The protective effect of piperacillin against the nephrotoxicity of vancomycin was examined in rabbits. Nephrotoxicity was induced by the intravenous administration of vancomycin at a dose of 300 mg/kg (body weight). Piperacillin was intravenously administered at a dose of 600, 300 and 80 mg/kg (body weight) and immediately followed by the administration of vancomycin. Rabbits receiving vancomycin (300 mg/kg) showed elevation of blood urea nitrogen and creitinine concentration, and showed an increase in kidney weight in comparison with controls at 24 h after vancomycin dosing. Histological, slight tubular necrosis, severe tubular dilatation and severe hyaline cast formation were seen. Electron microscopically, degenerative features were observed in the proximal tubular epithelium. However, piperacillin (600, 300 and 80 mg/kg) significantly reduced these toxicological parameters. Although the administration of vancomycin slightly elevated the excretion of urinary phospholipids, elevation was prevented by the administration of piperacillin. These results suggest that piperacillin may have a protective effect against the nephrotoxicity of vancomycin in rabbits.

View full abstract

The rat carboxymethyl cellulose (CMC) pouch, which has the advantage of allowing quantitative evaluation of inflammation, is utilized as an experimental model of infection. We used this model in the assessment of antibiotics against infections with Staphylococcus aureus, and obtained some valuable data. In the CMC pouch with inflammation due to an infection, cefotiam, imipenem/cilastatin and vancomycin attained a higher concentration than the blood concentration, which indicated that all drugs were absorbed well into the pouch.Of the three drugs, vancomycin (VCM) attained the highest pouch concentration relative to its blood level and stayed the longest. In the pouch infected with Staphylococcus aureus Smith, imipenem/cilastatin (IPM/CS) and VCM were equally effective. In that infected with clinically isolated methicillin-resistant S. aureus, VCM was effective, reflecting its minimal inhibitory concentration, while IPM/CS and cefotiam (CTM) produced no effect. The combination of 0.39μg of IPM/CS per ml and 6.25μg CTM per ml, while providing good results with fractional inhibitory concentration index at 0.031 in the drug sensitivity test, did not produce an appreciable effect in the present experimental system. This is probably because it was difficult to maintain the two drugs constantly in such a ratio of concentration as promised a favorable effect, in the local region. Our results also suggest that, in the treatment of MRSA infections, the early use of VCM might produce a therapeutic effect comparable to that against methicillin-sensitive S. aureus. The present experimental model of infection seemed useful as it allows evaluation not only of the effect against the growth of organisms but the effect on the response of the host as well, that is, it allows evaluation of the in vivo effect of the antibiotic.

View full abstract

In order to study the most effective exposure schedules for new quinolones, I examined therelationship between the growth inhibition periods of bacteria and peak and/or maintenanceconcentrations of drugs using an in vitro model of the urinary bladder. The peak concentrations of drugs used were 1, 2, 5, 10, 20, 50, 100×MIC or more against the test organisms, and the maintenance concentrations used were 1/2-2×MIC. Norfloxacin (NFLX), ofloxacin (OFLX) and ciprofloxacin (CPFX) were used as the test drugs, and as the test organisms Escherichia coli (ECSA-1) and Citrobacter freundii (GUT-1) were used. With increases in the peak level of drugs (especially when the concentration was over 10 MIC), growth inhibition time was markedly elongated, and the growth of bacteria was effectively suppressed by the elongation of maintenance level. That is, both peak and maintenance levels were important, resulting in the importance of the combination of such exposure patterns. Under the limitation of drug amounts to 36 or 72 mg, it was found that the best exposure schedule was to keep 1 hour of peak level around 8 MIC and to follow this by a maintenance level around 1 MIC of the drugs. This was superior to using the entire amount of drug to keep the maintenance level.

View full abstract

We inverstigated the concentration of cefminox (CMNX) in the serum and pancreatic juice of 15 patients after intravenous injection of 2g CMNX to evaluate its organ penetration. The results obtained were as follows:
1. The peak concentration of CMNX in serum was 137.3±35.8μg/ml 10 minutes after administration.
2. The peak concentration of CMNX in pancreatic juice was 4.9±2.9μg/ml 20 minutes after administration.
3. High concentrations of CMNX in pancreatic juice were observed even 3 hours after administration.
4. Isolated bacteria in drainaged pancreatic juice were mainly Escherichia coli and Klebsiella pneumoniae, for which the MIC of CMNX were less than 1 μg/ml. Thus CMNX worked well for these bacteria in pancreatic juice.
5. Rates of penetration of CMNX into pancreas with fibrosis were lower than into that without fibrosis.

View full abstract

Continuous and intermittent administrations of vancomycin were performed in 7 and 17 patients, respectively, with methicillin-resistant Staphylococcus aureus (MRSA) infection. Continuous administration was done throughout 24 hours at a dose of 0.5 to 2.5 g for therapy. Intermittent administration was given at a dose of 0.5 to 2, 0g by 1-hour intravenous drip infusion (IVD) divided into one to three times a day. The results were as follows.
(1) Clinical efficacy was the same for both treatments. In the continuous and intermittent administrations of vancomycin, MRSA in the blood was eradicated in 6/6 and 7/8 patients, and in the sputum in 6/7 and 6/14 patients, respectively. The decrement in CRP% occurred earlier with continuous therapy than intermittent therapy.
(2) Plasma levels of vancomycin obtained by continuous administration made therapy easier than those obtained by intermittent therapy.
In conclusion, continuous vancomycin therapy against MRSA infections was more effective than intermittent therapy. This was characterized by rapid onset of efficacy and easy maintenance of adequate plasma level. MRSA infections in compromised hosts would be well suited to this treatment.

View full abstract

We evaluated the effect of prophylactic administration of antibiotics in 80 patients who underwent total abdominal hysterectomy. Patients were randomly selected and allocated to four groups:(A) no antibiotics, (B) one-day administration of piperacillin (PIPC), (C) three-day administration of PIPC or (D) five-day administration of PIPC. Incidence of postoperative in fection, fever index (FI), febrile morbidity (FM) and changes in ESR, WBC, and CRP were examined after surgery. The incidence of postoperative infection in the group without PIPC (55%) was significantly higher than in the other three groups. There was no significant difference in the incidence of postoperative infection in patients who received postoperative PIPC either for one, three or five days. In the group without PIPC administration, there was a significant difference in the value of CRP on the seventh postoperative day between patients with and without postoperative infection. There were no differences in ESR, WBC, FI or FM. Therefore, we conclude that (1) prophylactic administration following total abdominal hysterectomy was essential, (2) three-day administration of PIPC was desirable although one-day administration was useful and (3) CRP was the most efficient indicator of postoperative infection.

View full abstract

A multicenter, double-blind, double-placebo trial was conducted to compare the efficacy and safety of SY 5555, a new oral penem, with cefaclor (CCL) in the management of skin and skin structure infections. Patients, aged more than 15 years, with deep-seated hair structure infections (furuncle, furunculosis, carbuncle), impetigo, deep-seated diffuse infections (erysipelas, cellulitis, lymphangitis, lymphadenitis), and chronic pyodermas (infectious atheroma, hidradenitis suppurativa, miscellaneous abscesses) were enrolled after informed consent had been obtained. Patients assigned to the SY 5555 group received one 200 mg tablet of SY 5555 and one CCL placebo capsule three times a day after meals, and patients assigned to the CCL group received one SY 5555 placebo tablet and one CCL 250 mg capsule three times a day after meals. Patients were treated for 7 days except for those with chronic pyoderma, who were treated for 10 days. Patients were evaluated in terms of clinical efficacy, safety and bacteriologic response. Three hundred twenty-three patients (SY 5555 group, 161 patients; CCL group, 162 patients) were enrolled. The clinical efficacy rates were 89.0%(129/145) for the SY 5555 group and 90.7%(136/150) for the CCL group. Overall general improvement rates on day 5 were 85.9%(110/128) for the SY 5555 group and 81.6%(111/136) for the CCL group. The safety rates were 87.2%(130/149) for the SY 5555 group and 93.5%(143/153) for the CCL group. Adverse reactions were almost all of gastrointestinal origin and were minor in both groups. Abnormal laboratory findings were also all minor in both groups. Bacteriologic response rates were 93.5%(87/93) for the SY 5555 group and 89.8%(79/88) for the CCL group. These differences were not statistically significant. These data suggest that SY 5555 is as effective and safe as CCL in the management of skin and skin structure infections.

View full abstract

Flomoxef (FMOX) and aztreonam (AZT) were used concurrently to treat infections complicated by hematic disease. A total for 102 subjects were evaluated, and the total efficacy rate including “remarkably effective” and “effective” was 69.6%. Acute leukemia was found in the largest number of patients, 49, followed by 14 cases of malignant lymphoma and 10 cases of chronic myelogenous leukemia. By type of infection, patients suspected of having sepsis were the largest in number, being 78, and the efficacy rate was 69.2%. The efficacy rates for sepsis and pneumonia were 66.7%(6 cases) and 57.1%(7 cases), respectively. The efficacy rates by neutrophil count before administration of FMOX and AZT and at 7 days after administration were both 65.5% with doses less than 500/μl, both 53.8%with doses less than 100/μl and both 71.7% with doses more than 500/μl. The efficacy rate was 75.0% in the granulocyte colony stimulatirrg factor (G-CSF) concurrent use group and 68.3% in the non-concurrent use group. Patients whose neutrophil count before administration of the antibiotics was less than 100/μl included 5 cases of 8 (62.5%) in the concurrent use group and 7 cases of 14 (50.0%) in the nonconcurrent use group. As causal bacteria, Staphylococcus strain accounted for 45.5% of infections followed by Pseudomonas strain. The blood level of G-CSF reflected the severity of inflammation and was correlated with CRP. Concurrent treatment with FMOX and AZT exhibited a high level of safety in infections complicated by hematic disease and showed high efficacy rates.

View full abstract