We tested susceptibilities of 46 strains of clinical isolates of methicillin-resistant Staphylococcus aureus (MRSA) to arbekacin (ABK), tobramycin (TOB), ticarcillin (TIPC), clavulanic acid/ticarcillin (CVA/TIPC) and fosfomycin (FOM).
Twelve strains had penicillinase activity. Most strains were resistant to TOB, TIPC, FOM and CVA/TIPC, but ABK inhibited 80% of the 46 MRSA strains at a concentration of 1.56 μg/ml.
The combination of ABK and FOM was indifferent. Synergism was observed, however, between FOM and TIPC against 79% of penicillinase non-producing MRSA.
This synergism may mean that FOM inhibits the production of penicillin-binding protein 2' in some strains of penicillinase non-producing MRSA.

View full abstract

Institute of Medical Science, St. Marianna UniversityAntimicrobial activity of clarithromycin (CAM) in comparison with other 6 macrolides was determined against 419 recent clinical isolates including Streptococci, Enterococci, Staphylococci, Moraxella, Haemophilus and Bacteroides strains.
MICs₈₀'s of CAM against Streptococcus pneumoniae, Streptococcus pyogenes and Streptococcus agalactiae were 0.78, 0.10 and 0.10 μg/ml, respectively. MICs₈₀'s against Moraxella catarrhalis and Haemophilus influenzae were 0.05 and 1.56 μg/ml, respectively.
Laboratory-induced resistance to CAM in strains of S. pneumoniae, Enterococcus faecalis or methicillin-sensitive Staphylococcus epidermidis occurred in stepwise fashion and at a very low rate.
Adherence to silicon filter of strains of Pseudomonas aeruginosa or S. epidermidis was strongly repressed by the addition of sub-MIC of CAM or other macrolides.
Although tosufloxacin (TFLX) alone had no bactericidal activity against the sessile cells of P. aeruginosa strains tested, TFLX showed synergistic bactericidal activity when combined with sub-MICs of CAM or erythromycin.

View full abstract

The number of deep mycosis has been increasing because of increases in immunocompromised hosts and in fungal colonization associated with increasing use of broadspectrum antibacterial antibiotics. Based on these phenomenon, a simple test method for an early diagnosis of deep mycosis is urgently desired. We therefore investigated the usefulness of assaying a fungal cell component,(1→3)-β-D-glucan (β-glucan). The amount of β-glucan was obtained from the difference between the amounts determined using Toxicolor® and Endospecy®, and the serum levels of more than 10 μg/ml were considered positive signs for β-glucan. The following results were obtained: We found that β-glucan was positive in 75% of the patients who had been definitely diagnosed to have mycosis, and in 58.3% of the patients strongly suspected of mycosis. The numbers of β-glucan positive patients in these 2 groups of patients were significantly different from that in those without mycosis (14.7%, P<0.05). Thus a usefulness of β-glucan measurement for the dignosis of mycosis was demonstrated. However, β-glucan was sometimes negative even in patients with fungemia at an early phase of the disease and turned positive several days later. Even in a patient with definite lung mycosis, who had a latent circumscribed lesion (afebril and CRP-negative), β-glucan was also negative. From these findings, one should be aware that the β-glucan test produces false negatives even in patients with difinite mycosis and that the test should be repeated during the course of the disease.

View full abstract

Against main clinical isolates at our center in 1990 to 1992, the minimum inhibitory concentrations (MICs) of cefminox (CMNX) and some other comparable cephems were determined. The results are summarized as follows.
1. As to the strains resistant to cephems including CMNX, annual increases were observed for Streptococcus pneumoniae among Gram-positive bacteria and Proteus vulgaris among Gram-negative bacteria. Moreover, cephem-resistant strains of Escherichia coli were constantly isolated, and there were signs indicating that cephem-resistant strains would increase among strains of Klebsiella pneumoniae.
2. The annual increases in cephem-resistant strains of S. pneumoniae and P. vulgaris may respectively reflect the recent increases in the incidence of benzylpenicillin (PCG)-insensitive strains of S. pneumoniae (PISP) and multi-drug resistant strains including oxime type cephems and new quinolones introduced into clinical use in the latter half of the 1980s.
3. Concerning antimicrobial activities of CMNX against recent clinical isolates, the same problems as described above will remain. However, these tendencies have been observed only with regard to MIC₉₀. No remarkable changes have been noted for MIC₅₀ or MIC₉₀ at this time.

View full abstract

This study was conducted to investigate susceptibilities of clincal isolates to antibacterial agents at 149 hospitals throughout Japan from September to December in both 1989 and 1990. In this study, identifications and susceptibility testings were carried out at each hospital laboratory. The susceptibility testings were performed according to the disk diffusion method recommended by NCCLS.
Staphylococcus aureus and coagulase-negative staphylococci showed high or moderate resistance rates to β-lactam antibiotics, but Streptococcus pyogenes and Streptococcus pneumoniae were highly susceptible to them. Enterococcus faecalis was susceptible to imipenem (IPM) and piperacillin but resistant to β-lactam antibiotics and aminoglycosides. Haemophilus influenzae, Escherichia coli, Klebsiella pneumoniae and Proteus mirabilis were susceptible to β-lactam drugs and aminoglysides.Enterobacter cloacae, Serratia marcescens, Proteus vulgaris, Morganella morganii and Pseudomonas aeruginosa had a good susceptibility to IPM and aminoglycosides. Bacteroides fragilis was highly susceptible to IPM. IPM had strong antibacterial activity to many species of clinical isolates, including strains which were resistant to commonly used antibiotics.

View full abstract

In vivo synergistic effects of cefodizime (CDZM) were investigated in combination with aminoglycosides (AGs), sisomicin (SISO) or dibekacin (DKB) against Pseudomonas aeruginosa in immunocompromised tumour bearing mice. Fractional effective dose (FED) indices showed that either synergistic or additive effects were observed between CDZM and AGs. The synergistic intraperitoneal bactericidal effect of CDZM in combination with SISO or DKB was also observed in immunocompromised tumour bearing mice. The post antibiotic effect (PAE) of AGs was prolonged by the addition of CDZM. Moreover, the strong synergistic bactericidal effects of CDZM and AGs against P. aeruginosa were observed in the presence of immunocompromised tumour bearing murine polymorphonuclear leukocytes (PMN).
These results suggest that the strong therapeutic efficacy of CDZM in combination with AGs was caused by synergistic bactericidal effect of CDZM and AGs in the presence of PMN.

View full abstract

As one of the biodefense mechanisms, lactoferrin (LFN) in the secreta of female genital organ may be an interesting biological material in view of its antimicrobial activity. In the present study, we investigated antimicrobial activities of LFN and its combination with cefpodoxime proxetil (CPDX-PR), we also as evaluated clinical effect of CPDX-PR. The following results were obtained.
1. Antimicrobial activities of LFN were tested against 15 strains of 10 species of bacteria, and potent activities against Staphylococcus aureus 209P, Escherichia coli, Klebsiella pneumoniae and Proteus spp. were found.
2. In a concomitant use of LFN with CPDX-PR (a checkerboard method), synergistic actions were observed against S. aureus 209P, E. coli STf, K. pneumoniae 602 and Pseudomonas aeruginosa 1046, and additive actions against E. coli NIHJ and Providencia rettgeri 1603. In 3 strains, the MICs of CPDX-PR in the presence of LFN were reduced to <1/64.
3. In the evaluation of clinical effect of CPDX-PR, efficacy rates were 53/57 (92.9%) in a patient group with infections. The incidence of adverse reaction was 0/57.

View full abstract

The primary objective of this study is to confirm the efficacy and safety of combination therapy with antibacterial and antifungal drugs for patients with hematological disorders complicated with infections of unknown causative orgainsms. The subjects consisted of 55 patients with hematological disorders, 28 males and 27 females, ranging from 1 to 78 years of age, with an average age of 34 years. The breakdown of the patients by disease was: 41 leukemias, 10 malignant lymphomas, 3 myelodysplastic syndromes and an aplastic anemia. All patients were treated with sulbactam/cefoperazone (SBT/CPZ) and aminoglycoside (AG) plus fluconazole (FLCZ) as an empiric therapy. Overall efficacy rate was 54.5% for all the patients: 57.7% for patients with suspected sepsis and 0% for those with pneumonia from which unknown organisms were detected. The efficacy rate was 59.4% for patient who had been previously treated with other antibiotics and 47.8% for those who had not previously been treated.
The above results suggested that this combination therapy might be effective for severe infections of unknown causative organisms associated with hematological disorders.

View full abstract

Temafloxacin (TMFX, TA-167) is a new quinolone antimicrobial agent that has a broad antibacterial spectrum against Gram-positive, Gram-negative and anaerobic bacteria.
We obtained the following results from laboratory and clinical studies on TMFX.
1. TMFX showed good penetration into the female genital organs and C_max's in various organs were 2.77-4.24 μg/g when 300mg was administered, and these values were equal to or higher than C_max in vein blood.
2. The clinical efficacy rate was 95.4% in a clinical study involving 219 cases. The bacterial eradication rate was 96.4% in 139 cases.
3. Nine cases of side effects and 1 case of abnormal change in laboratory findings were noted in 254 cases involved, but none of them was serious.
Based on these findings, TMFX is expected to be a useful antimicrobial agent for the treatment of obstetric and gynecological infections.

View full abstract