We compared the in vitro activity of tosufloxacin (TFLX) against Chlamydia trachomatis D/UW-3/Cx to that of ofloxacin (OFLX). Antichlamydial activity of the drugs was evaluated by the counting of the number of chlamydial inclusions, observation of the density of chlamydial cells in chlamydial inclusions, and measurement of the number of infectious chlamydial cells. Infected HeLa 229 cells were exposed to 1 and 3μg/mL of TFLX and OFLX at 0-6, 6-12, and 24-30 h after inoculation of C.trachomatis D/UW-3/Cx. The 0-6 h exposure to 3μg/mL of TFLX and OFLX reduced the number of chlamydial inclusions to 43.4% and 93.6% of controls. The 6-12 h exposure to 3μg/mL of TFLX and OFLX reduced the number of chlamydial inclusions to 7.0% and 33.5% of controls. The 24-30 h exposure to 3μg/mL of TFLX and OFLX did not reduce the number of chlamydial inclusions. The 0-6 h exposure to TFLX reduced the density of chlamydial cells in chlamydial inclusions but the 0-6 h exposure to OFLX did not. The 6-12 and 24-30 h exposure to TFLX and OFLX reduced the density of chlamydial cells in chlamydial inclusions. The 0-6 h exposure to 3μg/mL of TFLX reduced the number of infectious chlamydial cells to 3.6% of controls but the 0-6 h exposure to OFLX did not. The 6-12 h exposure to 3μg/mL of TFLX and OFLX reduced the number of infectious chlamydial cells to 0.7% and 15.1% of controls. The 24-30 h exposure to 3μg/mL of TFLX and OFLX reduced the number of infectious chlamydial cells to 1.1% and 9.2% of controls. The inhibitory effect of 1μg/mL of TFLX and OFLX on the growth of chlamydia was equal to that of 3μg/mL of TFLX and OFLX. In conclusion, the in vitro antichlamydial activity of TFLX was superior to that of OFLX in each period of the chlamydial life cycle.

View full abstract

We obtained 100 isolates of methicillin-resistant Staphylococcus aureus (MRSA) from 100 hospitals in Japan during 2000 and studied their drug resistance. About two thirds of MRSA strains were isolated from sputum (48%) and pus (13%). Among MRSA isolates collected in the survey, 89% had sero-type II coagulase, and only a few had sero-type I (1%), III (9%) or VII (1%) coagulase. Most MRSA isolates showed high resistance to β-lactam agents including imipenem and flomoxef, and were also resistant to erythromycin and tobramycin. Antibacterial activities of 8 agents with potent activity for gram-positive cocci against MRSA isolates were determined. The MIC₉₀ of arbekacin (ABK), vancomycin (VCM), teicoplanin (TEIC), linezolid (LZD), quinupristin /dalfopristin (QPR /DPR), rifampicin (RFP), sulfamethoxazole-trimethoprim (ST), and mupirocin (MUP) were 2, 1, 2, 2, 0.5, ≤0.063, 1 and 0.5 mg/mL, respectively. Only a small percentage of strains was resistant (MIC, ≥8mg/mL) to ABK, TEIC, RFP or MUP, and all MRSA isolates tested were susceptible to VCM, LZD, QPR/DPR, and ST. The bactericidal activity of ABK for 5 MRSA strains was the most potent among those of VCM, TEIC, LZD, and QPR/DPR.

View full abstract

Susceptibility to 7 β-lactam antibiotics: cefepime, cefpirome, ceftazidime, cefoperazone/sulbactam, imipenem, and piperacillin (gram-negative) or oxacillin (gram-positive) was studied. A common protocol and method (Etest; AB Biodisk, Sweden) was used at 43 medical centers. No strains resistant to these β-lactams except for ceftazidime and/or cefpirome were found in oxacillin-susceptible Staphylococcus aureus and coagulase-negative staphylococci. In Escherichia coli, 11.9% of clinical strains were resistant to piperacillin, while only 0.5-1.0% were resistant to other antibiotics. All clinical strains of Klebsiella spp. were susceptible to imipenem. Isolates of Enterobacer spp. and Citrobacter spp. were most susceptible to imipenem. Isolates of Serratia spp. were more susceptible to imipenem (4.5% resistance), cefepime (6.5%), cefpirome (7.7%), and ceftazidime (7.7%) than other β-lactams tested. No indole-positive Proteus was resistant to cefepime or cefpirome, but 0.9% of strains were resistant to imipenem. Isolates of Pseudomonas aeruginosa were more susceptible to ceftazidime (10.8% resistance) and cefepime (12.5%) than cefoperazone/sulbactam (13.2%), piperacillin (15.7%), imipenem (20.3%), and cefpirome (26.0%). These results clearly indicate that emergence of strains resistant to cefepime is lower than to other β-lactam antibiotics tested.

View full abstract

We studied the combined effects of cefditoren (CDTR) and fosfomycin (FOM) against penicillin-resistant Streptococcus pneumoniae (PRSP) in antibacterial and bactericidal activity, affinity to penicillin-binding proteins, and in vivo efficacy. The antibacterial activity of CDTR against PRSP was increased 2-to 4-fold when FOM alone was used. The bactericidal activity of CDTR and FOM used concomitantly, was superior to that of either one used alone. Regarding the mechanism of combination effects, we concluded that FOM inhibited production of PBPs, which increased CDTR antibacterial. The therapeutic efficacy of CDTR-PI and FOM-Ca combination against PRSP-induced respiratory tract infection in mice was superior to that of either applied alone. Therapeutic efficacy was not influenced by the administration sequence or CDTR-PI and FOM-Ca interval.

View full abstract

The development of antimicrobial agents followed improvement in treatment of infections, but subsequent increase of drug-resistant bacteria has also been reported. We reconsidered the selection and usage of antimicrobial agents. Taking into consideration the characteristics of levofloxacin we orally administered 400 mg of levofloxacin (LVFX) twice a day for 7 days in 11 patients, 7 men and 4 women, with community-acquired pneumonia. We evaluated these patients clinically. This treatment proved efficacious, with detected pathogenic organisms eradicated, including penicillin-resistant Streptococcus pneumoniae (PISP and PRSP). This indicated that treatment by LVFX at 400 mg twice a day is an optimal dosage regimen for community-acquired pneumonia with mild and moderate severity.

View full abstract

1. In the clinical situations, antibiotics are more frequently used in elderly people and serious infectious diseases, however, there are few clinical trials conducted to target those population.
2. Antibiotics which are approved with CAP clinical trial data only, have been used for both CAP and HAP. Clinical trials for HAP are also necessary in the future.
3. Doses of oral β-lactams should be reconsidered according to its PK, Breakpoints and MIC.

View full abstract