In vitro activity of azlocillin, metronidazole and its hydroxy metabolite against anaerobes. Bacteriostatic synergism studies

The in vitro inhibitory activity of azlocillin (Securopen), metronidazole (Cloni) and its hydroxy metabolite was determined against 27 gram-negative and 13 gram-positive species of anaerobes by means of agar dilution tests. The 63 anaerobic strains were also tested against the pairs azlocillin-metronidazole and azlocillin-hydroxy metabolite by means of agar dilution tests. Gram-negative species (Bacteroides spp., Fusobacterium spp. etc.) were inhibited by 0.125-256 micrograms/ml azlocillin, 0.01-4 micrograms/ml metronidazole and 0.01-4 micrograms/ml hydroxy metabolite. With gram-positive anaerobes (Clostridium spp., Peptococcaceae etc.) the MIC ranges were 0.125-4 micrograms/ml for azlocillin, 0.03-1 micrograms/ml for metronidazole and 0.125-2 micrograms/ml for the hydroxy metabolite. A synergistic effect was observed exclusively with gram-negative anaerobes (Bacteroides fragilis, B. thetaiotaomicron, B. disiens etc.). There were few instances of antagonism, likewise with gram-negative species. The preponderant combination effect against gram-positive anaerobes was addition. In view of the broad antiaerobic spectrum of azlocillin, the present in vitro findings do not preclude combined therapy with metronidazole in cases of anaerobic-aerobic poly-bacterial infections.     

Activity of linezolid against anaerobic bacteria

Minimal inhibition concentrations (MICs) were determined for linezolid (LZD) and compared with those of reference antibiotics against 265 anaerobes. For the Bacteroides fragilis group, MIC range for LZD was 2-4 mg/l. Strains resistant to the other antibiotics were detected including one strain of B. fragilis showing high level resistance to metronidazole (64 mg/l). LZD MIC(50) was 4 mg/l for prevotella and 1 mg/l for fusobacteria. LZD MICs were <1 mg/l for porphyromonas and veillonellae and 相似文献   

The comparative activity of twelve 4-quinolone antimicrobials against gram-positive and gram-negative anaerobes

The minimal inhibitory concentrations (MICs) of twelve 4-quinolone antimicrobials were determined for the Bacteroides fragilis group (50), Bacteroides melaninogenicus (20), Bacteroides bivius (10), Fusobacterium spp. (10), anaerobic Gram-positive cocci (50) and Clostridium spp. (20). MICs were determined using an agar dilution technique in Mueller-Hinton agar supplemented with 10% lysed horse blood. The inoculum used was approximately 10(4) colony-forming units, contained in 10 microliter of Mueller-Hinton broth, which was applied to the agar plates using a multipoint inoculator. Following inoculation, plates were incubated at 37 degrees C for 48 h in an anaerobic atmosphere. The MIC of each antimicrobial for each isolate examined was determined as the lowest concentration of the antimicrobial which completely inhibited growth of the inoculum. The minimum concentrations required to inhibit the growth of 50% (MIC50) and 90% (MIC90) of the organism examined were also determined. All of the more recently synthesised 4-quinolones showed increased activity against the anaerobic bacteria used in this study. Ciprofloxacin and ofloxacin were the most active compounds examined (Bacteroides fragilis group MIC90 ciprofloxacin 4 micrograms/ml; ofloxacin 4 microgram/ml; Bacteroides melaninogenicus MIC90 ciprofloxacin 2 micrograms/ml, ofloxacin 2 micrograms/ml; Bacteroides bivius MIC90 ciprofloxacin 16 micrograms/ml, ofloxacin 32 micrograms/ml; Fusobacterium spp. MIC90 ciprofloxacin 2 micrograms/ml, ofloxacin 4 micrograms/ml; Clostridium spp. MIC90 ciprofloxacin 1 microgram/ml, ofloxacin 1 microgram/ml and anaerobic Gram-positive cocci MIC90 ciprofloxacin 4 micrograms/ml, ofloxacin 4 micrograms/ml).     

In vitro activity of U-57930E against anaerobic bacteria and its comparison with clindamycin, ampicillin, carbenicillin and tetracycline

The in vitro activity of U-57930E, a pipecolic acid amide of clindamycin, was compared with those of clindamycin, ampicillin, carbenicillin and tetracycline against 321 anaerobic clinical isolates. The MIC (micrograms/ml) of U-57930E that inhibited 95% Bacteroides fragilis, Peptococcus prevotii, B. melaninogenicus and P. asaccharolyticus was 0.0625; 0.03125 for Peptostreptococcus anaerobius, B. vulgatus, Propionibacterium and Peptococcus species. Clindamycin, on the other hand, gave MIC values of 0.5 microgram/ml for B. fragilis, P. prevotii and P. asaccharolyticus, 0.25 for Propionibacterium sp. All strains of Clostridium perfringens were inhibited by 0.5 microgram/ml of U-57930E. Both clindamycin and U-57930E showed similar MIC values for all strains of Fusobacterium nucleatum and Propionibacterium acnes tested. The MIC values for ampicillin, carbenicillin and tetracycline were within the expected range. U-57930E had a 4 approximately 8 fold lower MIC than clindamycin and is significantly active against anaerobic bacteria.     

In vitro activity of flomoxef compared to moxalactam, cefoxitin, cefotaxime, and clindamycin against anaerobes

To assess the in vitro activity of flomoxef (6315-S), moxalactam, cefoxitin, cefotaxime, and clindamycin against anaerobes 197 clinical isolates (27 Bacteroides fragilis, 42 B. thetaiotaomicron, 10 B. vulgatus, 7 B. ovatus, 6 B. uniformis, 6 B. distasonis, 7 Bacteroides melaninogenicus group, 11 Bacteroides oralis group, 21 Clostridium difficile, 7 C. perfringens, 3 C. sporogenes, 3 Clostridium spp., 33 Propionibacterium acnes, 14 Peptococcaceae) were studied by means of agar dilution tests. The MIC90 of B. fragilis was less than 2 micrograms/ml for flomoxef, less than 4 micrograms/ml for moxalactam, less than 16 micrograms/ml for cefoxitin, less than 128 micrograms/ml for cefotaxime and less than 2 micrograms/ml for clindamycin. The respective MIC90's of B. thetaiotaomicron were less than 64, less than 128, less than 32, less than 256 and 8 micrograms/ml. Strains of the other Bacteroides species and groups were more susceptible to flomoxef and the other antibiotics than B. thetaiotaomicron. Against Clostridium difficile flomoxef (MIC90 less than 4 micrograms/ml) proved to be superior to the other agents tested. Most of the Clostridium strains other than C. difficile were also susceptible to flomoxef; anaerobic grampositive cocci and Propionibacterium acnes were very sensitive (MIC90's less than 1 and less than or equal to 0.125 micrograms/ml, respectively). Its anti-anaerobic activity, together with its efficacy against aerobes, should make flomoxef a useful adjunct to the arsenal of modern antibiotic therapy.     

The in vitro activity of roxithromycin (RU 28965) compared with four oral antibiotics

The in vitro activity of roxithromycin (RU 28965), a new semisynthetic macrolide, was compared with that of amoxycillin, cephradine, doxycycline and erythromycin against 160 respiratory and skin isolates including 10 methicillin-resistant Staph. aureus, 10 beta-lactamase-producing Haemophilus influenzae and 30 anaerobes. The MIC determinations were performed by an agar dilution method using a final inoculum of 10(4)-10(5) c.f.u./ml and results were recorded as the lowest concentration of the drug that inhibited visible growth (MIC). All organisms were incubated aerobically at 37 degrees C for 18 h, except anaerobes which were incubated in an anaerobic chamber at 37 degrees C for 48 h. The MICs of roxithromycin against staphylococci (30 strains, 10 of which were erythromycin-resistant, MIC greater than or equal to 2 mg/l) ranged from 0.03 to greater than or equal to 16 mg/l. The MIC90 against erythromycin-sensitive staphylococci was 1.0 mg/l. The MICs of roxithromycin ranged from 0.03-4 mg/l (MIC90 0.25 mg/l) against streptococci (50 strains), from 1 to 32 mg/l (MIC90 8 mg/l) against Haemophilus spp. (40), and from 0.06 to 0.25 mg/l (MIC90 0.125 mg/l) against B. catarrhalis (10). Roxithromycin was less active than erythromycin against fusobacteria (MIC 0.05 to greater than or equal to 128 mg/l) and against Veillonella spp. (MIC greater than 128 mg/l). Roxithromycin was more active than cephradine, doxycycline and amoxycillin against the aerobic organisms (except for amoxycillin against streptococci, where the activity was similar) but less active against the anaerobes examined. Taken together with reported kinetic advantages, these results suggest that roxithromycin may be a useful antibiotic in selected circumstances and studies to determine its efficacy seem indicated.     

Clinical evaluation of tinidazole on anaerobic infections in the field of obstetrics and gynecology

The bacteriological and clinical effect of tinidazole (TDZ) was evaluated in 16 cases of intrauterine, intrapelvic and vulvar infection caused by anaerobic organisms and the following results were obtained. Anaerobes were detected in 16 cases, including 1 case with anaerobes alone and 15 cases with mixed anaerobes and aerobes. Eight different species and 24 strains were detected. A single species was isolated from 9 cases, 2 species from 6 cases and 3 species from 1 case. The main species detected were Bacteroides fragilis and Peptostreptococcus spp. of which 9 strains (37.5%) each were isolated. Escherichia coli and B. fragilis was the most frequently occurring combination. The peak MIC values of TDZ were 0.78 micrograms/ml for B. fragilis and 1.56 micrograms/ml for Peptostreptococcus spp. Most other organisms were also sensitive to TDZ. The bacteriological response of the anaerobic infections to TDZ was 87.5% and overall clinical efficacy was 87.5%. Few side effects were observed.     

A collaborative study of French laboratories to assess any evolution of antibiotic resistance within the Bacteroides fragilis group

Antibiotic susceptibility testing of anaerobes by a same methodology allows the authors to draw up suggestions about the evolution of antibiotic resistance within the B. fragilis group. Cefoxitin resistance rates were stable until 1985 and were slowly increasing later. Until 1985 piperacillin was able to inhibit all tested strains. In 1987 the two groups noticed an increasing resistance to piperacillin (4 to 9%). During the 1970's clindamycin resistance was a minor event (less than 1%) then the resistance rate increased rapidly to 10% in 1980. MICs determinations from 1981 to 1985 demonstrated well that clindamycin resistance was stable at this 10% rate. Since 1987 the clindamycin resistance was again increasing and reached respectively 14 to 19% for the two groups of investigators. Metronidazole has kept a good activity against Bacteroides fragilis group strains but some strains with reduced susceptibility (MIC 2 to 8 mg/l) have been described since 1983. Three strains with MIC greater than 8 mg/l were recently described by one of the groups. Until 1987, the clavulanic amoxicillin combination was able to inhibit all strains of the B. fragilis group but only imipenem remained still active on all investigated strains with no change at all for the values of MIC50 and MIC90 determined by the investigators of this study. All these results emphasize the need for periodical surveys within the B. fragilis group in each country.     

Antibacterial and bactericidal activity of tinidazole against anaerobic bacteria comparing with metronidazole (author's transl)]

Antibacterial activity of tinidazole (1-2-(ethylsulfonyl)-2-methyl-5-nitroimidazole) against anaerobic bacteria including Peptococcus, Peptostreptococcus, Eubacterium, Propionibacterium, Bacteroides and Fusobacterium was studied by agar dilution method comparing with metronidazole. In addition to this work, bactericidal effect of tinidazole and metronidazole against P. prevotii, B. fragilis ss. fragilis and F. varium was examined by quantitative culture method after incubation in GAM broth containing of 4 MIC, 2 MIC, 1 MIC and 1/2 MIC of both drugs against each of three strains for 1, 3, 6, 12 and 24 hours. All the strains of Peptococcus and Peptostreptococcus including P. anaerobius, P. saccharolyticus, P. prevotii and Ps. anaerobius and others were susceptible to a concentration of 6.25 mcg/ml of this drug. A concentration of 3.13 mcg/ml inhibited all strains of Bacteroides including B. fragilis ss. fragilis (12 strains), ss. vulgatus (5 strains), ss. thetaiotaomicron (4 strains) and ss. distasonis (2 strains). To this concentration all strains of Fusobacterium including F. varium (20 strains), F. mortiferum (2 strains) and other Fusobacterium sp. (5 strains) were susceptible. On the contrary, Propionibacterium acnes (6 strains) was resistant to 100 mcg/ml or more of tinidazole and metronidazole. The antibacterial activity of tinidazole was stronger against Bacteroides than that of metronidazole, while almost equal against Peptococcus, Peptostreptococcus, Eubacterium and Fusobacterium. Tinidazole was bactericidal against F. varium in a concentration of 2 MIC till 24 hours of incubation but did not show such an activity on B. fragilis ss. fragilis in same concentration even after 12 hours of incubation. On the other hand, metronidazole was bactericidal against B. fragilis ss. fragilis while was not against F. varium. Against P. prevotii bactericidal activity of both drugs was similar. Tinidazole as well as metronidazole is an excellent chemotherapeutic agent against anaerobic bacteria excluding Propionibacterium acnes and Bifidobacterium adolescentis.     

In vitro activity of vancomycin and teicoplanin against anaerobic bacteria

The in vitro activity of vancomycin and teicoplanin, a new glycopeptide antimicrobial, was determined against a total of 286 anaerobic bacteria including Bacteroides fragilis group (100), B. melaninogenicus (21), B. bivius (16), Fusobacterium spp. (15), Peptococcus spp. (20), Peptostreptococcus spp. (21), Clostridium perfringens (23), C. difficile (41) and Propionibacterium acnes (29). Minimum inhibitory concentrations (MIC) were determined using an antimicrobial incorporation technique in Wilkins-Chalgren agar approximately 10(4) colony forming units (cfu) contained in 10 microliters Wilkins-Chalgren broth, which was applied to the surface of the agar plates using a multipoint inoculator. Following inoculation, plates were incubated for 48 h at 37 degrees C in an anaerobic atmosphere. Both vancomycin and teicoplanin were highly active against all the Gram-positive anaerobic bacteria examined, 90% of all isolates being inhibited by 0.5 micrograms/ml of either antimicrobial. Isolates of B. fragilis group and Fusobacterium spp. were resistant to vancomycin (MIC90 64 micrograms/ml) and teicoplanin (MIC90 128 micrograms/ml). Unexpectedly, isolates of B. melaninogenicus and B. bivius which were resistant to vancomycin (MIC90 64 and 128 micrograms/ml respectively) were sensitive to teicoplanin (MIC90 2 and 2 micrograms/ml respectively).     

Bactericidal studies of penicillin-gentamicin combinations against group B streptococci.

The bactericidal activity of penicillin-aminoglycoside combinations was studied in 16 strains of Group B streptococci. Minimal inhibitory concentrations (MIC) against kanamycin or gentamicin were greater than 50 microgram/ml, whereas ampicillin or penicillin inhibitory concentrations were uniformly less than 0.1 microgram/ml. Although all strains had bactericidal concentrations (MBC) less than 0.1 microgram penicillin/ml, penicillin at a concentration equal to each strains respective MBC reduced inoculum colony forming units (CFU) 2 logs in only 6 of 16 strains in bactericidal kinetic studies. However, the addition of gentamicin in concentrations of 5.0 or 10.0 microgram/ml to penicillin markedly enhanced bactericidal activity in all strains tested. The addition of lower concentrations of gentamicin (1.0 microgram/ml) had minimal advantage over penicillin alone. No distinct advantage was noted for combinations including either ampicillin or kanamycin. The theoretical advantage of penicillin-aminoglycoside combinations in experimental conditions, suggests that the use of antibiotic combinations in clinical infections due to Group B streptococci, may result in a more rapid eradication of these organisms.     

Bacteriological, pharmacokinetic and clinical studies on a rokitamycin dry syrup in the pediatric field

Bacteriological, pharmacokinetic and clinical studies were done on the effect of rokitamycin (RKM, TMS-19-Q) in the field of pediatrics. The results are summarized below. 1. Antibacterial activities Antibacterial activities of RKM against Staphylococcus aureus (including 50 methicillin-sensitive and 50 methicillin-resistant strains), 18 strains of Haemophilus influenzae and 50 strains of Campylobacter jejuni were studied comparatively with activities of josamycin (JM), midecamycin (MDM), erythromycin (EM) and cefaclor (CCL) or ampicillin. Minimum inhibitory concentrations (MICs) of the 5 antibiotics against methicillin-sensitive S. aureus showed a wide variation but RKM was somewhat superior among them. MIC80 of those antibiotics tested against methicillin-sensitive S. aureus were as follows; RKM 1.56, JM 12.5, MDM 12.5, EM 6.25, and CCL 3.13 micrograms/ml. Among methicillin-resistant S. aureus (MRSA), ratios of strains highly resistant to these antibiotics (MIC greater than or equal to 100 micrograms/ml) to total number of strains tested were: 18% to RKM, and 26%, 34% and 48% to JM, MDM and EM, respectively, again showing the superiority of RKM and the proliferation of resistant organisms to EM. MICs of RKM against H. influenzae were distributed in a range between 0.78 and 12.5 micrograms/ml, which were similar to MIC range of CCL, and approximately twice as high as that of EM, but 4 folds lower than those of JM and MDM. Against C. jejuni, the MIC range of RKM was quite broad, 0.10-12.5 micrograms/ml, with a peak value of 0.20 micrograms/ml. The cumulative number of strains vs. MIC curve was similar to that of EM, and RKM was approximately 4 to 8 folds more effective than the other 3 antibiotics. 2. Absorption and excretion The absorption and the excretion of RKM were studied with its dry syrup preparations. Dose levels examined were 5 mg/kg in 2 cases, 10 mg/kg in 7 cases, 15 mg/kg in 2 cases and 20 mg/kg in 1 case. Peak concentrations of RKM in blood were not dose-dependent and were 0.16-0.23, 0.29-0.91, 0.35-0.46 microgram/ml and 0.53 microgram/ml, respectively, for the 4 dose levels. Most of drug levels dropped below the detection limit in 4 hours after the administration when dose levels up to 10 mg/kg were used, and when dose levels were at or above 15 mg/kg, 0.07-0.09 microgram/ml of RKM was detected in blood at 6 hours after the administration. Urinary recovery rates in 6 hours were between 0.19 and 3.31%.(ABSTRACT TRUNCATED AT 400 WORDS)     

Comparative in vitro activities of several antimicrobial agents against Helicobacter pylori

Comparative in vitro activities of several antimicrobial agents against Helicobacter pylori were evaluated. Minimum inhibitory concentrations against 41 strains of H. pylori were determined by using E test. All 41 strains were isolated from gastric mucosa of patients suspected to have gastric ulcer. The ranges of MIC of amoxicillin was from 0.016 microgram/ml and less to 0.064 microgram/ml. The ranges of MIC of clarithromycin, erythromycin, and azithromycin were from 0.016 microgram/ml and less to 64 micrograms/ml, from 0.016 microgram/ml and less to more than 256 micrograms/ml, from 0.064 to more than 256 micrograms/ml, respectively. The ranges of MIC of ciprofloxacin, sparfloxacin, levofloxacin, norfloxacin were from 0.016 microgram/ml and less to 32 micrograms/ml, from 0.002 microgram/ml and less to more than 32 micrograms/ml, from 0.002 microgram/ml and less to more than 32 micrograms/ml, from 0.064 to more than 32 micrograms/ml, respectively.     

In vitro activity against aerobes and anaerobes of trospectomycin versus spectinomycin.

The general antibacterial properties of trospectomycin (TRO) were compared with those of spectinomycin (SPEC) in an in vitro study using a collection of recent clinical isolates: 50 Gram-positive and 25 Gram-negative aerobes and 30 Gram-positive and 15 Gram-negative anaerobes. Minimum inhibitory concentrations (MIC) and minimum bactericidal concentrations (MBC) were determined for all strains by microtitre using serial dilutions in Mueller-Hinton broth for aerobes and Brucella broth for anaerobes. The final inoculum in each well was 10(5) cfu/ml. This study shows that none of the Gram-negative organisms was sensitive to TRO; the most sensitive were streptococci aerobic strains; TRO exhibited antibiotic activity against all anaerobes tested, which was not seen with SPEC, and also exhibited bactericidal activity. The MICs of Staphylococcus epidermidis and Bacteroides fragilis tested with TRO and SPEC were not significantly affected by the size of bacterial inoculum tested, and the nature of the growth medium did not alter the susceptibility tests.     

Nationwide sensitivity surveillance of ciprofloxacin and various parenteral antibiotics against bacteria isolated from patients with severe infections--the first Ciproxan IV special investigation in 2001

The parenteral injection of ciprofloxacin (CPFX), a fluoroquinolone antimicrobial drug, was approved in September 2000 and a re-examination period of 6 years was set at that time. As a special investigation to apply for re-examination of this drug, it has been planned to conduct 3 nationwide surveillances during the re-examination period by collecting clinically isolated bacteria from patients with severe infections, to whom the drug was mainly indicated, and examining drug susceptibilities of the bacteria to various parenteral antimicrobial drugs including CPFX. This time, we determined the minimum inhibitory concentrations (MICs) of various parenteral antimicrobial drugs including CPFX against 1,220 strains isolated from patients with severe infections by the micro-liquid dilution method and compared susceptibilities of various clinically isolated bacteria to CPFX with those to other antimicrobial drugs. Gram-positive bacteria were less susceptible to CPFX than to carbapenems except 2 bacterial species, Enterococcus faecium and Enterococcus avium but susceptibilities of methicillin-susceptible Staphylococcus aureus (MSSA), Staphylococcus epidermidis and Enterococcus faecalis to CPFX were comparable to those to cefozopran. Susceptibility of Streptococcus pneumoniae to CPFX did not differ among ampicillin (ABPC)-susceptible Streptococcus pneumoniae (MIC of ABPC: < 0.25 microgram/ml), ABPC-intermediate S. pneumoniae (MIC of ABPC: 0.25-2 micrograms/ml) and ABPC-resistant S. pneumoniae (MIC of ABPC: > or = 4 micrograms/ml) MIC90 of CPFX: 1 microgram/ml) and a decrease in the antimicrobial activity seen among cephem and carbapenem antimicrobial drugs against penicillin-intermediate strains was not noted with CPFX. Gram-negative bacteria were susceptible to CPFX similarly to carbapenems and the MIC90 values of CPFX were in the range from < or = 0.063 to 2 micrograms/ml against strains except Stenotrophomonas maltophilia and Burkholderia cepacia. Pseudomonas aeruginosa was most susceptible to CPFX among the antibacterial drugs examined and the MIC90 was 2 micrograms/ml. CPFX also showed the lowest MIC90 value (0.5 microgram/ml) against beta-lactam-resistant P. aeruginosa among the drugs examined. When extended-spectrum beta-lactamase (ESBL) production and class B beta-lactamase production were examined in 439 strains of Enterobacteriaceae and 168 strains of glucose non-fermentative bacteria out of the Gram-negative bacteria collected this time, 3 strains (0.49%) producing ESBL and 7 strains (1.15%) producing class B beta-lactamase were found. The MIC range of CPFX to these 10 strains was between < or = 0.063 to 8 micrograms/ml and 5 strains among those showed susceptibilities (MIC of CPFX: 1 microgram/ml) based on the NCCLS breakpoint. CPFX also showed a satisfactory result concerning susceptibilities of major causal bacteria based on the report of the committee of Japan Society of Chemotherapy on the standard method for determination of susceptibility to antimicrobial agents, the breakpoint of pneumonia. Furthermore, susceptibilities of various bacteria isolated clinically from patients with severe infections this time did not differ much from the result of the nationwide surveillance which we conducted in 1997. Thus, it was concluded that the antimicrobial activity of CPFX was maintained in the post-marketing surveillance for its parenteral preparation.     

In vitro activities of levofloxacin and other antibiotics against fresh clinical isolates

In this study, the in vitro activity of levofloxacin (LVFX) against 1,020 fresh bacterial clinical isolates was compared with the activities of a range of ofloxacin, ciprofloxacin (CPFX), ampicillin (ABPC), cefaclor, cefpodoxime, methicillin and benzylpenicillin. The clinical isolates except Vibrio cholerae were collected in Japan during 1998 from patients with infectious diseases. MICs were determined using the agar dilution method according to the recommendations by the Japan Society of Chemotherapy. Some isolates of methicillin resistant Staphylococcus aureus (MRSA) and coagulase negative Staphylococcus were resistant to fluoroquinolones, but the MIC50 of LVFX against MRSA was 6.25 micrograms/ml. LVFX was the most active against MRSA among the antibiotics tested. Most of Staphylococcus epidermidis strains were susceptible to the fluoroquinolones. LVFX showed greater activity against all streptococci strains compared with fluoroquinolones tested. In particular, all Streptococcus pneumoniae strains including PRSP were susceptible to LVFX at < or = 1.56 micrograms/ml. Among Enterococcus, ABPC showed superior activity against Enterococcus faecalis but many isolates of Enterococcus species were resistant to ABPC. LVFX was more active against to these Enterococcus species compared with other fluoroquinolones. On the other hand, LVFX and CPFX showed similar activity against isolates of Enterobacteriaceae. CPFX had an MIC50/90 of 0.20, 0.39 microgram/ml and LVFX showed an MIC50/90 of 0.78, 1.56 micrograms/ml against Pseudomonas aeruginosa. LVFX (MIC50/90 0.10, 0.20 microgram/ml) was more active against Acinetobacter species than CPFX (MIC50/90 0.10, 0.39 microgram/ml). Haemophilus influenzae, Branhamella (Moraxella) catarrhalis and V. cholerae were inhibited by low concentration of the fluoroquinolones tested. The MIC90 of LVFX and CPFX were < or = 0.10 microgram/ml against above three species. Some isolates of Neisseria gonorrhoeae and Campylobacter species were moderately resistant to the fluoroquinolones tested but the MIC50 of LVFX and CPFX were < or = 0.39 microgram/ml. Among anaerobes, Propionibacterium acnes was more susceptible than Peptostreptococcus species, and the MIC90 of beta-lactams and fluoroquinolones tested were < or = 0.78 microgram/ml. In conclusion, this study, performed on large number of strains, confirmed an excellent and wide spectrum antibacterial activity of LVFX compared with the fluoroquinolones and beta-lactams tested. And our results suggest that LVFX may be useful in the treatment of various bacterial infections.     

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 studies on 9, 3"-diacetylmidecamycin in respiratory tract infections in the field of pediatrics (author's transl)

Laboratory and clinical studies were performed on 9, 3"-diacetylmidecamycin (MOM), a new macrolide antibiotic in the field of pediatrics, and the results were as follows. Antibacterial activity: For 32 clinically isolated strains of Staphylococcus aureus, the MIC of MOM ranged from 0.78 to 1.56 micrograms/ml for 17 of the 32 strains, and exceeded 100 micrograms/ml for the 15 remaining strains with both inoculum sizes of 10(8) cells/ml and 10(6) cells/ml. For 27 strains of Streptococcus pyogenes, the MIC range was wide, varying from 0.10 to greater than or equal to 100 micrograms/ml and less than 1.56 micrograms/ml for about 2/3 of all the 27 strains. For 9 strains of Bordetella pertussis, the MIC ranged from 0.10 to 0.78 microgram/ml and 0.10 to 0.39 microgram/ml with the inoculum size of 10(8) cells/ml and 10(6) cells/ml, respectively. Comparing the antibacterial activity of MOM with that of midecamycin (MDM) and erythromycin (EM) against these 3 bacterial species, MOM was almost comparable to MDM, but about 2 or 3 tubes inferior to EM. Absorption and excretion: MOM was administered to 5 children (from 5 to 8 years old) at a dose of 10 mg/kg or 20 mg/kg at 30 minutes before breakfast. The peak of serum concentration was observed 30 minutes to 1 hour after administrations of both dosages: 0.52 to 1.71 micrograms/ml with 10 mg/kg and 0.88 to 1.77 micrograms/ml with 20 mg/kg. 0.09 to 1.10% and 0.94 to 1.19% of MOM were excreted in the urine within the first 6 hours, respectively. Clinical results: MOM was administered to 28 pediatric patients with acute respiratory tract infections (acute pharyngitis; 2, acute purulent tonsillitis; 19, acute bronchitis; 4, acute pneumonia; 2 and whooping cough; 1). The overall clinical response was excellent in 10, good in 10, fair in 3 and poor in 5; the efficacy rate was 71.4%. Isolated S. pyogenes strains were eradicated in 6 out of 11 strains, reduced in 3 and unchanged in 2 strains. One strain of S. aureus was eradicated. One strain of non group A beta-Streptococcus was reduced. Haemophilus influenzae strains were reduced in 1 of the 4 strains and unchanged in 3 strains. The overall eradication rate was 41.2%. No side effects or abnormal laboratory findings were observed, but 1 case complained of a bitter taste.     

Clinical studies of cefotaxime (CTX, HR 756) for infectious diseases in the field of obstetrics and gynecology (author's transl)

Ten cases of gynecological infection were treated successfully by a new cephalosporin derivative, cefotaxime (HR 756, CTX), which proved excellent in 4 cases and good in 6 cases. No adverse reaction was found to be induced by administration of this drug. Post-administration results were all normal for both renal and hepatic function tests. It is extremely difficult to accurately assess bacteriological efficacy of a drug in treatment of female genital infections. Nevertheless, we determined its MICs for a few number of strains we could isolate from clinical cases. Its MIC against 4 strains of B. fragilis inoculated at 10(8) cells/ml was 25 approximately 50 mcg/ml and was 1.56 approximately 3.13 mcg/ml at 10(6) cells/ml inoculation. Its MIC against 2 strains of Ps. cepacia was 12.5 mcg/ml at 10(8) cells/ml inoculation and 6.25 mcg/ml at 10(6) cells/ml inoculation. These MICs suggest that this drug is a very promising antimicrobial agent for treatment of gynecological infections, as been already indicated by clinical results of this drug.     

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)