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G Marklein

Publications and source records attributed to G Marklein.

At least 37 records · Page 2Linked to original sources
PubMed1999

Itraconazole trough concentrations in antifungal prophylaxis with six different dosing regimens using hydroxypropyl-beta-cyclodextrin oral solution or coated-pellet capsules.

We have previously shown that a trough concentration of at least 500 ng ml-1 itraconazole is necessary for an effective antifungal prophylaxis in neutropenic patients. Since the bioavailability of itraconazole is reduced in these patients, a satisfactory dosing regimen remains to be defined. In this study, six dosing regimens with itraconazole capsules 400, 600 or 800 mg day-1, itraconazole solution 400 mg day-1 (additional loading dose: 400 mg day-1 solution for 2 days), 800 mg day-1 or 400 mg day-1 (additional loading dose: 800 mg day-1 capsules for 7 days, s/c1200) were compared during 160 courses of myelosuppressive chemotherapy in 123 patients with acute leukaemia. After the first week, patients taking 800 mg day-1 or 400 mg day-1 (s/c1200) itraconazole solution achieved significantly higher trough concentrations (high-performance liquid chromatography) than patients in other groups (P < 0.05) and 87 and 100%, respectively, of these had concentrations > 500 ng ml-1. Contrary to a dose of 400 mg day-1, a dose of 800 mg day-1 itraconazole solution induced severe nausea and vomiting in 46% of the patients. We conclude that 400 mg day-1 itraconazole solution with a loading dose of 800 mg day-1 capsules for 7 days resulted in sufficient trough concentrations from the first week onwards and appears to be suitable for antifungal prophylaxis in neutropenic patients.

2-Hydroxypropyl-beta-cyclodextrin↗
PubMed1998

[Quantitative cultures in diagnosis of pneumonia--a method for routine practice?].

Quantitative cultures of respiratory secretions represent a valid technique for the diagnosis of ventilator-associated pneumonia. Contamination, colonization and true infection can be differentiated with a reasonable specificity using established cut-offs of bacterial colony counts. Quantitative investigations provide local epidemiological databases as a framework for empirical antimicrobial policies and may also prove helpful in the guidance of individual antimicrobial therapy. Another reasonable indication is HIV-associated pneumonia. However, the use of this technique in routine practice is hampered by the high expertise and experience that will be necessary to be successfully used. Nevertheless, in view of the need to identify bacterial susceptibility patterns, at least large treatment centers should routinely use this most powerful diagnostic technique.

AIDS-Related Opportunistic Infections↗
PubMed1998

Antifungal prophylaxis with itraconazole in neutropenic patients with acute leukaemia.

The efficacy of antifungal prophylaxis with itraconazole capsules and its serum concentrations were evaluated in patients intensively treated for acute leukaemia. A consecutive group of patients without systemic antifungal prophylaxis (January 1993 to August 1994, period 1) was compared with another consecutive group of patients (period 2) who received itraconazole capsules (September 1994 to April 1995 400 mg/day, from May 1995 onwards 600 mg/day). All patients admitted with acute leukaemia and standard or high-dose chemotherapy were included into the study. Clinical endpoint was mortality from proven fungal infection. Seventy-six patients and 148 courses of cytotoxic chemotherapy were analysed in the control group as well as 47 patients and 112 treatment courses in the intervention group. Antifungal prophylaxis led to a significant decrease of mortality from invasive fungal infections (8.8%-0.9%, P = 0.005). The median trough concentration of itraconazole of all measurements was 520 ng/ml (range 230-793) in patients who received 400 mg/day and 760 ng/ml (370-1200) in patients receiving a dosage of 600 mg/day (P = 0.002). These findings suggest that itraconazole is an effective drug for antifungal prophylaxis but also that a considerable number of patients do not reach the desired trough levels (>500 ng/ml) with itraconazole capsules.

Acute Disease↗
PubMed1998

[Nosocomial ventilator-associated pneumonias caused by Aspergillus fumigatus in non-immunosuppressed, non-neutropenic patients].

We observed three cases of severe ventilator-associated pneumonia due to Aspergillus fumigatus in non-immunosuppressed, non-neutropenic patients. Autopsy confirmed an angioinvasive pattern of spreading with septic foci. In all cases conditions associated with temporary immunodysfunction like underlying diseases, antecedent sepsis or pneumonia, coinfections or steroid therapy were present. Although Aspergillus fumigatus was isolated in all cases in cultures of tracheobronchial secretions, the correct diagnosis was not obtained during lifetime. Our cases demonstrate that pneumonia due to Aspergillus fumigatus must be taken into account also in this patient population.

Adult↗
PubMed1996

Comparison of BBL Crystal ANR ID Kit and API rapid ID 32 A for identification of anaerobic bacteria.

BBL Crystal ANR ID Kit and the API System rapid ID 32 A are miniaturized identification systems for anaerobes using enzymatic tests. The incubation period of both systems is 4 hours. A comparative evaluation of the BBL Crystal Identification System Anaerobe ID Kit (Becton Dickinson Microbiology Systems, Cockeysville, USA) with anaerobes grown on Columbia and Schaedler agar plates (Becton Dickinson Microbiology Systems, Cockeysville, USA) and the API System rapid ID 32 A (BioMérieux SA, Lyon, France) with bacteria grown on Columbia agar (Becton Dickinson Microbiology Systems, Cockeysville, USA) which is recommended by the manufacturer as cultivation medium, was performed with 207 mostly fresh clinical anaerobe isolates, including 104 gram-negative bacilli, 12 gram-negative cocci, 15 gram-positive cocci, 14 gram-positive sporeforming bacilli and 62 representatives of gram-positive non-sporeforming bacilli. With supplemental testing the Crystal system with inocula from Columbia and Schaedler agar and API inoculates from Columbia agar identified to genus level 144 (69.6%), 152 (73.4%) and 109 (52.7%) isolates, respectively. Misidentification to genus level was found by Crystal from Columbia and Schaedler agar and by API from Columbia agar in 17 (8.2%), 15 (7.3%) and 12 (5.8%) isolates, respectively. 36 isolates were not determined to species level by classical anaerobic methods or the systems only identified to genus level. 26 anaerobes were not included in the database of the Crystal or API system. From the remaining 145 clinical isolates with supplemental testing, Crystal from Columbia and Schaedler agar plates correctly identified 91 (62.8%) and 102 (70.3%), respectively, and API, 69 (47.6%) isolates. For the correct identification to genus and species level of the 207 clinical isolates tested, the Crystal system from Columbia and Schaedler agar and API system from Columbia agar required supplemental testing, as specified by the manufacturer, for 39 (27.1%), 34 (22.4%) and 14 (12.8%) isolates, respectively. Among the 207 clinical isolates tested, 27 had been frozen and 26 had been lyophilized. In a comparative evaluation, the fresh isolates showed a slightly to significantly better identification rate than the frozen or lyophilized specimens in all three tests. The individual reproducibility of the Crystal ANR ID, which had been tested before the accuracy study was performed, ranged from 90.8% to 100%. The overall reproducibility was determined to be 97.3%. Time consumption studies and cost analysis did not show a significant difference between both systems, but Crystal ANR ID was found to be easier to use than API rapid ID 32.

Bacteria, Anaerobic↗
PubMed1996

Value of routine microbial investigation in community-acquired pneumonia treated in a tertiary care center.

The study was conducted at a tertiary care and teaching hospital with about 200 beds for internal medicine. The objective was to determine the diagnostic yield and value in directing antibiotic therapy of a routine microbial approach in patients with community-acquired pneumonia referred to a tertiary care center. We studied 93 episodes in a retrospective study. 69/93 (74%) cases were treated with at least one empirical antibiotic therapy prior to admission. Microbial investigation was performed in 83/93 cases (89%). An etiological agent was established in 19/83 (23%) cases including 7/50 (14%) by blood culture and 12/52 (23%) by serology. Bronchoscopy with 18 protected specimen brush and 20 bronchoalveolar lavage examinations was definitely diagnostic in only 1/25 (4%) cases, and this case was also identified by blood culture. 5/25 (20%) were probably diagnostic. Three pathogens, Streptococcus pneumoniae, Mycoplasma pneumoniae and Legionella pneumophila, accounted for 15/19 (79%) of the identified agents. The diagnostic results directed a change in antibiotic therapy in 6/19 (32%) of cases with definitely proven pathogens. 4/19 (21%) of cases would have been treated with an inappropriate regimen without diagnostic results. The diagnostic yield of routine microbial investigation in pretreated patients is low. The routine approach reveals its limited value especially in patients with severe courses. The role of bronchoscopy remains to be defined for patients with severe (and pretreated) community-acquired pneumonia.

Adolescent↗
PubMed1996

Quinolones in everyday clinical practice: respiratory tract infections and nosocomial pneumonia.

Currently available fluoroquinolones have established their value in the treatment of lower respiratory tract infections due to gram-negative rods and Staphylococcus aureus. The fact that these drugs are absorbed (and well tolerated) when given orally is a major positive feature. The once daily dosage of fleroxacin [400 mg once daily intravenously (i.v.) for 2-4 days followed by oral doses of 400 mg for up to 10 days] was compared with twice daily ciprofloxacin (400 mg twice daily i.v. for 2-4 days followed by oral doses of 2 x 500 mg for up to 10 days) for treatment of inpatients with pneumonia confirmed by clinical signs and chest X ray. To date, 93 evaluable patients have been enrolled in this study. Clinical cure and improvement rates were 73.3% in the fleroxacin group and 79.2% in the ciprofloxacin group. The rate of adverse clinical or laboratory events was similar in both study groups.

Adult↗
PubMed1995

[Diagnostic value of protected bronchoalveolar lavage in HIV-associated pneumonia].

OBJECTIVE: The concept of the protected bronchoalveolar lavage (PBAL) is to improve the diagnostic yield in bacterial pneumonia by unifying the high sensitivity of bronchoalveolar lavage (BAL) and specificity of the protected specimen brush (PSB). HIV-infected patients have been shown to have a high incidence of bacterial pneumonia as well as bacterial colonisation of the tracheobronchial tree. We therefore studied the value of PBAL in this population. METHODS: During a period of twelve months 40 episodes in 36 patients with symptoms suggestive of pneumonia were investigated retrospectively. In all cases without infiltrates on chest radiograph a CT-scan of the chest was performed. Patients without infiltrates also in CT-scan served as controls. Bronchoscopic investigation included a PSB and a PBAL in the same lung segment most prominently affected. Microbiological workup was performed for bacterial agents, mycobacteria, fungi, viruses and parasites. Quantitative cultures for bacteria were considered significant in case of > or equal to 10(3) cfu/ml in PSB and > or equal to 10(4) cfu/ml in PBAL. RESULTS: 32 episodes in 28 patients were identified as pneumonia. A definite diagnosis could be established in 19/32 (59%) of cases. Bacteria accounted for 10/19 (53%). Pneumocystis carinii for 9/19 (47%) of cases including one case that revealed mixed infection with Streptococcus pneumoniae and Pneumocystis carinii. Another pneumonia was due to Aspergillus fumigatus. The sensitivity for bacterial pneumonia was 44% for PSB and 56% for PBAL, the specificity 100%. The overall diagnostic accuracy was 60% and 68%, respectively. The yield for Pneumocystis carinii was 8/9 (89%). CONCLUSIONS: PBAL as compared to PSB had a superior diagnostic yield for bacterial pneumonia. As PBAL additionally conserved the yield of BAL reported for Pneumocystis carinii, it may represent a rational diagnostic technique for pneumonia in HIV-infected patients.

AIDS-Related Opportunistic Infections↗
PubMed1993

Pneumocystis carinii infections in HIV-infected hemophiliacs during aerosolized pentamidine prophylaxis.

The frequency, presentation, diagnosis and clinical course of Pneumocystis carinii infections (PCI) were studied during aerosolized pentamidine prophylaxis (AP) and its impact on the spectrum of AIDS-related and other pulmonary infections in HIV-infected hemophiliacs. We conducted an open study on primary (PP) and secondary (SP) AP. Breakthrough P. carinii infections (BPCI) and other infectious complications were analyzed retrospectively. Hemophiliacs without prior P. carinii pneumonia (PCP) who had been reluctant to any prophylaxis and who developed PCP served as control group. Statistical analysis of the efficacy of prophylaxis was performed by calculating confidence intervals of binomial p. Of 73 hemophiliacs (56 on PP and 17 on SP) 10 developed BPCI (7 in PP and 3 in SP) during a mean observation time of 14.9 months (range 0.5-30); total 13.6% (6.7%; 23.7%), PP 12.5% (5.1%; 24%), SP 17.6% (3.7%; 43.4%), confidence intervals at a level of 95%. Three BPCI presented atypically with cavitation (1), pneumothorax (2), Pneumocystis pleuritis (1), dissemination (2) as compared to none in the control group. Sensitivity of bronchoalveolar lavage (BAL) was 88.9%, specificity 100% (both 100% in the control group). PCP was the leading AIDS manifestation (21.3%), CNS manifestations taken together were more frequent (36.2%). Bacterial pneumonia was the most frequent respiratory infection. One patient of the study group with recurrent pneumothorax possibly died of BPCI as compared to no BPCI-related deaths in the control group. Efficacy of prophylaxis in hemophiliacs was comparable to other risk groups. AP alone may be insufficient for the control of PCI in patients with long-term profound immunodeficiency, especially in SP. 30% of BPCI presented atypically.(ABSTRACT TRUNCATED AT 250 WORDS)

AIDS-Related Opportunistic Infections↗
PubMed1992

In vitro investigations into the formation and dissolution of infection-induced catheter encrustations.

Encrustations are the most frequent complications occurring with indwelling catheters and urine drainage systems. The conditions for bacterial infections, using synthetic urine and controlled contamination by Proteus vulgaris, were standardised by using an in vitro model. Crystal deposits on catheters were analysed by infra-red spectroscopy and scanning electron microscopy. The main components of deposits in all investigations were struvite (MgNH4PO4.6H2O) 60-70% and carbonate apatite (Ca10(PO4,CO3)6 (OH,CO3)2) 30-40%. Investigations as to the quality and quantity of encrustations confirmed the analysis. Irrigation treatment was carried out with physiological saline solution and citric acid solution (Suby G) to study and quantify the dissolution of crystal deposits. Regular irrigation with citric solution resulted in a 70% dissolution of encrustations and ensured free flow as ascertained by measuring flow rates.

Animals↗
PubMed1991

[A case of AIDS-associated histoplasmosis in Germany].

In a thirty-year-old patient with AIDS the diagnosis of disseminated histoplasmosis was established via biopsy and culture. The patient had grown up in Argentina, where histoplasmosis is endemic. He had not been in an endemic region during the last two years anteceding the manifestation of systemic histoplasmosis. Accordingly, in patients with a progressive immunodeficiency syndrome, reactivation of a former (possibly inapparent) infection with Histoplasma capsulatum must be considered. Therapy with Amphotericin B lead to a remarkable improvement of clinical, laboratory and sonographic findings. Due to the fact that total eradication of H. capsulatum from the infected host cannot be achieved with any known drug regimen, a life-long follow-up therapy was begun. The patient showed no signs of relapse after a follow-up of 7 months.

Acquired Immunodeficiency Syndrome↗
PubMed1990

[Listeria meningoencephalitis in a 2-year-old boy].

We report the unusual case of a two year old boy with encephalomeningitis caused by Listeria monocytogenes. The patient was hospitalized with the classical signs of severe bacterial meningitis. The microbiological investigations gave proof of Listeria monocytogenes as causative agent 36 hours later. Antibiotic treatment with ampicillin and gentamicin resulted in a prompt improvement of the boy's condition. The boy was discharged four weeks later.

Anti-Bacterial Agents↗
PubMed1990

[Bronchopulmonary penetration of ciprofloxacin].

We determined ciprofloxacin levels in plasma, saliva, bronchial secretions, lavage fluid, and alveolar macrophages in 9 patients five hours following the last administration of the drug (2 x 750 mg ciprofloxacin daily over a period of at least 3 days). The ciprofloxacin concentration in the alveolar film was determined using urea as internal marker for the lavage. On average it was 2.51 micrograms/ml (= 186% of the plasma level), and clearly exceeded the minimal inhibition concentrations for the facultative pathogenic organism. This means that, in the alveolar film--which represents the barrier to descending pneumonia--an effective accumulation of the quinolone takes place.

Bacterial Infections↗
PubMed1989

[Bronchopulmonary penetration of enoxacin].

We analysed enoxacin concentrations in plasma, saliva, bronchial secretions, bronchoalveolar lavage fluid, and alveolar macrophages in nine patients five hours after the last dose (400 mg enoxacin b.i.d. per os for at least three days). The enoxacin levels in the alveolar film were extrapolated from the lavage content by using urea as an internal marker (lavage dilution factor = plasma/lavage urea concentration ratio). The concentration in the alveolar film amounted to 7.62 mg/l ( = 381% of the plasma value), on average, and exceeded the minimal inhibitory concentrations of the pathogens isolated from the patients. Thus, enoxacin is effectively concentrated in the surface film of the lung which represents an important barrier against pulmonary infections.

Bronchoalveolar Lavage Fluid↗