We investigated the in vitro combination effects of arbekacin (ABK), vancomycin (VCM) or teicoplanin (TEIC) and cefepime (CFPM) on methicillin-resistant Staphylococcus aureus (MRSA) and Pseudomonas aeruginosa isolated from various clinical specimens.
Using checkerboard titration technique by agar dilution, combinations of ABK, VCM or TEIC and CFPM exhibited synergistic effects on 25 MRSA strains. The similar effects were also observed on ABK-resistant MRSA. Combination of ABK and CFPM exhibited a good effect on P. aeruginosa, but combinations of VCM or TEIC and CFPM exhibited no synergistic effect on P. aeruginosa. In vitro bactericidal activities of ABK, VCM or TEIC and CFPM against mixed cultures of MRSA with P. aeruginosa were examined at concentration of each drug that corresponds to the serum concentration at 3 hours after the usual therapeutic dosage. VCM or TEIC alone showed bacteriostatic effects against MRSA, and no enhancements were observed when combined with CFPM. ABK alone showed good bactericidal activity against MRSA and combination with CFPM enhanced the bactericidal activity. Against P. aeruginosa, ABK or CFPM alone showed the bactericidal activity, and strong bactericidal activity was induced by the combination of ABK and CFPM. VCM and TEIC showed no bactericidal activities against P. aeruginosa. When CFPM combined with VCM or TEIC, the bactericidal activity of CFPM was not enhanced against P. aeruginosa.

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We investigated the susceptibility of Pseudomonas aeruginosa (isolated from the sputum of patients with respiratory infection in 4 medical institutions in Fukushima Prefecture) to 8 β-lactam antibiotics including three carbapenems and relationships among MICs of antibiotics tested. The MIC₉₀ values for a total of 216 strains were 6.25μg/ml for meropenem, 12.5 μg/ml for imipenem and ceftazidime, 25 μg/ml for panipenem and cefsulodin, 50 μg/ml for cefpirome and over than 200μg/ml for cefoperazone and piperacillin. The frequency of resistance of these strains to each antibiotic was as follows: The resistant strains were 19 (8.8%) for meropenem, 34 (15.7%) for imipenem and ceftazidime, 50 (23.1%) for cefsulodin, 72 (33.3%) for panipenem, 76 (35.2%) for piperacillin and 90 (41.7%) for cefpirome.
Eighteen srains (18.3%) of 19 meropenem resitant strains were resistant to imipenem and panipenem, but 16 strains of the 34 imipenem-resistant strains and 54 strains of the 72 panipenem-resistant strains were susceptible to meropenem.
In investigation of isolation of multi-resistant Pseudomonas aeruginosa, the susceptibility of strains tested to 7 antibiotics except cefoperazone was as follows: The strains susceptible to all the 7 antibiotics were 92 strains (42.6%), and 33 strains (15.2%) were resistant to 2 antibiotics, 31 strains (14.4%) were resistant to 1 antibiotic, 21 strains (9.7%) were resistant to 3 antibiotics, 13 strains (6.0%) were resistant to 5 antibiotics, 9 (4.2%) were resistant to 4 and 7 antibiotics, and 8 strains (3.7%) were reistant to 6 antibiotics. Since the emergence of these multi-resistant strains is closely related to frequent use of antibiotics for nosocomial infections, special attention should be paid to the antimicrobial susceptibility of Pseudomonas aeruginosa and the situation of antibiotic resistant strains.

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Cefozopran (CZOP) and amikacin (AMK) were used concomitantly to treat infections complicated by hematological diseases. A total of 103 subjects were evaluated, and the allover efficacy rate was 69.9%. Acute leukemia was found in the largest number of patient, 57, followed by 29 cases of malignant lymphoma and 7 cases of myelodysplastic syndrome. By type of infection, patients having unknown origin were the largest in number, being 66, and the efficacy rate was 71.2%. The efficacy rates for sepsis, pneumonia and upper respiratory infection were 42.9% (7 cases), 71.4% (14 cases) and 90% (10 cases) respectively. The efficacy rates by neutrophil counts before administration of CZOP and AMK and at 1 week after administration were both 53.3% in the group of less than 100/μl, both 60% in the group of less than 500/μl. The efficacy rate by neutrophil counts at 1 week after administration was 58.6% in the group of less than 100/μl. The efficacy rate was 75.4% in the group of granulocyte colony stimulating factor (G-CSF) concomitant usage, and 61.9% in the group of nonconcomitant usage group. The efficacy rates by serum albumin levels before administration of CZOP and AMK and at 1 week after administration were both 92.9% in the group of over than 4g/dl, both 50% in the group of less than 3g/dl. Concomitant treatment with CZOP and AMK exhibited a high level of safety and efficacy rates in infections complicated by hematological diseases.

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We studied the transference of cefcapene pivoxil (CFPN-PI) into the maternal cubital blood, umbilical blood and amniotic fluid as well as its clinical usefulness. 58 pregnant women without complications who had a premature rupture of membranes after day 0 of the 36 th week of pregnancy and delivered a child with a normal transvaginal labor were enrolled this study. As a result, we found that the maternal serum level of CFPN-PI reached a detectable level at 1 hr 15 min post dose, reached the maximum (C_max) at 2hr 30min, and was maintained at 0.15-1.14μg/ml until 4hr 35min. In the umbilical serum, the drug concentration reached a detectable level at 1 hr 45 min post dose, was maintained at C_max of 0.40 μg/ml from 3 hr 3 min until 4 hr 27 min, and showed a level as high as 0.14μg/ml at 7 hr 7min. In the amniotic fluid, the drug concentration reached a detectable level of 0.09 μg/ml at 2 hr 48 min post dose, reached C_max at 3 hr 55 min, and was maintained at 0.15-0.61μg/ml until 13 hr 37 min. Concerning the prophylactic effects of CFPN-PI against infections, one case of puerperal intrauterine infection in the parent and two cases of neonatal infection were observed, showing an effectiveness of 95%. In terms of adverse events, neither abnormality in maternal laboratory test data suspected as due to CFPN-PI, nor abnormality in subjective and objective findings was observed. In the neonates, no abnormality suspected as due to CFPN-PI was detected, either, including growth retardation until the 3-month medical examination. We think that CFPN-PI can be a first choice drug for prophylaxis of infections in cases of premature rupture of membranes after the 36th week of pregnancy, because of convenience of oral administration, coupled with excellent safety and potent prophylactic effectiveness against infections resulting from a long term maintenance of high levels in the umbilical blood and amniotic fluid.

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