ANTIMICROBIAL AGENTS AND CHEMOTHERAPY, Apr. 1991, p. 750-752
Vol. 35, No. 4
0066-4804/91/040750-03$02.00/0
Copyright C) 1991, American Society for Microbiology
Loracarbef versus Cefaclor in the Treatment of Urinary Tract Infections in Women ABDOLLAH IRAVANI Division of Nephrology, Department of Pediatrics, College of Medicine, University of Florida, Gainesville, Florida 32610-0296 Received 4 September 1990/Accepted 5 February 1991 a double-blind, prospective, randomized study, 108 college women with acute urinary tract infections treated for 7 days with either loracarbef (LY163892) at 200 mg once daily (n = 53) or cefaclor at 250 mg three times daily (n = 55). The cure rates at 5 to 9 days after treatment in the loracarbef and cefaclor groups were 96 and 90%, respectively. Both loracarbef and cefaclor are safe, well tolerated, and effective in the treatment of urinary tract infections in women.
In
were
Loracarbef (LY163892) is a new beta-lactam antibiotic with in vitro activity similar to those of cefaclor and amoxicillin-clavulanate potassium and superior to that of cephalexin (4, 11, 19). Loracarbef is absorbed well from the bowel, attaining high levels above the MICs for susceptible organisms in plasma; it is excreted mostly in the urine in the active form. Loracarbef is resistant to plasmid-mediated 1-lactamases and has greater biochemical stability than cefaclor (3, 21, 22). These favorable characteristics make loracarbef a suitable antibiotic for once-a-day treatment of urinary tract infections (UTIs). One purpose of this double-blind, randomized trial was to compare the safety and efficacy of a 7-day course of loracarbef (200 mg once daily) with cefaclor (250 mg three times a day) (Eli Lilly & Co., Indianapolis, Ind.) for treatment of acute UTIs. To maintain the blind study design, placebos were given to patients in the loracarbef group. A second purpose was to assess the emergence of resistant organisms in the genital and rectal aerobic flora. Prior to initiation, the trial was approved by our Institutional Review Board and signed written consent was obtained from each patient. The patients studied were college women who came to the Kidney Clinic of the University of Florida Student Health Care Center. A criterion for inclusion was the presence of i105 CFU of the same bacterium per ml in each of two consecutive urine specimens. Excluded from the study were pregnant or lactating women; those with impaired renal or liver function, radiographically proven obstructive uropathy, or a history of allergy to penicillins or cephalosporins; and anyone receiving antimicrobial agents during the preceding week. Two clean-catch midstream urine specimens were obtained within 48 h before treatment for analysis and culture. Specimens were collected from genitals and recta with Culturette rayon-tipped swabs (Scientific Products Div., Evanston, Ill.) for nonquantitative aerobic culture pretherapy and 5 to 9 days posttherapy. Urinary bacterial isolation was performed and quantitative counts were determined as previously described (8, 16, 20, 26). Antibiotic susceptibility was tested by the disk diffusion method by using 30-R,g disks of loracarbef and 30-p.g disks of cephalothin (1). Bacterial isolates were considered susceptible to loracarbef or cefaclor when the disk zone sizes were 218 mm. Intermediate susceptibility was defined as 50 CFU. Susceptibility was tested as described above. Vaginal swabs were also tested for Candida albicans before and 5 to 9 days posttherapy as previously described (15, 16). Escherichia coli isolates were identified by serotype as previously reported (9, 23). Clinical and bacteriological evaluations were repeated within 2 to 4 days of initiation of treatment and 5 to 9 days and 4 to 6 weeks posttherapy. During therapy, patients used diaries to record times of medication taking, voiding, and resolution of dysuria and urgency. Complete disappearance of symptoms by 5 to 9 days posttherapy was termed clinical cure, incomplete resolution was termed clinical improvement, and no apparent response was termed clinical failure. Bacteriologic responses were classified as short-term cures, long-term cures, failures, relapses, and reinfections, as described previously (15). The life table method and the chi-square and Fisher exact tests were used to analyze the data (5, 7). Of 108 patients who entered the study (53 in the loracarbef group, 55 in cefaclor group), 104 (96.3%) were symptomatic, with a combination of dysuria, urgency, and suprapubic pain; 7 (15.7%) had costovertebral angle tenderness, and 1 had a fever of >380C. There were no differences between the two groups with regard to pretherapy demographic findings and clinical presentation. In the loracarbef group, the mean age was 22.2 + 4 years, symptoms were present 4.4 ± 4 days pretherapy, 17 patients (32.1%) had recurrent UTIs, and 51 (96.2%) had pyuria. In the cefaclor group, the mean age was TABLE 1. Distribution of urinary pathogens and results of
in vitro susceptibility testing Pathogen
Escherichia coli Klebsiella pneumoniae Proteus mirabilis Enterobacter aerogenes Citrobacter sp. Nonhemolytic staphylococci Enterococci "
750
No. of isolates (no. resistant)
Loracarbef
Cefaclora
36 (0) 4 (0) 4 (0) 2 (2) 1 (0) 6 (1) 0 (0)
38 (0) 4 (0) 4 (0) 3 (2) 4 (0) 3 (1) 1 (0)
Two patients in the cefaclor group each had two pathogens initially.
NOTES
VOL. 35, 1991
751
TABLE 2. Distribution of patients by treatment group and bacteriologic response through 4 weeks after treatment ended
Trete group Loracarbef Cefaclor
Who completed treatment
~~follow-up (5-9 days
and
With short-term:
posttherapy)
Cure
Failure
46 51
44 (96) 46 (90)
2 (4) 5 (10)
22.3 + 3 years and symptoms were present 3.5 + 12 days pretherapy. Fifteen patients- (27.3%) had recurrent UTIs, and 55 (100%) had pyuria. The mean times until disappearance of symptoms after initiation- of therapy were 48 (range, 4 to 234) h in the loracarbef group and 41 (range, 6 to 137) h in the cefaclor group. Four patients were asymptomatic. Distributions of urinary pathogens and their in vitro susceptibilities were comparable between groups (Table 1). Ninetysix percent of the urinary pathogens were susceptible to loracarbef, and 95% were susceptible to cefaclor. The 74 E. coli isolates were all susceptible to loracarbef and cefaclor. Four of five isolates of Enterobacter aerogenes were resistant to both agents. These results are in agreement with previous reports that loracarbef and cefaclor have comparable in vitro activities that are superior to that of cephalexin (2, 4, 11). In the loracarbef group, 52 of 53 patients had sterile urine cultures after 2 to 4 days of therapy. One patient had a resistant pathogen pretherapy, and her urine culture remained positive. Her therapy was discontinued, as was that of three others, for the following reasons: one because of a low pretherapy bacterial count and two because of adverse reactions. In the cefaclor group, all 55 patients had sterile urine cultures after 2 to 4 days of therapy. Of the patients returning at 5 to 9 days posttherapy, 96% of the loracarbef group and 90% of the cefaclor group had short-term cures. Long-term cures occurred in 81% of the patients initially enrolled in each group who were available for long-term follow-up. Bacteriologic responses through 4 weeks posttherapy are shown in Table 2. Initially identified urinary pathogens remained eradicated at 4 to 6 weeks posttherapy in 37 (90%) and 39 (93%) of the patients in the loracarbef and cefaclor groups, respectively (P > 0.10). The therapeutic results of the two groups were favorable and comparable to those previously attained with antimicrobial agents, including cephalosporins, in young women (6, 10, 12-14, 16-18). Periurethral, vaginal, and rectal specimens were obtained from 46 patients in the loracarbef group and 51 patients in the cefaclor group. After therapy in both groups, the numbers of patients with cultures positive for colonizing E. coli in the periurethral (P < 0.001), vaginal (P < 0.001), and rectal (P < 0.01) flora were reduced. No significant change occurred in either (i) the number of patients with positive cultures for other members of the family Enterobacteriaceae or (ii) the susceptibility patterns of the bacteria colonizing these sites in either group. The findings related to cefaclor are in agreement with those previously reported (17, 18). In the loracarbef group, five patients experienced adverse events: therapy was discontinued for two patients because of nausea, headache, and abdominal pain; two had nausea, one combined with a rash; and one experienced difficulty breathing and diarrhea on the last day of therapy. In the cefaclor group, three patients reported adverse events: two experienced diarrhea, one with nausea, and one developed a rash
No. (%) of patients Lost to follow-up after 59dy
othrp
5-9 days posttherapy
3 4
With long-term:
Relapse 4 (10) 3 (7)
Reinfection 2 (5) 1 (3)
Cure 35 (81) 38 (81)
on the last day of therapy. Therapy was not interrupted for these three patients. By 5 to 9 days posttherapy, Candida vaginitis developed in 8 (15.1%) of the patients in the loracarbef group and 11 (20.0%) of the patients in the cefaclor group. Laboratory test results did not significantly change for any patients in either group. These findings are consistent with those previously reported for cefaclor (13-15, 17, 18, 24, 25, 27, 28). In conclusion, loracarbef and cefaclor are safe, well tolerated, and effective in the treatment of UTIs in women. The assistance of Barbara Peters, Dorothy Ellerbe, Lisa Duncanson, Janice Barnhart, Lee Stutevoss, and Elizabeth Patrick for the study and preparation of the manuscript is acknowledged and appreciated. A grant for this study was supplied by Eli Lilly Pharmaceuticals to the University of Florida Division of Sponsored Research. REFERENCES 1. Bauer, A. C. O., W. M. M. Kirby, J. L. Sherris, and M. Turck. 1966. Antibiotic susceptibility testing by a standardized single dose method. Am. J. Clin. Pathol. 45:493-496. 2. Bill, N. J., and J. A. Washington II. 1977. Comparison of in vitro activity of cephalexin, cephradine, and cefaclor. Antimicrob. Agents Chemother. 11:470-474. 3. Black, H. R., K. A. Desante, J. D. Wolny, and G. L. Brier. 1988. Program Abstr. 28th Intersci. Conf. Antimicrob. Agents Chemother., abstr. 123. 4. Cao, C., N. X. Chin, and H. C. Neu. 1988. In vitro activity and P-lactamase stability of Ly163892. J. Antimicrob. Chemother. 22:155-165. 5. Colton, T. 1974. Statistics in medicine, 1st ed., p. 151-188. Little, Brown & Co., Boston. 6. Cox, C. E., J. M. Sherrill, and D. M. Cocchetto. 1987. Evaluation of cefuroxime axetil, cefaclor and cephalexin in the treatment of urinary tract infections in adults. Curr. Ther. Res. 42:124-137. 7. Cutler, B. J. 1958. Maximum utilization of the life table method in analyzing survival. J. Chronic Dis. 8:699-712. 8. Edwards, P. R., and W. H. Ewing. 1972. Identification of Enterobacteriaceae, 3rd ed., p. 7-47. Burgess Publishing Co., Minneapolis. 9. Ewing, W. H. 1956. Production of Escherichia coli antiserum. Public Health Lab. 14:138-141. 10. Gurwith, M. J., G. E. Stein, and D. Gurwith. 1983. Prospective comparison of amoxicillin-clavulanic acid and cefaclor in treatment of uncomplicated urinary tract infections. Antimicrob. Agents Chemother. 24:716-719. 11. Howard, A. J., and K. T. Dunkin. 1988. Comparative in vitro activity of a new oral carbacephem, Ly163892. J. Antimicrob. Chemother. 22:445-456. 12. Iravani, A., N. Pryor, and G. A. Richard. 1982. Treatment of acute uncomplicated urinary tract infections by cephalexin, with special reference to the antibody-coated bacteria. Int. J. Clin. Pharmacol. 20:97-100. 13. Iravani, A., and G. A. Richard. 1982. Treatment of urinary tract infections with a combination of amoxicillin and clavulanic acid. Antimicrob. Agents Chemother. 22:672-677. 14. Iravani, A., and G. A. Richard. 1985. Single-dose ceftriaxone
752
15.
16.
17.
18.
19. 20.
NOTES versus multiple-dose trimethoprim-sulfamethoxazole in the treatment of acute urinary tract infections. Antimicrob. Agents Chemother. 27:158-161. Iravani, A., and G. A. Richard. 1986. Amoxicillin-clavulanic acid versus cefaclor in the treatment of urinary tract infections and their effects on the urogenital and rectal flora. Antimicrob. Agents Chemother. 29:107-111. Iravani, A., and G. A. Richard. 1989. Single-dose cefuroxime axetil versus multiple-dose cefaclor in the treatment of acute urinary tract infections. Antimicrob. Agents Chemother. 33: 1212-1216. Iravani, A., G. A. Richard, and H. Baer. 1981. Treatment of uncomplicated urinary tract infections with trimethoprim versus sulfisoxazole, with special reference to antibody-coated bacteria and fecal flora. Antimicrob. Agents Chemother. 19:842-850. Iravani, A., G. A. Richard, D. Johnson, and A. B. Bryan. 1988. A double-blind, multicenter, comparative study of the safety and efficacy of cefixime versus amoxicillin in the treatment of acute urinary tract infections in adult patients. Am. J. Med. 85(Suppl. 3A):17-23. Jones, R. N., and A. L. Barry. 1988. Antimicrobial activity of Ly163892, an orally administered 1-carbacephem. J. Antimicrob. Chemother. 22:315-320. Jordan, P. A., A. Iravani, G. A. Richard, and H. Baer. 1980. Urinary tract infection caused by Staphylococcus saprophyticus. J. Infect. Dis. 142:510-515.
ANTIMICROB. AGENTS CHEMOTHER. 21. Knapp, C. C., and J. A. Washington II. 1988. In vitro activities of LY163892, cefaclor, and cefuroxime. Antimicrob. Agents Chemother. 32:131-133. 22. Nelson, J. D., S. Shelton, and H. Kusmiesz. 1988. Pharmacokinetics of LY163892 in infants and children. Antimicrob. Agents Chemother. 32:1738-1739. 23. 0rskov, I., F. 0rskov, B. Jann, and K. Jann. 1977. Serology, chemistry, and genetics of 0 and K antigens of Escherichia coli. Bacteriol. Rev. 41:667-710. 24. Rotschafer, J., K. Crossley, D. Zaske, and R. Viste. 1979. Comparative study of cefaclor and amoxicillin in the treatment of urinary tract infection. Urology 14:233-236. 25. Rous, S. N. 1981. Comparison of cefaclor versus trimethoprimsulfamethoxazole combination in the treatment of acute urinary infections. J. Urol. 125:228-229. 26. Smith, P. B., K. M. Tomfohrde, D. L. Rhoden, and A. Balows. 1972. API system: a multitube micromethod for identification of Enterobacteriaceae. Appl. Microbiol. 24:449-452. 27. Trager, G. M., G. W. White, P. E. Porembski, and A. P. Panwalker. 1980. A comparison of cefaclor and trimethoprim/ sulfamethoxazole in the treatment of urinary tract infections. Curr. Ther. Res. 28:419-423. 28. Williams, K. J., E. M. Hebblethwaite, G. W. Brown, D. M. Cox, and S. J. Plested. 1987. Cefuroxime axetil in the treatment of uncomplicated UTI: a comparison with cefaclor and augmentin. Drugs Exp. Clin. Res. 13(2):95-99.
Vol. 35, No. 4
0066-4804/91/040750-03$02.00/0
Copyright C) 1991, American Society for Microbiology
Loracarbef versus Cefaclor in the Treatment of Urinary Tract Infections in Women ABDOLLAH IRAVANI Division of Nephrology, Department of Pediatrics, College of Medicine, University of Florida, Gainesville, Florida 32610-0296 Received 4 September 1990/Accepted 5 February 1991 a double-blind, prospective, randomized study, 108 college women with acute urinary tract infections treated for 7 days with either loracarbef (LY163892) at 200 mg once daily (n = 53) or cefaclor at 250 mg three times daily (n = 55). The cure rates at 5 to 9 days after treatment in the loracarbef and cefaclor groups were 96 and 90%, respectively. Both loracarbef and cefaclor are safe, well tolerated, and effective in the treatment of urinary tract infections in women.
In
were
Loracarbef (LY163892) is a new beta-lactam antibiotic with in vitro activity similar to those of cefaclor and amoxicillin-clavulanate potassium and superior to that of cephalexin (4, 11, 19). Loracarbef is absorbed well from the bowel, attaining high levels above the MICs for susceptible organisms in plasma; it is excreted mostly in the urine in the active form. Loracarbef is resistant to plasmid-mediated 1-lactamases and has greater biochemical stability than cefaclor (3, 21, 22). These favorable characteristics make loracarbef a suitable antibiotic for once-a-day treatment of urinary tract infections (UTIs). One purpose of this double-blind, randomized trial was to compare the safety and efficacy of a 7-day course of loracarbef (200 mg once daily) with cefaclor (250 mg three times a day) (Eli Lilly & Co., Indianapolis, Ind.) for treatment of acute UTIs. To maintain the blind study design, placebos were given to patients in the loracarbef group. A second purpose was to assess the emergence of resistant organisms in the genital and rectal aerobic flora. Prior to initiation, the trial was approved by our Institutional Review Board and signed written consent was obtained from each patient. The patients studied were college women who came to the Kidney Clinic of the University of Florida Student Health Care Center. A criterion for inclusion was the presence of i105 CFU of the same bacterium per ml in each of two consecutive urine specimens. Excluded from the study were pregnant or lactating women; those with impaired renal or liver function, radiographically proven obstructive uropathy, or a history of allergy to penicillins or cephalosporins; and anyone receiving antimicrobial agents during the preceding week. Two clean-catch midstream urine specimens were obtained within 48 h before treatment for analysis and culture. Specimens were collected from genitals and recta with Culturette rayon-tipped swabs (Scientific Products Div., Evanston, Ill.) for nonquantitative aerobic culture pretherapy and 5 to 9 days posttherapy. Urinary bacterial isolation was performed and quantitative counts were determined as previously described (8, 16, 20, 26). Antibiotic susceptibility was tested by the disk diffusion method by using 30-R,g disks of loracarbef and 30-p.g disks of cephalothin (1). Bacterial isolates were considered susceptible to loracarbef or cefaclor when the disk zone sizes were 218 mm. Intermediate susceptibility was defined as 50 CFU. Susceptibility was tested as described above. Vaginal swabs were also tested for Candida albicans before and 5 to 9 days posttherapy as previously described (15, 16). Escherichia coli isolates were identified by serotype as previously reported (9, 23). Clinical and bacteriological evaluations were repeated within 2 to 4 days of initiation of treatment and 5 to 9 days and 4 to 6 weeks posttherapy. During therapy, patients used diaries to record times of medication taking, voiding, and resolution of dysuria and urgency. Complete disappearance of symptoms by 5 to 9 days posttherapy was termed clinical cure, incomplete resolution was termed clinical improvement, and no apparent response was termed clinical failure. Bacteriologic responses were classified as short-term cures, long-term cures, failures, relapses, and reinfections, as described previously (15). The life table method and the chi-square and Fisher exact tests were used to analyze the data (5, 7). Of 108 patients who entered the study (53 in the loracarbef group, 55 in cefaclor group), 104 (96.3%) were symptomatic, with a combination of dysuria, urgency, and suprapubic pain; 7 (15.7%) had costovertebral angle tenderness, and 1 had a fever of >380C. There were no differences between the two groups with regard to pretherapy demographic findings and clinical presentation. In the loracarbef group, the mean age was 22.2 + 4 years, symptoms were present 4.4 ± 4 days pretherapy, 17 patients (32.1%) had recurrent UTIs, and 51 (96.2%) had pyuria. In the cefaclor group, the mean age was TABLE 1. Distribution of urinary pathogens and results of
in vitro susceptibility testing Pathogen
Escherichia coli Klebsiella pneumoniae Proteus mirabilis Enterobacter aerogenes Citrobacter sp. Nonhemolytic staphylococci Enterococci "
750
No. of isolates (no. resistant)
Loracarbef
Cefaclora
36 (0) 4 (0) 4 (0) 2 (2) 1 (0) 6 (1) 0 (0)
38 (0) 4 (0) 4 (0) 3 (2) 4 (0) 3 (1) 1 (0)
Two patients in the cefaclor group each had two pathogens initially.
NOTES
VOL. 35, 1991
751
TABLE 2. Distribution of patients by treatment group and bacteriologic response through 4 weeks after treatment ended
Trete group Loracarbef Cefaclor
Who completed treatment
~~follow-up (5-9 days
and
With short-term:
posttherapy)
Cure
Failure
46 51
44 (96) 46 (90)
2 (4) 5 (10)
22.3 + 3 years and symptoms were present 3.5 + 12 days pretherapy. Fifteen patients- (27.3%) had recurrent UTIs, and 55 (100%) had pyuria. The mean times until disappearance of symptoms after initiation- of therapy were 48 (range, 4 to 234) h in the loracarbef group and 41 (range, 6 to 137) h in the cefaclor group. Four patients were asymptomatic. Distributions of urinary pathogens and their in vitro susceptibilities were comparable between groups (Table 1). Ninetysix percent of the urinary pathogens were susceptible to loracarbef, and 95% were susceptible to cefaclor. The 74 E. coli isolates were all susceptible to loracarbef and cefaclor. Four of five isolates of Enterobacter aerogenes were resistant to both agents. These results are in agreement with previous reports that loracarbef and cefaclor have comparable in vitro activities that are superior to that of cephalexin (2, 4, 11). In the loracarbef group, 52 of 53 patients had sterile urine cultures after 2 to 4 days of therapy. One patient had a resistant pathogen pretherapy, and her urine culture remained positive. Her therapy was discontinued, as was that of three others, for the following reasons: one because of a low pretherapy bacterial count and two because of adverse reactions. In the cefaclor group, all 55 patients had sterile urine cultures after 2 to 4 days of therapy. Of the patients returning at 5 to 9 days posttherapy, 96% of the loracarbef group and 90% of the cefaclor group had short-term cures. Long-term cures occurred in 81% of the patients initially enrolled in each group who were available for long-term follow-up. Bacteriologic responses through 4 weeks posttherapy are shown in Table 2. Initially identified urinary pathogens remained eradicated at 4 to 6 weeks posttherapy in 37 (90%) and 39 (93%) of the patients in the loracarbef and cefaclor groups, respectively (P > 0.10). The therapeutic results of the two groups were favorable and comparable to those previously attained with antimicrobial agents, including cephalosporins, in young women (6, 10, 12-14, 16-18). Periurethral, vaginal, and rectal specimens were obtained from 46 patients in the loracarbef group and 51 patients in the cefaclor group. After therapy in both groups, the numbers of patients with cultures positive for colonizing E. coli in the periurethral (P < 0.001), vaginal (P < 0.001), and rectal (P < 0.01) flora were reduced. No significant change occurred in either (i) the number of patients with positive cultures for other members of the family Enterobacteriaceae or (ii) the susceptibility patterns of the bacteria colonizing these sites in either group. The findings related to cefaclor are in agreement with those previously reported (17, 18). In the loracarbef group, five patients experienced adverse events: therapy was discontinued for two patients because of nausea, headache, and abdominal pain; two had nausea, one combined with a rash; and one experienced difficulty breathing and diarrhea on the last day of therapy. In the cefaclor group, three patients reported adverse events: two experienced diarrhea, one with nausea, and one developed a rash
No. (%) of patients Lost to follow-up after 59dy
othrp
5-9 days posttherapy
3 4
With long-term:
Relapse 4 (10) 3 (7)
Reinfection 2 (5) 1 (3)
Cure 35 (81) 38 (81)
on the last day of therapy. Therapy was not interrupted for these three patients. By 5 to 9 days posttherapy, Candida vaginitis developed in 8 (15.1%) of the patients in the loracarbef group and 11 (20.0%) of the patients in the cefaclor group. Laboratory test results did not significantly change for any patients in either group. These findings are consistent with those previously reported for cefaclor (13-15, 17, 18, 24, 25, 27, 28). In conclusion, loracarbef and cefaclor are safe, well tolerated, and effective in the treatment of UTIs in women. The assistance of Barbara Peters, Dorothy Ellerbe, Lisa Duncanson, Janice Barnhart, Lee Stutevoss, and Elizabeth Patrick for the study and preparation of the manuscript is acknowledged and appreciated. A grant for this study was supplied by Eli Lilly Pharmaceuticals to the University of Florida Division of Sponsored Research. REFERENCES 1. Bauer, A. C. O., W. M. M. Kirby, J. L. Sherris, and M. Turck. 1966. Antibiotic susceptibility testing by a standardized single dose method. Am. J. Clin. Pathol. 45:493-496. 2. Bill, N. J., and J. A. Washington II. 1977. Comparison of in vitro activity of cephalexin, cephradine, and cefaclor. Antimicrob. Agents Chemother. 11:470-474. 3. Black, H. R., K. A. Desante, J. D. Wolny, and G. L. Brier. 1988. Program Abstr. 28th Intersci. Conf. Antimicrob. Agents Chemother., abstr. 123. 4. Cao, C., N. X. Chin, and H. C. Neu. 1988. In vitro activity and P-lactamase stability of Ly163892. J. Antimicrob. Chemother. 22:155-165. 5. Colton, T. 1974. Statistics in medicine, 1st ed., p. 151-188. Little, Brown & Co., Boston. 6. Cox, C. E., J. M. Sherrill, and D. M. Cocchetto. 1987. Evaluation of cefuroxime axetil, cefaclor and cephalexin in the treatment of urinary tract infections in adults. Curr. Ther. Res. 42:124-137. 7. Cutler, B. J. 1958. Maximum utilization of the life table method in analyzing survival. J. Chronic Dis. 8:699-712. 8. Edwards, P. R., and W. H. Ewing. 1972. Identification of Enterobacteriaceae, 3rd ed., p. 7-47. Burgess Publishing Co., Minneapolis. 9. Ewing, W. H. 1956. Production of Escherichia coli antiserum. Public Health Lab. 14:138-141. 10. Gurwith, M. J., G. E. Stein, and D. Gurwith. 1983. Prospective comparison of amoxicillin-clavulanic acid and cefaclor in treatment of uncomplicated urinary tract infections. Antimicrob. Agents Chemother. 24:716-719. 11. Howard, A. J., and K. T. Dunkin. 1988. Comparative in vitro activity of a new oral carbacephem, Ly163892. J. Antimicrob. Chemother. 22:445-456. 12. Iravani, A., N. Pryor, and G. A. Richard. 1982. Treatment of acute uncomplicated urinary tract infections by cephalexin, with special reference to the antibody-coated bacteria. Int. J. Clin. Pharmacol. 20:97-100. 13. Iravani, A., and G. A. Richard. 1982. Treatment of urinary tract infections with a combination of amoxicillin and clavulanic acid. Antimicrob. Agents Chemother. 22:672-677. 14. Iravani, A., and G. A. Richard. 1985. Single-dose ceftriaxone
752
15.
16.
17.
18.
19. 20.
NOTES versus multiple-dose trimethoprim-sulfamethoxazole in the treatment of acute urinary tract infections. Antimicrob. Agents Chemother. 27:158-161. Iravani, A., and G. A. Richard. 1986. Amoxicillin-clavulanic acid versus cefaclor in the treatment of urinary tract infections and their effects on the urogenital and rectal flora. Antimicrob. Agents Chemother. 29:107-111. Iravani, A., and G. A. Richard. 1989. Single-dose cefuroxime axetil versus multiple-dose cefaclor in the treatment of acute urinary tract infections. Antimicrob. Agents Chemother. 33: 1212-1216. Iravani, A., G. A. Richard, and H. Baer. 1981. Treatment of uncomplicated urinary tract infections with trimethoprim versus sulfisoxazole, with special reference to antibody-coated bacteria and fecal flora. Antimicrob. Agents Chemother. 19:842-850. Iravani, A., G. A. Richard, D. Johnson, and A. B. Bryan. 1988. A double-blind, multicenter, comparative study of the safety and efficacy of cefixime versus amoxicillin in the treatment of acute urinary tract infections in adult patients. Am. J. Med. 85(Suppl. 3A):17-23. Jones, R. N., and A. L. Barry. 1988. Antimicrobial activity of Ly163892, an orally administered 1-carbacephem. J. Antimicrob. Chemother. 22:315-320. Jordan, P. A., A. Iravani, G. A. Richard, and H. Baer. 1980. Urinary tract infection caused by Staphylococcus saprophyticus. J. Infect. Dis. 142:510-515.
ANTIMICROB. AGENTS CHEMOTHER. 21. Knapp, C. C., and J. A. Washington II. 1988. In vitro activities of LY163892, cefaclor, and cefuroxime. Antimicrob. Agents Chemother. 32:131-133. 22. Nelson, J. D., S. Shelton, and H. Kusmiesz. 1988. Pharmacokinetics of LY163892 in infants and children. Antimicrob. Agents Chemother. 32:1738-1739. 23. 0rskov, I., F. 0rskov, B. Jann, and K. Jann. 1977. Serology, chemistry, and genetics of 0 and K antigens of Escherichia coli. Bacteriol. Rev. 41:667-710. 24. Rotschafer, J., K. Crossley, D. Zaske, and R. Viste. 1979. Comparative study of cefaclor and amoxicillin in the treatment of urinary tract infection. Urology 14:233-236. 25. Rous, S. N. 1981. Comparison of cefaclor versus trimethoprimsulfamethoxazole combination in the treatment of acute urinary infections. J. Urol. 125:228-229. 26. Smith, P. B., K. M. Tomfohrde, D. L. Rhoden, and A. Balows. 1972. API system: a multitube micromethod for identification of Enterobacteriaceae. Appl. Microbiol. 24:449-452. 27. Trager, G. M., G. W. White, P. E. Porembski, and A. P. Panwalker. 1980. A comparison of cefaclor and trimethoprim/ sulfamethoxazole in the treatment of urinary tract infections. Curr. Ther. Res. 28:419-423. 28. Williams, K. J., E. M. Hebblethwaite, G. W. Brown, D. M. Cox, and S. J. Plested. 1987. Cefuroxime axetil in the treatment of uncomplicated UTI: a comparison with cefaclor and augmentin. Drugs Exp. Clin. Res. 13(2):95-99.
