Neuroleptic drugs in the treatment of tuberculosis: Minimal inhibitory concentrations of different phenothiazines against Mycobacterium tuberculosis.

Due to an increase of drug resistant TB, alternative drugs that are not currently listed in the WHO guidelines on MDR TB treatment are currently being evaluated. Our group tested 100 susceptible, 20 MDR and 2 XDR Mtb strains against the phenothiazine derivatives thioridazine, trifluoperazine and triflupromazine. MIC testing was performed on Middlebrook 7H10 agar and was defined as the lowest drug concentration that inhibits ≥99% of the bacterial population. We confirm very good in vitro activity of phenothiazines against Mycobacterium tuberculosis. In >77% of all strains MICs of ≤10 µg/ml were found.

The frequency of EGFR and KRAS mutations in non-small cell lung cancer (NSCLC): routine screening data for central Europe from a cohort study.

OBJECTIVES: Owing to novel therapy strategies in epidermal growth factor receptor (EGFR)-mutated patients, molecular analysis of the EGFR and KRAS genome has become crucial for routine diagnostics. Till date these data have been derived mostly from clinical trials, and thus collected in pre-selected populations. We therefore screened 'allcomers' with a newly diagnosed non-small cell lung carcinoma (NSCLC) for the frequencies of these mutations. DESIGN: A cohort study. SETTING: Lung cancer centre in a tertiary care hospital. PARTICIPANTS: Within 15 months, a total of 552 cases with NSCLC were eligible for analysis. PRIMARY AND SECONDARY OUTCOME MEASURES: Frequency of scrutinising exons 18, 19 and 21 for the presence of activating EGFR mutation and secondary codon 12 and 13 for activating KRAS mutations. RESULTS: Of the 552 patients, 27 (4.9%) showed a mutation of EGFR. 19 of these patients (70%) had deletion E746-A750 in codon 19 or deletion L858R in codon 21. Adenocarcinoma (ACA) was the most frequent histology among patients with EGFR mutations (ACA, 22/254 (8.7%) vs non-ACA, 5/298 (1.7%); p<0.001). Regarding only ACA, the percentage of EGFR mutations was higher in women (16/116 (14%) women vs 6/138 (4.3%) men; p=0.008). Tumours with an activating EGFR mutation were more likely to be from non-smokers (18/27; 67%) rather than smoker (9/27; 33%). KRAS mutation was present in 85 (15%) of all cases. In 73 patients (86%), the mutation was found in exon 12 and in 12 cases (14%) in exon 13. Similarly, ACA had a higher frequency of KRAS mutations than non-ACA (67/254 (26%) vs 18/298 (6.0%); p<0.001). CONCLUSIONS: We found a lower frequency for EGFR and KRAS mutations in an unselected Caucasian patient cohort as previously published. Taking our results into account, clinical trials may overestimate the mutation frequency for EGFR and KRAS in NSCLC due to important selection biases.

Viral colonization in intubated patients: initial pathogen pattern and follow-up.

INTRODUCTION: Colonization of the lower respiratory tract is an independent risk factor for ventilator-associated pneumonia. Little is known about the frequency of viral colonization on intubation and during mechanical ventilation. METHODS: Overall, 65 eligible intubated patients with no initial signs of pulmonary infection were studied over a period of up to 7 days. Tracheobronchial aspirates were taken: (i) within 48 h after intubation; and (ii) when clinical signs of nosocomial tracheobronchitis were present, before extubation, or after 7 days. Presence of respiratory viruses was investigated using quantitative polymerase chain reaction. RESULTS: Patients were 67 +/- 11 years old and had been in hospital for 5.1 +/- 8.4 days when intubated (major cause for intubation: cardio-pulmonary resuscitation 25/65, 38%). The average Acute Physiology and Chronic Evaluation II score was 27.3 +/- 4.9. Microbiology detected Candida spp. (17/65; 26%) and Staphylococcus aureus (methicillin sensitive: 11/65; 17%; methicillin resistant: 3/65; 5%) and only few respiratory viruses (4/65, 6%). Thirty-eight percent of the samples (25/65) were sterile. At the given endpoints, 27/65 (42%) patients were available for follow-up and only one aspirate became positive for respiratory syncytial virus (RSV). CONCLUSIONS: After endotracheal intubation, fungi, but not viruses were most frequently isolated. Only one patient acquired RSV, therefore colonization with respiratory viruses does not seem to play a major role early after intubation.

[Improvement of cardiopulmonary exercise capacity in patients with obstructive sleep apnea syndrome under CPAP therapy]. / Verbesserung der kardiopulmonalen Leistungsfähigkeit bei Patienten mit obstruktivem Schlafapnoesyndrom unter CPAP-Langzeittherapie.

BACKGROUND AND PURPOSE: Obstructive sleep apnea syndrome (OSAS) is regarded as a cardiovascular risk factor. Therefore, cardiopulmonary exercise capacity in patients with OSAS before and under treatment with continuous positive airway pressure (CPAP) was investigated. PATIENTS AND METHODS: Cardiopulmonary exercise capacity was investigated in 36 patients with untreated OSAS using spiroergometry. A follow-up after at least 6 months was performed in 17 of these patients being treated with CPAP and in eight CPAP-neglecting patients, who served as controls. RESULTS: Maximum oxygen uptake ( O(2max)) was significantly reduced in all 36 patients with untreated OSAS (17.68 +/- 6.1 ml/min/kg) compared with reference values (30.72 +/- 4.9 ml/min/kg; p < 0.001). After an average of 305.7 +/- 104.8 nights of CPAP therapy, O(2max) rose from 15.33 +/- 4.8 to 18.53 +/- 6.9 ml/min/kg, whereas O(2max) remained unchanged in controls. Further spirometric parameters of exercise capacity as well as arterial blood pressure were also significantly improved under CPAP therapy. CONCLUSION: Cardiopulmonary exercise capacity is markedly reduced in patients with OSAS. Long-term CPAP therapy leads to a significant improvement of reduced cardiopulmonary exercise capacity in these patients.

Treatment with sequential intravenous or oral moxifloxacin was associated with faster clinical improvement than was standard therapy for hospitalized patients with community-acquired pneumonia who received initial parenteral therapy.

BACKGROUND: Although third-generation cephalosporins, such as ceftriaxone (CTRX), and pneumococcal fluoroquinolones, such as moxifloxacin (MXF), are currently recommended first-line antibiotics for empirical treatment of inpatients with community-acquired pneumonia, CTRX and MXF have never undergone a head-to-head comparison. We therefore compared the efficacy, safety, and speed and quality of defervescence of sequential intravenous or oral MXF and high-dose CTRX with or without erythromycin (CTRX+/-ERY) for patients with community-acquired pneumonia requiring parenteral therapy. METHODS: In this prospective, multicenter, randomized, controlled, nonblinded study, 397 patients were randomly assigned to receive either MXF (400 mg once daily intravenously, possibly followed by oral tablets) or CTRX (2 g intravenously once daily) with or without ERY (1 g intravenously every 6-8 h) for 7-14 days. RESULTS: Among 317 patients evaluable for efficacy and safety, 138 (85.7%) of 161 MXF-treated patients and 135 (86.5%) of 156 CTRX+/-ERY-treated patients (59 [37.8%] of whom received CTRX and ERY) achieved continued clinical resolution. Defervescence and relief of symptoms, such as chest pain, occurred significantly earlier in the MXF-treated group than in the CTRX+/-ERY-treated group. Both regimens were generally well tolerated. CONCLUSIONS: For adult patients hospitalized with community-acquired pneumonia, sequential MXF therapy was clinically equivalent to high-dose CTRX+/-ERY therapy but led to a faster clinical improvement.

Cost analyses of community-acquired pneumonia from the hospital perspective.

STUDY OBJECTIVES: Community-acquired pneumonia (CAP) is a widespread disease with important implications for health-care systems worldwide. This study investigated direct costs, treatment patterns, and outcomes associated with two patient cohorts hospitalized with CAP. DESIGN: The study design was naturalistic, prospective, and open. PATIENTS: The study enrolled 580 patients. Two hundred sixty-one patients were treated initially with IV moxifloxacin (45%, cohort M); the remaining 319 patients received nonstandardized treatment (cohort S). SETTING: Twenty-two hospitals in Germany. RESULTS: Clinical success rates were similar between treatment groups (cohort M, 242 of 256 patients, 95%; cohort S, 286 of 312 patients, 92%; p = 0.208). Mean +/- SD length of hospital stay was 10.8 +/- 5.2 days, with cohort M having a significantly shorter hospital stay (10.0 +/- 4 days) compared to cohort S (11.5 +/- 6 days; p < 0.001). Median of all direct costs was dollar 1,333 (minimum, dollar 127; maximum, dollar 9,488), with direct costs of dollar 1,250 in cohort M (minimum, dollar 372; maximum, dollar 9,488) and dollar 1,409 in cohort S (minimum, dollar 127; maximum, dollar 9,366) per treated episode of CAP (p = 0.066). CONCLUSIONS: Major determinants of costs were length of hospital stay and ICU admission, whereas costs for staff and hotel were major contributors to direct costs. Initial antibiotic therapy with moxifloxacin resulted in similar clinical efficacy and direct costs compared to nonstandardized therapy; however, patients treated with moxifloxacin benefited with an earlier hospital discharge.

[Self-Management of Anti-Obstructive Therapy for Severe COPD with a Subcutaneous Terbutaline Pump]. / Einsatz eines subkutanen Terbutalin-Infusatsystems zur Selbstapplikation der Bedarfsmedikation bei schwerer chronisch-obstruktiver Atemwegserkrankung (COPD).

BACKGROUND: Patients with chronic obstructive pulmonary disease (COPD) may be difficult to stabilize with standard inhaled and oral medication. In those cases, outpatient care may even be impossible. Alternative therapeutic strategies, like subcutaneous self-application of terbutaline, could help to further improve health status. CASE REPORT: A 42-year old patient with severe COPD was admitted to the hospital. Despite maximal anti-obstructive therapy he required additional intravenous relief therapy and discharge was not possible. We treated this patient with a subcutaneous terbutaline pump for continuous and demand medication. We could show a significant decrease in additional intravenous medication, and the patient could leave the hospital. CONCLUSION: The use of terbutaline applied by a subcutaneous pump in addition to standard therapy may be helpful in severely ill patients suffering from COPD. This measure increased quality of life and shortened hospital stay.

Noninvasive ventilation during persistent weaning failure: a randomized controlled trial.

To assess the efficacy of noninvasive ventilation (NIV) in patients with persistent weaning failure, we conducted a prospective, randomized, controlled trial in 43 mechanically ventilated patients who had failed a weaning trial for 3 consecutive days. This trial was stopped after a planned interim analysis. Patients were randomly extubated, receiving NIV (n = 21), or remained intubated following a conventional-weaning approach consisting of daily weaning attempts (n = 22). Compared with the conventional-weaning group, the noninvasive-ventilation group had shorter periods of invasive ventilation (through tracheal intubation) (9.5 +/- 8.3 vs. 20.1 +/- 13.1 days, p = 0.003) and intensive care unit (ICU) (14.1 +/- 9.2 vs. 25.0 +/- 12.5 days, p = 0.002) and hospital stays (27.8 +/- 14.6 vs. 40.8 +/- 21.4 days, p = 0.026), less need for tracheotomy to withdraw ventilation (1, 5% vs. 13, 59%, p < 0.001), lower incidence of nosocomial pneumonia (5, 24% vs. 13, 59%, p = 0.042) and septic shock (2, 10% vs. 9, 41%, p = 0.045), and increased ICU (19, 90% vs. 13, 59%, p = 0.045) and 90-day survival (p = 0.044). The conventional-weaning approach was an independent risk factor of decreased ICU (odds ratio: 6.6; p = 0.035) and 90-day survival (odds ratio: 3.5; p = 0.018). Earlier extubation with NIV results in shorter mechanical ventilation and length of stay, less need for tracheotomy, lower incidence of complications, and improved survival in these patients.

Obstructive Sleep Apnea and Hypopnea Efficacy and Safety of a Long-Acting beta2-Agonist.

The effect of inhaled long-acting beta2-agonists in obstructive sleep apnea syndrome (OSAS) is unknown, although from the pharmacological point of view both therapeutic and adverse effects need to be considered. The purpose of this study was to obtain data on the efficacy and safety of salmeterol in patients with OSAS. In a randomized, double-blind, placebo-controlled, cross-over study, effects of salmeterol on respiration during sleep and sleep quality were investigated in 20 patients with OSAS. Of these, 4 patients were female, 16 male; the average age was 53.0 +/- 7.8 years, with average body mass index 28.0 +/- 3.0 kg small middle dot m(-2) and average apnea hypopnea index 35.6 +/- 17.8 h(-1). Patients with asthma, chronic obstructive pulmonary disease (COPD), and left heart failure were excluded. Placebo or verum (50 &mgr;g salmeterol) was administered at 7 pm by meter dose inhaler and spacer device. All patients underwent full polysomnography during baseline, placebo, and verum night. Statistical analysis was performed by StudentOs t-test (p > 0.05). Between the placebo and verum there were no differences in total sleep time, sleep stages, apnea index (AI), apnea hypopnea index (AHI), and nadir oxygen saturation. There was, however, 1) a significant deterioration of mean oxygen saturation (SaO2m; placebo 93.1 +/- 2.0 vs. verum 92.5 +/- 2.2%; p = 0.01), 2) of percent of time spent with an oxygen saturation (SaO2)