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.     

Increased activity of a new chlorofluoroquinolone, BAY y 3118, compared with activities of ciprofloxacin, sparfloxacin, and other antimicrobial agents against anaerobic bacteria

A total of 435 clinical isolates of anaerobes were tested with a broth microdilution method to determine the activity of BAY y 3118 compared with those of other agents against anaerobic bacteria. All strains of Bacteroides capillosus, Prevotella spp., Porphyromonas spp., Fusobacterium spp., Clostridium spp., Eubacterium spp., Peptostreptococcus spp., and Veillonella parvula were susceptible (MICs of < or = 2 micrograms/ml) to BAY y 3118. Against the 315 strains of the Bacteroides fragilis group, five strains required elevated MICs (> or = 4 micrograms/ml) of BAY y 3118. Only imipenem and metronidazole were active against all anaerobes. Overall, BAY y 3118 was more active than ciprofloxacin, sparfloxacin, piperacillin, cefotaxime, and clindamycin against the test isolates.     

Antibacterial activity of teicoplanin against Clostridium difficile

The in vitro inhibitory action of teicoplanin, vancomycin, metronidazole and clindamycin against clinical isolates of Clostridium difficile was investigated. Minimum inhibitory concentrations (MICs) were determined using E test. Teicoplanin (MIC range 0.023-0.75 microgram/ml), vancomycin (MIC range 0.5-3 micrograms/ml) and metronidazole (MIC range 0.19-1 microgram/ml) were all very active against the isolates examined. No resistant strains of C. difficile to those three antimicrobial agents were observed, whereas resistance to clindamycin was found in 39.5% of the tested strains. Teicoplanin was about 4-times more potent than vancomycin. It appears to be a more promising antimicrobial for treatment of C. difficile enteric disease.     

In vitro activities of two glycylcyclines against gram-positive bacteria

The glycylcyclines designated CL 329,998 and CL 331,002 are N,N-dimethylglycylamido derivatives of minocycline and 6-demethyl-6-deoxytetracycline, respectively. In vitro activities of these two antimicrobial agents were compared with those of tetracycline, minocycline, and seven other antimicrobial agents against 412 gram-positive organisms. Both new drugs were significantly more active than minocycline against methicillin-resistant Staphylococcus aureus (MICs for 90% of isolates tested, 0.25 and 0.5 microgram/ml versus 4 micrograms/ml). CL 329,998 inhibited all streptococci, lactobacilli, and Leuconostoc spp. at concentrations of < or = 0.5 microgram/ml, with CL 331,002 slightly less active against some species. All enterococci, including minocycline-resistant and multidrug-resistant isolates, were inhibited at < or = 0.5- and < or = 1.0-microgram/ml concentrations of the new drugs, respectively. Only bacteriostatic activity was evident by time-kill curves. The two glycylcyclines demonstrated activities in vitro that were superior to those of minocycline against several gram-positive bacterial species, and at relatively low concentrations, they inhibited isolates resistant to both tetracycline and minocycline.     

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.     

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.     

Non-alcoholic steatohepatitis (NASH): a disease of emerging identity and importance

The agar dilution MIC method was used to test the activity of cefminox, a beta-lactamase-stable cephamycin, compared with those of cefoxitin, cefotetan, moxalactam, ceftizoxime, cefotiam, cefamandole, cefoperazone, clindamycin, and metronidazole against 357 anaerobes. Overall, cefminox was the most active beta-lactam, with an MIC at which 50% of isolates are inhibited (MIC50) of 1.0 microg/ml and an MIC90 of 16.0 microg/ml. Other beta-lactams were less active, with respective MIC50s and MIC90s of 2.0 and 64.0 microg/ml for cefoxitin, 2.0 and 128.0 microg/ml for cefotetan, 2.0 and 64.0 microg/ml for moxalactam, 4.0 and > 128.0 microg/ml for ceftizoxime, 16.0 and > 128.0 microg/ml for cefotiam, 8.0 and >128.0 microg/ml for cefamandole, and 4.0 and 128.0 microg/ml for cefoperazone. The clindamycin MIC50 and MIC90 were 0.5 and 8.0 microg/ml, respectively, and the metronidazole MIC50 and MIC90 were 1.0 and 4.0 microg/ml, respectively. Cefminox was especially active against Bacteroides fragilis (MIC90, 2.0 microg/ml), Bacteroides thetaiotaomicron (MIC90, 4.0 microg/ml), fusobacteria (MIC90, 1.0 microg/ml), peptostreptococci (MIC90, 2.0 microg/ml), and clostridia, including Clostridium difficile (MIC90, 2.0 microg/ml). Time-kill studies performed with six representative anaerobic species revealed that at the MIC all compounds except ceftizoxime were bactericidal (99.9% killing) against all strains after 48 h. At 24 h, only cefminox and cefoxitin at 4x the MIC and cefoperazone at 8x the MIC were bactericidal against all strains. After 12 h, at the MIC all compounds except moxalactam, ceftizoxime, cefotiam, cefamandole, clindamycin, and metronidazole gave 90% killing of all strains. After 3 h, cefminox at 2 x the MIC produced the most rapid effect, with 90% killing of all strains.     

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.     

Susceptibility of anaerobic bacteria to 23 antimicrobial agents

The antimicrobial susceptibility of 492 anaerobic bacteria, the majority of which were recent clinical isolates, was determined by the agar dilution technique. Penicillin G was active against most of the strains tested at 32 U or less/ml, but only 72% of Bacteroides fragilis strains were susceptible at this level and 9% required 256 U or more/ml. Ampicillin was effective against most of the strains except B. fragilis at 16 mug or less/ml. Amoxicillin was active against only 31% of B. fragilis, 76% of other Bacteroides species, and 67% of Fusobacterium species at 8 mug/ml. Two new penicillins, mezlocillin and azlocillin, were similar to ampicillin in their activity. Carbenicillin and ticarcillin inhibited all but a few strains at 128 mug or less/ml. BLP 1654 was somewhat more active than penicillin G against B. fragilis but had similar activity against other anaerobes. Cephalothin was inactive against B. fragilis, and only 65% of other Bacteroides species were inhibited by 32 mug or less/ml. It was effective against all other anaerobes at that level. Cefamandole showed somewhat greater activity than cephalothin against B. fragilis but generally less activity against gram-positive organisms. Cefazaflur (SKF 59962) was comparable to cephalothin against B. fragilis. Cefoxitin was distinctly more active than cephalothin against B. fragilis. These latter two agents were less active than cephalothin against the gram-positive anaerobes. Chloramphenicol remains active against anaerobic bacteria at 16 mug or less/ml, with rare exceptions. Thiamphenicol was similar to chloramphenicol in its activity. Clindamycin was very active against most of the anaerobes at 8 mug or less/ml. Erythromycin and josamycin were also tested, with josamycin showing greater activity against B. fragilis than either erythromycin or clindamycin. A new oligosaccharide, everninomicin B, was less active than clindamycin against B. fragilis but more active against clostridia and some of the other strains tested. Most of the groups of bacteria tested demonstrated a trend toward resistance to tetracycline. Doxycycline and minocycline were somewhat more active than was tetracycline. Metronidazole was active against the majority of the anaerobes tested; resistance ws demonstrated by some of the gram-positive cocci and gram-positive, non-sporeforming bacilli.     

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     

Enterococcus faecium: in vitro activity of antimicrobial drugs, singly and combined, with and without defibrinated human blood, against multiple-antibiotic-resistant strains

The minimal inhibitory (MICs) and bactericidal concentrations of 14 antimicrobial drugs were determined against 17 clinical isolates of Enterococcus faecium, including 4 glycopeptide-resistant strains. Both teicoplanin and vancomycin lacked bactericidal activity against all 13 susceptible isolates. Time-kill experiments served to test various antibiotic combinations chiefly against glycopeptide-resistant strains in Mueller-Hinton broth (MHB) and in MHB supplemented with 65% (v/v) fresh defibrinated human blood. Co-trimoxazole, fusidic acid, and novobiocin yielded bacteriostatic effects. Rifampin was bactericidally active against rifampin-susceptible strains (MICs = 0.125 micrograms/ml), but less so against low-level-rifampin-resistant (MICs = 2-8 micrograms/ml) strains in MHB. However, in the presence of human blood, rifampin (2 micrograms/ml) combined with co-trimoxazole (0.25/4.75 micrograms/ml) killed rifampin-susceptible and low-level-rifampin-resistant, but not moderate-level-rifampin-resistant (MICs = 16-32 micrograms/ml) strains of E. faecium. Of two topical drugs examined, mupirocin merely inhibited strains of E. faecium; conversely, taurolidine at 2,000 micrograms/ml was efficacious against all strains examined, although the kinetics of bactericidal activity were retarded somewhat in the presence of 65 vol% human blood.     

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.     

Drug resistance of Helicobacter pylori strains isolated from patients with inflammation of stomach mucous membrane and peptic ulcer of stomach and duodenum

Twelve strains of H. pylori were tested. They were isolated from biosamples from 23 patients with stomach inflammation (16 persons) and stomach (3) and duodenum peptic ulcer. By application of solid medium dilution of MIC50 and MIC90-16 antibiotics and antimicrobials were tested. Values of MIC50 and MIC90 for antibiotics from the tetracycline group were, respectively 0.25-0.5 microgram/ml and 0.12-1.0 microgram/ml. Similar results were obtained with macrolide antibiotics. All strains were sensitive to penicillin (MIC 0.03-0.12 microgram/ml, ampicillin (MIC 0.06-0.5 microgram/ml) and amoxicillin and rifampicin (MIC 0.07-0.3 microgram/ml). Ten out of 12 investigated strains were resistant to metronidazole (MIC90 = 30 micrograms/ml). Results of this study may be important for etiotropic treatment of infections with H. pylori.     

Cbl: complex formation and functional implications

Although the influence of tetracyclines on periodontal connective tissue cells has been the topic of many in vitro and in vivo studies, data regarding their effects on gingival epithelial cells are scarce. The present in vitro study was designed to examine the influence of minocycline, a semi-synthetic analog of tetracycline, on human gingival keratinocyte (HGK) attachment and migration. Attachment tests were performed with HGK prelabeled by tritiated amino-acids. Increasing concentrations of minocycline (10, 50, 100 micrograms/ml) in the medium produced no significant modification of cell adhesion kinetics compared to control conditions, except for 100 micrograms/ml which statistically significantly (p < 0.05) reduced the number of attached cells beyond 6 h. A 24-h cell preincubation in 10 micrograms/ml of minocycline did not alter the kinetics of HGK attachment. Scanning electron microscopic observations of attached HGK showed that the presence of 10 micrograms/ml of minocycline in the "attachment medium" induced the production of multiple filopodial extensions. Migration tests in Boyden chambers for 40 h demonstrated that HGK preincubation for 24 h in a 10 micrograms/ml minocycline-HCl solution increased significantly (p < 0.005) cell migration towards a gradient of fetal calf serum. The presence of 10 micrograms/ml of minocycline in contact with the keratinocytes in the upper compartment of the migration chambers also produced a significant (p < 0.005) result. In contrast, the presence of minocycline in the lower compartments did not produce any chemoattractive effect. Within the limits of their significance, these results suggest that, at concentrations not beyond 50 micrograms/ml, minocycline could fasten the periodontal wound coverage by epithelial cells and allow the normal reformation of a junctional epithelium.     

In vitro and in vivo antibiotic susceptibility of Lyme disease Borrelia isolated from the ixodid tick in Japan

Antimicrobial susceptibility of the Lyme disease Borrelia, strain HP1 vi, isolated from the tick ixodes persulcatus in Hokkaido, Japan, was determined in vitro and in vivo. A broth dilution technique was used to determine the minimum inhibitory concentrations (MICs) and minimum borreliacidal concentrations (MBCs) of five antimicrobial agents. Strain HP1 vi was most susceptible to minocycline (MBC, 0.2 micrograms/ml). The other antimicrobial agents tested, aspoxicillin, cefmetazole sodium, imipenem cilastatin sodium, and panipenem betamipron, had higher MBCs of 12.5 micrograms/ml, 25 micrograms/ml, > 25 micrograms/ml, and > 25 micrograms/ml, respectively. In vivo antibiotic susceptibility study using a ddY mouse model demonstrated that minocycline and amoxicillin were effective; minocycline had a lower 50% effective dose (ED50) value (6.25 mg/kg) than amoxicillin (30 mg/kg).     

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     

Antimicrobial susceptibility testing of 59 strains of Campylobacter fetus subsp. fetus

The susceptibilities of 59 Campylobacter fetus subsp. fetus isolates to eight antibiotics were studied by the agar dilution, E-test, and disk diffusion methods. None of the isolates were beta-lactamase producers. All were susceptible to ampicillin, gentamicin, imipenem, and meropenem as determined by the three methods, with MICs at which 90% of the isolates are inhibited (MIC90s) (determined by agar dilution) of 2, 1, < or = 0.06, and 0.12 microgram/ml, respectively. Twenty-seven percent of the isolates were resistant to tetracycline, with complete agreement between the agar dilution and disk diffusion results. The MIC90s determined by agar dilution were 2 micrograms/ml for erythromycin, 1 microgram/ml for ciprofloxacin, and 8 micrograms/ml for cefotaxime.     

Evaluation of Vitek GPS-SA card for testing of oxacillin against borderline-susceptible staphylococci that lack mec

Fifty-one Staphylococcus aureus strains lacking mec for which oxacillin MICs were 1 to 8 micrograms/ml were tested against oxacillin and the combination of oxacillin and clavulanic acid with the Vitek GPS-SA card, the reference broth microdilution method, and the oxacillin agar screen plate. Of the 51 strains, 44 (86%) did not grow on the oxacillin agar screen plate, broth microdilution MICs were 1 to 2 micrograms/ml, and GPS-SA card MICs were < or = 2 micrograms/ml, with the exception of 3 strains that failed to grow in the card on repeated attempts. Another seven strains did grow on the oxacillin agar screen plate. For four of the latter group of strains, oxacillin broth microdilution MICs were > 4 micrograms/ml and GPS-SA card MICs were > or = 4 micrograms/ml; for the other 3 strains, corresponding MICs were 4 and < or = 2 micrograms/ml, respectively. The GPS-SA card classified 86% of strains as oxacillin susceptible.     

In vitro activities of azithromycin, clarithromycin, erythromycin, and tetracycline against 13 strains of Chlamydia pneumoniae

Thirteen strains of Chlamydia pneumoniae were evaluated for their in vitro susceptibilities to azithromycin, clarithromycin, erythromycin, and tetracycline. The MIC ranges were 0.125 to 0.5 micrograms/ml for azithromycin, 0.031 to 1.0 micrograms/ml for clarithromycin, 0.125 to 1.0 micrograms/ml for erythromycin, and 0.25 to 1.0 micrograms/ml for tetracycline. The ranges for the minimal lethal concentrations were 0.125 to 0.5 micrograms/ml for azithromycin, 0.031 to 1.0 micrograms/ml for clarithromycin, 0.125 to 1.0 micrograms/ml for erythromycin, and 0.25 to 1.0 micrograms/ml for tetracycline. Clarithromycin and azithromycin were the most active antibiotics against C. pneumoniae in vitro.     

Gingival fluid tetracycline release from bioerodible gels

Intracrevicular antimicrobial therapy is consistent with the site-specific nature of periodontitis. Considerable research has focused on the use of nonresorbable fibers. However, a bioerodible system is desirable. The purpose of this study was to assess tetracycline release and safety following a single application of a syringable 35% tetracycline hydrochloride in a lactic-glycolic acid gel. 31 generally healthy adult volunteers (mean age = 59 years) were enrolled in and completed this randomized, double-blind eight day study. 2, 6-10 mm non-adjacent interproximal pockets that bled on pocket probing were chosen as experimental sites in each subject. I experimental site and the surrounding gingival crevice received small particle size tetracycline in gel while the other site received larger particle size tetracycline in gel. Gingival crevicular fluid (GCF) was collected prior to treatment and 15 min, 1, 2, 3, 4 and 8 days post-treatment. GCF tetracyline concentrations were determined by agar diffusion bioassay and GCF volume measurements. 61% and 71% of sites had > or = 100 micrograms/ml tetracycline 3 days following application of large (mean concentration = 430 +/- 92 micrograms/ml) and small particle gels (mean concentration = 418 +/- 70 micrograms/ml), respectively. 37% and 55% of sites had measurable tetracycline 8 days after placement of large (mean concentration = 86 +/- 31 micrograms/ml) and small particle gels (mean concentration = 293 +/- 79 micrograms/ml), respectively. The most common adverse event was "bitter taste" (10% of subjects). Based upon the reduction in probing depths and % of sites bleeding on probing at 8 days relative to pretreatment, and the absence of any serious adverse events, it is concluded that these bioerodible gels are safe, and since the bacteriostatic range for most putative periodontopathogens is in the 2-10 micrograms/ml range, the tetracycline levels observed at days 3 and 8 likely represent significant antimicrobial efficacy.