Preliminary Study
C l a i r E . C o x , S u s a n V. C a l l e r y , K. J. T a c k
Clinical Experience with Ofloxacin in Urinary Tract Infection
Summary: Preliminary data from the U.S. regarding
the safety and efficacy of ofloxacin in the treatment of
urinary tract infections are presented. Treatment of
uncomplicated urinary tract infections with either 200
mg or 300 mg ofloxacin b.i.d, was as effective as treat-
ment with a standard therapy, co-trimoxazole. In an-
other series of patients with underlying abnormalities
of the urinary tract, ofloxacin therapy resulted in fewer
failures and relapses than co-trimoxazole treatment.
Ofloxacin was well tolerated in these studies.
Zusammenfassung: Klinische Erfahrungen mit Oflox-
acin bei Harnwegsinfektionen. Vorl~iufige Ergebnisse
von in den USA durchgeffihrten klinischen Studien zur
Sicherheit und Wirksamkeit yon Ofloxacin in der Be-
handlung von Harnwegsinfektionen werden vorge-
stellt. Die Behandlung komplizierter Harnwegsinfek-
tionen mit 200 mg oder 300 mg Ofloxacin zweimal t~ig-
lich erwies sich als ebenso wirksam wie die Standard-
therapie mit Co-trimoxazol. Bei Patienten mit Infek-
tion bei anatomischen Verfinderungen der Harnwege
wurden bei Behandlung mit Ofloxacin weniger Thera-
pieversager beobachtet als mit Co-trimoxazol. In die-
sen Studien erwies sich Ofloxacin als gut vertr~iglich.
Introduction
Ofloxacin is a new broad-spectrum carboxyquinolone an-
timicrobial agent. It is active against many organisms re-
sistant to commonly-used antimicrobial agents such as
Pseudomonas. The high tissue concentrations and urinary
levels achieved after oral administration of the drug make
it a promising agent for the treatment of urinary tract in-
fections (UTI), including those infections involving renal
parenchymal tissue.
In this paper, preliminary United States experience with
ofloxacin in the treatment of both uncomplicated and
complicated urinary tract infections are reviewed.
Patients and Methods
The results presented represent a preliminary analysis of initial
data available from two clinical trials performed in the United
States in I985 and 1986. One of these studies was directed at the
treatment of uncomplicated UTI, i.e. UTI without underlying
abnormality of the urinary tract. The second involved patients
with complicated UTI, defined as an infection in the presence of
an anatomic or functional abnormality of the urinary system.
To be eligible for either study patients were required to have
- 105 cfu/ml of at least one pathogen in a clean-catch urine spec-
imen. They were seen during therapy three to four days after en-
Infection 14 (1986) Suppl. 4 © MMV Medizin Verlag GmbH Mtinchen, M0nchen 1986
rollment and again five to nine days after completion of therapy,
when repeat urine cultures were obtained. Patients were also
asked to return for additional follow-up at four to six weeks. To
be considered a cure, the urine culture during therapy and five
to nine days post-therapy had to be negative.
Uncomplicated UTI study: The uncomplicated UTI study was
performed at several centers; the pooled results are presented
here. Patients had no known abnormalities of the urinary tract.
After admission to the study, patients were randomized to re-
ceive one of three treatment regimens: a) ofloxacin, 200 mg p.o.
q12h, b) ofloxacin, 300 mg p.o. ql2h, or c) co-trimoxazole, 960
mg p.o. ql2h. All regimens were given for a total of seven days.
Investigators participating in the study were: C. Cox, Memphis,
TN; C. Horsburgh, Denver, CO; J. Kann, Pittsburgh, PA; R.
Latham, Salt Lake City, UT; W. Mogabgab, New Orleans, LA;
F. Randall, Montgomery, AL; M. Rein, Charlottesville, VA;
W. Stature, Seattle, WA; B. Umland, Alburquerque, NM; (7.
Wlodaver, Oklahoma City, OK; and E. Wong, Richmond, VA.
Complicated UTI study: The complicated UTI study patients re-
ported here were enrolled at a single center, as part of a larger
multicentric study. All patients had documented anatomic and/
or neurologic abnormalities of the urinary tract. After admis-
sion, patients were randomized to receive either a) ofloxacin,
200 mg p.o. ql2h, or b) co-trimoxazole, 960 mg p,o. ql2h, both
regimens given for ten days.
Results
317 Patients were entered into the uncomplicated UTI
study. A total of 209 patients are evaluable, i.e. had a pa-
thogen identified at admission and returned for required
follow-up visits. Efficacy results are shown in Table 1 for
each of the three treatment groups. Cure rates ranged
from 98.5% to 100%. There was one failure in each of the
two ofloxacin treatment groups, consisting of a positive
culture for the original pathogen at five to nine days post-
therapy. Both failures were due to ofloxacin-susceptible
Escherichia coil Relapses (re-appearance of original pa-
thogen four to six weeks post-therapy) were seen with
comparable frequency in the co-trimoxazole and ofloxa-
cin groups. Superinfections (appearance of a new urinary
pathogen during antimicrobial therapy) was also seen in
each treatment group, and were due to S. agalactiae, Can-
dida albicans, and enterococcus in the ofloxacin groups,
and S. agalactiae in the co-trimoxazole group.
All three treatment regimens were well tolerated in this
study. Two patients dropped out of the uncomplicated
UTI study for adverse drug effects, one patient in the
ofloxacin 300 mg treatment group, and one patient in the
Prof. Clair E. Cox, M.D., Department of Urology', University of Ten-
nessee, Memphis, U.S.A.;
Susan V. Callery, K. J. Tack, M.D., Ortho Pharmaceutical Corpor-
ation, Raritan, New Jersey 08869, U.S.A.
S 303
C. E. Cox et al.: Ofloxacin in UTI

Table t : Demographics, pathogens, and results, uncompli- co-trimoxazole treatment group. Both complained of diz-
cated UTI study. ziness.
For the complicated UTI study, a total of 71 patients
were entered. On admission, all patients h a d underlying
disease of the urinary tract, and all pathogens were sus-
ceptible to both study drugs. Pathogen identity and sus-
Patients 69 67 73 ceptibility data are shown in Table 2. Efficacy results are
Male 19 12 14 shown in Table 3. All patients in the ofloxacin treatment
Escherichia coli 45 49 57 group were cured microbiologically. One patient in the
Klebsiella spp. 10 4 5 co-trimoxazole group, with a Klebsiella pneumoniae in-
Staphylococcus saplvphyticus 4 5 2 fection failed. Her organism became resistant during ther-
Proteus mirabilis 3 2 2 apy, with a pretreatment MIC of 2.0 mg/l, and a post-
Citrobacter spp. 2 3 4 treatment MIC of > 256 rag/1. Three superinfections also
Enterobacter spp. 3 2 3 occurred in the co-trimoxazole group. Two were due to
Enterococcus 0 1 0
co-trimoxazole-resistant but ofloxacin-susceptible Pseu-
Streptococcus agalactiae 1 0 0
Staphylococcus aureus 1 1 0 domonas aeruginosa, and one due to co-trimoxazole-sus-
ceptible Acinetobacter anitratus.
Failures 1 l 0 Evaluation of the complicated UTI patients four t o six
Relapses at 4 to 6 weeks 3 2 2 weeks post-therapy showed no relapses in the ofloxacin
Superinfections 2 2 1 group, but two relapses in the co-trimoxazole group, both
due to co-trimoxazole-susceptible E. coli. There was also
one reinfection in the co-trimoxazole group, due to an E.
coli isolate with an MIC for co-trimoxazole of > 256 mg/1.
Table 2: Susceptibility data on 71 pathogens* from the One patient dropped out of each study arm in the compli-
complicated urinary tract study. cated UTI study due to adverse drug reactions, both rash-
es. There were no other clinical adverse effects of the
drugs.
Discussion
A variety of antimicrobial agents can be used for the
treatment of urinary tract infections. Increasing antimi-
* 30 Escherichia coli, 10 Klebsiella pneumoniae, 10 Proteus mi- crobial resistance, however, has led to a tendency to treat
rabilis, 3 each of Enterobacter aerogenes, Enterobacter cloa- with intrinsically more active agents such as co-trimox-
cae, Citrobacter freundii, Proteus vulgaris, Proteus rettgeri, azole rather than sulfonamides alone or ampicillin.
and Serratia marscescens, 2 Citrobacter diversus and 1 entero- The data presented here show that treatment of uncom-
COCCUS.
plicated U T I ' s with ofloxacin is as effective as treatment
with co-trimoxazole, with a high cure rate (98.5 to 100%)
in each of the three treatment groups. Superinfection
rates and relapses were also comparable in ofloxacin and
Table 3: Microbiological results in complicated urinary co-trimoxazole treated groups.
tract infection
In UTI's in patients with underlying abnormalities of the
urinary tract, a more resistant group of infecting agents
i!ii iill¸!i!i!i!iiiii!ii!i!ii!!i!!li
iii was seen, as expected. Again, ofloxacin and co-trimoxa-
zole cure rates were essentially equivalent, 97 to 100% in
each group. Of note is the development of resistance to
Patients entered 36 35
co-trimoxazote in one isolate of K. pneumoniae during
Patients evaluable therapy in the co-trimoxazole treatment group, and
5 to 9 days post-therapy 35 34 superinfection due to co-trimoxazole-resistant organisms
Microbiological cure 35 30 (P. aeruginosa) in the same group.
Microbiological failure 0 1
Both ofloxacin and co-trimoxazole appeared to be well
Superinfections 0 3
tolerated, with similar drop-out rates due to adverse drug
Patients evaluable reactions. Rashes and dizziness were responsible for pa-
4 to 6 weeks post-therapy 32 29 tients discontinuing therapy.
Microbiological relapses 0 2 In conclusion, based on the data available for analysis at
Microbiological 0 1 this time, ofloxacin is a safe and effective agent for the
re-infections treatment of both uncomplicated and complicated urinary
tract infections.

S 304 Infection 14 (1986) Suppl. 4 © MMV Medizin Verlag GmbH Mtinchen, Mtinchen 1986