In Vitro and In Vivo Antibacterial Activities of S-4661, a New Carbapenem
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ABSTRACT The in vitro and in vivo antibacterial activities of S-4661, a new 1β-methylcarbapenem, were compared with those of imipenem, meropenem, biapenem, cefpirome, and ceftazidime. The activity of S-4661 against methicillin-susceptible staphylococci and streptococci was comparable to that of imipenem, with an MIC at which 90% of the strains tested were inhibited (MIC 90 ) equal to 0.5 μg/ml or less. S-4661 was highly active against members of the family Enterobacteriaceae , Haemophilus influenzae , and Moraxella catarrhalis , with MIC 90 s ranging from 0.032 to 0.5 μg/ml. Against imipenem-resistant Pseudomonas aeruginosa , S-4661 was the most active among test agents (MIC 90 , 8 μg/ml). Furthermore, S-4661 displayed a high degree of activity against many ceftazidime-, ciprofloxacin-, and gentamicin-resistant isolates of P. aeruginosa . The in vivo efficacy of S-4661 against experimentally induced infections in mice caused by gram-positive and gram-negative bacteria, including penicillin-resistant Streptococcus pneumoniae and drug-resistant P. aeruginosa , reflected its potent in vitro activity and high levels in plasma in mice. We conclude that S-4661 is a promising new carbapenem for the treatment of infections caused by gram-positive and -negative bacteria, including penicillin-resistant S. pneumoniae and drug-resistant P. aeruginosa.Keywords:
Cefpirome
Moxalactam
Objectives: The first objective was to investigate the in vitro activity of telithromycin against respiratory tract pathogens in comparison with other antimicrobial agents. The second objective was to identify the influence of the erm(B) and mef(A) genes on the susceptibility of Streptococcus pneumoniae to telithromycin.
Telithromycin
Ketolide
Moraxella (Branhamella) catarrhalis
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ABSTRACT A total of 124 Pseudomonas aeruginosa strains were tested for synergy between levofloxacin and cefpirome, ceftazidime, gentamicin, and meropenem. Checkerboards yielded synergistic fractional inhibitory concentration (FIC) indices (≤0.5) with 25 of 496 possible combinations. All other FIC indices were >0.5 to 2 (additive or indifferent), with no antagonism. Time-kill studies with 12 strains showed that levofloxacin (0.06 to 0.5 μg/ml) was synergistic with cefpirome, ceftazidime, gentamicin, and meropenem in 10, 9, 4, and 11 strains, respectively.
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The present study assessed the comparative in vitro killing kinetics of telithromycin, azithromycin and clarithromycin. Minimal inhibitory concentrations (MIC) and minimal bactericidal concentrations (MBC) were determined against Streptococcus pneumoniae , β‐haemolytic streptococci, Haemophilus influenzae and Moraxella catarrhalis strains characterized by different susceptibilities to β‐lactams and macrolides. For each bacterial species, representative strains were chosen for time‐kill studies. Telithromycin showed high activity against all the tested strains with MIC ranging from ≤0.004 to 0.5 mg/L for streptococci, from 0.008 to 8 mg/L for H. influenzae , and from 0.008 to 0.5 mg/L for M. catarrhalis. In time‐kill studies, telithromycin showed an overall superior bactericidal activity in respect to macrolides, particularly against resistant strains. In conclusion, telithromycin proved to possess bactericidal activity against a wide range of respiratory pathogens, including strains resistant to common macrolides.
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Ketolide
Minimum bactericidal concentration
Moraxella (Branhamella) catarrhalis
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Meropenem, a new parenteral carbapenem demonstrated increased activity as compared to imipenem against 336 strains of Neisseria gonorrhoeae , 119 strains of Haemophilus influenzae , and 110 strains of H. ducreyi . Neither carbapenem was affected by the β -lactamase activity of the organisms tested. Ceftriaxone and ciprofloxacin demonstrated activity superior to that of both carbapenems while the activity of ceftazidime was similar to that of meropenem.
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Haemophilus ducreyi
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Meropenem was 8- to 32-fold more active (MIC for 90% of strains = 0.125 micrograms/ml) than imipenem against a collection of Haemophilus influenzae strains characterized as either susceptible to ampicillin or resistant to that agent by virtue of beta-lactamase or nonenzymatic mechanisms. MBCs and kinetic kill curve tests showed that meropenem (as well as imipenem, several cephalosporins, and amoxicillin-clavulanate) was bactericidal against all strains at or within four times the respective MICs. Thus, meropenem demonstrated greater inhibitory activity than imipenem and activity comparable to that of cefotaxime against these selected strains.
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The in vitro activity of L-627, a new parenterally administered carbapenem, was compared with those of imipenem, meropenem, FCE 22101 (a penem), ceftazidime, and ceftriaxone. L-627 was active against members of the family Enterobacteriaceae (MIC for 90% of strains tested [MIC90] ranging from 0.03 to 4 micrograms/ml). L-627 displayed activity equal to that of meropenem against Pseudomonas aeruginosa (MIC90, 2 micrograms/ml), although, as with other carbapenems, the antipseudomonal activity was reduced against D2-deficient strains. Staphylococci and streptococci were susceptible (MIC90 of 1.0 micrograms/ml for Staphylococcus aureus and 0.015 micrograms/ml for group A streptococci). L-627 also had activity against anaerobic bacteria (MIC90, 2.0 micrograms/ml for Bacteroides fragilis). Neisseria gonorrhoeae and Neisseria meningitidis were highly susceptible (MIC90, 0.06 micrograms/ml), and against the common respiratory pathogens (Haemophilus influenzae, Streptococcus pneumoniae, and Moraxella catarrhalis), the MIC90s were less than or equal to 2.0 micrograms/ml. The protein binding of L-627 ranged from 13.8 to 22%, depending on the concentration. The presence of human serum had little effect on the MIC or MBC of L-627. These results suggest that L-627 merits further study in the treatment of infections caused by a wide range of pathogens.
Bacteroides fragilis
Moraxella (Branhamella) catarrhalis
Carbapenem
Ertapenem
Haemophilus parainfluenzae
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ABSTRACT Phenotypic tolerances to antibiotics of mature and young Pseudomonas aeruginosa PAO1 biofilms and released planktonic bacteria were compared for four antibiotics. Resistance levels were similar for gentamicin and ciprofloxacin but differed for ceftazidime and meropenem. β-Lactamase mapping showed that, after 5 h of ceftazidime exposure, mature biofilms produced more β-lactamase than young biofilms, facilitating the growth of released planktonic bacteria. This shows the importance of early treatment and choice of antibiotics for P. aeruginosa biofilm infections.
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ABSTRACT The in vitro and in vivo antibacterial activities of S-4661, a new 1β-methylcarbapenem, were compared with those of imipenem, meropenem, biapenem, cefpirome, and ceftazidime. The activity of S-4661 against methicillin-susceptible staphylococci and streptococci was comparable to that of imipenem, with an MIC at which 90% of the strains tested were inhibited (MIC 90 ) equal to 0.5 μg/ml or less. S-4661 was highly active against members of the family Enterobacteriaceae , Haemophilus influenzae , and Moraxella catarrhalis , with MIC 90 s ranging from 0.032 to 0.5 μg/ml. Against imipenem-resistant Pseudomonas aeruginosa , S-4661 was the most active among test agents (MIC 90 , 8 μg/ml). Furthermore, S-4661 displayed a high degree of activity against many ceftazidime-, ciprofloxacin-, and gentamicin-resistant isolates of P. aeruginosa . The in vivo efficacy of S-4661 against experimentally induced infections in mice caused by gram-positive and gram-negative bacteria, including penicillin-resistant Streptococcus pneumoniae and drug-resistant P. aeruginosa , reflected its potent in vitro activity and high levels in plasma in mice. We conclude that S-4661 is a promising new carbapenem for the treatment of infections caused by gram-positive and -negative bacteria, including penicillin-resistant S. pneumoniae and drug-resistant P. aeruginosa.
Cefpirome
Moxalactam
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ABSTRACT The in vitro activity of ABT-773 was evaluated against Streptococcus pneumoniae , Haemophilus influenzae , and Moraxella catarrhalis isolates. ABT-773 was the most active antimicrobial tested against S. pneumoniae . ABT-773 and azithromycin were equivalent in activity against H. influenzae and M. catarrhalis and more active than either clarithromycin or erythromycin.
Moraxella (Branhamella) catarrhalis
Ketolide
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Carbapenem
Amp resistance
Beta-lactamase
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