had a urologic work-up including an intravenous pyelogram. Some of the patients had been previously treated with antibiotics. (5 of 32), and the majority of them ...
© 1983 S. Karger AG, Basel 0042-1138/83/0383-013552.75/0
Urol. int. iS; 135-137 (1983)
Randomized Prospective Study of the Comparative Efficacy of Spectinomycin and Gentamicin in Urinary Tract Infections Dawn //. Sasvary, Andreas G. Tzakis, Noel L. Smith, S. Ali Khan, Harry S. Soroff Departments of Surgery, State University of New York at Stony Brook, Stony Brook, N.Y., and the Veterans Administration Medical Center, Northport. N.Y.. USA
Key Words. Spectinomycin • Urinary tract infection Abstract. A prospective, randomized study was undertaken in 32 hospitalized patients with urinary tract infections to compare the efficacy of spectinomycin versus gentamicin. Spectinomycin was found to be of equal efficacy if not more efficacious in eradicating Escherichia coli, Klebsiella and Proteus mirabilis in our patient population. No significant side-effects were noted. A review of the literature with emphasis on the use of spectinomycin in infections other than anogenital gonorrhea is made.
Introduction The use of spectinomycin in treating bactériurie pa tients has been suggested recently, in view of the in vitro activity of spectinomycin against urinary tract isolates [ 51.
A prospective, randomized study was undertaken to compare the safety and efficacy of spectinomycin versus gentamicin in the treatment of hospitalized patients with urinary tract infections.
Some of the patients had been previously treated with antibiotics (5 of 32), and the majority of them had urological disorders treated prior to the study. The patients did not receive any other antibiotics from the beginning of the study until urine cultures were com pleted. Susceptibility to spectinomycin and gentamicin was determined by the Kirby-Bauer method [2] using 100-pg spectinomycin and 10pg gentamicin discs. Informed consent was obtained. Spectinomycin 2 g i.v./i.m. at 6- to 8-hour intervals or gentamicin 1 mg/kg i.v./i.m. at 6-8 h was given for 5-10 days. Urine cultures and other laboratory studies were repeated at 3,7,14 and 30 days. Positive urine cultures were considered those with growth greater than 105 colonies per cubic centimeter on spontaneous voiding. The intravenous and intramuscular injection sites were inspected daily, and the presence or absence of local infammation was noted.
Materials and Methods Table
I. Urologic diagnoses
Urologic diagnosis
Trobicin
Gentamicin
None Prostatectomy or cystectomy Renal calculus Benign prostatic hypertrophy Urinary retention Bladder tumor Incontinence Prostatitis Bladder neck obstruction Other
3 3 1 3 1 1 2 1 1 1
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32 patients were studied and received spectinomycin and gen tamicin in random order, utilizing a table provided by the sponsor. Patients admitted to the study were over 18 years of age, had signs and symptoms of urinary tract infection, and had at least two posi tive urine cultures with the same organism sensitive to both of the above drugs. Urine specimens were collected with a clean-catch tech nique. Positive urine cultures were those with colony counts greater than 1OVcm3. Patients with indwelling catheters were excluded, as were those with impaired renal function and drug allergies. Urologic diagnoses are summarized in table I. The studies included: CBC. urinalysis, urine osmolarity, SGOT, alkaline phosphatase, BUN, serum creatinine and audiometric ex amination (250, 500, 1,000 2,000, 4,000, 8,000 Hz). Each patient had a urologic work-up including an intravenous pyelogram.
136
Fig. 1. Culture results of treatment with spectinomycin and gen tamicin.
Results Duration of treatment was 6.9 ± 1.89 days with spec tinomycin and 6.8 ± 1.79 days with gentamicin. Urine cultures obtained during the study (fig. 1) gave the follow ing results: At 3 days: in the spectinomycin group, cultures were sterile in 14 of 16. Growth of the same organism was observed in 1 of 16 and growth of a different organism in 1 of 16. In the gentamicin group, specimens were not available in 3 of 16 and sterile in 12 of 13. Growth of the same organism was observed in 1 of 13. At 7 days: in the spectinomycin group, specimens were not available in 1 of 16 and sterile in 11 of 15. Growth of the same organism was observed in 3 of 15 and growth of a different organism in 1 of 15. In the gentamicin group, specimens were unavailable in 1 of 16 and sterile in 14 of 15. Growth of a different organism was observed in 1 of 15. At 14 days: in the spectinomycin group, specimens were not available in 4 of 16 and sterile in 7 of 12.
Growth of the same organism was observed in 4 of 12 and growth of a different organism in 1 of 12. With gen tamicin, specimens were not available in 1 of 16 and ster ile in 12 of 15. Growth of a different organism was observed in 3 of 15. At 30 days: in the spectinomycin group, urine was ster ile in 11 of 16. Growth of the same organism was observed in 4 of 16, still sensitive in vitro to both gen tamicin and spectinomycin, and a different organism, sensitive to both gentamicin and spectinomycin was ob served in 1 of 16. In the gentamicin group, specimens were not available in 1 of 16 and sterile in 5 of 15. Growth of a different organism, still sensitive to both gentamicin and spectinomycin, was observed in 4 of 15 and growth of a different organism in 6 of 15, of which 5 were sensitive to gentamicin and 1 was sensitive to spec tinomycin. Specific organisms: Escherichia coli was isolated in 12 patients, Klebsiella in 8 patients, Proteus mirabilis in 5 patients, Citrobacter in 3 patients, Serratia marcescens in 2 patients, Enterococcus, Proteus rettgeri and Enterobacter species each in 1 patient. Citrobacter and Serratia were both isolated from 1 patient. Spectinomycin eradi cated E. coli in 4 of 6 cases while in 1 case, E. coli per sisted, still sensitive to both spectinomycin and gentami cin, and in 1 case was succeeded by Klebsiella, sensitive to both spectinomycin and gentamicin. In the gentamicin group, 1 specimen was contaminated. E. coli was cleared in 2 of 5 cases. E. coli persisted in 1 of 5 cases, remaining sensitive in vitro to both gentamicin and spectinomycin. 2 cases showed growth of 5. marcescens sensitive to spec tinomycin and resistant to gentamicin. Klebsiella was encountered in 8 cases. Spectino mycin eradicated the organism in 3 of 5 cases while in 2 of 5 cases it persisted, still sensitive in vitro to both spectinomycin and gentamicin, and in 2 cases was succeeded by different pathogens (Pseudomonas and Enterococcus), sensitive to gentamicin and resistant to spectinomycin. P. mirabilis was treated in 5 cases. Spectinomycin era dicated the organism in 3 cases while after gentamicin it persisted in both cases remaining sensitive to both spec tinomycin and gentamicin in vitro. CBC, urine osmolarity, BUN, creatinine, alkaline phosphatase and SGOT did not change significantly. Nor were there any appreciable changes in the urinalysis, with the exception of the usual reduction of WBC and RBC count in the urine after treatment. The audiometric ex amination did not demonstrate hearing loss in any of the patients.
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Sasvary/T zakis/Smith/Khan/Soroff
Efficacy of Spectinomycin and Gentamicin
Spectinomycin is an aminocyclitol antibiotic similar to the aminoglycosides but lacking the nephro- and oto toxicity of the latter [1,4]. Due to the lack of toxicity, high serum levels (100 pg/ml) and much higher urine levels (100 pg/ml) are obtained with the currently used therapeutic regimen. There is no cross-sensitivity between spectinomycin and the aminoglycosides, and in the experimental investiga tion no allergy to spectinomycin has been elicited [13]. Spectinomycin has a ncurotransmitter action similar to that of neomycin [ 11 ]. It has been used with success in the treatment of anogenital gonorrhea [7, 10, 15, 16, 18], and is considered generally less active in vitro against gram negative and gram-positive bacteria than the aminogly cosides [12, 17]. The in vitro activity of spectinomycin against urinary tract isolates was found to be superior to that of ampicillin or tetracycline but inferior to that of gentamicin, and it was suggested that bactériurie patients with pathogens resistant to drugs such as ampicillin and tetracycline could be successfully treated with spectinomycin rather than with an aminoglycoside such as gentamicin [5]. Sim ilarly, the use of spectinomycin has been suggested for treatment of infection due to Bacteroides fragilis [3, 6, 8, 9, 14, 17, 19]. In evaluating the results of our study, we noted that the patients treated were all surgical patients who underwent several procedures including instrumentations prior to the study and had hospital-acquired urinary tract infections. The results of the cultures verify the fact that good early response to either one of the antibiotics used does not mean cure and can be followed by a recurrence. In our study, this seems to be more true with gentamicin. The value of prompt follow-up with repeated urine cultures cannot be overemphasized. The therapeutic effects of spectinomycin and gentamicin with E. coli, Klebsiella and P. mirabilis are probably not surprising in view of the known minimal inhibitory concentrations of spectinomy cin and gentamicin against these organisms. The absence of other organisms, like pseudomonas, usually seen in urinary tract infections, is notable in our study, likely due to a lack of sensitivity to both agents used. References 1 Akiyoshi, M.; Yano, S.; Ikeda, T.: Ototoxicity of spectinomycin (author’s translation). J. Antibiot., Tokyo 29: 771-782 (1976). 2 Bauer, A.; Kirby, W.M.M.; Sherris, J.C.; Turck, M.: Antibiotic susceptibility testing by a standardized single disk method. Am.
J. clin. Path. 45:493 (1966); Standardized disk susceptibility test. Federal Register 39: 19182-19184; National Committee for Clin ical Laboratory Standards. Approved standard: ASM-2, Perfor mance standards for antimicrobial disk susceptibility test (1975) . 3 Churcher, G.M.; Human, R.P.; Assessment of the in vitro activ ity against Bacteroides species of spectinomycin metronidazole and clindamycin. J. antimicrob. Chemother. 3: 363-370 (1977). 4 Dickering, L.; Hohl. S.: Recent advances in antimicrobial thera py. Sth. med. J.. Nashville 70 (1977). 5 Fass, R.; Prior, R.: In vitro activity of spectinomycin against recent urinary tract isolates. Antimicrob. Agents Chemother. 12: 551-554 (1977). 6 Ferguson, I.R.; Smith, L.L.: The susceptibility of Bacteroides fragilis to spectinomycin chemotherapy. Proc. 9th Int. Congr. Chemother., vol. 1, pp. 247-254 (1976). 7 Fiumara. N.J.: Treating gonorrhea. Am. Family Phys. 23: 123— 126 (1981). 8 Flyder, M.G.; Bywater, M.J.; Holt, H.A.: Concentration achieved in serum acid pelvic tissue after various antibiotic regimens given perspectively. Current Chemotherapy. Proc. 10th Int. Congr. Chemotherapy, vol. 1 (1978). 9 Gibbs, R.S.: A trial of spectinomycin hydrochloride compared with aqueous penicillin G plus kanamycin for treatment of severe pelvic inflammatory disease. Sex. transm. Dis. 7; 21-23 (1980). 10 Judson, L.N.: Gonococcal urethritis. Diagnosis and treatment. Archs Androl. 3: 329-335 (1979). 11 Muekiyo, K.; Oshima, H.; Horikawa, A.: Effect of spectinomycin on neuromuscular transmission. Jap. J. Pharmacol. 28: 927-930 (1978). 12 Phillips, I.; Eykyn, S.; King, B.A.; et al.: The in vitro antibacterial activity of nine aminoglycosides and spectinomycin on clinical isolates of common gram-negative bacteria. J. antimicrob. Che mother. 3: 403^» 10 (1977). 13 Raap, W.P.: Spectinomycin-experimental investigations on pos sible side-effects. Int. J. clin. Pharm. Biopharm. 14: 44-47 (1976) . 14 Ralph, E.: Amatnieks, Y.E.: Potentially synergistic antimicrobial combinations with metronidazole against Bacteroides fragilis. Antimicrob. Agents Chemother. 17: 379-382 (1980). 15 Rettig, P.J.; Nelson, J.D.; Kusmiesz, H.: Spectinomycin therapy for gonorrhea in prepubertal children. Am. J. Dis. Child. 134: 359-363 (1980). 16 Sands, M.: Treatment of anorectal gonorrhea infections in men. J. Am. med. Ass. 21: 1143-1144 (1980). 17 Washington. J.; Yu, A.P.: In vitro antibacterial activity of specti nomycin. Antimicrob. Agents Chemother. 2: 427-430 (1972). 18 Williams, R.A.: Penicillinase-producing Neisseria gonorrhoeae. Am. Family Phys. 24: 117-119 (1981). 19 Wise, R.; Andrews, J.M.; Beford, K.A.: The activity of four antimicrobial agents, including three nitromidazole compounds against Bacteroides. Chemotherapy 23: 19-24 (1977). Received: September 6, 1982 Accepted: November 2, 1982 Harry S. Soroff. MD. Professor and Chairman, Department of Surgery, State University of New York at Stony Brook, Stony Brook, NY 11794 (USA)
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Discussion
137
