Trimethoprim-sulfamethoxazole therapy of experimental Escherichia coli meningitis in rabbits

We used two strains of ampicillin-susceptible Escherichia coli to produce meningitis in rabbits and utilized these models (i) to compare the killing effects of parenteral trimethoprim-sulfamethoxazole (TMP-SMZ) and ampicillin on E. coli in cerebrospinal fluid after 8 h of treatment and (ii) to measure the penetration of TMP-SMZ and ampicillin into cerebrospinal fluid and the brain. At 16 h after intracisternal inoculation with a test strain, rabbits were treated with TMP (6 mg/kg per h) and SMZ (30 mg/kg per h), ampicillin (40 mg/kg per h), or saline intravenously for 8 h. TMP-SMZ levels were measured by high-pressure liquid chromatography, and ampicillin levels were measured by microbiological assay. Mean +/- standard deviation concentrations of TMP, SMZ, and ampicillin in cerebrospinal fluid (mean percent penetration) at the completion of 8 h of therapy were 0.80 +/- 0.41 (18%), 15.7 +/- 21.1 (27.2%), and 2.6 +/- 1.7 (8.9%) microgram/ml, respectively. TMP, SMZ, and ampicillin levels in brain homogenate after 8 h of therapy were 0.23 +/- 0.07 (6.6%), 3.31 +/- 3.3 (5.5%), and 0.6 +/- 4.53 (1.9%) microgram/g, respectively. TMP-SMZ infusion for 8 h produced a significant reduction in mean bacterial counts in cerebrospinal fluid in both models of meningitis compared with saline controls. The decrease in mean bacterial counts with TMP-SMZ therapy was equivalent to that produced by ampicillin.

[1]  Reportofthesecondneonatalmeni INTRAVENTRICULAR GENTAMICIN THERAPY IN GRAM-NEGATIVE BACILLARY MENINGITIS OF INFANCY , 1980 .

[2]  T. Beam,et al.  Comparison of cefamandole, cephalothin, ampicillin, and chloramphenicol in experimental Escherichia coli meningitis , 1980, Antimicrobial Agents and Chemotherapy.

[3]  J. Perfect,et al.  Comparison of cotrimoxazole, ampicillin, and chloramphenicol in treatment of experimental Haemophilus influenzae type B meningitis , 1980, Antimicrobial Agents and Chemotherapy.

[4]  S. Iwarson,et al.  Cerebrospinal fluid concentrations of trimethoprim during oral and parenteral treatment. , 1979, The Journal of antimicrobial chemotherapy.

[5]  G. Bodey,et al.  Clinical Pharmacology of Intravenously Administered Trimethoprim-Sulfamethoxazole , 1979, Antimicrobial Agents and Chemotherapy.

[6]  C. Wilfert E. coli meningitis: K1 antigen and virulence. , 1978, Annual review of medicine.

[7]  M. Finland,et al.  Quantitative Inhibition of Haemophilus influenzae by Trimethoprim/Sulfamethoxazole , 1977, Antimicrobial Agents and Chemotherapy.

[8]  T. Beam,et al.  Blood, Brain, and Cerebrospinal Fluid Concentrations of Several Antibiotics in Rabbits with Intact and Inflamed Meninges , 1977, Antimicrobial Agents and Chemotherapy.

[9]  M. Sande,et al.  Cefamandole and ampicillin therapy in experimental Haemophilus influenzae meningitis. , 1977, The Journal of infectious diseases.

[10]  M. Sande,et al.  Cefamandole in the therapy of experimental pneumococcal meningitis. , 1976, The Journal of antimicrobial chemotherapy.

[11]  Z. Farid,et al.  Trimethoprim-Sulfamethoxazole and Bacterial Meningitis , 1976 .

[12]  B. Greene,et al.  Trimethoprim-Sulfamethoxazole and Brain Abscess , 1975 .

[13]  Kirwan Wo Cerebrospinal fluid cotrimoxazole levels. , 1974 .

[14]  M. Finland,et al.  Trimethoprim-sulfamethoxazole : microbiological, pharmacological, and clinical considerations , 1974 .

[15]  W. Kirwan Cerebrospinal fluid cotrimoxazole levels. , 1974, Journal of the Irish Medical Association.

[16]  M. Finland,et al.  Susceptibility of recently isolated pathogenic bacteria to trimethoprim and sulfamethoxazole separately and combined. , 1973, The Journal of infectious diseases.

[17]  S. Bushby,et al.  Trimethoprim-sulfamethoxazole: in vitro microbiological aspects. , 1973, The Journal of infectious diseases.

[18]  J. Rieder Metabolism and techniques for assay of trimethoprim and sulfamethoxazole. , 1973, The Journal of infectious diseases.

[19]  G. Mccracken The rate of bacteriologic response to antimicrobial therapy in neonatal meningitis. , 1972, American journal of diseases of children.

[20]  H. Cserr Physiology of the choroid plexus. , 1971, Physiological reviews.

[21]  L. Roy SULPHAMETHOXAZOLE‐TRIMETHOPRIM IN INFANCY , 1971, The Medical journal of Australia.

[22]  R. Griffith,et al.  Antibiotic penetration of the brain. A comparative study. , 1969, Journal of neurosurgery.

[23]  R. Morzaria,et al.  Neonatal meningitis treated with trimethoprim and sulphamethoxazole. , 1969, British medical journal.

[24]  R. Petersdorf,et al.  STUDIES ON THE PATHOGENESIS OF MENINGITIS. IV. PENICILLIN LEVELS IN THE CEREBROSPINAL FLUID IN EXPERIMENTAL MENINGITIS. , 1964, The Journal of laboratory and clinical medicine.

[25]  O. H. Lowry,et al.  HISTOCHEMICAL CHANGES ASSOCIATED WITH AGING I. METHODS AND CALCULATIONS , 1942 .