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Biomedical subjects

D Adam

Publications and source records attributed to D Adam.

At least 37 records · Page 2Linked to original sources
PubMed1990

Interventional antimicrobial strategy in febrile neutropenic patients. Results of a multicenter study in 1,260 patients with hematological malignancies. The Interventional Antimicrobial Strategy Study Group, Paul Ehrlich Society for Chemotherapy.

In a prospective, randomized multicenter trial of the Paul Ehrlich society different concepts for sequential empirical antimicrobial strategy for the treatment of patients with neutropenia less than 1.0/nl and fever greater than 38.5 degrees C and/or documented infection were studied. In phase I, patients with unexplained fever (FUO) were randomized for the combination of acylaminopenicillin plus aminoglycoside or third-generation cephalosporin plus aminoglycoside or double beta lactam therapy. Non-responders received additional vancomycin or all three substances of phase I in phase II. In phase III, all patients with persistent fever were then treated with amphotericin B plus 5-flucytosine and rifampin and randomized for the continuation of the double beta lactam regimen or additional imipenem/cilastatin. 667 (52.9%) of 1260 evaluable patients had FUO during the whole study period, of which 62.5% could be cured in phase I, 43.2% of non-responders in phase II and 55% of persistently febrile patients in phase III. The overall rate of complete response was 79.5%. 2.8% were non-responders, 11.7% were not evaluable for response and 40 patients (6%) died during the study, 24 (60%) of whom due to the underlying disease or the toxicity of antileukemic therapy. A significant difference between the treatment groups could not be detected in either of the three study phases.

Agranulocytosis↗
PubMed1990

Interstitial fluid concentrations of ceftriaxone (1 g.i.v.) in the subperitoneal space after hysterectomy.

The ability of an antibiotic to penetrate into the extravascular site of infection is particularly important for a successful perioperative antibiotic prophylaxis and postoperative therapy of bacterial infection. We, therefore, measured interstitial fluid concentrations of ceftriaxone in the subperitoneal space following hysterectomy using Rubinstein's disc method after intravenous administration of 1 g of ceftriaxone preoperatively. After removal of the uterus, two disc units were implanted intraoperatively in the right and left subperitoneal space of 16 patients and were drawn out through the open vaginal cuff after given periods of time. Five disc and blood specimens were obtained after 90 min and 2, 6, 12, 24, and 48 h, respectively. Ceftriaxone concentrations were determined by bioassay. After administration of 1 g of ceftriaxone, interstitial fluid concentrations following hysterectomy were above the MIC90 of most pathogens encountered in gynecologic infections over a period of 24 h.

Bacteriological Techniques↗
PubMed1989

Novel putative receptor tyrosine kinase encoded by the melanoma-inducing Tu locus in Xiphophorus.

Malignant melanoma in Xiphophorus fish hybrids is caused by the activity of a dominant oncogene Tu. By combining genetic and molecular approaches, we have isolated the melanoma oncogene. We show that its level of expression correlates with the degree of malignancy of the tumour. The corresponding proto-oncogene is developmentally regulated. The Tu gene codes for a novel receptor tyrosine kinase which is closely related to the receptor for epidermal growth factor.

Amino Acid Sequence↗
PubMed1989

[In-vitro activity of enoxacin: a multicenter study].

The in vitro activity of enoxacin was tested in 14 German microbiological centers shortly after the introduction of the drug in Germany. 2748 unselected clinical isolates including 15 bacterial species were analysed using microtiter plates. The MIC90-values were as follows: Staphylococcus aureus 4 mg/l, Enterococcus faecalis 16 mg/l, Enterobacteriaceae 0.5 mg/l, Pseudomonas aeruginosa 8 mg/l. There is good correlation between these results and those of former investigations. It is known that quinolones are only moderately active against enterococci. 8.5% of S. aureus, and 1.4% of Enterobacteriaceae were found to be resistant (MIC greater than 4 mg/l). As to P. aeruginosa, the study revealed that despite a generally low rate of resistance in specific clinical settings, specific problems can arise: in one institution, the MIC90 of P. aeruginosa was 32 mg/l, with a resistance rate of 56.1% (n = 57). In the other centers the MIC90 was 2 mg/l and the resistance rate 5.0% (n = 302). In the first center, many of the isolates were from paraplegic patients or patients with cystic fibrosis pretreated with quinolones. This study will be repeated in two years' time in order to determine an eventual change in resistance.

Bacteria↗
PubMed1989

[Bactericidal activity of enoxacin and ciprofloxacin in body fluids].

Until present studies are lacking which investigate the bactericidal activity of new quinolones in body fluids. Therefore, we determined bactericidal titers of enoxacin (en) and ciprofloxacin (cip) against a typical pathogen in urinary tract infections (Escherichia coli) in urine and against a typical pathogen in respiratory tract infections (Streptococcus pyogenes) in sputum, in each case at the time of peak and trough levels (In vitro data of the test strains: E. coli - MICen = 0.06 mg/l, MICcip = 0.06 mg/l, MBCen = 0.5 mg/l, MBCcip = 0.25 mg/l; Streptococcus pyogenes - MICen = 32 mg/l, MICcip = 1 mg/l, MBCen greater than 64 mg/l, MBCcip greater than 64 mg/l). Following a randomization list, ten healthy volunteers took either 400 mg enoxacin b.i.d. for three days, then (after a break of at least three days) 500 mg ciprofloxacin b.i.d. for three days, or vice versa. Two and 12 hours after the final dose, samples of sputum were taken, urine was collected 2-4 h and 10-12 h after the final dose. The bactericidal titers against E. coli in urine were greater than 1:512 (2-4 h after the final dose) and greater than 1:64 (10-12 h after the final dose) for both quinolones in all cases. On the other hand, as to S. pyogenes were found growth in every dilution of sputum. These results confirm the scepticism against quinolone therapy of respiratory tract infections caused by streptococci.

Ciprofloxacin↗
PubMed1989

[Enoxacin concentrations in lung tissue].

For successful treatment of bacterial lung infections the administered antibiotic must reach sufficiently high concentrations in lung tissue. Therefore, the concentrations of enoxacin in this tissue were measured in ten patients requiring pulmonary surgery. In order to prevent postoperative infection, the patients received 400 mg enoxacin b.i.d. for three days. Eight h after the final dose samples of venous blood were drawn and a sample of lung tissue was removed. Using a microbiological assay, we found the following concentrations (mean +/- S.D.):serum 2.36 (+/- 0.65) mg/l, lung 6.48 (+/- 1.54) mg/kg. With the HPLC-technique the corresponding values method were 2.37 (+/- 0.80) mg/l and 7.41 (+/- 3.01) mg/kg. Thus concentrations of enoxacin in lung tissue are about three times higher than the corresponding serum concentrations.

Aged↗
PubMed1989

[Enoxacin concentration in bone tissue].

For successful treatment of bacterial osteomyelitis the administered antibiotic must reach sufficiently high concentrations in bone tissues. Therefore concentrations of enoxacin in bone in ten patients requiring hip surgery were measured. To prevent a postoperative infection, 400 mg enoxacin b.i.d. for two days were administered. On an average 120 (90-210) min after the final dose samples of venous blood and bone tissue were taken. The bone pieces were divided into corticalis and spongiosa. Using a bio-assay-method the following concentrations were found: (mean +/- S.D.): serum 2.88 ( +/- 0.90) mg/l, corticalis 5.90 ( +/- 0.79) mg/kg, spongiosa 3.95 ( +/- 1.01) mg/kg. Thus enoxacin reaches higher levels in bone tissue than in serum.

Aged↗
PubMed1989

Penetration of ticarcillin/clavulanate into cartilage.

The penetration of ticarcillin and clavulanate into cartilage was investigated in 20 subjects undergoing funnel chest correction. Cartilage samples, obtained 120 or 180 min after administration of ticarcillin/clavulanate (mean dose: ticarcillin 70.0 mg/kg, clavulanate 4.7 mg/kg), were divided into core samples and outer covering portions. After 120 min, the mean ticarcillin in the outer portion was 11.0 mg/kg and that in the core sample was 0.81 mg/kg; at 180 min the mean concentration in the outer portion was 6.47 mg/kg and ticarcillin was undetectable in all but two core samples. Clavulanate was shown to decline with time in spiked cartilage preparations and the results in this investigation may underestimate penetration. Clavulanate was undetectable in most core samples. In the outer portion the mean concentration was 1.30 mg/kg at 120 min and 0.62 mg/kg at 180 min. The penetration gradient requires further elucidation and should be considered when chemotherapy for infection in cartilage is discussed.

Adolescent↗
PubMed1989

Cerebrospinal fluid penetration after single or multiple dosage with ticarcillin/clavulanate.

Penetration of ticarcillin and clavulanate into the cerebrospinal fluid was studied in ten patients with varying degrees of impairment of the blood-brain barrier. In general, penetration of both drugs was relatively low and variable (5.4 +/- 5.8% for clavulanate and 2.0 +/- 4.0% for ticarcillin) but markedly better in those patients with impaired blood/brain barrier.

Adolescent↗
PubMed1989

Pharmacokinetics of ticarcillin/clavulanate in severely burned patients.

A pharmacokinetic trial with ticarcillin/clavulanate was undertaken in patients with severe burns. Timentin 5.2 g (ticarcillin 5 g + clavulanate 200 mg) was administered by iv infusion over 20 min, two or three times daily. Fifteen patients with varying amounts of total body surface (TBS) burned could be evaluated for pharmacokinetic calculations (group A, greater than 20% TBS, n = 7; group B, less than 10% TBS, n = 8). Both groups presented similar pharmacokinetic behaviour. Compared with healthy volunteers, the volume of distribution for both ticarcillin and clavulanate was increased 2.5 times. For ticarcillin the mean elimination half-lives in serum were 95.1 (A) and 86.1 min. (B), respectively; for clavulanate, the half-lives were 144.0 (A) and 132.1 min (B), respectively. The 0-8-h urine recovery of ticarcillin was 84% (A) and 83% (B), and for clavulanate it was 86% (A) and 88% (B) of the administered dose. As a consequence of the increased distribution volumes and the increased AUC's in severely burned patients the highest recommended dose of ticarcillin/clavulanate appears suitable.

Burns↗
PubMed1989

Penetration of amoxycillin/clavulanate into human bone.

Twenty patients undergoing orthopaedic surgery for total hip replacement received a single prophylactic intravenous dose of 2.2 g Augmentin (2 g amoxycillin + 200 mg clavulanate). Bone samples removed during the operation were saved for amoxycillin and clavulanate assay. The proportion of inorganic matter in the bone samples was determined to calculate the concentrations of the drugs in their distribution volume. The cortical and cancellous bone were penetrated to a comparable extent by both compounds yielding maximum concentrations at one hour after the end of the infusion. The mean concentrations of amoxycillin in the cortex and spongy layer were 26.0 and 18.2 mg/kg within 1 h, 23.8 and 19.8 mg/kg in the interval from 1 to 2 h after infusion, and 9.2 and 5.9 mg/kg between 2 and 5 h. The corresponding values for clavulanate were 2.3 and 1.6 mg/kg, 2.5 and 1.6 mg/kg, and 1.0 and 0.7 mg/kg, respectively. No postoperative wound infections occurred in these patients.

Aged↗
PubMed1989

[Hemostasis disturbance caused by cephalosporins with an N-methylthiotetrazole side chain. A randomized pilot study].

The mechanism of hypoprothrombinemia induced by cephalosporins containing the N-methylthiotetrazole (NMTT) side chain has been investigated in a randomized clinical, trial (pilot study) with 14 hospitalized patients (main inclusion criteria: age greater than or equal to 50 years, urinary tract infection, normal prothrombin time. Therapy groups: latamoxef (n = 5), cefoperazone (n = 5), cefotaxime (control, n = 4). Duration of treatment: 7 days). Two patients under cefoperazone exhibited a significant increase of prothrombin time, accompanied by the appearance of PIVKA II (prothrombin induced in vitamin K absence). Both cefoperazone (in 4 patients) and latamoxef (in 3 patients) caused the appearance of endogenous vitamin K1 2,3-epoxide, whereas cefotaxime did not. This confirms the hypothesis that NMTT-cephalosporins are inhibitors of hepatic vitamin K epoxide reductase, and that this is at least partly responsible for the clinically observed hypoprothrombinemia. In older patients treated with these antibiotics, prothrombin time should be controlled before as well as under therapy. Unexpectedly, the patients displaying an appearance of vitamin K1 2,3-epoxide showed a statistically significant increase of endogenous plasma vitamin K levels. This effect needs further investigation.

Aged↗