scholarly journals Gemifloxacin Is Efficacious against Penicillin-Resistant and Quinolone-Resistant Pneumococci in Experimental Meningitis

2002 ◽  
Vol 46 (5) ◽  
pp. 1607-1609 ◽  
Author(s):  
Philippe Cottagnoud ◽  
Fernando Acosta ◽  
Marianne Cottagnoud ◽  
Martin G. Täuber
Keyword(s):  
Antibacterial Activity ◽  
Standard Deviation ◽  
Bactericidal Activity ◽  
Resistant Strain ◽  
Activity Change ◽  
Standard Regimen ◽  
Pneumococcal Strain ◽  
Time Kill

ABSTRACT In experimental rabbit meningitis, gemifloxacin penetrated inflamed meninges well (22 to 33%) and produced excellent bactericidal activity (change in log10 [Δlog10] CFU/ml/h, −0.68 ± 0.30 [mean and standard deviation]), even superior to that of the standard regimen of ceftriaxone plus vancomycin (−0.49 ± 0.09 Δlog10 CFU/ml/h), in the treatment of meningitis due to a penicillin-resistant pneumococcal strain (MIC, 4 mg/liter). Even against a penicillin- and quinolone-resistant strain, gemifloxacin showed good bactericidal activity (−0.48 ± 0.16 Δlog10 CFU/ml/h). The excellent antibacterial activity of gemifloxacin was also confirmed by time-kill assays over 8 h in vitro.

scholarly journals Efficacies of BMS 284756 against Penicillin-Sensitive, Penicillin-Resistant, and Quinolone-Resistant Pneumococci in Experimental Meningitis

2002 ◽  
Vol 46 (1) ◽  
pp. 184-187 ◽  
Author(s):  
Philippe Cottagnoud ◽  
Fernando Acosta ◽  
Marianne Cottagnoud ◽  
Marc Pfister ◽  
Martin G. Täuber
Keyword(s):  
Antibacterial Activity ◽  
Bactericidal Activity ◽  
Resistant Strain ◽  
Sensitive Strain ◽  
Standard Regimen

ABSTRACT BMS 284756 penetrated well into inflamed meninges (44% ± 11%) and produced good bactericidal activity (−0.82 ± 0.22 Δlog10 CFU/ml · h) in the treatment of experimental meningitis in rabbits due to a penicillin-sensitive strain. BMS 284756 monotherapy had a greater potency than the standard regimen of ceftriaxone and vancomycin (−0.49 ± 0.08 Δlog10 CFU/ml · h) against a penicillin-resistant strain (MIC, 4 mg/liter). Even against a penicillin- and quinolone-resistant strain, BMS 284756 showed good bactericidal activity (−0.52 ± 0.12 Δlog10 CFU/ml · h). The antibacterial activity of BMS 284756 was confirmed by time-killing assays over 8 h in vitro.

scholarly journals Activities of Ertapenem, a New Long-Acting Carbapenem, against Penicillin-Sensitive or -Resistant Pneumococci in Experimental Meningitis

2003 ◽  
Vol 47 (6) ◽  
pp. 1943-1947 ◽  
Author(s):  
P. Cottagnoud ◽  
M. Pfister ◽  
M. Cottagnoud ◽  
F. Acosta ◽  
M. G. Täuber
Keyword(s):  
Cerebrospinal Fluid ◽  
Antibacterial Activity ◽  
Bactericidal Activity ◽  
Resistant Strain ◽  
Half Life ◽  
Resistant Mutant ◽  
Viable Cell ◽  
Cell Counts ◽  
Long Acting

ABSTRACT The penetration of ertapenem, a new carbapenem with a long half-life, reached 7.1 and 2.4% into inflamed and noninflamed meninges, respectively. Ertapenem had excellent antibacterial activity in the treatment of experimental meningitis due to penicillin-sensitive and -resistant pneumococci, leading to a decrease of 0.69 ± 0.17 and 0.59 ± 0.22 log10 CFU/ml · h, respectively, in the viable cell counts in the cerebrospinal fluid. The efficacy of ertapenem was comparable to that of standard regimens (ceftriaxone monotherapy against the penicillin-sensitive strain and ceftriaxone combined with vancomycin against the penicillin-resistant strain). In vitro, ertapenem in concentrations above the MIC was highly bactericidal against both strains. Even against a penicillin- and quinolone-resistant mutant, ertapenem had similar bactericidal activity in vitro.

scholarly journals Daptomycin Is Highly Efficacious against Penicillin-Resistant and Penicillin- and Quinolone-Resistant Pneumococci in Experimental Meningitis

2004 ◽  
Vol 48 (10) ◽  
pp. 3928-3933 ◽  
Author(s):  
Philippe Cottagnoud ◽  
Marc Pfister ◽  
Fernando Acosta ◽  
Marianne Cottagnoud ◽  
Lukas Flatz ◽  
...  
Keyword(s):  
Cerebrospinal Fluid ◽  
Streptococcus Pneumoniae ◽  
Bactericidal Activity ◽  
Resistant Strain ◽  
Pneumococcal Meningitis ◽  
Standard Regimen ◽  
Bacterial Titer ◽  
Lipopeptide Antibiotic ◽  
Experimental Pneumococcal Meningitis

ABSTRACT The penetration of daptomycin, a new lipopeptide antibiotic, into inflamed meninges ranged between 4.37 and 7.53% (mean, 5.97%). Daptomycin was very efficacious in the treatment of experimental pneumococcal meningitis, producing a decrease of −1.20 ± 0.32 Δlog10 CFU/ml · h in the bacterial titer of Streptococcus pneumoniae against a penicillin-resistant strain and of −0.97 ± 0.32 Δlog10 CFU/ml · h against a penicillin- and quinolone-resistant strain found in cerebrospinal fluid (CSF). For both strains, daptomycin was significantly superior to the standard regimen of a combination of ceftriaxone with vancomycin, sterilizing 9 of 10 CSF samples after 4 h. In vitro, daptomycin produced highly bactericidal activity in concentrations above the MIC.

scholarly journals In Vitro Activity of S-3578, a New Broad-Spectrum Cephalosporin Active against Methicillin-Resistant Staphylococci

2003 ◽  
Vol 47 (3) ◽  
pp. 923-931 ◽  
Author(s):  
Takaji Fujimura ◽  
Yoshinori Yamano ◽  
Isamu Yoshida ◽  
Jingoro Shimada ◽  
Shogo Kuwahara
Keyword(s):  
Antibacterial Activity ◽  
Population Analysis ◽  
Low Frequency ◽  
Methicillin Resistant ◽  
Gram Positive Bacteria ◽  
Highly Active ◽  
In Vitro Antibacterial Activity ◽  
Mrsa Strains ◽  
Time Kill

ABSTRACT The in vitro antibacterial activity of S-3578, a new parenteral cephalosporin, against clinical isolates was evaluated. The MICs of the drug at which 90% of the isolates were inhibited were 4 μg/ml for methicillin-resistant Staphylococcus aureus (MRSA) and 2 μg/ml for methicillin-resistant Staphylococcus epidermidis, which were fourfold higher than and equal to those of vancomycin, respectively. The anti-MRSA activity of S-3578 was considered to be due to its high affinity for penicillin-binding protein 2a (50% inhibitory concentration, 4.5 μg/ml). In time-kill studies with 10 strains each of MRSA and methicillin-susceptible S. aureus, S-3578 caused more than a 4-log10 decrease of viable cells on the average at twice the MIC after 24 h of exposure, indicating that it had potent bactericidal activity. Furthermore, in population analysis of MRSA strains with heterogeneous or homogeneous resistance to imipenem, no colonies emerged from about 109 cells on agar plates containing twice the MIC of S-3578, suggesting the low frequency of emergence of S-3578-resistant strains from MRSA. S-3578 was also highly active against penicillin-resistant Streptococcus pneumoniae (PRSP), with a MIC90 of 1 μg/ml, which was comparable to that of ceftriaxone. S-3578 also had antibacterial activity against a variety of gram-negative bacteria including Pseudomonas aeruginosa, though its activity was not superior to that of cefepime. In conclusion, S-3578 exhibited a broad antibacterial spectrum and, particularly, had excellent activity against gram-positive bacteria including methicillin-resistant staphylococci and PRSP. Thus, S-3578 was considered to be worthy of further evaluation.

scholarly journals In vitro anti-mycobacterial activity of (E)-N´-(monosubstituted-benzylidene) isonicotinohydrazide derivatives against isoniazid-resistant strains

2012 ◽  
Vol 4 (1) ◽  
pp. 13 ◽  
Author(s):  
Tatiane S. Coelho ◽  
Jessica B. Cantos ◽  
Marcelle L.F. Bispo ◽  
Raoni S.B. Gonçalves ◽  
Camilo H.S. Lima ◽  
...  
Keyword(s):  
Antibacterial Activity ◽  
Resistant Strain ◽  
Mechanisms Of Action ◽  
Susceptible Strain ◽  
Clinical Isolates ◽  
Coding Region ◽  
Resistant Strains

A series of twenty-three <em>N-acylhydrazones</em> derived from isoniazid (INH 1-23) have been evaluated for their <em>in vitro</em> antibacterial activity against INH- susceptible strain of <em>M. tuberculosis</em> (RG500) and three INH-resistant clinical isolates (RG102, RG103 and RG113). In general, derivatives 4, 14, 15 and 16 (MIC=1.92, 1.96, 1.96 and 1.86 mM, respectively) showed relevant activities against RG500 strain, while the derivative 13 (MIC=0.98 mM) was more active than INH (MIC=1.14 mM). However, these derivatives were inactive against RGH102, which displays a mutation in the coding region of <em>inhA</em>. These results suggest that the activities of these compounds depend on the inhibition of this enzyme. However, the possibility of other mechanisms of action cannot be excluded, since compounds 2, 4, 6, 7, 12-17, 19, 21 and 23 showed good activities against <em>katG</em>-resistant strain RGH103, being more than 10-fold more active than INH.

Nemonoxacin enhances antibacterial activity and anti-resistant mutation ability of vancomycin against methicillin-resistant Staphylococcus aureus in an in vitro dynamic pharmacokinetic/pharmacodynamic model

2021 ◽  
Author(s):  
Junchen Huang ◽  
Siwei Guo ◽  
Xin Li ◽  
Fang Yuan ◽  
You Li ◽  
...  
Keyword(s):  
Staphylococcus Aureus ◽  
Antibacterial Activity ◽  
Bactericidal Activity ◽  
Pharmacodynamic Model ◽  
Methicillin Resistant ◽  
Mutant Prevention Concentration ◽  
Mrsa Infection ◽  
Independent Risk Factors ◽  
Resistant Mutation

Reduced susceptibility and emergence of resistance to vancomycin in methicillin-resistant Staphylococcus aureus (MRSA) have led to the development of various vancomycin based combinations. Nemonoxacin is a novel nonfluorinated quinolone with antibacterial activity against MRSA. The present study aimed to investigate the effects of nemonoxacin on antibacterial activity and the anti-resistant mutation ability of vancomycin for MRSA and explore whether quinolone resistance genes are associated with a reduction in the vancomycin minimal inhibitory concentration (MIC) and mutant prevention concentration (MPC) when combined with nemonoxacin. Four isolates, all with a vancomycin MIC of 2 μg/mL, were used in a modified in vitro dynamic pharmacokinetic/pharmacodynamic model to investigate the effects of nemonoxacin on antibacterial activity (M04, M23 and M24) and anti-resistant mutation ability (M04, M23 and M25, all with MPC ≥19.2 μg/mL) of vancomycin. The mutation sites of gyrA , gyrB , parC , and parE of 55 clinical MRSA isolates were sequenced. We observed that in M04 and M23, the combination of vancomycin (1g q12h) and nemonoxacin (0.5g qd) showed a synergistic bactericidal activity and resistance enrichment suppression. All clinical isolates resistant to nemonoxacin harbored gyrA (S84→L) mutation; gyrA (S84→L) and parC (E84→K) mutations were the two independent risk factors for the unchanged vancomycin MPC in combination. Nemonoxacin enhances the bactericidal activity and suppresses resistance enrichment ability of vancomycin against MRSA with a MIC of 2 μg/mL. Our in vitro data support the combination of nemonoxacin and vancomycin for the treatment of MRSA infection with a high MIC.

scholarly journals Microbiological Assay for Ceftazidime Injection

2007 ◽  
Vol 90 (5) ◽  
pp. 1379-1382 ◽  
Author(s):  
Andréia De Haro Moreno ◽  
Hérida Regina Nunes Salgado
Keyword(s):  
Antibacterial Activity ◽  
Regression Analysis ◽  
Standard Deviation ◽  
Staphylococcus Epidermidis ◽  
Test Organism ◽  
Calibration Graph ◽  
Microbiological Assay ◽  
Parallel Model ◽  
Relative Standard

Abstract A simple, sensitive, and specific biodiffusion assay for the antibacterial ceftazidime was developed using a strain of Staphylococcus epidermidis (ATCC 12228) as the test organism. Ceftazidime was measured in powder for injection at concentrations ranging from 100 to 400 g/mL. The calibration graph for ceftazidime was linear (r2 = 1), and the method validation showed that it was precise (relative standard deviation = 0.415) and accurate. The results obtained by biodiffusion assay were statistically calculated by linear parallel model and by means of regression analysis and were verified using analysis of variance. It was concluded that the microbiological assay is satisfactory for in vitro quantification of the antibacterial activity of ceftazidime in pharmaceuticals.

scholarly journals In vitro antibacterial activity of omeprazole and its selectivity for Helicobacter spp. are dependent on incubation conditions.

1996 ◽  
Vol 40 (3) ◽  
pp. 621-626 ◽  
Author(s):  
J E Sjöström ◽  
J Fryklund ◽  
T Kühler ◽  
H Larsson
Keyword(s):  
Antibacterial Activity ◽  
Proton Pump Inhibitors ◽  
Proton Pump ◽  
Bactericidal Activity ◽  
Fetal Calf Serum ◽  
Calf Serum ◽  
Antibacterial Activities ◽  
In Vitro Antibacterial Activity ◽  
H Pylori

Factors affecting the in vitro antibacterial activity of omeprazole were studied. Our data show that 3H-labeled omeprazole covalently bound to Helicobacter pylori and to other gram-negative and gram-positive bacteria. The compound was found to bind to a broad range of proteins in H. pylori, and at pH 5, binding was enhanced 15-fold compared with binding at pH 7. The bactericidal activity correlated to the degree of binding, and at pH 5, a pH at which omeprazole readily converts to the active sulfenamide form, beta-mercaptoethanol, a known scavenger of sulfenamide, and fetal calf serum, to which noncovalent protein binding of omeprazole is known to occur, reduced the level of binding and almost entirely abolished the bactericidal activity. At pH 7 the killing activities of omeprazole and structural analogs (e.g., proton pump inhibitors) were dependent on the time-dependent conversion (half-life) to the corresponding sulfenamide. The bactericidal activity exerted by the sulfenamide form at pH 5 was not specific for the genus Helicobacter. However, in brucella broth at pH 7 with 10% fetal calf serum, only Helicobacter spp. were susceptible to omeprazole, with MBCs in the range of 32 to 64 micrograms/ml, and MBCs for more stable proton pump inhibitors were higher. Wild-type H. pylori and its isogenic urease-deficient mutant were equally susceptible to omeprazole. Thus, the urease is not a lethal target for omeprazole action in H. pylori. In conclusion, the antibacterial activities of omeprazole and analogs are dependent on pH and the composition of the medium used. Thus, at a low pH in buffer, these compounds have a nonselective action, whereas in broth at neutral pH, the mechanism of action is selective for Helicobacter spp.

scholarly journals Does the Activity of the Combination of Imipenem and Colistin In Vitro Exceed the Problem of Resistance in Metallo-β-Lactamase-Producing Klebsiella pneumoniae Isolates?

2009 ◽  
Vol 53 (5) ◽  
pp. 2133-2135 ◽  
Author(s):  
Maria Souli ◽  
Panagiota Danai Rekatsina ◽  
Zoi Chryssouli ◽  
Irene Galani ◽  
Helen Giamarellou ◽  
...  
Keyword(s):  
Klebsiella Pneumoniae ◽  
Bactericidal Activity ◽  
Clinical Isolates ◽  
Type Gene ◽  
Time Kill

ABSTRACT Using time-kill methodology, we investigated the interactions of an imipenem-colistin combination against 42 genetically distinct Klebsiella pneumoniae clinical isolates carrying a bla VIM-1-type gene. Irrespective of the imipenem MIC, the combination was synergistic (50%) or indifferent (50%) against colistin-susceptible strains, while it was antagonistic (55.6%) and rarely synergistic (11%) against non-colistin-susceptible strains (with synergy being observed only against strains with colistin MICs of 3 to 4 μg/ml). The combination showed improved bactericidal activity against isolates susceptible either to both agents or to colistin.

scholarly journals Dalbavancin, Vancomycin and Daptomycin Alone and in Combination with Cefazolin against Resistant Phenotypes of Staphylococcus aureus in a Pharmacokinetic/Pharmacodynamic Model

Antibiotics ◽  
2020 ◽  
Vol 9 (10) ◽  
pp. 696 ◽  
Author(s):  
Jacinda C. Abdul-Mutakabbir ◽  
Razieh Kebriaei ◽  
Kyle C. Stamper ◽  
Zain Sheikh ◽  
Philip T. Maassen ◽  
...  
Keyword(s):  
Staphylococcus Aureus ◽  
Bactericidal Activity ◽  
Inhibitory Concentration ◽  
Pharmacodynamic Model ◽  
In Vitro Tests ◽  
Beta Lactam ◽  
Fold Reduction ◽  
The One ◽  
Time Kill

The most efficacious antimicrobial therapy to aid in the successful elimination of resistant S. aureus infections is unknown. In this study, we evaluated varying phenotypes of S. aureus against dalbavancin (DAL), vancomycin (VAN), and daptomycin (DAP) alone and in combination with cefazolin (CFZ). The objective of this study was to observe whether there was a therapeutic improvement in adding a beta-lactam to a glycopeptide, lipopeptide, or a lipoglycopeptide. We completed a series of in vitro tests including minimum inhibitory concentration testing (MIC) of the antimicrobials in combination, time-kill analysis (TKA), and a 168 h (7-day) one-compartment pharmacokinetic/pharmacodynamic (PK/PD) model on two daptomycin non-susceptible (DNS), vancomycin intermediate S. aureus strains (VISA), D712 and 6913. Results from our MIC testing demonstrated a minimum 2-fold and a maximum 32-fold reduction in MIC values for DAL, VAN, and DAP in combination with CFZ, in contrast to either agent used alone. The TKAs completed on four strains paralleled the enhanced activity demonstrated via the combination MICs. In the one-compartment PK/PD models, the combination of DAP plus CFZ or VAN plus CFZ resulted in a significant (p < 0.001) improvement in bactericidal activity and overall reduction in CFU/ml over the 7-day period. While the addition of CFZ to DAL improved time to bactericidal activity, DAL alone demonstrated equal and more sustained overall activity compared to all other treatments. The use of DAL alone, with or without CFZ and the combinations of VAN or DAP with CFZ appear to result in increased bactericidal activity against various recalcitrant S. aureus phenotypes.

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