The in vitro antibacterial activity of cefditoren (CDTR) against β-lactamase-negative ampicillin (ABPC)-resistant Haemophilus influenzae(BLNAR) was compared to those of cefcapene (CFPN), cefdinir (CFDN), and cefaclor (CCL). Therapeutic efficacy of cefditoren pivoxil (CDTR-PI) against respiratory tract infection caused by BLNAR in mice was also compared to those of cefcapene pivoxil (CFPN-PI), cefdinir (CFDN), and levofloxacin (LVFX). MIC₉₀ values of CDTR, CFPN, CFDN and CCL against 125 strains of β-lactamase-negative H. influenzae were 0.25, 1, 4, and 32μg/mL, showing the strongest activity of CDTR among tested antibiotics. Based on the susceptibility of these strains to ABPC, they were classified into 3 groups. MIC range of ABPC for groups were 0.03-0.25μg/mL, 0.5-1μg/mL and 2-4μg/mL, and the susceptibility of each group to CDTR, CFPN, CFDN, and CCL was compared. The 4 antibiotics increased their MICs as MIC of ABPC increased, but an increase in MIC of CDTR was less than those of the other 3 antibiotics. We examined the therapeutic efficacy of CDTR-PI, CFPN-PI, CFDN, and LVFX against respiratory tract infection due to BLNAR in mice. Therapeutic efficacy of CDTR-PI against models was dose-dependent and higher than those of other oral cephem antibiotics, as reflected in in vitro antimicrobial activity. In this study, we showed that CDTR-PI may have potential therapeutic efficacy against BLNAR infection for which other antibiotics are not effective.

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To evaluate the effects of renal function on teicoplanin pharmacokinetics and side effects, we studied correlations between creatinine clearance (Ccr) and pharmacokinetic parameters and between serum teicoplanin concentrations and the renal and hepatic functions in 42 inpatients who received teicoplanin therapy for MRSA infection. No correlation was observed between Ccr and distribution volume. Although no good correlation was observed between Ccr and terminal half-life in patients whose Ccr exceeded 40mL/min, a good negative correlation was observed between the 2 parameters in patients whose Ccr was below 40mL/mim. No correlation was observed between serum teicoplanin concentration and serum creatinine and serum asparatate aminotransferase. A slight correlation was observed between concentration and serum alanine aminotransferase. These results suggest that efficacy and a safe therapeutic range is maintainable by administration of 400 mg once a day of teicoplanin in patients whose Ccr exceeds 40mL/min, but the concentration must be carefully monitored in patients whose Ccr exceeds 40mL/min, but the concentration must be carefully monitored in patients whose Ccr is below 40mL/min. Although renal function is not affected by teicoplanin administration, hepatic function may be adversely affected.

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The bactericidal activity of biapenem (BIPM) against Pseudomonas aeruginosa was compared with that of imipenem/cilastatin (IPM/CS), meropenem (MEPM) and ceftazidime (CAZ) in a short-term in vitro pharmacokinetic model simulating the typical plasma levels of these drugs in human. The short-term bactericidal activity of BIPM against P. aeruginosa was similar to that of IPM/CS. The initial bactericidal activity of BIPM against P. aeruginosa was stronger than those of MEPM or CAZ. The short-term bactericidal activity of BIPM and IPM/CS against P. aeruginosa was not affected by the inoculum size. The bactericidal activity against P. aeruginosa in a model simulating the plasma level after a drip infusion of BIPM (300mg/30min) in humans was equal to those of IPM/CS (500mg/30min) and MEPM (500mg/30min). These.results suggest that BIPM is useful for the treatment of infectious disease caused by P. aeruginosa.

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The activity of various antibacterial agents against clinical isolates of 1, 126 strains of gram-positive cocci (30 species) and 166 strains of anaerobic bacteria (23 species) was assessed by determining their agar-dilution MICs. The strains tested, were clinical isolates obtained in 2000 at 16 facilities in Japan. Methicillin-resistant strains accounted for 61.5% of the Staphylococcus aureus and for 82.0% of the Staphylococcus epidermidis. Arbekacin (ABK), quinupristin/dalfopristin (QPR/DPR), and vancomycin (VCM) had high antibacterial activity against methicillin-resistant S. aureus (MRSA) and methicillin-resistant S. epidermidis (MRSE), with MIC₉₀ values≤1.56μg/mL. Penicillin (PC)-intermediate strains and PC-resistant strains accounted for 27.3% and 30.5%, respectively, of the Streptococcus pneumoniae. Cefpirome, carbapenems (CBPs), VCM, teicoplanin (TEIC), and QPR/DPR displayed high antibacterial activity against PRSP, inhibiting the growth of all strains at≤0.78μg/mL. VCM, TEIC, and linezolid were effective against Enterococcus faecalis and Enterococcus faecium with MTC₉₀ values≤3.13μg/mL. No VCM-resistant strains were found among the gram-positive coccus isolates tested, including MRSA, MRSE, and Enterococcus species, except Enterococcus casseriflavus and Enterococcus gallinarum. However, TEIC-resistant strains were detected in some species, such as MRSE and Staphylococcus haemolyticus. Among the anaerobes, CBPs displayed potent antibacterial activity against all anaerobic bacteria, however, the decrease in susceptibility of Bacteroides fragilis and Prevotella spp. to CBPs should be noted.

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We used MIC determinations by the agar-dilution method to assess the activity of various antibacterial agents against clinical isolates of 1, 227 strains of gram-negative aerobic bacteria (19 species) isolated at 16 facilities in Japan in 2000. There was no decrease in the antibacterial activity of most β-lactams against Enterobacteriaceae compared to our previous report on isolates in 1998, but the number of strains resistant to new quinolones (NQs) had increased. Strains that were not susceptible to ceftriaxone, ceftazidime, aztreonam, or cefpodoxime accounted for 9.8% of the Escherichia coli, 4.0% of the Klebsiella spp., and 8.3% of the Proteus spp. Most of the agents displayed high antibacterial activity against Neisseria gonorrhoeae and Branhamella catarrhalis. However, the proportion of NQs-resistant N. gonorrhoeae strains was 92%, and was higher than in 1998.β-Lactamase was produced by 7% of the Haemophilus influenzae strains isolated, which was lower than in 1998. However, the proportion of β-lactamase-negative ampicillin-resistant H. influenzae increased greatly, from 3.3% in 1992 and 3.5% in 1994, to 15.6% in 1996, 24.4% in 1998, and 37.0% in 2000. The agents that displayed comparatively high antibacterial activity against Pseudomonas aeruginosa were tobramycin, doripenem, meropenem, and arbekacin, all of which had an MIC₉₀ of ≤6.25μg/mL. The distribution of the activity of 11 antipseudomonal agents against P. aeruginosa indicated a decrease in number of multi-resistant strains and an increase in strains that exhibited susceptibility to all of the agents, compared with our previous reports in 1998. The activity of antibacterial agents against other glucose non-fermentative gram-negative rods, was slightly higher than in 1998.

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