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[A comparative study between cefodizime (CDZM) and cefotaxime (CTX) in respiratory tract infections].

The clinical efficacy and safety of Cefodizime (CDZM), a new cephem antibiotic, was objectively compared with that of Cefotaxime (CTX) in patients with respiratory infections under a well-controlled comparative study. Patients were administered CDZM or CTX by drip infusion b.i.d. for 14 days in principle at a daily dose of two grams. The parameters assessed were clinical efficacy, safety and clinical usefulness. The following results were obtained: 1. On the basis of committee judgement the clinical efficacy rate was 78.1% (125/160) for the CDZM group, 82.7% (124/150) for the CTX group, and no significant difference was observed between the two drug groups. On the other hand, on the basis of judgement by physicians in charge, the clinical efficacy rate was 83.1% (133/160) for the CDZM group, 83.9% (125/149) for the CTX group, and no significant difference was observed between the two groups. 2. The corresponding figures for patients with pneumonia and pulmonary suppuration were 82.4% (70/85) for the CDZM group, 79.7% (59/74) for the CTX group and no significant difference was observed according to the committee judgement. The judgement by physicians in charge also revealed 83.5% (71/85) for the CDZM group and 82.2% (60/73) for the CTX group. No significant difference was noted between the two groups. While, the committee judgement for the clinical efficacy in patients with chronic respiratory tract infections showed 73.3% (55/75) for the CDZM group, 85.5% (65/76) for the CTX group, and no significant difference was observed between the two drug groups. The corresponding figures were 82.7% (62/75) for the CDZM group, 85.5% (65/76) for the CTX group, and no significant difference was observed between the two drug groups on the judgement by physicians in charge. Furthermore, the clinical efficacy of both drugs on chronic respiratory tract infections was assessed according to "Criteria for Evaluation of Clinical Efficacy of Chemotherapeutics on Chronic Respiratory Tract Infection". It was 76.8% (53/69) for the CDZM group, 76.3% (58/76) for the CTX group, and no significant difference was observed between the two groups. 3. The bacteriological eradication rate of causative pathogens was 92.4% out of 66 patients treated with CDZM and 95.5% out of 67 patients treated with CTX in whom judgement was possible. No significant difference was observed between the two drug groups. 4. The adverse reactions occurred in 4 (2.2%) patients for the CDZM group and 8 (4.5%) patients for the CTX group respectively, with no significant inter-group difference in frequency of these reactions for all cases.(ABSTRACT TRUNCATED AT 400 WORDS)

Anti-Bacterial Agents↗

Immunoglobulin-containing cells and the origin of immunoglobulins in the respiratory tract of sheep.

The amounts of immunoglobulins formed in the respiratory tract of sheep were investigated by comparing the distribution of radiolabelled immunoglobulin between plasma and lymph from the caudal mediastinal lymph node efferent duct which drains 50-70% of lung lymph. In addition, immunoglobulin-containing cells in the lymph node lymph and in the respiratory mucosa were counted by immunofluorescence. Whereas 91.6 +/- 5.92% and 67.73 +/- 10.07% of IgG1 and IgG2 respectively were plasma-derived, only 35.89 +/- 7.09% of IgA was plasma-derived. IgM and albumin were wholly plasma-derived. There was no evidence for selective transport of any immunoglobulins from plasma into lymph. It was estimated that mediastinal lymph node lymph contributed 0.12 g IgA to the circulation daily, the bulk of this being of local origin. There were only few cells expressing IgA in the caudal mediastinal lymph node and its efferent lymph indicating that, unlike gut-associated lymphoid tissue, bronchus-associated lymphoid tissue in sheep is not a major site of IgA cell precursor production. Despite this finding, IgA was the most frequent isotype of Ig-expressing cells in the respiratory mucosa and it is concluded that the locally formed IgA in lymph node lymph originated from mucosal plasma cells. IgM- and IgG-expressing cells were much less numerous than IgA-cells in the mucosa, but were the predominant isotype in the caudal mediastinal lymph node and regional lymph nodes and in mediastinal lymph node efferent lymph. These experiments have established that the respiratory tract of sheep is qualitatively similar to the intestine with respect to immunoglobulin synthesis in that the bulk of IgA is locally derived and a smaller but significant local contribution of IgG1 and IgG2 occurs, but that it is a poor source of IgA cell precursors. This implies that the IgA plasma cell population in the respiratory mucosa probably originates from distant mucosal sites.

Animals↗

Effect of altered G levels on deposition of particulates in the human respiratory tract.

The primary mode of depositon of particles in the respiratory tract in the size range 0.5-10 mum diam (unit density) is sedimentation. The rate of sedimentation is directly proportional to the velocity of settling of the particle. Therefore, the total deposition of particles in the respiratory tract as well as the region of deposition is affected by changes in gravity. Human subjects were exposed to aerosols of 2.02-mum-diam polyvinyltoluene particles at 0, 0.5, 1.0, and 2.0 G. Total deposition was measured at each G level. Results indicate an almost linear increase in total deposition with increasing G levels over the range studied. The deposition measured at 1 G was less than reported in earlier experiments and the deposition at levels less than 1 G was less than had been calculated by Muir and Beeckmans. These data show that although sedimentation plays the major role in depostion of 2.02 mum particles, it is less than previously described.

Acceleration↗

Salivary and bronchial immunoglobulins in patients with respiratory tract carcinoma.

Patients with carcinoma of the respiratory tract have been demonstrated to have elevated levels of immunoglobulins in the secretions bathing these areas. The clinical significance of this finding has remained unclear. In the present study, IgA and IgG levels were correlated with 5 year survival statistics in 53 patients with oral squamous cell carcinoma. Our findings indicate that there is no correlation between local IgA or IgG level and length of patient survival.

Adenocarcinoma↗

Empirical antibiotic therapy and lower respiratory tract infections: European guidelines and current practices.

Guidelines for the management of lower respiratory tract infection have been published in four European countries. The scope of each of these articles is reviewed and the similarities, differences and deficiencies highlighted. Very little is known about how lower respiratory tract infections (LRTIs) are managed in routine practice in Europe, especially in the community. The available data suggest major differences in antibiotic use between countries which is likely to be multifactorial in origin.

Anti-Bacterial Agents↗

Respiratory tract distribution and bioavailability of spiramycin in calves.

Pharmacokinetic determinants of spiramycin and its distribution into the respiratory tract were studied in 2 groups of calves, 4 to 10 weeks old. Group-A calves (n = 4) were used to determine pharmacokinetic variables of spiramycin after IV (15 and 30 mg/kg of body weight) and oral administrations of the drug (30 mg/kg) and to measure distribution of spiramycin into nasal and bronchial secretions. Group-B calves (n = 4) were used to determine distribution of spiramycin into lung tissue and bronchial mucosa. Spiramycin disposition was best described by use of an open 3-compartment model. Mean (+/- SD) elimination half-life was 28.7 +/- 12.3 hours, and steady-state volume of distribution was 23.5 +/- 6.0 L/kg. Bio-availability after oral administration was 4 +/- 3%. High and persistent concentrations of spiramycin were achieved in the respiratory tract tissues and fluids. Tissue-to-plasma concentration ratio was 58 for lung tissue and 18 for bronchial mucosa at 3 hours after spiramycin administration and 137 and 49, respectively at 24 hours. Secretion-to-plasma concentration ratio was 4 for nasal secretions and 7 for bronchial secretions, and remained almost constant with time. Thus, spiramycin penetrates well into the respiratory tract, although the value in bronchial secretions is lower than that in lung tissues and bronchial mucosa. Calculations indicate that a loading dose of 45 mg/kg, administered IV, followed by a maintenance dose of 20 mg/kg, IV, once daily is required to maintain active concentrations of spiramycin against bovine pathogens in bronchial secretions.

Animals↗

Ceftazidime in the treatment of lower respiratory tract infection.

Forty patients with acute lower respiratory tract infection requiring hospital admission were treated with ceftazidime. One patient developed acute dyspnoea after the first dose of the drug which was considered to be drug related and treatment was discontinued. All remaining patients were clinically assessed as being either cured or improved. In all cases that were bacteriologically assessable the pathogens were eradicated. One patient developed erythema multiforme after the end of ceftazidime treatment; this was considered to be possibly drug related.

Adolescent↗

Upper airway reactivity and upper respiratory tract infection: effect of nebulized lidocaine.

Patients presenting for elective anaesthesia and surgery may be suffering with, or recovering from, a recent upper respiratory tract infection. Airway reflexes are heightened and these individuals may be more likely to suffer airway complications on administration of general anaesthesia. We have examined the effect of nebulized lidocaine on upper airway reflexes in such subjects. Using dilute ammonia as a chemical stimulus to the upper airway, we measured upper airway reactivity in 15 volunteers (aged 22-43 yr) with symptoms of an upper respiratory tract infection for 4 days or less. The threshold concentration of ammonia producing a brief reduction in inspiratory flow was determined. Measurements were made before and after administration of a nebulized solution of 4% lidocaine 4 ml or saline. After a 2-h interval the procedure was repeated with the alternative solution. The order of administration was randomized. The observer was blind to the solution given. Ammonia threshold was found to increase in subjects after nebulized lidocaine, from a median value of 327 (range 76-878) ppm to 878 (251-1620) ppm (P = 0.0007, Wilcoxon); there was no significant change after nebulized saline. After a convalescence period of at least 4 weeks, with no return of symptoms in the preceding 2 weeks, ammonia threshold was reassessed. It was found to be increased in all 15 subjects. Comparison of the five different times of measurement showed a highly significant difference (P < 0.001, Friedman). Subsequent analysis showed significant differences (P < 0.05, Wilcoxon) between convalescent ammonia threshold and both baseline and post-saline nebulizer values. There was no significant difference between convalescent and post-lidocaine ammonia threshold. We conclude that in adult subjects, nebulized lidocaine attenuated the heightened airway reflex sensitivity associated with symptoms and signs of upper respiratory tract infection.

Adult↗

A novel pancoronavirus RT-PCR assay: frequent detection of human coronavirus NL63 in children hospitalized with respiratory tract infections in Belgium.

BACKGROUND: Four human coronaviruses are currently known to infect the respiratory tract: human coronaviruses OC43 (HCoV-OC43) and 229E (HCoV-229E), SARS associated coronavirus (SARS-CoV) and the recently identified human coronavirus NL63 (HCoV-NL63). In this study we explored the incidence of HCoV-NL63 infection in children diagnosed with respiratory tract infections in Belgium. METHODS: Samples from children hospitalized with respiratory diseases during the winter seasons of 2003 and 2004 were evaluated for the presence of HCoV-NL63 using a optimized pancoronavirus RT-PCR assay. RESULTS: Seven HCoV-NL63 positive samples were identified, six were collected during January/February 2003 and one at the end of February 2004. CONCLUSIONS: Our results support the notation that HCoV-NL63 can cause serious respiratory symptoms in children. Sequence analysis of the S gene showed that our isolates could be classified into two subtypes corresponding to the two prototype HCoV-NL63 sequences isolated in The Netherlands in 1988 and 2003, indicating that these two subtypes may currently be cocirculating.

Adolescent↗

Experimental production of respiratory tract disease in cebus monkeys after intratracheal or intranasal infection with influenza A/Victoria/3/75 or influenza A/New Jersey/76 virus.

A total of 28 cebus monkeys were inoculated intratracheally or intranasally with 10(6) 50% tissue culture infective doses of A/New Jersey/76 virus or 10(7) 50% tissue culture infective doses of A/Victoria/75 virus, and 8 additional monkeys received sterile allantoic fluid. Each of the animals became infected as evidenced by a serological response and/or shedding of the virus. Of the 10 animals inoculated intratracheally with A/Victoria/75 virus, 8 developed a systemic illness, and pulmonary infiltration was detected by X-ray in 7 of the 8. Administration of A/New Jersey/76 virus intratracheally to 10 monkeys produced a mild systemic illness in 2 animals and an upper respiratory tract illness in 6, but no illness developed in the remaining 2 monkeys; none of the animals developed X-ray evidence of lower respiratory tract disease. Intranasal administration of either virus failed to induce any illness or produced, at most, mild illness confined to the upper respiratory tract. These studies demonstrate that cebus monkeys are susceptible to respiratory tract infection with influenza A viruses and that the development of pulmonary disease is reflected in the appearance of easily recognizable radiological changes.

Animals↗

Serologic response to measles-mumps-rubella vaccine among children with upper respiratory tract infection.

The influence of concurrent upper respiratory tract infection (URTI) on immune response to MMR (measles, mumps, rubella) vaccine was evaluated by measuring IgG levels for each viral component immediately before vaccination and 6 months after vaccination in 198 12-month-old children (101 children without URTI and 97 with URTI at time of vaccination). None of the children had antibodies to measles, mumps or rubella before vaccination. Seroconversion rates and the geometric means of the antibody titers in children without URTI and in children with URTI at the time of vaccination were similar. MMR vaccination should not be delayed in children with such infections.

Antibodies, Viral↗

Effect of an educational program on the treatment of RSV lower-respiratory-tract infection.

The effectiveness and outcomes of an educational program to decrease ribavirin and antimicrobial prescribing rates and associated costs for patients with respiratory syncytial virus (RSV) lower-respiratory-tract infection are described. An educational program on the appropriate treatment for RSV infections was conducted for attending physicians and medical residents with multiple methods and forums during the 1994-95 RSV season. A retrospective chart review of 2396 patients admitted to a pediatric teaching hospital from July 1, 1991, through June 30, 1998, was conducted to measure the frequencies of ribavirin and antimicrobial prescribing in infants and young children hospitalized with RSV lower-respiratory-tract infection. The results before and after the educational program were compared. Ribavirin was prescribed for 37.9% of patients before the program, and only 9.0% received it afterward (p < 0.001). Before the program, 24.8% of patients with no risk factors received ribavirin compared with 1.6% of patients after the program (p < 0.001). However, more patients with three or more risk factors for morbidity and mortality received ribavirin before the program than afterward (97.8% versus 39.2%, respectively). A broad-spectrum i.v. antimicrobial was prescribed for 85.6% of patients before the program while 60.6% received one afterward (p < 0.001). The cost savings for ribavirin and antimicrobials during the three-year period after the program were $1,235,484 and $34,839, respectively. Hospital length of stay decreased from 5.6 to 5.1 days (p < 0.001). No readmissions occurred during the study period. A multifaceted educational intervention program may have been somewhat effective in modifying physician's prescribing habits for the treatment of RSV lower-respiratory-tract infection.

Antiviral Agents↗

An international clinical trial on the efficacy and safety of roxithromycin in 40,000 patients with acute community-acquired respiratory tract infections.

An ongoing eight-country study is being conducted in an unprecedented number of general practice patients with acute upper and lower respiratory tract infections to compare the efficacy and tolerance of roxithromycin 150 mg b.i.d. for 7-14 days with the data acquired in the prelaunch studies of these same parameters. The target population is 40,000 (to be achieved by the end of 1991) and we report the interim results from 32,405 patients, 18,020 with upper and 14,385 with lower respiratory tract infections. In acute pharyngitis/tonsillitis sinusitis, and otitis, clinical resolution or improvement has been achieved in 97%, 96%, and 96% of cases, respectively. The figures for bronchitis, exacerbation of chronic bronchitis, and pneumonia are 97%, 94%, and 95%. Side effects have been reported in only 4% of patients to date, 75% consisting of moderate gastrointestinal upsets. Of the patients, 1% withdrew from treatment because of side effects. These interim figures confirm the data from the prelaunch, controlled comparative trials and show roxithromycin to be an appropriate choice of first-line antibiotic therapy in the management of respiratory tract infections in general practice.

Acute Disease↗

The Use of Macrolides in Treatment of Upper Respiratory Tract Infections.

Antimicrobial resistance is a growing problem among upper respiratory tract pathogens. Resistance to beta-lactam drugs among Streptococcus pneumoniae, Haemophilus influenzae, and Streptococcus pyogenes is increasing. As safe and well-tolerated antibiotics, macrolides play a key role in the treatment of community-acquired upper respiratory tract infections (RTIs). Their broad spectrum of activity against gram-positive cocci, such as S. pneumoniae and S. pyogenes, atypical pathogens, H. influenzae (azithromycin and clarithromycin), and Moraxella catarrhalis, has led to the widespread use of macrolides for empiric treatment of upper RTIs and as alternatives for patients allergic to b-lactams. Macrolide resistance is increasing among pneumococci and recently among S. pyogenes, and is associated with increasing use of the newer macrolides, such as azithromycin. Ribosomal target modification mediated by erm(A) and erm(B) genes and active efflux due to mef(A) and mef(E) are the principal mechanisms of resistance in S. pneumoniae and S. pyogenes. Recently, ribosomal protein and RNA mutations have been found responsible for acquired resistance to macrolides in S. pneumoniae, S. pyogenes, and H. influenzae. Although macrolides are only weakly active against macrolide-resistant streptococci species producing an efflux pump (mef) and are inactive against pathogens with ribosomal target modification (erm), treatment failures are uncommon. Therefore, macrolide therapy, for now, remains a good alternative for treatment of upper RTIs; however, continuous monitoring of the local resistance patterns is essential.

Journal Article↗

Distribution of DNA adducts in the respiratory tract of rats exposed to diesel exhaust.

Diesel exhaust, inhaled chronically at high concentrations, was previously found to be a pulmonary carcinogen in rats. The exhaust-induced tumors were located exclusively in the peripheral lung, although all of the respiratory tract tissues were exposed to the exhaust. The purpose of this study was to determine whether there were differences in the level of DNA adducts among the regions of the respiratory tract that paralleled the site of tumors. Groups of male F344/N rats were exposed 7 hr/day, 5 day/week for 12 weeks to diesel engine exhaust at a soot concentration of 10 mg/m3 or were sham-exposed to air. The maxilloturbinates, ethmoturbinates, trachea, left mainstem bronchus (airway generation 1), axial airway (airway generations 2-12), and peripheral lung tissue were dissected from the respiratory tract. DNA was isolated from the dissected samples and analyzed for the presence of adducts using the 32P-postlabeling assay. Chromatographic maps of DNA adducts demonstrated unique patterns of DNA adducts for each of the regions. The highest level of total DNA adducts occurred in peripheral lung tissue (approximately 20 adducts per 10(9) bases). The level of DNA adducts detected in the nasal tissues was about one-fourth to one-fifth that detected in peripheral lung. There were less than three adducts per 10(9) bases in each of the regions of the major conducting airways (i.e., trachea, bronchi, axial airway). In control rats, levels of DNA adducts ranged from one adduct per 10(9) bases (mainstem bronchi, axial airway) to about nine adducts per 10(9) bases (parenchyma). The data from this study indicate that higher levels of total DNA adducts and exhaust-induced adducts (i.e., exposed minus control adducts) were present in tissues where exhaust-induced tumors were located. These data suggest that DNA adduct levels in discrete locations of the respiratory tract may be good measures of the "effective dose" of carcinogenic compounds.

Animals↗

Outcome for children under 5 years hospitalized with severe acute lower respiratory tract infections in Yemen: a 5 year experience.

Between 1991 and 1995, 2554 children under 5 years old hospitalized with severe acute lower respiratory tract infection in Al-Sabe'en, Sana'a, Yemen were studied. 47.7 per cent (1218) were under 6 months of age and 74.1 per cent (1893) were in their first 12 months. Sixty-four per cent (1633) were males. Of the 2554 cases, 221 died (overall, a case fatality rate of 8.7 per cent). 118 of the deaths (53.4 per cent) were in the under 6 months age group and 188 (85 per cent) were in the first 12 months age group. During 1995 the hospital started adopting the WHO standard case-management guidelines for treating severe acute lower respiratory tract infections. There were no significant reductions in case fatality rates in 1995 (CFR 9.8 per cent) compared with those of 1991 (CFR 7.9 per cent), 1992 (CFR 9.4 per cent), 1993 (CFR 7 per cent), or 1994 (CFR 8.5 per cent). Factors such as late hospital admission with cyanosis, malnutrition, rickets as well as increased resistance of the common causative organisms (pneumococci and H. influenzae) to antibiotics recommended by the WHO may have contributed to such a high case fatality rate remaining unchanged. In addition to reducing the risk of developing pneumonia and dying from pneumonia by improving maternal nutrition, health education, promoting breastfeeding, and preventing rickets and nutritional anaemia among the vulnerable age groups, vaccination against pneumococci and H. influenzae type b should be seriously considered as one of the strategies to reduce lower respiratory tract infection-related mortality.

Acute Disease↗

[Studies on 9,3"-diacetylmidecamycin dry syrup in pediatric acute respiratory tract infections (author's transl)].

The authors have carried out some studies on MOM dry syrup in the field of pediatrics and the results were as follows. 1. After oral administration of MOM at 20 mg/kg, the serum level peaked at 30 minutes and MOM could still be detected in the serum at up to 4 hours. The half-life was 0.67 hour. The urinary recovery rate of MOM was 1.43% up to 6 hours after this oral administration. 2. The clinical efficacy rates with MOM continuous treatment at a daily dose of 19.4 to 50.0 mg/kg (almost about 30 mg/kg) were 85.7% for upper respiratory tract infections, 66.7% for lower respiratory tract infections and 95.7% for Mycoplasma pneumonia. 3. It was easy to administer MOM orally even to the younger children. Although MOM was administered for 4 to 21 days, no side effects were observed locally or systemically except for transient slight diarrhea. These results confirmed the usefulness of MOM in the treatment of acute respiratory tract infections in children.

Administration, Oral↗

Upper respiratory tract infections in children: antibiotic treatment.

Upper respiratory tract infections, particularly pharyngitis and acute otitis media (AOM) are the commonest diseases in children. Although viruses are the main causative agents, bacteria may play an important role. With regard to antibiotic therapy, clinicians must solve two problems: differentiation between viral and bacterial aetiology and choice of the optimal drug for each bacterial disease. In patients with pharyngitis the identification of group A haemolytic streptococci as the causative agent may be very difficult if only clinical and haematological data are considered. Throat culture is time consuming and difficult to perform in ambulatory practice; the recent techniques for rapid detection of streptococcal antigens are a possible answer to this problem. In bacterial pharyngitis a single injection of benzathine penicillin is considered to be first choice. However local pain and the significant increase of the relative risk of allergic problems in comparison with the decrease of incidence of rheumatic fever may shift therapeutic preference towards macrolides. The recently marketed ones, especially miocamycin, seem to offer easier administration, fewer side-effects and better efficacy. With regard to AOM, the differentiation between bacterial and viral disease is less important because over 70% of cases are of bacterial origin. Besides, an exact aetiological diagnosis is possible only by tympanocentesis, an invasive method. In Italy amoxicillin is still the drug of choice: a twice-daily regimen has been demonstrated to be as effective as the traditional thrice-daily schedule.

Anti-Bacterial Agents↗