The efficacy, safety and usefulness of tazobactam/piperacillin (TAZ/PIPC), in bacterial pneumonia and lung abscess were determined with PIPC as the control in a multi-institutional comparative study a penicillin antibiotic for injection prepared by combining a newly developed β-lactamase inhibitor, tazobactam (TAZ), with a broad spectrum penicillin antibiotic, piperacillin (PIPC), at a ratio of 1: 4.
TAZ/PIPC was intravenously injected at a dose of 2.5 g (titer) twice a day, and PIPC at a dose of 2.0 g (titer) twice a day as a rule for 14 days.
The following results were obtained:
1. The efficacy rates for bacterial pneumonia and lung abscess were 94% (80/85) in TAZ/PIPC group and 89% (70/79) in PIPC group, showing no significant difference between the twogroups.
2. In a comparison of degrees of improvement in clinical symptoms, signs and laboratory findings, there were no significant differences between the two groups except for results on thoracic rales after three days of administration.
3. As for bacteriological effects, the elimination rates of causative organisms were 98% (40/41) in the TAZ/PIPC group and 80% (28/35) in the PIPC group. Thus, the TAZ/PIPC group was significantly superior to the PIPC group. The TAZ/PIPC group showed significantly better eradication of bacateria as well. Bacteria considered to be pyogenic were detected in 80 patients (43 administered TAZ/PIPC and 37 administered PIPC), but β-lactamase production was confirmed in only 11 patients of each group. There were no significant differences in bacteriological effects among these patients. Minimum inhibitory concentrations of TAZ/PIPC against β-lactamase producing organisms were distinctly superior to those of PIPC.
4. Side effects occurred in 10% (10/96) of the TAZ/PIPC group and 7% (7/95) of the PIPC group. Abnormal clinical laboratory test values were observed in 22% (20/92) of the TAZ/PIPC group and 18% (17/93) of the PIPC group. Thus, there were no significant differences between the two administration groups.
5. The usefulness rate in the TAZ/PIPC group was 87% (75/86) and it was 85% (67/79) in the PIPC group, showing no significant difference between them.
The results suggest that TAZ/PIPC administered at a dose of 2.5 g (titer) twice a day is more useful than PIPC administered at a dose of 2.0g (titer) twice a day in the treatment of bacterial pneumonia.

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The efficacy, safety and usefulness were evaluated for a combined antibiotic tazobactam/ piperacillin (TAZ/PIPC) consisting of a new β-lactamase inhibitor, tazobactam (TAZ), and a broad spectrum penicillin antibiotic, piperacillin (PIPC), in chronic respiratory tract infections with PIPC as the control in a multi-institutional comparative study.
The drugs used were a preparation containing 0.5 g of TAZ and 2.0 g of PIPC per vial (TAZ/PIPC group) and a preparation containing 2.0 g of (PIPC group). The drugs were intravenously injected one vial at a time twice a day for 14 days as a rule.
The following results were obtained:
1. Clinical effect
There was no significant difference between TAZ/PIPC (86% or 76/88) and PIPC (81% or 69/85).
2. Bacteriological effect
There was no significant difference between TAZ/PIPC (93% or 42/45) and PIPC (88% or 36/41) in terms of bacterial eradication rates. In 34 patients with β-lactamase-producing pyogenic bacteria, there was no significant difference between TAZ/PIPC (77% or 10/13) and PIPC (88% or 15/17).
3. Degrees of improvement in clinical symptoms, signs and laboratory findings
The TAZ/PIPC group was likely to show reductions in fever and the amount of sputum soon after administration.
4. Side effects
Incidences of side effects were 7% (7/96) in the TAZ/PIPC group and 3% (3/89) in the PIPC group, showing no significant difference between the two groups. The main symptoms were allergic reaction and gastrointestinal symptoms.
5. Abnormal clinical laboratory test values
The incidence was 17% (15/89) in the TAZ/PIPC group and 21% (18/87) in the PIPC group. The main symptoms were eosinophilia and hepatic dysfunction, and most of these symptoms were mild.
6. Usefulness
The usefulness rates in the TAZ/PIPC group were 80% (71/89) and 78% (66/85) in the PIPC group, showing no significant difference.
Thus, TAZ/PIPC exhibited excellent clinical effects and presented no troubles with safety. When comprehensively evaluated, TAZ/PIPC appears to be a very useful drug for the treatment of chronic respiratory tract infections.

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A combination antibacterial therapy with fosfomycin (FOM) and sulbactam/cefoperazone (SBT/CPZ) was applied to 78 patients with severe infections associated with hematological diseases. In this protocol, FOM was followed by SBT/CPZ and each drug was administered for 1 hour intravenously and consecutively.
Among 72 evaluable patients, 43 patients had acute leukemia, myeloblastic or lymphoblastic, 22 had malignant lymphoma, 3 had multiple myeloma, and 4 had other hematological diseases as underlying diseases. Bacterial infections diagnosed were sepsis in 21 patients, suspected sepsis in 47, and other infections in 4.
The overall efficacy rate of this treatment was 72.2%, and those for individual infections were 66.7% for sepsis, 74.5% for suspected sepsis, and 75.0% for other infectious diseases. Among 22 bacteria separated from patients with sepsis, 78.6% (11/14 strains) were eradicated by this treatment. This protocol was also effective in 57.1 % (8/14) of patients whose granulocyte count was less than 100/mm3 during the course of treatment as well as in 83.3% (15/18) of patients with granulocyte count over 500/mm3. There was no difference in effectiveness between those patients to whom G-CSF was administrated and those to whom it was not (17/24, 70.8% vs 35/48, 72.9%). As an adverse reaction, a transient increase of GOT and/or GPT was observed in 2 patients (2.8%).
The consecutive administration treatment of FOM and SBT/CPZ is thus an effective and safe regimen for the treatment of patients with hematological diseases complicated by severe infections.

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The clinical usefulness of cefpodoxime proxetil (CPDX-PR) was investigated in the treatment of pneumonia and chronic airway infections occurring in patients first visiting our outpatient clinic or those being treated at the outpatient clinic.
CPDX-PR was orally administered twice a day after meals at a dose of 100-200 mg for acute respiratory tract infections and at a dose of 200 mg for chronic respiratory tract infections.
Excellent, good, fair, and poor responses were observed in 20, 33, 10, and 3 of 66 patients (4 with acute bronchitis, 27 with pneumonia, and 35 with acute exacerbation of chronic airway infection), respectively, demonstrating an 80.3% efficacy rate (53/66). Causative organisms, including Streptococcus pneumoniae, were all eradicated from the patients whose causative organisms were examined over time, although 2 of the patients were superinfected with Pseudomonas aerugi-nosa. There were no serious adverse reactions or abnormal changes in laboratory test results.
It was concluded that CPDX-PR could be used as a first-choice drug for the treatment of respiratory tract infections at an outpatient clinic, and that this drug should acquire greater importance in particular consideration of recent increases in infections with S. pneumoniae.

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Antimicrobial activities were examined for sulbactam/ampicillin (SBT/ABPC) against clinically isolated microbial strains in 1987, 1990, 1994. Besides, the β-lactamase productivity and MICs of these strains were measured, and the following conclusions were obtained.
1. The ratio of β-lactamase producing strains were 90% of methicillin (DMPPC)-susceptible Staphylococcus aureus subsp. aureus (MSSA), about 80% of DMPPC-resistant S. aureus (MRSA), 100% of Escherichia coli,Klebsiella pneumoniae subsp. pneumoniae and Proteus mirabilis, 95% of Moraxella subgenus Branhamella catarrhalis and 15-20% of Haemophilus influenzae. Several kinds of β-lactamase productivity were observed.
2. Antimicrobial activities of SBT/ABPC against β-lactamase producing strains of MSSA, M.(B.) catarrhalis, H. influenzae, and almost all of Enterobacteriaceae were stronger than those of ampicillin (ABPC) and piperacillin (PIPC), but antimicrobial activities of SBT/ABPC were weak against MRSA and cephems (CEPs)-resistant strains detected in some of Enterobacteriaceae.
3. It appeared that benzylpenicillin (PCG)-insensitive Streptococcus pneumoniae(PISP) or PCG-resistant S. pneumoniae (PRSP) and CEPs-resistant Escherichia coli increased year by year.
4. Antimicrobial activities of SBT/ABPC were strong against Streptococcus pyogenes,S. pneumoniae,M.(B.) catarrhalis and H. influenzae including β-lactamase producing strains. Additionally, β-lactamase inhibiting effect of SBT was observed against β-lactamase produced by S. aureus and K. pneumoniae which demonstrate indirect pathogenicity. Thus, SBT/ABPC is an injectable antibiotic that is expected to demonstrate clinical usefulness, especially as the first line drug for the respiratory tract infections that are community-acquired.

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Postantibiotic effects (PAE's) of macrolide antibiotics were determined for Staphylococcus aureus and Enterococcus faecalis using viable counting and Bioscreen C method and the two methods were compared.
No major differences between the two methods were observed. The Bioscreen C method was less laborious than the viable counting.
The durations of PAE for S. aureus following exposures to erythromycin (EM), josamycin (JM) and rokitamycin (RKM) for 2 hours at twice the MICs were in ranges of 0.85 to 1.45, 2.36 to 3.48 and 1.93 to 5.45 hours, respectively.
A definite PAE of 1.0 to 5.8 hou rs was also observed in E. faecalis strains exposed for 2 hours to EM, JM and RKM at twice the MICs.

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The in vitro antimicrobial activity of cephamycin, e.g. cefmetazole and cephalosporin, such as cefazolin, cefotiam, cefamandole and cefoperazone, alone and in combination, was studied employing 9 strains of methicillin-sensitive Staphylococcus aureus (MSSA) and 30 strains of methicillin-resistant Staphylococcus aureus (MRSA). Using the checkerboard agar dilution method, strong synergism was demonstrable in a majority of MSSA and MRSA strains for cefmetazole combined with these cephalosporins, with the minimum fractional inhibitory concentration index ≤0.5.
In the presence of a concentration ≤6.25μg/ml of these cephalosporins in Mueller-Hinton agar medium, the activity of cefmetazole against MRSA was most prominently potentiated by cefotiam, followed by cefamandole, cefazolin and cefoperazone. At a concentration of 12.5 μg/ml, cefotiam and cefamandole showed a similar effect in potentiation of cefmetazole activity.
In hypertonic agar medium containing 4% NaCl, these synergistic combination effects were reduced. However, the activity of cefmetazole and cefamandole in combination under these conditions was influenced to a lesser extent and more potent than that of other combinations.

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The inoculum effect was studied on the activity of cefmetazole and cefotiam, cefamandole or cefoperazone alone and in combination against 9 strains of methicillin-sensitive Staphylococcus aureus (MSSA) and 20 strains of.methicillin-resistant Staphylococcus aureus (MRSA) by mean of the checkerboard titration method with Mueller-Hinton agar plate using 10⁶ and 10⁸ CFU/ml.
The antimicrobial activity against MSSA and MRSA was potentiated synergistically in combination of cefmetazole and these cephalosporins either with inoculum size 10⁶ or 10⁸ CFU/ml. At a concentration of cephalosporins ≤6.25μg/ml, the combination effect of cefmetazole and cefotiam or cefamandole against MRSA was more potent than that of cefmetazole and cefoperazone. With a higher inoculum size the effect was reduced. Under these conditions with a low dose level of drugs, the enhancement of the activity of cefmetazole by cefotiam was least influenced by inoculum size among cephalosporins studied.

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In order to evaluate the antimicrobial activity of piperacillin (PIPC), along with control agents, minimum inhibitory concentrations (MIC's) were determined against fresh clinically isolated strains from January to June, 1994.
1. The MIC₇₀'s of PIPC against major strains were approximately equal to those reported in the mid 1980s.
2. Strains for the study were supplied in approximately equal numbers from communityacquired hospitals and general hospitals. The ratios of bacteria resistant to β-lactams including PIPC were low in the former group and high in the latter.
3. “New types of, β-lactam-resistant strains” which did not exist in mid 1980s but found at this time included benzylpenicillin (PCG)-insensitive Streptococcus pneumoniae, PCG-resistant S. pneumoniae, cephems-resistant Escherichia coli and β-lactamase producing Prevotella spp. These bacteria were also found among strains obtained from community-acquired hospitals.

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