Scand J Infect Dis 22: 339-344, 1990
Norfloxacin vs. Pivmecillinam in the Treatment of Uncomplicated Lower Urinary Tract Infections in Hospitalized Elderly Patients MARIANNE JONSSON,' GUNNAR ENGLUND' and KERSTIN NORGARD2
Scand J Infect Dis Downloaded from informahealthcare.com by University of Sydney on 01/03/15 For personal use only.
From the 'Department of Community Health Sciences, Section of Gcwatric Medicine, University of L i d , Varnhems Hospital, Malmo, and 'Astra AIab AB. Sodertal~e.Sweden
In a single-blind, randomized study of multicentre trial design 343 hospitalized geriatric patients (median age 83 years) suffering from symptomatic urinary tract infections (UTI) were treated with either norfloxacin 200 mg twice daily or pivmecillinam 200 mg 3 times daily orally for 7 days to compare the clinical eftlacy and safety of the antibiotics in the elderly. The pathogen was Escherichia coli in 56.7 96, other gram-negative rods in 37.2 % and gram-positive cocci in 6.1 %. Up to 18 days after cessation of treatment the original pathogen was eradicated in 60.5 % of the I14 who were assessable for the effect of norfloxacin therapy and in 36.5 % of the 96 patients in the pivmecillinam group (p< 0.001). Adverse drug reactions, mostly gastrointestinal disturbances, were noticed in single cases.
M . Jonsson, MD, PhD, Departmen#of Community Healtk Sciences, Section of Geriatric Medicine, University of Lund, Varnhems Hospital, 4 2 1 2 16 Malmo, Sweden
INTRODUCTION Bacteriuria is very common in the elderly, especially in women, but generally no treatment is required. Symptomatic urinary tract infections (UTI) are also very frequent. Women have a greater prevalence than men and epidemiological studies (1-3) have shown that 10-20'%n of women and 3-5 Yo of men, 70 years of age, have a history of UTI. The figures are even higher in older age groups. Debilitated people in nursing homes and geriatric clinics are more prone to UTI than those living at home: men 12-34% and women 30-34% (4-6). Norfloxacin has a high in vitro activity against gram-negative and gram-positive bacteria causing UTI in the elderly (7). The urinary concentration is high in patients with normal renal function. In large clinical studies norfloxacin has been shown to be highly effective and well tolerated (8, 9). However, few studies have included patients > 65 years of age and this led us to perform a large scale comparative study using norfloxacin for treatment of UTI in elderly hospitalized people. Pivmecillinam was chosen as reference drug, since its use in the treatment of UTI is well documented (10).
PATIENTS A N D METHODS Study design. The present multicentre study was carried out as a randomized single-blind trial with parallel group design. Seven geriatric clinics/nursing homes participated in the study, which was approved by local ethics committees. Verbal and written information was given. All patients or family members were required to give verbal consent before the patients entered the study. Patients. 343 patients, at least 6 5 years of age, with signs or symptoms of UTI including frequency, dysuria, suprapubic pain, haematuria and malodorous urine, entered the study between December 1986 and March 1988. Exclusion criteria were: known hypersensitivity or initial resistance of isolated pathogen to either of the drugs tested; any antibiotics given during the preceding 7 days; complicated UTI or pyelonephritis; severe underlying diseases; known impairment in liver or kidney function; treatment with drugs which can interact with norfloxacin (e.g. theophylline). Characteristics of patients and UTI are given in Table 1. The treatment groups were comparable with respect to age and sex. Relatively more patients had
Scand J Infect Dis Downloaded from informahealthcare.com by University of Sydney on 01/03/15 For personal use only.
340 M. Jonsson et al.
Scand J Infect Dis 22 (1 990)
recurrent UTI in the norfloxacin group compared to the pivmecillinam group. Concomitant diseases were reported in 97.4%, and 96.9 Yo respectively. The most frequent diseases were: senile dementia, cardiovascular diseases, diabetes, arthritis/arthrosis, Parkinson's syndrome and hip fractures. All diseases were similarly distributed between the treatment groups. Long-term medication was reported for 98.2% of the patients in the norfloxacin group compared to 91.7% in the pivmecillinam group. Most frequent long-term medications were: sedatives and hypnotics, analgetics, cardiovascular medication, laxatives, antiparkinson drugs and oestriol. Methods. Information about underlying diseases, concomitant medication and indwelling catheters was recorded and the UTI was classifed as sporadic ( 1 2 UTI episodes during the last 6 months and < 3 during the last 12 months) or recurrent. Urine samples (midstream or catheterized) were obtained for culture within 72 h before the first dose, on days 10-1 2 and days 20-22 after start of therapy. Significant bacteriuria was defined as > 10' bacterialml urine. Urine samples containing more than 2 bacterial species were considered contaminated. Isolated organisms were identified by standard procedures. Sensitivity testing was performed using the conventional disc diffusion technique. To be included in the efficacy analysis patients were required to have significant bacteriuria and to have taken the drug for at least 5 days. The bacteriological outcome was classifed as: elimination, persistence (significant growth of initial pathogen without previous post treatment elimination), relapse (significant growth of initial pathogen following previous post treatment elimination) and reinferlion (significant growth of a new pathogen post treatment). The results are given 2-8 days post treatment and up to 18 days post treatment. Clinical symptoms were recorded initially, and at the follow-up visits days 3-4, 10-12 and 20-22. The time to disappearance of symptoms was recorded. Patients who had received at least 1 dose of the drug were included in safety assessments. Adverse reactions were reported spontaneously by the patients or observed by the nursing staff. Before and after treatment renal function was checked by serum creatinine clearance according to Cockcroft and Gault ( I I). Treatment. Using a randomization list in blocks of 4 with stratification per centre the patients were consecutively assigned to oral treatment with norfloxacin 200 mg twice daily or pivmecillinam 200 mg 3 times daily for 7 days. The tablets were blister-packaged in aluminium strips and to satisfy the single-blind procedure, the norfloxacin-treated patients received 1 placebo tablet at midday. Compliance was checked by nursing staff. Statistical methods. The non-elimination rates were compared by chi-square tests, 2-sided 95 O/o confidence intervals and Mantel-Haenszel tests. Possible differences adjusted for the prognostic factors (sex, type of UTI, CAD and initial etiology) were investigated using the Breslow-Day test. Wilcoxon 2-samples tests for bacteriological response (elimination vs. reinfection vs. persistence/relapse) were used for the efficacy and to compare the time to disappearance of clinical symptoms. Adverse effects were compared by using chi-square test and 95 Yo confidence intervals.
RESULTS
Bacteriological outcome 274 randomized patients had significant bacteriuria. One single species was cultured from 250 patients and 2 species from 24. The pathogens were Escherichia coli in 56.7%, other gramnegative rods in 37.2 Yo and gram-positive cocci in 6.1 O/o (Table 11). The sensitivity test showed that 95.5 O/o were sensitive and 3.8% intermediate sensitive to norfloxacin; the respective figures for pivmecillinam were 84.7% and I 1 %. 26 patients had pathogens resistant to pivmecillinam while 2 had pathogens resistant to both drugs. These 28 patients were excluded from the efficacy analysis (Table I). Both immediately after the course and 2 weeks later the elimination rates were significantly higher in the norfloxacin group than in the pivmecillinam group (Table 111). CAD and recurrent UTI tended to influence the elimination rates unfavourably in pivmecillinam-treated patients, while in the norfloxacin group these factors had no effect on elimination rates. Etiology and elimination of the causative species in 210 patients are shown in Table IV. Reinfections occurred in 45 patients. 42 were reinfected with a single pathogen (no. of patients; norfloxacin vs. pivmecillinam): E. coli (0+ I), Klebsiella (5+2), Enterobacter (1 +O), Proteus ( 1 +8), staphylococci (5 +O), enterococci (10+4), streptococci (4+0) and Micrococcus (0+ 1). Three patients ( 2 + 1) were reinfected with 2 species: Enterococcus + Klebsiella, Pseudomanas + Streptococcus group B and Proteus + Enterococcus.
Norfloxacin and UTI in elderly patients 34 1
Scand J Infect Dis 22 (1990)
Clinical outcome Due to underlying diseases it is sometimes difficult to assess clinical symptoms in the elderly. Disappearance of symptoms could be registered for 165/210 patients. The time to disappearance was 4-6 days. Cure was noted in 81 Yo and 71 O/o for norfloxacin and pivmecillinam, respectively. This difference was not statistically significant (p=0.065). Table I. Patient characteristics and validity for efficacy and safety Norfloxacin ( n = 170)
Scand J Infect Dis Downloaded from informahealthcare.com by University of Sydney on 01/03/15 For personal use only.
No. of patients
Pivmecillinam (n=173) No. of patients
Yo
Patients valid for safety
168
98.8
170
98.3
Patients valid for efficacy Age (years) Median Range Sex Male Female Type of UTI Sporadic Recurrent Unknown CAD
1 I4
67.1
96
55.5
83 65-103
Reasons for non-validity No significant bacteriuria Urine cultures not valid Initial bacteria resistant to study drugs" Other reasonsb a
83 65-101
25 89
21.9 78.1
21 75
21.9 78. I
46 45 23 7
40.3 39.5 20.2 6.1
48 24 24 9
50 25 25 9.4
22 20
12.9
41 12
23.7
12 2
16
8
All 28 strains were resistant to pivmecillinam, 2 strains were resistant to norfloxacin. Concurrent antibiotic treatment (4 patients), treatment < 15 doses (4 patients), asymptomatic bacteriuria (1 patient) and lost to follow-up (1 patient).
Table 11. Initial bacterialJindings Strains in 274 patients with significant bacteriuria
Strains in 210 patients valid for efficacy
Pathogen
No.
Yo
No.
YO
Escherichia coli Proteus spp. Klebsiella/Enterobacter spp Pseudomonas spp. Coliform bacteria Enterococcus faecalis Streptococcus spp. Staphylococcus aureus
169 59 29 18 5 9 6 3
56.1 19.8 9.7 6
144 44 20 5 3 2 3 2
64.6 19.7 9 2.2
Total
298"
24 patients had 2 bacterial species. 13 patients had 2 bacterial species.
223'
342 M. Jonsson et al.
Scand J Infect Dis 22 (1990)
Safety assessments Out of the 338 patients valid for safety analysis, 2 patients in the norfloxacin group compared to 6 patients in the pivmecillinam group reported adverse reactions, mostly gastrointestinal. One patient given pivmecillinam had to discontinue the treatment due to nausea and vomiting. In the other 7 patients symptoms were mild. Six patients, 3 in each group, died of underlying diseases during the treatment or follow-up period. None of the deaths were reported to have any association with the drugs. Serum creatinine tests showed values slightly above the upper normal limit in 7 patients. These abnormalities could be explained by underlying diseases and were judged to have no relation to the drugs.
Scand J Infect Dis Downloaded from informahealthcare.com by University of Sydney on 01/03/15 For personal use only.
DISCUSSION Old people are very prone to UTI and old women to recurrent UTI. In this study 33% of the patients had a history of recurrent UTI. Although the dominating etiological agent was E. coli (56.7 O/o), other pathogens and multiresistant strains were often isolated. Recurrent infections were often caused by Proteus, EnterobacterKlebsiella and Pseudomonas spp. In these patients all bacteria belonging to these species were sensitive to norfloxacin compared with 80.4%to pivmecillinam. The high activity of norfloxacin against these bacteria and especially Pseudomonas should be given particular consideration in the context of hospital- and nursing home-acquired infections. The isolated pathogen was eradicated in 78.4 vs. 5 1.6 Yo 2-8 days post treatment and in 60.5 vs. 36.59/0 up to 18 days post treatment with norfloxacin and pivmecillinam, respectively. The antibacterial eficacy of norfloxacin was significantly better than that of pivmecillinam, even though 28 patients with pathogens initially resistant to pivmecillinam (2 of these strains were also resistant to norfloxacin) were excluded from the analysis. The difference between the 2 antibiotics was especially marked with regards to persistencehelapse of the initial pathogen (15 vs. 46 %). Persistence of E. coli was twice and other pathogens almost 10-fold as frequent in the pivmecillinam group. These figures are to be seen mainly as a result of the different antibiotic spectra of the antibiotics. The elimination rates are, however, about 10-20°/0 lower than those obtained earlier with norfloxacin or other antibiotics in treatment of UTI (8, 9, 12-15). Those patients were, however, younger, lived in the community, had less underlying diseases and the isolated
Table 111. Bacteriological outcome in 210 patients valid for eflcacy Norfloxacin
2-8 days post treatment No. of patients (04
Up to 18 days post treatment No. of patients
(W
*
Pivmecillinam Persistence/ relapse
Elimination
Reinfection
Persistence/ reI apse
8 (7.2)
47 (5 1.6)'
11 (12.1)
33 (36.3)
1 7a
35 (36.5)'
17 (1 7.7)
44* (45.8)
Elimination
Reinfection
87 (78.4)'
16 (14.4)
69 (60.5)'
28 (24.6)
(14.9)
p
Norfloxacin vs. Pivmecillinam in the Treatment of Uncomplicated Lower Urinary Tract Infections in Hospitalized Elderly Patients MARIANNE JONSSON,' GUNNAR ENGLUND' and KERSTIN NORGARD2
Scand J Infect Dis Downloaded from informahealthcare.com by University of Sydney on 01/03/15 For personal use only.
From the 'Department of Community Health Sciences, Section of Gcwatric Medicine, University of L i d , Varnhems Hospital, Malmo, and 'Astra AIab AB. Sodertal~e.Sweden
In a single-blind, randomized study of multicentre trial design 343 hospitalized geriatric patients (median age 83 years) suffering from symptomatic urinary tract infections (UTI) were treated with either norfloxacin 200 mg twice daily or pivmecillinam 200 mg 3 times daily orally for 7 days to compare the clinical eftlacy and safety of the antibiotics in the elderly. The pathogen was Escherichia coli in 56.7 96, other gram-negative rods in 37.2 % and gram-positive cocci in 6.1 %. Up to 18 days after cessation of treatment the original pathogen was eradicated in 60.5 % of the I14 who were assessable for the effect of norfloxacin therapy and in 36.5 % of the 96 patients in the pivmecillinam group (p< 0.001). Adverse drug reactions, mostly gastrointestinal disturbances, were noticed in single cases.
M . Jonsson, MD, PhD, Departmen#of Community Healtk Sciences, Section of Geriatric Medicine, University of Lund, Varnhems Hospital, 4 2 1 2 16 Malmo, Sweden
INTRODUCTION Bacteriuria is very common in the elderly, especially in women, but generally no treatment is required. Symptomatic urinary tract infections (UTI) are also very frequent. Women have a greater prevalence than men and epidemiological studies (1-3) have shown that 10-20'%n of women and 3-5 Yo of men, 70 years of age, have a history of UTI. The figures are even higher in older age groups. Debilitated people in nursing homes and geriatric clinics are more prone to UTI than those living at home: men 12-34% and women 30-34% (4-6). Norfloxacin has a high in vitro activity against gram-negative and gram-positive bacteria causing UTI in the elderly (7). The urinary concentration is high in patients with normal renal function. In large clinical studies norfloxacin has been shown to be highly effective and well tolerated (8, 9). However, few studies have included patients > 65 years of age and this led us to perform a large scale comparative study using norfloxacin for treatment of UTI in elderly hospitalized people. Pivmecillinam was chosen as reference drug, since its use in the treatment of UTI is well documented (10).
PATIENTS A N D METHODS Study design. The present multicentre study was carried out as a randomized single-blind trial with parallel group design. Seven geriatric clinics/nursing homes participated in the study, which was approved by local ethics committees. Verbal and written information was given. All patients or family members were required to give verbal consent before the patients entered the study. Patients. 343 patients, at least 6 5 years of age, with signs or symptoms of UTI including frequency, dysuria, suprapubic pain, haematuria and malodorous urine, entered the study between December 1986 and March 1988. Exclusion criteria were: known hypersensitivity or initial resistance of isolated pathogen to either of the drugs tested; any antibiotics given during the preceding 7 days; complicated UTI or pyelonephritis; severe underlying diseases; known impairment in liver or kidney function; treatment with drugs which can interact with norfloxacin (e.g. theophylline). Characteristics of patients and UTI are given in Table 1. The treatment groups were comparable with respect to age and sex. Relatively more patients had
Scand J Infect Dis Downloaded from informahealthcare.com by University of Sydney on 01/03/15 For personal use only.
340 M. Jonsson et al.
Scand J Infect Dis 22 (1 990)
recurrent UTI in the norfloxacin group compared to the pivmecillinam group. Concomitant diseases were reported in 97.4%, and 96.9 Yo respectively. The most frequent diseases were: senile dementia, cardiovascular diseases, diabetes, arthritis/arthrosis, Parkinson's syndrome and hip fractures. All diseases were similarly distributed between the treatment groups. Long-term medication was reported for 98.2% of the patients in the norfloxacin group compared to 91.7% in the pivmecillinam group. Most frequent long-term medications were: sedatives and hypnotics, analgetics, cardiovascular medication, laxatives, antiparkinson drugs and oestriol. Methods. Information about underlying diseases, concomitant medication and indwelling catheters was recorded and the UTI was classifed as sporadic ( 1 2 UTI episodes during the last 6 months and < 3 during the last 12 months) or recurrent. Urine samples (midstream or catheterized) were obtained for culture within 72 h before the first dose, on days 10-1 2 and days 20-22 after start of therapy. Significant bacteriuria was defined as > 10' bacterialml urine. Urine samples containing more than 2 bacterial species were considered contaminated. Isolated organisms were identified by standard procedures. Sensitivity testing was performed using the conventional disc diffusion technique. To be included in the efficacy analysis patients were required to have significant bacteriuria and to have taken the drug for at least 5 days. The bacteriological outcome was classifed as: elimination, persistence (significant growth of initial pathogen without previous post treatment elimination), relapse (significant growth of initial pathogen following previous post treatment elimination) and reinferlion (significant growth of a new pathogen post treatment). The results are given 2-8 days post treatment and up to 18 days post treatment. Clinical symptoms were recorded initially, and at the follow-up visits days 3-4, 10-12 and 20-22. The time to disappearance of symptoms was recorded. Patients who had received at least 1 dose of the drug were included in safety assessments. Adverse reactions were reported spontaneously by the patients or observed by the nursing staff. Before and after treatment renal function was checked by serum creatinine clearance according to Cockcroft and Gault ( I I). Treatment. Using a randomization list in blocks of 4 with stratification per centre the patients were consecutively assigned to oral treatment with norfloxacin 200 mg twice daily or pivmecillinam 200 mg 3 times daily for 7 days. The tablets were blister-packaged in aluminium strips and to satisfy the single-blind procedure, the norfloxacin-treated patients received 1 placebo tablet at midday. Compliance was checked by nursing staff. Statistical methods. The non-elimination rates were compared by chi-square tests, 2-sided 95 O/o confidence intervals and Mantel-Haenszel tests. Possible differences adjusted for the prognostic factors (sex, type of UTI, CAD and initial etiology) were investigated using the Breslow-Day test. Wilcoxon 2-samples tests for bacteriological response (elimination vs. reinfection vs. persistence/relapse) were used for the efficacy and to compare the time to disappearance of clinical symptoms. Adverse effects were compared by using chi-square test and 95 Yo confidence intervals.
RESULTS
Bacteriological outcome 274 randomized patients had significant bacteriuria. One single species was cultured from 250 patients and 2 species from 24. The pathogens were Escherichia coli in 56.7%, other gramnegative rods in 37.2 Yo and gram-positive cocci in 6.1 O/o (Table 11). The sensitivity test showed that 95.5 O/o were sensitive and 3.8% intermediate sensitive to norfloxacin; the respective figures for pivmecillinam were 84.7% and I 1 %. 26 patients had pathogens resistant to pivmecillinam while 2 had pathogens resistant to both drugs. These 28 patients were excluded from the efficacy analysis (Table I). Both immediately after the course and 2 weeks later the elimination rates were significantly higher in the norfloxacin group than in the pivmecillinam group (Table 111). CAD and recurrent UTI tended to influence the elimination rates unfavourably in pivmecillinam-treated patients, while in the norfloxacin group these factors had no effect on elimination rates. Etiology and elimination of the causative species in 210 patients are shown in Table IV. Reinfections occurred in 45 patients. 42 were reinfected with a single pathogen (no. of patients; norfloxacin vs. pivmecillinam): E. coli (0+ I), Klebsiella (5+2), Enterobacter (1 +O), Proteus ( 1 +8), staphylococci (5 +O), enterococci (10+4), streptococci (4+0) and Micrococcus (0+ 1). Three patients ( 2 + 1) were reinfected with 2 species: Enterococcus + Klebsiella, Pseudomanas + Streptococcus group B and Proteus + Enterococcus.
Norfloxacin and UTI in elderly patients 34 1
Scand J Infect Dis 22 (1990)
Clinical outcome Due to underlying diseases it is sometimes difficult to assess clinical symptoms in the elderly. Disappearance of symptoms could be registered for 165/210 patients. The time to disappearance was 4-6 days. Cure was noted in 81 Yo and 71 O/o for norfloxacin and pivmecillinam, respectively. This difference was not statistically significant (p=0.065). Table I. Patient characteristics and validity for efficacy and safety Norfloxacin ( n = 170)
Scand J Infect Dis Downloaded from informahealthcare.com by University of Sydney on 01/03/15 For personal use only.
No. of patients
Pivmecillinam (n=173) No. of patients
Yo
Patients valid for safety
168
98.8
170
98.3
Patients valid for efficacy Age (years) Median Range Sex Male Female Type of UTI Sporadic Recurrent Unknown CAD
1 I4
67.1
96
55.5
83 65-103
Reasons for non-validity No significant bacteriuria Urine cultures not valid Initial bacteria resistant to study drugs" Other reasonsb a
83 65-101
25 89
21.9 78.1
21 75
21.9 78. I
46 45 23 7
40.3 39.5 20.2 6.1
48 24 24 9
50 25 25 9.4
22 20
12.9
41 12
23.7
12 2
16
8
All 28 strains were resistant to pivmecillinam, 2 strains were resistant to norfloxacin. Concurrent antibiotic treatment (4 patients), treatment < 15 doses (4 patients), asymptomatic bacteriuria (1 patient) and lost to follow-up (1 patient).
Table 11. Initial bacterialJindings Strains in 274 patients with significant bacteriuria
Strains in 210 patients valid for efficacy
Pathogen
No.
Yo
No.
YO
Escherichia coli Proteus spp. Klebsiella/Enterobacter spp Pseudomonas spp. Coliform bacteria Enterococcus faecalis Streptococcus spp. Staphylococcus aureus
169 59 29 18 5 9 6 3
56.1 19.8 9.7 6
144 44 20 5 3 2 3 2
64.6 19.7 9 2.2
Total
298"
24 patients had 2 bacterial species. 13 patients had 2 bacterial species.
223'
342 M. Jonsson et al.
Scand J Infect Dis 22 (1990)
Safety assessments Out of the 338 patients valid for safety analysis, 2 patients in the norfloxacin group compared to 6 patients in the pivmecillinam group reported adverse reactions, mostly gastrointestinal. One patient given pivmecillinam had to discontinue the treatment due to nausea and vomiting. In the other 7 patients symptoms were mild. Six patients, 3 in each group, died of underlying diseases during the treatment or follow-up period. None of the deaths were reported to have any association with the drugs. Serum creatinine tests showed values slightly above the upper normal limit in 7 patients. These abnormalities could be explained by underlying diseases and were judged to have no relation to the drugs.
Scand J Infect Dis Downloaded from informahealthcare.com by University of Sydney on 01/03/15 For personal use only.
DISCUSSION Old people are very prone to UTI and old women to recurrent UTI. In this study 33% of the patients had a history of recurrent UTI. Although the dominating etiological agent was E. coli (56.7 O/o), other pathogens and multiresistant strains were often isolated. Recurrent infections were often caused by Proteus, EnterobacterKlebsiella and Pseudomonas spp. In these patients all bacteria belonging to these species were sensitive to norfloxacin compared with 80.4%to pivmecillinam. The high activity of norfloxacin against these bacteria and especially Pseudomonas should be given particular consideration in the context of hospital- and nursing home-acquired infections. The isolated pathogen was eradicated in 78.4 vs. 5 1.6 Yo 2-8 days post treatment and in 60.5 vs. 36.59/0 up to 18 days post treatment with norfloxacin and pivmecillinam, respectively. The antibacterial eficacy of norfloxacin was significantly better than that of pivmecillinam, even though 28 patients with pathogens initially resistant to pivmecillinam (2 of these strains were also resistant to norfloxacin) were excluded from the analysis. The difference between the 2 antibiotics was especially marked with regards to persistencehelapse of the initial pathogen (15 vs. 46 %). Persistence of E. coli was twice and other pathogens almost 10-fold as frequent in the pivmecillinam group. These figures are to be seen mainly as a result of the different antibiotic spectra of the antibiotics. The elimination rates are, however, about 10-20°/0 lower than those obtained earlier with norfloxacin or other antibiotics in treatment of UTI (8, 9, 12-15). Those patients were, however, younger, lived in the community, had less underlying diseases and the isolated
Table 111. Bacteriological outcome in 210 patients valid for eflcacy Norfloxacin
2-8 days post treatment No. of patients (04
Up to 18 days post treatment No. of patients
(W
*
Pivmecillinam Persistence/ relapse
Elimination
Reinfection
Persistence/ reI apse
8 (7.2)
47 (5 1.6)'
11 (12.1)
33 (36.3)
1 7a
35 (36.5)'
17 (1 7.7)
44* (45.8)
Elimination
Reinfection
87 (78.4)'
16 (14.4)
69 (60.5)'
28 (24.6)
(14.9)
p
