Vol. 114, December Printed in U.S.A.
THE JOURNAL OF UROLOGY
Copyright© 1975 by The Williams & Wilkins Co.
SULFACYTINE: A NEW SULFONAMIDE. DOUBLE-BLIND COMPARISON WITH SULFISOXAZOLE IN ACUTE UNCOMPLICATED URINARY TRACT INFECTIONS JACK HUGHES, LOUIS C. ROBERTS
ALTON J. COPPRIDGE
A new sulfonamide, sulfacytine, was compared in a double-blind study with sulfisoxazole for the treatment of acute uncomplicated urinary tract infection in 98 outpatients. Patients received either 4 gm. sulfisoxazole or 1 gm. sulfacytine daily for 10 days. Evaluation was made of the bacteriologic and clinical success within the period of treatment and at some point after treatment. Bacteriologic success, or reduction of urine bacterial count from 100,000 or more micro-organisms per ml. to 1,000 or less, was observed in 95 to 100 per cent of the patients in each group during treatment as well as at the post-treatment evaluation. Clinical success, or the abolition of dysuria and frequency of urination and the reduction of pyuria to less than 10 white blood cells per high power field, was observed in 75 to 85 per cent of the patients. Adverse reactions were rare, involving 1 instance each of headache, nausea and hematuria in the sulfisoxazole group, and drug attributability was only possibly established. Mild laboratory abnormalities occurred in each group, 2 cases each of decreased white blood count and 1 instance of a lowered hemoglobin in a patient in the sulfacytine group. The results of our study seem to indicate that sulfacytine is an effective drug for the treatment of acute uncomplicated urinary tract infections. Sulfonamides are effective therapy in cases of urinary tract infections caused by susceptible organisms. 1 They also offer the advantages of economy and relative safety, and superinfections rarely occur with their use. 2 Clinical evaluation of new, effective sulfonamides helps define their place in treatment programs. A new sulfonamide, sulfacytine* (1-ethyl-N-sulfanilylcytosine), has been described by Doub and associates.' When tested in mice with an acute lethal infection, sulfacytine was 25 to 50 times as potent as sulfamethizole, 3 to 10 times as potent as sulfisoxazole and sulfisomidine and up to 5 times as potent as sulfachlorpyridazine. 4 Some characteristics of the absorption and excretion of sulfacytine suggest that it may have advantages over other short-acting sulfonamides in treating acute urinary tract infections. The drug is rapidly absorbed and excreted in the urine almost entirely as the unchanged active form. 5 The rapid excretion into the urine may produce a more rapid therapeutic effect. Sulfacytine is also more soluble than other short-acting sulfonamides and forms supersaturated solutions in urine which may be less likely to crystallize in the kidney tubules. 3 This feature might be important if an overdose is given or if the drug is given to a severely dehydrated patient. Accepted for publication May 2, 1975. * Renoquid (sulfacytine), provided for investigational use only by Parke, Davis & Co., Detroit, Michigan 48232.
Results of clinical studies have been promising. •-s Since sulfacytine appears to be an attractive anti-infective agent for acute urinary tract infections, the double-blind study described herein was conducted to further define its clinical utility in comparison with sulfisoxazole. MATERIALS AND METHODS
Patients. The patients were 98 men and women with uncomplicated urinary tract infections (table 1). They were randomly assigned to medication groups, 48 receiving sulfacytine and 50 receiving sulfisoxazole. Characteristics of the patients in the 2 groups were comparable. The most common diagnosis among the patients was cystitis, which occurred in 98 per cent of the cases (table 2). Patients were entered in the study if they had frequency of urination and dysuria, pyuria of 10 or more white blood cells (WBCs) per high power field and a bacterial count of 100,000 or more pathogenic micro-organisms (Escherichia coli, Proteus, Klebsiella, Aerobacter or Enterococci) per ml. of urine. Three patients in the sulfacytine group (6 per cent) and 4 in the sulfisoxazole group (8 per cent) did not have bacterial counts of 100,000 or more but they are included for the change in symptomatology and pyuria. Patients were excluded if they had a history of chronic urinary tract infection, sulfonamide sensitivity, anemia, obstructive uropathy, or cardiovascular, respiratory or central nervous system abnormalities or metabolic defects which would interfere with drug metabolism.
SULFACYTINE: NEW SULFONAMIDE
Procedure. Before rece1vmg the drug each patient underwent a complete physical examination and the hemoglobin, total WBC and blood urea nitrogen were determined. A urine specimen was obtained by sterile catheterization (or occasionally by midstream clean voiding technique) for urinalysis and culturing. All bacteria isolated from the urine specimens were tested for to sulfacytine with disks impregnated with 250 µg. su!facytine. Drug treatment was initiated on a randomized schedule. Each bottle of drug contained tablets for 1 full course and the bottle was labeled with a number. A master code list indicated which patients received which drug. Initially, each patient received a loading dose of dmg-0.5 gm. sulfacytine (4 tablets) or 2.0 gm. sulfisoxazole (4 tablets). After this dose the regular schedule was 1 gm. sulfacytine daily (250 mg. 4 times a day) and 4 gm. sulfisoxazole daily (1 gm. 4 times a day). Drug treatment generally was continued for 10 days. Laboratory tests were performed again on day 8. Urinalysis, urine cultures and sensitivitv testing were repeated on day 8, during treatmen"t and on day 17 or 1 week after completion of treatment. The criterion for bacteriological success was reduction of micro-organism count to 1,000 or less per ml. of urine. The criteria for clinical success TABLE
1. Patient characteristics Sulfacvtine
Sulfisoxazole (4 gm. per day)
(1 gm. per day)
No. pts. Sex: Male Female Age: