OTHER COMPOUNDS USED IN ANTIBACTERIAL THERAPY 171 



the power of the latter to lower surface tension, and thus to concentrate on or 

 in the bacterial cell. Fuller (1942) reached the same conclusion from a study 

 of 40 long-chain aliphatic compounds — amines, amidines, guanidines and quaternary- 

 ammonium compounds. Gram-positive organisms were more susceptible than 

 Gram-negative organisms ; though the strongly basic guanidines and quaternary 

 compounds had a relatively greater effect on Gram-negative bacteria, the less 

 strongly basic amines on Gram-positive bacteria. Basicity, however, was a less 

 important factor than chain length (and presumably, therefore, surface activity), 

 for bacteriostatic activity increased with the length of the carbon chain to a 

 maximum and, with some of the series, declined with a further increase in chain 

 length. 



Other Compounds used in Antibacterial Therapy 

 Arsenic Compounds. 



The oi'ganic arsenicals have been tested in the treatment of experimental and natural 

 bacterial infection. For instance. Bierbaum (1912) demonstrated some protection of 

 mice infected with Ery. rhusiopathiw by treatment with arsphenamine and neoarsphena- 

 mine. Kolle, Leupold, Schlossberger and Hundeshagen (1921) studied the same infection, 

 and extended the range of compounds tested to amino-arsenobenzol compounds. Com- 

 pounds which were active in vivo had little in vitro activity, and they concluded that 

 the active form was produced in the animal body. Christison (1934) also demonstrated 

 a curative effect in this disease of certain arsenopyridine compounds, notably 2-pyridine- 

 3-amino-5-arsenic acid. Allison (1918) found that arsphenamine had a protective effect 

 in rabbits against Sir. pyogenes infections. 



Arsphenamme and neoarsphenamine are bactericidal in vitro, in watery solution, in 

 blood, serum, and in the presence of leucocytes (Schiemann 1915, Douglas and Colebrook 

 1916, Osgood 1943). Susceptible bacteria include B. anthracis, Pf. mallei, Ery. rhusio- 

 pathice. Staph, aureus, Str. pyogenes, C. diphtherice, and Hcem. influenzce. The compounds 

 most active in vitro appear to be those with an arsenoxide group. Peters (1943) and 

 Albert, Talk and Rubbo (1944) suggest that the arsenoxides interfere with thiol groups 

 in the essential enzyme systems of the bacteria, and in this respect resemble the mercurial 

 antiseptics, whose action was first interpreted by Fildes (19406) along the same lines. 

 Neoarsphenamine has been used in the treatment of human infections, notably puerperal 

 fever (Colebrook 1928) ; anthrax (see, for example, Lucchesi and Gildersleeve 1941) and 

 Str. viridans endocarditis (Osgood 1942, 1944). The low therapeutic index that obtains 

 for these drugs when used against bacterial infections precludes their unrestricted use 

 in human infections ; Osgood maintains that their use is justified in infections with a 

 mortahty greater than five per cent., if safer drugs prove ineffective. 

 Sulphones. 



Diaminodiphenyl sulphone (H2NC6H4-S02-C6H4-NH2) and its acetyl derivative are 

 more active than sulphanilamide against streptococci, both in vitro and in vivo, and though 

 they are more toxic, their high activity ensures a higher chemotherapeutic index than 

 sulphanilamide (Buttle et al. 1937, Bauer and Rosenthal 1938). An N-phosphoryl deriva- 

 tive of diaminodiphenyl sulphone, which was less toxic in mice, proved to be active 

 against streptococcal and pneumococcal infections (Smith, Rosenthal and Jackson 1942). 



" Promin," which is diaminodiphenyl sulphone N,N' dighicose sulphonate, has been 

 used with some success in the treatment of tuberculous infections of guinea-pigs. The 

 life of the animals is prolonged, the character of the tuberculous lesion is changed, and 

 in some cases regression of the lesion occurs (Feldman. Mann and Hinshaw 1942a, b, 

 Barach, Molomut and Soroka 1942, Feldman and Hinshaw 1943). Its action in human 

 tuberculosis is less striking, partly owing to its relatively low therapeutic index (Hinshaw, 

 Pfuetze and Feldman 1943, Tytler and Lapp 1942, Heaf et al. 1943 ; see also Raiziss 1943, 

 CaUomon 1943). 



