Comparative in vitro activity of aztreonam and other antimicrobial agents against Salmonella species

The in vitro activity of aztreonam, the first monobactam antibiotic, was compared with that of 17 other antimicrobial agents against 79 strains of Salmonella species. The microorganisms were isolated from hospitalized patients, surface waters and seafoods during the decade 1975-1984. They included the following species: Salmonella typhi 63, Salmonella typhimurium 5, Salmonella wien 5, Salmonella heidelberg 2, Salmonella arizonae 2, Salmonella paratyphi B 1 and Salmonella enteritidis 1. The minimum inhibitory concentration (MIC) values of the antibiotics were determined using a serial dilution method in agar. A final inoculum size of 10(5) colony-forming units (CFU) X ml-1 of the tested microorganisms was used. Aztreonam exhibited a superior antimicrobial activity to that of the other antibiotics tested. Aztreonam inhibited 90% of the strains by 0.8 micrograms X ml-1 (MIC range was 0.05 to 1.56 micrograms X ml-1). There was no major difference between minimum bactericidal concentration and MIC values of aztreonam and the effect of inoculum size upon MIC values was observed at 10(7) CFU X ml-1.     

Synthesis and antimicrobial activity of 4-carbethoxymethyl-2-[(alpha-haloacyl)amino] thiazoles and 5-nonsubstituted/substituted 2-[(4-carbethoxymethylthiazol-2-yl)imino]-4-thiazolidinones

4-Carbethoxymethyl-2-[(chloroacetyl/alpha-chloropropionyl/al pha- bromobutyryl/alpha-chloro-(alpha-phenylacetyl)amino]thiazoles (I-IV) were synthesized by reacting 4-carbethoxymethyl-2-aminothiazole with chloroacetyl chloride, alpha-chloropropionyl chloride, alpha-bromobutyryl bromide and alpha-chloro-alpha-phenylacetyl chloride, respectively. Furthermore, I-IV were refluxed with ammonium thiocyanate to give 2-[(4-carbethoxymethylthiazol-2-yl)imino]-4-thiazolidinones (V-VIII). V was refluxed with various aromatic aldehydes to give 5-arylidene-2-[(4-carbethoxymethylthiazol-2-yl)imino]-4-t hiazolidinones (IX-XIV). The structures of synthesized compounds were confirmed by elemental analyses, hydrolysis, UV, IR, 1H-NMR and EI mass spectral data. The antimicrobial activities of the compounds were assessed by microbroth dilution technique using Mueller-Hinton broth and Mueller-Hinton Agar. In this study, Staphylococcus aureus ATCC 6538, Staphylococcus epidermidis ATCC 12228, Escherichia coli ATCC 8739, Klebsiella pneumoniae ATCC 4352, Pseudomonas aeruginosa ATCC 1539, Salmonella typhi, Shigella flexneri, Proteus mirabilis and Candida albicans ATCC 10231 were used as test microorganisms. Among the tested compounds, XI and XIV showed activity against S. aureus (MIC: 78 micrograms/ml, 1.6 micrograms/ml), whereas compound V had an activity against S. flexneri (MIC: 39 micrograms/ml) and compound I against C. albicans (MIC: 125 (micrograms/ml). Compounds I, IV-XIV were also evaluated for antituberculosis activity against Mycobacterium tuberculosis H37Rv using the BACTEC 460 radiometric system and BACTEC 12B medium. Only compounds I and XIV showed 86% and 67% inhibition in the primary screen.     

Antibacterial activity of fosfomycin against the causative bacteria isolated from bacterial enteritis

The in vitro antibacterial activities of fosfomycin (FOM) and 3 fluoroquinolones against Salmonella spp., pathogenic Escherichia coli, Campylobacter spp. and Shigella spp. were investigated. The activity upon the environmental condition in the inflammation was compared with standard condition in vitro. On standard condition, the MIC90 of tosfloxacin (TFLX), norfloxacin (NFLX) and levofloxacin (LVFX) against E. coli (77 strains), Shigella spp. (50) and Salmonella spp. (41) were < or = 0.025-0.10, 0.10, and 0.05 microgram/ml, respectively. The MIC90 of FOM against those organisms was 0.39-1.56 micrograms/ml. The MIC90 of TFLX, NFLX, LVFX against Campylobacter spp. were 6.25, 100 and 3.13 micrograms/ml, respectively. The MIC90 of FOM was 50 micrograms/ml. The activity of FOM was unaffected by pH and in anaerobic condition. On the other hand, the activity of NFLX was decreased in low pH and in anaerobic condition. In the presence of horse blood and addition of Na+, the activities of both agents were unaffected. These results suggested that FOM is equally active with or superior to fluoroquinolone in the intestinal infection treatment.     

The comparative in vitro activity of twelve 4-quinolone antimicrobials against enteric pathogens

The minimal inhibitory concentrations (MICs) of twelve 4-quinolone antimicrobials were determined for Salmonella typhi (25), Salmonella spp. (50), Shigella spp. (50), Campylobacter jejuni (100), Vibrio cholerae (10), Vibrio parahaemolyticus (10), Yersinia enterocolitica (25), Aeromonas hydrophila (25) and Plesiomonas shigelloides (10). MICs were determined using an agar dilution technique in Mueller-Hinton agar (Oxoid, England) supplemented with 10% lysed horse blood. Antibiotic containing plates were inoculated with approximately 10(4) colony forming units of each organism, contained in 10 microliters of Mueller-Hinton broth (Oxoid, England), using a multipoint inoculator. Following inoculation plates were incubated aerobically for 18 hours at 37 degrees C, except for plates inoculated with Campylobacter jejuni which were incubated microaerophilically for 48 hours at 37 degrees C. The MICs of each antimicrobial for each isolate examined, together with the minimum concentrations of each antimicrobial required to inhibit 50% (MIC50) and 90% (MIC90) of the isolates examined, were also determined. The more recently synthesized 4-quinolones showed very good activity against all of the enteric pathogens examined with ciprofloxacin being the most active (MIC90: Salmonella typhi 0.015 microgram/ml, Salmonella spp. 0.015 microgram/ml, Shigella spp. 0.015 microgram/ml, Campylobacter jejuni 0.12 microgram/ml, Vibrio cholerae 0.008 microgram/ml, Vibrio parahaemolyticus 0.06 microgram/ml, Yersinia enterocolitica 0.015 microgram/ml, Aeromonas hydrophila 0.015 microgram/ml and Plesiomonas shigelloides 0.015 microgram/ml. Where considered clinically appropriate these compounds may have a useful role in the treatment and prevention of diarrhoeal disease caused by these enteric pathogens.     

Comparative studies on activities of antimicrobial agents against causative organisms isolated from patients with urinary tract infections (2000). I. Susceptibility distribution

The bacterial strains isolated from patients diagnosed as having urinary tract infections (UTIs) in 10 institutions in Japan were supplied between the period of August 2000 and July 2001. Then, the susceptibilities of them to many kinds of antimicrobial agents were investigated. The number of them were 511 strains. The breakdown of these strains was Gram-positive bacteria as 29.0% and Gram-negative bacteria as 71.0%. Susceptibilities of these bacteria to antimicrobial agents were as follows; vancomycin (VCM), ampicillin (ABPC) and imipenem (IPM) showed strong activities against Enterococcus faecalis. No increase in low-susceptible strains of E. faecalis observed against these antimicrobial agents. VCM showed a strong activity against MRSA preventing growth of all strains with 1 microgram/ml. In addition, the activity of arbekacin (ABK) was strong with the MIC90 of 2 micrograms/ml against MRSA and prevented growth of all strains with 4 micrograms/ml. ABK showed a strong activity against Staphylococcus epidermidis preventing growth of all strains with 0.5 microgram/ml. ABPC, cefotiam (CTM) and cefozopran (CZOP) also showed a relatively strong activity against S. epidermidis (MIC90: 4 to 8 micrograms/ml). Against Escherichia coli, carbapenems showed high activities: meropenem (MEPM) prevented growth of all strains within 0.125 microgram/ml; IPM prevented growth of all strains with 0.25 microgram/ml. CZOP and CTM also showed strong activities against E. coli: MIC90 of CZOP was within 0.125 microgram/ml; MIC80 and MIC90 of CTM were 0.25 and 0.5 microgram/ml, respectively. Quinolone resistant E. coli was detected at frequency of 14.0%, which was significantly higher than that in the last year. Almost all drugs showed strong activities against Klebsiella pneumoniae and Proteus mirabilis, and MEPM prevented growth of all strains within 0.125 microgram/ml. Against Pseudomonas aeruginosa, almost drugs were not so active. The MIC90 of carbapenems and gentamicin (GM) were 16 micrograms/ml and those of all other drugs were more than 32 micrograms/ml. Against Serratia marcescens, the MIC90 of IPM and GM were the lowest value being 2 micrograms/ml, and that of MEPM was 4 micrograms/ml.     

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)     

Clinical laboratory approach in estimating the effective dosage of cefamandole

Reliability of the cefamandole (CMD) disc susceptibility test in estimating approximate values of MICs was studied using various clinical isolates totaling 246 strains with Showa discs (8 mm diameter containing 30 micrograms of CMD). Clinical significance of a 4 category system for the interpretation of the CMD disc tests, which is normally used in Japan, was also evaluated to determine whether this system would be suitable or not for the evaluation of a proper dose of administration. 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 CMD 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. Only 4 (1.6%) out the 246 strains tested showed false positive results and 11 (4.5%) showed false negative results, showing the excellent reliability of this test. In this study, approximately 90% of strains of Escherichia coli, Klebsiella pneumoniae, and Proteus mirabilis isolated from clinical materials randomly were inhibited by CMD at concentrations less than 3.13 micrograms/ml. Proteus vulgaris and Enterobacter aerogenes were sensitive to CMD at 67 and 69% of strains, respectively, at concentrations below 6.25 micrograms/ml. CMD was not active against Pseudomonas aeruginosa, Serratia marcescens and Enterococcus faecalis. About 90% of Staphylococcus aureus were inhibited at dose levels smaller than 6.25 micrograms/ml and 70% of the strains at levels less than 3.13 micrograms/ml. Susceptibilities to 15 micrograms/ml CMD of highly methicillin-resistant strains (MIC greater than 30 micrograms/ml) of S. aureus were examined. Ten of 12 strains examined were found susceptible to CMD, but only 6 of the 12 to cefmetazole. Imipenem/cilastatin was effective to 5 of the 12 strains at levels lower than 3 micrograms/ml and to one at a level less than 15 micrograms/ml. Minocycline was effective against 11 strains at concentrations below 2 micrograms/ml.(ABSTRACT TRUNCATED AT 400 WORDS)     

Susceptibilities of Escherichia coli, Salmonella and Staphylococcus aureus isolated from animals to ofloxacin and commonly used antimicrobial agents

Susceptibilities of Escherichia coli, Salmonella and Staphylococcus aureus isolated from chickens, pigs and cattle to ofloxacin (OFLX) and commonly used antimicrobial agents were investigated. 1. E. coli (28 isolates) demonstrated the highest level of susceptibility of OFLX (MIC 0.10-0.39 micrograms/ml for all the isolates) among all the test drugs. Commonly used antimicrobial agents to which these isolates responded with relatively high susceptibilities (MIC50 0.78-6.25 micrograms/ml) included oxolinic acid (OXA), ampicillin (ABPC), kanamycin (KM) and chloramphenicol (CP) with their MIC50 values in the increasing order as above. Drugs to which these isolates responded with moderate to weak susceptibilities (MIC50 25 approximately greater than 800 micrograms/ml) were doxycycline (DOXY), streptomycin (SM), spectinomycin (SPCM) and sulfadimethoxine (SDMX) in the increasing order of MIC50. E. coli isolates with resistances to all the test drugs other than OFLX and OXA amounted to 7.1-57.1% of the isolates examined and 20 isolates (71.4%) in total. 2. Susceptibilities to OFLX and 4 existing pyridonecarboxylic acid derivatives of E. coli (48 samples) isolated recently from diarrheal pigs were compared. When evaluated in terms of MIC50, the values of OFLX and norfloxacin were both 0.10 micrograms/ml. The values increased by differences of 0.39-3.13 micrograms/ml in an order of OXA, pipemidic acid and nalidixic acid. 3. Salmonella (28 isolates) demonstrated the highest level of susceptibility to OFLX (MIC 0.20-0.39 micrograms/ml for all the isolates) among all the test drugs. The drugs to which these isolates responded with relatively high to moderate susceptibilities (MIC50 0.78-12.5 micrograms/ml) included ABPC, OXA, DOXY, KM, CP and SM with their MIC50 values increasing in this order. The drugs to which the isolates responded with low susceptibilities (MIC50 above 100 micrograms/ml) were SPCM and SDMX. Of all the 28 Salmonella isolates tested, 7.1-32.1% were resistant to all the test drugs other than OFLX and OXA. These resistant isolates amounted to a total of 12 isolates (42.9%). 4. S. aureus (28 isolates) were highly susceptible to OFLX (MIC50 and MIC90 were both 0.78 micrograms/ml). Commonly used antimicrobial agents to which the isolates responded with high to relatively high susceptibilities (MIC50 0.10-6.25 micrograms/ml) were, in the increasing order of MIC50: DOXY, ABPC, tylosin, tiamulin, KM, OXA and CP. Drugs with moderate to low bacterial susceptibilities (MIC50 12.5-100 microns/ml) were SD, SDMX and SPCM. Isolates resistant to all the test drugs except OFLX and SDMX amounted to 3.6-50% of the 28 isolates examined and they totalled 20 isolates (71.4%).(ABSTRACT TRUNCATED AT 400 WORDS)     

Comparative studies on activities of antimicrobial agents against causative organisms isolated from patients with urinary tract infections (1997). I. Susceptibility distribution

The frequencies of isolation and susceptibilities to antimicrobial agents were investigated on 560 bacterial strains isolated from patients with urinary tract infections (UTIs) in 9 hospitals during the period of June 1997 to May 1998. Of the above bacterial isolates, Gram-positive bacteria accounted for 29.3% and a majority of them were Enterococcus faecalis. Gram-negative bacteria accounted for 70.7% and most of them were Escherichia coli. Susceptibilities of several isolated bacteria to antimicrobial agents were as followed; 1. Enterococcus faecalis Ampicillin (ABPC) showed the highest activity against E. faecalis isolated from patients with UTIs. Its MIC90 was 1 microgram/ml. Imipenem (IPM) and vancomycin (VCM) were also active with the MIC90s of 2 micrograms/ml. The others had low activities with the MIC90s of 16 micrograms/ml or above. 2. Staphylococcus aureus including MRSA VCM and arbekacin (ABK) showed the highest activities against both S. aureus and MRSA isolated from patients with UTIs. The MIC90s of them were 1 microgram/ml. The others except minocycline (MINO) had low activities with the MIC90s of 32 micrograms/ml or above. More than a half of S. aureus strains (including MRSA) showed high susceptibilities to gentamicin (GM) and MINO, the MIC50s of 0.25 microgram/ml or 0.5 microgram/ml. 3. Enterobacter cloacae IPM showed the highest activity against E. cloacae. The MICs for all strains were equal to or lower than 1 microgram/ml. The MIC90s of ciprofloxacin (CPFX) and tosufloxacin (TFLX) were 1 microgram/ml, the MIC90s of amikacin (AMK) and ofloxacin (OFLX) were 4 micrograms/ml, the MIC90 of GM was 16 micrograms/ml. Among E. cloacae strains, those with low susceptibilities to quinolones have decreased in 1997, compared with those in 1996. But the other drugs were not so active in 1997 as 1996. 4. Escherichia coli All drugs except penicillins were active against E. coli with the MIC90s of 8 micrograms/ml or below. Particularly, flomoxef (FMOX), cefmenoxime (CMX), cefpirome (CPR), cefozopran (CZOP), IPM, CPFX and TFLX showed the highest activities against E. coli with the MIC90s of 0.125 microgram/ml or below. 5. Klebsiella pneumoniae K. pneumoniae was susceptible to almost all the drugs except penicillins. Carumonam (CRMN) had the strongest activity with the MICs for all strains equal to or lower than 0.125 microgram/ml. FMOX, CPR, CZOP, CPFX and TFLX were also active with the MIC90s of 0.125 microgram/ml or below. The MIC90s of quinolones had changed into a better state in 1997, compared with those in 1996. 6. Proteus mirabilis Almost all the drugs except ABPC and MINO showed high activities against P. mirabilis. CMX, ceftazidime (CAZ), latamoxef (LMOX), CPR, cefixime (CFIX), cefpodoxime (CPDX) and CRMN showed the highest activities against P. mirabilis. The MICs of them for all strains were equal to or lower than 0.125 microgram/ml. CPFX and TFLX were also active with the MIC90s of 0.125 microgram/ml or below. 7. Pseudomonas aeruginosa The MIC90 of GM was 8 micrograms/ml, the MIC90s of AMK, IPM and meropenem (MEPM) were 16 micrograms/ml. The others were not so active against P. aeruginosa with the MIC90s of 32 micrograms/ml or above. The MIC90s of quinolones had changed into a lower state in 1997, compared with those in 1996. 8. Serratia marcescens IPM showed the highest activity against S. marcescens. Its MIC90 was 2 micrograms/ml. GM was also active with the MIC90 of 4 micrograms/ml. The MIC90s of the others were 16 micrograms/ml or above. The MIC50s of CRMN was 0.125 microgram/ml or below, the MIC50s of CPR and CZOP were 0.25 microgram/ml.     

Clinical study of cefpodoxime proxetil dry syrup for skin and soft tissue infections in the field of pediatrics

Concurrently with administering a newly developed cephem derivative antibiotic (CEP), cefpodoxime proxetil (CPDX-PR, CS-807) dry syrup, to children with skin and soft tissue infections, activities of 7 drugs against a group of microorganisms were tested. The drugs tested included 4 drugs of the cephem group, R-3746, a Na-salt form of CPDX, cefaclor (CCL), cephalexin (CEX) and cefadroxil (CDX), and 3 drugs of the penicillin group, ampicillin (ABPC), methicillin (DMPPC) and cloxacillin (MCIPC). The bacterial strains tested were 71 strains of Staphylococcus aureus and 1 strain of Streptococcus pyogenes, all isolated from the above cases of pediatric infections. Inoculum sizes used in these tests were 10(6) and 10(8) cfu/ml. Ages of children in those cases to which the drug was administered ranged from 2 months to 15 years. A total of 66 cases were treated, including 60 cases of impetigo, 5 cases of subcutaneous abscess and 1 case of phlegmon. The drug was administered for an average of 6 days with a daily average dose level of 9.4 mg/kg divided into 3 doses except 1 case where a twice daily dose regimen was used. Clinical and bacteriological effects were examined, and the occurrence of adverse reactions and abnormal laboratory test results were recorded. The results of these tests are summarized below. 1. The activity test for R-3746 (Na-salt of CPDX) against 71 strains of S. aureus performed at an inoculum level of 10(8) cfu/ml showed 2 peaks of MIC values, one in a range of 1.56 to 6.25 micrograms/ml and the other higher than 100 micrograms/ml. The most prevalent MIC value was 3.13 micrograms/ml with MIC against 51 strains or 71.8% of the strains tested showing this value, and MIC values of 25 micrograms/ml or higher were obtained for 13 strains or 18.3% of the strains tested. The MIC80 was 6.25 micrograms/ml. Thus, R-3746 showed an antibacterial activity slightly weaker than MCIPC and DMPPC but similar to CCL, CEX and CDX. MIC values obtained at an inoculum level of 10(6) cfu/ml also had 2 peaks, one in a range of 1.56 to 3.13 micrograms/ml and the other higher than 25 micrograms/ml. Strains against which R-3746 had the MIC value of 3.13 micrograms/ml were the most numerous with 47 strains or 66.2%, and strains against which the MIC value of higher than 25 micrograms/ml was obtained were next with 13 strains or 18.3%.(ABSTRACT TRUNCATED AT 400 WORDS)     

Antibacterial activities and electron microscopic studies of imipenem in combination with fosfomycin against methicillin and fosfomycin resistant strains of Staphylococcus aureus

Imipenem (IPM) and fosfomycin (FOM) have been reported to possess a synergistic relationship in their activities against both methicillin (DMPPC)-susceptible and -resistant strains of Staphylococcus aureus. However it was not concluded whether these antibacterial activities were bacteriostatic or bactericidal. The purpose of this report is to elucidate this point clearly. Activities of the 2 antibiotics against 15 strains S. aureus resistant to both DMPPC and FOM were investigated by means of the killing-curve method and electron microscopic studies. MICs of DMPPC and FOM against these strains determined using the agar dilution method were greater than or equal to 50 micrograms/ml and MICs of IPM by the broth dilution method ranged from 12.5 to 50 micrograms/ml. The killing-curves with the following drug concentration combinations were examined in Mueller-Hinton broth: 1. FOM 25 micrograms/ml, 2. FOM 25 micrograms/ml + IMP 1/2 MIC, 3. IPM 1MIC, 4. FOM 25 micrograms/ml + IPM 1 MIC and 5. FOM 25 micrograms/ml + IPM 2MIC. Morphological changes produced in 1 strain by 2 of the combinations, 2. FOM 25 micrograms/ml + IPM 1/2 MIC and 4. FOM 25 micrograms/ml + IPM 1MIC, were observed using scanning and transmission electron microscopy. The following results were obtained; (1) The synergistic effects were found in 6/15 strains (40%) and no antagonistic effect was found. (2) Electron microscopic observation showed that IPM in combination with FOM caused lysis of the cells. Conclusions: IPM in combination with FOM produced bactericidal and bacteriolytic effects on DMPPC-resistant S. aureus (MRSA). This combination therapy should be evaluated for FOM resistant MRSA infections.     

千根草粗取物体外抑菌活性部位的筛选研究

目的 以金黄色葡萄球菌、大肠杆菌、变异链球菌、绿脓杆菌、伤寒杆菌、痢疾杆菌为试验菌株研究千根草的体外抑菌活性.方法 通过K-B纸片扩散法及利用连续（试管）稀释法对70%醇提物,水层、正丁醇、乙酸乙酯、石油醚相萃取物测定抑菌活性.结果 总提物对金黄色葡萄球菌、绿脓杆菌、伤寒杆菌、痢疾杆菌的最低抑菌浓度（MIC）为25.00g·L-1.粗分部位中,乙酸乙酯相萃取物对金黄色葡萄球菌、大肠杆菌、绿脓杆菌、痢疾杆菌抑菌活性最好,其最低抑菌浓度分别为25、12.5、3.13、25g·L-1,水层无抑菌活性.结论 千根草的抑菌活性成分主要存在于乙酸乙酯萃取相中.     

Antimycoplasmal activities of ofloxacin and commonly used antimicrobial agents on Mycoplasma gallisepticum

In vitro activities of ofloxacin (OFLX), a new quinolone derivative, against 29 strains of Mycoplasma gallisepticum was compared with those of 4 commonly used antimicrobial agents, doxycycline (DOXY), tylosin (TS), spectinomycin (SPCM) and thiamphenicol (TP). Antimycoplasmal activities of the drugs were evaluated on the MIC (final MIC) and MPC (minimum mycoplasmacidal concentration) values which were determined by a broth dilution procedure. The following results were obtained. 1. The MIC90s of OFLX and DOXY were both 0.20 micrograms/ml. The MICs of TS were distributed through a wide range (less than or equal to 0.006 - 0.78 micrograms/ml), and its MIC90 was 0.78 micrograms/ml. Of 29 M. gallisepticum strains, 27.6% were recognized as TS-resistant. The MIC90 values of SPCM and TP were 1.56 micrograms/ml and 3.13 micrograms/ml, respectively. The MIC90 of OFLX was equal to that of DOXY and 4- to 16-fold smaller than the values of the other 3 antibiotics. 2. The MPC of OFLX was the lowest among the antibiotics tested, its MPC90 value was 0.39 micrograms/ml and was followed by DOXY (1.56 micrograms/ml). The MPCs of TS were distributed in a wide range (0.012 - 3.13 micrograms/ml), and its MPC90 was 3.13 micrograms/ml. The MPC90 values of SPCM and TP were both 6.25 micrograms/ml. Therefore, the mycoplasmacidal activity of OFLX evaluated with MPC90 values was 4- to 16-fold greater than those of the other 4 antibiotics.     

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)     

Fundamental and clinical studies on aspoxicillin in the pediatric field

Fundamental and clinical studies of aspoxicillin (ASPC, TA-058), a new penicillin antibiotic, were performed in pediatric field. Antimicrobial activity MIC of ASPC was compared with that of piperacillin (PIPC), ampicillin (ABPC) and carbenicillin (CBPC) for clinical isolates of S. aureus (24 strains), S. pyogenes (22 strains), H. influenzae (18 strains), E. coli (21 strains) and K. pneumoniae (23 strains). MIC of ASPC against S. pyogenes was distributed in less than 0.39 microgram/ml and this numerical value of MIC was very superior. MIC distributions of ASPC against S. aureus, H. influenzae and E. coli had 2 peaks respectively. It was presumed that the results are due to an existence of beta-lactamase producing strains. The sensitive strains in those were distributed in less than 1.56-12.5, less than or equal to 0.10 and 0.78-3.13 micrograms/ml, respectively, and those numerical value of MIC was superior. While against K. pneumoniae, all strains were distributed in more than 12.5 micrograms/ml and the antimicrobial activity of ASPC was very inferior. ASPC was as active as PIPC and ABPC against S. pyogenes, but more active then CBPC, ASPC was less active against S. aureus than PIPC and ABPC, but more active than CBPC. And ASPC was less active against H. influenzae and E. coli than PIPC, but more active than ABPC and CBPC. Against K. pneumoniae, strains that showed somewhat low numerical value of MIC at only PIPC were observed, but antimicrobial activities of ABPC and CBPC, as well as ASPC were very inferior. Absorption and excretion Serum level and urinary excretion of ASPC in 6 pediatric patients of 4 months to 12 years of age after one shot intravenous injection of 20 mg/kg were examined. The serum mean levels were 51.7 micrograms/ml at 1/4 hour, 38.2 micrograms/ml at 1/2 hour, 22.9 micrograms/ml at 1 hour, 3.0 micrograms/ml at 4 hours and 1.0 microgram/ml at 6 hours after injection, respectively. The mean half-life of serum level was 1.03 hours. The mean urinary levels were 4,646 micrograms/ml for 0-2 hours, 1,773 micrograms/ml for 2-4 hours and 299 micrograms/ml for 4-6 hours. The mean urinary recovery rate within 6 hours after injection was 64.7%. Clinical studies In order to evaluate clinical response, bacteriological response and side effects, ASPC was applied to 28 cases, i.e., 5 cases of acute purulent tonsillitis, 2 cases of acute purulent otitis media, 2 cases of acute bronchitis and 19 cases of acute pneumonia.(ABSTRACT TRUNCATED AT 400 WORDS)     

Antibacterial activity of norfloxacin on methicillin-resistant Staphylococcus aureus. Comparison with oral antibacterial agents

Minimum inhibitory concentrations (MIC) of norfloxacin (NFLX) to 133 strains of methicillin-resistant Staphylococcus aureus (MRSA) isolated from clinical patients were investigated and compared with those of minocycline (MINO), erythromycin (EM), amoxicillin (AMPC), cefaclor (CCL) and fosfomycin (FOM). MIC90 of these drugs were 3.13 micrograms/ml with NFLX, 0.39 micrograms/ml with MINO, greater than 100 micrograms/ml with EM, 50 micrograms/ml with AMPC, greater than 100 micrograms/ml with CCL and greater than 100 micrograms/ml with CCL and greater than 100 micrograms/ml with FOM. MIC distribution patterns with 2 peaks were recognized with EM and FOM. Of 55 strains resistant to all of EM, AMPC, CCL and FOM, 50 and 54 strains were well susceptible to NFLX and MINO, respectively. The present investigation demonstrated relatively potent antibiotic effect of NFLX against MRSA. Considering the safety of NFLX to children which have been confirmed and reported separately, it can be concluded that NFLX is a useful oral antimicrobial drug in the treatment of children with MRSA infections.     

RU 29 246, the active compound of the cephalosporin-prodrug-ester HR 916. I. Antibacterial activity in vitro.

The aminothiazolyl-cephalosporin RU 29 246 is the active metabolite of the prodrug-pivaloyl-oxyethyl-ester HR 916. RU 29 246 in vitro activity includes a wide range of clinically relevant bacterial pathogens. Against methicillin-sensitive Staphylococci RU 29 246 (MIC90 of 0.25 approximately 2 micrograms/ml) was clearly more active than cefaclor, cefuroxime, cefpodoxime, cefixime and ceftibuten, but slightly less active than cefdinir. RU 29 246 inhibited hemolytic Streptococci of the serogroups A, B, C and G as well as penicillin-sensitive Streptococcus pneumoniae at concentrations similar to cefdinir, cefpodoxime and cefuroxime (MIC90 less than or equal to 0.13 micrograms/ml), but less than the other oral cephalosporins investigated (cefixime, cefaclor and ceftibuten). MIC90s of RU 29 246 against Escherichia coli, Klebsiella pneumoniae, Klebsiella oxytoca, Salmonella spp., Shigella spp., Proteus mirabilis and Haemophilus influenzae were less than or equal to 0.5 micrograms/ml. Only RU 29 246 and cefdinir demonstrated moderate activity against Acinetobacter baumannii (MIC90 greater than or equal to 4 micrograms/ml). Most strains of Pseudomonas spp., Serratia marcescens, Enterobacter spp., Hafnia alvei and Bacteroides spp. were resistant to RU 29 246. RU 29 246 killed Escherichia coli and Staphylococcus aureus at a rate of 99% to 99.9% at concentrations of two times MIC. The pH value of the medium (range 5.5 to 8.5) and the inoculum size (range 10(5) to 10(7) cfu/ml) had no or only low influence on the antibacterial activity of RU 29 246. RU 29 246 is a broad spectrum cephalosporin including in its activity both Gram-positive and Gram-negative pathogens and therefore--depending on the bioavailability of its prodrug--looks promising as to its therapeutic perspective.     

Comparative studies on activities of antimicrobial agents against causative organisms isolated from urinary tract infections (1985). I. Susceptibility distribution

The results of determinations of sensitivities of bacterial strains to various antibiotics are summarized as follows: 1. Against Escherichia coli, ofloxacin (OFLX) showed the strongest activity among oral antibacterial and antibiotic agents. Its MIC90 was below 0.10 micrograms/ml. The next strongest activity was found in mecillinam (MPC), cefaclor (CCL) and pipemidic acid (PPA); MIC90's of these agents 3.13 micrograms/ml. Cefotiam (CTM), cefotaxime (CTX), ceftizoxime (CZX), cefmenoxime (CMX) and latamoxef (LMOX) had MIC90 below 0.39 micrograms/ml. MIC90's of cefmetazole (CMZ) and cefoperazone (CPZ) were 1.56 micrograms/ml. Aztreonam (AZT) and carumonam (CRMN) in the monobactam group showed strong activities with MIC90's at 0.20 micrograms/ml. 2. Although Klebsiella pneumoniae had a strong resistance to ampicillin (ABPC) and showed relatively low sensitivities to other oral antibacterial and antibiotic agents, OFLX maintained high activity against this species and showed MIC90 of 0.39 micrograms/ml. Among injectable antibiotics, third generation cephems showed the strongest activity to this species with MIC90 of CZX below 0.10 micrograms/ml, of CTX and CMX 0.20 micrograms/ml, and of LMOX 0.78 micrograms/ml. MIC90 of CPZ was 6.25 micrograms/ml, which was the same as those of cefazolin (CEZ) and cefoxitin (CFX). CTM had similar MIC90 to LMOX, namely, 1.56 micrograms/ml. MIC90 of CMZ was 3.13 micrograms/ml. Monobactams AZT and CRMN showed strong activities to this species; their MIC90's were below 0.10 micrograms/ml and 0.20 micrograms/ml. 3. Although Citrobacter freundii generally exhibited low sensitivities to antibacterial and antibiotic agents examined, it showed high sensitivity to OFLX, at MIC80 of 0.78 micrograms/ml. This species showed low sensitivities to MPC, nalidixic acid (NA), PPA, and sulfamethoxazole-trimethoprim (ST). Among injectable antibiotics, LMOX and CMX had activities against this species; namely, MIC80's were 6.25 and 3.13 micrograms/ml, respectively. Among monobactams, AZT showed MIC80 of 12.5 micrograms/ml, and CRMN had that of 6.25 micrograms/ml. 4. Against Enterobacter cloacae, the strongest antibacterial activity was found with OFLX which had MIC90 of 0.39 micrograms/ml. A relatively strong activity was seen with MPC. MIC80 of MPC was 1.56 micrograms/ml. Except to CTM, this species had poor sensitivities to injectable first and second generation cephems, and their MIC80's were over 200 micrograms/ml. MIC80 of CTM was 25 micrograms/ml.(ABSTRACT TRUNCATED AT 400 WORDS)     

MICs and MBCs of cefotaxime, desacetylcefotaxime and ceftriaxone against four principal bacteria causing meningitis

The MICs and MBCs of cefotaxime (CTX), desacetylcefotaxime (Des-CTX) and ceftriaxone (CTRX) were determined in relation to 4 of the principal bacterial species which cause meningitis, i.e., S. pneumoniae, S. agalactiae, H. influenzae and E. coli. These tests were performed using final inocula of 10(8) cells/ml and 10(6) cells/ml. Comparison was made with the MIC and MBC values of benzylpenicillin (PCG) and ampicillin (ABPC). 1. Against 25 strains of S. pneumoniae, the MIC 90 values with inocula levels of 10(8) and 10(6) cells/ml were as follows: CTX, 0.05 and 0.024 micrograms/ml; Des-CTX, 0.39 and 0.20 micrograms/ml; CTRX, 0.10 and 0.05 micrograms/ml, respectively; and PCG, less than 0.012 micrograms/ml at both size. Similarly, the MBC 90 values were: CTX, 0.01 and 0.05 micrograms/ml; Des-CTX, 0.78 and 0.39 micrograms/ml; CTRX, 0.20 and 0.10 micrograms/ml; and PCG, 0.024 and 0.012 micrograms/ml, respectively. It is thus apparent that PCG showed the lowest values for both the MIC and MBC, followed by CTX, CTRX and then Des-CTX. Against 25 strains of S. agalactiae, the MIC 90 values with inocula of 10(8) and 10(6) cells/ml were as follows: CTX, 0.05 and 0.05 micrograms/ml; Des-CTX, 0.39 and 0.20 micrograms/ml; CTRX, 0.10 and 0.05 micrograms/ml; and PCG, 0.39 and 0.20 micrograms/ml, respectively. Similarly, the MBC 90 values of Des-CTX were 0.78 and 0.39 micrograms/ml, while the other 3 antibiotics showed the same values with both the 10(8) and 10(6) cells/ml inocula: 0.10 micrograms/ml for CTX, 0.20 micrograms/ml for CTRX and 0.39 micrograms/ml for PCG. Accordingly, CTX showed the lowest values, followed by CTRX and then PCG being about the same as Des-CTX. Against 25 strains of H. influenzae, the MIC 90 values with inocula levels of 10(8) and 10(6) cells/ml were as follows: CTX, 0.10 and 0.05 micrograms/ml; Des-CTX, 0.39 and 0.39 micrograms/ml; CTRX, 0.10 and 0.05 micrograms/ml; and ABPC, 50 and 6.25 micrograms/ml, respectively. Similarly, the MBC 90 values were: CTX, 0.20 and 0.10 micrograms/ml; Des-CTX, 1.56 and 1.56 micrograms/ml; CTRX, 0.39 and 0.20 micrograms/ml; and ABPC, greater than 100 and 50 micrograms/ml, respectively. Accordingly, in terms of the MIC 90, CTX and CTRX showed the same values, but in terms of the MBC 90 CTX was superior. (ABSTRACT TRUNCATED AT 400 WORDS)     

Comparative studies on activities on antimicrobial agents against causative organisms isolated from patients with urinary tract infections (2000). III. Secular changes in susceptibility

The bacteria (Enterococcus faecalis, Staphylococcus aureus, Escherichia coli, Klebsiella spp. and Pseudomonas aeruginosa) isolated from patients diagnosed as having urinary tract infections (UTIs) in 10 institutions in Japan were supplied between August 2000 and July 2001. Then, the susceptibilities of these bacteria to various antimicrobial agents were examined, and the results were compared with those obtained between 1992 and 1999. Comparison was made by classifying strains isolated from patients into those in uncomplicated UTIs and those in complicated UTIs (including with or without indwelling catheter). E. faecalis showed good susceptibility to ampicillin (ABPC) and imipenem (IPM), and the MIC90s were 2 micrograms/ml. Also, E. faecalis showed good susceptibility to vancomycin (VCM). However, the MIC90, which was 2 micrograms/ml between 1992 and 1999, rose to 4 micrograms/ml in patients with complicated UTIs because the strains inhibited at 4 micrograms/ml increased more than before. The low susceptibility of S. aureus to arbekacin (ABK) in complicated UTIs, as shown in 1998 and 1999, recovered in 2000, and no strains inhibited at > or = 4 micrograms/ml were detected. E. coli showed good susceptibility to CTM (MIC90: 0.25-0.5 microgram/ml) and CZOP (MIC90: < or = 0.125 microgram/ml) and was not resistant to those. E. coli also showed good susceptibility to the other drugs except to penicillins. Decreases in susceptibility of E. coli to quinolones, ciprofloxacin (CPFX), and sparfloxacin (SPFX) were observed in the patients with complicated UTIs. The susceptibility of Klebsiella spp. to all drugs did not significantly change in 2000 and was generally good except to penicillins. Although the susceptibility of P. aeruginosa to carbapenems was notable, the MIC90 went up from 4 micrograms/ml to 16 micrograms/ml in complicated UTIs compared with those observed in the previous year.