A Bacteriologic Study of the Factors Affecting the Efficacy of Streptomycin Therapy of Urinary Tract Infections 12

Abstract

Streptomycin appears to be the most useful antibiotic available at present for the treatment of infections due to gram-negative bacilli. The absorption, distribution, and excretion of the drug following various modes of administration have been studied (1). The results of clinical trials of the drug in various types of infections have been reported (2). Treatment schedules and the influence of various factors in determining the optimum dosage of streptomycin have been investigated clinically, and the results are being reported elsewhere (3). The observation that the most common cause of therapeutic failure was the development of bacterial resistance or fastness 8 to streptomycin focused attention on the necessity for further bacteriologic studies in relation to concentrations of streptomycin. The cases of urinary tract infection afforded an opportunity for further investigation of the effect of streptomycin on bacteria. MATERIALS AND METHODS Bacteriologic methodsIn each case an attempt was made to detect all the flora involved. Urine was collected by catheterization in all females and in many of the males; in the remainder of the males voided specimens were collected after thorough cleansing of the glans and meatus with a 1: 1,000 solution IThe streptomycin used in this study was furnished by the Committee on Chemotherapeutics and Other Agents of the National Research Council.2 These studies were aided by a grant from Miss Edith Pipkin and Mrs. J. B. Pipkin. 8 Although the term resistance has been used to denote a lack of response by the organism to the drug, the possibility of confusion with resistance (immunity) of the host would suggest that another term such as insensitivity, refractoriness, fastness, or non-susceptibility should be used when referring to the bacteria. Refractoriness or fastness would imply the development of insensitivity in a previously susceptible organism. At present this is known to develop only after exposure to the drug. of mercuric chloride. After a small amount of urine had been voided to wash out the urethra, the stream was interrupted with a sterile test tube for the collection of the specimen.The urine was centrifuged and smears were made and stained by the Gram method. Cultures were made routinely on beef extract broth, blood agar slants or plates adjusted to a pH of 7.5., and desoxycholate plates. Individual colonies were transplanted to differential sugars for further identification. When the presence of organisms which required special bacteriologic methods was suspected, the necessary conditions of partial or complete anaerobiosis or increased carbon dioxide tension were achieved.Therapy was usually started as soon as gram-negative bacilli were detected on a smear or culture, without awaiting complete identification. During therapy, cultures were usually made daily. One or more additional cultures were done at least 24 hours after the completion of therapy, before the patient was discharged from the hospital, and a culture was made on each follow-up visit. In vitro sensitiv...

Chloramphenicol-Fastness: Development in Vivo and Experimental Production in Vitro1

“…Under such circumstances the local defense mechanisms of the host would be more effective (10) and further mutation to higher degrees of resistance should occur less frequently. These factors may explain why some of the drugfast strains were cleared from the urine during continued therapy.…”