respiratory distress syndrome.

Collagenase activity in the bronchoalveolar lavage (BAL) of patients with adult respiratory distress syndrome (ARDS) was measured against Type I collagen (17 patients) and against Type III collagen (13 patients). Serine protease activity was also measured against Type III collagen (13 patients). Type I collagenase activity was detectable in 12 of 17 and Type III collagenase was detectable in 12 of 13 patients with ARDS. The 10 control subjects had no detectable Types I or III collagenase activity. Total and differential white cell counts were analyzed in the lavage fluid. Although the total counts did not differ between patients with ARDS and control subjects, the percentage of neutrophils was increased more than 25-fold and the percentage of macrophages was reduced almost 10-fold in the ARDS patients. Serial collagenase activity was followed in 1 ARDS survivor. In this patient Type III collagenase activity peaked before the Type I collagenase activity or serine protease activity reached their maximums. Both the latter enzyme activities paralleled the total recoverable cells in the BAL.

Adult↗
PubMed1985

Development of cell-mediated cytotoxic activity in the respiratory tract after experimental infection with respiratory syncytial virus.

The development of natural killer cell and other antibody-independent cellular cytotoxic response to RSV were studied in splenic and pulmonary mononuclear effector cells obtained from groups of 6-week-old cotton rats after subcutaneous (SC) or intranasal (IN) immunization with live virulent or ultra-violet (UV) inactivated respiratory syncytial virus (RSV). No virus-induced cytotoxic activity was observed after SC immunization with live virus or IN inoculation of inactivated non-infectious virus. On the other hand significant cytotoxic activity was observed after IN infection with live RSV. The peak responses appeared on day 4 in the pulmonary cells and on day 7 in the splenic mononuclear cells. These cytotoxic activities declined to baseline levels 10 and 15 days after immunization in pulmonary and splenic cells respectively. In addition, the amount of 51Cr released was significantly reduced when unlabelled 'cold' HEp-2 cells were added to 51Cr-labelled RSV-infected CRF target cells and vice versa in the cytotoxic assay. It is suggested that viral replication at the mucosal site is essential for the induction of local as well as systemic cytotoxic activity following RSV infection. The development of such cellular reactivity may be important in the elimination of RSV following human infection.

Animals↗
PubMed1999

[Rudolf-Virchow Prize 1999. Genetics of respiratory tract carcinomas: correlation of genotype and phenotype].

In contrast to carcinomas of the upper respiratory tract lung cancer shows a considerable variety of histological differentiations and is particularly known for its morphological heterogeneity. Of clinical relevance, however, is only the distinction between small cell carcinomas (SCLC) and non-small cell lung cancer (NSCLC). We meanwhile investigated a tumor collective of several hundred respiratory tract carcinomas by Comparative Genomic Hybridization (CGH) and developed computer software for the statistical comparison of tumor groups. The analysis revealed recurrent patterns of chromosomal imbalances which are associated with morphological histotypes and biological phenotypes, e.g. there are chromosomal imbalances predominantly found in SCLC compared to NSCLC but also a considerable overlap between both entities. Specifically, the pattern of metastasizing lung squamous cell carcinomas (SCC) approaches that of SCLC. In addition, the analysis of a metastasizing combined SCLC after microdissection showed a clonal relationship between the SCC component of the primary tumor and the SCLC metastasis. These findings have direct consequences for the pathogenesis and classification of lung cancer. First, SCLC should be differentiated into primary and secondary carcinomas. Whereas primary SCLC as the predominant tumor type evolve directly from a precursor cell of probably epithelial origin, secondary SCLC develop via a NSCLC intermediate. Second, neuroendocrine differentiation in lung carcinomas should be used as a marker for dedifferentiation, worse prognosis and rapid tumor progression rather than an indicator of a putative tumor stem cell. The primary data is available at our online tumor database at http://amba.charite.de/cgh/.

Awards and Prizes↗
PubMed1991

[Virological surveillance of acute respiratory tract illnesses of children in Morioka, Japan. I. Epidemiological patterns of infection with respiratory viruses over a 10-year period].

A virological surveillance of acute respiratory tract illnesses (RTI) of children in Morioka, Japan, was maintained from September 1973 to December 1983. Nasal and throat swabs were collected from 4,334 children with RTI. These patients consisted of 3,500 children (80.8%) with upper RTI (URTI) and 834 children (16.2%) with lower RTI. When these patients with URTI were classified by maximum temperature recorded into 4 groups (less than or equal to 37.0 degrees C, 37.1-37.9 degrees C, 38.0-38.4 degrees C, and greater than or equal to 38.5 degrees C), the number of patients in each group was 1,909 (44.0% of all patients), 702 (16.2%), 378 (8.7%), and 512 (11.8%), respectively. The viruses were recovered from 932 patients (21.5%). The most frequently recovered virus was rhinovirus (HRV; 31.7% of positive patients). The other common viruses were respiratory syncytial virus (RSV; 15.3% of positives), enteroviruses (13.9%), adenoviruses (13.6%), and influenza viruses (11.1%). Coronaviruses (HCV) were isolated from 2 patients and dual infections were detected in 20 patients (2.1% of positives). HRVs were isolated from 8.9% of afebrile URTI, in addition to 7.4% of bronchitis and 12.8% of asthmatic bronchitis. RSVs were mainly isolated in the winter, but some of them were isolated in the summer of 1974 and 1975. HCVs were isolated from 2 patients with afebrile URTI in the spring of 1979. Consistent patterns have been observed in clinical manifestation, seasonal occurrence, and age distribution of infections; we indicated that HRV was not only most important pathogen of URTI, but also it was important in bronchitis and asthmatic bronchitis of children.

Adolescent↗
PubMed2006

Prevalence of viral respiratory tract infections in children with asthma.

BACKGROUND: Previous studies support a strong association between viral respiratory tract infections and asthma exacerbations. The effect of newly discovered viruses on asthma control is less well defined. OBJECTIVE: We sought to determine the contribution of respiratory viruses to asthma exacerbations in children with a panel of PCR assays for common and newly discovered respiratory viruses. METHODS: Respiratory specimens from children aged 2 to 17 years with asthma exacerbations (case patients, n = 65) and with well-controlled asthma (control subjects, n = 77), frequency matched by age and season of enrollment, were tested for rhinoviruses, enteroviruses, respiratory syncytial virus, human metapneumovirus, coronaviruses 229E and OC43, parainfluenza viruses 1 to 3, influenza viruses, adenoviruses, and human bocavirus. RESULTS: Infection with respiratory viruses was associated with asthma exacerbations (63.1% in case patients vs 23.4% in control subjects; odds ratio, 5.6; 95% CI, 2.7- 11.6). Rhinovirus was by far the most prevalent virus (60% among case patients vs 18.2% among control subjects) and the only virus significantly associated with exacerbations (odds ratio, 6.8; 95% CI, 3.2-14.5). However, in children without clinically manifested viral respiratory tract illness, the prevalence of rhinovirus infection was similar in case patients (29.2%) versus control subjects (23.4%, P > .05). Other viruses detected included human metapneumovirus (4.6% in patients with acute asthma vs 2.6% in control subjects), enteroviruses (4.6% vs 0%), coronavirus 229E (0% vs 1.3%), and respiratory syncytial virus (1.5% vs 0%). CONCLUSION: Symptomatic rhinovirus infections are an important contributor to asthma exacerbations in children. CLINICAL IMPLICATIONS: These results support the need for therapies effective against rhinovirus as a means to decrease asthma exacerbations.

Adolescent↗
PubMed2000

Colonization of the respiratory tract by a virulent strain of avian Escherichia coli requires carriage of a conjugative plasmid.

The E3 strain of E. coli was isolated in an outbreak of respiratory disease in broiler chickens, and experimental aerosol exposure of chickens to this strain induced disease similar to that seen in the field. In order to establish whether the virulent phenotype of this strain was associated with carriage of particular plasmids, four plasmid-cured derivatives, each lacking two or more of the plasmids carried by the wild-type strain, were assessed for virulence. Virulence was found to be associated with one large plasmid, pVM01. Plasmid pVM01 was marked by introduction of the transposon TnphoA, carrying kanamycin resistance, and was then cloned by transformation of E. coli strain DH5alpha. The cloned plasmid was then reintroduced by conjugation into an avirulent plasmid-cured derivative of strain E3 which lacked pVM01. The conjugant was shown to be as virulent as the wild-type strain E3, establishing that this plasmid is required for virulence following aerosol exposure. This virulence plasmid conferred expression of a hydroxamate siderophore, but not colicins, on both strain E3 and strain DH5alpha. Carriage of this plasmid was required for strain E3 to colonize the respiratory tracts of chickens but was not necessary for colonization of the gastrointestinal tract. However, the virulence plasmid did not confer virulence, or the capacity to colonize the respiratory tract, on strain DH5alpha. Thus, these studies have established that infection of chickens with E. coli strain E3 by the respiratory route is dependent on carriage of a conjugative virulence plasmid, which confers the capacity to colonize specifically the respiratory tract and which also carries genes for expression of a hydroxymate siderophore. These findings will facilitate identification of the specific genes required for virulence in these pathogens.

Animals↗
PubMed1980

[Role of sympathetic innervation of the upper respiratory tract in the reflex effects of its mechanoreceptors].

In anesthetized cats, stimulation of the mechanoreceptors of the pharynx, under--and subfold spaces of the larynx, and trachea evoked electrical responses in the peripheral and central parts of the cervical sympathetic nerve. Bilateral transection of the cervical sympathetic nerves diminished the respiratory and vasomotor reflexes from the mechanoreceptors. The signals from the receptors of the upper respiratory tract seem to reach the c. n. s. not only by the vagal fibers but the sympathetic afferent fibers as well. The reflex influences from the receptors of the upper respiratory tract on the respiratory and cardiovascular systems and on the upper respiratory tract itself are realized both by vagal and the sympathetic ways.

Animals↗
PubMed1999

Upper respiratory tract infections.

In reviewing recent advances in upper respiratory tract infections, we focus on five key topics. First, the use of ribavirin in the treatment of respiratory syncytial virus infection has been limited to the immunosuppressed. Prophylaxis in high-risk patients with specific immunoglobulin is effective and a new monoclonal antibody shows promise. Second, the efficacy of neuraminidase inhibitors in the treatment of influenza has become established. There are unresolved concerns about early implementation of therapy without a firm diagnosis; resource implications are enormous. Third, an outbreak of influenza due to avian influenza virus (H5N1) raised the possibility of a new pandemic. However, there was minimal person-to-person spread although much was learned about pathogenesis of infection. Fourth, evidence favoring the use of ciprofloxacin rather than rifampicin for meningococcal chemoprophylaxis is reviewed. Efficacy in eradicating nasopharyngeal carriage is excellent. Finally, the management of sore throat has been considered. This remains controversial but evidence supporting antibiotic therapy in adults is lacking. If treatment is indicated in childhood, shorter courses of antibiotics may be effective.

Adult↗
PubMed1991

Mycobacterium gordonae: a possible opportunistic respiratory tract pathogen in patients with advanced human immunodeficiency virus, type 1 infection.

STUDY OBJECTIVE: To determine if Mycobacterium gordonae is an opportunistic respiratory tract pathogen in patients infected with human immunodeficiency virus, type 1 (HIV-1). DESIGN: Retrospective review of medical records of all patients with positive cultures for M gordonae from 1987 to 1989. PATIENTS: Fifteen patients had positive sputum cultures for M gordonae: five patients had AIDS or had HIV-1 infections with less than or equal to 180 CD4 cells/cu mm, and ten patients had no clinical evidence of HIV-1 infection. RESULTS: Three of the five HIV-1 infected patients had clinical, roentgenographic, and microbiologic evidence of pulmonary infection due to M gordonae that responded to antimycobacterial therapy. One of the two remaining HIV-1 infected patients had disseminated M tuberculosis and possible coinfection with M gordonae, and the other was lost to follow-up. None of the ten patients without evidence of HIV-1 infection was considered to have M gordonae respiratory tract infection. CONCLUSIONS: Sputum isolates of M gordonae should be considered potential opportunistic respiratory tract pathogens in patients with advanced HIV-1 infection and with otherwise unexplained pulmonary infection.

Acquired Immunodeficiency Syndrome↗
PubMed1995

Deposition of inhaled asbestos and man-made mineral fibres in the respiratory tract.

This paper reviews publications dealing with the deposition of fibrous particles, including asbestos and man-made mineral fibres, in the respiratory tract of man and experimental animals, particularly of the rat. The effects of fibre diameter and length on total, thoracic and alveolar deposition are discussed. Total deposition in the respiratory tract of the rat increases quite steeply with aerodynamic diameter (Dae) from about 20% at a Dae of 1 micron to 100% at a Dae of 5 microns. Deposition in the alveolar region reaches a peak of about 10% at a Dae of about 2 microns, which corresponds to an actual fibre diameter of about 0.4 microns. For fibres with diameters greater than this, alveolar deposition falls rapidly. For example, long glass fibres with an actual diameter of 1.5 microns or short glass fibres with an actual diameter of 3 microns are essentially non-respirable in the rat. The fate of fibres deposited in different regions of the respiratory tract of the rat is also discussed and the factors which predispose fibres either to remain in alveolar macrophages or to be transferred to the interstitium and pulmonary lymphatics. Finally, the distributions in the lungs of fibres administered by inhalation and by intratracheal instillation are compared, and the advantages and drawbacks of each method of delivery discussed.

Administration, Inhalation↗
PubMed1999

Using pharmacodynamic and pharmacokinetic surrogate markers in clinical practice: optimizing antimicrobial therapy in respiratory-tract infections.

Pharmacodynamic and pharmacokinetic surrogate markers and their relationship to outcomes in respiratory-tract infections are reviewed. While several limitations affect the universal application of antimicrobial pharmacodynamic principles in clinical practice, recent studies have suggested that these principles may allow optimization of selected therapies. For the fluoroquinolones, the pharmacodynamic variable that has been correlated with antimicrobial efficacy is the ratio of the area under the serum concentration-time curve to the minimum inhibitory concentration. On the basis of their pharmacodynamic profiles, the newer fluoroquinolones, including such investigational agents as gatifloxacin, should produce satisfactory clinical and microbiological outcomes against pathogens commonly associated with community-acquired respiratory-tract infections. An assessment of the individual agent's pharmacodynamic profile will assist in choosing the best fluoroquinolone regimen; however, consideration should also be given to the agent's adverse-event potential.

Biomarkers↗
PubMed1991

A randomized study of ciprofloxacin versus ceftriaxone in the treatment of nursing home-acquired lower respiratory tract infections.

OBJECTIVE: To compare the efficacy and safety of ciprofloxacin and ceftriaxone in patients with nursing home-acquired lower respiratory tract infections requiring initial hospitalization. DESIGN: Prospective, randomized trial. SETTING: Extended care nursing homes affiliated with a teaching hospital. PATIENTS: Fifty patients aged 60 years or older with normal or mildly impaired renal function admitted to the hospital for treatment of lower respiratory tract infections. INTERVENTIONS: Twenty-four patients received initial therapy with intravenous ciprofloxacin, 200 mg every 12 hours (19 patients) or 400 mg every 12 hours (5 patients) during the acute phase followed by 750 mg orally every 12 hours during the convalescence phase. Twenty-six patients received initial therapy with intravenous ceftriaxone, 2 g every 24 hours during the acute phase followed by 1 g administered intramuscularly every 24 hours during the convalescent phase. The total duration of therapy was 14 days. MAIN OUTCOME MEASUREMENTS: Successful outcome was defined as resolution or marked improvement in clinical signs and symptoms of lower respiratory tract infection upon completion of the treatment course. RESULTS: Twelve (50%) of the ciprofloxacin-treated and 14 (54%) of ceftriaxone-treated patients had successful outcomes. Recurrent oropharyngeal aspiration was the reason for treatment failure in most patients refractory to either antibiotic. Mortality during therapy was 8% in each group. From 21 satisfactory sputum specimens collected, S. pneumoniae was the most common isolate, followed by H. influenzae and other Gram-negative bacteria. Ciprofloxacin therapy was well tolerated; ceftriaxone therapy was discontinued in two patients (8%) due to adverse reactions (intramuscular pain and drug fever). CONCLUSIONS: Sequential intravenous/oral ciprofloxacin appears to be as safe and effective as sequential intravenous/intramuscular ceftriaxone. The optimal dosage of intravenous ciprofloxacin in this patient population appears to be 400 mg every 12 hours; however, additional clinical and pharmacokinetic studies with this regimen are warranted.

Administration, Oral↗
PubMed2003

The use of lasers for treatment of upper respiratory tract disorders.

Lasers have become important tools for the equine surgeon in the treatment of upper respiratory tract disease in the horse. Multiple wavelengths and delivery systems are available. Indications for the use of lasers in the upper respiratory tract primarily include minimally invasive procedures not possible with conventional surgical instrumentation. New applications for the use of lasers to treat upper respiratory disease are likely to evolve with the development and introduction of new wavelengths and delivery systems.

Animals↗