Five clinical areas were defined as research subjects for the Piperacillin Research Group (Chairman, YASUSHI UEDA, The Jikei University School of Medicine) which was founded in June 1985. For bacteriological investigation, clinical isolates were collected from the following subject areas:(1) infections associated with tumors, (2) combination therapy of piperacillin with aminoglycosides in intractable respiratory tract infections, (3) combination therapy in abdominal surgery, (4) prophylactic chemotherapy in urology and (5) burns in emergency medicine. The minimal inhibitory concentrations (MIC) of PIPC against the isolates thus collected, including strains obtained directly from patients, were determined and compared with the results of similar studies which were then presented at the New Drug symposium of the 23 rd Eastern Congress of the Japanese Society of Chemotherapy held in November, 1976.
1) No appreciable differences were observed between the new and old data regarding MIC₅₀and MIC₈₀of PIPC againstE. faecalis, E. coli, K. pneumoniae, Enterobacter spp., P. aeruginosa, H. influenzaeandBacteroidesspp., when cultured with an inoculum size of 10⁶cfu/ml. AgainstS. aureus, however, MIC₅₀and MIC₈₀havc changed greatly over the years, from 1.56μg/ml to 50μg/ml and from 6.25μg/ml to>100μg/ml, repectively.
2) Strains ofS. aureushighly resistant to penicillins (PCs) were frequently detected in this study. The results of further investigation showed most of these to be methicillin-resistantS. aureus (MRS A).
3) We confirmed that PIPC is retaining its antimicrobial activity against the major clinical isolates except for MRSA even today in the late 1980's.

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A multi-center study was carried out to evaluate clinical efficacy and safety in treatment with Piperacillin (PIPC) for infections accompanying tumors of the hematopoietic organs and cancers by the Piperacillin Research group, which was founded in June 1985 (Chairman: YASUSHI UEDA, The Jikeikai University School of Medicine).
1) There are few cases in which malignant hematological disorders have been treated with PIPC alone, therapy combining PIPC with other antibiotics having been used in most cases. Aminoglycosides, in particular are most often used as the combination therapy. PIPC, combination therapies with two or three agents, including aminoglycosides, amounted to 56.9%(140/240) in the above cases, while single administration of PIPC was 76.0%(24/34) in cases of cancer.
2) Efficacy rates were 61.0% against respiratory tract infections, 58.0% against septicemia, 50.6% against suspected septicemia and 44.0% against other infections. As a whole, the efficacy rate was 53.8% of 314 cases.
3) As to the relation between efficacy rate and the number of granulocytes before and after treatment, cases having≤100/mm³, >100-<500/mm³and≥500/mm³after treatment amounted to 39%, 57.4%, and 60.3%, respectively. The efficacy rate was lower in cases with granulocytes of≤100/mm³after treatment.

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Chemotherapy with mainly Piperacillin (PIPC) was performed in total of 54 cases of patients with infections associated with burns or for prevention of infections, and its efficacy as well as safety were investigated in 11 medical institutions throughout Japan. At the same time, criteria for evaluating clinical efficacy were drawn up. Changes in blood PIPC concentrations and transfer into vesicles in burn patients were also investigated.
1. Changes in blood PIPC concentrations in burn patients, unlike those in healthy adults, decr eased sharply after termination of administration. PIPC concentrations in vesicular fluid revealed possible effect of the drug in infections associated with burns.
2. The secondary infections included mainly sepsis and wound infections. The wider the burn areas, the severer were the infections, and consequently the efficacy ratio was found to be low in these patients.
3. There were 43 cases of infections associated with burn and 11 cases where PIPC was used to prevent infection. The efficacy ratio evaluated by the attending physicians was 35.0% and 44.4%, respectively, whereas-evaluated by the proposed evaluation criteria it was 38.5% and 88.9%, respectively. The efflcacy ratio evaluated by proposed evaluation criteria was 53.3% in PIPC alone, 29.2% in combined with another antibiotics in 43 cases of infections, respectively.
4. In the 79 strains of causal bacteria, S. aureus (19 strains, 24.1%) andP. aeruginosa (13 strains, 16.5%) were most frequently isolated.

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The prophylactic effect of piperacillin (PIPC) on postoperative infection following prostatectomy was compared with that of second generation cephems (CEPs II).
Two grams of PIPC or 1-2g of CEPs II were given twice a day for 5 days from the morning of the operation day, and effects of these drugs were evaluated using such indicators as the incidence of postoperative infection, fever index and febrile morbidity. A total of 145 patients without urinary tract infection before operation were used as subjects; 71, 46 and 28 of the patients were included in the PIPC 4g group, the CEPs II 2g group and the CEPs II 4g group, respectively. Of these 87.6% had undargone transurethral prostatectomy.
Postoperative infection occurred in 8.5% of the PIPC 4g group, 6.5% of the CEPs II 2g group, and 3.6% of the CEPs it 4g group, showing no significant differences among the 3 groups. Of 10 patients who developed postoperative infection, 9 had urinary tract infection, and the remaining one had epididymitis. None suffered from serious infection, such as septicemia. Although background factors were investigated in those patients with postoperative infection, no apparent risk factors in postoperative infection could be defined. When the prophylactic effect on postoperative infection was evauatedl (based on the overall results of the fever index, febrile morbidity, peripheral white blood cell counts and CRP, and the incidence of postoperative infection) clinical responses was obtained in 89.9% of the PIPC 4g group, 87.0% of the CEPs II 2g group and 89.3% in the CEPs II 4g group, showing no significant differences among the 3 groups. There were also no intergroup differences in the incidence of side effects. Based on these results, the prophylactic effect of piperacillin on postoperative infection following prostatectomy was thought to be almost equal to that of second-generation cephems.

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Since combined use of piperacillin (PIPC) and aminoglycosides (AGs) shows a synergistic effectin vitro, a clinical examination of this combination therapy was carried out from August 1985 to January 1987 by a well controlled study. Drugs were administered at 4 g daily of PIPC alone, 120 mg of tobramycin (TOB) combined with 4 g of PIPC, or 200mg netilmicin (NTL) combined with 4 g of PIPC.
1. The clinical efficacy rates in all cases evaluated by the attending committee members were 66.0 in PIPC alone, 73.3% in PIPC combined with TOB, and 71.7% in PIPC combined with NTL, respectively. No significant difference was observed between PIPC alone and PIPC combined with AGs.
There was also no significant difference in clinical effect between PIPC alone and PIPC combined with AGs evaluated by the committee members, in patients with pneumonia or pulmonary suppuration, and with chronic respiratory tract infection.
2. Bacteriological respose against causative organisms in all cases tends to be significantly superior in PIPC combined with AGs than in single use of PIPC. Particularly in infections due toPseudomonas aeruginosa, the eradication rate was much superior. 20% in PIPC alone but 56% in PIPC combined with AGs.
3. There was no significant difference between PIPC alone and combined PIPC with regard to side effects or abnormality in laboratory findings.
4. There was no significant difference in usefulness between single use of PIPC and combined PIPC as evaluated by the committee members.
In conclusion, we consider that combination therapy of PIPC with AGs was more effective than PIPC alone, particularly in treating chronic respiratory tract infections due toP. aeruginosa, and was just as safe.

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A well-controlled comparative study was performed to evaluate the efficacy, safety and utility of combination therapy of piperacillin (PIPC) and netilmicin (NTL) in the treatment of purulent peritonitis. 1. The clinical efficacy rate was 71.6% (48/68) in the PIPC group and 66.2% (43/66) in the PIPC+NTL group.
2. The final overall clinical improvement rate was 91.2% (62/68) in the PIPC group and 83.3% (55/66) in the PIPC+NTL group, with no statistically significant difference between the two groups.
3. As for bacteriological effect; the eradication rate was 94.7% (36/38) in the PIPC group and 92.0% (46/50) in the PIPC+NTL group, with no satistically significant difference between the two groups.
4. Side effects were observed in 1 of 66 patients (1.5%) in the PIPC+NTL group, whereas abnormal laboratory fndings were observed in 9 of 68 patients (13.2%) in the PIPC group and 9 of 66 patients (13.6%) in the PIPC+NTL group. In the incidence of adverse effects and abnormal laboratory findings, there was no statistically significant difference between the two groups.
5. Overall clinical utility was 62.1% (41/66) in the PIPC group and 65.6% (42/64) in the PIPC+NTL group, with no satistically significant difference between the two groups.

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