Biomedical subjects

Hartmut Lode

Publications and source records attributed to Hartmut Lode.

30 records · Page 2Linked to original sources

PubMed2003

Electron microscopic findings in BAL of a fire-eater after petroleum aspiration.

Hydrocarbon pneumonitis, known also as fire-eater pneumonia, always develops after aspiration of low-viscosity, volatile hydrocarbides. Despite the presence of clear-cut indicators for an infection, it is considered to be an acute pseudoinfectious lung disease. In this article, we report on a relatively rare clinical picture of a 30-year-old man after accidental petroleum aspiration. In addition to the usual clinical and instrumental examinations, we also performed, for the first time, electron microscopic investigations of the BAL specimen. A striking finding was the occurrence of macrophages (40%) with numerous lipoid inclusions that exhibited all morphologic signs of an activation as well as neutrophil granulocytes (33%), lymphocytes (21%), and eosinophils (6%). Despite a large and necrotizing infiltration of the right lower lobe, the clinical course was uneventful with complete recovery.

Adult↗

PubMed2003

Fluoroquinolones in the elderly: safety considerations.

Fluoroquinolones such as ciprofloxacin, levofloxacin, moxifloxacin and gatifloxacin are widely used for the treatment of bacterial infections. Fluoroquinolone-induced adverse effects have not been reported to occur with increased frequency in the elderly, but large trials comparing the tolerability in aged and young individuals are not available. Renal function declines consistently with age and recommendations for dosage changes of renally eliminated fluoroquinolones (ofloxacin, levofloxacin, gatifloxacin) are related to changes in kidney function rather than to age per se. However, during routine clinical work, creatinine clearance data are usually not available; thus it seems more practical to recommend dosage adjustment for elderly individuals in whom low creatinine clearance values can be expected. Reactions of the gastrointestinal tract are the most often observed adverse effects during therapy with fluoroquinolones; however, compared with many other antibacterials, fluoroquinolones are less frequently associated with diarrhoea. Similarly, hypersensitivity reactions, as observed during therapy with penicillins and other beta-lactam agents, occur more rarely during fluoroquinolone therapy. Adverse reactions of the CNS are of particular concern for the elderly population. Elderly patients with impairments of the CNS (e.g. epilepsy, pronounced arteriosclerosis) should be treated with fluoroquinolones only under close supervision. Probably, many signs of possible adverse reactions such as confusion, weakness, loss of appetite, tremor or depression are often mistakenly attributed to old age and remain unreported. Fluoroquinolones can cause QT interval prolongation. Therefore, they should be avoided in patients with known prolongation of the QT interval, patients with uncorrected hypokalaemia or hypomagnesaemia and patients receiving class IA (e.g. quinidine, procainamide) or class III (e.g. amiodarone, sotalol) antiarrhythmic agents. Chondrotoxicity of fluoroquinolones, as observed in immature animals, has led to restricted use in paediatric patients, but there is no indication that similar effects could occur in joint cartilage of adults. Tendinitis and tendon ruptures have occurred in rare cases as late as several months after treatment with some fluoroquinolones. Chronic renal diseases, concomitant use of corticosteroids and age over 60 years have been recognised as risk factors for fluoroquinolone-induced tendon disorders. Overall, the widely used fluoroquinolones discussed in this review are generally well tolerated. Nevertheless, as with all drugs, their specific adverse effect profiles must be considered when they are chosen for treatment of bacterial infections. Because of physiological changes in renal function and in case of certain comorbidities, some special considerations are necessary when fluoroquinolones are used to treat elderly patients.

4-Quinolones↗

PubMed2002

Efficacy and safety of voriconazole in the treatment of acute invasive aspergillosis.

To evaluate the efficacy and safety of voriconazole in acute invasive aspergillosis (IA), an open, noncomparative multicenter study was conducted. Immunocompromised patients with IA were treated with intravenously administered voriconazole 6 mg/kg twice a day (b.i.d.) twice and then 3 mg/kg b.i.d. for 6-27 days, followed by 200 mg b.i.d. administered orally for up to 24 weeks. Response was assessed by clinical and radiographic change. A total of 116 patients were assessable. IA was proven in 48 (41%) and probable in 68 patients. Voriconazole was given as primary therapy in 60 (52%). Good responses were seen in 56 (48%); 16 (14%) showed complete response and 40 (34%) partial response. A stable response was seen in 24 patients (21%), and 36 (31%) of the infections failed to respond to therapy. Good responses were seen in 60% of those with pulmonary or tracheobronchial IA (n=84), 16% with cerebral IA (n=19), 58% with hematologic disorders (n=67), and 26% of allogeneic stem cell transplant recipients (n=23). Voriconazole is efficacious in treating acute IA.

Acute Disease↗

PubMed2002

Oral gemifloxacin versus sequential therapy with intravenous ceftriaxone/oral cefuroxime with or without a macrolide in the treatment of patients hospitalized with community-acquired pneumonia: a randomized, open-label, multicenter study of clinical efficacy and tolerability.

OBJECTIVE: This study aimed to compare the efficacy and safety of oral gemifloxacin, an enhanced-affinity quinolone, with sequential therapy with IV ceftriaxone followed by oral cefuroxime (with or without a macrolide) in patients hospitalized for community-acquired pneumonia (CAP). METHODS: A randomized, open-label, multicenter study comprised adults hospitalized with a clinical and radiologic diagnosis of CAP. Patients were randomized 1:1 to receive either (1) oral gemifloxacin 320 mg once daily (7-14 days); or (2) IV ceftriaxone 2 g once daily (1-7 days) followed by oral cefuroxime 500 mg twice daily (1-13 days) for a total of < or = 14 days. Patients receiving ceftriaxone/cefuroxime were allowed concomitant macrolide treatment. RESULTS: A total of 345 patients were randomized, of whom 341 received at least 1 dose of study medication (gemifloxacin, 169/172; ceftriaxone/cefuroxime, 172/173). Clinical success rates in the clinically evaluable (CE) population at follow-up (day 21-28 post-therapy), the primary end point, were 92.2% (107/116) for gemifloxacin and 93.4% (113/121) for ceftriaxone/cefuroxime (treatment difference, -1.15; 95% CI, -7.73 to 5.43). In patients in Fine risk classes IV and V, the clinical success rate was 87.0% (20/23) for gemifloxacin versus 83.3% (20/24) for ceftriaxone/cefuroxime. No difference in clinical response at follow-up was noted based on macrolide use. Bacteriologic success rates at follow-up in the bacteriologically evaluable (BE) population were 90.6% (58/64) for gemifloxacin and 87.3% (55/63) for ceftriaxone/cefuroxime (treatment difference 3.32; 95% CI, -7.57 to 14.21). The clinical success rate in bacteremic patients at follow-up (BE population) was 100.0%. Both treatments were generally well tolerated. The frequency and types of adverse events were similar between the 2 groups. The most common treatment-related adverse events with gemifloxacin were diarrhea, liver-function adverse events, and rash; with ceftriaxone/cefuroxime, they were diarrhea, elevated hepatic-enzyme activity, and moniliasis. CONCLUSION: The clinical efficacy and tolerability of oral gemifloxacin 320 mg once daily were similar to those of IV ceftriaxone followed by oral cefuroxime (with or without a macrolide) in the treatment of adult patients hospitalized with moderate to severe CAP. Both treatments were effective in bacteremic patients and those at increased risk of mortality.

Administration, Oral↗

PubMed2002

Single- and multiple-dose pharmacokinetics of oral moxifloxacin and clarithromycin, and concentrations in serum, saliva and faeces.

Moxifloxacin and clarithromycin are important antibacterial drugs in the treatment of community-acquired respiratory tract infections. In a double-blind, randomized, 2-period cross-over study the pharmacokinetics of moxifloxacin versus clarithromycin were determined after single and multiple doses in 12 healthy male volunteers. The concentrations of the antibiotics in serum, saliva and faeces were measured by validated high-performance liquid chromatographic methods. In serum, moxifloxacin exhibited a mean peak concentration of 3.1 +/- 0.6 mg/l after a time to peak concentration of 1.67 +/- 0.96 h on day 1, with a significant increase to 3.98 +/- 1.10 mg/l on day 7 (p < 0.05). The area under the curve-12 revealed a highly significant increase from 28.2 + 4.1 mg*h/l on day 1 to 39.5 +/- 6.6 mg*h/l on day 7 (p < 0.01). There were also significant differences in terminal half-life between day 1 and day 7 [10.6 h (range 9.0-12.8) vs 14.9 h (range 12.6-28.1); p < 0.01] and in mean residence time (15.1 +/- 1.9 vs 18.2 +/- 2.4 h; p < 0.01). The concentrations of moxifloxacin in saliva were well equilibrated with serum at a relatively constant saliva-serum ratio of about 0.8. Pharmacokinetic parameters of clarithromycin and its metabolite, 14-hydroxy-clarithromycin, were similar to previously published data. Accumulation was found. No serious adverse events were observed with either study drug.

Administration, Oral↗

PubMed2002

Single- and multiple-dose pharmacokinetics of linezolid and co-amoxiclav in healthy human volunteers.

In an open, randomized, two-period crossover study the pharmacokinetics of linezolid and co-amoxiclav were investigated after single- and multiple-dose administration in 12 healthy volunteers (six females and six males). Linezolid was given in tablets of 600 mg twice a day for 7 days and co-amoxiclav in tablets of 1000 mg (875 + 125 mg) once a day for 7 days. The wash-out period was 4 weeks between the administration of the two antibacterial agents. Blood and urine samples were collected on days 1 and 7 before and at different time points up to 24 h after medication. The concentrations of the antibiotics in serum and urine were measured by validated high-performance liquid chromatography methods. Linezolid exhibited a mean C(max) of 14.5 +/- 4.6 mg/L after T(max) of 47.5 +/- 20.1 min on day 1, with a significant increase to 24.0 +/- 6.9 mg/L on day 7 (P < 0.01). The AUD(tot) (total area under the data) revealed a significant increase from 140.5 +/- 28.3 mg.h/L on day 1 to 220.2 +/- 42.6 mg.h/L on day 7 (P < 0.01). There were no significant differences in terminal elimination half-life between days 1 and 7 (9.53 +/- 2.87 versus 7.97 +/- 3.08 h) or in total clearance (71.6 +/- 17.6 versus 81.5 +/- 14.7 ml/min.1.73 m(2)). Results are in agreement with the assumption of a limited accumulation of linezolid under the dosage regimen given. Serum linezolid concentrations in females were always higher than those in males. The volume of distribution V(ss)/f differed significantly between females and males (41.6 +/- 4.2 versus 52.2 +/- 3.3 L/70 kg; P < 0.01). Pharmacokinetic parameters of amoxicillin and clavulanic acid found in this study were similar to previously published data. No accumulation was found with co-amoxiclav. No serious adverse event was observed with the study drugs.

Acetamides↗

PubMed2002

Pharmacokinetics of lansoprazole, amoxicillin and clarithromycin after simultaneous and single administration.

In a randomized, double-blind, placebo-controlled, four-way crossover study, possible influences of the triple therapy with amoxicillin, clarithromycin and the proton pump inhibitor lansoprazole on the pharmacokinetics of each of the drugs and the active 14-OH-clarithromycin metabolite were assessed. Twelve Helicobacter pylori-negative healthy male volunteers (age 27 +/- 4.3 years; creatinine clearance 7.0 +/- 2.0 L/h) were given lansoprazole 30 mg, amoxicillin 1 g and clarithromycin 500 mg, alone and in triple combination. Drug elimination intervals were at least 9 days between the dosing periods. The study medication was administered twice daily for 4 days. On the fifth day of each period, drugs were only given once in the morning, and blood and urine samples were collected for 12 h. The concentrations of the three substances administered, and 14-OH-clarithromycin, were determined by validated HPLC methods. Alterations in the serum kinetics were found for lansoprazole and the active 14-OH-clarithromycin metabolite (all data expressed as mean +/- S.D.). For lansoprazole, the elimination half-life (t(1/2)) was significantly prolonged (1.46 versus 1.7 h, P < 0.05) and the area under the concentration-time curve from 0 to 8 h (AUC(0-8)) was significantly increased (3.65 versus 4.59 mg.h/L, P < 0.05) by combination of the drugs. For 14-OH-clarithromycin, the peak concentration (C(max)) was 0.95 versus 1.18 mg/L and the AUC from 0 to 12 h (AUC(0-12)) was 8.3 versus 10.5 mg.h/L (augmented significantly, P < 0.05). The amoxicillin concentrations were slightly elevated by concomitant administration of lansoprazole and clarithromycin but without statistical significance (11.1 versus 12.6 mg/L). For clarithromycin, the time to maximum concentration of drug in serum (T(max)) was increased (2.73 versus 3.31 h, P < 0.05), whereas AUC and C(max) remained unchanged. Simultaneous administration of lansoprazole, amoxicillin and clarithromycin increases the serum concentrations of lansoprazole and the active 14-OH-clarithromycin metabolite significantly. These effects were not so pronounced as to have any therapeutic influence, making dosage adjustment unnecessary.

2-Pyridinylmethylsulfinylbenzimidazoles↗

PubMed2002

Community-acquired lower respiratory tract infections: clinical experience with beta-lactam/beta-lactamase inhibitors.

Once universally susceptible to aminopenicillins and cephalosporins, an increasing percentage of the common respiratory pathogens that cause community-acquired pneumonia (CAP) and acute exacerbations of chronic bronchitis (AECB) are now resistant to these agents and exhibit cross-resistance to other commonly used antibiotics. In an era of multidrug resistance, guidelines for the management of both CAP and AECB can help to guide appropriate antibiotic prescribing, encourage the rational use of antibiotics, which will help to limit the emergence of resistance, and conserve the use of new antimicrobial agents for more serious infections. Central to all current management guidelines is risk assessment, which includes an appreciation of local antibiotic resistance patterns. beta-Lactam antibiotics are still considered among the drugs of choice for the treatment of CAP and AECB, although their use can be compromised by high rates of resistance. The beta-lactam/beta-lactamase inhibitor combinations, such as ampicillin/sulbactam, provide a means of overcoming such resistance and represent a suitable alternative.

Anti-Bacterial Agents↗

PubMed2000

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.

Journal Article↗

PubMed1999

Changes in fecal flora and comparative multiple-dose pharmacokinetics of ceftibuten, cefpodoxime proxetil and amoxycillin/clavulanate.

OBJECTIVE: To investigate changes in fecal flora and multiple-dose pharmacokinetics with the oral antibiotics ceftibuten 400 mg daily and cefpodoxime proxetil (CPX) 200 mg every 12 h, compared to amoxycillin/clavulanate 500/125 mg every 8 h during and following 1 week of medication. METHODS: In an open randomized triple crossover design, 18 (nine female, nine male) healthy volunteers received each drug for 7 days, followed by a 'washout' period of 4 weeks. Serum and urine levels of the substances were determined by bioassay, and for ceftibuten isomers by high-pressure liquid chromatography. Statistical analysis of quantitative aerobic and anaerobic cultures of feces was performed, and beta-lactamase activity was determined. RESULTS: Ceftibuten showed a mean Cmax of 18.9 (SD 3.0) mg/L, a terminal half-life of 2.89 h, and an AUCtot of 100 (21.8) mg.h/L; protein binding was 63.7 (5.1)%, and accumulation was marginal. Cefpodoxime proxetil had a Cmax of 1.92 (0.61) mg/L, a terminal half-life of 1.97 (0.42) h and an AUCtot of 10.8 (3.3) mg.h/L; no accumulation was seen. Amoxycillin and clavulanate had Cmax values of 7.15 (2.16) mg/L and 3.39 (1.31) mg/L, terminal half-life values of 1.03 (0.15) h and 0.93 (0.17) h, AUCtot values of 20.0 (4.2) mg.h/L and 8.87 (3.10) mg.h/L, and there was no accumulation. Statistical analysis for ech microorganism in fecal samples showed significant differences between amoxycillin/clavulanate and the two third-generation cephalosporins, but virtually no differences between ceftibuten and cefpodoxime proxetil. Eleven of 12 volunteers reported loose stools (days 2-7, mean duration 4.4 (SD 2.7) days) with amoxycillin/clavulanate, but nobody during ceftibuten administration and one volunteer during cefpodoxime proxetil administration. CONCLUSIONS: Ceftibuten showed excellent and cefpodoxime favorable pharmacokinetic properties, with significantly less pronounced fecal flora changes and intestinal side effects compared to amoxycillin/clavulanate. The multiple crossover design allows powerful microbiological statistical analysis and pharmacokinetic parameter comparisons.

Journal Article↗

PubMed1997

Pharmacokinetics of cefetamet pivoxil and interaction with cisapride and N-acetylcysteine.

OBJECTIVE: To evaluate the pharmacokinetics of cefetamet pivoxil and possible interaction with N-acetylcysteine and cisapride in healthy volunteers. METHODS: In a double-blind, randomized three-way crossover study with 12 healthy male volunteers, serum and urine concentrations of cefetamet were determined over 12 h by a validated bioassay method after oral administration of 0.5 g cefetamet pivoxil and, randomly, placebo, 5x20 mg cisapride, or 0.6 g N-acetylcysteine. RESULTS: The study medications were well tolerated, although there were 10 cases of altered bowel movements, two cases of mild, transient headache and one case of increased serum transferase levels (AST and ALT). The mean peak serum level of cefetamet pivoxil in the placebo group was 4.86plus minus1.35 mg/L. The urine recovery/24 h in the placebo group was 41.9plus minus3.8% of the oral dose. The elimination half-life was 3.56plus minus0.92 h. N-Acetylcysteine had no effect on the pharmacokinetics of cefetamet pivoxil. With concomitant administration of cisapride there was an accelerated absorption of cefetamet pivoxil and a slightly increased Cmax of cefetamet. The Cmax values differed significantly (p<0.05) only between the cisapride group (5.76plus minus1.50 mg/L) and the N-acetylcysteine group (4.53plus minus1.18 mg/L). CONCLUSION: None of the small pharmacokinetic differences between the three groups is expected to have any relevance in the treatment of infectious diseases with cefetamet pivoxil.

Journal Article↗

PubMed1996

Comparative pharmacokinetics of macrolide antibiotics and concentrations achieved in polymorphonuclear leukocytes and saliva.

OBJECTIVES: The pharmacokinetics of macrolide antibiotics --- erythromycin (ER), clarithromycin (CL), roxithromycin (RO), azithromycin (AZ), dirithromycin (DI) and the concentrations achieved in polymorphonuclear neutrophils (PMNs) and saliva were investigated. METHODS: In a four-way crossover trial, 10 healthy volunteers received 1000 mg ER twice a day, 500 mg CL twice a day, 150 mg RO twice a day and 500 mg AZ every day over a period of 3 days. In a second trial, 10 healthy volunteers received 500 mg DI every day over a period of 5 days. Concentrations of these antibiotics were measured in serum, urine, saliva and PMNs by high-performance liquid chromatography (HPLC) on days 1 and 3 in the first trial and on days 1 and 5 in the second trial. RESULTS: We found considerable differences in the pharmacokinetics, not only in serum, but also in PMNs and saliva. All substances except RO exhibited higher concentrations in PMNs than in serum, indicating excellent intraphagocytic distribution. In contrast, concentrations in saliva were lower than those measured in serum, with the exception of AZ. ER is characterized by low serum concentrations and moderate concentrations in saliva and PMNs. CL reached considerable concentrations in serum, saliva and PMNs. RO achieved the highest serum levels, but concentrations in saliva and in PMNs were below the detection limit. In contrast, AZ and DI yielded the lowest serum concentrations and the highest saliva and PMN concentrations. CONCLUSIONS: Our data emphasize the importance of tissue distribution, in addition to serum kinetics, in evaluating the pharmacokinetic profiles of antibiotics.

Journal Article↗