Investigation of in-line filter replacement intervals for infusion.

BACKGROUND: In-line filters in peripheral and central venous catheters are used to remove bacterial cells mechanically. A recent study indicated an extension of the use of infusion sets to 7 days. There is no evidence regarding replacement intervals for in-line filters. AIM: To test in-line filters that were used continuously for 7 days in order to investigate their ability to remove bacteria and assess the flow rate. METHODS: Three different in-line filters were attached to an ELNEOPA-NF No. 2 premixed infusion bag of intravenous hyperalimentation, into which Staphylococcus epidermidis ATCC12228 or Escherichia coli ATCC25922 was inoculated. These experiments were compared with a control infusion. The infusion was dropped at a flow rate of 40 mL/h and replaced at 24-h intervals for 7 days. Samples were collected 24 h after drop initiation. FINDINGS: S. epidermidis was not detected in droplets between Days 1 and 6, but In-line filters 1 and 2 showed droplets containing 6-10 colony-forming units/mL on Day 7. E. coli was not detected in any of the filters after 7 days of continuous use. Flow rates <40 mL/h were observed on Day 7 for In-line filter 3 in studies of S. epidermidis, and on Days 4 and 3 for In-line filters 2 and 3, respectively, in studies of E. coli. CONCLUSION: This study revealed differences in bacterial removal and flow rates under high inoculation between the three in-line filters tested. It is suggested that in-line filters can be used continuously for a maximum of 6 days, and reductions in flow rate after 48 h of continuous use should be noted carefully.

Impact of hospital environmental cleaning with a potassium peroxymonosulphate-based environmental disinfectant and antimicrobial stewardship on the reduction of hospital-onset Clostridioides difficile infections.

BACKGROUND: A 1% potassium peroxymonosulphate-based environmental disinfectant (PPED) produces sodium hypochlorite when combined with sodium chloride, which functions as a disinfectant. However, little is known about the impact of hospital cleaning with PPED on hospital-onset Clostridioides difficile infection (HO-CDI). AIM: To reduce HO-CDI, we promoted antimicrobial stewardship and hospital ward cleaning with PPED: this study was conducted to evaluate their impact. METHODS: We began a promotion of post-prescription review with feedback for broad-spectrum antimicrobials and hospital ward cleaning with PPED. We reviewed the ratio of HO-CDI, PPED consumption, and days of therapy (DOT) of broad-spectrum antimicrobials between July 2014 and March 2018, dividing this time into the pre-promotion (July 2014 to June 2015) and post-promotion periods (July 2015 to March 2018). FINDINGS: Using interrupted time series analysis, an immediate significant change in HO-CDI was observed after intervention (P=0.03), although a downward trend was not observed over this period (P=0.19). Trends in PPED consumption significantly changed over this period (P=0.02). DOT of carbapenems decreased immediately after the intervention began (P<0.01). A Poisson regression analysis showed that PPED consumption and DOT of carbapenems were independent factors affecting HO-CDI (P=0.039 and 0.016, respectively). CONCLUSION: We revealed that DOT of carbapenems and use of PPED were associated with the HO-CDI ratio and that both interventions reduced the rate of HO-CDI. This is the first report on the impact of hospital ward cleaning with PPED on the reduction of HO-CDI.

Pharmacokinetics of miconazole in serum and exudate of pelvic retroperitoneal space after radical hysterectomy and pelvic lymphadenectomy.

Due to the increased number of compromised hosts with fungal infections, doctors have recently started prescribing antifungal agents. In the field of gynecology, however, the choice of which drug to use has been difficult. The efficacies of these drugs depend on their antifungal spectra, potencies and concentrations in tissues. The present study was designed to investigate the pharmacokinetics of miconazole in the exudate of the retroperitoneal space that is formed after radical hysterectomy and pelvic lymphadenectomy. A total of 600 mg of miconazole was administered to the patients for exactly 60 min using an automatic drip-infusion pump. The parameters of the formulas analyzed by the two-compartment model were determined using the least-squares method, and a simulation curve was made. The maximum drug concentration (Cmax) of miconazole in serum was 6.26 mg/l 1 h after drip infusion commencement and the t1/2 in serum was 8.86 h. The value of the area under the time-serum concentration curve (AUC) in serum was 19.13 mg/h per l. The Cmax of miconazole in the exudate of the retroperitoneal space was 0.13 mg/l 2.48 h after the drip infusion was started. The value of AUC in the exudate was 2.52 mg/h per l.

Therapeutic effects of cefluprenam (CFLP) on polymicrobial infections associated with Enterococcus faecalis in rat pyometra model.

Enterococcus faecalis plays an important role as one of the pathogens in polymicrobial infections. We evaluated the efficacy of cefluprenam (CFLP) using a polymicrobial pyometra of a model rat. Rats were infected with a mixed intrauterine inoculation of E. faecalis plus either Bacteroides fragilis or Prevotella bivia (minimal inhibitory concentration of CFLP: E. faecalis, 3.13 mug/ml; B. fragilis, 3.13 mug/ml; P. bivia, 3.13 mug/ml). Immediately after inoculating 10(5) cfu/rat of each organism, CFLP (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 count in the treated group were compared with those in the non-treated control group. CFLP significantly (P < 0.01) decreased the bacterial counts except for B. fragilis in the regimen of 80 mg/kg, b.i.d. However, the regimen of 40 mg/kg, q.i.d. significantly (P < 0.05) reduced the bacterial counts more than did that of 80 mg/kg, b.i.d. CFLP proved to demonstrate a good tissue concentration above 3 mug/g for 1 h. These results suggest that CFLP in a more divided dose is efficacious for the treatment of polymicrobial infections associated with E. faecalis in pyometra.

Intravaginal bacterial flora in patients with uterine cervical cancer. High incidence of detection of Gardnerella vaginalis.

Gynecological diseases may affect the growth of vaginal bacterial flora. We investigated the relationship between uterine cervical cancer and the vaginal bacterial flora. In 20 patients with uterine cervical cancer, we investigated the intravaginal bacterial flora, including Gardnerella vaginalis and Mobiluncus spp. In the patients with uterine cervical cancer, there was a mixed flora of aerobes and anaerobes and, of special note, G. vaginalis was detected in 50% of the patients with uterine cervical cancer (10/20). Bacterial vaginosis was present in 8 of these 10 patients (80%). The count of G. vaginalis detected was higher than that of the other coexisting species and was higher in both pre- and postmenopausal patients with uterine cervical cancer than in a control group of pre- and postmenopausal women with benign gynecological diseases. In contrast, none of Mobiluncus spp. was detected. G. vaginalis was detected at a high incidence in patients with uterine cervical cancer, suggesting that the lesions of uterine cervical cancer provide favorable conditions for the growth of G. vaginalis and anaerobes, which leads to bacterial vaginosis.

Bacterial flora detected of the uterine endometrial cavity of diabetic patients with myoma uteri.

Patients with diabetes frequently suffer from various postoperative complications, especially infection. Diabetic patients also have a high incidence of uterine endometrial cancer. The nature of the intrauterine bacterial flora may be related to both infection and carcinogenesis. Therefore, identification of the intrauterine bacterial flora in diabetic patients may be useful. Bacteria were detected in the uterine endometrial cavity of 100% of ten diabetic patients with myoma uteri. However, among 20 non-diabetic control patients with myoma uteri, only three 15% harbored bacteria. Members of the Enterobacteriaceae (Escherichia coli, Proteus spp., Enterobacter cloacae, and Klebsiella pneumoniae) were the predominant bacteria. We speculate that bacterial products contribute to carcinogenesis, as has been proposed for colon carcinoma. Antimicrobial agents active against Enterobacteriaceae should be used to prevent postoperative infections in gynecologic procedures in diabetic patients.

Internal bacterial flora of solid uterine cervical cancer.

Twenty-five patients with uterine cervical cancer (Two cases stage O; four cases stage Ia; five cases stage Ib; one case stage IIa; ten cases stage IIb; two cases stage IIIa; one case stage IVa) served as the subjects. The bacterial flora inside the cervical cancers was investigated using the optimal technique. There was mixed abnormal aerobic and anaerobic bacterial flora in all subjects. The average number of bacterial species isolated from inside the cervical cancers was 6.3. The predominant bacteria isolated were the aerobes, Staphylococcus haemolyticus, Streptococcus agalactiae, Escherichia coli and Gardnerella vaginalis, and Prevotella bivia. As the stages of cervical cancer progressed, G. vaginalis, B. distasonis and P. bivia were detected at higher rates and higher counts than other bacteria. These findings suggest that there is a relationship between G. vaginalis, B. distasonis and P. bivia and the onset and growth of cervical cancer.

[Incidence of Mobiluncus spp. from the patients with clinical bacterial vaginosis].

Aerobic and anaerobic cultures as well as a Gram stain and wet mount preparations were made of vaginal swabs in twenty patients with clinical bacterial vaginosis. Mobiluncus spp. were detected in 7 cases (35%). Cultures appeared to indicate that mixed abnormal flora between aerobic and anaerobic bacteria are found in bacterial vaginosis, and that Mobiluncus spp. may play a role in bacterial vaginosis.

Endometrial bacterial flora detected in patients with uterine endometrial cancer.

Certain bacteria produce some carcinogens such as N-nitro compounds, n-butyric acid and n-valeric acid. From this point of view, the examination of intrauterine bacterial flora in patients with uterine endometrial cancer may provide important information. Twenty patients with the diagnosis of uterine endometrial cancer and 20 patients without complications other than myoma uteri were enrolled in the study. Enterobacteriaceae, Streptococcus agalactiae and anaerobic bacteria were mainly detected. The products of these bacteria might be considered to contribute to the initiation of endometrial carcinogenesis. Mixed abnormal flora between aerobic and anaerobic bacteria were detected in all patients with uterine endometrial cancer. It is suggested that uterine endometrial cancer provides favorable conditions for bacterial growth. Mixed abnormal bacterial flora also might influence the onset and growth of uterine endometrial cancer.

[Pharmacokinetic and clinical studies on flomoxef in perinatal period].

Pharmacokinetic and clinical studies on flomoxef (FMOX) in the perinatal period were carried out. The results are summarized as follows. 1. The concentration of FMOX in umbilical cord serum was about 10 micrograms/ml in about 30 minutes after 1 g one shot intravenous injection. Amniotic fluid concentration was 7 micrograms/ml in 41 minutes after administration. By 1 hour intravenous drip infusion, FMOX concentration in umbilical cord serum was about 5 micrograms/ml in 2-3 hours after administration. Amniotic fluid concentration of about 20 micrograms/ml was found in 1 case. 2. FMOX 1-2 g x 2-3/day was given by intravenous drip infusion to 7 cases of perinatal infection for 4-26 days. Clinical efficacies were evaluated a good for all cases. Neither side effect nor abnormal laboratory test value was observed. Consequently, FMOX was considered to be highly effective and safe for its clinical use in perinatal period infections.

[Study on the therapeutic effect of panipenem/betamipron on perinatal infection in pregnant women].

An investigation was carried out to determine the therapeutic effect of panipenem/betamipron (PAPM/BP), a injectable carbapenem antimicrobial agent, on infections in pregnant women during perinatal period. Of the 41 patients enrolled in the study, 34 were subjected to the analysis, with 1 exemption because of protocol violations (regimen), 3 because of uncertain evidence symptoms of infection, and 3 because of failure to undergo laboratory tests. PAPM/BP was administered by intravenous drip infusion at doses of 0.5 g twice or three times a day daily for periods of 3 to 14 days. The efficacy rate according to the evaluation of the Drug Efficacy Evaluation Committee and the attending physicians was 79.4% (27/34), with 49 of the 61 clinical isolates (80.3%) being eradicated. Safety was evaluated as "safe" in 39 of the 41 assessable patients (94.1%). Mild headache and nausea were experienced by 1 patient (2.4%) as adverse drug reactions, but the symptoms disappeared after the completion of treatment. Slight elevations of GOT, GPT and LDH in laboratory tests were observed in 1 patient (2.4%), but these values returned to normal after the completion of treatment. These results suggested that PAPM/BP may be a useful drug in the treatment of bacterial infections during the perinatal period. To firmly establish its safety, however, further clinical and pharmacokinetic studies are needed in larger populations.

Bacterial flora detected in the uterine endometrial cavity of normal puerperae on the puerperal first day and on the puerperal fifth day after incidental use of cefpodoxime proxetil.

In Japan, oral antimicrobial agents are prophylactically used with oxytocics after normal delivery to prevent puerperal infections. The present study was designed to investigate bacterial floras in the endometrial cavity immediately after normal delivery and the effect of prophylactic use of anti-microbial agents on those floras. Sixty-six puerperae who underwent uneventful courses of pregnancy and delivery were subjected for this study. Intrauterine contents were collected on the first day and the fifth day of the puerperium and submitted to microbiological examinations. Cefpodoxime proxetil (CPDX-PR) was orally given to the puerperae for prophylaxis for 5 days after the initial sampling. On the puerperal first day, a total of 98 strains (71 strains of aerobic bacteria, 27 strains of anaerobic bacteria) was detected in the uteri of the 66 subjects. The incidences of aerobic Gram-positive cocci, aerobic Gram-negative bacilli and anaerobic bacteria were 59.2%, 12.2%, 27.6% of the 98 strains, respectively. On the puerperal fifth day, a total of 82 strains (51 strains of aerobic bacteria and 31 strains of anaerobic bacteria) were detected in the uteri of the 66 subjects. The incidences of aerobic Gram-positive cocci, aerobic Gram-negative bacilli and anaerobic bacteria were 52.5%, 8.6% and 37.7% of 82 strains, respectively.

[Effects of levofloxacin once-a-day therapy on uterine cervicitis].

An investigation was carried out to determine the therapeutic effect of levofloxacin (LVFX) once-a-day oral therapy at the dose of 200 mg/day for 7 days on uterine cervicitis, in comparison with LVFX twice-a-day oral therapy at the dose of 200 mg/day for 7 days. Of the 102 patients enrolled in the study, 90 were subjected to the analysis. The efficacy rate on uterine cervicitis of the once-a-day therapy and twice-a-day therapy groups according to the evaluation of the Drug Efficacy Evaluation Committee were 72.0% (36/50) and 82.5% (33/40), respectively. The efficacy rate on uterine chlamydial cervicitis of the once-a-day therapy and twice-a-day therapy groups according to the evaluation of the Drug Efficacy Evaluation Committee were 88.0% (22/25) and 85.7% (18/21), respectively. Safety was evaluated as "safe" in 88 of the 90 assessable patients (97.8%). Side effects were seen in two cases, which belong to the once-a-day therapy group; mild candidiasis and mild breast distension sense. As the antimicrobial treatment started, the levels of the inflammatory cytokines, interleukin-6 (IL-6) and interleukin-8 (IL-8) in the cervical mucus, decreased. It is suggested that IL-6 and IL-8 can be useful indicators of the antimicrobial treatment in the uterine cervicitis. These results suggested that the LVFX once-a-day therapy can be useful on uterine cervicitis.

[The frequency of Streptococcus pneumoniae strains and sensitivity surveillance for several antibiotics in Gifu Prefecture].

The frequency and the antibacterial sensitivity of Streptococcus pneumoniae strains isolated from 6 key hospitals (in 5 areas) and 1 otorhinolaryngology clinic in Gifu Prefecture from February to March, 1999, were investigated with several antibiotics. A total of 128 strains of Streptococcus pneumoniae were isolated throughout the study: 47 strains (36.7%) of penicillin-susceptible S. pneumoniae (PSSP), 51 strains (39.8%) of penicillin-intermediate S. pneumoniae (PISP), and 30 strains (23.4%) of penicillin-resistant S. pneumoniae (PRSP); the resistant bacteria being relatively prominent. In these hospitals, PSSP was isolated by 38.8% in all the key hospitals and by 30% in the otolaryngology clinic with almost no discernible difference. PISP was isolated by 63.3%, higher in the otolaryngology clinic and PRSP by 28.6%, higher in the key hospitals conversely. The MIC90s in PISP and PRSP were determined with the antibiotics. In result, only cefditoren (CDTR) showed favorable antibacterial activities with the MIC90 of 0.78 microgram/ml among penicillins or oral cephems. The MIC90s of carbapenems such as imipenem (IPM), meropenem (MEPM), and panipenem (PAPM) were less than 0.39 microgram/ml; particularly, PAPM showed the highest antibacterial activities. Among new quinolones such as tosufloxacin (TFLX), levofloxacin (LVFX), sparfloxacin (SPFX), and ciprofloxacin (CPFX), TFLX showed the highest antibacterial activities with the MIC90 of 0.39 microgram/ml. Other agents showed very low antibacterial activities as the MIC90s were 25 micrograms/ml in minocycline (MINO) and more than 100 micrograms/ml in clarithromycin (CAM) and clindamycin (CLDM).

[Clinical efficacy of cefpirome sulfate against Bacteroides species, Prevotella species and Porphyromonas species. Society of Anaerobic Bacterial Infections in the fields of obstetrics and gynecology in Gifu].

The injectable cephalosporin cefpirome (CPR) was launched in Japan in 1993. It has widely been used in the various infectious diseases. We therefore studied the clinical and bacteriological efficacy of CPR against infections caused by Bacteroides species, Prevotella species and Porphyromonas species frequently isolated from the obstetric and gynecologic infections. Thirteen institutions were involved in this study which ran from March 1994 to January 1999. The administration dosage of CPR was 2 to 4 gram per day administered by drip infusion or intravenous infusion. The duration of treatment was from 3 to 15 days. The evaluations were performed before and after the treatment. CPR was administered to 194 patients with obstetric and gynecologic infections, and 146 of 194 cases were acceptable for the evaluation of drug efficacy. Bacteroides species were identified in 102 patients. Clinical efficacy in 146 cases was excellent in 12 patients, good in 110, fair in 9 and poor in 15 patients. The eradication rate for Bacteroides species could be in 37 cases out of 54 evaluable cases; Prevotella species in 38 out of 49; and Porphyromonas species in 5 out of 5. The overall assessment of bacteriological efficacy was "eradicated" in 91 cases out of 133 (68.4%). Adverse reactions including abnormal findings in laboratory tests were seen in 8 patients (4.76%). Based on these results, CPR promises efficacy and safety in the treatment of obstetric and gynecologic infections due to Bacteroides species.

The effects of the extension of transit times on qualitative and quantitative bacterial culture after clinical sampling.

The effects of the extension of transit times on qualitative and quantitative bacterial culture after clinical sampling were investigated with the clinical samples, using the bacterial flora from the cancer portion inside the uterine cervix in 25 patients with the uterine cervical cancer. In the qualitative bacterial study, the strains of both aerobic and anaerobic bacteria detected were rather preserved for 6 hours after clinical sampling and decreased in a time-dependent manner in the samples of more than 6 hours after clinical sampling. In particular, number of anaerobic bacterial species detected remarkably decreased in the samples of more than 12 hours after clinical sampling. Therefore, prompt bacterial culture after clinical sampling, possibly within 6 hours after clinical sampling, may be crucial in order to detect most probable pathogenic anaerobic bacteria, particularly when anaerobic infection is suspected. In the quantitative bacterial study, the quantity of bacteria detected were rather preserved for 3 hours after clinical sampling and decreased in a time-dependent manner in the samples of more than 3 hours after clinical sampling. Therefore, quantitative bacterial culture should be performed within 3 hours after clinical sampling.

Preventive procedures against GBS infection by means of antibody measurement.

OBJECTIVE: Screening group B Streptococcus (GBS) in the vagina of pregnant women and measuring serum level of its type-specific antibody would be useful for cost-benefit of the prevention against GBS infection. STUDY DESIGN: The subjects included a total of 1,150 pregnant women who consented to the study. Serotypes of GBS detected were classified with antiserum. Serum type-specific antibody titers were measured by a bacterial agglutination method. RESULTS: Of a total of 1,150 pregnant women, 250 cases (21.7%) had GBS in the vagina. The turn of GBS serotype occurrence was types VI (NT6) (27. 2%), VIII (JM9) (25.2%), III (11.2%), Ia (8.8%), and Ib (8.0%). None or low type-specific antibody titer was 41.0% of Ia, 20.0% of Ib, 22. 0% of II, 15.0% of III, 65.0% of VI, and 69.0% of VIII incarriers. Noneonatal GBS infection occurred under the empirically treatment. CONCLUSION: The measurement of serum type-specific antibody against GBS would be informative for the cost-benefit treatment of the vaginal GBS in pregnant women.