PENICILLIN AND PROBENECID: A CONTROLLED STUDY OF PENICILLIN LEVELS IN PLASMA OF PATIENTS WITH BACTERIAL ENDOCARDITIS
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Cerebrospinal fluid and serum penicillin levels were determined in patients with latent syphilis. Mean serum concentration one week after the third weekly dose of 2.4 million units penicillin G benzathine was 0.32 units/mL. Concurrent administration of probenecid orally produced a mean serum penicillin level of 0.41 units/mL. Doubled penicillin doses without and with daily orally administered probenecid resulted in mean serum concentrations of 0.75 and 1.00 units/mL, respectively. Two of six patients in the last group had CSF penicillin concentrations greater than 0.03 units/mL. (JAMA1981;246:2583-2584)
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Cerebrospinal fluid and serum penicillin levels were determined in patients with latent syphilis. Mean serum concentration one week after the third weekly dose of 2.4 million units penicillin G benzathine was 0.32 units/mL. Concurrent administration of probenecid orally produced a mean serum penicillin level of 0.41 units/mL. Doubled penicillin doses without and with daily orally administered probenecid resulted in mean serum concentrations of 0.75 and 1.00 units/mL, respectively. Two of six patients in the last group had CSF penicillin concentrations greater than 0.03 units/mL.
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This slender volume reports in lively form a 1962 Symposium concerned with the theoretical aspects of resistance of staphylococci to penicillin, and recent attempts to find new penicillins which would obviate this problem of resistance. Although it has been possible in the laboratory to render staphylococci penicillin-resistant without their producing penicillinase, nevertheless all naturally occurring penicillin-resistant strains of staphylococci are, without exception , penicillinase-producers. Small structural changes in the penicillin molecule might therefore be expected to alter markedly the affinity of the enzyme penicillinase for its substrate; recognition of this fact led several groups of organic chemists to systematically attempt to modify the benzyl penicillin (= penicillin G) molecule.
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SummaryThe present study has shown the following: (1) Two strains of pneumococcus developed resistance to penicillin as a result of serial passage through mice treated with this drug. (2) The rate at which resistance developed and the degree of resistance acquired varied significantly with the different strains. (3) The resistance of the one strain tested was not impaired by 30 serial passages through normal mice, indicating that, once established, resistance to penicillin is retained for a considerable period. (4) The development of resistance to penicillin in vivo was accompanied by an increase in resistance to this drug in vitro. (5) The response of the pneumococci to sulfonamides was not altered by the development of resistance to penicillin.
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(1952). Influence of probenecid on serum penicillin concentration after oral administration of penicillin. Scandinavian Journal of Clinical and Laboratory Investigation: Vol. 4, No. 2, pp. 83-88.
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