RESUMO
OBJECTIVE: To test the activity of telithromycin against 1034 Streptococcus pneumoniae isolates from pediatric patients in ten centers from ten central and eastern European countries during 2000-2001, and to compare it with the activities of erythromycin A, azithromycin, clarithromycin, clindamycin, and quinupristin-dalfopristin. METHODS: The minimum inhibitory concentrations (MICs) of telithromycin, erythromycin A, azithromycin, clarithromycin, clindamycin, levofloxacin, quinupristin-dalfopristin and penicillin G were tested by the agar dilution method with incubation in air, and mechanisms of resistance to macrolides and quinolones were investigated. RESULTS: Strains were isolated from sputum, tracheal aspirates, ear, eye, blood, and cerebrospinal fluid. Among S. pneumoniae strains tested, 36% had raised penicillin G MICs (>/= 0.12 mg/L). Susceptibilities were as follows: telithromycin, quinupristin-dalfopristin and levofloxacin, >/= 99%; clindamycin, 83%; and erythromycin A, azithromycin and clarithromycin, 78%. Of 230 (22.3%) erythromycin A-resistant S. pneumoniae strains, 176 (79.6%) had erm(B), 38 (16.1%) had mef(A), and 10 (4.3%) had mutations in 23S ribosomal RNA or in ribosomal protein L4. The rates of drug-resistant S. pneumoniae are high in all centers except Kaunas, Riga, and Prague. CONCLUSION: Telithromycin had low MICs against all strains, irrespective of macrolide, azalide or clindamycin resistance. Ribosomal methylation was the most prevalent resistance mechanism among all resistant strains, except in Sofia, where the prevalence of the efflux mechanism was higher.
Assuntos
Antibacterianos/farmacologia , Cetolídeos , Macrolídeos , Streptococcus pneumoniae/efeitos dos fármacos , Adolescente , Criança , Pré-Escolar , Farmacorresistência Bacteriana/fisiologia , Eletroforese em Gel de Campo Pulsado , Humanos , Lactente , Recém-NascidoRESUMO
In total, 1039 pediatric Streptococcus pyogenes isolates from Bulgaria, Croatia, the Czech Republic, Hungary, Latvia, Lithuania, Poland, Romania, Slovakia and Slovenia were studied. All strains were susceptible to penicillin G, levofloxacin, and quinupristin-dalfopristin, 91-100% to telithromycin, and 82-100% to erythromycin, azithromycin, and clarithromycin, and 90-100% to clindamycin. Macrolide resistance occurred mainly in Slovakia (25%), the Czech Republic (17.3%), and Croatia (15.8%). Overall, 9.7% of S. pyogenes isolates were erythromycin resistant due to erm(B)- or erm(A)-encoded methylases (72.3%) or to a mef(A)-encoded efflux pump (25.7%). One strain had alterations of both 23S rRNA (A2058G Escherichia coli numbering) and ribosomal protein L22 (G95D).
Assuntos
Antibacterianos/farmacologia , Cetolídeos , Macrolídeos , Infecções Estreptocócicas/tratamento farmacológico , Streptococcus pyogenes/efeitos dos fármacos , Adolescente , Criança , Pré-Escolar , Farmacorresistência Bacteriana , Europa (Continente)/epidemiologia , Humanos , Lactente , Recém-Nascido , Metilação , Ribossomos/metabolismo , Infecções Estreptocócicas/epidemiologia , Streptococcus pyogenes/isolamento & purificaçãoRESUMO
Agar dilution MIC was used to test the activity of RWJ 54428, a new cephalosporin derivative, compared to imipenem, meropenem, ceftriaxone, piperacillin, piperacillin-tazobactam, clindamycin and metronidazole against 363 anaerobes isolated from clinical specimens. RWJ 54428 had low MICs against most beta-lactamase-negative Gram-negative rods, and all Gram-positive strains except Clostridium difficile. Imipenem and meropenem had the lowest MICs (MIC50s of 0.125 mg/L and MIC90s of 1.0 mg/L). Piperacillin-tazobactam, clindamycin and metronidazole were active against most strains, and ceftriaxone was active mainly against beta-lactamase-negative organisms.
Assuntos
Bactérias Anaeróbias/efeitos dos fármacos , Cefalosporinas/farmacologia , Bactérias Anaeróbias/crescimento & desenvolvimento , Testes de Sensibilidade MicrobianaRESUMO
Agar dilution MIC methodology was used to compare the activity of BMS 284756 with those of ciprofloxacin, levofloxacin, moxifloxacin, trovafloxacin, amoxicillin-clavulanate, piperacillin-tazobactam, imipenem, clindamycin, and metronidazole against 357 anaerobes. Overall, the respective MICs at which 50% of the isolates tested were inhibited (MIC(50)s) and MIC(90)s (in micrograms per milliliter) were as follows: BMS 284756, 0.5 and 2.0; ciprofloxacin, 2.0 and 16.0; levofloxacin, 1.0 and 8.0; moxifloxacin, 0.5 and 4.0; trovafloxacin, 0.5 and 2.0; amoxicillin-clavulanate, 0.5 and 2.0; piperacillin-tazobactam, 0.25 and 8.0; imipenem, 0.06 and 1.0; clindamycin, 0.25 and 8.0; and metronidazole, 1.0 and >16.0. BMS 284756 is a promising new quinolone with excellent antianaerobic activity.
Assuntos
Anti-Infecciosos/farmacologia , Bactérias Anaeróbias/efeitos dos fármacos , Fluoroquinolonas , Indóis , Quinolonas , Bactérias Anaeróbias/enzimologia , Ácido Clavulânico/farmacologia , Resistência Microbiana a Medicamentos , Inibidores Enzimáticos/farmacologia , Testes de Sensibilidade Microbiana , Inibidores de beta-LactamasesRESUMO
GAR-936, a new glycylcycline, had lower MICs (< or =0.016 to 0.125 microg/ml) for 201 penicillin- and tetracycline-susceptible and -resistant pneumococcal strains than tetracycline (< or = 0.06 to 128 microg/ml), minocycline (< or =0.06 to 16.0 microg/ml), or doxycycline (< or =0.06 to 32.0 microg/ml). GAR-936 was also bactericidal against 11 of 12 strains tested at the MIC after 24 h, with significant kill rates at earlier time points.
Assuntos
Antibacterianos/farmacologia , Minociclina/análogos & derivados , Streptococcus pneumoniae/efeitos dos fármacos , Contagem de Colônia Microbiana , Testes de Sensibilidade Microbiana , Minociclina/farmacologia , Resistência às Penicilinas , Tigeciclina , Fatores de TempoRESUMO
The activity of gemifloxacin against Haemophilus influenzae and Moraxella catarrhalis was compared to those of 11 other agents. All quinolones were very active (MICs, =0.125 microgram/ml) against 248 quinolone-susceptible H. influenzae isolates (40.7% of which were beta-lactamase positive); cefixime (MICs, =0.125 microgram/ml) and amoxicillin-clavulanate (MICs =4.0 microgram/ml) were active, followed by cefuroxime (MICs, =16.0 microgram/ml); azithromycin MICs were =4.0 microg/ml. For nine H. influenzae isolates with reduced quinolone susceptibilities, the MICs at which 50% of isolates are inhibited (MIC(50)s) were 0.25 microgram/ml for gemifloxacin and 1.0 microgram/ml for the other quinolones tested. All strains had mutations in GyrA (Ser84, Asp88); most also had mutations in ParC (Asp83, Ser84, Glu88) and ParE (Asp420, Ser458), and only one had a mutation in GyrB (Gln468). All quinolones tested were equally active (MICs, =0.06 microgram/ml) against 50 M. catarrhalis strains; amoxicillin-clavulanate, cefixime, cefuroxime, and azithromycin were very active. Against 10 H. influenzae strains gemifloxacin, levofloxacin, sparfloxacin, and trovafloxacin at 2x the MIC and ciprofloxacin at 4x the MIC were uniformly bactericidal after 24 h, and against 9 of 10 strains grepafloxacin at 2x the MIC was bactericidal after 24 h. After 24 h bactericidal activity was seen with amoxicillin-clavulanate at 2x the MIC for all strains, cefixime at 2x the MIC for 9 of 10 strains, cefuroxime at 4x the MIC for all strains, and azithromycin at 2x the MIC for all strains. All quinolones except grepafloxacin (which was bactericidal against four of five strains) and all ss-lactams at 2x to 4x the MIC were bactericidal against five M. catarrhalis strains after 24 h; azithromycin at the MIC was bactericidal against all strains after 24 h. The postantibiotic effects (PAEs) against four quinolone-susceptible H. influenzae strains were as follows: gemifloxacin, 0.3 to 2.3 h; ciprofloxacin, 1.3 to 4.2 h; levofloxacin, 2.8 to 6.2 h; sparfloxacin, 0.6 to 3.0 h; grepafloxacin, 0 to 2.1 h; trovafloxacin, 0.8 to 2.8 h. At 10x the MIC, no quinolone PAEs were found against the strain for which quinolone MICs were increased. Azithromycin PAEs were 3.7 to 7.3 h.
Assuntos
Anti-Infecciosos/farmacologia , Fluoroquinolonas , Haemophilus influenzae/efeitos dos fármacos , Moraxella catarrhalis/efeitos dos fármacos , Naftiridinas/farmacologia , Antibacterianos/farmacologia , Proteínas de Bactérias/genética , Contagem de Colônia Microbiana , Resistência Microbiana a Medicamentos/genética , Gemifloxacina , Infecções por Haemophilus/microbiologia , Haemophilus influenzae/crescimento & desenvolvimento , Humanos , Testes de Sensibilidade Microbiana , Moraxella catarrhalis/crescimento & desenvolvimento , Reação em Cadeia da Polimerase , Análise de Sequência de DNARESUMO
The antipneumococcal activity of MEN 10700 was compared with those of nine other compounds by MIC and time-kill kinetics. MIC90s (mg/L) of 202 penicillin-susceptible, -intermediate and -resistant pneumococci were: 0.06, 1.0 and 2.0 (MEN 10700); 0.06, 0.5-1.0 and 2.0 (amoxycillin +/- clavulanate); 0.06, 0.5 and 4.0 (cefotaxime); 0.125, 0.5 and 2.0 (cefepime); 0.016, 0.125 and 0.25 (imipenem); 0.03, 0.5 and 1.0 (meropenem); 2.0 (ciprofloxacin); 0.125, >64.0 and >64.0 (clarithromycin); and 0.5 (vancomycin). Time-kill kinetics showed that MEN 10700, at 4 x MIC, was bactericidal for all 12 isolates tested at 4 x MIC. Kinetics of other beta-lactams were similar to those of MEN 10700, relative to MICs. Ciprofloxacin, at 4 x MIC, was uniformly bactericidal after 24 h. Clarithromycin exhibited slow kill kinetics, after 24 h. Vancomycin was bactericidal against 11/12 isolates at 2 x MIC after 24 h.
Assuntos
Antibacterianos/farmacologia , Lactamas , Streptococcus pneumoniae/efeitos dos fármacos , Humanos , Cinética , Testes de Sensibilidade Microbiana , Resistência às Penicilinas , Penicilinas/farmacologia , Fatores de TempoRESUMO
An agar dilution MIC method was used to test the activity of gatifloxacin, a new broad-spectrum fluoroquinolone, compared with ciprofloxacin, levofloxacin, sparfloxacin, trovafloxacin, amoxycillin, cefuroxime, ceftriaxone and clarithromycin against 71 penicillin-susceptible, 81 penicillin-intermediate and 55 penicillin-resistant pneumococci. Quinolone activity was unaffected by penicillin susceptibility, with MIC50/MIC90s (mg/L) of 0.25/0.5 for gatifloxacin; 1/2 for ciprofloxacin; 1/2 for levofloxacin; 0.25/0.5 for sparfloxacin; 0.125/0.25 for trovafloxacin. beta-Lactam and clarithromycin MICs rose with those of penicillin G; MIC50/MIC90 values (mg/L) for penicillin-susceptible, -intermediate and -resistant strains were: 0.03/0.06, 0.25/1, 2/4 for penicillin G; 0.03/0.03, 0.125/1, 2/4 for amoxycillin; 0.03/0.125, 0.5/4, 8/16 for cefuroxime; 0.03/0.03, 0.25/0.5, 2/4 for ceftriaxone; 0.03/0.06, 0.03/>64, 1/>64 for clarithromycin. Time-kill testing of four penicillin-susceptible, four -intermediate and four -resistant strains showed that levofloxacin at the MIC, gatifloxacin and sparfloxacin at 2 x MIC, and trovafloxacin and ciprofloxacin at 4 x MIC, were bactericidal (99.9% killing) for all strains after 12 h and 24 h. By contrast, amoxycillin, cefuroxime and ceftriaxone showed bactericidal activity after 24 h against all strains at 4, 8 and 4 x MIC, respectively. Against ten organisms with clarithromycin MICs of 0.03-4.0 mg/L, clarithromycin was bactericidal against seven strains at 8 x MIC after 24 h. Quinolones showed more rapid killing at lower concentrations and earlier time periods than did beta-lactams and clarithromycin.
Assuntos
Anti-Infecciosos/farmacologia , Fluoroquinolonas , Streptococcus pneumoniae/efeitos dos fármacos , Amoxicilina/farmacologia , Ceftriaxona/farmacologia , Cefuroxima/farmacologia , Cefalosporinas/farmacologia , Ciprofloxacina/farmacologia , Claritromicina/farmacologia , Gatifloxacina , Levofloxacino , Testes de Sensibilidade Microbiana , Naftiridinas/farmacologia , Ofloxacino/farmacologia , Resistência às Penicilinas , Streptococcus pneumoniae/fisiologiaRESUMO
Agar dilution was used to test the activities of HMR 3647, erythromycin A, azithromycin, clarithromycin, roxithromycin, clindamycin, and quinupristin-dalfopristin against 235 strains of Enterococcus faecalis. HMR 3647 was the most active compound (MICs at which 50 and 90% of the isolates are inhibited [MIC50 and MIC90, respectively] of 0.06 and 4.0 microg/ml, respectively). The MIC50 and MIC90 (with the MIC50 given first and the MIC90 given second; both in micrograms per milliliter) for other compounds were as follows: 4.0 and >32.0 for erythromycin A, 16.0 and >32.0 for azithromycin, 2.0 and >32 for clarithromycin, 32.0 and >32.0 for roxithromycin, 32.0 and >32.0 for clindamycin, and 8.0 and 16.0 for quinupristin-dalfopristin. All compounds were only bacteriostatic.
Assuntos
Antibacterianos/farmacologia , Enterococcus faecalis/efeitos dos fármacos , Cetolídeos , Macrolídeos , Contagem de Colônia Microbiana , Resistência Microbiana a MedicamentosRESUMO
The microdilution MICs of HMR 3647, erythromycin A, azithromycin, clarithromycin, roxithromycin, and pristinamycin against 50/90% of 249 Haemophilus influenzae and 50 Moraxella catarrhalis isolates were 2/4, 0.06/0.125; 8/16, 0.25/0.25; 2/4, 0.06/0.125; 16/16, 0.25/0.25; 32/>32, 1/2; and 2/4, 0.5/0.5 microg/ml. Azithromycin was bactericidal against all 10 H. influenzae and 3 of 5 M. catarrhalis isolates and HMR 3647, erythromycin A, clarithromycin, roxithromycin, and pristinamycin were bacteriostatic, against all 15 strains after 24 h at the MIC.
Assuntos
Antibacterianos/farmacologia , Haemophilus influenzae/efeitos dos fármacos , Cetolídeos , Macrolídeos , Moraxella catarrhalis/efeitos dos fármacos , Meios de Cultura , Humanos , Testes de Sensibilidade MicrobianaRESUMO
The activities of piperacillin, piperacillin-tazobactam, ticarcillin, ticarcillin-clavulanate, ampicillin, ampicillin-sulbactam, vancomycin, and teicoplanin were tested against 212 Enterococcus faecalis strains (9 beta-lactamase producers) by standard agar dilution MIC testing (10[4] CFU/spot). The MICs at which 50 and 90% of the isolates were inhibited (MIC50s and MIC90s, respectively) were as follows (microg/ml): piperacillin, 4 and 8; piperacillin-tazobactam, 4 and 8; ticarcillin, 64 and 128; ticarcillin-clavulanate, 64 and 128; ampicillin, 2 and 2; ampicillin-sulbactam, 1 and 2; vancomycin, 1 and 4; and teicoplanin, 0.5 and 1. Agar dilution MIC testing of the nine beta-lactamase-positive strains with an inoculum of 10(6) CFU/spot revealed higher beta-lactam MICs (piperacillin, 64 to >256 microg/ml; ticarcillin, 128 to >256 microg/ml; and ampicillin, 16 to 128 microg/ml); however, MICs with the addition of inhibitors were similar to those obtained with the lower inoculum. Time-kill studies of 15 strains showed that piperacillin-tazobactam was bactericidal (99.9% killing) for 14 strains after 24 h at four times the MIC, with 90% killing of all 15 strains at two times the MIC. After 12 and 6 h, 90% killing of 14 and 13 strains, respectively, was found at two times the MIC. Ampicillin gave 99.9% killing of 14 beta-lactamase-negative strains after 24 h at eight times the MIC, with 90% killing of all 15 strains at two times the MIC. After 12 and 6 h, 90% killing of 14 and 13 strains, respectively, was found at two times the MIC. Killing by ticarcillin-clavulanate was slower than that observed for piperacillin-tazobactam, relative to the MIC. For the one beta-lactamase-producing strain tested by time-kill analysis with a higher inoculum, addition of the three inhibitors (including sulbactam) to each of the beta-lactams resulted in bactericidal activity at 24 h at two times the MIC. For an enzyme-negative strain, addition of inhibitors did not influence kinetics. Kinetics of vancomycin and teicoplanin were significantly slower than those of the beta-lactams, with bactericidal activity against 6 strains after 24 h at eight times the MIC, with 90% killing of 12 and 14 strains, respectively, at four times the MIC. Slower-kill kinetics by both glycopeptides were observed at earlier periods.
Assuntos
Antibacterianos/farmacologia , Quimioterapia Combinada/farmacologia , Enterococcus faecalis/efeitos dos fármacos , Inibidores Enzimáticos/farmacologia , Glicopeptídeos , Penicilinas/farmacologia , Inibidores de beta-Lactamases , Enterococcus faecalis/enzimologia , Testes de Sensibilidade Microbiana , Resistência às Penicilinas/genética , Fatores de TempoRESUMO
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.