1) We investigated the bacteriological characteristics of 54 strains of methicillin-resistant Staphylococcus aureus (MRSA) isolated from patients in the Clinical Laboratory Department, School of Medicine, Yokohama City University between January 1991 and July 1991. 2) Coagulase type-II strains accounted for 98.1% of the isolates, and enterotoxin C was produced by 48.1%. Approximately 74% of the isolates produced β-lactamase. All strains tested possessed the mecA gene. 3) Combination of piperacillin (PIPC) with imipenem/cilastatin (IPM/CS), with meropenem (MEPM), with flomoxef (FM0X), and with cefmetazole (CMZ) in vitro yielded potent synergistic activities (FIC index:<0.25) against 74.0%, 72.2%, 74.0%, 79.6%, respectively of the isolates. 4) Based on the morphological findings, when treated with the PIPC plus IPM combination, the MRSA cells became swollen and disintegrated. 5) Although the mechanism of the synergism between PIPC and the above 4 drugs is unknown, it appears that the affinity of these drugs for S. aureus, PBP 4 is related to this phenomenon.
The incidence of multi-drug-resistant Staphylococcus epidermidis in Showa University Hospital was surveyed from April 1991 to March 1992. Multi-drug-resistant S. epidermidis comprised 18.2%(218/1, 198 strains) of all S. epidermidis isolated. Multi-drug-resistant S. epidermidis were frequently isolated from respiratory system and urinein specimens 22.0% and 22.3%, respectively. Minocycline, ofloxacin and cefotiam retained their efficacy against multi-drug-resistant S. epidermidis, The combinations imipenem plus amikacin, imipenem plus flomoxef, and cefotiam plus amikacin were shown to be effective by the in vitro checkerboard titration method. The effect of the combinations was unrelated to β-lactamase production.
The antibacterial effect of boric acid, especially as it relates to dermatological infectious disease, was studied. Boric acid was once one of the most important reagents applied to the treatment of dermatological infectious diseases. Since the 19 th century it was widely used and thought to be one of the most effective antibacterial reagents. Since 1950, though, many side effects of boric acid have been strongly pointed out, including accidental death. As a result, use of boric acid was stopped in spite of its usefulness. In this study, we examined the antibacterial effect of boric acid and obtained very interesting results. The growth of all bacteria and fungi tested here was completely inhibited by 1%(wt/vol) of boric acid added to the media. MICs were distributed between 0.125%, to 1%, and bacteria belonging to the same species showed similar MICs. Compared with 16 years ago, the antibacterial effect against Staphylococcus aureus has not changed at all, and there have been no differences in the MICs between methicillin-resistant S. aureus (MRSA) and methicillin-sensitive S. aureus (MSSA). This shows that MRSA might have difficulty in acquiring resistance to boric acid. The effect on MRSA suggests that this formerly used reagent might be able to be used to treat infection with MRSA. This study suggests that the antibacterial effect of boric acid should be reevaluated, and that use at appropriate dosages may be beneficial in treating bacterial skin infections.
Mupirocin demonstrated excellent antibacterial activities against gram-positive bacteria other than Micrococcus luteus. The growth of all the staphylococci tested in the present study, including methicillin-resistant Staphylococcus aureus (MRSA), was inhibited by the agent at a concentration of 0.39 μg/ml. Mupirocin showed marked antibacterial activities against erythromycin-minocycline-and gentamicin-resistant S. aureus. It was confirmed that mupirocin did not show cross-resistance with any of these agents. Among gram-nagative bacteria, mupirocin demonstrated marked antibacterial activities against Haemophilus influenzae and Branhamella catarrhalis. In the test of the bactericidal activities of mupirocin against MRSA, mupirocin was not active at low concentrations, but was bactericidal at a concentration of 200 μg/ml after a 6-hour period of incubation. In the determination of minimum bactericidal concentrations (MBCs) against clinical isolates of MRSA, mupirocin showed MBCs of 50 μg/ml or less against all the MRSA strains tested. The development of resistance to mupirocin by MRSA was determined in vitro by performing transfers in broth. Minimum inhibitory concentrations (MICs) increased only by eight times after 18 transfers. Laboratory-induced resistance of MRSA occurred in a very slow, stepwise fashion.
The present study was undertaken to investigate the effects of kanamycin (KM), bekanamycin (AKM) and ribostamycin (RSM), aminoglycoside antibiotics, onthe contractile response of isolated guinea pig was deferens. The contractile response of isolated was deferens induced by electrical stimulation with rectangular pulses (50 volt, 5 Hz) of 0.5 msec duration for a period of 5 sec was abolished by guanethidine and tetrodotoxin, but was not affected by hexamethonium. Therefore, the intramural nerves supplying the was deferens are undoubtly the postganglionic sympathetic nerves, and the above-mentioned ontractile response may be due to a stimulus effect of the electrical current on the intramural nerves of the was deferens (electrical nerve stimulation). Further, the contractile response of isolated was deferens induced by electrical stimulation with rectangular pulses (50 volt, 5 Hz) of 50 msec duration for a period of 5 sec in the presence of tetrodotoxin may be due to a stimulus effect of the electrical current on the muscle of the was deferens (electrical muscle stimulation). It has been proposed, moreov r, that noradrenaline and adenosine triphosphate are simultaneously released from sympathetic nerves in the was deferens, and act as co-transmitters, while the isolated was deferens evoked a contractile response by exogenously added noradrenaline as well as exogenously added adenosine triphosphate. KM (1 ×10-5 g/ml-1 ×10-3 g/ml), AKM (5 ×10-6 g/ml-1 ×10-3 g/ml) and RSM (5 × 10-5 g/ml-1 ×10-3 g/ml) reduced the amplitude of the contractile response induced by electrical nerve stimulation in a concentration-dependent manner. KM, AKM and RSM, each at a concentration of 5 ×10-4 g/ml, reduced, withmuch approximation, the amplitudes of contractile responses induced by the three treatments, that is, electrical muscle stimulation, exogenously added noradrenaline and exogenously added adenosine triphosphate. However, each of these antibiotics at the concentration mentioned was exceedingly potent in reducing the effect on the amplitude of the contractile response induced by electrical nerve stimulation. All these findings may bring about a conclusion that KM, AKM and RSM affect both intramural sympathetic nerves and muscle of the was deferens. It also seems possible that the effects of these antibiotics are greater on the former than they are on the latter.
We studied the effectiveness of tosufloxacin tosilate (TFLX) in preventing infection in neutropenic patients with hematological malignancies and compared it with polymyxin B (PL-B). We randomly divided 119 patients into a PL-B group (300 mg/day), TFLX group (600 mg/day) and PL-B plus TFLX group. Patients received prophylactic treatment throughout the entire period of neutropenia until their neutrophil count exceeded 1, 000/μl. Clinical prophylactic efficacy was observed in 43.6% of the PL-B group, 73.7% of the TFLX group and 81.0% of the PL-B plus TFLX group. Efficacy was significantly higher in the TFLX group than in the PL-B group, however, difference between the TFLX group and PL-B plus TFLX group was not significant. Bacteriological effect for preventing gram-negative bacillary infection was significantly better in the TFLX group than in the PL-B group, andthere were no markeddifferencesbetween the TFLXgroup and PLB plus TFLX group. No adverse reactions or abnormal laboratory test values in response to TFLX, were observed. These findings suggest that TFLX is a more efficacious oral antimicrobial agent than PL-B. TFLX is a very useful drug which provides high prophylactic efficacy for the prevention of infection, safety, and excellent compliance in neutropenic patients with hematological malignancies.
The duration of pyuria.after transurethral prostatectomy was compared in patients treated with a short (two weeks: Group 1) and prolonged (Group 2) course of oral cephalosporin therapy. After excluding the 12 patients found to have preoperative bacteriuria (Group 3), the 68 patients were randomized in to the above 2 groups. Prolonged administration significantly shortened the duration of post-TURP pyuria (Group 1 vs. Group 2: p <0.05).
To evaluate the effectiveness and the safety of DQ-2556, a new parenteral cephem antibiotic, and to find its optimal dose in the treatment of complicated urinary tract infections (UTI), multicenter clinical trials were conducted. Data were summarized according to the criteria of the Japanease UTI committee (the third edition). 1) Open clinical trials DQ-2556 was administered mainly at doses of 0.5 g, 1.0 g and 2.0 g twice a day. In the 80 evaluable patients, 32 had excellent, 24 moderate and 24 poor results; the overall efficacy rate was 70.0%. Twice-a-day medication was dose-dependently effective (moderate or excellent): efficacy rates for treatment at doses of 0.5 g b.i.d., 1.0 g b.i.d. and 2.0 g b.i.d. were 59.1% in 22 patients, 73.0% in 37 patients and 80.0% in 10 patients. DQ-2556 was effective in 77.8% of 54 non-indwelling-catheter patients and in 53.8% of 26 indwelling-catheter patients. The overall bacteriological eradication rate was 82.2%(106/129); 40 at 49 gram-positive bacteria (81.6%) and 66 of 80 gram-negative bacteria (82.5%) were eradicated. Clinical adverse reactions were observed in three in 116 patients (2.6%): a patient vomited severely with nausea three days after the commencement of treatment and another showed mild to moderate eruption. Laboratory adverse reactions were seen in 14 in 109 patients (12.8%); the main findings were abnormalities of liver function represented by elevation of GOT and/or GPT, which were observed in 10 patients. 2) Dose-determination study Complicated UTI without indwelling catheters and also without prostatectomy, i.e., the 3 rd, 4 th and 6 th groups were enrolled. The patients were randomly assigned to receive 5-day medication regimens with DQ-2556 at daily dosages of 0.5 g b.i.d.(DQ-1.0 group) or 1.0 g b.i.d.(DQ-2.0 group) and with ceftazidime (CAZ) at daily dosages of 1.0 g b.i.d. as the control group (CAZ group). The clinical efficacies of these three regimens were compared. Eleven patients in the DQ-1.0 group, 11 in the DQ-2.0 group and 12 in the CAZ group were evaluated. As for background characteristics of the patients, mild renal function failure was seen only in three patients in the DQ-2.0 group, and bacteria with low susceptibility to the compounds were distributed more in the DQ-1.0 and CAZ groups than in the DQ-2.0 group. Except for these characteristics, no significant differences were not found among the three groups. Overall clinical efficacy rates were 100%(11/11) in the DQ-1.0 group, 90.9%(10/11) in the DQ-2.0 group and 83.3%(10/12) in the CAZ group. Bacteriological eradication rates were 100%(12/12) in the DQ-1.0 group, 90.9%(10/11) in the DQ-2.0 group and 86.7%(13/15) in the CAZ group. As for these two rates, there were no significant differences among the three groups. On exclusion of Enterococcus faecalis, which is not indicated, both the overall efficacy rate and the bacteriological eradication rate were both 100% in the CAZ group. A clinical adverse reactions were seen in only one patient in the DQ-2.0 group, whoshowed mild facial erythema. Abnormal laboratory findings were found in two patients in each of the three groups. As to the incidence of clinical and laboratory adverse reactions, there were no significant differences among the three groups. The results of this open clinical trial and the dose-determination study suggest that DQ-2556 is effective against complicated UTI and that the optimal daily dosage is 0.5g twice a day (0.5 g b.i.d.), although a dose of more than 1.0 g b.i.d. may be needed for intractable UTI such as that associated with indwelling-catheter disease.
Imipenem/cilastatin sodium (IPM/CS) were administered 2g/day to 34 patients with moderate or severe intractable respiratory tract infections (15 cases of pneumonia, 2 of lung abscess and 17 of bronchitis which were secondary infections or acute exacerbations of chronic respiratory disease). Thirty-three of the 34 patients had chronic respiratory disease as an underlying disorder and one had cerebral infarction. Clinical efficacy was excellent in 10 cases, good in 18, fair in 3 and poor in 3, thus the efficacy rate was 82.4%. A good clinical response was obtained in severely infected patients and old patients. MICs were measured in 12 of 42 isolated organisms, and the MICs of IPM against these organisms were lower than 3.13 μg/ml. No adverse reactions occurred, but mildly abnormal laboratory data were detected in 6 patients (17.6%). These results indicate that IPM/CS is effective against moderate or severe intractable respiratory infections.
The efficacy and safety of injectable clindamycin-2-phosphate (CLDM) and a β-lactam antibiotic in combination were assessed at 25 institutions in Japan, focusing especially on CLDM's inhibitory effect on the production of β-lactamase. A total of 31 cases were included in the study. There were 4 cases the responded well to the β-lactam antibiotic alone and the one case also treated with a steroid. The other 26 cases consisted of 10 cases of chronic bronchitis, 8 of bronchictasis, 1 of diffuse panbronchiolitis, 6 of pneumonia, and 1 of lung abscess. The medication was started with intravenous drip infusion of a recommended dose of, β-lactam antibiotic divided in two doses, and when the drug did not show efficacy by treatment day 3, 1, 200-2, 400 mg/day of CLDM in two equal doses was added starting on day 4. CLDM was given generally up to day 7, but up to day 10 in some cases, to assess the efficacy of combination therapy. Final clinical efficacy was good in 90.0%(9/10) of the cases of chronic bronchitis, 71.4%(5/7) of the cases of bronchiectasis, 100%(1/1) of the cases of diffuse panbronchiolitis, and 100%(5/5) of the cases of pneumonia, but poor in the single case of lung abscess. Sputum β-lactamase activity had decreased by day 4 of combination therapy in all cases which had shown low or moderate (< 500 μU/ml)β-lactamase activity before the addition of CLDM. In 8 of the 9 patients with high β-lactamase activity (>500μU/ml), it started to tend to decline on day 1 of combination therapy. Clinical efficacy and β-lactamase activity were correlated: r=0.665 (p < 0.01) in the high, β-lactamase activity group and r=0.666 (p < 0.01) in the low/moderate activity group. Side effects wer noted in 2 of the 31 cases, but both were mild and allowed continued treatment. A slight rise in S-GOT was detected in one case, but it returned to normal after the completion of therapy. These findings suggest the clinical usefulness of combination therapy with CLDM and a β-lactam antibiotic, partly due to CLDM's inhibitory effect on the. production of β-lactamase.