CHEMOTHERAPY

COMBINATIONS OF THREE ANTIMICROBIAL AGENTS (I)

EXPERIMENTAL THREE-DIMENSIONAL CHECKERBOARD DILUTION METHOD FOR QUANTITATIVE ANALYSIS OF THE IN VITRO COMBINED EFFECT OF THREE ANTIMICROBIAL AGENTS

AKIRA WATANABE, KOTARO OIZUMI, KIYOSHI KONNO

1988 Volume 36 Issue 9 Pages 613-616
Published: September 25, 1988
Released on J-STAGE: August 04, 2011

DOIhttps://doi.org/10.11250/chemotherapy1953.36.9_613

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We have established an experimental three-dimensional checkerboard dilution method for quantitative analysis of the in vitro combined effect of three antimicrobial agents. We designed this method through a modification of the checkerboard dilution method used for two antimicrobial agents. In this experiment, we used a micro-broth dilution method using the Dynatech MIC-2000 system. A two-fold serial dilution of a third agent was added to the checkerboard containing the first and second agents. Then, 0.0015 ml of a bacterial suspension was inoculated and incubated for 24 hours at 37°C. The results obtained were plotted on a three-dimensional cubic graph so as to describe a spherical surface, and the volume under the surface (VUS) was calculated. By comparing the VUS, with the relative proportion of the three agents fixed at a certain ratio, it was possible to compare the efficacy of triple antimicrobial combinations. For example, by application of the three-dimensional checkerboard method, we could evaluate the effect of the combination of a combined agent with a single agent, or the combination of equal amounts of three agents.

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STUDIES ON THE PATHOGENICITY OF ENTEROCOCCUS FAECALIS

E XPERIMENTAL ASCENDING PYELONEPHRITIS IN NON-TREATED AND DIABETIC MICE

GAKU KAWABATA, SOICHI ARAKAWA, SADAO KAMIDONO

1988 Volume 36 Issue 9 Pages 617-631
Published: September 25, 1988
Released on J-STAGE: August 04, 2011

DOIhttps://doi.org/10.11250/chemotherapy1953.36.9_617

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We experimentally investigated the pathogenicity of clinically isolated Enterococcus faecalis (E. faecalis) in urinary tract of non-treated and diabetic mice. The results are summarized as follows.
(1) In vitro, new pyridonecarbonic acids (CPFX, OFLX, ENX and NFLX) were most effective against 23 clinically isolated strains of E. faecalis, followed by ST, MINO, ABPC and IPM/CS. Most of the isolates showed high resistance to cephems.
(2) In non-treated mice, ascending pyelonephritis occurred with 9 of 11 E. faecalis strains tested. These strains showed similar pathogenicity (ID₅₀) compared with four standard Gram-negative species.
(3) In streptozotocin-induced diabetic mice, ascending pyelonephritis occurred with 5 of 5 E. faecalis strains tested and values of ID₅₀ were 1/1.3-1/477 of those in non-treated mice.
(4) As to drug efficacy against experimental ascending pyelonephritis in non-treated mice, CPFX was most effective, followed by OFLX, MINO and ENX.
(5) Against experimental ascending pyelonephritis in streptozotocin-induced diabetic mice, ABPC was most effective, followed by CPFX, MINO and ENX; a longer administration period was necessary to eradicate E. faecalis than in non-treated mice.

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PENETRATION OF ANTIBIOTICS INTO INFLAMMATION FOCI

KIHACHIRO SHIMIZU, TEPPEI KUMADA, KYOICHI TOTSUKA, JUNICHI KATAHIRA, T ...

1988 Volume 36 Issue 9 Pages 632-639
Published: September 25, 1988
Released on J-STAGE: August 04, 2011

DOIhttps://doi.org/10.11250/chemotherapy1953.36.9_632

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It is known that serum protein binding is an important factor in the penetration of antibiotics into inflammation foci. In order to examine antibiotic penetration, tissue cages were prepared on the back of rabbits, which are similar to man in their protein binding rate of antibiotics.
As a result, it was thought that the free antibiotic around the inflammation focus (or cage) penetrated into the cage.
Since the antibiotic was administered by drip infusion, the free concentration of antibiotic around the inflammation focus was thought to be almost in equilibrium with that in serum.
The velocity of drug penetration into the inflammation focus was nearly proportionate to the free antibiotic concentration in serum.
Since the penetration of antibiotics into an inflammation focus is dependent on their free concentration in serum, it is important to maintain a high free antibiotic concentration in serum for maximum drug efficacy.

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NETILMICIN CONCENTRATION IN THE NASAL CAVITY DURING NASAL AEROSOL THERAPY

TAKESHI SHIBAHARA, MAYUMI SHOSHIHARA, MINORU ISHIDA

1988 Volume 36 Issue 9 Pages 640-644
Published: September 25, 1988
Released on J-STAGE: August 04, 2011

DOIhttps://doi.org/10.11250/chemotherapy1953.36.9_640

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We determined netilmicin (NTL) concentrations in the nasal cavity of patients on aerosol therapy.
Since aminoglycoside antibiotics (AGs) have a relatively low distribution in the nasal mucosa, it is difficult to evaluate the efficacy of aerosol therapy from the AG concentration. We therefore tried to determine NTL concentration after aerosol administration in gauze (1cm²) placed in the nasal cavity. Though difficult, since AGs are strongly adsorbed to cellulose, quantitative analysis by bioassay and HPLC, using 0.5 M Na₂HPO₄ as extraction solvent, was well controlled.
We determined NTL in 76 samples from 25 patients with paranasal sinusitis by bioassay and HPLC. Both assay data agreed closely, and the coefficient of correlation was 0.963.
As it was possible to determine the concentration of NTL in the nasal cavity after aerosol administration, these data are a useful parameter in investigating the efficacy of aerosol therapy.

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MECHANISM OF RENAL EXCRETION OF NY-198, A NEW PYRIDONECARBOXYLIC ACID ANTIMICROBIAL AGENT, IN RABBITS AND DOGS

MASUHISA NAKAMURA, TOMOJI KAWABATA, TAKAKO ITOH

1988 Volume 36 Issue 9 Pages 645-651
Published: September 25, 1988
Released on J-STAGE: August 04, 2011

DOIhttps://doi.org/10.11250/chemotherapy1953.36.9_645

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We studied the mechanism of renal excretion of NY-198 in rabbits by renal clearance methods and in beagles by stop-flow analysis. In rabbits, renal clearance of NY-198 was approximately 2.2-fold that of creatinine, which corresponded to 60% of that of PAH (p-aminohippuric acid). With administration of probenecid, the clearance ratio was reduced by 1.1. This observation suggests that NY-198 secretion occurs in the proximal portion of the renal tubules. In dogs, the stop-flow pattern of NY-198 showed no peak corresponding to the PAH location but did show a trough at the distal portion of the tubules. These results indicate that there is reabsorption but no secretion of NY-198 in canine renal tubules. Thus, renal excretion of NY-198 differed with the animal species.

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OFLOXACIN TREATMENT OF ACUTE PNEUMONIA IN OUTPATIENTS

NORIO KIKUCHI, IKUSHI ONOZAKI

1988 Volume 36 Issue 9 Pages 652-656
Published: September 25, 1988
Released on J-STAGE: August 04, 2011

DOIhttps://doi.org/10.11250/chemotherapy1953.36.9_652

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The clinical efficacy of ofloxacin (OFLX) was investigated in 47 outpatients and 8 inpatients with mild or moderate pneumonia from October 1985 to December 1987.
Chronic respiratory disease was present in 40% of the patients, whose mean age was 43.4 years old. Etiological organisms were determined in 20 cases. The organisms included H. influenzae (13), S. pneumoniae (3), M. pneumoniae (2), C. psittaci (2).
OFLX was given orally at 200 mg three times per day, and the duration of treatment was from five to twenty-five days (mean: 11.7). Fifty-three patients (96.4%) were cured, one showed improvement and another no improvement. Side-effects were noted in 3 patients (0.55%), eruption in 2 and nausea in 1.
All three cases of pneumococcal pneumonia were mild and treated successfully with OFLX, as were two cases of mycoplasmal pneumonia. Of two cases of psittacosis treated with OFLX soon after onset, one was cured and the other showed improvement.
We conclude that ofloxacin is very useful in the treatment of acute pneumonia in outpatients.

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[title in Japanese]

1988 Volume 36 Issue 9 Pages 657-683
Published: September 25, 1988
Released on J-STAGE: August 04, 2011

DOIhttps://doi.org/10.11250/chemotherapy1953.36.9_657

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