Prevention of bacteremia caused by alpha-hemolytic streptococci by roxithromycin (RU-28 965) in granulocytopenic patients receiving ciprofloxacin.

We previously demonstrated that ciprofloxacin prevents infections caused by gram-negative bacilli in patients with granulocytopenia. However, in patients with intensive cytotoxic treatment leading to severe mucosal damage a high incidence of bacteremias caused by alpha-hemolytic streptococci was seen. In the present study 45 consecutive patients undergoing intensive cytotoxic treatment received a short course of roxithromycin (10 days) in addition to ciprofloxacin for prevention of bacteremias caused by alpha-hemolytic streptococci. The results of this study were compared with the results obtained in previous comparable patients receiving ciprofloxacin alone. During the days with addition of roxithromycin no infections caused by alpha-hemolytic streptococci occurred, while in the control group of 80 patients 16 bacteremias (20%) were seen. Although roxithromycin was shown to antagonize bactericidal action of ciprofloxacin on gram-negative bacilli in vitro, in vivo study based on serum bactericidal titers and on results of surveillance cultures showed no antagonistic interactions.

[Studies on the metabolic fate of 14C-rokitamycin. III. Transmigration to fetus or milk].

Transmigration of 14C-radioactivity to fetus or milk were studied in 17-18 day-pregnant rats and mother rats on the 14th day after parturition after a single oral administration of 14C-rokitamycin (TMS-19-Q) at a dose of 200 mg/kg. The blood concentration of the drug in the mother reached a maximum level of 22.8 micrograms/ml at 2 hours after administration. Maximum concentrations of TMS-19-Q in placenta, ovary and uterus were attained in 2 hours, and were 28.9, 26.0 and 26.2 micrograms/g, respectively. The distribution to these tissues were considered good. The maximum concentration of TMS-19-Q in the amniotic fluid was attained in 2 hours, at a level of 5.4 micrograms/ml. The transmigration to the amniotic fluid was considered poor. The maximum concentration of the drug in the fetus was achieved in 2 hours at a level of 13.7 micrograms/g. Maximum concentrations of the drug in fetal liver and brain were attained in 4 hours, and were 32.8 and 11.4 micrograms/g, respectively. Whole body autoradiography was done when the radioactivity in maternal blood reached peak concentration. It was found that radioactivities in placenta and fetal membrane were similar to the radioactivity in maternal blood, while the radioactivity in fetal brain was considerably lower than that in maternal blood. Maximum concentrations were found at 1 hour in the blood and at 4 hours in the milk, and were 14.8 and 21.5 micrograms/ml, respectively. Transmigration to the milk was good.

Tiamulin in drinking water for treatment and development of immunity to swine dysentery.

The diarrhea of swine dysentery receded in swine treated with 60 or 45 mg of tiamulin/L of drinking water (60 or 45 ppm). However, within 2 to 10 days (average 4.1 days) after drug withdrawal, diarrhea recurred. Tiamulin (22.5 mg/L in drinking water) did not markedly reduce the diarrhea during medication, and tylosin (66 mg/L in the drinking water) was not effective. In swine treated with 120 mg of dimetridazole/L of drinking water, there was no recurrence of diarrhea. After the recurrence of diarrhea in swine, repeated medication with tiamulin in drinking water reduced the severity of diarrhea and prevented deaths. After 1 to 3 retreatments, swine were immune to exposure with swine dysentery inoculum, and there was a significant (P less than 0.05) increase in their serum anti-Treponema hyodysenteriae antibodies. Seemingly, drug withdrawal permitted the occurrence and recurrence of diarrhea that was necessary to stimulate immunity.

[Clinical evaluation of TMS-19-Q, a new macrolide antibiotic, in otorhinolaryngological infections].

The clinical study for TMS-19-Q.O tablet was performed with multicenter trial. The results obtained were as follows; Final global improvement rating in 332 cases of otorhinolaryngological infections were excellent in 99, good in 142, fair in 40 and poor in 51 and the effective rate was 72.6%. Those of 266 cases with acute infection were excellent in 93 and good in 121 and the effective rate was 80.5%. Optimum daily doses would be 600 mg based on the analysis of 144 cases of the acute infection with sensitive bacteria (MIC: less than or equal to 3.13 micrograms/ml). In acute infection, major causative bacteria were Gram-positive cocci (GPC) indicating the frequency of 72.0% in total isolates and 87.5% in singly isolated cases. In chronic infection, although GPC were also dominant, Gram-negative bacilli were observed in 31.9%. Clinical and bacteriological effective rates of 160 cases of acute infection with single species were 80.6% and 90.3%, and those of 43 cases in chronic infection were 44.2% and 72.7%, respectively. The resistant rates of isolates in acute infection to TMS-19-Q were 13.3% in S. aureus, 7.7% in S. epidermidis, 6.0% in S. pyogenes and 0% in S. pneumoniae. Those in chronic infection were 20.0% in S. aureus and 25.0% in S. epidermidis. Slight adverse reactions, such as skin eruption or gastrointestinal disorders were observed in 14 cases and no severe one was observed. Slight elevation of GOT, GPT, Al-P, BUN, S-Cr. or eosinophil were observed in 12 cases. These results suggest that TMS-19-Q would be useful antibiotic for otorhinolaryngological infections.

[Clinical studies on TMS-19-Q.O tablets, the preparation of a new macrolide antibiotic, in the field of oral surgery].

Multicenter clinical trial or TMS-19-Q.O tablet was performed to evaluate the usefulness in oral surgery. The results obtained were as follows: Clinical efficacy was assessed by clinical points. The patients entered into the trial were 77 cases with periodontitis, 23 with pericoronitis, 92 with osteitis of jaw and 18 with other infections, and the each effective rates were 80.5, 60.9, 83.7 and 72.2%, respectively. Overall effective rate was 79.0%. Isolation frequency of organisms were 33.8% in periodontitis, 34.8% in osteitis of jaw and 17.4% in pericoronitis. Bacteria isolated were aerobic organisms (63.1%) and anaerobic organisms (36.9%). TMS-19-Q.O tablet was well tolerated, and no adverse reaction was observed.

Diagnosis and successful treatment of subacute erysipelas in a captive dolphin.

Ersipelas, a common disease of swine, is caused by Erysipelothrix rhusiopathiae. The organism was isolated in a blood culture taken from an infected captive dolphin. The dolphin showed typical subacute symptoms of square- and diamond-shaped skin lesions as seen in swine. It was surmised, in retrospect, that the disease was secondary to a primary pneumonia. The symptoms, clinical pathology and other special examinations, treatment and response are discussed.

Evaluation of spiramycin in meningococcal carriage.

Spiramycin was administered to healthy carriers of meningococci in doses of 1.5 g twice daily or 2.5 g once daily for 3 days, or 1.5 g once daily for 10 days. Meningococci were eliminated from the nasopharynx and throat in approximately 50% of the carriers with all dose schedules. In the remaining carriers only a temporary suppression of the strain was achieved. Elimination occurred only in carriers where spiramycin saliva concentrations reached or surpassed the MIC value of respective strain for 42 h or more. Evidence of reinfection from close contacts was not obtained. Due to side effects the dose of spiramycin could not be increased. Further trials with spiramycin as the sole agent for eliminating meningococci in carriers do not seem warranted.

Hemostatic function in swine as influenced by warfarin and an oral antibacterial combination.

Pertinent literature on naturally occurring hemorrhagic diseases in poultry and livestock were reviewed and compared with reports on recent outbreaks of a hemorrhagic syndrome in swine. Epizootiologic, clinical, and hematologic data from porcine hemorrhagic disease suggest vitamin K-responsive hypoprothrombinemia. In weanling pigs, the toxicity of warfarin was compared with that in swine given tylosin and sulfamethazine antibacterial combination versus those given warfarin only. Toxicosis was induced in weanling swine fed warfarin daily at dose level of 0.055 mg/kg of body weight. Approximately 5 days after feeding was started, signs of poisoning appeared: lameness, anorexia, subcutaneous hematomata, melena, and periarticular enlargement. Administration of warfarin at dose level of 0.017 mg/kg did not cause clinical toxicosis, and 0.028 mg/kg produced significant increases in one-stage prothrombin time (OSPT) and activated partial thromboplastin time (APTT), but no evidence of clinical bleeding. When tylosin-sulfamethazine antibacterial combination was fed at normal and high dose levels concurrently with warfarin at dose level of 0.017 mg/kg of body weight, increase of clotting time, OPST, or APTT did not occur due to antibacterial influence. The antibacterial combination fed alone did not produce changes in clotting time, OSPT, APTT, fibrinogen, total protein, differential leukocyte count, or packed cell volume.

Evaluation of spiramycin as a therapeutic agent for elimination of nasopharyngeal pathogens. Possible use of spiramycin for middle ear infections and for gonococcal and meningococcal nasopharyngeal carriage.

Varying doses of spiramycin were administered orally to healthy volunteers, and concentrations in serum and saliva were determined. The absorption of the drug was not significantly influenced by concomitant food intake. Saliva peak concentrations were 1.3--4.8 times higher than peak concentrations in serum. The elimination half life was 2--3 h in serum, and 4--8 h in saliva. Accumulation of the drug was seen in saliva but not in serum. The possible effect of spiramycin in eliminating bacteria from the nasopharynx was evaluated in vitro by comparing the spiramycin saliva concentrations with the MICs of bacteria known to establish themselves in the nasopharynx. At a concentration of 1.2 microgram/ml, spiramycin inhibited all investigated strains of group A streptococci, pneumococci and Branhamella catarrhalis, and at 2.4 microgram/ml all investigated gonococci. Concentrations of 19 and 38 microgram/ml, respectively, were required to inhibit all meningococci and Haemophilus influenzae. Following administration of 1.5 g spiramycin as a single daily dose for 3 days, the mean concentration in saliva reached or surpassed the MIC values of streptococci, pneumococci and Branhamella for 45 h, and of gonococci for 25 h. The possible use of spiramycin for prevention of relapses in acute otitis media and in treatment of serous otitis media is discussed, as well as the possible use of the drug in gonococcal and meningococcal nasopharyngeal carriage.