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Pefloxacin in the treatment of lower respiratory tract infections in geriatrics.

Pefloxacin was administered to 24 geriatric patients as treatment for lower respiratory tract infections contracted in hospital. Efficacy was evaluated by clinical, bacteriological and radiological parameters. Two-thirds of the patients responded well to therapy. Only two of 30 pathogens were not eradicated, but seven patients had superinfection or colonization by another organism. Tolerance was excellent, with only slight gastro-intestinal disorders. Pefloxacin was shown to be an effective and safe therapy for lower respiratory tract infections contracted in hospital in elderly patients.

Aged↗

Mathematical modeling of heat and water transport in human respiratory tract.

Excessive heat and water losses from the airways are stimuli to asthma. To study heat and water vapor transport in the human respiratory tract, a time-dependent model, based on a single differential equation with an analytical solution, was developed that could predict the intra-airway temperatures and water vapor contents. The key feature is the dependence of the temperature and water vapor along the respiratory tract as a function of the air residence time at each location. The model assumes disturbed laminar flow leading to enhanced transport mechanisms and wall temperature profiles modeled according to experimental data (E. R. McFadden, Jr., B. M. Pichurko, H. F. Bowman, E. Ingenito, S. Burns, N. Dowling, and J. Soloway. J. Appl. Physiol. 58: 564-570, 1985). It predicts that 1) the air equilibrates with the wall before it reaches body conditions (37 degrees C, 99.5% relative humidity); 2) conditioning of the inspired air involves several generations, with the number depending on the respiratory conditions; and 3) the walls of the upper airways are unsaturated, although it is difficult to judge at this state the depth of the respiratory tract affected.

Air↗

[Role of alveolar macrophages and neutrophils in the defense system against infection of Pseudomonas aeruginosa in the respiratory tract and the effect of derivative of muramyl dipeptide].

We investigated the role of alveolar macrophages and neutrophils on the defense system against infection of Pseudomonas aeruginosa (P. aeruginosa) in the lower respiratory tracts of rats. Intratracheal inoculation of formalin-inactivated P. aeruginosa to normal rats showed an increased number of neutrophils in bronchoalveolar lavage (BAL) fluid obtained at 24 hours after the inoculation. This response of neutrophils was induced by intravenous administration of MDP-Lys, which is muramyl dipeptide. Phagocytic activity of neutrophils for P. aeruginosa was higher than that of alveolar macrophages, indicating that neutrophils are essential phagocytes in the defense system against P. aeruginosa infection in the lower respiratory tract. Alveolar macrophages released neutrophil chemotactic factor after phagocytosis of P. aeruginosa. This function of alveolar macrophages was increased by MDP-Lys administration. These results indicated that alveolar macrophages play an important role in neutrophil accumulation by release of neutrophil chemotactic factor after the P. aeruginosa phagocytosis in the lower respiratory tract. Moreover MDP-Lys can amplify the neutrophil-dependent defense system against P. aeruginosa by activation of the alveolar macrophage function in vivo.

Acetylmuramyl-Alanyl-Isoglutamine↗

Antimicrobial use in febrile children diagnosed with respiratory tract illness in an emergency department.

BACKGROUND: In an era of increasing antibiotic resistance, the prevalence of antibiotic usage and associated factors should be ascertained to optimize their use. We set out to determine the prevalence of antibiotic use in febrile children diagnosed with respiratory tract illnesses at a children's hospital emergency department; to determine how often viral studies were conducted; and to identify patient characteristics associated with antibiotic use. METHODS: We conducted a retrospective study of antibiotic use in febrile children 3 months to 10 years old presenting with respiratory illnesses during two 1-month periods. Patient charts and laboratory tests were reviewed. Antibiotic use was related to diagnosis by logistic regression. RESULTS: A total of 836 patient visits were selected. Antibiotics were prescribed for otitis media in 96% of patients, for pneumonia in 100%, for pharyngitis in 66%, for bronchiolitis in 38%, for reactive airway disease in 24% and for viral or "upper respiratory tract illness" in 14%. For viral illness or upper respiratory tract infection, antibiotic use was associated with a fever duration of >48 h [odds ratio (OR), 3.2; 95% confidence interval (CI) 1.7, 5.9] and having a chest radiograph performed (OR 2.1; 95% CI 1.02, 4.37). Patients with pharyngitis who had a throat swab were less likely to receive an antibiotic (OR 0.08; 95% CI 0.02, 0.4) than those who did not have a swab. In this emergency department antibiotic use for these indications decreased by 11% during the 1997 to 1998 study interval (P < 0.001). CONCLUSION: Antibiotics were commonly prescribed for pharyngitis, bronchiolitis and reactive airway disease, which are conditions principally caused by viruses. Addressing reasons why there is a difference between guidelines and antibiotic use in these conditions may be important.

Anti-Bacterial Agents↗

Lung microdialysis--a powerful tool for the determination of exogenous and endogenous compounds in the lower respiratory tract (mini-review).

In vivo measurement of concentrations of drugs and endogenous substances at the site of action has become a primary focus of research. In this context the minimal invasive microdialysis (MD) technique has been increasingly employed for the determination of pharmacokinetics in lung. Although lung MD is frequently employed to investigate various drugs and endogenous substances, the majority of lung MD studies were performed to determine the pharmacokinetic profile of antimicrobials that can be related to the importance of respiratory tract infections. For the lower respiratory tract various methods, such as surgical collection of whole lung tissue and bonchoalveolar lavage (BAL), are currently available for the determination of pharmacokinetics of antimicrobials. Head-to-head comparison of pharmacokinetics of antibiotics in lung revealed high differences between MD and conventional methods. MD might be regarded as a more advantageous approach because of its higher anatomical resolution and the ability to obtain dynamic time-vs-concentration profiles within one subject. However, due to ethical objections lung MD is limited to animals or patients undergoing elective thoracic surgery. From these studies it was speculated that the concentrations in healthy lung tissue may be predicted reasonably by the measurement of concentrations in skeletal muscle tissue. However, until now this was only demonstrated for beta-lactam antibiotics and needs to be confirmed for other classes of antimicrobials. In conclusion, the present review shows that MD is a promising method for the determination of antimicrobials in the lung, but might also be applicable for measuring a wide range of other drugs and for the investigation of metabolism in the lower respiratory tract.

Animals↗

Recurrent respiratory tract infections during the first 3 years of life and atopy at school age.

BACKGROUND: The hypothesis that infections reduce the risk of atopy was investigated by estimating the association between recurrent respiratory tract infections during the first 3 years of life and atopy at school age. METHODS: According to surveys in three different areas of Norway, children were classified into three groups: asthma, wheeze without asthma (wheeze), and no asthma/no wheeze. The skin prick test (SPT) was conducted on a stratified random sample of children (n = 502). The outcome was at least one positive SPT. The exposure variable was retrospective parental report of respiratory tract infections during the first 3 years of life. RESULTS: Infections were negatively associated with atopy, crude odds ratio (cOR) = 0.3, 95% confidence interval (95% CI) 0.1-0.7, in the asthma group. A similar association was present in children with wheeze cOR = 0.4 (95% CI 0.1-1.2). The number of siblings was not associated with atopy in any group. Infections remained negatively associated with atopy in children with asthma, aOR = 0.3 (95% CI 0.1-0.7), in a logistic regression model adjusting for confounding factors. A similar pattern was present in the wheeze group. CONCLUSIONS: Recurrent respiratory tract infections during the first 3 years of life are negatively associated with atopy at school age in children with asthma.

Adolescent↗

Experience with cefsulodin therapy for lower respiratory tract infections caused by Pseudomonas aeruginosa in adults without cystic fibrosis or granulocytopenia.

Cefsulodin was administered as the sole antipseudomonal therapy to 14 adults without cystic fibrosis or granulocytopenia for infection of the lower respiratory tract caused by susceptible strains of Pseudomonas aeruginosa. At dosages of 1.0-1.5 g intravenously every 6 hr, peak serum antipseudomonal activity consistently exceeded 1:16. Twelve patients (86%) showed a favorable therapeutic response: six (43%) with eradication of P. aeruginosa from the respiratory tract and six (43%) with persistent colonization. Two patients (14%) did not respond to cefsulodin therapy. In five cases (36%), P. aeruginosa resistant to cefsulodin appeared during the course of therapy, in two cases contributing to therapeutic failure; three strains also acquired cross-resistance to two or more other antipseudomonal beta-lactam antibiotics. Cefsulodin was well tolerated, with no evidence of organ toxicity or other adverse effects discerned. These therapeutic results are comparable with or superior to those reported with other antipseudomonal drugs studied in single-drug regimens for treatment of P. aeruginosa lower respiratory tract infections in this patient population.

Adult↗

Treatment of respiratory tract infections with a combination of amoxycillin and clavulanic acid.

Forty-four patients with respiratory tract infections were treated using a new formulation of amoxycillin and clavulanic acid. Clinical diagnosis was classified as follows: 19 cases of acute exacerbations of chronic bronchitis, 10 cases of bronchiectasis, and 15 cases of diffuse or localized pneumonia. Amoxycillin/clavulanic acid combination (amoxycillin 250 mg + clavulanic acid 125 mg per tablet) was administered as 2 tablets three times per day for 7-14 days. The efficacy was as follows: chronic bronchitis 94.7%, bronchiectasis 80.0% and pneumonia 93.3%. No severe adverse reactions occurred in treated patients and no renal, hepatic or hematological toxicity was observed. Amoxycillin/clavulanic acid combination was a safe and effective antimicrobial agent for the treatment of respiratory tract infections.

Adult↗

Self-reported prescribing of antibiotics for children with undifferentiated acute respiratory tract infections with cough.

BACKGROUND: Physicians are often called on to manage children with acute respiratory tract infections with cough when the clinical presentation may not allow a differentiation between viral and bacterial etiology. To develop guidelines for appropriate antibiotic use, it is necessary to understand the present prescribing patterns of physicians who manage children presenting with such an undifferentiated acute respiratory tract infection with cough (UARTIC). OBJECTIVES: To determine the variability of self-reported prescribing habits for antibiotics for children with UARTIC. METHODS: In this cross-sectional survey by a modified Dillman's Total Design Method, a mail-out questionnaire was administered to a random sample of 181 primary care family physicians and pediatricians (Toronto, Ontario, Canada) to assess perceptions of their own antibiotic-prescribing habit. RESULTS: Completed questionnaires were received from 136 (75%) eligible physicians; 32% reported that > 10% of their office visits were for UARTIC. For a 3-day history of UARTIC 24% reported prescribing antibiotics or antibiotics in reserve (i.e. a prescription to be filled if the patient's condition does not improve) always or most times. This increased to 45% when UARTIC had worsened in the 24 h before the office visit (P < 0.001). CONCLUSION: When a pediatric patient presented with UARTIC, antibiotics or antibiotics in reserve were prescribed in the absence of clear indicators of bacterial infection. Research- and evidence-based guidelines are needed to support rational antibiotic use for UARTIC.

Acute Disease↗

[Clinical studies of cefoxitin for the treatment of chronic respiratory tract infections (author's transl)].

1. Serum and sputum concentrations of cefoxitin were measured at fixed intervals following a one hour drip infusion of 2 g to a total of three patients with chronic respiratory tract diseases. The peak levels in serum were found to be 142.1-273.6 microgram/ml at the end of the infusion and those in sputum were found to be 0.92-2.30 microgram/ml at 2 to 4 hours after initiation of the infusion. 2. Cefoxitin was administered to a total of five patients with chronic respiratory tract infections who had failed to respond to the previous treatments with conventional antibiotics. The results were that in one case the therapeutic effect was judged as excellent, in three cases as good, and in one case it was difficult to evaluate. In all cases, there was no significant abnormality indicative of side effects regarding clinical symptoms and laboratory tests of renal and hepatic functions. In a view of the findings stated above, it is considered that cefoxitin is a new antibiotic which can be used for the treatment of chronic respiratory tract infections.

Aged↗

[Pharmacovigilance study of azithromycin tablets (500 mg) in the treatment of adult patients with respiratory tract infections].

Our aim was to study a new form of azithromycin (500 mg tablets) in order to evaluate the tolerability and the influence of the ingestion of food on tolerability, the efficacy and treatment compliance in a large number of patients with respiratory tract infections. We carried out an open, non-comparative, multicenter, observational and prospective pharmacovigilance study of 3223 outpatients with respiratory tract infections randomly assigned to receive a daily dose of azithromycin for three months taken either during or outside meals. Patients were evaluated during an initial visit and two later ones in order to record the adverse events and establish the clinical efficacy. The diagnostics were as follows: pharyngotonsillitis (1200), acute otitis media (394), acute bronchitis (1134), exacerbation of chronic bronchitis (436), and community-acquired pneumonia (53). The overall therapeutic efficacy was satisfactory (cure or improvement) in 96% to 97% at the second visit and in 93% to 94% in the third (pharyngotonsillitis, 93%; acute otitis media, 91%; acute bronchitis, 94%; exacerbation of chronic bronchitis, 94%; and community-acquired pneumonia, 96%). A total of 170 adverse events were reported in 141 patients (4.4%); 12 were severe yet not related to the study medication. Eighty-eight patients showed adverse events presumed to be related to azithromycin; most were in the digestive tract. No differences in tolerability were observed in relation to food intake. Treatment compliance was high (97%). The elevated clinical efficacy, adequate compliance and the excellent tolerability profile of azithromycin tablets make them a safe and effective alternative in the treatment of respiratory tract infections.

Adolescent↗

An aerosolized fluorescent microsphere technique for evaluating particle deposition in the avian respiratory tract.

The objective of this study was to examine the feasibility of using aerosolized fluorescent microspheres to examine particle distribution in the respiratory tract of birds following aerosol exposure. Adult domestic pigeons (Columbia livia domestica; n = 5 birds per microsphere size) were exposed to aerosolized monodispersed populations of various sized carboxylate microspheres (0.5, 1.0, 2.0, 3.0, 6.0, and 10.0 microm) for 30 min. For aerosol-exposure purposes, the birds were anesthetized with injectable anesthetics, intubated, and placed on positive-pressure ventilation using a mechanical ventilator. Immediately following aerosol exposure, the birds were euthanatized, and carcasses were preserved via intravenous infusion of modified paraformaldehyde/gluteraldehyde fixative (pH = 7.2 and 340 mOsm). Initial evaluation of microsphere distribution in air sacs (cranial and caudal thoracic and abdominal) and at the level of the ostia was performed using a stereoscopic microscope with an epifluorescent module. More detailed examination of the distribution of microspheres within the respiratory tract was achieved using a confocal scanning laser microscope with a krypton argon laser and a scanning electron microscope. The results from this study revealed that positive-pressure ventilation resulted in distribution of smaller sized fluorescent microspheres (sizes 1.0, 2.0, and 3.0 microm) throughout the pigeon's respiratory tracts, and these microspheres were in highest concentration in the secondary bronchi and ostia for all of the examined air sacs. The larger sized beads (6.0 and 10.0) were confined to the upper airway (trachea and primary bronchi). The results from this study allow for a better understanding of particle deposition following positive-pressure ventilation and aerosol exposure in birds.

Aerosols↗

The relationship between atopic status and IL-10 nasal lavage levels in the acute and persistent inflammatory response to upper respiratory tract infection.

We examined the influence of atopy on virus-induced airway inflammation by comparing the nasal response to naturally acquired upper respiratory tract infection in atopic and nonatopic subjects by measurement of cytokine, chemokine, and mediator levels in nasal lavage from 44 adults (23 atopic) taken during the acute and the convalescent phases of the common cold. Nasal aspirates were examined for the presence of upper respiratory viruses by RT-PCR. In atopic and nonatopic subjects there were increased levels of IL-1beta, IL-6, IL-8, TNF-alpha, RANTES, sICAM-1, MPO, ECP, IL-10, and IFN-gamma in nasal lavage during the acute compared with the convalescent phase (p < 0.001). During the acute phase histamine levels were significantly higher in the atopic than in the nonatopic subjects (p < 0.05), whereas IL-10 levels were significantly greater in the nonatopic than in the atopic subjects (p < 0.05). At convalescence levels of IL-1beta, IL-6, sICAM-1, ECP, RANTES and albumin were significantly higher in the atopic group (p < 0.05). An upper respiratory tract virus was found in 27 volunteers (61%) during the acute stage and in two volunteers (4%) at convalescence. We conclude that virus-induced inflammatory changes within the nose are more prolonged in atopic than in nonatopic subjects and that this is associated with reduced IL-10 levels in atopic compared with nonatopic subjects during the acute phase of upper respiratory tract infection.

Acute-Phase Proteins↗

Association of Ureaplasma urealyticum infection of the lower respiratory tract with chronic lung disease and death in very-low-birth-weight infants.

Endotracheal aspirates from 200 infants who weighted less than or equal to 2500 g and who had evidence of respiratory disease were cultured within 24 h of birth for mycoplasmas, chlamydiae, viruses, and bacteria to evaluate the relation between lower respiratory tract infection and development of chronic lung disease and/or death. Ureaplasma urealyticum, an organism not visible on gram stain, not recovered on routine bacteriological media, and not susceptible to antibiotics commonly used to treat neonatal infections, was the single most common organism isolated. 14% of isolates were from infants born by caesarean section with intact membranes, which indicated that infection had occurred in utero. The findings probably represented true infection of the lower respiratory tract because the organism was recovered in pure culture in numbers greater than 10(3) from 85% of the infants, and also from the blood in 26% of infants. Those infants less than or equal to 1000 g with Ureaplasma urealyticum infection of the lower respiratory tract were twice more likely to have chronic lung disease or to die than were infants of similar birth-weight but who were uninfected, or infants greater than 1000 g. Very-low-birth-weight infants infected with ureaplasmas did not differ from those uninfected, either in demographic features or in potential risk factors for chronic lung disease.

Animals↗

Meta-analysis on the association between environmental tobacco smoke (ETS) exposure and the prevalence of lower respiratory tract infection in early childhood.

The aim of this study was to obtain quantitative information from published data on the association between environmental tobacco smoke (ETS) exposure and the prevalence of serious lower respiratory tract infections (LRTI) in infancy and early childhood. We identified 21 relevant publications on the relation between ETS and the prevalence of serious LRTI by reviewing reference lists in relevant reports and by conducting manual and computer searches (Medline database; Dissertation abstracts index of Xerox University Microfilms) of published reports between 1966 and 1995. Thirteen studies were included in a quantitative overview using random effects modeling to derive pooled odds ratios. Sensitivity analyses were conducted to test the decision rules used in extracting odds ratio data. The results of community and hospital studies are broadly consistent and show that the child of a parent who smokes is at approximately twice the risk of having a serious respiratory tract infection in early life that requires hospitalization. This association was pronounced in children younger than age two and diminished after the age of two. The combined odds ratio for hospitalization for lower respiratory tract infections in infancy or early childhood is 1.93 (95% CI 1.66-2.25); the combined odds ratio of prevalence of serious LRTI at age less than 2 years, between 0 and 6 years, and between 3 and 6 years were 1.71 (95% CI 1.33-2.20); 1.57 (1.28-1.91), and 1.25 (0.88-1.78), respectively. There was no evidence of heterogeneity across the studies in these combined odds ratios. We conclude that this meta-analysis provides strong evidence that exposure to ETS causes adverse respiratory health outcomes such as either a serious LRTI or hospitalization for LRTI. New public health campaigns are urgently needed to discourage smoking in the presence of young children.

Age Distribution↗

Normal mechanisms of heat and moisture exchange in the respiratory tract.

The initial conditioning of the inhaled gases occurs in the upper respiratory tract. The conditioned gases are at approximately 32 degrees C and more than 95% relative humidity as they enter the lower respiratory tract. This level of heat and humidity will preserve the body's defense mechanisms. When the upper airway is bypassed the gases being delivered to the lower airways need to be as close to physiologic levels as possible based on the length of time the endotracheal tube will be in place. The delivery of gases above or below normal physiologic levels has been shown to produce clinical problems.

Body Temperature Regulation↗

Cross-protection against influenza A virus infection by passively transferred respiratory tract IgA antibodies to different hemagglutinin molecules.

Mice that were intranasally immunized with different influenza A virus hemagglutinins (HA), derived from PR8 (H1N1), A/Yamagata (H1N1) or A/Fukuoka (H3N2) virus, together with cholera toxin B subunit as an adjuvant, were examined for protection against PR8 infection; PR8 HA and A/Yamagata HA immunization conferred complete protection, while A/Fukuoka HA immunization failed to confer protection. In parallel with protection, PR8 HA-, A/Yamagata HA-, and A/Fukuoka HA-immunized mice produced a high, a moderate and a low level of PR8 HA-reactive IgA in the respiratory tract, respectively. These IgA antibodies were not only higher in content in the nasal secretions, but also more cross-reactive than IgG. The purified IgA antibodies from respiratory tract washings of PR8 HA-immunized mice, which contained the HA-specific IgA corresponding to the amount detected in the nasal wash, were able to protect mice from PR8 challenge when transferred to the respiratory tract of naive mice. The transfer of IgA from A/Yamagata HA-immunized mice also afforded cross-protection against PR8 infection, whereas the IgA from A/Fukuoka HA-immunized mice failed to provide protection. The ability of transferred IgA to prevent viral infection was dependent on the amount of HA-reactive IgA remaining in the respiratory tract of the host at the time of infection. These experiments directly demonstrate that IgA antibodies to influenza A virus HA by themselves play a pivotal role in defence not only against homologous virus infection, but also against heterologous drift virus infection at the respiratory mucosa, the portal of entry for the viruses.

Animals↗

Hypoxaemia in infants with respiratory tract infections.

Nineteen infants who were graduates from special care baby units underwent two overnight tape recordings of oxygen saturation (SaO2) and breathing movements; one during an upper (n = 12) or lower (n = 7) respiratory tract infection and the other when free of infection. Baseline SaO2 was lower during infection (median 99.6 vs 100%, p less than 0.01), with four patients having values (84.3-95.5%) below the normal lower limit for full-term infants (97%). The median number of apnoeic pauses was also lower during respiratory tract infection (4.7 vs 15.7/h, p less than 0.02). The median number of episodic desaturations (SaO2 less than or equal to 80%) did not change significantly (1.3 vs 1.9/h, p greater than 0.05), with the exception of one patient who had extremely increased values during infection for both apnoeic pauses (63/h) and desaturations (112/h). No infant, however, was considered clinically hypoxaemic. Clinically unsuspected hypoxaemia may thus occur during respiratory tract infection in a proportion of infants graduating from special care baby units. Such hypoxaemia may have potentially deleterious effects.

Apnea↗