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Introduction: With an increase in the incidence of Staphylococcus aureus infections in the healthcare settings and in the community, trimethoprim/sulfamethoxazole (TMP/SMX) has been suggested as a convenient treatment option. However, the appropriate dosage regimen of TMP/SMX is unclear. Objective: This study aimed to examine the pharmacokinetics/pharmacodynamics (PK/PD) of TMP/SMX against S. aureus using a neutropenic murine thigh infection model. Methods: Five S. aureus isolates with TMP/SMX (1:5 fixed ratio) minimum inhibitory concentrations (MICs) of 0.032–64 μg/mL were tested. The antimicrobial efficacy of TMP/SMX (1–689 mg/kg/day: dose shown as SMX dosage) was calculated as the change in bacterial density after 24 h of treatment. The plasma concentrations of TMP/SMX were detected using high-performance liquid chromatography. Results: After TMP/SMX single dose (130 mg/kg), the half-life, area under the blood concentration curve (AUC0–∞), and the protein binding ratio of SMX were 1.5 h, 718.2 μg h/mL, and 73.0 ± 8.3%, respectively. The free AUC/MIC and free %time (%T) above the MIC of SMX were better correlated with the in vivo antimicrobial activity than Cmax/MIC (free AUC/MIC, R2 = 0.69; free %T > MIC, R2 = 0.71; free Cmax/MIC, R2 = 0.53). The distributed doses (2–3 times per day) of TMP/SMX (130, 260, and 390 mg/kg/day) showed higher antimicrobial activity than the single dosage. However, TMP/SMX did not show its antimicrobial activity at T > MIC. Conclusions: The TMP/SMX treatment demonstrated that the free AUC/MIC of SMX was the better predictor of the PK/PD index of TMP/SMX.

Previous clinical studies have showed the clinical benefits of the initiation of treatment with a daptomycin (DAP) loading dose, but only a few studies have evaluated its antimicrobial benefits. We evaluated the efficacy of a DAP loading dose against methicillin-resistant Staphylococcus aureus (MRSA) infections in a neutropenic murine thigh infection model. Three MRSA isolates (DAP MIC: 0.5, 1, and 2 mg/L) were tested. Four DAP regimens simulating human concentration-time profiles, i.e., (i) day 1: 8 mg/kg and day 2: 6 mg/kg, (ii) days 1 and 2: 6 mg/kg/day, (iii) day 1: 8 mg/kg and day 2: 4 mg/kg, and (iv) days 1 and 2: 4 mg/kg/day, were administered to the mice. Efficacy was calculated as the change in bacterial density. DAP loading-dose regimen iii showed greater antimicrobial activity against MRSA with MIC 1 mg/L than nonloading regimen iv (-3.10 ± 0.63 vs. -0.71 ± 0.34 log10 CFU; p < 0.01). Loading-dose regimen iii achieved greater log10 CFU changes than nonloading regimen ii, while the total DAP dose for 2 days was the same (-3.10 ± 0.63 vs. -1.46 ± 0.48 log10 CFU; p < 0.05). DAP loading-dose regimen iii showed enhanced antimicrobial activity against MRSA with DAP MIC 0.5 mg/L when compared with nonloading regimen iv. However, loading-dose regimens i and iii did not reduce bacterial density for MRSA with DAP MIC 2 mg/L. Our data suggest that a DAP loading-dose regimen would be an advantageous procedure for patients infected with MRSA with DAP MIC ≤1 mg/L.

With an increase in the incidence of Staphylococcus aureus infections in the healthcare settings and in the community, trimethoprim/sulfamethoxazole (TMP/SMX) has been suggested as a convenient treatment option. However, the appropriate dosage regimen of TMP/SMX is unclear.This study aimed to examine the pharmacokinetics/pharmacodynamics (PK/PD) of TMP/SMX against S. aureus using a neutropenic murine thigh infection model.Five S. aureus isolates with TMP/SMX (1:5 fixed ratio) minimum inhibitory concentrations (MICs) of 0.032-64 μg/mL were tested. The antimicrobial efficacy of TMP/SMX (1-689 mg/kg/day: dose shown as SMX dosage) was calculated as the change in bacterial density after 24 h of treatment. The plasma concentrations of TMP/SMX were detected using high-performance liquid chromatography.After TMP/SMX single dose (130 mg/kg), the half-life, area under the blood concentration curve (AUC0-∞), and the protein binding ratio of SMX were 1.5 h, 718.2 μg h/mL, and 73.0 ± 8.3%, respectively. The free AUC/MIC and free %time (%T) above the MIC of SMX were better correlated with the in vivo antimicrobial activity than Cmax/MIC (free AUC/MIC, R2 = 0.69; free %TMIC, R2 = 0.71; free Cmax/MIC, R2 = 0.53). The distributed doses (2-3 times per day) of TMP/SMX (130, 260, and 390 mg/kg/day) showed higher antimicrobial activity than the single dosage. However, TMP/SMX did not show its antimicrobial activity at100% free %TMIC.The TMP/SMX treatment demonstrated that the free AUC/MIC of SMX was the better predictor of the PK/PD index of TMP/SMX.

Background: Reports of Pseudomonas aeruginosa with high antimicrobial resistance have steadily emerged, threatening the utility of a mainstay in antipseudomonal therapy. This study evaluated the antimicrobial activities of various combination therapies against P. aeruginosa with high antimicrobial resistance, including multidrug-resistant P. aeruginosa (MDRP) using an in vitro and in vivo study. Methods: We evaluated 24 combination therapies, including colistin, aztreonam, meropenem, ceftazidime, ciprofloxacin, amikacin, rifampicin, arbekacin and piperacillin against 15 MDRP isolates detected at Aichi Medical University Hospital with the break-point checkerboard method. Based on the results of the in vitro study, we evaluated antimicrobial activity against highly antimicrobial-resistant P. aeruginosa with an in vivo murine thigh infection model. Results: The combination regimens including colistin and aztreonam showed higher antimicrobial activity against the 15 MDRP isolates. In the in vivo study, the high-dose colistin monotherapy (16 mg/kg every 12 h) achieved greater log10 CFU changes than the normal-dose colistin regimen (8 mg/kg every 12 h) against 5 P. aeruginosa isolates, including 2 MDRP isolates (p < 0.05). Aztreonam monotherapy (400 mg every 8 h) yielded bacterial densities similar to untreated control mice for the MDRP isolate evaluated. The combination therapy with a higher dose of colistin had superior antimicrobial activity against 5 P. aeruginosa with colistin (MIC 0.5 μg/ml) and aztreonam (MIC ≥128 μg/ml) than colistin monotherapy. Conclusion: The data suggest that the combination treatment of colistin and aztreonam could be the most useful for treating highly resistant P. aeruginosa with a higher susceptibility to colistin, including MDRP infections.

Reports of Pseudomonas aeruginosa with high antimicrobial resistance have steadily emerged, threatening the utility of a mainstay in antipseudomonal therapy. This study evaluated the antimicrobial activities of various combination therapies against P. aeruginosa with high antimicrobial resistance, including multidrug-resistant P. aeruginosa (MDRP) using an in vitro and in vivo study.We evaluated 24 combination therapies, including colistin, aztreonam, meropenem, ceftazidime, ciprofloxacin, amikacin, rifampicin, arbekacin and piperacillin against 15 MDRP isolates detected at Aichi Medical University Hospital with the break-point checkerboard method. Based on the results of the in vitro study, we evaluated antimicrobial activity against highly antimicrobial-resistant P. aeruginosa with an in vivo murine thigh infection model.The combination regimens including colistin and aztreonam showed higher antimicrobial activity against the 15 MDRP isolates. In the in vivo study, the high-dose colistin monotherapy (16 mg/kg every 12 h) achieved greater log10 CFU changes than the normal-dose colistin regimen (8 mg/kg every 12 h) against 5 P. aeruginosa isolates, including 2 MDRP isolates (p0.05). Aztreonam monotherapy (400 mg every 8 h) yielded bacterial densities similar to untreated control mice for the MDRP isolate evaluated. The combination therapy with a higher dose of colistin had superior antimicrobial activity against 5 P. aeruginosa with colistin (MIC 0.5 μg/ml) and aztreonam (MIC ≥128 μg/ml) than colistin monotherapy.The data suggest that the combination treatment of colistin and aztreonam could be the most useful for treating highly resistant P. aeruginosa with a higher susceptibility to colistin, including MDRP infections.

Background: Telithromycin is one of the ketolides, characterised by a 3-keto group instead of L-cladinose and a C11–C12 carbamate link by an alkyl chain to a pyridinum and imidazolium ring side chain. We evaluated in vitro and in vivo antibacterial activities of telithromycin against gynaecological pathogens. Methods: In the vitro study, the antibacterial activity of telithromycin against 180 isolates (isolated in the year 2000) of Streptococcus agalactiae (n = 33), Enterococcus faecalis (n = 22), Neisseria gonorrhoeae (n = 30), Peptostreptococcus anaerobius (n = 20), Finegoldia magna (n = 20), Bacteroides fragilis (n = 25) and Prevotella bivia (n = 30) was compared with that of erythromycin A, clarithromycin, azithromycin, ampicillin and levofloxacin. In the in vivo study, the efficacy of telithromycin was evaluated using experimental intra-abdominal abscesses in mice caused by B. fragilis (minimum inhibitory concentration of telithromycin 0.5 mg/l). Results: In the in vitro study, telithromycin inhibited more than 50% of clinical isolates of S. agalactiae, E. faecalis, N. gonorrhoeae, P. anaerobius, F. magna, B. fragilis and P. bivia at concentrations of 0.016, 0.063, 0.063, 0.032, 0.032, 0.5 and 0.25 mg/l, respectively. Telithromycin inhibited more than 90% of these clinical isolates at concentrations of 0.016, 4, 0.125, 0.063, 0.063, 4 and 1 mg/l, respectively. In the in vivo study, telithromycin inhibited abscess formation and significantly decreased viable cell counts in abscesses in comparison with the untreated group. Conclusions: These in vitro and in vivo antibacterial activities suggest that telithromycin could be a potential candidate for the treatment of bacterial infections complicated by chlamydial infection.

Biapenem is a new injectable carbapenem antibiotic which has favorable pharmacokinetic properties, and is stable to hydrolysis by dehydropeptidase I. Biapenem inhibited more than 90% of clinical isolates of Streptococcus agalactiae, Escherichia coli, Peptostreptococcus magnus, Bacteroides fragilis and Prevotella bivia at the concentration of 3.13 mg/l. The MIC90 of biapenem against Pseudomonas aeruginosa was lower than that of panipenem, equivalent to that of imipenem, and greater than that of meropenem. The in vivo efficacy of biapenem was evaluated using the experimental infection model of uterine endometritis. The accumulation of neutrophils in the uterus in the biapenem- treated group was less marked than in the nontreated group, as well as bacteriological response. These results suggest that the new antimicrobial agent biapenem might be useful for the treatment of polymicrobial infections in the fields of obstetrics and gynecology.

Prevotella bivia is common in pelvic inflammatory diseases. Parenteral antimicrobial agents have been widely used against those infections. We investigated the bactericidal activities of three cephalosporins, i.e. cefluprenam (CFLP), ceftazidime (CAZ) and cefotaxime (CTX) and of two other antimicrobial agents, i.e. clindamycin (CLDM) and imipenem (IPM) against P. bivia. We also investigated the in vitro morphological changes induced by these agents in P. bivia. Cephalosporins exhibited bactericidal activities against P. bivia and induced time- and concentration-dependent morphological changes in P. bivia (filamentation). CLDM and IPM also had bactericidal activities, but induced different morphologic alterations: formation of spheroblasts and lysis. These results confirm the fact that each antimicrobial agent has characteristic aspects.

S-1090 is a new synthetic, nonesterified, oral cephalosporin with a broad spectrum of antibacterial activity. The activities of S-1090 against the causative organisms in the fields of obstetrics and gynecology are superior to those of the currently prescribed oral cephems, cefdinir, cefpodoxime, and cefaclor. The in vivo efficacy of S-1090 was evaluated using uterine endometritis of model rats. The accumulation of neutrophils in the uterus in the S-1090-treated group was milder than that in the nontreated group, and the same was true for the bacteriological response. S-1090 is a promising oral cephalosporin antibiotic for the treatment of infections in the fields of obstetrics and gynecology.

Polymicrobial infections with aerobes and anaerobes are common in female genital tract infections. We evaluated the efficacy of an injectable new quinolone, pazufloxacin, using a uterine endometritis model. Rats were infected with a mixed inoculation of Escherichia coli plus Bacteroides fragilis (MIC of pazufloxacin and ceftazidime: E. coli: 0.05 and 1.56 µg/ml, respectively, B. fragilis: 3.13 and 3.13 µg/ml, respectively). After inoculating 107 cfu/rat of each organism, pazufloxacin or ceftazidime (10 or 20 mg/kg, respectively, i.v., b.i.d., 3 days) was administered and compared with the nontreated group. The viable cell counts of the uterine corpus and uterine cervix in pazufloxacin-treated and ceftazidime-treated groups were decreased, compared with the nontreated group. The viable cell counts of the adnexa in the pazufloxacin-treated group were significantly decreased, compared with the ceftazidime-treated group. These results suggest that pazufloxacin would be useful for the treatment of polymicrobial infections, especially adnexitis.

The bacteriological epidemiology of bacterial vaginosis (BV) and the efficacy of vaginal or oral treatment of BV with clindamycin (CLDM) were investigated. The epidemiology of BV was investigated in 100 symptomatic women before CLDM therapy. Two groups consisting of 50 patients each with the diagnosis of symptomatic BV were treated with either oral administration of 450 mg CLDM three times daily or 2% CLDM phosphate in vaginal cream (self-made) 5 g once a day, for 7 days. There was no significant difference in efficacy among vaginal and oral therapies with CLDM. Vulvovaginal irritation occurred in 3 patients orally treated and in 1 patient vaginally treated. Gastrointestinal disturbances were observed in 4 orally treated patients. A slight abnormal elevation of the glutamine-oxaloacetic transaminase level was also found in 1 patient orally treated. Since there were no statistically significant differences in efficacy rates between vaginal and oral CLDM treatments, we favor vaginal treatment of BV, based on less adverse effects.

To evaluate in vivo efficacy of macrolides; erythromycin (EM) and clarithromycin (CAM), in the different treatment schedules of Chlamydia trachomatis uterine cervicitis im women. Cervical C. trachomatis was detected by the polymerase chain reaction. EM was orally administered to 8, 15 and 18 Japanese patients, at a dosage of 600 mg, t.i.d. for 5, 7 and 14 days, respectively. CAM was orally administered to 10, 26 and 19 Japanese patients at a dosage of 400 mg, b.i.d. for 5, 7 and 14 days, respectively. The eradication rate and the recurrence rate in the different treatment schedules of C. trachomatis were evaluated. The eradication rates after 5, 7 or 14 days of treatment with EM were 1/8, 8/15 or 13/18, respectively. The recurrence rates after 5, 7 or 14 days of treatment with EM were 1/1, 3/8 or 2/13, respectively. On the other hand, the eradication rates after 5, 7 or 14 days of treatment with CAM were 5/10, 26/26 or 19/19, respectively. The recurrence rates after 5, 7 or 14 days of treatment with CAM were 3/5, 0/26 or 0/19, respectively. A 7-day treatment with CAM would be adequate and effective for C. trachomatis uterine cervicitis.

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.

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.

T-3762 is an injectable new quinolone with a broad spectrum of antibacterial activity. Pazufloxacin (T-3761) is an active form of T-3762. The minimal inhibitory concentrations (MICs) of pazufloxacin for 50% of the clinical isolates tested were 3.13 µg/ml for Streptococcus agalactiae, 6.25 µg/ml for Gardnerella vaginalis, 0.025 µg/ml for Escherichia coli, 0.78 µg/ml for Pseudomonas aeruginosa, 6.25 µg/ml for Peptostreptococcus magnus, 6.25 µg/ml for Bacteroides fragilis and 12.5 µg/ml for Prevotella bivia. The MICs of T-3762 for 90% of the clinical isolates tested were 3.13 µg/ml for S. agalactiae, 6.25 µg/ml for G. vaginalis, 0.10 µg/ml for E. coli, 12.5 µg/ml for P. aeruginosa, 25 µg/ml for P. magnus, 12.5 µg/ml for B. fragilis and 25 µg/ml for P. bivia. The results of this study suggest that, subject to confirmation by clinical trials, T-3762, in combination with an agent with reliable activity against anaerobic bacteria, is suitable as an empirical therapy of patients with obstetric and gynecological infections.

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.

E1101 is a new oral cephalosporin with a broad spectrum of antibacterial activity. It inhibited more than 90% of clinical isolates of Streptococcus agalactiae, Escherichia coli and Peptostreptococcus magnus at the concentration of 3.13 mg/l. E1101 was the most active agent against S. agalactiae and E. coli. Since none of the compounds was sufficiently active against the Bacteroides fragilis and Prevotella bivia isolates, they are not appropriate in the treatment of patients with infections caused by these organisms. The results of this study suggest that, subject to confirmation by clinical trials, E1101, in combination with an agent with reliable activity against anaerobic bacteria, is suitable as empirical therapy of patients with obstetric and gynecological infections.

Polymicrobial infections with aerobes and anaerobes are common in pelvic inflammatory diseases. New parenteral cephalosporins have been widely used against those infections. We investigated in vitro morphologic changes and bactericidal activities on Escherichia coli and Bacteroides fragilis by cephalosporins; cefluprenam (CFLP), ceftazidime (CAZ) or cefotaxime (CTX). CFLP induced morphologic changes (filamentation) and bactericidal activities on E. coli and B. fragilis. Morphologic changes were observed by electron microscope. The filamentation induced by CFLP was time and concentration dependent. The bactericidal activity of CFLP against E. coli was almost equal to those of CAZ and CTX. The bactericidal activity of CTX against B. fragilis was superior to those of CFLP and CAZ. These results suggest that there are characteristic aspects in each cephalosporin.

Enterococcus faecalis plays an important role as a pathogen in polymicrobial infections. We evaluated the efficacy of cefozopran (CZOP) using polymicrobial pyometra rats. Rats were infected with a mixed intrauterine inoculation of E. faecalis plus either Bacteroides fragilis or Prevotella bivia (minimal inhibitory concentration of CZOP; E. faecalis: 6.25 µg/ml, B. fragilis: 12.5 µg/ml, P. bivia: 12.5 µg/ml). Immediately after inoculating 105 CFU of each organism/rat, CZOP (either 40 mg/kg, i.v., q.i.d., for 5 days or 80 mg/kg, i.v., b.i.d., for 5 days) was administered. The intrauterine inflammatory change and bacterial counts in the CZOP-treated group were compared with those in the nontreated control group. CZOP significantly (p < 0.01) decreased the bacterial counts except for B. fragilis in the regimen of 80 mg/kg b.i.d. However, the 40 mg/kg, q.i.d., regimen significantly (p < 0.05) reduced bacterial counts compared to 80 mg/kg, b.i.d. These results suggest that CZOP in a more divided dose is efficacious for the treatment of polymicrobial infections associated with E. faecalis in pyometra.

The antibacterial activity of BO-2727 against 100 clinical isolates of Streptococcus agalactiae (20 strains), Escherichia coli (20 strains), Peptostreptococcus magnus (20 strains), Bacteroides fragilis (20 strains) and Prevotella bivia (20 strains) was compared with those of imipenem, panipenem, meropenem, biapenem and ceftazidime (CAZ). Minimal inhibitory concentrations (MICs) for 50% of tested strains (MIC50s) of BO-2727 against S. agalactiae, E. coli, P. magnus, B. fragilis and P. bivia were 0.05, 0.05, 0.1, 0.78 and 0.78 mg/l, respectively. MIC90s of BO-2727 against S. agalactiae, E. coli, P. magnus, B. fragilis and P. bivia were 0.05, 0.05, 0.1, 0.78 and 0.78 mg/l, respectively. The efficacy of BO-2727 was evaluated using a polymicrobial pyometra model (E. coli and B. fragilis) in rats. Both the inflammatory changes in the uterus, from the point of view of neutrophil accumulation, and the bacteriological response in the treated group were milder than those in either the nontreated group or the CAZ-treated group. These results indicate that BO-2727 may be useful for the treatment of polymicrobial infections in patients with pyometra.

We investigated the effects of clarithromycin (CAM) on clinical and endometrial immune responses in chronic intrauterine infection (pyometra). CAM was orally administered in a dose of 200 mg once a day for 4 months (long-term/low-dose treatment) in patients with pyometra. Lavage fluid of the uterine endometrial cavity was obtained from 5 healthy women (controls) and 5 patients with pyometra to investigate the levels of neutrophil and interleukin-8 (IL-8), which is a neutrophil chemotactic factor. All patients showed clinical improvement at the end of treatment. In the assessment of the immune responses, neutrophils were accumulated in the lavage fluid of the uterine endometrial cavity in pyometra (p < 0.001, versus controls) and decreased by CAM treatment (p < 0.001). The level of IL-8 was significantly higher in the lavage fluid of patients with uterine endometritis than in the controls (p < 0.001), and decreased by CAM treatment (p < 0.01). There was a close correlation (r = 0.982) between neutrophil count and IL-8 level in the endometrial lavage of patients with pyometra. The reduction of the uterine endometrial neutrophil migration in chronic inflammatory sites may partially be a direct effect of CAM.

We investigated the effect of long-term administration of roxithromycin (RXM) on clinical responses and immune responses to chronic intrauterine infection, pyometra. One hundred and fifty milligrams of RXM were orally administered once a day for 3 months to patients with pyometra. Neutrophils and interleukin-8 (IL-8), which is a neutrophil chemotactic factor, in the lavage fluid of the uterine endometrial cavity obtained from 5 normal women and 18 patients with pyometra were investigated. Sixteen (88.9%) of the 18 patients showed a clinical improvement at the end of treatment. The immune responses occurred in the lavage fluid from the uterine endometrial cavity. Neutrophils accumulated in the lavage fluid of the uterine endometrial cavity before RXM treatment (p < 0.001 vs. normal subjects and decreased after RXM treatment (p < 0.001). The levels of IL-8 were significantly higher in the lavage fluid of pyometra patients than in normal women (p < 0.001), and tended to decrease after RXM treatment (p < 0.01). These results indicate that RXM decreases uterine endometrial cavity inflammation through reduction of neutrophil migration in inflammatory sites and is effective in treating chronic intrauterine infection.

One hundred symptomatic women with clinical bacterial vaginosis (BV) were enrolled in this study. The bacteriological epidemiology of BV and efficacy of oral or vaginal administration of antimicrobial agents for treatment of BV were investigated. The epidemiology of BV was investigated before antimicrobial therapy. Fifty patients were treated with oral administration of metronidazole (MTN), 500 mg twice a day, and 50 patients with 2% clindamycin (CLDM) phosphate in a vaginal cream, 5 g once a day for 7 days. The major organisms occurring were Streptococcus agalactiae, Escherichia coli, Gardnerella vaginalis, Peptostreptococcus species, Bacteroides species, Prevotella species, and Mobiluncus species and opportunistic pathogens such as Staphylococcus epidermidis and Enterococcus faecalis. The therapeutic efficacy of CLDM cream on BV appeared to be preferable to oral MTN from clinical and bacteriological aspects. The clinical and bacteriological effectiveness of MTN and CLDM in the treatment of BV suggests that anaerobes might play a major role in causing the clinical symptoms in patients with BV.

Bacterial vaginosis (BV) is considered to be one of the most common vaginal infections in women. Fifteen symptomatic women with BV were enrolled in this study. Ten patients with the diagnosis of BV were treated with 10 days oral administration of metronidazole (MTN), 500 mg twice a day, and five patients with cefdinir (CFDN), 300 mg three times a day. In the MTN therapy, the rate of abnormal vaginal discharge subjectively decreased from 100 to 60%, the rate of abnormal vaginal discharges objectively decreased from 100 to 20%, the rate of positive amine tests decreased from 100 to 20%, the rate of genital malodor and abnormal pH of vaginal discharges decreased substantially from 100 to 10%, and the rate of the presence of clue cells also decreased notably from 90 to 10%. However, in the CFDN therapy, none of these factors improved. With respect to susceptibility to CFDN and MTN, CFDN demonstrated good antibacterial activity against almost all bacteria isolated except Gardnerella vaginalis. On the other hand, MTN demonstrated excellent activity against anaerobic bacteria except Peptostreptococcus spp., and had no antibacterial activity against aerobic bacteria. Since the therapeutic effect of MTN in BV appeared to be better than that of CFDN, anaerobes may play a major role in causing clinical symptoms in patients with BV.

The antibacterial activity of a new parenteral cephalosporin, FK037 was assessed against recent aerobic and anaerobic strains isolated from patients in the fields of obstetrics and gynecology during the period between January 1992 and June 1993. The MICs of FK037 for 90% of the clinical isolates tested were 0.10 microgram/ml for Escherichia coli and Klebsiella pneumoniae, 0.20 microgram/ml for Streptococcus agalactiae, 0.39 microgram/ml for Gardnerella vaginalis, 0.78 microgram/ml for Staphylococcus epidermidis, Peptostreptococcus anaerobius and Mobiluncus spp., 1.56 micrograms/ml for Peptostreptococcus magnus, 3.13 micrograms/ml for methicillin-sensitive Staphylococcus aureus, 25 micrograms/ml for methicillin-resistant S. aureus (MRSA), Bacteroides fragilis and Prevotella disiens, 100 micrograms/ml for Bacteroides thetaiotaomicron and Prevotella bivia; and > 100 micrograms/ml for Enterococcus faecalis. FK037 was superior in potency to ceftazidime against all strains except E. faecalis, P. anaerobius and P. bivia. It was 4- to 16-fold more active than cefotaxime against aerobic gram-positive bacteria and P. disiens, and its activity was similar to that of cefotaxime against the other strains. FK037 had 4- to 16-fold stronger activity than flomoxef against MRSA, S. agalactiae and E. coli and a similar activity to flomoxef against the other strains except G. vaginalis and B. fragilis that were 4-fold more sensitive to flomoxef than to FK037.