Effect of ring size on conformations of aromatic amine-DNA adducts: the aniline-C8 guanine adduct resides in the B-DNA major groove

We isolated strains of Helicobacter pylori from gastric mucosa of patients with peptic ulcer before and after eradication therapy, and studied their sensitivity to amoxicillin (AMPC) and clarythromycin (CAM). Of 85 strains of H. pylori isolated before therapy, MIC90 was 0.025 microgram/ml and no strains were resistant to AMPC. On the other hand, MIC90 of CAM was 0.05 microgram/ml and seven (8.2%) were already resistant to CAM. The H. pylori strains from eight cases of failed eradication therapy with lansoprazole + AMPC remained AMPC sensitive. However H. pylori strains from nineteen cases (82.6%) out of 23 of failed eradication therapy with lansoprazole + CAM became CAM resistant. The situation was similar for the cases of failed eradication therapy with lansoprazole + AMPC + CAM. Drug sensitivity tests prior to eradication therapy are to be recommended. A disc method may be used as a simple alternative to MIC measurement.     

Comparative studies on activities of antimicrobial agents against causative organisms isolated from patients with urinary tract infections (1996). I. Susceptibility distribution

The frequencies of isolation and susceptibilities to antimicrobial agents were investigated on 680 bacterial strains isolated from patients with urinary tract infections (UTIs) in 10 hospitals during the period of June 1996 to May 1997. Of the above bacterial isolates, Gram-positive bacteria accounted for 30.4% and a majority of them were Enterococcus faecalis. Gram-negative bacteria accounted for 69.6% and most of them were Escherichia coli. Susceptabilities 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 Arbekacin (ABK) and VCM showed the highest activities against both S. aureus and MRSA isolated from patients with UTIs. The MIC90S of them were 1 or 2 micrograms/ml. The others except minocycline (MINO) had low activities with the MIC90S of 32 micrograms/ml or above. 3. Staphylococcus epidermidis ABK and VCM showed the strongest activities against S. epidermis isolated from patients with UTIs. The MICs for all strains were equal to or lower than 2 micrograms/ml. Cefazolin (CEZ), cefotiam (CTM) and cefozopran (CZOP) were also active with the MIC90S of 4 micrograms/ml. Compared with antimicrobial activities of cephems is 1995, the MIC90S of them had changed into a better state. They ranged from 4 micrograms/ml 16 micrograms/ml in 1996. 4. Streptococcus agalactiae All drugs except MINO were active against S. agalactiae. ABPC, CZOP, IPM, and clarithromycin (CAM) showed the highest activities. The MICs for all strains were equal to or lower than 0.125 micromilligrams. Tosufloxacin (TFLX) and VCM were also active with the MIC90S of 0.5 micromilligrams. 5. Citrobacter freundii Gentamicin (GM) showed the highest activity against C. freundii isolated from patients with UTIs. Its MIC90 was 0.5 micrograms/ml. IPM and amikacin (AMK) were also active with the MIC90S of 1 microgram/ml and 2 micrograms/ml, respectively. Cefpirome (CPR) and CZOP were also active with the MIC90S of 8 micrograms/ml. The MIC90S of the others were 16 micrograms/ml or above. 6. Enterobacter cloacae IPM showed the highest activity against E. cloacae. The MICs for all strains were equal to or lower than 0.5 microgram/ml. The MIC90S of ciprofloxacin (CPFX) and TFLX were 1 microgram/ml, the MIC90 of AMK was 2 micrograms/ml, the MIC90S of CZOP, GM and ofloxacin (OFLX) were 4 micrograms/ml. The MIC50S of cephems except CEZ, cefmetazole (CMZ) and cefaclor (CCL) had changed into a better state in 1996, compared with those in 1995. 7. Escherichia coli All drugs except penicillins and MINO were active against E. coli. Particularly CPR, CZOP and IPM showed the highest activities against E. coli. The MIC90S of them were 0.125 microgram/ml or below. Among E. coli strains, those with low susceptibilities to cephems except CEZ, cefoperazone (CPZ), latamoxef (LMOX) and CCL have increased in 1996, compared with those in 1995. 8. Klebsiella pneumoniae K. pneumoniae was susceptible to all drugs except penicillins, with the MIC90S of 2 micrograms/ml or below. CPR had the strongest activity, the MICs for all strains were equal to or lower than 0.25 microgram/ml. Flomoxef (FMOX), cefixime (CFIX), CZOP and carumonam (CRMN) were also active with the MIC90S of 0.125 microgram/ml or below. 9. Pseudomonas aeruginosa All drugs except quinolones were not so active against P. aeruginosa with the MIC90S were 32 micrograms/ml or above. Quinolones were more active in 1996 than 1995. The MIC90S of them were between 4 micrograms/ml and 8 micrograms/ml, and the MIC50S of them were between 1 microgram/ml and 2 micrograms/ml. 10. Serratia marcescens GM showed the highest activity against S. marcescens. Its MIC90 was 1 micro     

In vitro activity of biapenem against beta-lactamase producing Enterobacteriaceae

The activity of biapenem was compared with that of imipenem and cefotaxime against 108 strains of beta-lactamase producing Enterobacteriaceae. Biapenem and imipenem were very active, inhibiting 90% of the strains at a concentration of 0.5 microgram/ml. Both carbapenems were very active against plasmidic beta-lactamase producers, with MIC90s below 1 microgram/ml. However, the MIC90 of biapenem for cephalosporinase producers was 1 microgram/ml. Against strains producing extended-spectrum beta-lactamases, biapenem exhibited better activity against TEM-type producers (MIC90 0.25 microgram/ml) than against SHV-type producers (MIC90 0.5 microgram/ml). Overall, the in vitro antibacterial activity of biapenem is similar to that of imipenem.     

Antimicrobial activity of RU-66647, a new ketolide

A new macrolide subclass called ketolides, possess a mode of action similar to the macrolide-lincosamide-streptogramin (MLS) compounds. Utilizing reference in vitro tests, the in vitro activity of RU-66647 (a ketolide) was compared to other MLS compounds against 376 Gram-positive organisms and over 400 representative strains of Gram-negative bacilli. The ketolide's spectrum was most similar to clindamycin and an earlier drug in the series (RU-64004 or RU-004) against staphylococci and streptococci. However, RU-66647 was more active than erythromycin and azithromycin against oxacillin-resistant Staphylococcus spp. and vancomycin-resistant enterococci. Ketolide activity was more potent than other MLS drugs against vancomycin-susceptible enterococci (MIC90, 0.25-4 micrograms/ml) and all streptococci (MICs, < or = 0.25 microgram/ml). Erythromycin-resistant (constitutive) strains were generally inhibited by < or = 2 micrograms RU-66647/ml (staphylococci, 31 to 36%; streptococci, 100%; enterococci, 72%). RU-66647 was active against Haemophilus influenzae (MIC90, 2 micrograms/ml), Moraxella catarrhalis (MIC90, 0.12 microgram/ml), and pathogenic Neisseria spp. (MIC90 0.5 microgram/ml). The ketolide failed to inhibit Enterobacteriaceae, nonfermentative Gram-negative bacilli, and Bacteriodes fragilis group strains. RU-66647 was observed to be a promising new compound directed toward some organisms resistant to other MLS-class drugs.     

Susceptibilities of bacteria isolated from patients with lower respiratory infectious diseases to antibiotics (1996)

The bacteria isolated from the patients with lower respiratory tract infections were collected by institutions located throughout Japan, since 1981. Ikemoto et al. have been investigating susceptibilities of these isolates to various antibacterial agents and antibiotics, and characteristics of the patients and isolates from them each year. Results obtained from these investigations are discussed. In 16 institutions around the entire Japan, 557 strains of presumably etiological bacteria were isolated mainly from the sputa of 449 patients with lower respiratory tract infections during the period from October 1996 to September 1997. MICs of various antibacterial agents and antibiotics were determined against 98 strains of Staphylococcus aureus, 93 strains of Streptococcus pneumoniae, 84 strains of Haemophilus influenzae, 84 strains of Pseudomonas aeruginosa (non-mucoid strains), 17 strains of Pseudomonas aeruginosa (mucoid strains), 31 strains of Moraxella subgenus Branhamella catarrhalis, 21 strains of Klebsiella pneumoniae etc., and the drug susceptibilities of these strains were assessed except for those strains that died during transportation. 1) S. aureus S. aureus strains for which MICs of oxacillin (MPIPC) were higher than 4 micrograms/ml (methicillin-resistant S. aureus) accounted for 67.3%. The frequency of the drug resistant bacteria increased comparing to the previous year's 52.7%. Arbekacin (ABK) and vancomycin (VCM) showed the highest activities against both S. aureus and MRSA with MIC80s of 1 microgram/ml. 2) S. pneumoniae Imipenem (IPM) and panipenem (PAPM) of carbapenems showed the most potent activities with MIC80s of 0.063 microgram/ml. Faropenem (FRPM) showed the next potent activity with MIC80 of 0.125 microgram/ml. The other drugs except erythromycin (EM), clindamycin (CLDM) and tetracycline (TC) were active against S. pneumoniae tested with MIC80s of 8 micrograms/ml or below. 3) H. influenzae The activities of all drugs were potent against H. influenzae tested with MIC80s of 4 micrograms/ml or below. Cefotiam (CTM), cefmenoxime (CMX), cefditoren (CDTR) and ofloxacin (OFLX) showed the most potent activities with MIC80s of 0.063 microgram/ml. 4) P. aeruginosa (mucoid strains) Tobramycin (TOB) showed the most potent activity against P. aeruginosa (mucoid strains) with MIC80 of 1 microgram/ml. Ceftazidime (CAZ), cefsulodin (CFS), IPM, gentamicin (GM), ABK and ciprofloxacin (CPFX) showed the next potent activities, with MIC80s of 2 micrograms/ml. The MIC80s of the other drugs ranged from 4 micrograms/ml to 16 micrograms/ml. 5) P. aeruginosa (non-mucoid strains) TOB and CPFX showed the most potent activities against P. aeruginosa (non-mucoid strains) with MIC80s of 1 microgram/ml. The MIC80s of piperacillin (PIPC) and cefoperazone (CPZ) were 16 micrograms/ml in 1995, and they were 64 micrograms/ml in 1996. 6) K. pneumoniae All drugs except ampicillin (ABPC) were active against K. pneumoniae. CMX, cefpirome (CPR), cefozopran (CZOP) and carumonam (CRMN) showed the most potent activities against K. pneumoniae with MIC80s of 0.125 microgram/ml. The MIC80s of the other drugs ranged from 0.25 microgram/ml to 2 micrograms/ml. 7) M.(B) catarrhalis Against M.(B.) catarrhalis, all drugs showed good activities with MICs of 4 micrograms/ml or below. IPM and minocycline (MINO) showed the most potent activities with MICs of 0.063 microgram/ml. Also, we investigated year to year changes in the characteristics of patients, their respiratory infectious diseases, and the etiology. Patients' backgrounds were examined for 557 isolates from 449 cases. The examination of age distribution indicated that the proportion of patients with ages over 60 years was 71.0% of all the patients showing a slight increase over that in 1994. Proportions of diagnosed diseases were as follows: Bacterial pneumonia and chronic bronchitis were the most frequent with 35.9% and 30.3% respectively. They were followed by bronchiectasis with a proportion of 10.     

Expression patterns of proliferating cell nuclear antigen in the small intestine of mice infected with Metagonimus yokogawai and Metagonimus Miyata type

The in vitro antimicrobial activities of AM-1155, a new fluoroquinolone, tosufloxacin and fleroxacin were tested against 55 clinical isolates of Neisseria gonorrhoeae using the agar dilution method. In our previous study, all the strains had been examined for mutations in the region corresponding to the quinolone-resistance determining region of the Escherichia coli gyrA gene and the analogous region of the parC gene, and tested for susceptibility to ciprofloxacin. In this study, the 55 isolates of N. gonorrhoeae were assigned to one of three categories based on the presence or absence of alterations in GyrA and ParC. In each category, the antimicrobial activity of AM-1155 against the isolates was compared with those of tosufloxacin and fleroxacin. The MICs of AM-1155 for 11 highly fluoroquinolone-resistant isolates with alterations in both GyrA and ParC ranged from 0.06 to 1.0 microgram/ml. The MICs inhibiting 50% (MIC50) and 90% (MIC90) of these isolates were 0.125 and 1.0 microgram/ml, respectively. The MICs of AM-1155 for 20 moderately fluoroquinolone-resistant isolates with alterations only in GyrA ranged from 0.03 to 0.25 microgram/ml (MIC50, 0.06 microgram/ml; MIC90m, 0.125 microgram/ml). The MICs of AM-1155 for 24 of the quinolone-susceptible isolates without alterations in either GyrA or ParC ranged from 0.004 to 0.03 microgram/ml (MIC50, 0.008 microgram/ml. MIC90, 0.015 microgram/ml). There were significant differences between the MIC distribution of AM-1155 and each corresponding MIC distribution of tosufloxacin and fleroxacin in these three categories to which the 55 isolates were assigned (p < 0.05). Based on the MIC90S of the tested fluoroquinolones, AM-1155 was two- and eightfold more active against the highly fluoroquinolone-resistant isolates than tosufloxacin and fleroxacin, respectively. Against the moderately fluoroquinolone-resistant isolates, AM-1155 was four- and sixteenfold more active than tosufloxacin and fleroxacin, respectively. Against the quinolone-susceptible strains, AM-1155 was also two- to fourfold more active than the other fluoroquinolones. Overall, AM-1155 exhibited more potent in vitro activity against both quinolone-resistant and quinolone-susceptible isolates of N. gonorrhoeae than tosufloxacin and fleroxacin. In ciprofloxacin treatment failures of gonorrhea at single doses of 500 mg. MICs for the causative organisms have ranged from 1.0 to 16.0 micrograms/ml. The MICs of AM-1155 for the isolates harboring quinolone resistance-associated genetic alterations, including strains exhibiting ciprofloxacin MICs of 2.0 and 8.0 micrograms/ml, still ranged from 0.03 to 1.0 microgram/mL A single-dose study in humans has demonstrated higher peak serum concentrations and longer half-lives of AM-1155, resulting in the AUC0-00 values of AM-1155, which are threefold greater than those of ciprofloxacin at the single doses of 400 and 600 mg. Because of its potent in vitro antimicrobial activity and advantageous pharmacokinetic behavior, AM-1155 may be a clinically useful agent for treating gonorrhea including that caused by quinolone-resistant strains.     

MIC and time-kill study of antipneumococcal activities of RPR 106972 (a new oral streptogramin), RP 59500 (quinupristin-dalfopristin), pyostacine (RP 7293), penicillin G, cefotaxime, erythromycin, and clarithromycin against 10 penicillin-susceptible and -resistant pneumococci

Broth MICs and time-kill studies were used to test the activity of RP 59500 (quinupristin-dalfopristin), RPR 106972, pyostacine (RP 7293), erythromycin, clarithromycin, and cefotaxime for four penicillin-susceptible (MICs of 0.008 to 0.03 microgram/ml), two penicillin-intermediate (MIC of 0.25 microgram/ml), and four penicillin-resistant (MIC of 2.0 to 4.0 micrograms/ml) strains of pneumococci: 6 of 10 strains were resistant to macrolides (MICs of > or = 0.5 microgram/ml). MICs of RP 59500 (0.5 to 1.0 microgram/ml), RPR 106972 (0.125 to 0.25 microgram/ml), and pyostacine (0.125 to 0.25 microgram/ml) did not alter with the strain's penicillin or macrolide susceptibility status. Three penicillin-susceptible strains and one penicillin-intermediate strain were susceptible to macrolides (MICs of < or = 0.25 microgram/ml); the macrolide MICs for the remaining strains were > or = 4.0 micrograms/ml. Cefotaxime MICs rose with those of penicillin G, but all strains were inhibited at MICs of < or = 2.0 micrograms/ml. RP 59500 was bactericidal for all strains after 24 h at 2 x MIC and yielded 90% killing of all strains at 6 h at 2 x MIC; at 8 x MIC, RP 59500 showed 90% killing of six strains within 10 min (approximately 0.2 h). In comparison, RPR 106972 was bactericidal for 9 of 10 strains at 2 x MIC after 24 h and yielded 90% killing of all strains at 2 x MIC after 6 h; 90% killing of six strains was found at 8 x MIC at 0.2 h. Results for pyostacine were similar to those of RPR 106972. Erythromycin and clarithromycin were bactericidal for three of four macrolide-susceptible strains after 24 h at 4 x MIC. Clarithromycin yielded 90% killing of three strains at 8 x MIC after 12 h. Cefotaxime was bactericidal for all strains after 24 h at 4 x MIC, yielding 90% killing of all strains after 6 h at 4 x MIC. All three streptogramins yielded rapid killing of penicillin- and erythromycin-susceptible and -resistant pneumococci and were the only compounds which killed significant numbers of strains at 0.2 h.     

Cervical stenosis and dystonic cerebral palsy

We have tested the in vitro activities of eight fluoroquinolones against 160 Brucella melitensis strains. The most active was sitafloxacin (MIC at which 90% of the isolates are inhibited [MIC90], 0.12 microg/ml). In decreasing order, the activities (MIC90s) of the rest of the tested fluoroquinolones were as follows: levofloxacin, 0.5 microg/ml; ciprofloxacin, trovafloxacin, and moxifloxacin, 1 microg/ml; and ofloxacin, grepafloxacin, and gatifloxacin, 2 microg/ml.     

Antimicrobial susceptibility of Capnocytophaga

Capnocytophaga (Bacteroides ochraceus, Center for Disease Control biogroup DF-1) is associated with sepsis in granulocytopenic patients and is isolated in large numbers from the affected periodontal pockets in patients with juvenile periodontosis. The minimal inhibitory concentrations (MICs) and minimal bactericidal concentrations (MBCs) of 17 antimicrobial agents for 13 strains of Capnocytophaga organisms were determined. In addition, the ratio of the MBC to the MIC for each antimicrobial agent was determined for each strain. At concentrations of 1 microgram/ml or less, penicillin, ampicillin, carbenicillin, erythromycin, and clindamycin killed 90% of the strains. At concentrations of 3.12 microgram/ml or less, tetracycline, metronidazole, cefoxitin, and chloramphenicol killed 90% of the strains. None of the aminoglycosides tested demonstrated antibacterial activity at 50 microgram/ml. Penicillin, ampicillin, carbenicillin, and cefoxitin exhibited MBC/MIC ratios of 4 or less with all strains. Erythromycin, tetracycline, and metronidazole exhibited MBC/MIC ratios of 4 or less for 12 of 13 strains. The MICs of cephalothin and cefazolin for 90% of the strains were 25 and 50 microgram/ml, respectively. The MBC/MIC ratios for these drugs were 4 or less for 12 of 13 and 7 of 13 strains, respectively. The MIC of cefamandole for 90% of the strains was 3.12 microgram/ml; however, only nine strains had an MBC/MIC ratio of 4 or less.     

Comparative studies on activities of antimicrobial agents against causative organisms isolated from patients with urinary tract infections (1995). I. Susceptibility distribution]

The frequencies of isolation and susceptibilities to antimicrobial agents were investigated on 704 bacterial strains isolated from patients with urinary tract infections (UTIs) in 11 hospitals during the period of June 1995 to May 1996. Of the above bacterial isolates, Gram-positive bacteria accounted for 29.8% and a majority of them were Enterococcus faecalis. Gram-negative bacteria accounted for 70.2% and most of them were Escherichia coli. Susceptibilities of several isolated bacteria to antimicrobial agents were as followed; 1. Enterococcus faecalis Ampicillin (ABPC) and imipenem (IPM) showed the highest activities against E. faecalis isolated from patients with UTIs. The MIC90S of them were 1 microgram/ml. Vancomycin (VCM) and piperacillin (PIPC) were also active with the MIC90S of 2 micrograms/ml and 4 micrograms/ml, respectively. The others had low activities with the MIC90S of 16 micrograms/ml or above. 2. Staphylococcus aureus including MRSA VCM showed the highest activities against S. aureus isolated from patients with UTIs. Its MIC90 was 1 microgram/ml against both S. aureus and MRSA. Arbekacin (ABK) was also active with the MIC90 of 2 micrograms/ml. The other except minocycline (MINO) had very low activities with the MIC90S of 64 micrograms/ml or above. 3. Staphylococcus epidermidis ABK and MINO showed the strongest activities against S. epidermidis isolated from patients with UTIs. The MIC90S of them were 0.25 microgram/ml. VCM was also active with the MIC90 of 1 microgram/ml. The MIC90S of cephems ranged from 2 micrograms/ml to 16 micrograms/ml in 1994, but they ranged from 8 micrograms/ml to 128 micrograms/ml in 1995. These results indicated that some resistances existed among S. epidermidis to cephems. 4. Streptococcus agalactiae All drugs except gentamicin (GM) were active against S. agalactiae. ABPC, cefmenoxime (CMX), IPM, erythromycin (EM), clindamycin (CLDM) and clarithromycin (CAM) showed the highest activities. The MICs for all strains were lower than 0.125 microgram/ml. The MIC90S of the others were 2 micrograms/ml or below. 5. Citrobacter freundii IPM showed the highest activity against C. freundii isolated from patients UTIs. Its MIC90 was 1 microgram/ml. GM was also active with the MIC90 of 2 micrograms/ml. Cefpirome (CPR), cefozopran (CZOP) and amikacin (AMK) were also active with the MIC90S of 4 micrograms/ml. Penicillins and cephems except CMX, CPR and CZOP showed low activities with MIC90S of 256 micrograms/ml or above. 6. Enterobacter cloacae IPM showed the highest activity against E. cloacae. The MICs for all strains were equal to or lower than 1 microgram/ml. MINO and tosufloxacin (TFLX) were also active with the MIC90S of 8 micrograms/ml. Penicillins and cephems except CPR and CZOP showed lower activities with the MIC90S of 256 micrograms/ml or above. 7. Escherichia coli. Most of the antimicrobial agents were active against E. coli. Particularly CPR, CZOP and IPM showed the highest activities against E. coli. The MICs for all strains were equal to or lower than 0.5 microgram/ml. CMX and TFLX were also active with the MIC90S of 0.125 microgram/ml or below. Penicillins were slightly active with MIC90S of 128 micrograms/ml or above. 8. Klebsiella pneumoniae K. pneumoniae was susceptible to all drugs except penicillins, with MIC90S of 2 micrograms/ml or below. Carumonam (CRMN) had the strongest activity against K. pneumoniae, the MICs for all strains were equal to or lower than 0.125 microgram/ml. Comparing with the result of 1994, the sensitivities of K. pneumoniae against all drugs had obviously changed into a better state. For example, the MIC90S of cephems ranged from 0.25 microgram/ml to 16 micrograms/ml in 1994, but they were all lower than 2 micrograms/ml in 1995. 9. Proteus mirabilis P. mirabilis was susceptible to a majority of drugs. CMX, ceftazidime (CAZ), cefixime (CFIX), and CRMN showed the highest activities against P. mirabilis isolated from patients with UTIs. MICs of CRMN for all     

Susceptibility testing interpretive criteria for levofloxacin when testing respiratory pathogens, Haemophilus influenzae and Moraxella catarrhalis

The more active L-isomer, levofloxacin, of the racemic ofloxacin mixture has been under development for therapeutic use. In this study, we evaluated the activity of ofloxacin, levofloxacin, and D-ofloxacin against the fastidious respiratory tract pathogens Haemophilus influenzae and Moraxella catarrhalis. Levofloxacin was two-fold more active than ofloxacin against H. influenzae (MIC90, 0.015 microgram/ml), and D-ofloxacin was least active (MIC90, 1 microgram/ml). For M. catarrhalis the MIC90 values were 0.03 microgram/ml, 0.06 microgram/ml, and 2 micrograms/ml for levofloxacin, ofloxacin, and D-ofloxacin, respectively. For disk diffusion susceptibility testing, Chocolate Mueller-Hinton agar (CMH) was considered preferable to Haemophilus test medium (HTM) because it supported the growth of all of 105 H. influenzae strains whereas five strains failed to grow on HTM. In addition, the margins of the zones of inhibition were more distinct on CMH and the Haemophilus species strains with elevated fluoroquinolone MICs were readily distinguished. The superior growth on CMH was reflected in a reduction of inhibition zone diameters of 2-3 mm relative to the inhibition zone diameters on HTM. The previously proposed interpretive criteria for the 5 microgram disk diffusion susceptibility test (susceptible at > or = 17 mm) results in complete categorical agreement with the reference microdilution broth method for M. catarrhalis on Mueller Hinton agar and for H. influenzae on HTM and CMH. However, the minimum diameter of the zone of inhibition recorded for a member of the dominant population of either species was considerably greater (25 mm) than 17 mm on any of the media tested.     

N-1-tert-butyl-substituted quinolones: in vitro anti-Mycobacterium avium activities and structure-activity relationship studies

We determined the MICs of 63 quinolones against 14 selected reference and clinical strains of the Mycobacterium avium-Mycobacterium intracellulare complex. Sixty-one of the compounds were selected from the quinolone library at Parke-Davis, Ann Arbor, Mich., including N-1-tert-butyl-substituted agents. T 3761 and tosufloxacin were also tested. The activities of all 63 compounds were compared with those of ciprofloxacin and sparfloxacin. The results showed 45 of the quinolones to be active against the M. avium-M. intracellulare complex, with MICs at which 50% of the strains were inhibited (MIC50s) of less than 32 micrograms/ml. Twenty-four of these quinolones had activities equivalent to or greater than that of ciprofloxacin, and nine of them had activities equivalent to or greater than that of sparfloxacin. The most active compounds were the N-1-tert-butyl-substituted quinolones, PD 161315 and PD 161314, with MIC50s of 0.25 microgram/ml and MIC90s of 1 microgram/ml; comparable values for ciprofloxacin were 2 and 4 micrograms/ml, respectively, while for sparfloxacin they were 1 and 2 micrograms/ml, respectively. The next most active compounds, with MIC50s of 0.5 microgram/ml and MIC90s of 1 microgram/ml, were the N-1-cyclopropyl-substituted quinolones, PD 138926 and PD 158804. These values show that the tert-butyl substituent is at least as good as cyclopropyl in rendering high levels of antimycobacterial activity. However, none of the quinolones showed activity against ciprofloxacin-resistant laboratory-derived M. avium-M. intracellulare complex strains. A MULTICASE program-based structure-activity relationship analysis of the inhibitory activities of these 63 quinolones and 109 quinolones previously studied against the most resistant clinical strain of M. avium was also performed and led to the identification of two major biophores and two biophobes.     

N,N-dimethylglycyl-amido derivative of minocycline and 6-demethyl-6-desoxytetracycline, two new glycylcyclines highly effective against tetracycline-resistant gram-positive cocci

The in vitro activities of the N,N-dimethylglycyl-amino derivative of minocycline (DMG-MINO) and 6-dimethyl-6-dexoxytetracycline (DMG-DMDOT), members of a new generation of tetracyclines, were evaluated by an agar dilution method and were compared with those of tetracycline and minocycline against 224 tetracycline-resistant and 73 tetracycline-susceptible recent clinical isolates of gram-positive cocci, including multiple-antibiotic-resistant methicillin-resistant Staphylococcus aureus and penicillin-resistant Streptococcus pneumoniae. The MICs of DMG-MINO and DMG-DMDOT were up to 500- to 2,000-fold lower than those of tetracycline against methicillin-resistant S. aureus and Streptococcus pneumoniae (MIC for 50% of strains tested [MIC50], < 0.06 microgram/ml). Against Streptococcus groups A, B, C, and G and Enterococcus faecalis, the MIC50 was 0.5 microgram/ml. MIC50s were greater only for coagulase-negative staphylococci (2 micrograms/ml). These data indicate that DMG-MINO and DMG-DMDOT are very potent drugs, and further in vitro and in vivo studies are warranted.     

In vitro activity of dirithromycin against Chlamydia trachomatis

Dirithromycin is a new macrolide antibiotic with an active metabolite, erythromycylamine. We evaluated the in vitro activities of both drugs against 16 isolates of Chlamydia trachomatis and compared them with that of doxycycline. In vitro susceptibility testing was performed with McCoy cell monolayers. The MIC was defined as the lowest concentration of antibiotic without inclusions. The MBC was defined as the lowest concentration of antibiotic yielding no inclusions after passage onto 24-h-old antibiotic-free McCoy cell monolayers. Dirithromycin and erythromycylamine appeared to be equally effective against these 16 strains of C. trachomatis (MIC for 90% of strains tested, 1 mg/ml; MBC for 90% of strains tested, 2 micrograms/ml). Both were less active than doxycycline (MIC for 90% of strains tested, 0.06 micrograms/ml; MBC for 90% of strains tested, 0.12 micrograms/ml). The combination of dirithromycin and erythromycylamine appeared to be additive.     

Decreased nitrogen rates and irrigation effect on celery yield and internal quality

Sparfloxacin, a new orally administered fluoroquinolone, was tested against 14,182 clinical strains isolated (generally blood stream and respiratory tract cultures) at nearly 200 hospitals in the United States (USA) and Canada. Sparfloxacin activity was compared with 13 other compounds by Etest (AB BIODISK, Solna, Sweden), broth microdilution, or a standardized disk diffusion method. Using the Food and Drug Administration/product package insert MIC breakpoint for sparfloxacin susceptibility (< or = 0.5 microgram/ml), 94% of Streptococcus pneumoniae (2666 isolates) and 89% of the other streptococci (554 isolates) were susceptible. However, at < or = 1 microgram/ml (the breakpoint for all nonstreptococcal species) sparfloxacin susceptibility rates increased to 100% and 98%, respectively, for the two groups of streptococci. Only 50% and 65% of pneumococci were susceptible to ciprofloxacin (MIC90, 3 micrograms/ml) and penicillin (MIC90, 1.5 micrograms/ml), respectively. Although there were significant differences between regions in the USA in the frequency of penicillin-resistant pneumococcal strains, results indicate that the overall sparfloxacin MIC90 was uniformly at 0.5 microgram/ml. Nearly all (> or = 99%) Haemophilus species and Moraxella catarrhalis, including those harboring beta-lactamases, were susceptible to sparfloxacin, ciprofloxacin, and amoxicillin/clavulanic acid. Only cefprozil and macrolides demonstrated lower potency and spectrum against these two species. Sparfloxacin was active against oxacillin-susceptible Staphylococcus aureus (96 to 97%), Klebsiella spp. (95%), and other tested enteric bacilli (93%). Comparison between broth microdilution MIC and disk diffusion interpretive results for M. catarrhalis, Staphylococcus aureus, and the Enterobacteriaceae showed an absolute intermethod categorical agreement of > 95% using current sparfloxacin breakpoints, in contrast to those of cefpodoxime for S. aureus where a conspicuous discord (98% versus 59%) between methods was discovered. These results demonstrate that sparfloxacin possesses sufficient in vitro activity and spectrum versus pathogens that cause respiratory tract infections (indications), especially strains resistant to other drug classes such as the earlier fluoroquinolones, oral cephalosporins, macrolides, and amoxicillin/clavulanic acid. The sparfloxacin susceptibility breakpoint for streptococci may require modification (< or = 1 microgram/ml) based on the MIC population analysis presented here. A modal MIC (0.38 to 0.5 microgram/ml) was observed at the current breakpoint. Regardless, sparfloxacin inhibited 89% (nonpneumococcal Streptococcus spp.) to 100% (Haemophilus spp., M. catarrhalis) of the isolates tested with a median activity of 97% against indicated species.     

Antigonococcal activity of 11 drugs used for therapy or prophylaxis of malaria

Antibacterial agents are often used in malarial endemic areas for antimalarial prophylaxis (such as doxycycline and clindamycin). Gonococcal infections may coexist in the same geographic area, thus becoming suppressed by compounds directed toward malarial parasites. We tested 11 drugs with activity for Plasmodium species against 105 Neisseria gonorrhoeae strains. Traditional or investigational antimalarials such as arteflene (Ro 42-1611), chloroquine, primaquine, pyrimethamine, quinacrine, and quinine were observed to be inactive. Fansidar (sulfadoxine-pyrimethamine) and mefloquine possess marginal action in a minority of gonococcus strains (< 10%). Doxycycline [minimum inhibitory concentration inhibiting 90% of tested strains (MIC 90) 2 micrograms/ml] and azithromycin (MIC 90, 0.5 microgram/ml) among the antibacterials were very active, indicating a dual role as antimalarial and antigonococcal agents. Thus, the gonorrhea and sexually transmitted disease epidemiologic data from geographic regions where doxycycline or newer macrolides may be used for malarial prophylaxis or therapy could be significantly altered.     

Metronidazole and clarithromycin resistance in Helicobacter pylori determined by measuring MICs of antimicrobial agents in color indicator egg yolk agar in a miniwell format. The Gastrointestinal Physiology Working Group of Universidad Peruana Cayetano Heredia and the Johns Hopkins University

Resistance of Helicobacter pylori to metronidazole often causes failure of commonly used combination drug treatment regimens. We determined the MICs of metronidazole and clarithromycin against 18 H. pylori strains from Peru using tetrazolium egg yolk (TEY) agar. The MIC results obtained by agar dilution with petri dishes were compared with the results found through a miniwell format. The results of the two protocols for measuring drug susceptibility differed by no more than 1 dilution in all cases. On TEY agar, bright-red H. pylori colonies were easy to identify against a yellow background. Sixty-one percent (11 of 18) of the strains were resistant to metronidazole (MIC, > or = 4 micrograms/ml) and 50% (9 of 18) were resistant to clarithromycin (MIC, > or = 0.125 micrograms/ml), whereas none (0 of 5) of the strains tested were resistant to tetracycline (MIC, > or = 1 micrograms/ml). Thus, the prevalence of metronidazole and clarithromycin resistance in Peru is higher than that in developed regions of the world. The miniwell plate with TEY agar allows easy H. pylori colony identification, requires about one-third less of the costly medium necessary for petri dish assaying, conserves space, and yields MICs equivalent to those with agar dilution in petri dishes.     

Susceptibilities of Legionella spp. to newer antimicrobials in vitro

The in vitro activities of 13 antimicrobial agents against 30 strains of Legionella spp. were determined. Rifapentine, rifampin, and clarithromycin were the most potent agents (MICs at which 90% of isolates are inhibited [MIC90s], < or = 0.008 microgram/ml). The ketolide HMR 3647 and the fluoroquinolones levofloxacin and BAY 12-8039 (MIC90s, 0.03 to 0.06 microgram/ml) were more active than erythromycin A or roxithromycin. The MIC90s of dalfopristin-quinupristin and linezolid were 0.5 and 8 micrograms/ml, respectively. Based on class characteristics and in vitro activities, several of these agents may have potential roles in the treatment of Legionella infections.     

Resistance of bovine and porcine Pasteurella to florfenicol and other antibiotics

The resistance pattern of 221 (89 bovine, 132 porcine) pasteurella strains isolated in 1996 against 16 antibiotics or chemotherapeutics was determined by agar diffusion. Pasteurella haemolytica showed a higher level of resistance compared to Pasteurella multocida; porcine strains were more resistant than bovine strains. Over 90% of porcine Pasteurella multocida were sensible to penicillin G, ampicillin, cephalothin, polymyxin B, enrofloxacin, chloramphenicol and florfenicol. In addition, bovine strains were at least 90% sensible to oxacillin, erythromycin, gentamycin and sulfmethoxazole-trimethoprim. More than 90% of porcine Pasteurella haemolytica were classified as sensible to polymyxin B, enrofloxacin und florfenicol; bovine strains to cephalothin, neomycin und chloramphenicol as well. In 1996, 2 years after the chloramphenicol ban for food rendering animals, only 6.3% of bovine pasteurella strains proved to be resistant against chloramphenicol compared to a 16.27% fraction in 1994. The mean MIC-values of florfenicol against pasteurella spp. were nearly the same in bovine and porcine isolates with 0.53 microgram/ml and 0.52 microgram/ml respectively. Pasteurella haemolytica, however, showed higher MIC-values (0.68 microgram/ml in bovine, 0.70 microgram/ml in porcine isolates) than Pasteurella multocida with 0.47 microgram/ml in bovine and 0.51 microgram/ml in porcine strains. No isolate had a MIC of florfenicol greater than 1.0 microgram/ml, all pasteurella strains were classified sensible to florfenicol.     

Ceftizoxime interpretive criteria for in vitro susceptibility tests with Neisseria gonorrhoeae

Ceftizoxime was tested in triplicate against 100 clinical strains of Neisseria gonorrhoeae in accordance with National Committee for Clinical Laboratory Standards guidelines to establish susceptibility testing interpretive criteria. The MICs for 50 and 90% of the strains tested were 0.008 and 0.03 microgram/ml, respectively. These results confirm those of other studies reporting ceftizoxime's excellent activity against gonococci. Because no resistant strains were identified, a breakpoint MIC of < or = 0.5 microgram/ml was selected, with a correlate zone diameter of > or = 32 mm. Ceftizoxime appears to represent an alternative to other beta-lactamase-stable beta-lactams for cost-effective therapy of uncomplicated gonorrhea.