Phototoxicity of pazufloxacin mesilate (PZFX mesilate), a novel parenteral quinolone antimicrobial agent, were evaluated in vitro and in vivo studies. In vitro, phototoxicity for cultured cells of PZFX, which is active principle of PZFX mesilate, was studied, and stability for long-wavelength ultraviolet (UVA) was examined. In vivo, phototoxicity tests in guinea pigs and rats, and photoallergenicity tests in guinea pigs were conducted.
In the phototoxicity test on cultured cells, CHL/IU cells were irradiated UVA of 300-3000mJ/cm² in the presence of PZFX, ofloxacin (OFLX), lomefloxacin (LFLX) or sparfloxacin (SPFX) at 10μg/mL Phototoxicpotencies for cultured cells of the quinolones tested were SPFX>LFLX>OFLX>PZFX. In addition, changes in ultraviolet absorption spectrum and residual rate of PZFX, OFLX, LFLX and SPFX were examined after UVA irradiation of 300-3000 mJ/cm² to each solution. PZFX was stable for UVA compared with OFLX and LFLX.
In the phototoxicity test of guinea pigs, each quinolone was administered intraperitoneally daily for 7 days, and UVA of about 11 J/cm² was irradiated at 30 minutes after the last administration. Dose levels of each quinolone were 65 and 130 mg/kg of PZFX mesilate (dose levels converted to PZFX: 50 and 100 mg/kg), 50 and 100 mg/kg of nalidixic acid (NA), 100 mg/kg of OFLX, enoxacin (ENX), ciprofloxacin (CPFX), LFLX and SPFX. Grade of skin reaction (erythema) at 24 hours after UVA irradiation decreased in the order: SPFX>CPFX>NA>ENX=OFLX>LFLX>PZFX mesilate. Thus, PZFX mesilate was found to have the weakest phototoxicity. In the maximum plasma concentration of quinolones from 0.5 to 2.5 hours after administration, corresponding to the time of UVA irradiation, the concentration of the group administered PZFX mesilate was about 4.1 times higher than that of CPFX group, and about 1.3 times higher than that of SPFX group. The area under the blood concentration-time curve (AUC _.5-2.5) of the group administered PZFX mesilate was the same as that of SPFX group, and about 3.2 times larger than that of CPFX group. These data showed that phototoxicity of PZFX mesilate was also weaker than that of CPFX or SPFX in consideration of AUC _.5-2.5. In the phototoxicity test of rats injected intravenously, no phototoxicity was observed at 130 mg/kg of PZFX mesilate. In the photoallergenicity test of guinea pigs, no photoallergenicity was observed by PZFX mesilate.
As mentioned above, from in vitro studies PZFX was found to be stable for UVA irradiation compared with OFLX and LFLX, and phototoxicity for cultured cells of PZFX was weaker than that of SPFX, LFLX or OFLX. In addition, from in vivo studies phototoxicity of PZFX mesilate was found to be weaker than that of NA, OFLX, ENX, CPFX, LFLX or SPFX, and no photoallergenicity was observed. Therefore, photosensitive potency of PZFX mesilate might be less than that of other quinolones.

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Convulsanct ativity of pazufloxancni mesilate (PZFX mesilate), a new quinolone antibacterial agent for intravenous use, in combination with nonsteroidal anti-inflammatory drug (NSAID) was investigated in mice after intravenous or intracerebroventricular administration Following results were obtained.
1. In combination with 4-biphenylacetic acid (BPAA) at an oral dose of 100 mg/kg, PZFX mesilate did not induce any convulsions at intravenous doses up to 200 mg/kg. Reference quinolones induced convulsions at the following intravenous doses E: noxacin (ENX), 3.13mg/kg or more; norfloxacin (NFLX) and lomefloxacin (LFLX), 6.25mg/kg or more; ciprofloxacin (CPFX), 50 mg/kg or more; sparfloxacin (SPFX) and temafloxacin (TMFX), 100 mg/kg or more; fleroxacin (FLRX), 200mg/kg.
2. PZFX mesilate at an intravenous dose of 50 mg/kg did not induce convulsions in mice after oral administration of any of 14 kinds of NSAIDs. It induced convulsions at 200 mg/kg in combination with aspirin at an oral dose of 600 mg/kg, while it did not with the other 13 kinds of NSAIDs.
3. Convulsion-inducing dose of PZFX mesilate after intracerebroventricular administration was 100 mg/body, which was higher than those of reference quinolones (NFLX, CPFX, ENX, LFLX, TMFX, levofloxacin, ofloxacin, FLRX and SPFX) and β-lactam antibiotics (penicillin G, cefazoline, imipenem/ cilastatin and panipenem/betamipron). In addition, concurrent dosing of BPAA (1 μg/body) did not reduce the convulsion-inducing dose of PZFX mesilate.
These results suggest that PZFX mesilate has remarkably weak convulsant activity.

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One hundred ninety eight clinical isolates, including Enterobacteriaceae (70 strains), Pseudomonas aeruginosa (20 strains), Acinetobacter baumannii (10 strains), staphylococci (50 strains), enterococci (20 strains), Streptococcus pneumoniae (15 strains) and Haemophilus influenzae (13 strains) were tested for their antimicrobial susceptibilities by using the Rapid Lumi ‘Eiken’^® (RL). As a reference method, broth microdilution method according to the National Committee for Clinical Laboratory Standards was used. Then, each MIC obtained by both of these methods was compared. In order to improve the discrepancy between MICs obtained by both methods, modification of the RL method was studied.
All MICs using the RL method were obtained with an incubation period of 4 hours. The essential agreement (to within one twofold dilution) between MICs obtained by both methods was 82%. The false susceptible in the RL method test results (very major error) and the false resistant in the RL tests (major error) were 0.9% and 2.3%, respectively. The agreement of interpretive category (that is, when the categories obtained by both methods are in perfect agreement) was 89%. Proteus spp. and A. baumannii showed low essential agreements, 59% and 46% respectively. The differences were resulted from the RL methods MICs being higher than the reference method. In order to improve the difference between both methods, the RL method's procedure was modified in the inoculum size (10⁶CFU/mL to 10⁵CFU/mL), the menadione concentration (5 mg/L to 25 mg/L) and the interpretive criteria for Enterobacteriaceae and A. baumannii. As the results of the modification, the essential agreement in Proteus spp. and A. baumannii increased to 82% and 81%, respectively, and there was no significant change in the other species of Enterobacteriaceae. In the case of the modified RL method to Enterobacteriaceae and A. baumannii, the essential agreement, the very major error, the major error and the agreement of interpretive category of all 198 strains were 87%, 1.4%, 1.5% and 90%, respectively.
In conclusion, with only 4-hour incubation period, the RL method based on chemiluminescent assay gave reliable susceptibility testing among the most clinically important bacteria. Although several tests showed low essential agreement, it was possible to improve by use of the modified RL method. The Rapid Lumi ‘Eiken’^® will provide useful information f or choosing the most effective antibiotic for primary treatment to bacterial infections.

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To clarify a mechanism of acquired resistance of two Mycoplasma gallisepticum (MG) strains against ofloxacin (OFLX) along with tylosin (TS) and spectinomycin (SPCM) as the controls, in vitro resistance acquisition test was carried out for 10 subcultures of each strain with increasing the amount of antimicrobials, and maximum growth allowance concentrations (MAC) in 10th and primary subcultures were compared. Acquisition of resistance in the strains against OFLX was moderate and MAC of the 10th subculture increased twice for one strain and 16 times for another one as compared to that of their primary subcultures. Acquisition of resistance in the strains against TS was also moderate and MAC of the 10th subculture increased 8 times for both strains as compared to that of the primary subcultures. Acquisition of resistance against SPCM was quite different between the strains. Namely the MAC of one strain increased 512 times, while another one did not acquire any resistance.

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Epidemiological and microbiological studies were carried out using 575 strains of Haemophilus influenzae isolated from clinical specimens at Kitakyushu municipal medical center from January 1996 through December 1999. The strains isolated multiply were excluded.
The strains of H. influenzae did not increase for 4 years, and were detected more in summer season, peaked in July, and less in winter season.
Like the cases of Streptococcus pneumoniae, most (91.8%) of the strains was detected in the specimens from the respiratory tract, and also they were isolated mainly from infants under 4-years old (25.6%) and adults over 65-years old (24.2%)
MICs of 7 antimicrobial agents, such as ampicillin (ABPC), sulbactam/ABPC, cefaclor, imipenem, panipenem, meropenem (MEPM), and levofloxacin (LVFX) were determined using broth microdilution methods.
Among 575 strains of H. influenzae isolated from clinical specimens, 51 ABPC-resistant strains (8.9%) produced β-lactamase, and 67 strains (11.6%) were β-lactamase negative ampicillin resistant H. influenzae.The ABPC-resistant strains existed in 20.5%.
Both of MEPM and LVFX showed excellent antimicrobial activity against H. influenzae including ABPCresistant strains.
Four cases of meningitis were reviewed. All of H. influenzae isolated possessed type b capsular antigen. All patients recovered by appropriate antimicrobial treatment. But one adult patient developed serious sequela.

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