Acute hepatitis during hypersensitivity syndrome due to midecamycin.

We report here the first case of symptomatic acute hepatic injury due to midecamycin in a 58-year-old man. The clinical picture was compatible with a hypersensitivity syndrome with cutaneous, renal and hepatic involvement. Liver eosinophil polynuclear infiltrate, hypereosinophilia and acute interstitial nephritis were consistent with the hypothesis of an immunoallergic mechanism.

[Cholestatic hepatitis caused by midecamycin]. / Hepatitis colestásica por midecamicina.

Hepatotoxicity by macrolide antibiotics, particularly erythromycin and derivatives, is a side effect extensively described in the literature. Midecamycin is a semi-synthetic derivative of this family with a wide safety margin of which isolated references of possible secondary hepatobiliary effects have been referred. The present clinical observation describes a case of cholestatic hepatitis which, in our opinion, was related to the administration of diacetyl midecamycin which evolved favorably following discontinuation of the drug. Despite its exceptional frequency and based on the wide therapeutic diffusion of this group of antibiotics, we believe this case to be of interest.

A survey of the side effects of midecamycin acetate (Miocamycin) dry syrup after marketing.

Three-year post-marketing surveillance (PMS) on midecamycin acetate dry syrup from July, 1985 through April, 1988 resulted in collection of reports on 12,169 patients. Among these, a total of 66 patients (0.54%) with side effects were reported. The main side effects caused by this drug were gastrointestinal and skin appendages disorders. They included diarrhea, abdominal pain, eruption and others. Side effects, which had not been observed up to the approval were itchiness and multiple erythema. None of these side effects were serious. When the drug was administered to 26 patients hypersensitive to beta-lactam agents, no allergy symptoms developed. Based on these results, midecamycin acetate dry syrup can be evaluated to be a highly safe macrolide in clinical use.

Lack of effect of spiramycin on cyclosporin pharmacokinetics.

1. The influence of spiramycin coadministration on cyclosporin pharmacokinetics was studied in five renal transplant patients. The plasma concentrations of cyclosporin were measured both by non-specific radioimmunoassay (RIA) and high-performance liquid chromatography (h.p.l.c.). 2. The kinetics of cyclosporin were followed before treatment, and after 1 day and then 2 weeks of oral treatment with spiramycin (3 X 10(6) iu, twice daily). The main pharmacokinetic parameters (the area under the plasma drug concentration-time curve, the maximum plasma drug concentration and the time to reach it) obtained both by RIA and h.p.l.c. were not modified by spiramycin cotreatment after 1 day, nor after 2 weeks of spiramycin administration. Therefore, the pharmacokinetics of cyclosporin (parent drug and parent drug plus metabolites) are not influenced by the coadministration of spiramycin macrolide at therapeutic dosage. 3. Spiramycin may be preferable to other macrolide antibiotics known to interact with cyclosporin such as erythromycin or josamycin.

Roxithromycin as a possible agent for prophylaxis of endocarditis: a study in normal volunteers.

A single dose of roxithromycin, 300 mg, was taken by six healthy male volunteers on three occasions at consecutive weekly intervals. It was well tolerated. On the first two occasions, roxithromycin was assayed in serum samples taken at intervals up to 8 h after the administration. The mean peak concentration at 1 h was 3.0 mg/l (range 0.3-7.3). The serum samples from the volunteers showed variable bactericidal activity against a strain of Streptococcus sanguis isolated from a case of bacterial endocarditis. Roxithromycin was not detected in saliva or gingival fluid. Smooth surface plaque samples taken at intervals were investigated for the emergence of streptococci resistant to roxithromycin at 2 and 8 mg/l. Initially two volunteers had small number of roxithromycin-resistant streptococci. At the end of the study all six volunteers had resistant streptococci detectable in their plaque samples and these accounted for 100% of the streptococci in two volunteers. The most resistant isolates (in several cases with MIC greater than 64 mg/l) were Str. sanguis or Str. mitior; individual volunteers tended to yield the same strain on consecutive samplings.

Roxithromycin. A review of its antibacterial activity, pharmacokinetic properties and clinical efficacy.

Roxithromycin is an acid-stable orally administered antibacterial macrolide structurally related to erythromycin. It has an in vitro antibacterial profile similar to that of erythromycin, with activity against Staphylococcus aureus, S. epidermidis, Streptococcus pneumoniae, S. pyogenes, Branhamella catarrhalis, Mycoplasma pneumoniae, Legionella pneumophila, Chlamydia trachomatis, Gardnerella vaginalis, Haemophilus ducreyi, some anaerobes and other less common pathogens. Roxithromycin has a pharmacokinetic profile that is characterised by excellent enteral absorption achieving high concentrations in most tissues and body fluids. The results of clinical studies with roxithromycin have confirmed the potential for its use in a variety of infections, which was suggested by its antibacterial activity in vitro and pharmacokinetic profile. Clinical efficacy has been confirmed in the treatment of respiratory tract infections, including community-acquired and atypical pneumonias, ear, nose and throat infections, genitourinary tract infections, and skin and soft tissue infections. In a relatively small number of patients roxithromycin has generally been shown to be as effective as erythromycin and other appropriate antibacterial drugs in some of the above indications. Roxithromycin is well tolerated and has less potential than erythromycin to produce clinically significant drug interactions. Thus, roxithromycin is an orally active drug which should prove a useful alternative when selecting antibacterial therapy for indications where macrolides are appropriate.

Josamycin concentration in human ejaculate and its influence on sperm motility--a contribution to antibiotic therapy in andrological patients.

The concentration of josamycin was determined in the split ejaculate of 5 volunteers after oral administration for several days. One aim of this investigation was to examine the penetration of the macrolide antibiotic into the prostate and the seminal vesicles. 2.23 +/- 1.8 micrograms/ml josamycin was found in fraction I of the ejaculate, consisting mostly of prostatic secretion, and 1.56 +/- 1.37 micrograms/ml josamycin in fraction II comprising mainly secretions from the seminal vesicles. The concentrations of josamycin found in both fractions of the ejaculate are clearly comparable with serum levels of the antibiotic. Josamycin thus attains concentrations in the prostate and seminal vesicles which are effective against Mycoplasma and Chlamydia, pathogens of increasing importance in infections of the urogenital tract. In vitro studies on samples from 30 andrological patients showed that josamycin (0.5 micrograms/ml) did not impair, but even increased the motility of spermatozoa (p less than or equal to 0.01). On the basis of these results josamycin is recommended for the treatment of andrological patients. In particular, the specific antibacterial spectrum also indicates the use of this antibiotic for treatment of the partner when children are desired. The usual precautionary measures for pregnancy must then be adhered to.

[Effect of rokitamycin on upper gastrointestinal contractile activity. Analysis of side-effects on gastrointestinal tract].

In order to determine whether rokitamycin (RKM), one of the macrolide antibiotics, has any side effects on the gastrointestinal tract, the effect of intraduodenal administration of RKM (1.0, 3.0 and 9.0 mg/kg) on gastrointestinal contractile activity was studied by means of force transducers implanted chronically on the gastric body, gastric antrum, duodenum and upper jejunum in conscious dogs. Erythromycin (EM 0.3, 1.0 and 3.0 mg/kg) and kitasamycin (LM 1.0, 3.0 and 9.0 mg/kg), both macrolide antibiotics, were used as control drugs. RKM, when given at 3.0 mg/kg and 9.0 mg/kg doses, induced segmentation contractions only in the duodenum where it was administered. The duration of the RKM-induced contractions was 7.5 +/- 2.5 minutes for 3.0 mg/kg and 15.8 +/- 3.0 minutes for 9.0 mg/kg, and the contractile force of the contractions was 43 to 82% of the maximum contractile force of the interdigestive contractions in the duodenum. EM, at 0.3 mg/kg, evoked a series of strong contractions quite different from those induced by RKM but similar to the natural interdigestive contractions, and with large doses, dose-dependent long-lasting interdigestive contractions were induced. On the other hand, LM did not stimulate notable gastrointestinal contractile activity even at a 9.0 mg/kg dose. In order to eliminate the possibilities of the contraction being caused by the effect of RKM on the duodenum through the general circulation upon absorption, 3.0 mg/kg RKM was given intravenously. It was found that intravenous injection of RKM did not evoke any contractions attributable to the direct action of RKM in the circulation.(ABSTRACT TRUNCATED AT 250 WORDS)

Comparison of spiramycin with erythromycin for lower respiratory tract infections.

The efficacy and safety of 2 g oral spiramycin daily were compared with those of 2 g of oral erythromycin daily in a multicentre open prospective trial, involving 198 patients, with a mean age of 61.75 years, with a clinical and radiological diagnosis of acute lower respiratory tract infection. The diagnoses were: acute bronchitis (96), acute superinfection of chronic bronchitis (60) and pneumonia (42). The patients were assessed before therapy and after three and ten days of therapy. Seventy-four (76.3%) of the patients were cured in the spiramycin group and 64 (63.4%) were cured in the erythromycin group (P less than 0.05). Significantly more patients complained of side effects in the erythromycin group (41.4%) than in the spiramycin group (11.8%) P less than 0.001.

Comparison of spiramycin and doxycycline in the treatment of lower respiratory infections in general practice.

A total of 221 patients from 21 general practitioners was entered in a double-blind comparative study of spiramycin and doxycycline in the treatment of pneumonia and acute exacerbations of chronic bronchitis. One-hundred-and-five patients were randomized to treatment with spiramycin tablets for 5 1/2 days and 116 patients were randomized to treatment with doxycycline tablets for nine days. The efficacy and side effects of the two treatment regimens were observed. Of the 221 patients included, 191 were acceptable for evaluation, 91 in the spiramycin group and 100 in the doxycycline group. Three patients in the spiramycin group withdrew because of lack of efficacy and one patient in the doxycycline group withdrew because of side effects (feeling unwell and blurred vision). No significant differences in efficacy or safety were found between the two treatments.

The efficacy and safety of spiramycin in the treatment of nongonococcal urethritis in men.

Twenty-five male patients with nongonococcal urethritis including 15 chlamydial infections, were treated with spiramycin for ten days. All but four patients had been treated previously, mostly with tetracyclines. Chlamydia trachomatis was cultured in seven patients and was detected in three additional men by immunofluorescent smear. Five other patients had antibodies to chlamydia, and one patient yielded a positive culture for Ureaplasma urealyticum and Mycoplasma hominis. A successful clinical response was observed in 64% of the patients; C. trachomatis was eradicated from six of seven patients with positive cultures and the three positive direct smears were negative after treatment. It is concluded that spiramycin can be used effectively for the therapy of acute nongonococcal urethritis, as well as in patients who have failed to respond to previous treatment with tetracyclines and erythromycin.

Macrolides and gastrointestinal motility.

Erythromycin was the first macrolide used clinically, and it is still the most widely prescribed in spite of reports of gastrointestinal side-effects. Erythromycin was given iv or orally to fasted and fed dogs with sensors implanted on the gastrointestinal tract for the measurement of motility. There was a large increase in stomach and upper small bowel contractile activity, accompanied by nausea and vomiting, while the distal small bowel appeared inhibited. Similar effects were seen in man. By contrast, two 16-membered macrolides, spiramycin and josamycin, did not produce such side-effects when given either orally or intravenously to dogs.