INTERACTION BETWEEN BETA-LACTAM ANTIBIOTICS AND GENTAMICIN AGAINST STREPTOCOCCUS PNEUMONIAE IN VITRO AND IN VIVO

2009 ◽  
Vol 95B (1-6) ◽  
pp. 269-275 ◽  
Author(s):  
NIELS Frimodt-MØLler ◽  
VILLY FRØLUND Thomsen
Keyword(s):  
Streptococcus Pneumoniae ◽  
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.

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)

scholarly journals Antibiotic Treatment of Experimental Pneumonic Plague in Mice

1998 ◽  
Vol 42 (3) ◽  
pp. 675-681 ◽  
Author(s):  
William R. Byrne ◽  
Susan L. Welkos ◽  
M. Louise Pitt ◽  
Kelly J. Davis ◽  
Ralf P. Brueckner ◽  
...  
Keyword(s):  
Mouse Model ◽  
Antibiotic Treatment ◽  
Survival Rates ◽  
Blood Cultures ◽  
High Dose ◽  
Beta Lactam ◽  
Pneumonic Plague ◽  
Beta Lactam Antibiotics

ABSTRACT A mouse model was developed to evaluate the efficacy of antibiotic treatment of pneumonic plague; streptomycin was compared to antibiotics with which there is little or no clinical experience. Infection was induced by inhalation of aerosolized Yersinia pestisorganisms. Antibiotics were administered by intraperitoneal injection every 6 hours for 5 days, at doses that produced levels of drug in serum comparable to those observed in humans treated for other serious infections. These studies compared in vitro to in vivo activity and evaluated the efficacy of antibiotics started at different times after exposure. Early treatment (started 24 h after challenge, when 0 of 10 mice tested had positive blood cultures) with netilmicin, ciprofloxacin, ofloxacin, ceftriaxone, ceftazidime, aztreonam, ampicillin, and rifampin (but not cefazolin, cefotetan, or ceftizoxime) demonstrated efficacy comparable to streptomycin. Late treatment (started 42 h after exposure, when five of five mice tested had positive blood cultures) with netilmicin, ciprofloxacin, ofloxacin, and a high dose (20 mg/kg of body weight every 6 h) of gentamicin produced survival rates comparable to that with streptomycin, while all of the beta-lactam antibiotics (cefazolin, cefotetan, ceftriaxone, ceftazidime, aztreonam, and ampicillin) and rifampin were significantly inferior to streptomycin. In fact, all groups of mice treated late with beta-lactam antibiotics experienced accelerated mortality rates compared to normal-saline-treated control mice. These studies indicate that netilmicin, gentamicin, ciprofloxacin, and ofloxacin may be alternatives for the treatment of pneumonic plague in humans. However, the beta-lactam antibiotics are not recommended, based upon poor efficacy in this mouse model of pneumonic plague, particularly when pneumonic plague may be associated with bacteremia.

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