scholarly journals Lack of correlation between in vitro and in vivo studies of combinations of rifampin plus vancomycin or beta-lactam antibiotics against Streptococcus pneumoniae.

1996 ◽  
Vol 40 (6) ◽  
pp. 1573-1574 ◽  
Author(s):  
F Tuban ◽  
C Cabellos ◽  
J Liñares
Keyword(s):  
Streptococcus Pneumoniae ◽  
In Vivo Studies ◽  
Beta Lactam ◽  
Beta Lactam Antibiotics

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.

A Practical Look at the Clinical Usefulness of the Beta-Lactam/Beta-Lactamase Inhibitor Combinations

1996 ◽  
Vol 30 (10) ◽  
pp. 1130-1140 ◽  
Author(s):  
Susan M. Hart ◽  
Elaine M. Bailey
Keyword(s):  
English Language ◽  
Antimicrobial Agents ◽  
In Vivo Studies ◽  
Patient Specific ◽  
Beta Lactamase ◽  
Beta Lactam ◽  
Intraabdominal Infections ◽  
Lactamase Inhibitor

OBJECTIVE: To aid clinicians in developing an approach to the use of intravenous beta-lactam/beta-lactamase inhibitors on a patient-specific basis. To achieve this, the pharmacology, in vitro activity, and clinical use of the intravenous beta-lactam/beta-lactamase inhibitor combinations in the treatment of selected infections seen in hospitalized patients are discussed. DATA IDENTIFICATION: An English-language literature search using MEDLINE (1987–1995); Index Medicus (1987–1995); program and abstracts of the 32nd (1992), 33rd (1993), 34th (1994), and 35th (1995) Interscience Conference on Antimicrobial Agents and Chemotherapy; bibliographic reviews of review articles; and package inserts. STUDY SELECTION: In vitro and in vivo studies on the pharmacokinetics, microbiology, pharmacology, and clinical effectiveness of ampicillin/sulbactam, ticarcillin/clavulanate, and piperacillin/tazobactam were evaluated. DATA SYNTHESIS: Many properties of the beta-lactam/beta-lactamase inhibitor combinations are similar. Differences in dosing, susceptibilities, and clinical applications are important considerations for clinicians. Potential roles for these agents in the clinical setting include pneumonia, intraabdominal infections, and soft tissue infections. A short discussion on susceptibility data interpretation is also presented. CONCLUSIONS: There are important differences among the available beta-lactam/beta-lactamase inhibitor combinations, such as spectra of activity, which need to be considered in choosing an agent for a patient-specific case. These products can be useful alternatives to conventional two- to three-drug regimens in mixed infections such as foot infections in patients with diabetes and hospital-acquired intraabdominal infections.

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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