Aqueous humor penetration of fourth-generation fluoroquinolone ophthalmic solutions given by multiple administration in a rabbit model.

We investigated the aqueous humor concentration of topically applied gatifloxacin (GFLX) 0.3% and moxifloxacin (MFLX) 0.5% in a rabbit model of surgical and nonsurgical eyes. Topical administration in eyes was performed eight times, at 15-min intervals. Surgical eyes had undergone cataract surgery with the implantation of an intraocular lens (IOL). Aqueous humor was sampled at 5, 30, and 120 min after drug administration. Drug concentrations were determined by high-performance liquid chromatography (HPLC). The GFLX concentrations in surgical eyes at 5, 30, and 120 min post-administration were 12.1, 14.0, and 6.1 microg/ml, and those in nonsurgical eyes were 11.3, 11.5, and 7.1 microg/ml; there were no differences between surgical and nonsurgical eyes. The concentrations of MFLX in surgical eyes were 46.2, 42.7, and 31.1 microg/ml. The concentration of MFLX was higher than that of GFLX at 5 and 120 min post-administration (P < 0.05). A multiple-drop schedule produced much higher aqueous concentrations. There was no difference in drug penetration in eyes that had undergone cataract surgery compared with nonsurgical eyes.

[Evaluation of three selective enrichment media for detection of Group B Streptococcus in vaginal swabs].

As the most common cause of neonatal sepsis, Lancefield Group B Streptococcus (GBS) must be diagnosed as early as possible in pregnant women is prevent neonatal infection. A selective enrichment broth medium has been widely recommended to optimally recover GBS from genital and anorectal samples. To establish a culture suitable for screening vaginal swab specimens, we compared subcultures of three selective enrichment media to direct culture on agar medium. Vaginal swab samples were inoculated directly onto 5% sheep blood agar and into New Granada medium (Eiken), Lim broth (Becton, Dickinson, and Company), and Todd Hewitt broth with gentamicin and nalidixic acid (Becton, Dickinson, and Company, Todd). Of the 288 specimens tested, GBS was recovered from 43 samples (14.9%) on direct agar media, with 82 (28.5%), positive on New Granada medium subculture, 67 (23.3%) on Lim broth subculture, and 61 (21.2%) on Todd, subculture. These results demonstrates that selective enrichment broth media provides more superior sensitivity than direct agar media for detection of GBS colonization in vaginal specimens, underscoring the usefulness of selective enrichment broth media in GBS screening for vaginal swabs in pregnant woman.

Antifungal activity of micafungin against Candida and Aspergillus spp. isolated from pediatric patients in Japan.

The in vitro antifungal activities of micafungin in comparison to caspofungin, fluconazole, itraconazole, voriconazole, and amphotericin B were evaluated against 93 Candida and 23 Aspergillus isolates recovered from pediatric patients with fungal infections. MICs were determined by the CLSI M27-A2 and M38-A for Candida and Aspergillus species, respectively. Micafungin showed potent activity against Candida albicans, Candida tropicalis, and Candida glabrata with a MIC range of <= 0.002 to 0.015mug/ml. In contrast, micafungin demonstrated higher MIC levels against Candida parapsilosis with a MIC range of 0.12 to 2 mug/ml. Micafungin showed potent antifungal activity against Aspergillus species tested with a MIC range of 0.004 to 0.015 mug/ml. Overall, micafungin had excellent in vitro antifungal activities against Candida and Aspergillus species recovered from pediatric patients with fungal infections.

Preventive effect against post-cataract endophthalmitis: drug delivery intraocular lens versus intracameral antibiotics.

PURPOSE: To compare hydrophilic acrylic intraocular lenses (IOLs) as an antibiotic drug-delivery system with intracameral antibiotic administration in terms of the ability to prevent endophthalmitis. METHODS: Antibiotic solutions of 0.3% (3 mg/ml) and 0.5% (5 mg/ml) gatifloxacin (GFLX) and 0.5% (5 mg/ml) and 1.5% (15 mg/ml) levofloxacin (LVFX) were prepared. IOLs made of hydrophilic acrylic and silicone were used. Hydrophilic acrylic IOLs were allowed to adsorb the antibiotic solutions. A clinically isolated strain, KOS1, of Enterococcus faecalis was used to induce experimental endophthalmitis in vivo. Antibiotic concentrations were determined with high-performance liquid chromatography (HPLC). Twelve hydrophilic acrylic IOLs with antibiotics were used for the in vitro antibiotic concentration assay. In vivo experiments were conducted with 51 rabbits in total. Antibiotic concentrations in the aqueous humor and effects against bacterial proliferation were evaluated. RESULTS: Concentrations of released antibiotics in vitro were highest on the first day and had decreased by the second day. When a comparison was made between similar initial concentrations, GFLX was released to a significantly higher concentration than LVFX (p < 0.001). In the antibiotic-treated IOL group, GFLX concentrations in the aqueous humor reached a peak at four hours postoperatively and then decreased. The intracameral antibiotic group showed similar tendencies, with a remarkably higher peak concentration. Effects against bacterial proliferation were comparable between the antibiotic-treated IOLs and intracameral antibiotic administration. CONCLUSIONS: Preventive effects against endophthalmitis were similar between antibiotic-treated IOL implantation and intracameral antibiotic administration.

Biofilm formation on hydrophilic intraocular lens material.

PURPOSE: To estimate bacterial biofilm formation on the hydrophilic acrylic (hydrogel) intraocular lens (IOL) Meridian (HP60M, Baush & Lomb) and to investigate a preventive effect against biofilm formation of hydrogel IOLs presoaked in antibiotics. METHODS: Two Staphylococcus epidermidis strains, ATCC 12228 and ATCC 35984 (biofilm-producer), and an Enterococcus faecalis strain (KOS1, clinical isolate from an endophthalmitis patient) were used. Biofilms were cultivated on disks of different IOL materials: hydrogel, PMMA (polymethylmethacrylate), and acrylic. Biofilms were stained with crystal violet (CV), which served as an index of biofilm formation. The bacterial population was enumerated after biofilm homogenization. Biofilms were also examined by scanning electron microscopy (SEM). IOLs were presoaked in two antibiotics, levofloxacin (LVFX) and gatifloxacin (GFLX), and then the bacterial population was enumerated. As in vivo experiment, antibiotics-treated and nontreated Meridian IOLs were implanted in rabbit eyes, which served as an endophthalmitis model, and the bacterial population was enumerated. RESULTS: The amount of biofilm formed was the least on hydrogel from among the three materials tested after 48- and 72-hr incubation (p < 0.05 to 0.01). The bacterial population was the least on hydrogel from among the three materials with ATCC 12228 (p < 0.05 to 0.01), and the bacterial population was significantly different between hydrogel and acrylic after 72-hr incubation with ATCC 35984 (p < 0.05). Biofilm by the two S. epidermidis strains were recognized after 24-hr incubation. Rates of biofilm-positive SEM fields, which were defined as being occupied by biofilm over at least half of the area, were increased through 72 hr with ATCC 35984. While the E. faecalis strain showed no bacterial adherence on the antibiotics-treated hydrogel IOLs, adherence of the S. epidermidis strain, ATCC 35984 was recognized on the LVFX-treated IOLs after 48-hr incubation (103 to 104 CFU/ml). In the rabbit in vivo model, the bacterial populations in eyes with an antibiotics-treated Meridian IOL were significantly smaller than in eyes with a nontreated IOL for 72 hr after surgery (p < 0.05 to 0.01). CONCLUSIONS: The biofilm formation was less on hydrogel than on other two materials tested. Hydrogel presoaked in antibiotics exhibited a preventive effect against biofilm formation at least for 24 hr in vitro and against bacterial proliferation in the rabbit in vivo endophthalmitis model.

Biofilm formation by Staphylococcus epidermidis on intraocular lens material.

PURPOSE: To compare biofilm formation by Staphylococcus epidermidis on different intraocular lens (IOL) materials. METHODS: The S. epidermidis strains, ATCC 12228 (American Type Culture Collection) and ATCC 35984 (biofilm-producer) were used. Biofilms were cultivated on disks of different IOL materials: silicone, PMMA (polymethylmethacrylate), acrylic, or MPC (2-methacryloyloxyethyl phosphorylcholine) surface-modified acrylic. Biofilms were stained with crystal violet (CV) which served as an index of biofilm formation. The bacterial population was enumerated after biofilm homogenization. Biofilms were also examined by scanning electron microscopy (SEM). RESULTS: Among the four materials tested, the least amount of biofilm formed on silicone. Biofilm production was significantly different between acrylic and MPC surface-modified acrylic lenses at 48 hours (P<0.05-0.01). The bacterial populations were significantly different between acrylic and silicone over 72 hours (P<0.05-0.01). The population on acrylic and MPC surface-modified acrylic continued to increase over 72 hours. The biofilm was recognized after a 24-hour incubation. Rates of biofilm-positive SEM fields, which were defined as being occupied by biofilm over at least half of the area, were significantly different between acrylic and silicone at 72 hours (P<0.05-0.01). CONCLUSIONS: S. epidermidis formed biofilm most intensely on acrylic among the four IOL materials tested. MPC surface-modified acrylic has a preventive effect on biofilm formation.

An epidemiological study of the susceptibility and frequency of multiple-drug-resistant strains of Pseudomonas aeruginosa isolated at medical institutes nationwide in Japan.

The susceptibility of 3233 strains of Pseudomonas aeruginosa, isolated primarily in 2001, as agents of infection at 37 medical institutes with various specialties in seven regions of Japan (ranging from Hokkaido to Kyushu/Okinawa), to 18 antipseudomonal agents known to be active against P. aeruginosa was evaluated, in accordance with the National Committee for Clinical Laboratory Standards (NCCLS) guidelines. Of the 18 antipseudomonal agents, including some combinations of beta-lactamase inhibitors and antibacterial agents, ciprofloxacin had the lowest minimum inhibitory concentration (MIC)(50) (0.25 microg/ml) against P. aeruginosa, followed by meropenem, with an MIC(50) of 0.5 microg/ml. The MIC(50) of 7 of the examined antibacterial agents (ceftazidime, cefozopran, imipenem, biapenem, gentamicin, tobramycin, and levofloxacin) was between 1 and 2 microg/ml. Among the antipseudomonal agents tested, tobramycin showed the lowest MIC(90) (2 microg/ml), which was not significantly different from its MIC(50) (1 microg/ml). The MIC(90) of the other antibacterial agents examined ranged from 8 to 64 microg/ml and more. The susceptibility of the 3233 strains to the 12 antibacterial agents covered by the NCCLS guidelines was determined according to the standard method of the NCCLS guidelines. The frequency of strains resistant to meropenem, gentamicin, or tobramycin was relatively low (7.5%-8.3%). The frequency of strains showing intermediate to severe resistance to tobramycin was particularly low (8.0%). The frequency of strains resistant to aztreonam, imipenem, or levofloxacin was 16.7%-19.0%, about twice as high as the frequency of strains resistant to tobramycin. The susceptibility pattern of the 3233 strains (isolated from seven regions of Japan) to five antibacterial agents (ceftazidime, piperacillin, imipenem, gentamicin, and ciprofloxacin) was evaluated in relation to the regions from which they were isolated. The MIC(50) values of these antibacterial agents did not differ significantly among the regions. However, the MIC(90) values of ceftazidime and gentamicin were higher for strains isolated from the Kansai region than for strains isolated from other regions. The MIC(90) of ciprofloxacin was higher for strains isolated from the Tohoku, Kansai, and Kyushu/Okinawa regions than for strains isolated from other regions. Of the 3233 strains, 89 were classified as multiple-drug-resistant (imipenem, gentamicin, and ciprofloxacin) strains. Of these 89 strains, 42 were isolated from urine, 17 from sputum or pharyngeal mucus, 13 from pus, 8 from blood, 1 from cerebrospinal fluid, and 8 from other specimens. The frequency of multiple-drug-resistant strains was higher among strains isolated from the Tohoku and Kansai regions than in strains isolated from other regions.

Penetration of levofloxacin into human aqueous humor.

This study was designed to measure the concentration of levofloxacin in aqueous humor after topical and oral administration in patients undergoing cataract extraction. Patients were randomly divided into four groups. Levofloxacin concentration in the aqueous humor was the highest in the group in which 600 mg was given orally plus five topical instillations before surgery. The aqueous humor levels of levofloxacin after topical and oral administration exceeded the minimum inhibitory concentrations for certain bacterial species that frequently cause intraocular infection.

[The introduction of ICD, ICN in Japan, and future expectations].

Infection Control Doctor(ICD) and Infection Control Nurse(ICN) are known as specialist in infection control. In Western countries Infection Control Teams have already been organized under Hospital Infection Control Committees, and ICDs and ICNs have been deployed in them and actively participate in them. The organizations and personnel that should cope with hospital infections in this manner cannot be said to be sufficient in Japan, and there is an urgent need to train specialists for infection control. Accordingly, in 1999 an ICD accreditation system was inaugurated, principally by the Japanese Association for Infectious Diseases and the Japanese Society of Environmental Infections, and in 2000 the Japanese Nursing Association inaugurated an ICN accreditation system in the form of accredited nurses. This paper describes the introduction of ICD and ICN in Japan, future expectations, and associated problems.