p-AMINOBENZOIC ACID 517 



Different types of pneumococci 323, 324, 327 > 328, 332 vary in their suscepti- 

 bility to various sulfonamides. Similar results are obtained with different 

 strains of Clostridium, 320 gonococcus 329 and /^-hemolytic streptococci. 331, 333 

 Marked disparity in the inhibitory ability of a specific sulfonamide for 

 10 strains of Shigella sonnet has been noted. 325 



Although clinical and in vitro observations usually correspond, 329 - 334, 335 

 in vitro resistance does not always indicate in vivo resistance, and vice 

 versa. 528, 329, 332, 336 - 339 Sulfathiazole resistance was induced in vitro in 

 Shigella paradysenteriae Flexner, but this resistance was not exhibited in 

 vivo in white mice. 337 By isolating pneumococci from patients and fol- 

 lowing the changes in their resistance during the course of therapy, it 

 was found that the in vitro resistance of an organism was decreased. 332 

 Of organisms isolated from patients who have shown resistance in sul- 

 fonamide therapy, some are not resistant in vitro. Although variation in 

 resistance of isolated gonococci corresponded to the clinical reaction of 

 the patient in most cases, an in inYro-susceptible strain has been isolated 

 from a patient resistant to sulfathiazole therapy, and an in tnYro-resistant 

 strain has been isolated from a patient who had responded to this treat- 

 ment. 329 These and similar observations in clinical studies with gono- 

 cocci 339 suggest that this particular type of resistance is dependent 

 entirely upon the environment. It appears that in vivo resistance may 

 sometimes be due to a host factor (and in vitro resistance, to a constituent 

 of the culture medium) , which counteracts the action of the sulfonamide. 



Acquired Resistance. Organisms serially transferred in vitro in in- 

 creasing concentrations of the sulfonamides may be made resistant to the 

 action of these drugs. Resistance may also be developed in vivo during 

 sulfonamide administration to the host. Many organisms have been 

 shown capable of developing resistance to the sulfonamides: Escheri- 

 chia coli, 11 ' 25 °- 34 °- 344 hemolytic streptococci, 331, 345 349 Streptococcus pyo- 

 genes, 350 Neisseria gonorrheae, 334 ' 335 - 350a - 357 Neisseria meningitidis , 35G 

 Neisseria catarrhalis 35 * and Neisseria sicca 356 Brucella abortus, 12 Bru- 

 cella paramelitensis 342 pneumococci, 18, 26(5, 322, 324, 330, 332, 336, 338, 358 " 369 

 Staphylococcus aureus, 1 ' 18, 321, 342, 37 °- 37G Staphylococcus pyogenes, 350 

 Shigella paradysenteriae 337 ' 377 - 379 Shigella sonnei 18 ' 325, 337, 377, 37S Myco- 

 bacterium ranae, 380 Friedlander's bacillus, 343 Acetobacter sub oxy dans, 381 

 Polytomella caeca, 104 and Endamoeba histolytica. 382 Between strains of 

 one species there is often a wide variation in the ease with which resist- 

 ance may be developed, 351 ' 359 > 302 but the number of resistant organisms 

 developing from a single strain often does not vary significantly. 351 



Development of resistance in vivo may be rather difficult or may occur 

 readily, depending upon the organism. In a study of pneumococci from 

 72 infected patients, a strain with striking resistance developed in only 



