Diuretic Response to Chlorthalidone
Authors: A. Douglas, R. Hall, D. B. Horn, D. N. S. Kerr, D. T. Pearson, H. Richardson
Journal: BMJ (1961)

PENBRITIN," A NEW PENICILLIN BJRNA though-as with other penicillins so far tested-hyper- sensitivity to penicillin G means hypersensitivity also to this derivative.Drug-resistance can be induced easily in vitro but did not account for relapses in vivo, though there was evidence in two cases that it could occur in minor degree.In our present series we have deliberately excluded some respiratory infections in which a clinical response was observed; the bacteriology of such cases is often obscure and we are in these trials guided by the belief that two criteria are essential: disappearance of the target pathogens in cases and carriers, and parallel clinical improvement in cases.Without these criteria a therapeutic trial on an antibacterial agent is question- able.On this basis, we consider that the results reported here indicate a place for penbritin as a non- toxic penicillin of high bactericidal broad-spectrum activity in the oral treatment of urinary and possibly in systemic infections due to pyogenic cocci and sensitive Gram-negative bacilli.It warrants trial also in infections of the biliary tract and in some alimentary infections, peritonitis, and pre-operative intestinal surgery; it cannot at present be recommended for the treatment of intestinal carriers of salmonellae, despite the high sensitivity of these organisms in vitro.In view of the variation in sensitivity of typical coliforms toward the drug, its use in urinary and abdominal infections should be contingent upon adequate bacteriological control, which should include tests at concentrations attainable in the affected tissue.In assessing the novel features of this new compound we should not forget the fact that penicillin G itself has an inhibitory effect upon many coliforms (Abraham et al., 1941; Shwartzman, 1946), sometimes bactericidal and strong enough to enable it to be used therapeutically (Helmholtz and Sung, 1944;Stewart, 1945).Methicillin, phenethicillin, and phenoxypropylpenicillin lack such activity toward coliforms, so that penbritin represents a valuable chemical advance in thus enhancing a specific property within the penicillin family of substances.Summary "Penbritin " has a bactericidal action, comparable to that of penicillin G upon pyogenic cocci, upon a wide range of coccal and bacillary pathogens.It is affected by penicillinase and is therefore inactive against penicillinase-forming strains of Staph.aureus and certain coliforms.Given orally in doses of 50-100 mg./kg./day, the new compound is freely absorbed and maintains a bacteri- cidal level in the plasma for four hours or more.It is rapidly excreted, in very high concentration, in the urine.Apart from transient rashes in three carriers of salmonellae, no toxic effects were observed in 28 patients who received the drug for five days or more.Eight children with severe urinary infection due to coliforms and/or streptococci responded rapidly to treatment, as did six children with other infections; six carriers of Salm.typhi-murium and two of E. coli serotypes were not cleared of infection.Penbritin warrants further trial as a bactericidal penicillin-like drug with the antibacterial range of the tetracycines.Grateful acknowledgment is made to the following: Dr.