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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.

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.

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.

A case of hypomelia, hypotrichosis and facial hemangioma (pseudothalidomide S.) is presented, which according to bibliography consulted, is the first case in Spain and the tenth mentioned in world literature. A differential diagnosis with dysostosis is proposed. Authors described characteristic traits of the patient and indicate differences with those presented in previous publications emphasizing association with cleft lip, absence of eyes anomalies, and normal neurological development. The importance of the administration of tetracyclines and spiramycins to the mother during first month of gestation is also noted.

Spiramycin gives high tissue levels and has very-few side-effects. It is one of the best antibiotics in infections of the upper and lower respiratory tract and of the oral cavity. It is probably one of the most effective antibiotics against chlamydia. Spiramycin is useful when toxoplasmosis occurs during pregnancy or results in severe diseases in non-immunodepressed patients. For the reasons listed above, we believe that spiramycin has been underestimated. This is the result of assessing its value according to its rather high MIC rather than to it's effectiveness against infection in animals and humans.

The usefulness of a new macrolide antibiotic rokitamycin (RKM, TMS-19-Q) was evaluated in the field of pediatrics. 1. Twenty seven patients were enrolled in the study. One patient was excluded from the study because the illness was due to a viral infection. They included 14 boys and 13 girls with ages 7 months to 9 years 11 months. 2. The patients were treated with RKM at daily doses ranging 19.2-41.1 mg/kg, divided into 3 equal portions. The administration was done orally at fasting, lasting 2-15 days, with total doses of 22.2-500.0 mg/kg. 3. The patients were diagnostically classified into the following categories: 9 with acute pharyngitis, 15 with acute bronchitis, and one each with pneumonia, purulent lymphadenitis and Campylobacter enteritis. 4. The clinical response to the treatment was good or excellent in 22 of the patients with an overall efficacy rate of 81.5%. An efficacy rate of 88.9% was achieved for the patients with acute pharyngitis, 80.0% for those with acute bronchitis, and 100% for the patient with purulent lymphadenitis and the patient with Campylobacter enteritis. From the patient with pneumonia whose response was evaluated "fair" was Haemophilus influenzae isolated by culturing pharyngeal material. This organism was found resistant to RKM by the disk method. 5. Bacteriological responses were as follows; of 26 isolates presumed to be pathogens, 9 were eradicated, 5 decreased, 7 unchanged and 5 unknown, with an eradication rate of 42.9%. 6. Neither adverse reactions nor abnormal changes in laboratory findings were observed with the medication in any patients during and after the end of the treatment.(ABSTRACT TRUNCATED AT 250 WORDS)

Spiramycin, 3 g daily, was used to treat immunocompromised patients with chronic diarrhoea due to Cryptosporidium. Most patients treated had acquired immune deficiency syndrome. Among 37 patients evaluated, 28 had a favourable response, defined as a reduction in the daily number of bowel movements to less than 50% of baseline and fewer than five. Twelve of these individuals had Cryptosporidium oocysts eradicated from stool. Spiramycin was well tolerated. These data suggest that spiramycin is effective in alleviating cryptosporidial diarrhoea in some immunocompromised patients and may lead to eradication of cryptosporidial oocysts.

Roxithromycin sachets of 50 mg were given to 304 infants and children, aged 2 months to 14 years, suffering from respiratory and skin infections treated in 25 hospitals in France and one in Greece. The dosage range was from 2.5 to 5.0 mg/kg/12 h and the mean duration of therapy was 8.9 days. The cure rate was 89% of the 266 children evaluable for clinical efficacy and 90.3% of the 50 bacteriologically identified cases. The overall bacteriological efficacy was 82%. The antibiotic was well accepted by the 90% of the 304 children, while in 6.9% an adverse effect was reported, mainly vomiting. There were no toxic effects. Roxithromycin should be considered as an effective and safe oral antibiotic to treat children with upper and lower respiratory tract and skin infections due to common pathogens.

Clinical trials of 9,3"-diacetylmidecamycin (MOM), a new macrolide antibiotic were carried out on 46 pediatric patients of 1 month to 11 years old with infections (acute pharyngitis 12, acute tonsillitis 1, acute bronchitis 14, asthmatic bronchitis 10, acute pneumonia 1, primary atypical pneumonia 2, Mycoplasma pneumonia 4 and pertussis 2). As a rule, MOM was given orally at a daily dose of 20 approximately 40 mg/kg divided into 3 times. The clinical results were excellent in 5 patients, good in 21, fair in 7 and poor in 13 and the efficacy rate was 56.5%. Side effects were observed in 4 patients (diarrhea, exanthema, urticaria and eosinophilia, 1 patient respectively). MOM is easy to take and a useful antibiotic for treating patients with bacterial infections, in particular, respiratory tract infection caused by Mycoplasma pneumoniae.

Spiramycin, a macrolide antibiotic, has been advocated for the treatment of cryptosporidiosis. The disease most commonly occurs in patients with AIDS and can be debilitating, as diarrhea and malnutrition may be contributing factors in the death of these patients. Until recently, treatment for cryptosporidiosis has been largely symptomatic. Response rates with drug therapy such as metronidazole, quinidine-clindamycin, and pentamidine have been extremely poor. Although response to spiramycin has appeared promising, there have been several reported cases of treatment failure. Further investigation with the agent is advocated to determine its role in the treatment of cryptosporidiosis.

The efficacies of two dosage regimens (2.0 g and 1.5 g each day for four days) of rosaramicin were compared in 40 men with acute uncomplicated gonococcal urethritis. After treatment 39 (97%) of 40 patients were asymptomatic and had negative cultures. Gastrointestinal side effects were reported for 12 (28%) of 43 patients; however, only two patients (5%) discontinued therapy because of side effects.

The use of penicillins and macrolides in the management of community-acquired respiratory tract infections is evaluated in relation to such factors as antimicrobial activity, stability, pharmacokinetics and adverse reactions. Attention is directed to the side effects of drugs, e.g. to the clear advantages of 16 (e.g. spiramycin) vs. 14 (e.g. erythromycin)-membered ring macrolides, and examples are drawn to illustrate the tactics of antimicrobial therapy in the management of pneumonias.

Clinical investigation with a new macrolide antibiotic, midecamycin granules was performed with the results which may lead to the following conclusion. 1) Results of clinical treatment: When midecamycin granules were administered orally in 31 cases of representative infections in the otorhinolaryngological field, it was excellent in 7 cases, good in 20 cases, fair in one case and poor in 3 cases. When the cases in which it was excellent and good were considered together, good results were obtained in 27 cases, that is a ratio of effectiveness of 87.1 per cent. 2) Side effect: No side effect was shown with the oral administration of midecamycin granules.

The clinical efficacy and safety of acetylspiramycin for Mycoplasma pneumonia in children were studied at a dose level of 50 mg/kg/day q.i.d. and the following results were obtained. Acetylspiramycin showed effect in 24 patients out of 25 (96.0%). The level of transminase was increased in 3 cases on admission. One of them was an uneffective case, and eruption was seen after administrating the drug. Diarrhea and poor appetite were observed in one case as side effects, and they were controlled easily. It may be concluded from these results acetylspiramycin was relatively free from side effects and considered to be useful for Mycoplasma pneumonia.

In a study of rokitamycin (RKM) dry syrup for its usefulness in pediatric infections, the following results were obtained: 1. Frequencies of RKM-resistant strains among fresh isolates from sick children were very low, and 4.4% of 68 isolates of Staphylococcus aureus, 4.2% of 48 isolates of Streptococcus pneumoniae, and none of 96 isolates of Streptococcus pyogenes were found to be RKM-resistant. 2. Hypo- to achlorhydria was found in 2 (3.77%) of 53 children. 3. When children were administered once orally with 5, 10 and 15 mg/kg of RKM dry syrup at fasting, mean peak values of plasma concentration were 0.25, 0.55 and 0.74 micrograms/ml with a T1/2 (beta) of 2.18, 1.97 and 2.00 hours, respectively. Urinary recovery rates during the first 0-6 hours were quite low, and values were 1.21, 1.38 and 2.23%, respectively. 4. The clinical efficacy of RKM dry syrup was studied on children chiefly with acute pneumonia, mycoplasmal pneumonia and tonsillitis. Among 379 children from whom pathogens had been determined, responses to the treatment were excellent in 186, good in 144, fair in 24, poor in 20 and unknown in 5 patients, the overall efficacy rate being 88.2%. Among all 598 treated patients, including those with undetermined pathogens, responses were excellent in 247, good in 269, fair in 42, poor in 35 and unknown in 5 patients, the efficacy rate being 87.0%. 5. The clinical efficacy of the drug in treating Chlamydia infection in 12 patients including a Chlamydia carrier and the clinical efficacy in treating Campylobacter enteritis in 36 patients were studied. All the cases showed "good" responses. Among 66 patients with mycoplasmal pneumonia, responses were excellent in 33 and good in 27 patients, with an efficacy rate of 90.9%. 6. The optimal dose of RKM dry syrup seemed to be in the range between 20 and 40 mg/kg. It appeared, however, that a dose of about 40 mg/kg would be required to eradicate the pathogen from the pharynx in S. pyogenes infection. 7. Adverse reactions to RKM dry syrup were found in 9 (1.45%) of 622 patients. The reactions were gastrointestinal symptoms except eruption occurred in 1 patient, but they were all mild. Laboratory examinations revealed eosinophilia in 19 and abnormal hepatic enzyme activities in 8 of 455 patients studied, but such abnormalities were all transient and mild.

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 macrolide antibiotic rosaramicin inhibits in vitro growth of Chlamydia trachomatis. Rosaramicin (1 g daily given to 18 patients for seven days) and erythromycin stearate (2 g daily given to 19 patients for seven days) were compared in the treatment of chlamydial cervicitis. Cultures of cervical specimens obtained nine to 11 days and 24-32 days after commencement of therapy were negative for all rosaramicin-treated patients seen at follow-up. The first follow-up culture of one erythromycin recipient was positive. The extent of cervicitis decreased in all patients after treatment, but the only patients to achieve a completely normal cervical appearance were those with minimal-to-moderate lesions before treatment. Gastrointestinal side effects, including nausea, vomiting, and abdominal pain, occurred in ten of 19 patients given erythromycin and in 13 of 18 given rosaramicin. Minimally elevated levels of alanine aminotransferase in serum occurred in four (22.2%) of 18 rosaramicin recipients. It is concluded that rosaramicin and erythromycin stearate both eradicate C. trachomatis cervical infection but frequently cause adverse gastrointestinal effects.

This review deals with tolerance of a new macrolide, roxithromycin from data collected from a number of studies in adults. A total of 2917 adults, 2519 given roxithromycin 150 mg bid, were recruited into 17 multicentre comparative or non-comparative studies. Nine studies were double-blind, against doxycycline, erythromycin estolate (EES), lymecycline or cephradine. Overall the drug was well tolerated: side-effects possibly or probably related to roxithromycin were noted in only 4.1% (120/2917) of all patients, and in 3.1% (15/480) of elderly subjects. The gastrointestinal tolerance of roxithromycin was significantly better than that of doxycycline in four trials, and better than that of erythromycin ethylsuccinate in one study. The incidence of drug-related liver function test abnormalities following roxithromycin therapy was low and compared favourably with data published on erythromycin. Roxithromycin shows a satisfactory safety profile at the recommended daily dosage of 150 mg bid in adults.

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.

This study was designed to compare both clinical and microbiological changes during the treatment of advanced periodontal disease with mechanical debridement, with or without the adjunctive use of either spiramycin or tetracycline. The study, which included 96 patients with advanced periodontitis, was performed as a controlled double-blind parallel randomized trial. All patients received thorough scaling and root planing as well as adjunctive placebo or spiramycin or tetracycline. Probing depth measurements, attachment level changes, plaque level, gingival crevicular fluid, bleeding on probing and microbiological evaluation were carried out at baseline, 2-, 8-, 12- and 24-week visits. Seventy-nine patients (24 placebo, 27 tetracycline and 28 spiramycin) completed the study. At 24 weeks there were no intergroup differences in the improvement of any of the clinical parameters. Spiramycin was the only antibiotic which produced a significantly greater decrease in the proportion of spirochaetes than the placebo group at the 24-week visit. It was concluded that mechanical debridement alone was sufficient in decreasing the subgingival bacteria to a level which would result in the return to periodontal health. The study was not long enough to determine whether or not the difference in spirochaete level was an indication that the spiramycin group would have maintained the benefits of treatment for a longer time.

Two macrolide antibiotics, josamycin and erythromycin stearate, were administered orally to healthy, adult male volunteers for a comparative study of their pharmacological properties. In comparable doses, josamycin and erythromycin produced similar plasma concentrations, with similar half-lives and elimination constants. An initial loading dose of 1.5 g of josamycin produced greater peak concentrations of antibiotic throughout a 10-day period with a regimen of every 6 h. In addition, josamycin tended to reach higher peak and trough concentrations after regimens of every 6 or 8 h were maintained for 2 days. Josamycin penetrated into saliva, sweat, and tears, and it was better tolerated in fasting subjects than was erythromycin stearate.

The concept of residues of antibiotics used as feed additives or veterinary drugs in food producing animals is analysed, and implications on human public health are discussed. The examples of Tylosin and Penicillin are developed to illustrate the both notions of "high risk residue" and "toxicodisponibility" of residues. The "high risk residue" may be an active metabolite different by its chemical structure and by its pharmacological properties from the original drug administered. Slight modifications of the molecule, as the rupture of the beta lactam ring of the Penicillin, occuring in vivo, lead to a metabolite, e.g. penicilloyl group, that has lost all antibiotic activity but possesses allergenic potential. Toxicity of the residue, compared with that of the original drug, can then be modified or increased. On the other hand, such an active metabolite having a definite chemical structure, even if different from the original compound, can be present in the organism, either free or bound to serum or tissues proteins. Moreover, it is shown here, that in the case of a covalent binding of the drug or its metabolite (e.g. penicilloyl group) to serum albumin, the residues are mostly masked inside the tertiary structure of the albumin molecule, and are not accessible to antibodies. These different forms have then an effect upon the biodisponibility, the "toxicodisponibility", of the residues for the human consumer of animal products where they are present. These forms are only accessible with more and more specific and sensitive analytical methods which relates also the qualitative and quantitative notions of residue to the technological degree used for investigation, determination and identification. As to cooking techniques, they can lead to a thermodegradation of the residue or, on the opposite, to an unmasking of the residue present as a protein conjugate, e.g. penicilloyl-protein conjugate in milk.

An open multicentre clinical trial was conducted in Japan to study the efficacy and safety of roxithromycin in the treatment of acute odontogenic infections. Specimens were collected by needle aspiration only from closed abscesses. The MICs were determined for the pathogens isolated by an agar dilution method. Before and after administration of roxithromycin, whenever possible, a biological safety evaluation was performed. The drug was orally administered in a dosage of 200-400 mg daily, in two divided doses, before the morning and evening meals. Evaluation was objectively performed in accordance with the 'Evaluation Criteria for the Efficacy of Antibiotics by the Japan Society of Oral Surgeons'. A total of 144 bacterial strains were isolated from 73 of the 193 analysed subjects. The proportion of the strains sensitive to roxithromycin (MIC less than or equal to 3.13 mg/l) was 85.4%. One hundred and ninety three of a total of 216 subjects were included in the final analysis. The efficacy of the drug was assessed to be 85.5%. No dose-dependent difference in the clinical effect was observed. Adverse reactions were mainly gastrointestinal disorder, seen in five of 211 subjects (2.4%), while increased hepatic transaminases were observed in two of 92 subjects (2.2%).

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.

The effects resulting from the administration of therapeutic doses (1,200 mg/day for 8 days) of miocamycin, a novel macrolid derived from midecamycin, on theophylline elimination kinetic were investigated on 25 patients affected with chronic obstructive pathology on the respiratory tract. The curves of theophylline clearance, recorded before and after the treatment with miocamycin have shown to be perfectly overlapping (trend analysis). The assumption that the capacity of slackening the theophylline pharmacokinetic would be tightly bound to the particular structure of some macrolids appears to be fully confirmed by the results of the present investigation. When miocamycin is administered in combination with theophylline, the monitoring precautions of plasma levels of the latter are practically of no use.

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.

1. The dry syrup of MOM was administered orally to 17 patients mainly with heart diseases at doses of 10 mg/kg and 20 mg/kg. In 17 cases, the serum level was measured and in 4 cases, the urinary excretion rate including the metabolites of MOM. 2. The mean maximal concentrations were 0.54 mcg/ml at 30 minutes for the group of 10 mg/kg treatment and 0.33 mcg/ml at 1 hour for the group of 20 mg/kg treatment. The dose response was not observed obviously in both groups. 3. In each of the cases, the sum of excretion rates of metabolites in the 24-hour urine was about 1%. 4. MOM was administered clinically to 39 cases with respiratory tract infections and the overall efficacy rate was 85%. 5. In this study, 5 strains of S. pyogenes were isolated and the eradication rate was 60%. 6. Although severe side effects were not observed, gastrointestinal abnormalities like diarrhea and vomiting were seen in 3 cases. 7. Any pediatric patient did not refuse taking.

In a double blind randomised investigation in 76 patients, roxithromycin (150 mg bd) and doxycycline (200 mg once daily) were compared in two groups of patients who were well-matched for age, sex, body weight, diagnosis, duration and severity of disease and associated pathological conditions, with infected skin conditions. Clinical effectiveness was 92% for roxithromycin and 82% for doxycycline, and bacteriological effectiveness also 92% and 82% respectively, the differences not being statistically significant.

The therapeutic effect and clinical tolerance of an association of spiramycin and metronidazole were assessed in 20 patients with odontostomatological inflammation. The results were regarded as satisfactory with regard to the length of treatment and the progression of the clinical picture in 90% of the cases treated. Unwanted side-effects, not sufficiently severe to stop the treatment, were noted in only 2 cases. Comparison with the results obtained in a control series treated with spiramycin only showed that the combination was more effective, though the difference was not significant, and letter tolerated.

The treatment of cervical Chlamydia trachomatis infection in nonpregnant women was evaluated in a double-blind randomized study. Objective criteria were used to assess the response of cervicitis to therapy. Fifty patients were treated with tetracycline hydrochloride, 500 mg orally four times daily, and 50 patients were treated with rosaramicin, 250 mg orally four times daily, both for 7 days. Both agents were highly effective in eradicating C trachomatis. Both produced significant improvement in objective signs of cervicitis: eliminating mucopurulent endocervical discharge and edema of ectopy, and decreasing the clinical severity score of cervicitis. This trial shows that the 1-week course of tetracycline hydrochloride currently recommended for treatment of chlamydial urethritis in men is also highly effective for the treatment of chlamydial cervical infection in women. Rosaramicin, a macrolide antibiotic, was equally effective but produced a higher rate of gastrointestinal side effects.

The authors have carried out some studies on MOM dry syrup in the field of pediatrics and the results were as follows. 1. After oral administration of MOM at 20 mg/kg, the serum level peaked at 30 minutes and MOM could still be detected in the serum at up to 4 hours. The half-life was 0.67 hour. The urinary recovery rate of MOM was 1.43% up to 6 hours after this oral administration. 2. The clinical efficacy rates with MOM continuous treatment at a daily dose of 19.4 to 50.0 mg/kg (almost about 30 mg/kg) were 85.7% for upper respiratory tract infections, 66.7% for lower respiratory tract infections and 95.7% for Mycoplasma pneumonia. 3. It was easy to administer MOM orally even to the younger children. Although MOM was administered for 4 to 21 days, no side effects were observed locally or systemically except for transient slight diarrhea. These results confirmed the usefulness of MOM in the treatment of acute respiratory tract infections in children.

Twenty five children were treated with rokitamycin (RKM) and its clinical efficacy and side effects were evaluated. Ages of the patients ranged from 13 days to 10 years. Doses of RKM ranged 17.1-39.3 mg/kg/day for 2.3 to 17.7 days. Twenty four patients including 8 Mycoplasma pneumonia, 5 bronchopneumonia, 6 bronchitis, 2 streptococcosis, 1 otitis media, 1 tonsillitis and 1 Chlamydia conjunctivitis were evaluated for clinical efficacy. Results were excellent in 7, good in 12, fair in 4, and poor in 1 patient. One patient was excluded from the evaluation, because the patient was treated with erythromycin before entering this study. Out of the 25 patients, 3 cases showed eosinophilia, 2 cases showed elevated GOT and GPT but no adverse clinical signs due to RKM were observed. The pharmacokinetics of RKM was studied in 5 patients whose ages ranged from 8 to 12 years. Plasma peak concentrations of RKM in 2 patients were 0.14 and 0.16 micrograms/ml at 30 minutes after doses of 5 mg/kg. Peak concentrations in 3 patients ranged from 0.32 to 1.02 micrograms/ml after doses of 10 mg/kg. Portions of the drug excreted into urine within 6 hours were 0.49 and 1.03% in 2 patients each of whom was given doses of 5 mg/kg, and ranged from 1.16 to 1.30% in 3 patients, each given 10 mg/kg. Metabolic products in urine within 4 hours after doses of 5 to 10 mg/kg were studied in 4 patients. Leucomycin A7 and leucomycin V accounted for almost 90% of all the related compounds excreted.

Nine doses of oral spiramycin were administered to 59 adult healthy nasopharyngeal carriers of meningococci: a 2-gram loading dose followed by 1 g every 12 h for 4 days. There was a reduction in carriage of 85 and 59%, respectively, on the 2nd and 12th post-treatment day. There was no difference in vitro sensitivity to spiramycin and erythromycin of the meningococci isolated before and after treatment. Spiramycin may be advocated as an effective and safe alternative drug for the chemoprophylaxis of secondary meningococcal disease when sulphonamide resistance is suspected.

Rokitamycin dry syrup (RKM), a new macrolide antibiotic preparation, was evaluated for its safety, efficacy and pharmacokinetics in 19 children. RKM was effective in mycoplasmal pneumonia, Chlamydia trachomatis pneumonitis and Campylobacter gastroenteritis. Efficacies of RKM in streptococcal pharyngitis and Haemophilus influenzae pneumonia, however, were insufficient. Pharmacokinetic observations seemed to indicate that RKM achieved higher blood concentrations than older macrolides, but a large individual variation was observed. Diarrhea which was the only type of side effect observed in our cases, was encountered in 2 of 17 evaluable cases. From these data, RKM seems to have a place in the treatment of pediatric infectious diseases.