Vol. 35, No. 9ANTIMICROBIAL AGENTS AND CHEMOTHERAPY, Sept. 1991, p. 1777-17810066-4804/91/091777-05$02.00/0Copyright © 1991, American Society for Microbiology

Comparative, Double-Blind, Prospective, Multicenter Trial ofTemafloxacin versus Trimethoprim-Sulfamethoxazole in

Uncomplicated Urinary Tract Infections in WomenABDOLLAH IRAVANI

Division of Nephrology, Department of Pediatrics, University of FloridaCollege of Medicine, Gainesville, Florida 32610

Received 5 March 1991/Accepted 26 June 1991

In a double-blind, randomized, multicenter study, 400 women with symptoms of acute urinary tractinfections were treated with either a 7-day course of temafloxacin hydrochloride (400 mg once a day; n = 204)or a 10-day course of trimethoprim (160 mg) and sulfamethoxazole (800 mg) (TMP-SMZ) twice daily (n = 196).The bacteriologic cure rates at 5 to 9 days posttherapy were 100% in the temafloxacin group and 97% in theTMP-SMZ group (P = 0.035). The clinical cure rates were 93% in the temafloxacin group and 95% in theTMP-SMZ group (P > 0.1). Adverse events, including nausea, vomiting, rash, headache, and dizziness, wereexperienced by 19.6% of the temafloxacin group and 23.5% of the TMP-SMZ group. Transient leukopeniaoccurred in 0.5 and 4.1% of the temafloxacin and TMP-SMZ groups, respectively. Temafloxacin, 400 mg oncea day for 7 days, appears to be at least as safe and effective as a 10-day course ofTMP-SMZ in the managementof acute urinary tract infection in women.

Temafloxacin hydrochloride is a new fluoroquinolone witha broad spectrum of activity in vitro against both gram-negative and gram-positive uropathogens (12, 13, 24, 25).The in vitro activity of temafloxacin is comparable to thoseof ofloxacin and ciprofloxacin (13, 14). Pharmacokineticstudies indicate that temafloxacin has good gastrointestinalabsorption, with complete dose linearity and a half-life inplasma of approximately 8 h (23). The volume of distributionof temafloxacin is high because of significant intracellularpenetration and concentration. The major route of elimina-tion is by urinary excretion, with approximately 60% of adose being excreted in the urine in its active form (26). Thehigh levels of drug in plasma, tissue, and urine are wellabove the MIC for most urinary pathogens (23, 26). Tema-floxacin is well tolerated and is generally devoid of seriousadverse effects (26-28). The favorable pharmacokineticcharacteristics and antibacterial activity make temafloxacina suitable antimicrobial agent for once-a-day use in thetreatment of urinary tract infection (UTI).

In this double-blind, randomized, multicenter trial, thesafety and efficacy of a 7-day course of temafloxacin (400 mgonce daily) was compared with a 10-day course of tri-methoprim-sulfamethoxazole (TMP-SMZ; 160/800 mg twicedaily) in the treatment of UTI in women. TMP-SMZ waschosen as the control regimen because of its establishedsafety and efficacy and its wide use in the treatment of UTI(1, 3-5, 8, 10, 14, 17).

MATERIALS AND METHODS

Patient selection. Four hundred women from 28 study sitesnationwide (see below) were enrolled in the study. Allpatients were age 18 or older and had symptoms of acuteUTI. The criteria for inclusion were as follows: (i) symptomsof UTI, e.g., dysuria, frequency, and urgency; (ii) pyuria(>5 leukocytes per high-power field); and (iii) bacteriuria,with at least 105 CFU (per ml) of one or two pathogens notresistant to the study agents found on microscopic examina-tion of urine sediment within 48 h prior to treatment. Patients

had to meet all three criteria in order to be included in theefficacy analyses of the study. Pregnant or lactating women;patients who had more than one UTI within the previousyear or other signs of a complicated UTI; and those withimpaired renal or liver function, a history of folate defi-ciency, or a known hypersensitivity to quinolones, trimeth-oprim, or sulfonamides were excluded. Patients who hadreceived antimicrobial therapy within the preceding weekand those who were expected to consume antacids duringthe study period were also excluded.

Study sites. This multicenter trial was conducted by thefollowing principal investigators: Kerry Anders (privatepractice, Monroe, La.), Gloria Bacon (private practice,Chicago, Ill.), Jacques Caldwell (private practice, DaytonaBeach, Fla.), Richard Carson (Rehabilitation Clinic, Little-ton, Colo.), John Carter (private practice, Tucson, Ariz.),Frank Cascio (University of Kentucky, Lexington, Ky.),David Florence (Family Clinic, Manchester, Tenn.), RandyGoodwin (H & M Medical Clinic, Concord, N.C.), StephenGregg (Solo Internal Medicine, Albuquerque, N.M.), Rich-ard Griffin (Simon-Williamson Clinic, Birmingham, Ala.),Andrew Grubbs (Future Healthcare, Cincinnati, Ohio), Rob-ert Guthrie (Ohio State University, Columbus, Ohio), Mar-garet Hessen (Medical College of Pennsylvania, Philadel-phia, Pa.), Bruce Hetland (Mid Dakota Clinic, Bismarck,N.D.), Abdollah Iravani (University of Florida, Gainesville,Fla.), William Kerns (Front Royal Family Practice, FrontRoyal, Va.), Raza Khan (Urology, Waukegan, Ill.), MichaelKuglitsch (Madison Urologists, Madison, Wis.), MarkKunkel (Danbury Hospital, Danbury, Conn.), SivaprasadMadduri (Kneibert Clinic, Poplar Bluff, Mo.), GholamMalek (Jackson Clinic, Madison, Wis.), Charles Maletz(Cassidy Medical Clinic, Vista, Calif.), James McCarty(Valley Medical Center, Fresno, Calif.), Herzl Melmed(Colorado Medical Research, Englewood, Colo.), Peter Mis-urec (private practice, Berwyn, Ill.), Michael Moore (privatepractice, Bessemer, Ala.), Thomas Nolen (private practice,Columbiana, Ala.), C. Fredric Reid (private practice, Win-ston-Salem, N.C.), Howard Smith (Family Practice, Hous-

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ton, Tex.), Norman Stevens III (Family Medical Center,Jackson, Ala.), William M. Stevens (private practice, Wich-ita, Kans.), Barrett Sugarman (Michigan State University,East Lansing, Mich.), Neil Tarzy (private practice, Escon-dido, Calif.), Jerome Weinbaum (Chico Medical Group,Chico, Calif.), Jeff Whitfield (private practice, Nashville,Tenn.), Stephen Zellner (private practice, Ft. Myers, Fla.),and Wayne Zundel (private practice, Salt Lake City, Utah).

Study design. All patients enrolled in the study wereassigned by 1:1 computer-generated randomization to re-ceive either temafioxacin hydrochloride (400 mg; AbbottLaboratories, Abbott Park, Ill.) once a day for 7 days or acombination of TMP (160 mg) and SMZ (800 mg) (BectonDickinson Microbiology Systems, Cockeysville, Md.) every12 h for 10 days. To maintain the double blind, patients whoreceived temafloxacin took a daily dose of two 200-mgcapsules, followed 12 h later by two placebo capsules. Thisregimen continued for 7 days, and then the temafioxacindose was replaced by two placebo capsules daily for the final3 days of the study. Patients who received TMP-SMZ weregiven two capsules twice daily for 10 days.

Within 48 h before the start of treatment, each patientunderwent a general physical examination. At least oneclean-catch midstream or, in a few centers, a straight cath-eter urine specimen was obtained from each patient at thistime, and a blood sample was obtained for hematologic andchemical analyses. Clinical evaluation and urine cultureswere repeated 3 to 5 days and 8 to 10 days after the start oftherapy and 5 to 9 days after the end of therapy; blood testswere repeated at the 8- to 10-day visit. All blood and urinesamples were collected and handled in accordance withaccepted laboratory procedures.

Bacteriologic techniques. Urine was cultured by standardlaboratory practices (9, 30). If the culture could not beperformed immediately after collection, the urine could besafely stored in a refrigerator for up to 4 h. The microscopicexamination of urine was performed on a Gram-stained,centrifuged specimen.Colony counts and susceptibilities to temafloxacin and

TMP-SMZ were determined for each pathogen isolated,using either the disk diffusion or the MIC method. The counthad to be 210 CFU of a bacterium per ml of urine specimenfor the patient to be eligible for inclusion in the efficacyanalyses. Antibiotic susceptibility was tested by the diskdiffusion method with 10-,ug temafloxacin and 23.75/1.25-,ugTMP-SMZ disks (2). Pathogens were considered resistant totemafloxacin and TMP-SMZ if they had zone diameters of.c12 and s10 mm, respectively. Organisms for which theMIC was .8 mg/liter were considered to be resistant to bothtemafloxacin and TMP-SMZ. Patients whose urinary patho-gens were resistant to either study drug were not included inthe efficacy assessments.

Efficacy assessments. The complete disappearance ofsymptoms at 5 to 9 days after the end of treatment wasconsidered a clinical cure, while persistence of symptomswas considered a clinical failure. If symptoms improved butdid not completely resolve by days 5 to 9 posttreatment, thepatient was considered clinically improved.

Bacteriologic eradication was defined as the absence ofthe original pathogen or a colony count of <10' CFU/ml bydays 3 to 5 of treatment and up to 5 to 9 days after treatment.Persistence of the original pathogen at days 3 to 5 oftreatment or at 5 to 9 days after treatment indicated bacte-riologic eradication failure. The bacteriologic eradicationcure rate was defined as the percentage of patients whosepretreatment pathogens were all eradicated.

Safety assessment. Adverse events were monitored andrecorded. Changes in blood chemistry and complete bloodcell counts were determined.

Consent. This clinical trial was approved by the institu-tional review boards of the participating institutions. Asigned written consent form was obtained from each patientbefore she entered the study.

Statistical analyses. The sample size was preplanned toprovide 80% power to detect at least a 15% differencebetween the treatment groups. All statistical tests were twotailed, and a P value of <0,05 was considered statisticallysignificant. All analyses were performed by the SAS proce-dures (29).The comparative susceptibilities of the urinary pathogens

to the study drugs was analyzed by the McNemar test (11).To assess the comparability of treatment groups, quantita-tive variables such as age and weight were a,nalyzed by atwo-way analysis of variance. Categorical variables such asrace were analyzed by the Mantel-Haenszel test (11). Theinvestigator was the blocking or poststratification factor inthese analyses.

All efficacy variables were analyzed by a Fisher exact testor chi-square test for the comparison between treatmentgroups (6). To assess the differences between treatmentgroups with respect to vital signs and laboratory data, aone-way analysis of variance on the change from the base-line to each evaluation time point was performed. Withineach treatment group, shifts of laboratory values with re-spect to their normal ranges were assessed by the Stuart-Maxwell or McNemar test (11).

RESULTS

Study population. Of the 400 patients enrolled in the study,204 received temafloxacin hydrochloride and 196 receivedTMP-SMZ. The mean ages of the patients were 36 + 19years in the temafloxacin group and 38 + 21 years in theTMP-SMZ group. Demographic characteristics and prether-apy clinical findings are given in Table 1. Each patientpresented with various combinations of dysuria, frequency,and urgency. Some also showed upper UTI signs, such ascostovertebral angle pain or tenderness. For 70% of thepatients, this was the first UTI in at least 12 months. Thehistory of two or three UTIs in the past year in six patientswas not considered clinically significant, because all of themhad simple cystitis. In the temafloxacin group, 60 and 6patients had costovertebral angle tenderness and a fever of>38°C, respectively, whereas in the TMP-SMZ group, thecorresponding clinical findings were found in 53 and 11patients, respectively. These clinical findings are suggestiveof upper urinary tract involvement in these patients.The most common pathogens isolated in pretreatment

urine specimens were Escherichia coli (76% of all bacterialisolates), Proteus mirabilis (6%), and Klebsiella pneumoniae(4%). There were a total of 168 pretherapy bacterial isolatesin 151 patients in the temafloxacin group; 17 patients eachhad two bacterial isolates. The other 53 patients who re-ceived temafloxacin subsequently were found to have nega-tive pretherapy urine cultures. There were 158 pretherapybacterial isolates in 146 patients in the TMP-SMZ group; 12patients each had two pathogens, and 50 had negativepretherapy urine cultures. All pathogens were susceptible totemafloxacin, but 16 were resistant to TMP-SMZ. Nine ofthe patients with resistant pathogens were assigned to thetemafloxacin group, and the other seven patients wererandomly allocated to receive a treatment to which the

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TABLE 1. Patient demographics and pretherapy clinical findings

Race (no.) No. with:

(no.uoptes) Age (yr)a Wt (kg)'4(no. of patients) Age (yr) Wt (kg)a White Black Other No UTI in past Fever >38°C CVATb Hematuria'12 mo

Temafloxacin (204) 36 ± 19 140 t 37 176 20 8 142 6 60 84TMP-SMZ (196) 38 t 21 148 t 37 170 23 3 136 11 53 89

a Values are means ± standard deviations.b CVAT, costovertebral angle tenderness.c Hematuria was classified as >5 erythrocytes per high-power field.

pathogens showed resistance, that is, TMP-SMZ. The dif-ference in the susceptibility of E. coli (n = 239) to temaflox-acin (100%) and TMP-SMZ (90.4%) was statistically signifi-cant (P = 0.002).

Clinical and bacteriologic efficacy. Although all patientswere included in the analysis of safety, 75 patients in thetemafloxacin group were excluded from the bacteriologicefficacy analysis, and all but 3 of them were also excludedfrom the clinical efficacy analysis; 78 patients in the TMP-SMZ group were excluded from both the clinical and bacte-riologic efficacy analyses. Thus, 132 patients in the temaflox-acin group and 118 patients in the TMP-SMZ group wereclinically evaluable, and all of them except 3 patients in thetemafloxacin group were bacteriologically evaluable.The main reason for exclusion was failure to isolate a

pathogen in the pretreatment urine sample, which, as statedabove, occurred in 53 patients in the temafloxacin group and50 patients in the TMP-SMZ group. Missing examinations orcultures caused exclusion of 6 patients from the analysis oftemafloxacin's bacteriologic efficacy, 9 patients from theanalysis of temafloxacin's clinical efficacy, and 12 patientsfrom both efficacy analyses in the TMP-SMZ group. Resis-tance to either study drug eliminated eight more patientsassigned to the temafloxacin group and six patients assignedto the TMP-SMZ group. For five patients in each group,susceptibility tests were missing or inconclusive. Threepatients in the temafloxacin group and five patients in theTMP-SMZ group were excluded from the efficacy analysesbecause of noncompliance or insufficient treatment duration.The clinical and bacteriologic responses of evaluable

patients on days 5 to 9 after treatment are summarized inTable 2. In the temafloxacin group, 123 patients (93%)achieved a clinical cure, and 7 (5%) were improved 5 to 9days after therapy. The two clinical failures were in womenover age 70 years. A clinical cure was achieved by 112patients (95%) in the TMP-SMZ group, and the other 6patients (5%) improved clinically. There were no clinicalfailures in the TMP-SMZ group.

TABLE 2. Therapeutic responses at S to 9 days posttherapy

No. (%) of patientsResponse

Temafloxacin TMP-SMZ

Clinically evaluable 132 118Cure 123 (93) 112 (95)Improvement 7 (5) 6 (5)Failure 2 (2) 0

Bacteriologically evaluable 129 118Cure' 129 (100) 114 (97)Failure 0 4 (3)a P 0.035.

All 129 evaluable patients (100%) in the temafloxacingroup and 114 patients (97%) in the TMP-SMZ groupachieved a bacteriologic cure 5 to 9 days after therapy. Thefour patients in the TMP-SMZ group who were bacteriologicfailures all had E. coli infections; three of the four wereyounger than age 40 years. The difference in bacteriologicresponse between the two treatment groups was statisticallysignificant (P = 0.035).

Side effects. A total of 40 of the 204 patients (19.6%) whoreceived temafloxacin and 46 of the 196 patients (23.5%) whoreceived TMP-SMZ experienced adverse events. Table 3lists those adverse events that occurred in at least 1% ofeither treatment group. Therapy was discontinued becauseof adverse events in three patients in the temafloxacin groupand eight patients in the TMP-SMZ group. The most com-mon adverse events were nausea and vomiting, vaginitis,rash, and headache; all occurred more frequently in patientsreceiving TMP-SMZ. Whereas 65% of all adverse events inthe temafloxacin group were reported during the first 48 h,the corresponding value for TMP-SMZ was 38%.

TABLE 3. Adverse events and laboratory abnormalitiesoccurring in >1% of either treatment group

No. (%) of patientsAdverse event Temafloxacin TMP-SMZ

(n = 204) (n = 196)

Patients who experienced any 40 (19.6) 46 (23.5)adverse event

Patients who discontinued treat- 3 (1.5) 8 (4)ment because of adverse event

Adverse eventNausea or vomiting 9 (4.4) 16 (8.2)Candida vaginitis 7 (3.4) 10 (5)Rash 2 (1) 10 (5)Headache 5 (2.5) 8 (4.1)Dizziness 5 (2.5) 2 (1)Nervousness or depression 2 (1) 4 (2)Abdominal pain 3 (1.5) 3 (1.5)Asthenia 3 (1.5) 2 (1)Somnolence 2 (1) 3 (1.5)Pruritus 1 (0.5) 3 (1.5)

Patients with any abnormal 14 (6.9) 15 (7.7)laboratory tests

Laboratory abnormalityLeukopenia 1 (0.5) 8 (4.1)Eosinophilia 4 (2) 3 (1.5)Elevated lactose dehydrogenase 4 (2) 0 (0)Elevated SGPTa 2 (1) 3 (1.5)

" SGPT, serum glutamic pyruvi. ransaminase.

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Blood chemistry and hemograms. A total of 14 patients(6.9%) in the temafloxacin group and 15 patients (7.7%) inthe TMP-SMZ group developed abnormal laboratory tests.No clinically significant trends were observed. Total biliru-bin levels increased in two patients, and lactose dehydroge-nase levels increased in four patients in the temafloxacingroup. -y-Glutamyltranspeptidase levels increased in twopatients in each group. Serum glutamic oxaloacetic transam-inase levels rose in one patient in the temafloxacin group andin two patients in the TMP-SMZ group, whereas serumglutamic pyruvic transaminase levels were elevated in twopatients who took temafloxacin and in three patients whotook TMP-SMZ. All other blood chemistry values remainednormal during therapy.One patient in the temafloxacin group and eight patients in

the TMP-SMZ group developed transient leukopenia. Eosin-ophilia occurred in four patients in the temafloxacin groupand in three patients in the TMP-SMZ group (Table 3).

DISCUSSION

TMP-SMZ is used widely in the treatment of UTI in adultsand children (1, 3, 4, 10, 17, 32). The results of the presentstudy support its efficacy in the treatment of these infections.Our results are comparable to those achieved with otherantimicrobial agents, including the new quinolones, in thetreatment of UTI in women (1, 3, 7, 14, 16, 18-22, 31, 33).The favorable therapeutic results produced by temafloxacin(400 mg once daily) are consistent with the pharmacologiccharacteristics and broad-spectrum antimicrobial activity ofthis new quinolone (12, 13, 23-25).The urinary pathogens in this study consisted of species of

the family Enterobacteriaceae and gram-positive cocci,most of which were susceptible to both temafloxacin andTMP-SMZ. However, the difference between the in vitroactivity against 239 isolates of E. coli-100% for temaflox-acin and 90.4% for TMP-SMZ-was statistically significant(P = 0.002). These results are in agreement with previousreports of the in vitro activities of temafloxacin and TMP-SMZ against common uropathogens (4, 8, 12, 13, 24, 25, 34).At 5 to 9 days following the completion of therapy, clinical

success (cure or improvement) was achieved in 98% ofpatients in the temafloxacin group and 100% of patients inthe TMP-SMZ group. The bacteriologic eradication rate was100% in the temafloxacin group and 97% in the TMP-SMZgroup. Bacteriologic eradication was achieved in the twoclinical failures in the temafloxacin group, both of whomwere elderly women. Patients with symptoms and signs ofupper UTI were evenly distributed between the two treat-ment groups. Both drug regimens were similarly effective inthose patients with a successful response.

Temafloxacin and TMP-SMZ were well tolerated by 80.4and 76.5% of the patients, respectively. The adverse eventswere generally mild to moderate in severity and resolvedwithout any specific treatment after the drug was discontin-ued. However, adverse events were severe enough to re-quire discontinuation of therapy in three (1.5%) patients inthe temafloxacin group and eight patients in the TMP-SMZgroup.

In the treatment of over 4,000 patients, Hsu et al. (15)found that the incidence of discontinuation because of ad-verse events was comparable for temafloxacin, other quino-lones, and nonquinolone reference drugs. According toPernet et al. (28), the incidence of central nervous system-related adverse events with temafloxacin was comparable tothe incidence with nonquinolone reference drugs, and gas-

trointestinal symptoms were less common with temafloxacinthan they were with other quinolones. Parrish (27) reportedthat the incidence of adverse events (nausea, diarrhea,dizziness) was similar for temafloxacin and ciprofloxacin(27). In the study of Morrison et al. (26), the overallincidence of adverse drug events, as evaluated by subjects'diaries and investigators' global assessments, was signifi-cantly higher with placebo (75%) than it was with temaflox-acin (44%) (26).

In the present study, the incidence of Candida vaginitiswith temafloxacin (3.4%) and TMP-SMZ (5%) was lowerthan that in previous reports in comparable patient popula-tions (16, 18, 19). Laboratory tests such as transaminaseenzymes and complete cell counts remained normal in 93%of the temafloxacin group and 92% of the TMP-SMZ group.The laboratory abnormalities, including leukopenia and eo-sinophilia, were mild to moderate in severity and transient inboth treatment groups.

In summary, a 7-day course of temafloxacin (400 mg oncedaily) was as well tolerated and as efficacious as a 10-daycourse of TMP-SMZ (160/800 mg twice daily) in the treat-ment of UTI in women.

ACKNOWLEDGMENTS

I thank Janice Barnhart, Lisa Duncanson, Lee Stutevoss, andElizabeth Patrick for technical assistance and help in the preparationof the manuscript.

This work was supported in part by a grant supplied by AbbottLaboratories to the University of Florida Division of SponsoredResearch.

REFERENCES1. Allais, J. M., L. C. Preheim, T. A. Cuevas, J. S. Rooccaforte,

M. A. Meliencamp, and M. J. Bittner. 1988. Randomized,double-blind comparison of ciprofloxacin and trimethoprim-sulfamethoxazole for complicated urinary tract infections. An-timicrob. Agents Chemother. 9:1327-1330.

2. Bauer, A. C. O., W. M. M. Kirby, J. L. Sherry, and M. Turck.1966. Antibiotic susceptibility testing by a standardized singledose method. Am. J. Clin. Pathol. 45:493-4%.

3. Boyko, E. J., A. Iravani, M. H. Silverman, D. J. Scheiling, andR. A. Wright. 1990. A randomized, controlled trial of a 10-daycourse of amifloxacin versus trimethoprim-sulfamethoxazole inthe treatment of acute, uncomplicated urinary tract infection.Antimicrob. Agents Chemother. 34:665-668.

4. Brumfitt, W., and R. Purseli. 1972. Double-blind trial to com-pare ampicillin, cephalexin, co-trimoxazole and trimethoprim inthe treatment of urinary infection. Br. Med. J. 2:673-676.

5. Childs, S. J. 1988. Management of urinary tract infections. Am.J. Med. 85(Suppl. 3A):14-16.

6. Colton, T. 1974. Statistics in medicine, 1st ed., p. 151-188. LittleBrown & Co., Boston.

7. Craft, J., M. Hurley, P. Hsu, and A. Pernet. 1990. Abstr. 3rd Int.Symp. New Quinolones, abstr. 236, p. 298.

8. Darrell, H. H., L. P. Garrod, and P. M. Walerworth. 1968.Trimethoprim: laboratory and clinical studies. J. Clin. Pathol.21:202-209.

9. Edwards, P. R., and W. H. Ewing. 1972. Identification ofEnterobacteriaceae, 3rd ed., p. 7-47. Burgess Publishing Co.,Minneapolis.

10. Fennell, R. S., M. Luengnaruemitchai, A. Iravani, E. H. Garin,R. D. Walker, and G. A. Richard. 1980. Urinary tract infectionsin children: effects of short course antibiotic therapy on recur-rence rate in children with previous infections. Clin. Pediatr.19:121-124.

11. Fleiss, J. L. 1981. Statistical methods for rates and proportions,2nd ed., p. 119-123. John Wiley & Sons, Inc., New York.

12. Georgopoulos, A., W. Graninger, S. Brayer, M. Palatin, and M.Georgopoulos. 1990. Abstr. 7th Mediterranean Congr. Chemo-ther., abstr. 108.

1780 IRAVANI

on June 23, 2018 by guesthttp://aac.asm

.org/D

ownloaded from

TEMAFLOXACIN VERSUS TMP-SMZ IN UTI 1781

13. Hardy, D. J., C. W. Hanson, J. Beyer, D. M. Hensey, and J. J.Clement. 1990. 3rd Int. Symp. New Quinolones, abstr. 54, p. 73.

14. Hooton, T. M., R. H. Latham, E. S. Wong, C. Johnson, P. L.Roberts, and W. E. Stamm. 1989. Ofloxacin versus trimetho-prim-sulfamethoxazole for treatment of acute cystitis. Antimi-crob. Agents Chemother. 33:1308-1312.

15. Hsu, P., A. Pernet, and J. Craft. 1990. Abstr. 7th MediterraneanCongr. Chemother., abstr. 834.

16. Iravani, A. 1987. Urinary tract infections: epidemiology andtherapeutic approaches. Royal Society of Medicine ServicesLimited Int. Congr. Symp. Ser. 127:25-33.

17. Iravani, A., and G. A. Richard. 1985. Single dose ceftriaxoneversus multiple dose trimethoprim-sulfamethoxazole in thetreatment of acute urinary tract infections. Antimicrob. AgentsChemother. 27:158-161.

18. Iravani, A., and G. A. Richard. 1986. Amoxicillin-clavulanateacid versus cefaclor in the treatment of urinary tract infectionsand their effect on the urogenital and rectal flora. Antimicrob.Agents Chemother. 29:107-111.

19. Iravani, A., and G. A. Richard. 1989. Single-dose cefuroximeaxetil versus multiple-dose cefaclor in the treatment of acuteurinary tract infections. Antimicrob. Agents Chemother. 33:1212-1216.

20. Iravani, A., G. A. Richard, and H. Baer. 1981. Treatment ofuncomplicated urinary tract infections with trimethoprim versussulfisoxazole, with special reference to antibody-coated bacteriaand fecal flora. Antimicrob. Agents Chemother. 19:842-850.

21. Iravani, A., G. A. Richard, and H. Baer. 1982. Trimethoprimonce daily vs. nitrofurantoin in treatment of acute urinary tractinfections in young women, with special reference to periure-thral, vaginal, and fecal flora. Rev. Infect. Dis. 4:378-387.

22. Iravani, A., G. A. Richard, D. Johnson, and A. Bryant. 1982. Adouble-blind, multicenter comparative study of the safety andefficacy of cefixime versus amoxicillin in the treatment of acuteurinary tract infection in adult patients. Am. J. Med. 85(Suppl.

3A):17-25.23. Kinzig, M., G. Mahr, R. Seelmann, K. G. Naber, and F. Sorgel.

1990. Abstr. 3rd Int. Symp. New Quinolones, abstr. 127, p. 162.24. Loza, E., B. J. Martinez, J. Linares, et al. 1990. Abstr. 3rd Int.

Symp. New Quinolones, abstr. 53, p. 72.25. Martinez, B. J., E. Loza, C. M. Rodriquez, et al. 1990. Abstr.

3rd Int. Symp. New Quinolones, abstr. 52, p. 71.26. Morrison, P., T. Ment, G. Granneman, J. Cerasoli, and A.

Pernet. 1990. Abstr. 7th Mediterranean Congr. Chemother.,abstr. 834, p. 184.

27. Parrish, I. 1990. Abstr. 7th Mediterranean Congr. Chemother.,abstr. 836, p. 184.

28. Pernet, A., P. Hsu, and J. Craft. 1990. Abstr. 7th MediterraneanCongr. Chemother., abstr. 837, p. 184.

29. SAS Institute, Inc. 1985. SAS user's guide: statistics, version 5ed., p. 956. SAS Institute, Inc., Cary, N.C.

30. Schoenknecht, F. D., L. D. Sabath, and C. Thornsberry. 1985.Susceptibility tests: special tests, p. 1000-1004. In E. H. Len-nette, A. Balows, W. J. Hausler, Jr., and H. J. Shadomy (ed.),Manual of clinical microbiology, 4th ed. American Society forMicrobiology, Washington, D.C.

31. Selin, L. K., K. M. Godfrey, M. J. Thomson, J. K. Kennedy,B. A. Urias, and A. Ronald. 1990. Comparison of norfloxacinversus nalidixic acid in therapy of acute urinary tract infections.Can. J. Infect. Dis. 1:35-40.

32. Stamm, W. E., M. McKevitt, and G. W. Counts. 1987. Acuterenal infection in women: treatment with trimethoprim-sul-famethoxazole or ampicillin for two to six weeks. Ann. Intern.Med. 106:341-345.

33. Stein, G. E., and J. D. Craft. 1990. Abstr. 3rd Int. Symp. NewQuinolones, abstr. 235, p. 297.

34. Then, R. L. 1982. Mechanisms of resistance to trimethoprim,the sulfonamides, and trimethoprim-sulfamethoxazole. Rev. In-fect. Dis. 4:261-269.

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