H Mauch

Early Bactericidal Activity of Moxifloxacin in Treatment of Pulmonary Tuberculosis: a Prospective, Randomized Study

ABSTRACT Moxifloxacin is the most active fluoroquinolone against Mycobacterium tuberculosis in vitro. However, data about the efficacy in patients are not available. We enrolled 17 patients with tuberculosis in a prospective, randomized study. After 5 days of monotherapy with either moxifloxacin or isoniazid, we detected significant decreases in mean CFU per milliliter in sputum in both groups. The calculated early bactericidal activities for isoniazid and moxifloxacin were 0.209 and 0.273 log10 CFU per ml of sputum per day, respectively. According to the data from our study, moxifloxacin exhibits an early bactericidal activity that is comparable to that of isoniazid.

Procalcitonin as a diagnostic tool in lower respiratory tract infections and tuberculosis

The diagnostic significance of procalcitonin concentrations in lower respiratory tract infections and tuberculosis is not known. A prospective analysis was, therefore, performed in patients with acute exacerbation of chronic bronchitis (AECB), community-acquired pneumonia (CAP), hospital-acquired pneumonia (HAP) and tuberculosis and their procalcitonin levels compared with those of patients with noninfectious lung diseases (controls). In addition, standard inflammatory parameter data were collected. A prospective clinical study was performed with four different groups of patients and a control group that consisted of patients with noninfectious lung diseases. A total of 129 patients were included: 25 with HAP, 26 CAP, 26 AECB, 27 tuberculosis, and 25 controls. C-reactive protein level, blood cell counts and procalcitonin concentration were evaluated on the first day after onset of clinical and inflammatory symptoms prior to treatment. The median procalcitonin concentrations in HAP, CAP, AECB and tuberculosis were not elevated in relation to the cut-off level of 0.5 ng·mL−1. In the HAP group, in four of five patients who subsequently died, procalcitonin concentrations of >0.5 ng·mL−1 were found. In acute lower respiratory infections, such as HAP, CAP and AECB, significantly elevated levels were found in comparison to the control group, but below the usual cut-off level. No differences were observed between tuberculosis and the control group. Relative to the current cut-off level of 0.5 ng·mL−1, procalcitonin concentration is not a useful parameter for diagnosis of lower respiratory tract infections. However, compared to the control group, there were significantly elevated levels in patients with hospital-acquired pneumonia, community-acquired pneumonia and acute exacerbation of chronic bronchitis below the current cut-off level, which should be further investigated.

Characteristics and outcome of patients with active pulmonary tuberculosis requiring intensive care

Severe tuberculosis (TB) requiring intensive care unit (ICU) care is rare but commonly known to be of markedly bad prognosis. The present study aimed to describe this condition and to determine the mortality rate and risk factors associated with mortality. Patients with confirmed TB admitted to ICU between 1990 and 2001 were retrospectively identified and enrolled. Clinical, radiological and bacteriological data at admission and during hospital stay were recorded. A multivariate analysis was performed to identify the predictive factors for mortality. A total of 58 TB patients (12 females, mean age 48 yrs) admitted to ICU were included. Mean Acute Physiology and Chronic Health Evaluation (APACHE) II score at admission was 13.1±5.6 and 22 of 58 (37.9%) patients required mechanical ventilation. The in-hospital mortality was 15 of 58 (25.9%); 13 (22.4%) patients died in the ICU. The mean survival of patients who died was 53.6 days (range 1–229), with 50% of the patients dying within the first 32 days. The factors independently associated with mortality were: acute renal failure, need for mechanical ventilation, chronic pancreatitis, sepsis, acute respiratory distress syndrome, and nosocomial pneumonia. These data indicate a high mortality of patients with tuberculosis requiring intensive care unit care and identifies new independently associated risk factors.

Molecular diagnosis of tuberculosis: current clinical validity and future perspectives

The rapid development and availability of a variety of new molecular genetic technologies present the clinician with an array of options for the accurate diagnosis of infectious diseases. This is particularly the case for tuberculosis, since molecular methods have been rapidly introduced into all working areas of the mycobacteriology laboratory. Nucleic acid amplification methods to detect Mycobacterium tuberculosis in clinical specimens are increasingly used as a tool to diagnose tuberculosis. The bulk of recently available data from clinical evaluations performed under routine laboratory conditions indicate that these molecular methods are rapid and sensitive, but yet inferior, to culture with regard to sensitivity and specificity. Therefore, until gene amplification tests have proved to be reliable and quality control procedures exist, their clinical validity remains controversial. Consequently, definition of selected clinical applications of gene amplification to routine diagnosis of tuberculosis is important and need to be discussed. This review will focus on the clinical role of molecular methods in the direct detection and diagnosis of M. tuberculosis in clinical samples. In addition, molecular genetic approaches designed to determine drug susceptibility and to discriminate strains below the species level will be outlined and discussed in terms of their current and future clinical applicability.

A Prediction Model for Bacterial Etiology in Acute Exacerbations of COPD

Objectives:Bacteria play a leading role in acute exacerbations of chronic obstructive pulmonary disease (COPD), but we lack predictors of bacterial etiology. We developed a prediction model for infection with gram-negative enteric bacteria (GNEB) and Pseudomonas aeruginosa.Methods:Clinical presentation, sputum characteristics, microbial sputum patterns, lung function and previous and concomitant medication were prospectively recorded in patients with moderate to severe exacerbation of COPD. Risk factors for a specific bacterial etiology were c alculated and a prediction model developed.Results:A total of 193 patients with acute exacerbation were included. In 121 (62.6%) of them a microbial etiology could be identified, most frequently Haemophilus influenzae (32 strains), Streptococcus pneumoniae (22 strains) and P. aeruginosa (12 strains). Multivariate analysis identified severe airflow obstruction and use of systemic steroids as predictors for exacerbation due to gram-negative enteric bacilli and P. aeruginosa. A prediction model including FEV1 < 35% of predicted value, systemic steroid use and prior antibiotic therapy within preceeding 3 months had a negative predictive of 89%, being a helpful tool in excluding patients at risk of exacerbation due to gram-negative enteric bacilli and P. aeruginosa when all criteria are absent.Conclusion:A simple prediction model based on three factors may identify COPD patients at low risk for exacerbations with gram-negative enteric bacilli and P. aeruginosa. Bacterial Etiology in COPD Exacerbations.

Drug-resistant pulmonary tuberculosis in Berlin, Germany, 1987-1993

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 = 1,011) over the last 7 yrs. We therefore evaluated clinical data and results of susceptibility tests (breakpoint 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. Sixty nine percent 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) (95% confidence interval (95% CI)); 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. Both primary and acquired resistance were higher in foreign-born than in German-born patients. We conclude that there was a considerable increase in multidrug-resistant tuberculosis in our hospital from 1987 to 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.

Nosocomial pneumonia: epidemiology, pathogenesis, diagnosis, treatment and prevention.

Nosocomial pneumonia is the second most common nosocomial infection and the leading cause of death from hospital-acquired infection. Supine body position in mechanically ventilated patients, and cardiopulmonary resuscitation and continuous sedation are significant risk factors for developing nosocomial pneumonia. During the past 2 years some new therapeutic approaches for nosocomial pneumonia and modifications to established therapies have been described, such as optimal pharmacodynamic evaluations, monotherapy versus combination therapy, computer-assisted management programmes and antibiotic rotations.

Rapid drug susceptibility testing of Mycobacterium tuberculosis using conventional solid media

Radiometric methods for M. tuberculosis drug susceptibility testing yield much faster results than standard techniques; however, these methods require sophisticated equipment and are expensive. We investigated a rapid drug susceptibility testing method for isoniazid, rifampin, ethambutol, streptomycin and pyrazinamide in specimens from 197 patients with pulmonary tuberculosis using a simplified agar-dilution method. Middlebrook 7H11 agar solid medium and microcolony detection were used to test sputum from 64 smear-positive, and from 70 culture-positive but smear-negative patients. Culture-positive material from bronchoscopy, surgical biopsy, pleural fluid or gastric fluid of 63 patients was tested. In 64 smear-positive patients, the median time for final susceptibility results was 11 days (95% confidence interval (95% CI) 10-12 days) compared to 62 days (95% CI 56-66 days) with the standard method. In 133 smear-negative patients, results were available after a median of 35 days (95% CI 32-40 days) in contrast to 72 days (95% CI 62-83 days) with the standard method, regardless of whether or not sputum or other materials were used for primary culture. The rapid method detected all cases of single-drug resistance (n = 20) and multidrug resistance (n = 14) within 13 days (95% CI 9-17 days) in smear-positive patients (n = 8), or within 38 days (95% CI 35-48 days) in smear-negative patients (n = 26). Only one discrepancy was encountered in 985 resistance tests. Moreover, contamination was not observed. Our rapid susceptibility testing method for M. tuberculosis on Middlebrook 7H11 agar is fast, practical and inexpensive. It provides an alternative when more sophisticated techniques are not available or affordable.

NOSOCOMIAL PNEUMONIA IN THE CRITICAL CARE UNIT

Nosocomial pneumonia poses a major threat to the recovery of patients receiving mechanical ventilation. In addition, nosocomial pneumonia is often difficult to diagnose. This article examines the extent of the threat and some of the difficulties facing the critical care physician when diagnosing nosocomial pneumonia.

Sparfloxacin in the treatment of drug resistant tuberculosis or intolerance of first line therapy.

Patients with multiresistant tuberculosis (TB) and patients with intolerance of first line antituberculosis drugs present a major treatment problem. Sparfloxacin is highly active against mycobacteria, but the use is restricted by side effects and the contribution to antituberculosis therapy is unclear. A prospective study has therefore been performed to analyse the efficacy and tolerability of sparfloxacin in cases of resistant TB or intolerance of first line therapy. Between April 1993 and April 1999, 30 TB patients (28 with pulmonary TB and two with lymph node TB) were treated with combinations of sparfloxacin and at least two other drugs at the Chest Hospital Heckeshorn, Berlin. Sixteen patients were infected by resistant mycobacteria (one single drug resistance (SDR), one polyresistance, and 14 multidrug resistances (MDR); 14 males (age range 23-53 yrs), 2 females (68-74 yrs)). Twelve patients (11 males, one female, 27-80 yrs) had not tolerated first line antituberculosis drugs. Two additional male patients had continuous proof of Mycobacterium tuberculosis in sputum without resistance during therapy The duration of sparfloxacin therapy during hospitalization ranged 2.5-4 months. Twenty-five patients completed therapy and were cured according to this studys definition. Although sparfloxacin was generally well tolerated, five mild phototoxic reactions and six moderate prolongations of the electrocardiographic QT-interval (30-40 ms compared to baseline < or = 450 ms) were registered without clinical symptoms in the patient group. In summary, sparfloxacin proved an effective and safe alternative antituberculosis drug for complicated tuberculosis.