DIAG. MICROBIOL.INFECT. DIS, 1990;13:161-163

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Intravenous and Oral Ciprofloxacin versus Intravenous Ceftazidime for the Treatment of Severe Urinary Tract Infections Stacy J. Childs

INTRODUCTION Ciprofloxacin is a n e w quinolone antimicrobial agent active against a variety of aerobic Gram-negative and Gram-positive bacteria. It has been shown to be effective w h e n administered orally for the treatment of urinary tract infections (Arcieri et al., 1987). Ciprofloxacin and similar oral quinolones may have an impact on the methods of treating infections and on cost reduction in hospitals (Barriere, 1987). Ciprofloxacin is n o w available as an intravenous (IV) formulation for the treatment of serious infections in hospitalized patients. After initial response to IV ciprofloxacin therapy, patients can complete the course of treatment with the oral form after hospital discharge. The purpose of the study was to compare the efficacy and safety of sequential IV and oral ciprofloxacin with IV ceftazidime in the treatment of severe urinary tract infections.

PATIENTS AND METHODS

Enrollment Criteria Patients of either sex older and w h o had a caused by organisms acin and ceftazidime

w h o were 18 years of age or serious urinary tract infection susceptible to both ciprofloxwere eligible for enrollment.

From Southeastern Research, Birmingham, Alabama. Address reprint requests to: Dr. S.J. Childs, Southeastern Research, Shelby Professional Building, Suite 203, 1066First Street North, P.O. Box 985, Alabaster, AL 35007. Received January 10, 1990; revised and accepted January 12, 1990. © 1990 Elsevier Science Publishing Co., Inc. 655 Avenue of the Americas, New York, NY 10010 0732-8893/90/$3.50

The infection was confirmed by a pretreatment urine culture positive for >/10s colony-forming units (CFU)/ml) within 48 hr of the initiation of therapy; clinical signs and symptoms and microscopic examination of urine were to be consistent with the diagnosis. Patients considered ineligible were those with a history of allergy to quinolones or cephalosporins; mild infections that did not warrant parenteral antimicrobial therapy; severe underlying disease; likely to require concomitant treatment with an antimicrobial with a similar spectrum of activity; severe renal impairment; pregnant or lactating women; or gross lower or upper tract obstruction, severe neurogenic bladder disease, or chronic indwelling urinary catheters. Informed consent was obtained from all patients.

Pretreatment Clinical and Bacteriologic Evaluations Prior to the initiation of therapy, each patient gave a complete medical history, and a physical examination was performed by a physician. Cultures for the isolation, identification, and susceptibility testing of the infecting organisms were performed on urine samples.

Treatment Regimen The patients were assigned to the treatment groups according to a computer-generated randomization schedule. Those in the ciprofloxacin group received 200 mg of ciprofloxacin every 12 hr IV for 2-5 days, followed by 500 mg orally twice daily for up to 14 days. The patients were changed from the formulation to the oral formulation and discharged from the hospital after they became afebrile, the infection

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had lessened in severity, and the patients were able to tolerate oral medications. Patients assigned to the ceftazidime group were given 500 mg every 8 hours IV for a minimum of 4 days.

Clinical and Bacteriologic Evaluations Clinical response to therapy was based on serial examinations of the patient for signs and symptoms of infection and the results of pertinent laboratory tests or procedures that reflected the course of the infection. At the end of treatment, the clinical response was graded as resolution (disappearance of all signs and symptoms of infection), improvement (marked or moderate reduction in the severity and/or number of signs and symptoms), failure (insufficient lessening of the signs and symptoms of infection to qualify as improvement), or indeterminate (no evaluation possible). At the end of the study, a bacteriologic response was given for each causative organism, as well as for the urinary tract infection site, based on the results of urine cultures performed before treatment, on day 3 or 4 during treatment, and 5 to 9 days after treatment. The response for each causative organism was graded as eradication (causative organism present in numbers ~104 CFU/ml in any of the three cultures), persistence (causative organisms present in numbers ~104 CFU/ml at any time after the first 2 days of treatment or up to 9 days after treatment), superinfection (a n e w organism present in numbers ~104 CFU/ml at any time during or up to 9 days after treatment), or indeterminate (response not evaluable). The bacteriologic response by site of infection was graded as cure (eradication of all causative organisms), failure (persistence of one or more causative organisms or superinfection), or indeterminate.

Laboratory Evaluation The following laboratory tests were performed generally before, during, and after treatment: hematocrit, hemoglobin, complete blood cell count with white blood cell differential, platelet count, erythrocyte sedimentation rate, aspartate aminotransferase, alanine aminotransferase, lactate dehydrogenase, alkaline phosphatase, total bilirubin, cholesterol, triglycerides, total protein, albumin, blood glucose, serum creatinine, blood urea nitrogen, uric acid, serum electrolytes, and urinalysis, including microscopic examination of sediment.

RESULTS During a 6-month period, 63 patients with serious urinary tract infections were enrolled in this study. Twenty-three patients were excluded from the eval-

S.J. Childs

TABLE 1.

Characteristics of Patients Evaluated

Characteristics Age (years) Mean Range Infection diagnosis Urinary tract infection Acute pyelonephritis Acute prostatitis Epididymitis Status of infection Uncomplicated Complicated

Ciprofloxacin (n = 19)

Ceftazidime (n = 21)

56.7 28-85

53.3 23-83

8 9 2 0

10 8 2 1

4 15

6 15

uation of efficacy for the following reasons: no pretreatment culture or no organism isolated before treatment (10), no follow-up culture on day 3 or 4 during therapy and/or days 5-9 after therapy (7), organisms isolated in numbers ~105 CFU/ml (3), pathogen resistant to one or both study drugs (2), serum creatinine level ~2.0 mg/dl (1). Of the 40 evaluated patients, 19 were in the ciprofloxacin group and 21 were in the ceftazidime group. Table 1 shows the clinical characteristics of the patients. The 15 patients in each group with underlying urinary tract complications had interstitial cystitis, urinary diversion, lower tract obstruction, neurogenic bladder, or chronic pyelonephritis, or had recently undergone surgery or instrumentation. A total of 21 pathogens were isolated from the urine of the patients in the ciprofloxacin group, and 22 were isolated from those in the ceftazidime group, as shown in Table 2. Escherichia coli was isolated most frequently in both group.

TABLE 2.

Pathogens Isolated from Urine Number of Isolates

Escherichia coli Pseudomonas aeruginosa Enterobacter aerogenes Enterobacter cloacae Serratia marcescens Klebsiella oxytoca Klebsiella pneumoniae Proteus mirabilis Morganella morganii Citrobacter sp. Providencia rettgeri

Ciprofloxacin

Ceftazidime

10

14

3 0 1 1 0 1 0 1

2 2 1 1 1 0 1 0

1

0

1

0

Enterococcus

1

0

Staphylococcus aureus

1

0

21

22

Total

Ciprofloxacin versus Urinary Tract Infections

TABLE 3.

Clinical and Bacteriologic Responses to Therapy

Response

Ciprofloxacin Ceftazidime

Clinical response by patient Cure (%) Improvement (%) Failure (%)

n = 19 16 (84) 3 (16) 0

n = 21 16 (76) 4 (19) 1 (5)

Bacteriologic response by site of infection Cure (%) Failure (%)

n = 19

n = 21

18 (95) 1 (5)

18 (86) 3 (14)

Bacteriologic response by causative organism Eradication (%) Persistence (%) Superinfecting organisms

n = 21

n = 22

20 (95) 1 (5) 2

19 (86) 3 (14) 5

(%)

The 19 patients in the ciprofloxacin group received the drug IV for a mean of 4.4 days, with a range of 2-7 days; oral treatment followed sequentially for a mean of 7.6 days, with a range of 1.5-11 days. Intravenous ceftazidime was administered to the 21 patients in that group for a mean of 6.1 days, with a range of 4-9 days. Table 3 shows that at the end of IV and oral therapy with ciprofloxacin and IV ceftazidime therapy, 19 of the 21 patients (84%) were cured in the ciprofloxacin group and 16 of the 21 patients (76%) were cured in the ceftazidime group. Improvement was noted for the other three patients (16%) in the ciprofloxacin group and for four patients (19%) in the ceftazidime group, one ceftazidime-treated patient (5%) failed to respond. Bacteriologic cure was achieved at 18 of the 19 sites (95%) treated with ciprofloxacin, and the re-

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sponse at the other site was failure (5%) (Table 3). Among the 21 sites treated with ceftazidime, 18 (86%) were bacteriologic cures and 3 (14%) were failures. These response rates refected those for the causative organisms: All but one of the 21 pathogens in the ciprofloxacin group were eradicated, whereas three of the 22 organisms in the ceftazidime group persisted. There were two superinfections in the ciprofloxacin group and five in the ceftazidime group. Few adverse effects were reported for either group, although the incidence was slightly higher among the ciprofloxacin-treated patients. The most frequent was redness and discomfort at the side of IV infusion, which occurred in three patients in the ciprofloxacin group and one in the ceftazidime group. Nausea and/or diarrhea occurred infrequently in either group. Other adverse effects included rash at the injection site, vaginitis, yeast infection, ulcers on the tongue, gastritis, grand mal seizure, blurred vision, headache, strange sensation over body, hot, flushed feeling, and paranoia. Patients tolerated these effects well, and none required discontinuation of treatment with either drug. DISCUSSION In this study population of adult, hospitalized patients with serious urinary tract infections, sequential IV and oral therapy with ciprofloxacin was as effective as IV ceftazidime. All patients treated with ciprofloxacin were cured or their infection improved, 95% of the pathogens were eradicated, and few superinfections occurred. Adverse effects were few, and in no instance was therapy discontinued.

This work was supported by a grant from Miles, Inc., Pharmaceutical Division, West Haven, Connecticut.

REFERENCES Arcieri G, Griffith E, Gruenwaldt G, Heyd A, O'Brien B, Becker N, August R (1987) Ciprofloxacin: an update on clinical experience. Am J Med 82(suppl 4A):381-386.

Barriere SL (1987) Economic impact of oral ciprofloxacin: a pharmacist's perspective. Am J Med 82(suppl 4A):387390.

Intravenous and oral ciprofloxacin versus intravenous ceftazidime for the treatment of severe urinary tract infections.

DIAG. MICROBIOL.INFECT. DIS, 1990;13:161-163 161 Intravenous and Oral Ciprofloxacin versus Intravenous Ceftazidime for the Treatment of Severe Urina...
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