518 THE BIOCHEMISTRY OF B VITAMINS 



one case; 361 however, resistance of organisms isolated from patients after 

 prolonged treatment is usually increased. Gonococci isolated from infected 

 patients not cured after sulfathiazole had been administered for 6 days 

 (6 gm/day) were resistant to 0.5 mg per cent of sulfathiazole in vitro, 

 and some grew in 25-50 mg per cent, while strains from cured patients 

 were susceptible to this concentration. 355 



A wide variation in the extent to which resistance may be developed 

 in different strains has also been observed. 321, 359, 377 



Although resistance to a certain bacteriostatic concentration of one 

 sulfonamide is usually accompanied by an equal resistance to similar 

 bacteriostatic concentrations of the other sulfonamides, 327 - 341, 351, 353, 356, 

 357, 362, 363, 365 th} s j s no t a m \ e w jthout exceptions. 345, 350, 377 For example, 

 strains of Shigella paradysenteriae Flexner, Shigella sonnei (Ch) and 

 Shigella sonnei (Ma) , made resistant to sulfathiazole by transfer in in- 

 creasing concentrations, were resistant also to sulfapyridine, sulfadiazine 

 and sulfanilamide, but not to sulfapyrazine. Their resistance to sulfa- 

 cetamide varied. 377 - 378 



Cross-resistance between sulfonamides and penicillin does not appear 

 to take place, 330 - 344, 350 ' 359 and it has been shown that development of 

 resistance to sulfanilamide does not influence susceptibility to strepto- 

 mycin, atebrin, sodium salicylate, 3,5-dibromosalicylic acid and synthelin 

 (decamethylenediguanidine) . 344 



A high degree of resistance acquired after a great many transfers on 

 sulfonamide-containing media is usually permanent. 330, 338, 350, 356, 360, 363, 

 383, 384 However, partial resistance acquired through short contact with 

 the drug is usually temporary, and is lost after repeated transfer on sul- 

 fonamide-free media. 338, 360, 367, 383 



Several factors affecting the degree of resistance acquired have been 

 observed. It has been indicated that, unless the drug is present in suffi- 

 cient quantity to inhibit growth of Escherichia coli, very little resistance 

 is developed, and that the degree of resistance developed varies with the 

 concentration used. 341 However, it is also reported that by repeated trans- 

 fer of cultures of Escherichia coli on low concentrations of the drug, 

 resistant strains can be developed. 250 With Brucella abortus an increase 

 in the time of incubation increases the degree of resistance developed. 12 

 In the presence of p-aminobenzoic acid, no sulfonamide resistance could 

 be produced with Escherichia coli, and the presence of methionine delayed 

 its acquisition. 250 Organisms made resistant in a plain infusion broth con- 

 taining peptone were not resistant when tested in a synthetic medium. 250 



Because pneumococci surviving the first exposure to sulfapyridine were 

 significantly more resistant than any organisms of the original parent 



