[History and theory of therapeutic clinical research in chronic diseases, taking as example the chemotherapy of chronic pulmonary tuberculosis]. / Zu Geschichte und Theorie der therapeutisch-klinischen Forschung bei chronischen Krankheiten am Beispiel der Chemotherapie der chronischen Lungentuberkulose.

Historical and present problems of therapeutic clinical trials in chronic diseases are outlined and analysed, taking the chemotherapy of chronic pulmonary tuberculosis as an example.

Clinical evaluation of the efficacy of antituberculosis chemotherapy. A review of its methods.

The various methods for the evaluation of the efficacy of chemotherapy in pulmonary and extrapulmonary tuberculosis that have been developed over time are described, and their rationale is discussed. With growing experience and improvement of efficacy an ongoing need for change of techniques is to be observed, in the end always leading to higher specificity, sensitivity and reproducibility of evaluation.

[Pulmonary mycoses; laboratory diagnosis, antimycotic therapy]. / Lungen-Mykosen Laboratoriumsdiagnose, antimykotische Therapie

The microscopic, cultural and serological techniques for the diagnosis of European and non-European systemic mycoses involving the respiratory tract are reviewed. The antimicrobial, therapeutic and toxic properties of those antimycotic drugs are discussed, which can be used in the treatment of pulmonary mycoses. Data on biotransformation, kinetics and dosage are reported.

Comparative determination of minimal inhibitory and bactericidal concentrations of ciprofloxacin, cefotaxime and HR 810 for gram-negative bacteria either sensitive or resistant to ureidopenicillins and/or gentamicin.

The minimal inhibitory (MIC) and minimal bactericidal (MBC) concentrations of ciprofloxacin were compared with those of the cephalosporins HR 810 and cefotaxime in 250 strains from 10 species of Gram-negative bacteria with sensitivity or resistance to gentamicin and/or piperacillin. Ciprofloxacin had an inhibitory activity higher than, or practically equal to the best of the two cephalosporins. The MBC of ciprofloxacin was more often less than or equal to twice the MIC than with the beta-lactam antibiotics. Parallel resistance was found with pipemidic acid as representative of DNA-gyrase inhibitors. No direct parallel resistance was observed with resistance to gentamicin, piperacillin or cefotaxime.

The bactericidal activity of ampicillin, amoxicillin, tetracycline, and doxycycline against H. influenzae under various conditions of culture.

The bactericidal activities of ampicillin, amoxicillin, tetracycline, and doxycycline at a concentration of 1 mg/l were compared for 13 strains of H. influenzae with a typical minimal inhibitory concentration of these drugs. Conditions of culture used were: liquid medium in shaken flasks, stationary flasks and stationary tubes, with and without the addition of 30% human serum. Ampicillin and amoxicillin exerted the same bactericidal activity. Survival rates at 5 h were on the average near 1%, however, with large variations. At 24 h survival rate was uniformly below 0.12%. The bactericidal activity of the tetracyclines depended more on the cultural conditions. A marked reduction of the bacterial population below 1% was found at 24 h between 12 of 12 and 5 of 13 strains according to the experimental circumstances. Tetracycline was more bactericidal than doxycycline, especially in the presence of serum.

In vitro activity of temocillin, moxalactam and cefotaxime against gram negative bacteria sensitive or resistant to ureidopenicillins and/or cefacedone.

Minimal inhibitory concentrations (MIC's) of temocillin, cefotaxime and moxalactam were determined by agar dilution technique for 225 strains belonging to various species of Enterobacteriaceae and for 58 strains of H. influenzae and H. parainfluenzae. For Enterobacteriaceae, the MIC's of temocillin are distinctly higher than that of cefotaxime and moxalactam. But temocillin activity was not affected by resistance against ureidopenicillins and/or cefacedone. No resistant strains were encountered among E. coli, K. pneumoniae, Proteus spp. except one strain of P. vulgaris. In E. cloacae- strains with resistance against cefotaxime, temocillin was more active than moxalactam. S. marcescens- strains with a high MIC of temocillin were sensitive to cefotaxime and moxalactam. Temocillin is of the same order of activity as ampicillin against ampicillin-sensitive strains of H. influenzae and H. parainfluenzae. Its MIC is not influenced by beta-lactamases of these species.

[N-formimidoyl-thienamycin: in vitro activity in bacteria with resistance to beta-lactam antibiotics or gentamicin]. / N-Formimidoyl-Thienamycin: In-vitro-Aktivität bei Bakterien mit Resistenz gegen Beta-Laktam-Antibiotika oder Gentamicin.

The minimum inhibitory concentration (MIC) and the minimum bactericidal concentration (MBC) of N-formimidoyl-thienamycin were determined for 25 strains each of Escherichia coli, Klebsiella pneumoniae, Enterobacter cloacae, Serratia marcescens and Pseudomonas aeruginosa which were resistant to gentamicin and/or acylureido penicillins or cefotaxime, cefoperazone or moxalactam, and for 38 strains of the group D streptococci. The drug was very active against the most frequently encountered gram-negative resistant causative organisms of nosocomial infections. The MIC ranged from 0.25-1 mg/l for multiresistant Enterobacteriaceae, and from 0.5-4 mg/l for multiresistant P. aeruginosa. The group D streptococci (enterococci) showed a low MIC (median: 0.75 mg/l); the median of the MBC was greater than 64 mg/l, however.

[The efficacy of a maintenance dose of 100 mg doxycycline (Vibramycin) daily in bacterial infections of chronic bronchitis (author's transl)]. / Die Wirksamkeit einer Tagesdosis von 100 mg Doxycyclin (Vibramycin) bei bakteriellem Infekt der chronischen Bronchitis.

The efficacy and tolerance of a daily maintenance dose of 100 mg doxycycline (Vibramycin) was investigated in ambulant patients with chronic obstructive pulmonary disease (COPD) and bacterial infection by an open study with clinical, bacteriological and cytological control. The dosage was well tolerated and effective in the elimination of H. influenzae and pneumococci. A higher maintenance dose seems not to be necessary for this type of infections.

Bacteriological and biochemical criteria for the diagnosis of bacterial infections in chronic obstructive pulmonary disease (COPD).

In a prospective study the quantitated culture of washed sputum, the number of leukocytes and the concentration of albumin and fibrinogen in sputum were compared as diagnostic parameters for bacterial infections in patients with chronic obstructive pulmonary disease. No single criterium and no combination of criteria showed satisfactory specificity and sensitivity. Two reasons were established for the relatively loose correlation between the parameters: 1) they follow a different time course and 2) the biochemical and cellular signs of inflammation have a certain non-specificity with regard to bacterial infections. They also depend on the underlying disease. The selection of optimal criteria will become feasible only after the dynamics of bacterial and other inflammations of the respiratory tract have been studied in detail.

Heterozygosity in the Pi-system as a pathogenetic cofactor in chronic obstructive pulmonary disease (COPD).

A population (n = 526), consisting of employees with COPD, was compared with 2 control populations for the prevalence of Pi-phenotypes. In the patient group, the proportions of ZZ, SZ and MZ were significantly elevated. Among the patient population a prospective study was carried out to evaluate the role of alpha 1-antitrypsin deficiency as a cofactor in COPD. Severity of disease was estimated by standard pulmonary function tests, X-ray signs for emphysema and clinical assessment. Patients with ZZ, SZ and MZ were significantly worse than their MM partners. An influence of MS cannot be rejected. Phenotyping of all patients with COPD is advocated. Screening can also be by determining the ratio of alpha 1-antitrypsin and acid alpha 1-glycoprotein concentrations, which allowed detection of all ZZ, SZ, MZ and about 60% of the MS patients.

Prognostic value of chest radiograph, serum-angiotensin-converting enzyme and T helper cell count in blood and in bronchoalveolar lavage of patients with pulmonary sarcoidosis.

We studied the prognostic value of the initial radiologic stage, the serum-angiotensin-converting enzyme (SACE) and T helper cells in blood (OKT-4-Bl) and in bronchoalveolar lavage (OKT-4-BAL) for patients with biopsy-proven pulmonary sarcoidosis. Thirty-seven patients without prior treatment were followed up for a period of 2 years. A BAL was performed in 22 of them as part of the diagnostic workup. Clinical examination, chest radiographs, vital capacity, diffusion capacity for CO, airway resistance and PaO2 at rest and during exercise were determined initially and after 6, 12 and 24 months. According to these results, patients were classified as having progressive or nonprogressive disease. The radiologic stage and the initial SACE (38.3 +/- 10.2 vs. 43.7 +/- 13.0 nmol/ml/min) could not discriminate between the two groups. Patients with progressive disease had significantly fewer OKT-4-Bl cells (403.3/microliter +/- 146.7/microliter vs. 842.0/microliter +/- 430.1/microliter) and more OKT-4-BAL cells (24.5 +/- 15.4% vs. 7.0 +/- 2.6%) than patients with stable disease (p less than 0.01). A negative correlation between OKT-4-Bl and OKT-4-BAL cells was shown (Rs = -0.79; p less than 0.001). We conclude that the number of OKT-4-Bl and OKT-4-BAL cells can be used as prognostic parameter for patients with sarcoidosis.

[Resistance of Haemophilus influenzae to antibiotics in the Federal Republic of Germany (author's transl)]. / Antibiotikaresistenz von Haemophilus influenzae in der Bundesrepublik Deutschland.

In a multi-center study 523 strains of H. influenzae and H. parainfluenzae isolated from patients in eight towns of the Federal Republic of Germany were tested for their sensitivity to 15 different chemotherapeutic agents. 1.7% of the strains were resistant to ampicillin, 1,5% to chloramphenicol and 2.5% to tetracycline. All ampicillin-resistant strains produced beta-lactamase. For the first time, multiple resistant strains were isolated: two against ampicillin, chloramphenicol and tetracycline; one in addition also against co-trimoxazole. It is likely that there will be a spread of such resistant strains.

[Community-acquired pneumonia]. / Ambulant erworbene Pneumonien.

In a prospective study 212 patients were analysed who, between 1. 10. 1982-31.12. 1983 and 1. 10. 1985-31. 12. 1986, had been admitted to hospital because of pneumonia. The causative organism was identified in 127 of the 212 patients (60%). Pneumococcus was the most common organism (n = 64), as demonstrated by culture and immunological techniques of determining antigen or antibody. Next most common was Legionella (n = 15) of various species. Mixed infections were found in 11 patients, in all instances associated with pneumococci. There were 24 deaths (11.3%). It is concluded from these results that (1) determination of pneumococcal antigen in sputum, but not in urine or serum, can improve the identification of the causative organism; (2) Legionella is one of the most common causes of pneumonia acquired outside of hospital; and (3) adequate serological diagnosis of Legionnaire's disease is possible only if a large number of different species are tested for.

Precipitins to inhaled avian antigens: results of an inter-laboratory study.

Precipitins against avian antigens in sera from patients with extrinsic allergic alveolitis, asymptomatic pigeon and chicken breeders and from control individuals were tested with different antigen extracts in six laboratories by a variety of different methods. Eighty percent of the results coincided in identifying the positive sera from patients and 90% in identifying the controls. It seems possible therefore to exchange results among experienced laboratories with fair confidence.