Biomedical subjects

T Uete

Publications and source records attributed to T Uete.

At least 19 recordsLinked to original sources

PubMed1995

Synergistic enhancement of in vitro antimicrobial activity of imipenem and cefazolin, cephalothin, cefotiam, cefamandole or cefoperazone in combination against methicillin-sensitive and -resistant Staphylococcus aureus.

Synergistic enhancement of the in vitro antimicrobial activity of imipenem combined with cephalosporins against methicillin-resistant Staphylococcus aureus (MRSA) has been reported. In order to investigate which cephalosporin is more effective in enhancing the activity of imipenem against MRSA, the in vitro antimicrobial activities of imipenem, cefazolin, cephalothin, cefotiam, cefamandole and cefoperazone, alone and in combination, against methicillin-sensitive Staphylococcus aureus (MSSA) and MRSA were assessed. Using the checkerboard Mueller-Hinton agar dilution method, strong synergy was found in 97% to 100% of MRSA strains for imipenem and all tested cephalosporins except cefoperazone; fractional inhibitory concentration (FIC) indices were < or = 0.5. Among the cephalosporins studied, cefamandole most markedly increased the activity of imipenem against MRSA, followed, in order of decreasing effect, by cefotiam, cephalothin, cefazolin, and cefoperazone. The synergistic effect of imipenem combined with cefamandole or cefotiam was confirmed using the broth dilution method with 2% of NaCl.

Cefamandole↗

PubMed1995

Synergistic enhancement of in vitro antimicrobial activity of cefmetazole and cefazolin, cefotiam, cefamandole or cefoperazone in combination against methicillin-sensitive and -resistant Staphylococcus aureus. I. Effect of NaCl.

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 < or = 0.5. In the presence of a concentration < or = 6.25 micrograms/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 micrograms/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.

Cefamandole↗

PubMed1995

Synergistic enhancement of in vitro antimicrobial activity of cefmetazole and cefotiam, cefamandole or cefoperazone in combination against methicillin-sensitive and -resistant Staphylococcus aureus. II. Effect of inoculum size.

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 means of the checkerboard titration method with Mueller-Hinton agar plate using 10(6) and 10(8) CFU/ml. The antimicrobial activity against MSSA and MRSA was potentiated synergistically in combination of cefmetazole and these cephalosporins either with inoculum size 10(6) or 10(8) CFU/ml. At a concentration of cephalosporins < or = 6.25 micrograms/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.

Bacteriological Techniques↗

PubMed1994

[Clinical laboratory approach to evaluate administration dose of arbekacin. Reevaluation of in vitro MIC break points in the disk susceptibility test].

Antimicrobial activities of arbekacin (ABK) against various clinical isolates, 335 strains obtained in 1991, were determined and the reliability of the ABK disk susceptibility test in estimating approximate values of MICs was studied. In addition, clinical significance of two different systems for the interpretation of the disk tests was evaluated as to which system would be more useful for the evaluation of clinical efficacy of ABK. The 4 category system used in Japan, and the system proposed by the Japanese Society for Antimicrobial Chemotherapy were studied. In this study, MICs were determined using the Mueller-Hinton agar containing 50 mg/L of Ca and 25 mg/L of Mg at an inoculum level of 10(6) CFU/ml. MIC90 values of ABK against Staphylococcus aureus (MSSA and MRSA) and Staphylococcus epidermidis were both 3.13 micrograms/ml. Those against Escherichia coli, Klebsiella pneumoniae, Proteus mirabilis and Proteus vulgaris, Enterobacter spp., and Citrobacter spp., were also < or = 3.13 micrograms/ml. MIC90 values against Pseudomonas aeruginosa and Serratia spp. were both 50 micrograms/ml. The disk susceptibility test was carried out according to the instruction in the Showa disk manual. The inhibition zones obtained with the disk method were compared with MICs. Results of ABK disk susceptibility test with 30, 10, 5 or 2 micrograms disks were well correlated with MICs, showing the reliability of the disk method in estimating approximate values of MICs (r = -0.627 approximately -0.724, P < 0.01). In the 4 category classification system currently used, break points in MIC values of ABK proposed are (+ + +) MIC < 3 micrograms/ml, (++) MIC > 3-10 micrograms/ml, (+) MIC > 10-50 micrograms/ml and (-) MIC > 50 micrograms/ml. The results obtained with Showa 30 micrograms disks showed false positive in 13.4%, and false negative in 3.9% of the samples. With 10 micrograms disks, false positive and false negative were 8.1%, and 3.9%, respectively. Similarly, those with 5 micrograms and 2 micrograms disks were 6.9% and 7.2%, and 3.0% and 14.6%, respectively. In the break point classification system of Japanese Society for Antimicrobial Chemotherapy, the MIC break point for ABK proposed is 2 micrograms/ml. It appeared to be difficult to make out this break point on the inhibition zone diameters obtained with various disks used, since there were no significant difference in the inhibition zone diameters against strains with MIC values ranging 0.39-3.13 micrograms/ml. A pharmacokinetic examination with the recommended dose schedule for ABK (100 mg i.m. or i.v.) showed that plasma levels of ABK reached 3.7-11.3 micrograms/ml.(ABSTRACT TRUNCATED AT 400 WORDS)

Aminoglycosides↗

PubMed1993

[Enhancement of in vitro antimicrobial activity of cefmetazole and cefazolin in combination against methicillin-resistant Staphylococcus aureus studies by checkerboard MIC method and disc diffusion method using discs containing both drugs].

Antimicrobial activities of cefmetazole (CMZ) and cefazolin (CEZ) in combination were studied against clinical isolates of Staphylococcus aureus (9 methicillin-sensitive and 47 methicillin-resistant strains) using the checkerboard MIC method and the disc diffusion test using Mueller-Hinton agar with or without addition of 4% NaCl. MICs of CMZ and CEZ individually against 9 methicillin-sensitive strains (MSSA) were 0.78-1.56 micrograms/ml and 0.39-0.78 micrograms/ml without 4% NaCl, and 1.56-3.13 micrograms/ml and 0.39-0.78 micrograms/ml with 4% NaCl, respectively. In combination of CMZ and CEZ, the MICs of CMZ and CEZ against these MSSA decreased to 0.012-0.39 micrograms/ml and 0.10-0.20 micrograms/ml without 4% NaCl, and 0.20-0.78 micrograms/ml and 0.20-0.39 micrograms/ml with 4% NaCl, respectively, showing minimum FIC indexes of 0.385 to 1.013. Minimum FIC indexes < or = 0.5 were seen in 7 out of 9 strains. MICs of CMZ and CEZ individually against 47 methicillin-resistant strains (MRSA) were 3.13-100 micrograms/ml and 3.13-400 micrograms/ml without 4% NaCl, and 6.25-50 micrograms/ml and 50-400 micrograms/ml with 4% NaCl, respectively. In combination of CMZ and CEZ, MICs of these drugs against MRSA were reduced to 0.10-50 micrograms/ml and 0.39-200 micrograms/ml without addition of 4% NaCl and 0.39-12.5 micrograms/ml and 3.13-100 micrograms/ml with 4% NaCl, respectively. Minimum FIC indexes observed were 0.047 to 0.625, and those with values < or = 0.5 were observed in 43 out of 47 strains. By the disc diffusion method, between the CMZ disc and CEZ disc, a synergistic interaction against MRSA was well observed. In addition, discs containing both drugs showed a greater inhibitory zone diameter than discs containing the equivalent amount of CMZ or CEZ alone. These in vitro observations reported here suggest that the use of CMZ and CEZ in combination is more effective than the use of these drugs individually for the treatment of MSSA and slight to moderate resistant MRSA infection, as well as for surgical prophylaxis. Therefore, further study was carried out to assess the synergistic enhancement of antimicrobial activity of CMZ and CEZ in combination using discs containing various amounts of these drugs at various ratios. Using discs containing CMZ/CEZ (20 micrograms/10 micrograms), disc inhibitory zone diameters against MSSA and MRSA were well correlated negatively with MICs of CMZ or CEZ in combination. From inhibitory zone diameters obtained with these combination discs, enhanced MICs of CMZ or CEZ in combination can be assessed.

Cefazolin↗

PubMed1993

[In vitro MIC break point for appropriate clinical use of antibiotic].

In vitro antimicrobial susceptibility tests can play an essential role in clinical management of infectious diseases, and in vitro MIC break point is important in choice of antibiotic. Standardization of method for measuring MIC is necessary, if break points are to be fixed internationally. However, it is difficult to settle on uniform international break points, since standard doses of antibiotics and the preferred routes of administration differ in different parts of the world. With respect to in vitro MIC break points, the NCCLS system is used in the U.S.A., and in Japan, Showa disc system and the NCCLS system are both used. In Europe 6 different systems are utilized (BSAC, DIN, SFM, SIR, NCCLS, and WRG). There is a certain degree of similarity between different concentration values used to define break points in these systems. In general, however, the BSAC and DIN systems recommend lower break points and the NCCLS and SFM systems higher break points. The MIC values of the break points, +3 and +2 categories of Showa 4 category classification system (+3, +2, +, -) used in Japan, are similar to those of the BSAC system. Higher ratio of positive responses to bactericidal antibiotic therapies have been reported when ratios of peak concentrations of drugs in plasma/in vitro MIC are increased, and maximum responses are obtained when the ratio reaches about 8 in cases with aminoglycosides and beta-lactams. In neutropenic compromised patients, drug concentrations with ratios higher than 8 to 10 may be required to treat infections. Drug availabilities are different depending on drugs and sites of infections. Susceptibility patterns to antibiotics are also quite different with different organisms. From the evidence presented above, a multiple (at least 2, low and high) sensitivity MIC break point system appears to be more appropriate than a single sensitivity MIC break point system to cope with various infections. Multiplicity of break points should depend on types of organisms, antibiotic availabilities at sites of infections, and specific factors in patients. Pharmacokinetic data on antibiotics must be more precisely taken into account with respect to the diversity of dosages, and especially effective antibiotic concentrations at sites of infections.

Anti-Bacterial Agents↗

PubMed1993

[Enhancement of in vitro antimicrobial activity of cefmetazole and cefotiam in combination against methicillin-susceptible and -resistant Staphylococcus aureus studied using checkerboard MIC method and disc diffusion method with discs containing both drugs].

Antimicrobial activities of cefmetazole (CMZ) and cefotiam (CTM) in combination were studied against clinical isolates of Staphylococcus aureus (9 methicillin-susceptible strains and 47 methicillin-resistant strains) by the checkerboard MIC method and the disc diffusion test using Mueller-Hinton agar with or without addition of 4% NaCl. MICs of CMZ and CTM individually against 9 methicillin-susceptible strains (MSSA) were 0.78 approximately 1.56 micrograms and 0.39 approximately 0.78 micrograms/ml without 4% NaCl, and 1.56 approximately 3.13 micrograms/ml and 0.78 approximately 1.56 micrograms/ml with 4% NaCl, respectively. In combination of CMZ and CTM, MICs of CMZ and CTM against these MSSA decreased to 0.20 approximately 0.39 micrograms/ml and 0.20 micrograms/ml without 4% NaCl, and 0.20 approximately 0.78 micrograms/ml and 0.10 approximately 0.78 micrograms/ml with 4% NaCl, respectively, showing minimum FIC indexes of 0.313 to 0.628. FIC indexes < or = 0.5 were observed against 7 out of 9 strains. MICs of CMZ and CTM individually against 47 methicillin-resistant strains (MRSA) were 6.25 approximately 100 micrograms/ml and 3.13 approximately 800 micrograms/ml in the absence of 4% NaCl, and 6.25 approximately 100 micrograms/ml and 50 approximately greater than 800 micrograms/ml in the presence of 4% NaCl, respectively. In combination of CMZ and CTM, MICs of these drugs against MRSA were reduced to 0.20 approximately 25 micrograms/ml without 4% NaCl and 0.39 approximately 25 micrograms/ml and 3.13 approximately 200 micrograms/ml with 4% NaCl, respectively. The strains studied showed minimum FIC indexes of 0.02 to 0.5 either with 4% NaCl or not. By the disc diffusion method, between CMZ disc and CTM disc a synergistic interaction against MRSA was well observed. In addition, discs containing both drugs showed a greater inhibitory zone than discs containing the equivalent amount of CMZ or CTM alone. These in vitro observations reported here suggest that the use of CMZ and CTM in combination is more effective than the use of these drugs individually for the treatment of MSSA and slight to moderate resistant MRSA infection. Prophylactic use of CMZ and CTM in combination for surgical infection would be also more effective than the use of these drugs individually. The synergistic enhancement of antimicrobial activity of CMZ and CTM in combination was assessed using discs containing various amounts of these drugs at various ratios. In this investigation, discs containing CMZ/CTM (20 micrograms/10 micrograms) was selected. Using discs containing CMZ/CTM (20 micrograms/10 micrograms), disc inhibitory zone diameters against MSSA and MRSA were well correlated negatively with MICs of CMZ or CTM in combination.(ABSTRACT TRUNCATED AT 400 WORDS)

Cefmetazole↗

PubMed1992

Cross-resistance of clinical isolates of methicillin-resistant Staphylococcus aureus to aminoglycosides and fluoroquinolones.

Susceptibilities of 117 clinical isolates of methicillin-resistant Staphylococcus aureus (MRSA) to aminoglycosides and fluoroquinolones were investigated during 1987 and 1990. Gentamicin, tobramycin, sisomicin, micronomicin, and astromicin showed the bimodal antimicrobial activity pattern against MRSA, revealing cross-resistance to these antibiotics. However, amikacin, netilmicin, isepamicin and arbekacin (ABK) exhibited the monomodal antimicrobial activity pattern, suggesting the presence of less resistant strains. All 117 MRSA strains were susceptible to ABK with MICs less than 3 micrograms/ml. MRSA also showed the bimodal antimicrobial susceptibility pattern to fluoroquinolones such as ofloxacin (OFLX), ciprofloxacin (CPFX) and tosufloxacin (TFLX). Frequencies of TFLX susceptible MRSA isolates decreased progressively from 1987 to 1989 when this drug was not even in general clinical use. The cross-resistance of MRSA between TFLX and OFLX or CPFX persisted. Cross-resistance between aminoglycosides and fluoroquinolones, however, was less frequently observed.

Aminoglycosides↗

PubMed1992

[Evaluation of in vitro antimicrobial activity of cefazolin alone and in combination with cefmetazole or flomoxef using agar dilution method and disk diffusion method].

Antimicrobial activities of cefazolin (CEZ) against 251 strains of various clinical isolates obtained during 1989 and 1990 were determined using the Mueller-Hinton agar dilution method at an inoculum level 10(6) CFU/ml. The reliability of the disk susceptility test was also studied using Mueller-Hinton agar and various disks at inoculum levels of 10(3-4) CFU/cm2 in estimating approximate values of MICs. In addition, antimicrobial activities of CEZ and cefmetazole (CMZ) or flomoxef (FMOX) in combination were investigated against methicillin-sensitive and -resistant Staphylococcus aureus (MSSA and MRSA) using the checkerboard agar dilution MIC method and the disk diffusion test either with the disks contained CEZ, CMZ, and FMOX alone, or CEZ, and CMZ or FMOX in combination. In this study, the MICs of CEZ against S. aureus were distributed with the 3 peak values at 0.39 microgram/ml, 3.13 micrograms/ml and > 100 micrograms/ml. MICs against MSSA were 0.39 microgram/ml to 0.78 microgram/ml, whereas those against MRSA were greater than 0.78 microgram/ml. MICs against majority of strains of Enterococcus faecalis were 25 micrograms/ml. Over 90% of strains of Escherichia coli and Klebsiella pneumoniae were inhibited at the level of 3.13 micrograms/ml. About 60% of isolates of indole negative Proteus spp. were inhibited at the levels of less than 3.13 micrograms/ml and 100% at 6.25 micrograms/ml, but MICs against indole positive Proteus spp., Serratia spp. and Pseudomonas aeruginosa were over 100 micrograms/ml. The antimicrobial activities of CEZ against these clinical isolates were not significantly different compared to those reported about 15-20 years ago, except for S. aureus. Highly resistant strains of S. aureus to CEZ were more prevalent in this study. The inhibitory zones obtained with the disk test were compared with MICs. The results of CEZ disk susceptibility test with 30 micrograms disk (Showa) or 10 micrograms disk (prepared in this laboratory) were well correlated with MICs (r = -0.837 and -0.814, respectively), showing the reliavility of the disk method in estimating approximate values of MICs. In the 4 category classification system currently used in Japan, break points in MIC values proposed are () MIC < or = 3 micrograms/ml, (++) > 3-15 micrograms/ml, (+) > 15-60 micrograms/ml, (-) > 60 micrograms/ml. The results obtained with 30 micrograms disks showed false positive in 7.7% and false negative in 6.8% of the samples. The disk results with E. faecalis showed a higher ratio of false positive results.(ABSTRACT TRUNCATED AT 400 WORDS)

Bacteria↗

PubMed1992

[Clinical laboratory approach to evaluate efficacy of amikacin. Reevaluation of in vitro MIC break points in disc susceptibility test].

Antimicrobial activities of amikacin (AMK) against 269 strains of various clinical isolates obtained in 1989 were determined and the reliability of the AMK disc susceptibility test in estimating approximate values of MICs was studied. In addition, clinical significance of various systems for the interpretation of the disc tests was evaluated to determine more useful method in the evaluation of clinical efficacy of AMK. Included in the study were a 3 category system of NCCLS, a 4 category system used in Japan, and the system proposed by the British Society for Antimicrobial chemotherapy. In this study, MICs were determined using the Mueller-Hinton agar containing 50 mg/L of Ca and 25 mg/L of Mg at an inoculum level of 10(3-4) CFU/ml. MIC80 values of AMK against Staphylococcus aureus and Staphylococcus epidermidis were 6.25 and 25 micrograms/ml, respectively. Those against Escherichia coli, Klebsiella pneumoniae, Proteus mirabilis, Proteus vulgaris, Enterobactor aerogenes, and Citrobacter spp. were less than 3.13 micrograms/ml. MIC values against Pseudomonas aeruginosa and Serratia marcescens were both less than or equal to 12.5 micrograms/ml. The disc susceptibility test was carried out according to the instruction in the Showa disc manual. Inhibition zones obtained with the disc method were compared with MIC values. The results of AMK disc susceptibility test obtained either with 30 micrograms discs or 10 micrograms discs were well correlated with MICs, indicating that the disc method was reliable in estimating approximate values of MICs (r = -0.807 to -0.897, P less than 0.01 in both instances). In the 4 category classification system currently used in Japan, the break points in MIC values of AMK proposed are (+3) MIC less than or equal to 3 micrograms/ml, (+2) MIC greater than 3-15 micrograms/ml, and (+) MIC greater than 15-60 micrograms/ml. The results obtained with Showa 30 micrograms discs and 30 micrograms discs prepared in this laboratory showed false positive results in 13% and 10.8% of the samples, and false negative results in 1.5% and 3.3%, respectively. In the 3 category classification system of NCCLS, the MIC break points proposed are defined sensitive (S) for MIC less than or equal to 16 micrograms/ml and resistant (R) for MIC greater than or equal to 32 micrograms/ml. In this study, the 30 micrograms disc tests using the above-mentioned 2 different types of discs resulted in false positive responses in 6.3% and 5.2% of the samples tested and false negative results in 1.1% and 1.9% of the samples, respectively.(ABSTRACT TRUNCATED AT 400 WORDS)

Amikacin↗

PubMed1990

[Evaluation of synergistic enhancement of antimicrobial activities of piperacillin and amikacin against Pseudomonas aeruginosa using FIC index and disc diffusion method].

A preliminary study was carried out to see whether or not the synergistic enhancement of antimicrobial activity of piperacillin (PIPC) and amikacin (AMK) in combinations against Pseudomonas aeruginosa can be evaluated using combination discs of these antibiotics. A synergistic antimicrobial effect was observed between these antibiotics, when evaluated using FIC index, against piperacillin-sensitive strains with MIC less than or equal to 12.5 micrograms/ml under the conditions of the present investigation using the agar dilution method. However, no synergy was found between these antibiotics against piperacillin-resistant strains with MIC greater than or equal to 25 micrograms/ml, even when a higher concentrations of the drugs were used. Using strains of P. aeruginosa against which the synergistic effect between these antibiotics was observed, it was found that inhibitory diameters obtained with combination discs of PIPC/AMK at concentrations of 30 micrograms/30 micrograms or 30 micrograms/15 micrograms were more than 3 mm larger than those obtained with discs containing either PIPC or AMK alone. Using strains against which no synergistic effects were observed, however, the above mentioned enlargement of inhibitory zone diameters with combination discs were not clearly found. Further studies are deemed necessary to determine whether or not the combination discs of PIPC and AMK are useful in routine clinical work.

Amikacin↗

PubMed1990

[Clinical laboratory approach to estimate effective administrative dose of minocyclin. Reevaluation of in vitro MIC break points in disc susceptibility test].

Antimicrobial activities of minocycline (MINO) against various clinical isolates, 270 strains obtained in 1988, were determined and the reliability of the MINO disc susceptibility test in estimating approximate values of MICs was studied. Clinical significance of a 4 category system for the interpretation of the disc tests, which is widely used in Japan, and that of a 3 category system used in the USA and Europe, were also evaluated to determine which system would be more suitable for the evaluation of proper dose levels of administration. In this study, MICs were determined using the agar dilution method at an inoculum level of 10(6) CFU/ml. MIC80 values of MINO against Staphylococcus aureus, Staphylococcus epidermidis and Streptococcus pneumoniae were all less than or equal to 0.78 micrograms/ml. Those against Haemophilus influenzae, Escherichia coli, Klebsiella pneumoniae, Proteus mirabilis and Proteus vulgaris were 0.39, 6.25, 3.13, 25, 50 micrograms/ml, respectively. MIC80 values against Pseudomonas aeruginosa, Serratia marcescens, Enterobacter spp., and Citrobacter spp. were 50, 100, 50 and 12.5 micrograms/ml, respectively. The inhibition zones obtained with the disc method were compared with MICs. The results of MINO disc susceptibility test either with 200 micrograms disc (Showa) or 30 micrograms disc (prepared in this laboratory) were well correlated with MICs, showing the reliability of the disc method in estimating approximate values of MICs. In the 4 category classification system currently used, break points in MIC values proposed are ( ) MIC less than or equal to 2 micrograms/ml, (++) MIC greater than 2-10 micrograms/ml, (+) greater than 10-50 micrograms/ml, (-) MIC greater than 50 micrograms/ml. The results obtained with 200 micrograms and 30 micrograms discs showed false positive in 26.6% and 20.5% of the samples, and false negative in 5.8% and 23.6% of the samples, respectively. The disc results of S. aureus, S. epidermidis, S. pneumoniae, etc. were relatively well classified, but those of E. coli, K. pneumoniae, Proteus spp. were not, showing more false positive results. Changing the lower 2 MIC break points in the 4 category system to: ( ) MIC less than or equal to 3 micrograms/ml and (++) MIC greater than 3-15 micrograms/ml, the false positive results with both 200 micrograms and 30 micrograms discs were reduced to 12% and 6.2%, respectively. The false negative results were 5.8% and 23.6%, respectively.(ABSTRACT TRUNCATED AT 400 WORDS)

Bacteria↗

PubMed1990

[Clinical laboratory approach in estimating effective administrative dose of piperacillin. Reevaluation of MIC break points in 3 and 4 category systems of disc susceptibility test].

The reliability of the piperacillin (PIPC) disc susceptibility test in estimating approximate values of MICs was studied with various clinical isolates totaling 284 strains using Showa discs and the discs prepared in this laboratory (both 8 mm diameter containing 30 micrograms of PIPC). Clinical significance of a 4 category system for the interpretation of the PIPC disc tests, which is widely used in Japan, was reevaluated to determine whether this system would be suitable or not for the evaluation of proper dose levels of administration. Break points in MIC values proposed for the classification of bacteria into 4 categories of susceptibility were: ( ) MIC less than or equal to 3 micrograms/ml, (++) MIC greater than 3-15 micrograms/ml, (+) MIC greater than 15-60 micrograms/ml, (-) MIC greater than 60 micrograms/ml. A 3 category system for interpreting of disc test, which is generally used in the USA and Europe, was also evaluated. MIC break points in the 3 category system proposed for the classification of the PIPC test are sensitive (S) MIC less than or equal to 64 micrograms/ml and resistant (R) MIC greater than or equal to 256 micrograms/ml. In addition, British Society for Antimicrobial Chemotherapy recently proposed in vitro MIC break points for PIPC in therapeutic use, recommending MICs 16 and 64 micrograms/ml. MIC 16 micrograms/ml can be used for general infections treated with usual administrative doses for such infections and MIC 64 micrograms/ml may apply to increased dosage or to normal dosage when PIPC is locally concentrated (mainly urinary or biliary tract infections). The results obtained with the disc method were compared with MICs determined using the agar dilution method at an inoculum level of 10(6) CFU/ml. The results of the PIPC disc susceptibility test either with Showa discs or discs prepared in this laboratory were well correlated with MICs, showing the reliability of the disc method in estimating approximate values of MICs. In the 4 category classification system of the Showa disc test, 33 out of 284 strains (11.6%) tested showed false positive results and 5 strains (1.8%) false negative results. Similarly, in the test of 30 micrograms discs prepared in this laboratory, of 284 strains 26 (9.2%) showed false positive results and 8 (2.8%) false negative results. In the tests of Showa discs and discs prepared in this laboratory, both containing 30 micrograms of PIPC, no inhibitory zones were observed against the strains with MIC greater than 100 micrograms/ml.(ABSTRACT TRUNCATED AT 400 WORDS)

Bacteria↗

PubMed1989

[Clinical laboratory approach to estimating the effective administration dose of imipenem/cilastatin. Evaluation of the disk susceptibility test and its interpretation system].

In vitro activities of imipenem/cilastatin (IPM/CS) against 413 clinical isolates were studied through the evaluation of MICs and the results of disk susceptibility tests. The MICs were determined using the agar dilution method at an inoculum level of 10(6) CFU/ml. The MIC80s of imipenem (IPM) against Staphylococcus aureus and Staphylococcus epidermidis were 25 and 1.56 micrograms/ml, respectively, showing a bimodal MIC distribution. However, the distribution of MICs against other bacteria studied was of monomodal pattern. Group A Streptococcus, Enterococcus faecalis were inhibited by IPM at dose levels less than 0.025 and 6.25 micrograms/ml, respectively. IPM inhibited Escherichia coli at 0.20 microgram/ml, Klebsiella pneumoniae at 0.39 microgram/ml, Pseudomonas aeruginosa at 3.13 micrograms/ml except one strain showed a MIC of 25 micrograms/ml, Serratia spp. at 3.13 micrograms/ml except one with MIC greater than 100 micrograms/ml, Citrobacter freundii at 0.78 microgram/ml and Enterobacter spp. at 0.39 microgram/ml. Indole (-) Proteus and indole (+) Proteus were inhibited by this drug at levels of 3.13 and 1.56 micrograms/ml, respectively. The reliability of the IPM disk diffusion susceptibility test in quantitative estimation of antimicrobial activities was well demonstrated using commercialized 8 mm diameter Showa disks containing 30 micrograms antibiotic and also disks containing 1-30 micrograms prepared in this laboratory. For the interpretation of the Showa disk susceptibility test, a 4 category system was used. In the 4 category system for Showa IPM disk the following classification of inhibitory zone diameters has been proposed; ( ) MIC less than or equal to 3 micrograms/ml, (++) MIC greater than 3-15 micrograms/ml, (+) MIC greater than 15-60 micrograms/ml, (-) MIC greater than 60 micrograms/ml. The results of the test using Showa 30 micrograms disk against various clinical isolates were accurately classified into the 4 groups, showing false positive 8 out of 304 strains (2.6%) and false negative 1 of 304 strains (0.3%). With Showa 30 micrograms disks subclassification of strains with MIC less than 3 micrograms/ml cannot be achieved. In this study, however, the differentiation of strains with MICs less than 1 microgram/ml was made with disks containing 5-10 micrograms, which afforded to set MIC break points at 1 and 3 micrograms/ml. According to current concepts on pharmacokinetics for antibiotics including the penetration of drugs into tissues and inflammatory fluids, serum protein binding of drugs appears to be one of the important determinants of drug distribution in the body. Only free, unbound drug molecules can readily pass through capillary pores into tissue fluids except in the hepato-biliary system.(ABSTRACT TRUNCATED AT 400 WORDS)

Bacteria↗

PubMed1989

[Effects of sulbactam on the activity of cefoperazone against various clinical isolates].

Sulbactam/Cefoperazone (SBT/CPZ) have been used in clinical infusion at ratios of 1:1 and 1:2 in Japan and U.S.A., respectively. After an administration of these drugs as a 1:1 parenteral formulation, the ratio of levels of CPZ and SBT in blood was 1:1/4 to 1:1/5 for 1 to 2 hours, whereas the ratio of free, unbound drug levels was 1:1.4 to 1:1.5. In urine these drugs were excreted at a ratio between 1:1 and 1:4 during 6 hours after the infusion. Antimicrobial interaction studies using various combinations of CPZ and SBT were performed to obtain information with respect to the effect of SBT on the antimicrobial activity of CPZ in vivo and the most appropriate ratio of these drugs for the in vitro test system. Antimicrobial activities were determined using the agar dilution method and the disk diffusion susceptibility test. SBT increased the activity of CPZ against various clinical isolates tested except Enterococcus faecalis. CPZ-SBT at a fixed ratio of 1:1/5 significantly increased the antimicrobial activity of CPZ, resulting in decreases in MIC values and increases in disk inhibitory zone diameters. These drugs at ratios 1:1 to 1:3 maximized the synergistic enhancement of the activity. Therefore, a fixed ratio between 1:1/5 and 1:1 would be appropriate for the in vitro antimicrobial test system using either the agar dilution method or the disk susceptibility test. Based on pharmacokinetic data for CPZ and SBT, results of the present study on antimicrobial activity would support that the parenteral formulation of CPZ-SBT at the fixed ratios of 1:1 and 2:1 for the intravenous infusion used in Japan and U.S.A., respectively, are appropriate. The effect of SBT on the activity of CPZ was more marked against clinical isolates with greater production abilities of beta-lactamase than against those with less production abilities. SBT/CPZ, however, exerted a synergistic effect against methicillin-resistant Staphylococcus aureus without beta-lactamase production. The MIC80 of SBT/CPZ (1:1) against various clinical isolates with 10(6) CFU/ml inoculum size were as follows: S. aureus 12.5 micrograms/ml, Staphylococcus epidermis 3.13 micrograms/ml, and E. faecalis 50 micrograms/ml. Those of Gram-negative bacilli were: Escherichia coli 0.20 microgram/ml, Klebsiella pneumoniae 0.20 micrograms/ml, Proteus mirabilis 0.78 microgram/ml, Proteus vulgaris 0.78 microgram/ml, Pseudomonas aeruginosa 12.5 micrograms/ml, Serratia marcescens 25 micrograms/ml, Enterobacter spp. 3.13 micrograms/ml, Citrobacter spp. 12.5 micrograms/ml and Acinetobacter spp. 0.78 microgram/ml.

Bacteria↗

PubMed1989

[Clinical laboratory approach for estimating effective administrative dose of tobramycin. Reevaluation of in vitro MIC break points of disk susceptibility test].

The reliability of the tobramycin (TOB) disc susceptibility test in estimating approximate values of MICs was studied using various clinical isolates totaling 261 strains and using Showa discs (8 mm diameter containing 30 micrograms of TOB) and Difco discs (6 mm diameter containing 10 micrograms of TOB). Clinical significance of a 4 category system for the interpretation of the disc tests, which is widely used in Japan, and that of a 3 category system used in USA and Europe, were also evaluated to determine which system would be more suitable for the evaluation of proper dose levels of administration. Furthermore, the evaluation was made using these discs with respect to the in vitro MIC break points for therapeutic use of antibiotics proposed by the British Society for Antimicrobial Chemotherapy (J. Antimicr. Chemoth. 21:701-710, 1988). The results obtained with the disc method were compared with MICs determined using the agar dilution method at an inoculum level of 10(6) CFU/ml. The results of the TOB disc susceptibility test either with Showa or Difco discs were well correlated with MICs, showing the reliability of the disc method to estimate approximate values of MICs. Break points in MIC values proposed for the classification of bacteria into the 4 categories of susceptibility are () MIC less than or equal to 2 micrograms/ml, (++) MIC greater than 2-10 micrograms/ml, (+) MIC greater than 10-50 micrograms/ml, (-) MIC greater than 50 micrograms/ml. Those proposed in the 3 categories of susceptibility are Sensitive (S) MIC less than or equal to 4 micrograms/ml, Intermediate (I) MIC greater than 4-8 micrograms/ml, Resistance (R) MIC greater than 8 micrograms/ml. In the 4 category classification system of the Showa disc susceptibility test, 16 out of 261 strains (6.1%) tested showed false positive results and 7 (2.7%) did false negative results. If the classification was modified as follows: ( ) MIC less than or equal to 3 micrograms/ml, (++) MIC greater than 3-15 micrograms/ml, (+) MIC greater than 15-60 micrograms/ml, (-) MIC greater than 60 micrograms/ml, false positive results were markedly reduced. Only 6 out of 261 strains (2.3%) showed false positive results, and 7 (2.7%) did false negative results. With Difco disc, in the 4 category interpretation system, 8 out of 261 strains (3.1%) tested showed false positive and 35 (13.4%) did false negative results. No inhibitory zones were observed against a majority of strains with MIC greater than 25 micrograms/ml, thus unable to assess (+) susceptibility.(ABSTRACT TRUNCATED AT 400 WORDS)

Humans↗

PubMed1989

[Clinical laboratory approach for estimating effective administrative dose of cephalothin. Reevaluation of MIC break points in 4 category system of disc susceptibility test].

The reliability of the cephalothin (CET) disc susceptibility test in estimating approximate values of MICs was studied using various clinical isolates totaling 248 strains and using Showa discs (8 mm diameter containing 30 micrograms of CET) and Difco discs (6 mm diameter containing 30 micrograms of CET). Clinical significance of a 4 category system for the interpretation of the CET disc tests, which is widely used in Japan, was reevaluated to determine whether this system would be suitable or not for the evaluation of proper dose levels of administration. The results obtained with the disc methods were compared with MICs determined using the agar dilution method at an inoculum level of 10(6) CFU/ml. The results of the CET disc susceptibility test were well correlated with MICs, showing the reliability of the disc method to estimate approximate values of MICs. Break points in MIC values proposed for the classification of bacteria into 4 categories of susceptibility are ( ) MIC less than or equal to 3 micrograms/ml, (++) MIC greater than 3-15 micrograms/ml, (+) MIC greater than 15-60 micrograms/ml, (-) MIC greater than 60 micrograms/ml. With the Showa disc susceptibility test, 15 out of the 248 strains (6.0%) tested showed false positive results and 6 strains (2.4%) showed false negative results. With the Difco disc test, 18 out of the 248 strains (7.3%) tested showed false positive results and 6 (2.4%) showed false negative results. Excluding Enterococcus faecalis from the test, results because better in the quantitative estimation of MICs, resulting false positive rates of 3.2% (Showa), and 4.4% (Difco). A 3 category system of the interpretation of disc test is generally used in the USA and Europe. MIC break points proposed for the classification of the CET test are sensitive, MIC less than or equal to 8 micrograms/ml, and resistance, MIC greater than or equal to 32 micrograms/ml. With the Showa disc susceptibility test, 14 out of the 248 strains (5.6%) tested showed false positive results and 6 strains (2.4%) showed false negative results. With the Difco disc test 7 out of the 248 strains (2.8%) showed false positive results and 21 strains (8.5%) showed false negative results. In this study, MIC70S of CET against Staphylococcus aureus and Staphylococcus epidermidis were 1.56 and 0.78 micrograms/ml, respectively. CET was not so effective against Gram-negative rods except Klebsiella pneumoniae, Proteus mirabilis and Escherichia coli. MIC70S against K. pneumoniae, P. mirabilis, and E. coli were 6.25, 3.13, and 3.13 micrograms/ml, respectively.

Cephalothin↗

PubMed1988

[Clinical laboratory approach for estimating effective administrative dose of cefuzonam. Evaluation of disc susceptibility test and its interpretation system].

In vitro activities of cefuzonam (CZON) against 273 clinical isolates were studied through the evaluation of MIC's and the results of disc susceptibility test. The MIC's were determined using the agar dilution method at an inoculum level of 10(6)CFU/ml. The MIC80's of CZON against Streptococcus pneumoniae, Escherichia coli, Klebsiella pneumoniae, Proteus mirabilis, Proteus vulgaris, Haemophilus influenzae and Citrobacter spp. were less than 0.20 microgram/ml. The MIC80's against Serratia marcescens and Enterobacter aerogenes were both 6.25 micrograms/ml, and that against Pseudomonas aeruginosa was 100 micrograms/ml. The MIC80's against Staphy-lococcus epidermidis were 25 and 6.25 micrograms/ml, respectively. Approximately 70% of strains of S. aureus were inhibited at concentrations less than 1.56 microgram/ml. For the interpretation of the CZON Showa 30 micrograms disc susceptibility test a 4 category system was used. In the 4 category system for Showa disc containing CZON, the following classification inhibitory zone diameters has been proposed: ( ) MIC less than or equal to 3 micrograms/ml, (++) MIC greater than 3-15 micrograms/ml, (+) MIC greater than 15-60 micrograms/ml, (-) MIC less than 60 micrograms/ml. Reliability of the CZON disc tests in estimating approximate MIC values was studied using Showa 30 micrograms discs and discs prepared in this laboratory containing 1-10 micrograms CZON. A good negative correlation was observed between inhibitory zone diameters and MIC's, showing the reliability of the disc method. The results of the test using Showa 30 micrograms disc against various clinical isolates were accurately classified into the 4 groups except those against P. aeruginosa. Some strains of P. aeuruginosa showed false positive results, exhibiting relatively larger inhibitory zone diameters compared with MIC's against these organisms. As CZON is not effective against P. aeruginosa a much better overall correlation between MIC's and the disc test would result when P. aeruginosa was excluded. With Showa 30 micrograms discs of various cephalosporins, sub-classification of strains with MIC less than 3 micrograms/ml cannot be achieved. In this study, however, it was demonstrated that differentiation of strains with MIC's less than 0.5-1.56 micrograms/ml was possible when discs containing 1-10 micrograms of CZON were used. According to recent concepts on pharmacokinetics for antibiotics including penetration of drugs into tissues and inflammatory fluids, serum protein binding of drugs appears to be one of the important determinants of drug distribution in the body.(ABSTRACT TRUNCATED AT 400 WORDS)

Ceftizoxime↗