Oxazolidinones are a new class of antimicrobials with a unique mechanism of action. This class of bacterial protein synthesis inhibitors functions by binding to the 50 S ribosomal subunit and preventing formation of a functional initiation complex in bacterial translation systems.Linezolid (LZD), an oxazolidinone anti-bacterial agent with a mechanism of action distinct from those of conventional antibacterial agents, was recently developed and its effectiveness against methicillin-resistant Staphylococcus aureus (MRSA) or vancomycin-insensitive S. aureus (VISA) highly anticipated. LZD has been approved as a new antibiotic against infections with gram-positive organisms by many countries, including the United States. Aclinical trial with LZD against MRSA infection hes been done in Japan.

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A new penem oral antibacterial agent, faropenem sodium, was orally administered to 17 elderly hospitalized patients, whose ages averaged 78.4 years, with a confirmed infection at a dose of one tablet (150 mg) 3 times a day for 4-8 consecutive days, as part of a postmarketing clinical trial. Changes in blood concentration and its safety were studied and the following results below obtained.
1. Pharmacokinetic parameters
Pharmacokinetic parameters in elderly patients were Cmax 1.09±0.43, μg/mL, Tmax2.29±1.16h, T_1/22.42± 3.09h and AUC_0-24 5.03±2.57, μg·h/mL. Compared to healthy adult volunteers, a low Cmax and extended Tmax and T, 2 were found together with a trend toward slightly increased AUC_0-24.
2. Safety
Only 1 of the 17 patients experienced any side effects, symptoms of slight diarrhea. Slight abnormalities in laboratory test results with a possible positive relationship to this drug included elevated GOT and GPT in 1 patient and elevated GOT, GPT, ALP, and BUN in another. These changes were minimal in both cases.

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We conducted3open label clinical studies, a randomized, double-blinded dose-finding study, and 2 randomized, double-blinded clinical studies of gatifloxacin (GFLX), from January1992to October1998, for the treatment of infections in the field of internal medicine, and published results of individual studies in earlier issues of this journal.Recollation of case reports with source data has shown the necessity of some corrections in published papers. We therefore report collectively results based on our reanalysis of all data.
1. 3open label clinical studies Clinical effectiveness of GFLX for pneumonia, chronic bronchitis (acute exacerbation), bronchiectasis with infection, and chronic respiratory diseases with secondary infection was 91.8%(78/85), 93.8%(61/65), 92.1%(35/38), and97.0%(32/33).
2.Randomized, double-blinded dose-finding study
Clinical effectiveness in groups L (100mgb.i.d), M (150mgb.i.d), and H (200mgb.i.d) was97.1%(33/34), 86.7%(26/30), and 94.3%(33/35).No significant difference was seen among groups.A daily dosage of 200mg b.i.d. of GFLX was considered optimal for treatment of chronic respiratory tract infections.
3. 2 double-blinded comparative studies
1) GFLX and levofloxacin (LVFX) in pneumonia Clinical effectiveness was 98.0%(97/99) in the GFLX group and 94.9%(94/99) in the LVFX group. The clinical equivalency of GFLX to LVFX was confirmed at Δ=10% in effectiveness.
2) GFLX and LVFX in chronic respiratory tract infections Clinical effectiveness was 98.9%(91/92) in the GFLX group and 78.7%(70/89) in the LVFX group. The clinical equivalency of GFLX to LVFX was confirmed at Δ=10%in effectiveness, and the difference in effectiveness between groups was significant.
4.Clinical pharmacokinetics and penetration into sputum
Individual maximum concentrations of GFLX in sputum ranged from 1.45 to 7.11, ug/mL in patients with chronic respiratory tract infection.Penetration into sputum ranged from 1.09 to 6.25 against the concentration in serum.
In conclusion, results were consistent with those published, and indicate that GFLX is one of the most highly effective drugs for the treatment of respiratory tract infections.

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We conducted clinical studies of gatifloxacin (GFLX) from November 1993 to February 1997 for treating infections in the surgical field (surgery, dermatology, otorhinolaryngology, gynecology, ophthalmology, and oral surgery), and published the results of individual studies in earlier issues of this journal. Subsequent recollation of case reports with source data has shown the necessity of some corrections in published papers.We therefore collectively report results based on our reanalysis of all data.
1. Clinical pharmacokinetics and tissue penetration
GFLX penetration into tissue (gallbladder wall, skin, mucosa of middle ear and paranasal sinus, tonsil, parotid gland, pelvic genital organ, conjunctiva, tarsal gland, gingiva, and palatine mucosa) ranged from 1.24 to 4.64 and into bile, skin exudates, and exudate in oral surgery ranged from 1.24 to 9.47 versus concentration in serum.Data in all related areas of surgery reconfirmed that GFLX tissue penetration is as good as that of existing fluoroquinolones.
2. Clinical efficacy
Clinical efficacy by field was 88.3%(113/128) in surgery, 86.9%(139/160) in dermatology, 83.5%(162/194) in otorhinolaryngology, 93.8%(137/146) in gynecology, 94.2%(114/121) in ophthalmology, and 90.5%(153/169) in oral surgery.
3. Bacteriological response
Bacteriological efficacy by patient in each field was 88.9%(96/108) in surgery, 88.5%(85/96) in dermatology, 87.1%(142/163) in otorhinolaryngology, 87.0%(60/69) in gynecology, 96.0%(72/75) in ophthalmology, and 99.1%(109/110) in oral surgery. Bacteriological elimination by causative isolate in the surgical field was 93.0%(572/615) for gram-positive aerobes, 94.2%(195/207) for gram-negative aerobes, 96.5%(223/231) for gram-positive anaerobes, and 99.5%(198/199) for gram-negative anaerobes.
4. Safety
The incidence of adverse drug reactions and abnormal laboratory findings noted with GFLX in all studies is similar to that of existing fluoroquinolones. No event was serious or clinically significant.
In conclusion, results after reanalysis are consistent with those published, and indicate that GFLX is a highly effective drug for treating infections in all surgical fields indicated.

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We published clinical study results on gatifloxacin (GFLX) in genitourinary tract infections in earlier issues of this journal. Recollation of case reports with source data has shown the necessity of some corrections in published papers. We therefore collectively report results based on our reanalysis of all data.
1. Overview of reanalysis
The overall conclusion of clinical efficacy after reanalysis is consistent with the previous conclusion reported. Satistical analysis of data from the dose-finding study and the double-binded comparative study showed that results of reanalysis do not differ in either of the studies from results already reported.
2. Clinical pharmacokinetics and tissue penetration
GFLXwas reconfirmed to have good transfer into serum and urine. Tissue concentrations in the prostate and epididymis were higher than that in serum. GFLX penetrated into prostate fluid and showed almost the same concentration as that in serum.
3. Clinical efficay
1) Acute uncomplicated urinary tract infections Overall clinical efficacy by criteria of the Japanese UTI Committee (UTI criteria) was 99.1% in acute uncomplicated cystitis. The double-blinded study showed no significant difference in final cure based on UTI criteria between3-day treatment and7-day treatment with GFLX at 100mg, twice a day.
2) Complicated urinary tract infections Overall clinical efficacy by UTI criteria was 80.8% in complicated urinary tract infections in open label studies. In the dose-finding study, the efficacy of GFLX at 200mg, twice a day, was higher than that at other doses or regimens, although there was no statistically significant difference. Thus, the dosage of 200mg of GFLX, twice a day, was considered optimal for treatment of urinary tract infections. The clinical equivalency of GFLX to levofloxacin was confirmed at Δ=10% in evaluation of efficacy in the doubleblinded comparative study.
3) Urethritis
MIC₉₀ of GFLX against 36 strains of Neisseria gonorrhoeae isolated from urethritis patients was 0.063μg/mL. Overall clinical efficacy by UTI criteria was 100% in gonococcal urethritis. Overall clinical efficacy in chlamydial urethritis was 100% after 14 days of treatment.
4) Prostatitis
Overall clinical efficacy by UTI criteria was 100% in both acute and chronic bacterial prostatitis.
5) Epididymitis
Clinical efficacy evaluated by the doctor in charge was “good” or “excellent” in 7 of 8 patients with epididymitis.
In conclusion, results indicate that GFLX is one of the most highly effective drugs in the treatment of genitourinary tract infections.

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We conducted clinical studies of gatifloxacin (GFLX) and published results of individual studies in earlier issues of this journal. Recollation of case reports with source data has shown the necessity of some corrections in published papers. We therefore report collectively results based on our reanalysis of all safety data involving the2, 889patients treated.
1. Adverse Drug Reactions
Adverse drug reactions were evaluated in 2, 727 qualifed patients, and their incidence was 4.5%(122/2, 727).No large differences were seen in the incidence of reactions among medical fields and ageclassified strata. No increase in incidence was noted in the elderly. Adverse drug reactions were all mild or moderate and none serious. Specifically, 70%of all adverse drug reactions were gastrointestinal disorders with an incidence of 4.1%(112/2, 727), followed by central and peripheral nervous disorders with an incidence of 1.0%(26/2, 727).Major events include diarrhea (1.0%;26/2, 727), nausea (1.0%;26/2, 727), vomiting (0.4%;12/2, 727), rash (0.3%);9/2, 727), and dizziness (0.3%;8/2, 727). Photosensitive reaction, a common but rare symptom reported among the existing fluoroquinolones, was not seen in any patient in any study with GFLX.
2. Abnormal Laboratory Findings
Abnormal laboratory findings were evaluated in 2, 160qualified patients, and their incidence was 6.3%(136/2, 160).Major findings were increases in S-GPT (2.8%;59/2, 127), S-GOT (1.9%;41/2, 130), and eosinophilia (1.1%;19/1, 753).
Reanalysis of all data confirmed that the present conclusion in safety aspects of GFLX is consistent with results published. The incidence of adverse drug reactions and abnormal laboratory findings noted with GFLX in all studies are similar to those of existing fluoroquinolones. No event was serious or clinically significant.

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We retrospectively studied risk factors and incidence of adverse effects of cefoselis on the central nervous system.Cefoselis is a broad-spectrum injectable antibiotic.Subjects were all patients treated with cefoselis at 4, 120 institutions where cefoselis was delivered during 3 months from the date of initial marketing to the day of the “Dear Dr.” letter announcement. Of these institutions, 1, 254 took part in the investigation and 10, 641 patients were enrolled in the study, with about half of the 21, 119 patients regarded as having been treated with cefoselis over this period.
1.The case-control study on risk factors for adverse effects in the central nervous system indicated that the Mantel-Haenszel estimate of the odds ratio of exposure to dialysis or renal failure was 23.1 (95% confidential interval: 11.9-44.7), demonstrating that dialysis or renal failure was an obvious risk factor. Another similar study on risk factors for renal disorder was conducted by excluding patients with dialysis or renal failure, and indicated a Mantel-Haenszel estimate of the odds ratio of 1.5 (95% confidence interval: 0.5-5.1), which was not statistically significant.
2.Adverse effects on the central nervous system were observed in 93 of the 10, 174 patients (0.91%), while adverse effects were observed in 48 of the 9, 879 patients (0.49%) remaining after excluding patients with dialysis or renal failure for whom the cefoselis use was contraindicated. Logistic regression analysis showed 3 additional risk factors for adverse effects on the central nervous system: renal disorder severity, age, and daily dose.We estimated the incidence of adverse effects using the logistic regression model with these 3 factors for patients under 65 years old with cefoselis at the standard dosage, i.e., 1 g twice a day. The estimated incidence varied as follows: 0.05-0.18%in patients without renal disorder, 0.09-0.31%in those with mild renal disorder, 0.16-0.56%in those with moderate renal disorder, and 0.28-1.00% in those with severe renal disorder. The incidence of adverse effects in patients aged 65 years or more was estimated to vary as follows when cefoselis was administered at the initial standard dose for elderly patients (0.5 g twice a day): 0.07-0.24% in patients without renal disorder, 0.12-0.44% in those with mild renal disorder, 0.22-0.78%in those with moderate renal disorder, and 0.40-1.38%in those with severe renal disorder.
3.Our results indicate that the incidence of adverse effects on the central nervous system due to cefoselis varies with renal disorder severity, age, and daily dose. The dose of cefoselis should therefore be determined based on renal disorder severity and patient age.

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