scholarly journals Synergy between amoxicillin and gentamicin in combination against a highly penicillin-resistant and -tolerant strain of Streptococcus pneumoniae in a mouse pneumonia model.

1996 ◽  
Vol 40 (9) ◽  
pp. 2147-2151 ◽  
Author(s):  
C Darras-Joly ◽  
J P Bédos ◽  
C Sauve ◽  
P Moine ◽  
E Vallée ◽  
...  
Keyword(s):  
Streptococcus Pneumoniae ◽  
Beta Lactam ◽  
Single Drug ◽  
Beta Lactam Antibiotics ◽  
Combined Use ◽  
Bacteremic Pneumonia ◽  
Time Kill ◽  
Better Than

In vivo synergy with beta-lactam antibiotics and aminoglycosides has been studied only with penicillin-susceptible Streptococcus pneumoniae strains. We evaluated the interaction between amoxicillin (AMX) and gentamicin (GEN) on the basis of in vitro checkerboard and time-kill curves and of findings in a mouse model of acute bacteremic pneumonia due to a highly penicillin-resistant and -tolerant S. pneumoniae strain of serotype 19 (penicillin and AMX MICs of 4 micrograms/ml; gentamicin MIC of 16 micrograms/ml). Checkerboard results at 18 h of incubation showed indifference. With regard to AMX alone, in vitro time-kill curves demonstrated synergy between AMX (1 microgram/ml) and GEN (16 micrograms/ml) at 5 and 8 h of incubation and for AMX (16 micrograms/ml) in combination with GEN (16 micrograms/ml) at 3, 5, and 8 h of incubation. In leukopenic mice, pulmonary killing curves after a single drug injection demonstrated that AMX (100 mg/kg of body weight) with GEN (16 mg/kg) was more effective than AMX alone (P = 10(-4). With repeated-dose treatment, a synergy was apparent at 8 h after four injections with AMX (100 mg/kg) in combination with GEN (8 or 16 mg/kg) (P < or = 0.05). The cumulative survival rate with AMX (100 mg/kg) every 8 h, combined with GEN (4 or 8 mg/kg) every 8, 12, or 24 h, was better than with AMX alone. Combined use of AMX and GEN may be a valuable therapeutic alternative for pneumococcal pneumonia due to highly penicillin-resistant S. pneumoniae strains.

scholarly journals In Vitro Bactericidal Activities of ABT-773 against ermB Strains of Streptococcus pneumoniae

2003 ◽  
Vol 47 (3) ◽  
pp. 1132-1134 ◽  
Author(s):  
Melinda M. Neuhauser ◽  
Jennifer L. Prause ◽  
Larry H. Danziger ◽  
Susan L. Pendland
Keyword(s):  
Streptococcus Pneumoniae ◽  
Beta Lactam ◽  
Beta Lactam Antibiotics ◽  
Mueller Hinton ◽  
Amoxicillin Clavulanate ◽  
Horse Blood ◽  
Bactericidal Activities ◽  
Time Kill ◽  
Mueller Hinton Broth

ABSTRACT The bactericidal activities of ABT-773, a new ketolide, were compared to those of cefuroxime and amoxicillin-clavulanate against 10 strains of Streptococcus pneumoniae containing the ermB gene. MICs and time-kill curves were determined in duplicate per NCCLS guidelines with cation-adjusted Mueller-Hinton broth with 3% lysed horse blood. Viable counts were done at 0, 2, 6, and 24 h. Antibiotic concentrations tested were two and eight times the MIC. ABT-773 MICs ranged from 0.008 to 1.0 μg/ml. Bactericidal activity was observed with ABT-773 at eight times the MIC against 4 of 10 strains at 24 h compared to 10 of 10 strains with the beta-lactam antibiotics.

Morphologic changes produced by amdinocillin alone and in combination with beta-lactam antibiotics: In vitro and in vivo

1983 ◽  
Vol 75 (2) ◽  
pp. 30-41 ◽  
Author(s):  
Michael J. Kramer ◽  
Yolanda R. Mauriz ◽  
Maria D. Timmes ◽  
Tamara L. Robertson ◽  
Roy Cleeland
Keyword(s):  
Beta Lactam ◽  
Beta Lactam Antibiotics ◽  
Morphologic Changes

Kinetics of active efflux via choroid plexus of beta-lactam antibiotics from the CSF into the circulation

1994 ◽  
Vol 266 (2) ◽  
pp. R392-R399 ◽  
Author(s):  
M. Ogawa ◽  
H. Suzuki ◽  
Y. Sawada ◽  
M. Hanano ◽  
Y. Sugiyama
Keyword(s):  
Choroid Plexus ◽  
Maximum Velocity ◽  
Organic Anions ◽  
Dependent Manner ◽  
Beta Lactam ◽  
Active Efflux ◽  
Beta Lactam Antibiotics ◽  
Elimination Clearance

To examine the role of the choroid plexus in eliminating organic anions from the cerebrospinal fluid (CSF), a kinetic study was performed both in in vivo and in vitro experiments using [3H]benzylpenicillin (PCG) as a model compound. In vivo, after intracerebroventricular administration, [3H]PCG was eliminated from the CSF much more rapidly than [14C]mannitol. Analysis of the elimination clearance from the CSF revealed that 12 and 24% of the disappearance of [3H]PCG can be accounted for by convective loss at a rate equivalent to CSF turnover, and by diffusional loss across the ependymal surface into the brain extracellular space, respectively. Approximately two-thirds of [3H]PCG elimination was due to a saturable process [Michaelis constant (Km) = 43.0 +/- 17.8 microM, maximum velocity (Vmax) = 619 +/- 286 pmol.min-1 x rat-1]. These kinetic parameters obtained in vivo were comparable to those determined previously in vitro, i.e., [3H]PCG was accumulated by the isolated rat choroid plexus via an active transport mechanism (Km = 58 microM, Vmax = 504 pmol.min-1 x rat-1; H. Suzuki, Y. Sawada, Y. Sugiyama, T. Iga, and H. Hanano, J. Pharmacol. Exp. Ther. 242: 660-665, 1987). Furthermore, other organic anions (probenecid, ampicillin, cefodizime, cefotaxime, and ceftriaxone) reduced the transport of [3H]PCG in a dose-dependent manner both in vivo and in vitro. A good correlation was observed between the log inhibition constant (Ki) values obtained for these ligands in vivo and in vitro (r = 0.94, P < 0.01).(ABSTRACT TRUNCATED AT 250 WORDS)

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