Hiroshige Mikamo

Penetration of Ravuconazole, a New Triazole Antifungal, into Rat Tissues

Ravuconazole (BMS 207147, ER-30346) is a long-lasting triazole antifungal agent active against a broad spectrum of fungal pathogens including non-albicans Candida, Aspergillus, Cryptococcus and key dermatophytic fungi. The penetration of ravuconazole into rat tissues was examined. Fifty-five 7-week-old specific pathogen free female rats were used in this study. Plasma, lung and uterus tissue of rats were taken at 1, 2, 4, 8, 12, 16, 24, 32, 48, 60, and 72 h (n = 5) after oral administration of 10 mg/kg of ravuconazole. The quantitative assays of ravuconazole by HPLC after the extraction with diethylether were conducted for each tissue sample homogenate. tmax, t 1/2, and Cmax of ravuconazole is 8 h, 16.9 h and 1.68 µg/ml, respectively. The concentrations of ravuconazole in rat uterus and lung tissues were 2–to 6 times higher than the corresponding blood concentrations. The ratio of plasma to lung levels of ravuconazole was superior to the published data of other azoles. Considering its antifungal spectrum, ravuconazole would thus be a good candidate for treatment of deep-seated fungal infections caused by Candida, Aspergillus and Cryptococcus.

Studies on the clinical implications of anaerobes, especially Prevotella bivia, in obstetrics and gynecology

Prevotella bivia is one of the anaerobic bacteria found in the resident flora of the female genital tract. The detection rate ofP. bivia has been poor, however, mainly due to problems such as the poor survival of this microbe in the presence of oxygen. To identifyP. bivia, it is necessary to start the culture, within 1 hour after sampling. We were able to isolate 13 strains ofP. bivia (32.5%) from 40 cases of preterm premature rupture of membrane, 8 strains (40.0%) from 20 cases of puerperal uterine endometritis, 20 strains (40.0%) from 50 cases of pyometra, 6 strains (40.0%) from 15 cases of severe pelvic inflammatory disease, and 6 strains (17.1%) from 35 cases of bacterial vaginosis. Most clinical isolates ofP. bivia were susceptible to the commonly used antimicrobial agents.P. bivia was detected concomitantly with aerobic bacteria, related to the alteration of vaginal microbial flora during the menstrual cycle.P. bivia increased in the follicular phase of the menstrual cycle, suggesting that the growth of this microbe might be partly regulated by sex steroids.

Elastase activity of anaerobes isolated from amniotic fluid with preterm premature rupture of membranes

OBJECTIVE A total of 131 anaerobes isolated from amniotic fluid with preterm premature rupture of membranes and stored were examined for elastolytic activity by the method described by Williams et al (Lett Appl Microbiol 1988;7:173-6). STUDY DESIGN Each strain was spot inoculated on a Columbia blood agar plate containing 1% solubilized elastin and incubated for 5 days under anaerobic conditions. Undigested elastin was precipitated by flooding trichloroacetic acid solution onto the plate, and a clear zone was visible as the elastolytic reaction around the spot of bacterial growth. RESULTS Ninety-three (71.0%) of 131 organisms showed a positive elastolytic reaction. Eleven of 20 strains (55.0%) of Peptostreptococcus magnus, 9 of 18 strains (50.0%) of Peptostreptococcus micros, 12 of 12 strains (100.0%) of Fusobacterium nucleatum, 15 of 28 strains (53.6%) of Bacteroides fragilis, 8 of 15 strains (53.3%) of Bacteroides thetaiotaomicron, and 38 of 38 strains (100.0%) of Prevotella bivia were elastolytic. CONCLUSION Anaerobic bacterial species prevalent in the normal vaginal flora that were isolated from amniotic fluid of women with preterm rupture of membranes produced elastolytic activity, plausibly inducing the destruction of host constitutive components.

Preterm labor and bacterial intraamniotic infection: Arachidonic acid liberation by phospholipase A2 of Fusobacterium nucleatum ☆ ☆☆

OBJECTIVE The studies presented in this report were undertaken to evaluate whether Fusobacterium nucleatum, a common anaerobic isolate in intrauterine infection, stimulates arachidonic acid metabolism, a rate-limiting step for prostaglandin synthesis, in the human uterine endometrium. STUDY DESIGN Effects of F nucleatum on arachidonic acid liberation from human uterine endometrial cells and of F nucleatum extract on lysophosphatidylcholine production in human uterine endometrial cells were investigated. RESULTS When human uterine endometrial cells labeled with tritiated arachidonic acid to an isotopically steady state were exposed to an extract of F nucleatum, arachidonic acid liberation was stimulated, accompanied by lysophospholipid formation. Similar stimulatory effects on phospholipid degradation were also observed in the experiment with bacterially conditioned media. CONCLUSIONS These results suggest that F nucleatum stimulates endometrial phospholipid metabolism, related to activity of phospholipase A2, which might induce the onset of labor associated with intraamniotic infection.

Trends in serotypes and antimicrobial susceptibility of group B streptococci isolated in Korea

Abstract Studies of group B streptococci (GBS) have been limited in Korea, despite the necessity for such studies because of the increase in serious adult infections, the emergence of new serotypes, and the increase of resistance to certain antibiotics. In this study, trends in serotypes of GBS isolated in Korea were compared to determine any changes and emergence of new types, while antimicrobial susceptibility was tested and compared with that of group A streptococci (GAS). It was found that the most frequent infections caused by GBS were of the urinary tract, but other severe infections also occurred not only in newborns but also in adults. The prevalent serotypes were still Ia, Ib, and III, while new serotypes, VI and VIII, also emerged. GBS were susceptible to β-lactam antibiotics, but were much less so than GAS. The resistance rates to erythromycin and tetracycline were much higher than those in other countries, suggesting that these antibiotics are no longer very useful in Korea for the treatment of GBS infections.

Studies on the pathogenicity of anaerobes, especially Prevotella bivia, in a rat pyometra model.

OBJECTIVE: Prevotella bivia is one of the anaerobic bacteria that resides in the flora of the female genital tract. We studied the pathogenicity of P. bivia in a rat pyometra model. METHODS: The experimental animal (rat) model of pyometra was developed to investigate the pathogenicity of P. bivia in a rat pyometra model. RESULTS: In the groups inoculated with aerobes alone, the infection rate was 10% (1/10) in the Staphylococcus aureus- or Staphylococcus agalactiae-inoculated group and 20% (2/10) in the Escherichia coli-inoculated group. Infection was not established in the groups inoculated with anaerobes alone. High infection rates were observed in all the mixed-infection groups. In the S. agalactiae- and Bacteroides fragilis-, S. agalactiae- and P. bivia-, F. coli- and B. fragilis-, and E. coli- and P. bivia-inoculated groups, an infection rate of 100% (10/10) was demonstrated. The efficacy of antibiotics such as flomoxef (FMOX) could be determined using a rat pyometra model. In relation to the alteration of vaginal microbial flora during the menstrual cycle, estrogen increased the growth of P. bivia. CONCLUSION: Mixture of aerobic bacteria and P. bivia increased the pathogenicity of P. bivia. Estrogen would be useful for raising up the inflammatory change of the uterus in experimental models of genital tract infection due to P. bivia.

Comparative Study on the Effectiveness of Antifungal Agents in Different Regimens against Vaginal Candidiasis

Objective: A study was carried out to compare three treatment regimens for vaginal candidiasis. Methods: A total of 150 women with clinical and mycological evidence of vaginal candidiasis were randomized to receive daily a 200-mg dose of oral itraconazole for 3 days (50 women), a single oral 150 mg dose of fluconazole (50 women), or daily 100 mg dose of intravaginal clotrimazole for 6 days (50 women). They were assessed at 5–15 days (short-term assessment) and again at 30–60 days (long-term assessment) after discontinuation of the treatment. Results: At the short-term or long-term assessment, Candida species were completely eradicated from the vagina in 80 or 74% in the 3-day oral itraconazole group, 76 or 70% in the single oral fluconazole group, and 72 or 60% in the intravaginal clotrimazole group, respectively. The rates of clinical effectiveness were 92 or 88% in the 3-day oral itraconazole group, 80 or 76% in the single oral fluconazole group, and 72 or 58% in the intravaginal clotrimazole group, respectively. Treatment-related side effects were not found in any group. Conclusions: Our study suggests that the treatment of vaginal candidiasis with oral itraconazole or oral fluconazole would be effective and that an oral itraconazole or fluconazole therapy might be one choice in the treatment of vaginal candidiasis.

Effect of ravuconazole, a new triazole antifungal, in a rat intraabdominal abscess model

Background: Ravuconazole (BMS-207147) is a long-lasting triazole antifungal agent active against a broad spectrum of fungal pathogens including non-albicans Candida, Aspergillus, Cryptococcus and key dermatophytic fungi. Methods: The efficacy of ravuconazole was evaluated using an experimental intraabdominal abscess model in rats caused by Candida albicans (E81022). Two hundred milligrams of cyclophosphamide per kilogram was injected intraperitoneally into 40 rats. Four days (96 h) after the injection of cyclophosphamide, a mixture of C. albicans and autoclaved rat cecal contents [C. albicans 1.7 × 108 colony-forming units/rat] was inoculated into the peritoneal cavity. The rats were divided into four groups: ravuconazole treated, fluconazole treated, itraconazole treated and untreated. Each antifungal was given orally at a dose of 10 mg/kg twice a day for 5 days. On the day after the last administration, the rats were dissected and the viable fungi in the abscesses were determined. The number of C. albicans in each abscess was determined by a quantitative culture technique. Results: Ravuconazole inhibited abscess formation and significantly decreased the viable cell counts in abscesses in comparison with the untreated group. It’s efficacy was at least equivalent to fluconazole and itraconazole against this pathogen. The rank order of potency (inhibition) was ravuconazole > itraconazole > fluconazole. Conclusion: Taking into consideration the antifungal spectrum of ravuconazole, which includes non-albicans Candida as well as C. albicans and Aspergillus, it is suggested that ravuconazole would be a good agent for the treatment of fungal peritonitis.

Current Status and Fluconazole Treatment of Pelvic Fungal Gynecological Infections

The incidence of opportunistic fungal infections has recently been increasing in many clinical fields. Fluconazole is commonly used against systemic fungal infections. The present study was undertaken to investigate the current status and the efficacy of fluconazole in pelvic fungal gynecological infections. Thirty-eight patients aged 36–72 years old diagnosed with pelvic peritonitis with positive fungal culture in pelvic ascites were enrolled in this study and given fluconazole treatment. Forty-two pathogens were isolated from the 38 assessable patients. The predominant pathogen was Candida albicans with an incidence of 61.9% (26/42). Others included non-albicans Candida species amounting to 38.1% (16/42): 19.0% (8/42) Candida glabrata, 7.1% (3/42) Candida tropicalis, 7.1% (3/42) Candida parapsilosis and 4.8% (2/42) Candida krusei. The clinical cure rate at the end of fluconazole treatment was assessed as 30/38 (78.9%), and the fungal eradication rate as 26/42 (61.9%). Each rate was 29/38 (76.3%) and 26/42 (61.9%), respectively, at 1 week after the treatment, while the eradication rate of C. albicans and non-albicans species was 20/26 (76.9%) and 6/16 (37.5%), respectively. There was no adverse effect exept for slight elevations of GOT, GPT and LDH observed in 1 patient (2.6%), which returned to normal after the treatment. It seems there may be an increasing trend of non-albicans species in pelvic fungal gynecological infection, against which fluconazole appears to be rather effective.

Ovarian abscess caused by Peptostreptococcus magnus following transvaginal ultrasound-guided aspiration of ovarian endometrioma and fixation with pure ethanol.

BACKGROUND: Transvaginal ultrasound-guided aspiration of ovarian endometrioma has been applied and emphasized as a safe and simple procedure. CASE: Two 27-year-old infertile women, both gravida 0, para 0, underwent medical follow-up examinations for cases of ovarian endometrioma. Both had undergone transvaginal ultrasound-guided aspiration of ovarian endometrioma. Because both were continuously febrile and had abdominal pain and cysts with tenderness in spite of antibiotic therapies, both underwent laparotomies for treatment. In both cases, enucleation of the ovarian abscess revealed purulent and malodorous fluid that demonstrated Peptostreptococcus magnus in culture. CONCLUSION: We theorize that following transvaginal ultrasound-guided aspiration of ovarian endometrioma and fixation with pure ethanol, anaerobic infection by P. magnus occurred, and a cyst formed in the abscess.