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Biomedical subjects

Hartmut Lode

Publications and source records attributed to Hartmut Lode.

At least 19 recordsLinked to original sources
PubMed2006

Ultrastructural types of alveolar macrophages in bronchoalveolar lavages from patients with pulmonary sarcoidosis.

By routine applied quantitative BAL methods are particularly helpful for the diagnosis of pulmonary sarcoidosis. Here the morphology of the alveolar cells does not play a role. However, morphological and especially electron microscopic investigations might contribute to the clarification of the aetiology of this disease. In a prospective study we investigated the bronchoalveolar lavages (BALs) from 10 patients with recently histologically diagnosed, untreated pulmonary sarcoidosis. Commonly applied cytological and immunological BAL diagnostic techniques were accompanied by morphological investigations of alveolar cells, especially alveolar macrophages, using light and electron microscopy. All patients showed lymphocytic alveolitis with an increased number of CD4 positive lymphocytes as well as an increased CD4/CD8 ratio. A striking light microscopic finding was the great morphological variety of the alveolar macrophages. Electron microscopy revealed typical lymphocytes, neutrophils, and eosinophils as well as three different types of alveolar macrophages in all 10 patients: type I (approx. 30%) with a normal macrophage morphology, a vacuole-rich type II (approx. 30%) with myelin-like structures and type III (approx. 40%) with electron-dense inclusions. The occurrence of intracellular myelin figures in type II macrophages is a hint for increased phagocytotic processes of surfactant with or without its overproduction in the sense of a secondary alveolar proteinosis. Numerous electron-dense inclusions in type III also indicate an increased macrophage activity that leads to an increased release of cytokines, which in turn can trigger an inflammatory reaction.

Adult↗
PubMed2006

Voriconazole treatment for subacute invasive and chronic pulmonary aspergillosis.

BACKGROUND: Voriconazole is a novel triazole antifungal with a broad spectrum including Aspergillus species. We conducted an open, noncomparative multicenter study to evaluate the efficacy and safety of voriconazole in subacute invasive and chronic pulmonary aspergillosis (CPA). METHODS: Patients without profound neutropenia and a proven or probable diagnosis of subacute invasive aspergillosis (IA) or CPA received voriconazole 200 mg twice daily for a period of 4-24 weeks as primary or salvage therapy. Dose escalation was allowed if efficacy was suboptimal, and toleration and safety were satisfactory. Response was assessed by clinical, radiological and mycological changes. A complete or partial response in subacute IA and improved or stable in CPA were assessed as favorable responses. RESULTS: Of 39 patients treated, 36 were assessable. The majority of patients had subacute IA (n = 21), proven in all 11 extra-pulmonary and in 23/25 (92%) of the pulmonary cases. Voriconazole was given as primary therapy in 22 (61%). All patients receiving salvage therapy (n = 14) had refractory IA, having failed itraconazole or amphotericin B (AmB) or both. Overall, a complete or partial response was seen in 9/21(43%) of subacute IA and improved or stable in 12/15 (80%) of those with CPA. Adverse events, mainly liver function test abnormalities, skin reactions, and visual disturbances were mild and transient, leading to early discontinuation of treatment in 5 cases. CONCLUSIONS: In patients with subacute IA and CPA, voriconazole was efficacious as salvage or primary therapy.

Adult↗
PubMed2006

Treatment of pneumonia in elderly patients.

Pneumonia represents the leading cause of infection-related death and the fifth cause of overall mortality, in the elderly. Several risk factors for acquiring pneumonia in older age have been reported, such as alcoholism, lung and heart diseases, nursing home residence and swallowing disorders. The clinical characteristics of pneumonia in the elderly differ substantially compared with younger patients, and the severity of the disease is strongly associated with increased age and age-related comorbidities. Streptococcus pneumoniae is the leading pathogen responsible for pneumonia in elderly; enteric Gram-negative rods should be considered in nursing-home-acquired pneumonia, as well anaerobes in patients with aspiration pneumonia. Antimicrobial therapy should take into account the most recent guidelines, which are briefly presented in this review. A special consideration should be given to the preventive measures, including vaccination, oral care and nutrition.

Aged↗
PubMed2005

Apoptosis of peripheral blood neutrophils in COPD exacerbation does not correlate with serum cytokines.

The study investigated the relationship between apoptosis of peripheral blood neutrophils during exacerbation of chronic obstructive pulmonary disease (COPD) and the inflammatory response that characterises this condition. Twenty-six hospitalised patients with COPD exacerbation and 13 controls were included. Three sequential blood and sputum samples were obtained from patients at admission, after 3 days and at discharge. Blood apoptotic neutrophils were measured by flow-cytometry and light microscopy. Serum and sputum levels of IL-6, IL-8 and TNF-alpha were determined by an immunoassay technique. We found a significantly reduced percentage of apoptotic neutrophils at the onset of COPD exacerbation which increased over time (1.1+/-0.4% at admission vs. 2.4+/-0.4% at discharge, P<0.0001). Patients presented no changes in serum cytokines neither during exacerbation nor in comparison to controls. In contrast, sputum levels of cytokines were significantly increased compared to serum levels. There was no significant correlation between the apoptotic neutrophils and the cytokine concentrations in serum or sputum. None of the clinical parameters, such as smoking, microbial infection, corticosteroids or hypoxemia showed a correlation with neutrophil apoptosis. No relationship could be found between the reduced percentage of apoptotic neutrophils in blood and serum concentration of IL-6, IL-8 and TNF-alpha or other clinical parameters in patients with COPD exacerbation.

Aged↗
PubMed2005

Treatment and vaccines for severe acute respiratory syndrome.

The causative agent of severe acute respiratory syndrome (SARS), which affected over 8000 individuals worldwide and was responsible for over 700 deaths in the 2002-2003 outbreak, is a coronavirus that was unknown before the outbreak. Although many different treatments were used during the outbreak, none were implemented in a controlled fashion. Thus, the optimal treatment for SARS is unknown. Since the outbreak, much work has been done testing new agents against SARS using in-vitro methods and animal models. In addition, global research efforts have focused on the development of vaccines against SARS. Efforts should be made to evaluate the most promising treatments and vaccines in controlled clinical trials, should another SARS outbreak occur.

Animals↗
PubMed2005

New antibiotics for the treatment of severe staphylococcal infection in the critically ill patient.

PURPOSE OF REVIEW: Infection by Staphylococcus aureus in critically ill patients is usually associated with antimicrobial resistance and high mortality. A more effective antibiotic treatment is needed to replace older drugs that have limited efficacy. Novel substances active on methicillin-resistant Staphylococcus aureus, which are already available on the market or are still in development, are discussed in this review, with emphasis on nosocomial infections. RECENT FINDINGS: A number of new antibiotics are on the market (linezolid, quinupristin-dalfopristin, daptomycin) and there is good evidence regarding their efficacy, especially in methicillin-resistant Staphylococcus aureus infections. Linezolid is, to date, the best alternative in treating nosocomial pneumonia by methicillin-resistant Staphylococcus aureus. It is cost-effective; resistance levels are still very low but there are some concerns regarding its adverse events. Quinupristin-dalfopristin shows good activity in vitro but its efficacy in patients with pneumonia by methicillin-resistant Staphylococcus aureus is modest. Daptomycin is not recommended for pulmonary infections because of its reduced penetration in the lung tissue. Under current phase III trials in patients with nosocomial infections are tigecycline, ceftobiprole, and three new glycopeptides, all with particular activity against methicillin-resistant Staphylococcus aureus. SUMMARY: For the moment, there are limited and rather expensive therapeutic options for the infections by Staphylococcus aureus in the critically ill. No dramatic superiority of the new drugs in comparison to the standard therapies was observed in most of the clinical trials. Better results on the efficacy of the drugs under investigation are expected.

Acetamides↗
PubMed2004

Ertapenem pharmacokinetics and impact on intestinal microflora, in comparison to those of ceftriaxone, after multiple dosing in male and female volunteers.

The pharmacokinetics of ertapenem and ceftriaxone were investigated in an open, randomized, two-period crossover study after single- and multiple-dose administration in 10 healthy volunteers (five women and five men). Both antibiotics were administered intravenously once daily for 7 days at dosages of 1 g (ertapenem) and 2 g (ceftriaxone). The concentrations of the antibiotics in serum and urine were quantified by the agar well diffusion method bioassay and, in addition, for ertapenem only, by liquid chromatography coupled with tandem mass spectrometry (LC-MS/MS). For ertapenem the maximum concentration of the drug in plasma (C(max)) was 256 mg/liter, the half-life was 20.7 h, and the area under the plasma concentration-time curve (AUC) was 830 mg. h/liter. The concentrations in fecal samples were (mean value) 37.2 and 32.7 mg/kg on day 4 and day 8, respectively. Ceftriaxone exhibited a mean C(max) of 315 mg/liter, a half-life of 7.6 h, and an AUC of 1,556 mg. h/liter. The mean concentrations in fecal samples were 153 and 258 mg/kg on day 4 and day 8, respectively. No accumulation of ertapenem or ceftriaxone was detected at steady state. A slightly but significantly decreased AUC for ertapenem was detected for the female volunteers. No serious adverse event was observed. Both antibiotics induced a marked decrease in the anaerobic microflora (4-log-unit decreases in lactobacilli, bifidobacteria, clostridia, and bacteroides) and Escherichia coli, whereas the number of enterococci increased (4 log units). A slight overgrowth of yeasts was observed with both regimens. In all cases the microflora returned to normal levels on days 21 to 35.

Adult↗
PubMed2004

Early bactericidal activity of moxifloxacin in treatment of pulmonary tuberculosis: a prospective, randomized study.

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 log(10) 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.

Anti-Infective Agents↗
PubMed2004

Viral community-acquired pneumonia in nonimmunocompromised adults.

INTRODUCTION: Viral community-acquired pneumonia (CAP) has been poorly studied and clinically characterized. Using strict criteria for inclusion, we studied this type of infection in a large series of hospitalized adults with CAP. MATERIALS AND METHODS: All nonimmunocompromised adult patients with a diagnosis of CAP having paired serology for respiratory viruses (RVs) [338 patients] were prospectively included in the study from 1996 to 2001 at our 1,000-bed university teaching hospital, and subsequently were followed up. We compared patients with pure viral (PV), mixed viral (RV + bacteria), and pneumococcal CAP. RVs (ie, influenza, parainfluenza, respiratory syncytial virus, and adenovirus) were diagnosed by means of paired serology. RESULTS: Sixty-one of 338 patients (18%) with paired serology had an RV detected, and in 31 cases (9%) it was the only pathogen identified. Influenza was the most frequent virus detected (39 patients; 64%). Patients with chronic heart failure (CHF) had an increased risk of acquiring PV CAP (8 of 26 patients; 31%) when compared to a mixed viral/bacterial etiology (2 of 26 patients; 8%; p = 0.035) or CAP caused by Streptococcus pneumoniae (1 of 44 patients; 2%; p = 0.001). Multivariate analysis revealed that CHF (odds ratio [OR], 15.3; 95% confidence interval [CI], 1.4 to 163; p = 0.024) and the absence of expectoration (OR, 0.14; 95% CI, 0.04 to 0.6; p = 0.006) were associated with PV pneumonia compared to pneumococcal CAP. CONCLUSION: RVs are frequent etiologies of CAP (single or in combination with bacteria). Patients with CHF have an increased risk of acquiring a viral CAP.

Community-Acquired Infections↗
PubMed2004

Guidelines for empiric antimicrobial prescribing in community-acquired pneumonia.

Empiric antimicrobial prescribing for community-acquired pneumonia remains a challenge, despite the availability of treatment guidelines. A number of key differences exist between North American and European guidelines, mainly in the outpatient setting. The North American approach is to use initial antimicrobial therapy, which provides coverage for Streptococcus pneumoniae plus atypical pathogens. Europeans tend to focus on providing pneumococcal coverage with less emphasis on covering for an atypical pathogen. Ambulatory patients without comorbidity are more likely to receive macrolide therapy in North America, whereas in Europe these patients would probably receive a beta-lactam agent. Major issues that are fundamental to this difference include the importance of providing therapy for atypical pathogens and the clinical significance of macrolide-resistant S pneumoniae. Prospective data are required to evaluate which of these two approaches offers clinical superiority.

Canada↗
PubMed2004

Comparative efficacies and tolerabilities of intravenous azithromycin plus ceftriaxone and intravenous levofloxacin with step-down oral therapy for hospitalized patients with moderate to severe community-acquired pneumonia.

OBJECTIVE: To compare the efficacy and tolerability of ceftriaxone plus azithromycin with those of levofloxacin in the treatment of hospitalized patients with moderate to severe community-acquired pneumonia (CAP). DESIGN: Randomized, open-label multicenter trial with 1 : 1 treatment allocation in an inpatient setting. PATIENTS: 212 male or female inpatients with a clinical diagnosis of CAP were included in the study. In each treatment group >50% of patients had a pneumonia severity index of IV or V. INTERVENTIONS: Open-label treatment with either intravenous (IV) ceftriaxone 1g and IV azithromycin 500 mg daily or IV levofloxacin 500 mg daily. Patients who improved clinically were switched to oral follow-on therapy with either azithromycin 500 mg/day or levofloxacin 500 mg/day. At the clinician's discretion, oral cefuroxime axetil was added to the treatment regimen of patients who received oral azithromycin if a macrolide resistant pneumococcal isolate was documented. RESULTS: Overall, both study treatments were well tolerated. Favorable clinical outcomes in clinically evaluable patients were demonstrated in 91.5% of patients treated with ceftriaxone plus azithromycin and 89.3% (95% CI -7.1%, 11.4%) of patients treated with levofloxacin at the end of therapy visit and in 89.2% and 85.1% (95% CI -6.7%, 14.8%) patients, respectively, at the end of study visit. Bacteriological eradication rates for both treatments were equivalent with the exception of Streptococcus pneumoniae; 44% of isolates were eradicated with levofloxacin compared with 100% of isolates with ceftriaxone plus azithromycin. CONCLUSIONS: As acknowledged by international CAP treatment guidelines, the combination of a third-generation cephalosporin and a macrolide is at least as efficacious as monotherapy with a fluoroquinolone with enhanced anti-pneumococcal activity, for hospitalized patients with moderate to severe CAP. Combined medication with a macrolide and third-generation cephalosporin may be preferred over fluoroquinolones as first-line therapy of hospitalized patients with CAP to minimize the development of multiresistant nosocomial Gram-negative bacilli.

Administration, Oral↗
PubMed2003

Recent developments in antibiotic treatment.

Antibiotic resistance of gram-positive and gram-negative bacteria remains a major challenge for clinicians treating HAP. Since the recent release of linezolid and QD, treatment options for resistant gram-positive bacteria have improved. The development of new substances continues and it is hoped that some of them will be available soon. Investigation has centered on gram-positive bacteria, although multiresistant gram-negative pathogens, such as A haumanii, S maltophilia, and resistant P aeruginosa, are of major clinical relevance. New treatment options are unfortunately not in sight. No antibiotic, however, is a miraculous magic wand against resistant bacteria. The bugs are smart; they have been on this world far longer than humans. Regardless of how innovative the mechanism of action of new substances is, resistance will emerge. The solution is certainly not a nihilistic approach leading to a fearful restriction in the use of new substances. No antibiotic, regardless of its potency, can free the clinician from keeping the difficult balance between individual undertreatment and general overtreatment.

Anti-Bacterial Agents↗
PubMed2003

Beau's lines in a patient treated with moxifloxacin for anaerobic pulmonary infection.

Onychotoxicity of fluoroquinolones is a rare event. Previously described cases of fluoroquinolone-related nail disorders were due to onychophototoxicity. This report presents a case of nail toxicity after treatment with moxifloxacin for anaerobic pulmonary infection, which has not been described previously. The appearance and circumstances of this nail disorder were consistent with the diagnosis of Beau's lines.

Anti-Infective Agents↗
PubMed2003

Optimizing ceftazidime pharmacodynamics in patients with acute exacerbation of severe chronic bronchitis.

OBJECTIVES: Implementation of current pharmacodynamic knowledge could enhance clinical results, avoid resistance development and reduce treatment costs. In this open, randomized, multicentre study, we evaluated the clinical and bacteriological outcome and pharmacokinetic as well as pharmacodynamic parameters of two ceftazidime therapy regimens in patients with acute exacerbation of severe chronic bronchitis (AECB). METHODS: Eighty-one patients (56 males, 25 females, age 65.3 +/- 10.1 years) with AECB were included. A subgroup of 21 patients underwent pharmacokinetic and pharmacodynamic examination. The patients received either ceftazidime 2 g every 8 h (C3 x 2) or ceftazidime 2 g as a loading dose, followed by ceftazidime 2 g over 7 h every 12 h (C2 x 2) for 8-14 days. Clinical and bacteriological responses were monitored at day 8 or 9, and 72 h after the end of therapy (EOT). RESULTS: At EOT, clinical success was recorded in 90% and 90.2% of clinically evaluable patients receiving C3 x 2 and C2 x 2, respectively. Bacteriological success at EOT was achieved in 87.5% and 90.2% of evaluable patients treated with C3 x 2 and C2 x 2, respectively. C(max) (mg/L) varied between 168.9 +/- 34.1 and 144.0 +/- 9.8 in the C3 x 2 group, and between 60.1 +/- 34.1 and 54.2 +/- 30.4 at steady-state in the C2 x 2 group. Minimal concentrations were between 9.1 and 13.4 mg/L in the C3 x 2 group, and between 16.6 and 17.7 mg/L in the C2 x 2 group. Concentrations >4-5 x MIC were seen in all pathogens, except Staphylococcus aureus, during 100% of infusion time. CONCLUSION: The 2 x 7 h infusion of ceftazidime 2 g (C2 x 2) was clinically and bacteriologically as effective as the usual 3 x 2 g ceftazidime short-term infusion in the treatment of AECB, and demonstrated advantages in terms of pharmacodynamic parameters compared with the C3 x 2 regimen.

Acute Disease↗