Epidemiology of tuberculosis in Europe: still a matter of deep concern.
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Biomedical subjects
Publications and source records attributed to T Schaberg.
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A survey of first-line antibiotic prescription in community-acquired lower respiratory tract infection (LRTI) by general practitioners (GP) was carried out simultaneously, using the same methodology in France, Germany, Italy, Spain and the UK. Data were obtained from 2,056 patients and 605 GPs. There was no antibiotic prescription in 17% of all LRTIs and 13% of community-acquired pneumonia (CAP) in the five countries taken together; and in 32% of all LRTIs and in 23% of CAP in Germany. Of patients with acute bronchitis, exacerbation of chronic bronchitis and viral lower respiratory tract infection, 87, 92 and 71% received antibiotics, respectively. The most frequent prescriptions were penicillins in France and the UK, third-generation cephalosporin in Italy, tetracycline in Germany and macrolide in Spain. The daily dosage of aminopenicillin prescribed was: 41% <1.5 g; 49% > or = 1.5 g and <3 g; and 10% > or = 3 g. In Italy, 53% of all antibiotics were injected in all LRTIs, and 71% in CAP; in contrast, antibiotic injection was lower than 2% both in the UK and Germany, with an average of 14% in the five countries combined. We conclude that there are variations in antibiotic prescription by GPs in Western Europe; differences are likely to be multifactorial, but could, in part, be explained by differences in health systems and sources of information available to GPs.
A questionnaire survey was performed on the use of investigations and their impact on treatment of adult lower respiratory tract infection in the community. Data on the management of 2,056 such infections were obtained simultaneously from general practitioners in France, Germany, Italy, Spain and the UK. Diagnostic tests were only performed in 29% of cases. Chest radiographs were performed most frequently (22%), followed by peripheral blood white cell count (15%) and microbiological examination of sputum (7%), with major differences being found in the frequency of these tests both by clinical diagnosis and country. A change in initial antibiotic therapy was made in 12% of cases, with use of investigation being significantly linked to such changes. Second- and third-line antibiotics were significantly different to first-line therapy, with macrolides the most frequently prescribed second-line and quinolones the most frequently prescribed third-line antibiotics.
The aim of this study was to determine the current incidence of side-effects severe enough to cause intolerance of standard antituberculosis therapy with isoniazid, rifampin and pyrazinamide in patients hospitalized as a result of pulmonary tuberculosis. Five hundred and nineteen patients with proven pulmonary tuberculosis, who initially received standard antituberculosis therapy, were retrospectively studied in the department of infectious diseases in a teaching chest hospital. The incidence of severe side-effects related to the therapy, which led to the definitive termination of one of the three standard drugs, was measured and the risk factors for intolerance were analysed. Final termination of either isoniazid, rifampin or pyrazinamide because of severe side-effects was necessary in 121 of the 519 patients (23%). The most severe side-effects leading to final termination of one drug were hepatotoxicity (11%), exanthema (6%), and arthralgia (2%). Pyrazinamide showed more severe side-effects (15%) than isoniazid (7%) and rifampin (1.5%). Significant risk factors for intolerance of the standard therapy following a multivariate analysis were a history of hepatitis (odds ratio (OR) 3.4; 95% confidence interval (95% CI) 1.6-7.6; p = 0.0026) and an age > or = 60 yrs (OR 1.9; 95% CI 1.2-3.2; p = 0.017). Both of these risk factors were also significantly associated with the intolerance of pyrazinamide (history of hepatitis: OR 2.5; 95% CI 1.4-4.3; p = 0.0045; age > or = 60 yrs: OR 2.1, 95% CI 1.3-3.5; p = 0.0029) but not of isoniazid and rifampin. The side-effects of standard antituberculosis therapy are frequent in hospitalized patients aged > or = 60 yrs or with a history of previous hepatitis, and are probably due to pyrazinamide rather than to isoniazid or rifampin.
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Resistance of Mycobacterium tuberculosis (M. tb) strains is an increasing problem worldwide. Since no public health data are available for urban populations in Germany, we investigated resistance in our hospitalized patients (n = 1011) during the last seven years. We evaluated clinical data and results of susceptibility tests (break-point technique/proportion method) for isoniazid, streptomycin, rifampin, pyrazinamide, protionamide, and ethambutol. Since 1987 there has been a relatively constant rate of 5.9% (3.9-7.8%) for single-drug resistance (SDR) but an increasing rate of multidrug-resistant (MDR) strains (> or = 2 first-line drugs) from 1.7% in 1987 to 5.8% in 1993. 69% of patients with MDR strains showed resistance to two drugs and 31% to three or more drugs. Risk factors for SDR and MDR tuberculosis revealed previous therapy (odds ratio (OR) [CI95%] SDR: 2.2 [1.7-4.0]; MDR: 4.5 [2.3-8.8]) and foreign-born status (SDR: 2.2 [1.3-3.6]; MDR: 3.5 [1.8-6.8]) to be the most important factors associated with resistance (p < 0.006-0.0001). Both primary and acquired resistance was higher in foreign-born than in German-born patients (p < 0.005). There was a considerable increase in multidrug-resistant tuberculosis in our hospital during 1987 and 1993. Since previously treated patients and patients born in countries with a high level of primary resistance had an increased risk of drug-resistant tuberculosis, we would advise a four-drug regimen as initial therapy in those patients.
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UNLABELLED: During the period from January to September 1995, 19 patients suffering from ventilatory insufficiency were adjusted to nocturnal nasal intermittent positive pressure ventilation (nIPP) therapy with a new ventilatory apparatus conforming to German regulations governing medical equipment (MedGV III). This equipment had not been available previously. 5 patients were suffering from obstructive ventilatory disorder, 5 patients from an underlying neurological disease and 3 patients from thoracic restriction. In 6 patients the reason for their ventilatory disorder was obesity hypoventilation or disorder of central ventilatory regulation. The average age was 54 years (15-73 years). Whereas 14 patients were suffering from global respiratory insufficiency already during the day, the others had marked respiratory disorder only at night. In all cases ventilation was carried out during the whole night. RESULTS: nIPPV achieved normoxia in all patients whereas in 10 patients hypercapnia was not completely eliminated. In all cases, however, the previously elevated pCO2 could be reduced. Hence, sufficient nIPPV can be achieved also with a respirator complying with the new German MedGV III regulations.
Methicillin-resistant Staphylococcus aureus (MRSA) has become a major nosocomial pathogen. We investigated MRSA-infections in patients with pulmonary diseases referring to epidemiological aspects. Between 9/92 and 2/92 we found MRSA-infections in our hospital in 24 patients (11 female, 13 male, average age 54.6 years). Clinical presentation, main and accompanying disorders and previous antibiotic therapy regimens were registered. Strains were typed using DNA-RFLP and lysotyping. MRSA detection were done in specimen from sputum (12/24) and from the bronchial secret (9/24). In 18/24 cases the MRSA-colonisation was associated with infection. In 15/24 cases the first acquisition of MRSA happened in our hospital, 6/24 times the germ was carried off other institutions and in 3/24 cases it was possibly community acquired. Most frequently patients suffered from bronchial cancer (6/24), from chronical bronchitis (5/24), from pneumonia (4/24) or Cystic fibrosis (4/24). Usually the patients showed other severe comorbidity. 13/24 patients had an antibiotic course before detecting MRSA. Typing revealed a strain already known in different hospitals of Berlin, another known strain of northern Germany and two so far unknown strains. Of interest was a different behaviour of resistance and the lost of resistance of strains in the course. MRSA-infection in pulmonary medicine emerged as a problem mostly in patients with multimorbidity and severe underlying diseases. Change of resistance in strains and new strains were observed.
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Pneumonia in the intensive care unit (ICU) has been associated with highly virulent pathogens that often exhibit resistance to multiple antibiotics and mortality rates of 30-70%. Pseudomonas aeruginosa and Enterobacteriaceae are the leading pathogens, followed by Staphylococcus aureus and polymicrobial etiologies. Recent clinical studies using monotherapy for nosocomial pneumonias resulted in low eradication rates for P. aeruginosa and staphylococci. An additional problem of these studies was the development of resistance by P. aeruginosa during the antibiotic treatment; also the selection of highly resistant strains like Xanthomonas maltophilia and Acinetobacter species was a major concern. However, several prospective studies comparing monotherapy versus combination therapy in nosocomial pneumonia of ICU patients have shown that a response rate of 60% is achievable, which is comparable to historic rates for combination therapy regimens. Only infections induced by P. aeruginosa, S. aureus, or other highly resistant pathogens (Acinetobacter, X. maltophilia, etc.) should be treated with well-defined antibiotic combinations.
To assess whether or not concomitant omeprazole treatment influences the pharmacokinetics of lomefloxacin and ciprofloxacin, a randomized, double-blind four-way-crossover study was performed. Another objective was to compare the pharmacokinetics of lomefloxacin and ciprofloxacin. Twelve healthy volunteers participated. On days 1 to 4 of each study period, each of them took 20 mg of omeprazole or a placebo orally, and on day 4, each took 400 mg of lomefloxacin or 500 mg of ciprofloxacin orally. Blood and urine samples were collected and assayed for the quinolones by high-pressure liquid chromatography. The mean peak concentrations in plasma (Cmax) and the areas under the curves (AUC), respectively, of lomefloxacin and ciprofloxacin, respectively, after prior treatment with placebo were 2.88 +/- 0.73 (mean +/- standard deviation) as against 2.60 +/- 0.76 micrograms/ml and 24.9 +/- 3.13 as against 11.9 +/- 1.89 micrograms.h/ml, and 72.4% +/- 5.10% as against 36.1% +/- 7.50% of the doses of lomefloxacin and ciprofloxacin, respectively, were recovered from the urine. None of the pharmacokinetic parameters differed significantly after prior treatment with omeprazole compared with placebo. The Cmax of lomefloxacin was not significantly higher than that of ciprofloxacin, but lomefloxacin's AUC reached twice that of ciprofloxacin because of its significantly longer half-life in plasma (6.68 +/- 1.94 as against 4.15 +/- 0.92 h, respectively, P < or = 0.01). Concomitant therapy with omeprazole did not alter the pharmacokinetics of lomefloxacin or ciprofloxacin in these single-dose studies.
On the basis of previously published PCR primer sequences, we have designed a sensitive system for detecting DNA of the Mycobacterium tuberculosis complex (MTB) in patient sputum samples which employs a fast and simplified sample preparation method appropriate for routine diagnostic testing. In order to evaluate the accuracy of the PCR assay, we performed a prospective study with 103 patients, comparing PCR results with culture results of samples obtained from a parallel culture assay as well as with subsequent culture results. Using two MTB-specific PCR primer systems, we found 48 of 49 tuberculosis (Tb) patients to be PCR positive (PCR sensitivity, 0.98). Sixteen of 54 presumably non-Tb patients showed amplifiable MTB DNA (specificity, 0.7). The study demonstrates that for diagnostic applications of MTB PCR two MTB-specific primer pairs should be used. MTB infection is extremely unlikely in cases of MTB PCR-negative samples: with our method for the exclusion of active Tb, the validity of one PCR assay seems to be equivalent to those of at least three culturing procedures. Positive PCR results do not necessarily reflect active MTB infection. It remains to be shown whether positive PCR results in Tb-negative patients mean false-positivity, an early laboratory finding which predicts a subsequent reactivation of a prior Tb infection, or whether asymptomatic patients may carry PCR-amplifiable MTB DNA without any clinical relevance. It is important to point out that the validity of PCR results in clinical studies depends on the use of contamination controls parallel to all PCR steps and the simplicity of the DNA extraction method as well as on the specificity of the PCR results.
To determine the value of the PCR assay of lymphomonocytic blood cells for the diagnosis of pulmonary tuberculosis, we compared, in a prospective study, PCR results with results of conventional diagnostic methods of Mycobacterium tuberculosis detection. Clinical investigators who were unaware of the PCR data classified 162 immunocompetent patients, who had been hospitalized because of suspected pulmonary tuberculosis, in accordance with the recommendations of the American Thoracic Society (ATS). By testing blood samples from these patients for mycobacterial DNA with three different PCR systems, we were able to demonstrate that nonquantitative PCR of peripheral blood leukocytes is of little value for the specific diagnosis of pulmonary tuberculosis. However, semiquantitative PCR assays might have some significance since we found an increasing level of mycobacterial DNA copies in blood from patients classified in ATS groups 2 to 5.
To elucidate mechanisms of myocardial hypertrophy in spontaneously hypertensive rats (SHR), we examined by Northern blotting the expression of the proto-oncogenes c-myc, c-fos, c-sis, and c-fms in the hearts of 4- and 14-week-old SHR and normotensive Wistar-Kyoto (WKY) rats. No difference in c-myc or c-fos expression could be found between SHR and WKY rats. In SHR, c-sis gave a weak and c-fms a very strong signal at 14 weeks, whereas no signal for these oncogenes was found in either WKY rats or Sprague-Dawley controls. Since c-fms codes for the receptor of monocyte colony-stimulating factor, we next used in situ hybridization to localize the presence of c-fms in hearts of SHR at 14 weeks. We found strong signals for c-fms around small blood vessels and between cardiac myocytes in 14-week-old SHR but none in WKY rats. Immunohistochemical staining corroborated the presence of clusters of monocyte infiltration at these same perivascular sites in significantly greater numbers in SHR than in WKY rats. We conclude that c-fms expression and macrophage infiltration are increased in the perivascular space of hypertrophied hearts from SHR. We suggest that mononuclear cell recruitment and induction of c-fms may play a role in the development of hypertension-associated myocardial hypertrophy.