Journal of Chemotherapy
ISSN: 1120-009X (Print) 1973-9478 (Online) Journal homepage: http://www.tandfonline.com/loi/yjoc20
A Comparative Study on Aztreonam, Ceftazidime and Amikacin in the Treatment of Complicated Urinary Tract Infections M.D. Melekos, A. Skoutelis, C. Chryssanthopoulos & H.P. Bassaris To cite this article: M.D. Melekos, A. Skoutelis, C. Chryssanthopoulos & H.P. Bassaris (1991) A Comparative Study on Aztreonam, Ceftazidime and Amikacin in the Treatment of Complicated Urinary Tract Infections, Journal of Chemotherapy, 3:6, 376-382, DOI: 10.1080/1120009X.1991.11739124 To link to this article: http://dx.doi.org/10.1080/1120009X.1991.11739124
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Journal of Chemotherapy
A Comparative Study on Aztreonam, Ceftazidime and Amikacin in the Treatment of Complicated Urinary Tract Infections
Vol. 3 - n. 6 (376-382) - 1991
drugs were well tolerated. It is concluded that aztreonam, ceftazidime and amikacin are equally effective and safe for the treatment of complicated urinary ttact infections due to susceptible organisms. Key words: Aztreonam, ceftazidime, amikacin, urinary tract infections, complicated
INTRODUCTION
M.D. MELEKOS * - A. SKOUTELIS ** C. CHRYSSANTHOPOULOS ** H.P. BASSARIS **
Summary ---------------------- -------In a prospective, randomized trial, aztreonam (1 g intra· venously or inttamuscularly, twice daily) was compared with ceftazidime (1 g intravenously or intramuscularly, twice daily) and amikacin (500 mg intravenously or intramuscularly, twice daily) in 76 patients aged 24 to 84 years (mean, 59.7 years) with complicated urinary ttact infections. Initial pathogens included Escherichia coli (4 7. 5%), Pseudomonas aeruginosa (22.5%), Klebsiella spp. (9%), Proteus spp. (7.5%) and Enterobacter spp (6%). In four patients initial urine cultures yielded more than one organism. All pathogens were sensitive to the three study drugs. Including performance of 4- to 6week follow-up cultures, eradication of the pathogens occurred in 72% of patients treated with aztteonam, in 74% of those tteated with ceftazidime and in 71% treated with amikacin (p>0.05). Clinical success was observed in 84% of patients treated with aztreonam, in 82% of those treated with ceftazidime and in 85% treated with amikacin (p>0.05). All
Urinary tract infections are among the most common community and hospital acquired infections. In hospitalized patients or in patients with major structural or/and functional abnormalities of the urinary tract, Escherichia coli, Pseudomonas aeruginosa, Klebsiella species, Enterobacter species and other gram-negative aerobic bacilli are the usual pathogens 1 • 2 • In vitro studies have indicated that amikacin, ceftazidime and aztreonam are active against these organisms and also have favorable pharmacokinetics which make them suitable for the treatment of complicated urinary tract infections l13. In this prospective randomized trial we compared the efficacy and safety of ceftazidime, aztreonam and amikacin for the treatment of complicated urinary tract infections due to susceptible organisms. As far as we know, a study comparing these three antimicrobial agents has not previously been published.
PATIENTS AND METHODS Departments of Urology * and Medicine, Division of Infectious Diseases **, University of Parras School of Medicine, Rio-Patras, Greece. Correspondent: Michael D . Melekos, M .D., Agios Georgios Rio, 60 Iroon Polytechniou Street, 26500 Rio, Parras, G reece © Edizioni Ri viste Scientifiche - Firenze
Ninety-six patients (79 men and 17 women) with complicated urinary tract infections were enrolled in a prospective, non-blinded, randomized comparative trial. Eighty-two were evalISS N 1120-009X
377
Downloaded by [Australian Catholic University] at 09:51 25 August 2017
A COMPARATIVE STUDY ON AZTREONAM, CEFTAZIDIME AND AMIKACIN, ETC .
uable for safety and 76 (64 men and 12 women) were evaluable for efficacy. Twenty subjects were excluded because of lack of urine culture specimens during or after therapy, as well as of incorrectly taking of medication. Complicated urinary tract infection was defined as a bacterial count of at least 10 5 colony-forming units (cfu/ml) of urine in the presence of structural or functional abnormality of the urinary tract, accompanied by typical signs and symptoms of infection. Asymptomatic patients were eligible provided they had two pretreatment urine culture specimens yielding positive results for the same species of bacteria. Patients were randomly assigned into 3 groups depending on the antimicrobial agent which was administered intramuscularly or intravenously for 7 consecutive days: Group A included patients (n = 25) who
TABLE
received 1 g aztreonam (Squibb) every 12 hours, group B patients (n = 27) received 1 g ceftazidime (Glaxo) twice daily, and group C included patients (n = 24) who received 500 mg amikacin, (Bristol-Myers Squibb) twice daily. All patients gave informed consent and were required to have a pretreatment urine culture specimen with infecting organisms sensitive to all three antibiotics within 48 hours of the start of therapy. All patient-groups were comparable with respect to age, weight and concomitant underlying disorders of the urinary tract (Table 1). Patients with a history of allergy to cephalosporins and immediate hypersensitivity to penicillins or aminoglycosides were excluded from the study as well as subjects who had received antibiotics in the 5 days prior to enrollment. Patients with bacteremia or suspected bac-
1 - Characteristics of patient population and their underlying condition. Aztreonam (n = 25)
Ceftazidime (n = 27)
Amikacin (n = 24)
58.8:1: 14.8 34-81
59.4:1: 16.8 24-84.
60 .7:1:13.8 30-80
4 21
4 23
4 20
73.6±8.6 56-95
74 .5:1: 10.4 59-108
71.7±8.1 58-90
Age (years) Mean±SD Range Sex Female Male Weight (kg) Mean±SD Range Underlying abnormalities Benign prostatic hypertrophy Carcinoma of the prostate Bladder cancer Epididymitis Urethral stricture Urethral diverticulum Neurogenic bladder Ileal conduit Cutaneous ureterostomy Cutaneous nephrostomy Suprapubic catheter Vesical calculi Renal calculi Ureteral calculi Ureteric reflux Prostatitis Bladder neck contracture Chronic pyelonephritis Totals
7 3 3 1 2 0 1 0 1 0 0 1 3 0 0
25
9
6
2
2
4
3
1 1 0 1 0
1 0 2 0 2 0 2
2 1 0 0
0 1 0
27
24
1
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378
M.D. MELEKOS - A. SKOUTELIS - C. CHRYSSANTHOPOULOS - H.P. BASSARIS
teremia, as well as patients with significant unrelieved obstruction in the kidneys were not eligible, nor were those with significant liver disease or decreased renal function, determined by a serum creatinine of greater than 3 mg/dl. Pregnant or lactating women were also excluded. The safety of the drugs was assessed by monitoring renal, hepatic and hemopoietic function. Bacteriological efficacy was monitored by urine cultures 3 to 4 days after initiation of therapy, at the end of therapy, and at 5 to 9 days following therapy, while each patient with a bacteriologic response of eradication at the infection site returned for a follow-up evaluation 4 to 6 weeks after cessation of therapy. Clinical response und urine cultures were used to assess the therapeutic effects of the antibiotics, using the following criteria: A) Assessment of clinical response: 1) Resolution= disappearance of all symptoms and signs of urinary tract infection at day 5 to 9 following treatment; 2) Improvement= marked or moderate reduction in the severity and/or number of signs and symptoms 5 to 9 days after cessation of therapy, and 3) Failure= insufficient lessening of signs and symptoms to qualify as improvement. B) Assessment of bacteriologic response: 1) Eradication= negative culture during therapy, at the end of therapy, 5 to 9 days following therapy and 4 to 6 weeks after cessation of therapy; 2) Persistence= pretreatment infecting organism present during therapy, at the end of therapy and on days 5 to 9 following therapy; 3) Relapse = negative culture during therapy, at the end of therapy and 5 to 9 days following therapy, but positive for the pretreatment organism (with 2: 10s cfu/ml) at (or before) 4 to 6 weeks after cessation of therapy; 4) Reinfection= elimination of the pretreatment pathogen and the occurrence of a different organism (of 2: 10s cfu/ml) during, at the termination or following therapy, and 5) Superinfection= 2: 10s cfu/ml of the original organism plus a new pathogen at any time during or after therapy. After cessation of therapy, each patient with a bacteriologic response of eradication at the infection site returned in 5 to 9 days for evaluation, and the responders (with continuously negative cultures at the above period) returned again for a follow-up evaluation 4 -to 6 weeks after therapy.
Statistics. Statistical significance was determined by the use of the chi-square analysis, Student's t-test and Fisher's exact test, whenever expected frequencies were less than about 5. RESULTS
The causative pathogens in each patientgroup are shown in Table 2. Four patients had more than one type of organism (mixed infection). Escherichia coli was the organism isolated most frequently in all3 groups (in 47.5% of the total population). Pseudomonas aeruginosa (22.5%), Klebsiella species (9%), Proteus species (7.5%) and Enterobacter species (6%) were isolated in a lower incidence in each group . Fifty-six per cent (n= 14) of the aztreonamtreated patients, 63% (n= 16) of the ceftazidime and 54% (n = 13) of the amikacin had an operative procedure during or in the immediate proximity to study treatment. Forty-four per cent of the patients in group A, 44% of those in group B and 50% of the patients in group C had an indwelling catheter for 3 or more days during therapy. In all cases, however, in which an indwelling catheter was used, the latter was removed at least 24 hours before termination of study drug treatment. The therapeutic results were determined ac-
TABLE 2 -
Distribution of urine infecting organisms. Aztreonam
Escherichia coli Pseudomonas aeruginosa Proteus mirabilis Proteus vulgaris Klebsiella pneumoniae Klebsiella oxytoca Enterobacter cloacae En terobacter aerogenes Serratia marcescens Morganella morganil Providencia stuartii K. pneumonlae +E. cloacae E.coll + Citrobacter freundii Ps. aeruglnosa + P. mirabilis E. coli+ Ps. aeruginosa
12
Totals
27
5
Ceftazidime Amikacin 13 6
11
5
2
1 2
1
2
2 2
1 1
28
25
379
A COMPARATIVE STUDY ON AZTREONAM, CEFfAZIDIME AND AMIKACIN, ETC.
cording to clinical and urine bacteriologic response and are shown in Tables 3 and 4. Clinical response: In the group of patients treated with aztreonam 16 (84%) had clinical resolution of symptoms and signs at 5 to 9 days following therapy while 2 (10.5%) failed to respond. Six were not evaluable since they were either asymptomatic prior to treatment or had TABLE
3 - Clinical and bacteriologic response.
Aztreonam (n = 25) No.( % )
Downloaded by [Australian Catholic University] at 09:51 25 August 2017
symptoms before and after treatment due to nephrolithiasis, post-irradiation or lower urinary tract obstruction. In the ceftazidime-treated group the rates of resolution and persistence of symptoms were 82% and 9%, respectively, while in the amikacin group 85% and 10%, respectively (chi-square test, p > 0.05). Overall, 15 patients out of 76 in the present study were
Ceftazidime (n = 27) No.( % )
Am ikacin (n = 24) No.(%)
Clinical response at day 5 to 9 after cessation of therapy Resolution * Improvement Failure
16 (84.2) 1 (5.3) 2 (10.5)
18 (81.8) 2 (9 .1) 2 (9.1)
17 (85) 1 (5) 2 (10)
Tot a I
19
22
20
6
5
4
Not evaluable Bacteriologic response Day 3 of therapy Eradication * Persistence Reinfection/Superinfection
20 (80) 5 (20) 0
23 (85.2) 4 (14.8) 0
20 (83.3) 4 (16.7) 0
Tot a I
25
27
24
Eradication * Persistence Reinfection/Superinfection
22 (88) 2 (8) 1 (4)
23 (85 .2) 2 (7.4) 2 (7.4)
21 (87 .5) 2 (8.3) 1 (4.2)
Tot a I
25
27
24
20 (90.9) 1 (4.6) 1 (4.5)
22 (95 .7) 1 (4.3) 0
19 (90 .5) 1 (4 .8) 1 (4.7)
22
23
21
Eradication * Relapse Reinfection/Superinfection
18 (90) 1 (5) 1 (5)
20 (90.9) 2 (9.1) 0
17 (98 .5) 2 (10.5) 0
Tot a I
20
22
19
Eradication * Persistence Relapse Reinfection Superinfection
18 (72) 3 (12) 1 (4) 2 (8) (4)
20 (74.1) 3 (11.1) 2 (7 .4) (3.7) (3 .7)
17 (70 .8) 3 (12 .5) 2 (8.3) 1 (4.2) 1 (4.2)
Tot a I
25
27
24
End of therapy
5 to 9 days after therapy Eradication * Persistence Reinfection/Superinfection Tot a I 4 to 6-week follow-up
Overall bacteriologic response
* There were no statistically significant differences among groups (chi-square test, p> 0.05) .
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380
M.D. MELEKOS • A. SKOUTEUS • C. CHRYSSANTHOPOULOS • H .P. BASSARlS
not evaluable for clinical response due to pretreatment lack of signs and symptoms or the existence of symptoms before and after treatment because of nephrolithiasis, cancer, postirradiation or lower urinary tract obstruction. Bacteriologic response: At the end of therapy, the bacteriologic response at the site of urinary tract infection was eradication for 88% of the patients in the aztreonam group, 85% in the ceftazidime and 87.5% in the amikacin. Among the 66 patients who initially responded successfully to therapy, 91% of those in the aztreonam group, 96% in the ceftazidime and 90% in the amikacin group demonstrated negative cultures. When patients with bacteriologic responses of eradication at the above period returned again for a follow-up evaluation 4 to 6 weeks after treatment, the responses were graded as eradication at 18 sites m the aztreonam group (90%), at 20 sites (91%) in the ceftazidime and at 17 sites (89%) in the amikacin group. Overall, that is including culture evaluations at the end of therapy, 5 to 9 days after cessation of therapy and at 4 to 6-week follow-up, the bacteriologic response was eradication for 18 patients (72%) in the aztreonam group, for 20 patients (74%) in the ceftazidime and for 17 patients (71%) in the amikacin group (Table 3). All the above differences were remarkably comparable (chi-square test, p > 0.05). The bacteriologic responses for each causative organism correlated well in those for each site of infection, i.e . 20 of the 27 pathogens in the aztreonam group were eradicated, compared to 21 of the 28 in the ceftazidime group and 18 of the 25 in the amikacin group (Table 4). The 14 persisted (in 9 patients) or relapsed (in 5) infections included 5 Escherichia coli, 3 Pseudomonas aeruginosa, 2 Enterobacter cloacae and 4 other organisms: Proteus mirabilis, Serratia marcescens, Klebsiella pneumoniae and Citrobacter freundii (one patient with each). Two patients m the aztreonam group and one in each of the ceftazidime and amikacin groups were considered as failures due to reinfection with: Streptococcus faecalis and Enterobacter cloacae in group A, Streptococcus faecalis in group B and Escherichia coli in group C. Superinfection occurred in 3 patients (one in each group) due to: Pseudomonas aeruginosa in group A, Streptococcus faecalis in group B and Staphylococcus epidermidis in group C.
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ISSN: 1120-009X (Print) 1973-9478 (Online) Journal homepage: http://www.tandfonline.com/loi/yjoc20
A Comparative Study on Aztreonam, Ceftazidime and Amikacin in the Treatment of Complicated Urinary Tract Infections M.D. Melekos, A. Skoutelis, C. Chryssanthopoulos & H.P. Bassaris To cite this article: M.D. Melekos, A. Skoutelis, C. Chryssanthopoulos & H.P. Bassaris (1991) A Comparative Study on Aztreonam, Ceftazidime and Amikacin in the Treatment of Complicated Urinary Tract Infections, Journal of Chemotherapy, 3:6, 376-382, DOI: 10.1080/1120009X.1991.11739124 To link to this article: http://dx.doi.org/10.1080/1120009X.1991.11739124
Published online: 15 Jul 2016.
Submit your article to this journal
Article views: 1
View related articles
Citing articles: 1 View citing articles
Full Terms & Conditions of access and use can be found at http://www.tandfonline.com/action/journalInformation?journalCode=yjoc20 Download by: [Australian Catholic University]
Date: 25 August 2017, At: 09:51
Downloaded by [Australian Catholic University] at 09:51 25 August 2017
Journal of Chemotherapy
A Comparative Study on Aztreonam, Ceftazidime and Amikacin in the Treatment of Complicated Urinary Tract Infections
Vol. 3 - n. 6 (376-382) - 1991
drugs were well tolerated. It is concluded that aztreonam, ceftazidime and amikacin are equally effective and safe for the treatment of complicated urinary ttact infections due to susceptible organisms. Key words: Aztreonam, ceftazidime, amikacin, urinary tract infections, complicated
INTRODUCTION
M.D. MELEKOS * - A. SKOUTELIS ** C. CHRYSSANTHOPOULOS ** H.P. BASSARIS **
Summary ---------------------- -------In a prospective, randomized trial, aztreonam (1 g intra· venously or inttamuscularly, twice daily) was compared with ceftazidime (1 g intravenously or intramuscularly, twice daily) and amikacin (500 mg intravenously or intramuscularly, twice daily) in 76 patients aged 24 to 84 years (mean, 59.7 years) with complicated urinary ttact infections. Initial pathogens included Escherichia coli (4 7. 5%), Pseudomonas aeruginosa (22.5%), Klebsiella spp. (9%), Proteus spp. (7.5%) and Enterobacter spp (6%). In four patients initial urine cultures yielded more than one organism. All pathogens were sensitive to the three study drugs. Including performance of 4- to 6week follow-up cultures, eradication of the pathogens occurred in 72% of patients treated with aztteonam, in 74% of those tteated with ceftazidime and in 71% treated with amikacin (p>0.05). Clinical success was observed in 84% of patients treated with aztreonam, in 82% of those treated with ceftazidime and in 85% treated with amikacin (p>0.05). All
Urinary tract infections are among the most common community and hospital acquired infections. In hospitalized patients or in patients with major structural or/and functional abnormalities of the urinary tract, Escherichia coli, Pseudomonas aeruginosa, Klebsiella species, Enterobacter species and other gram-negative aerobic bacilli are the usual pathogens 1 • 2 • In vitro studies have indicated that amikacin, ceftazidime and aztreonam are active against these organisms and also have favorable pharmacokinetics which make them suitable for the treatment of complicated urinary tract infections l13. In this prospective randomized trial we compared the efficacy and safety of ceftazidime, aztreonam and amikacin for the treatment of complicated urinary tract infections due to susceptible organisms. As far as we know, a study comparing these three antimicrobial agents has not previously been published.
PATIENTS AND METHODS Departments of Urology * and Medicine, Division of Infectious Diseases **, University of Parras School of Medicine, Rio-Patras, Greece. Correspondent: Michael D . Melekos, M .D., Agios Georgios Rio, 60 Iroon Polytechniou Street, 26500 Rio, Parras, G reece © Edizioni Ri viste Scientifiche - Firenze
Ninety-six patients (79 men and 17 women) with complicated urinary tract infections were enrolled in a prospective, non-blinded, randomized comparative trial. Eighty-two were evalISS N 1120-009X
377
Downloaded by [Australian Catholic University] at 09:51 25 August 2017
A COMPARATIVE STUDY ON AZTREONAM, CEFTAZIDIME AND AMIKACIN, ETC .
uable for safety and 76 (64 men and 12 women) were evaluable for efficacy. Twenty subjects were excluded because of lack of urine culture specimens during or after therapy, as well as of incorrectly taking of medication. Complicated urinary tract infection was defined as a bacterial count of at least 10 5 colony-forming units (cfu/ml) of urine in the presence of structural or functional abnormality of the urinary tract, accompanied by typical signs and symptoms of infection. Asymptomatic patients were eligible provided they had two pretreatment urine culture specimens yielding positive results for the same species of bacteria. Patients were randomly assigned into 3 groups depending on the antimicrobial agent which was administered intramuscularly or intravenously for 7 consecutive days: Group A included patients (n = 25) who
TABLE
received 1 g aztreonam (Squibb) every 12 hours, group B patients (n = 27) received 1 g ceftazidime (Glaxo) twice daily, and group C included patients (n = 24) who received 500 mg amikacin, (Bristol-Myers Squibb) twice daily. All patients gave informed consent and were required to have a pretreatment urine culture specimen with infecting organisms sensitive to all three antibiotics within 48 hours of the start of therapy. All patient-groups were comparable with respect to age, weight and concomitant underlying disorders of the urinary tract (Table 1). Patients with a history of allergy to cephalosporins and immediate hypersensitivity to penicillins or aminoglycosides were excluded from the study as well as subjects who had received antibiotics in the 5 days prior to enrollment. Patients with bacteremia or suspected bac-
1 - Characteristics of patient population and their underlying condition. Aztreonam (n = 25)
Ceftazidime (n = 27)
Amikacin (n = 24)
58.8:1: 14.8 34-81
59.4:1: 16.8 24-84.
60 .7:1:13.8 30-80
4 21
4 23
4 20
73.6±8.6 56-95
74 .5:1: 10.4 59-108
71.7±8.1 58-90
Age (years) Mean±SD Range Sex Female Male Weight (kg) Mean±SD Range Underlying abnormalities Benign prostatic hypertrophy Carcinoma of the prostate Bladder cancer Epididymitis Urethral stricture Urethral diverticulum Neurogenic bladder Ileal conduit Cutaneous ureterostomy Cutaneous nephrostomy Suprapubic catheter Vesical calculi Renal calculi Ureteral calculi Ureteric reflux Prostatitis Bladder neck contracture Chronic pyelonephritis Totals
7 3 3 1 2 0 1 0 1 0 0 1 3 0 0
25
9
6
2
2
4
3
1 1 0 1 0
1 0 2 0 2 0 2
2 1 0 0
0 1 0
27
24
1
Downloaded by [Australian Catholic University] at 09:51 25 August 2017
378
M.D. MELEKOS - A. SKOUTELIS - C. CHRYSSANTHOPOULOS - H.P. BASSARIS
teremia, as well as patients with significant unrelieved obstruction in the kidneys were not eligible, nor were those with significant liver disease or decreased renal function, determined by a serum creatinine of greater than 3 mg/dl. Pregnant or lactating women were also excluded. The safety of the drugs was assessed by monitoring renal, hepatic and hemopoietic function. Bacteriological efficacy was monitored by urine cultures 3 to 4 days after initiation of therapy, at the end of therapy, and at 5 to 9 days following therapy, while each patient with a bacteriologic response of eradication at the infection site returned for a follow-up evaluation 4 to 6 weeks after cessation of therapy. Clinical response und urine cultures were used to assess the therapeutic effects of the antibiotics, using the following criteria: A) Assessment of clinical response: 1) Resolution= disappearance of all symptoms and signs of urinary tract infection at day 5 to 9 following treatment; 2) Improvement= marked or moderate reduction in the severity and/or number of signs and symptoms 5 to 9 days after cessation of therapy, and 3) Failure= insufficient lessening of signs and symptoms to qualify as improvement. B) Assessment of bacteriologic response: 1) Eradication= negative culture during therapy, at the end of therapy, 5 to 9 days following therapy and 4 to 6 weeks after cessation of therapy; 2) Persistence= pretreatment infecting organism present during therapy, at the end of therapy and on days 5 to 9 following therapy; 3) Relapse = negative culture during therapy, at the end of therapy and 5 to 9 days following therapy, but positive for the pretreatment organism (with 2: 10s cfu/ml) at (or before) 4 to 6 weeks after cessation of therapy; 4) Reinfection= elimination of the pretreatment pathogen and the occurrence of a different organism (of 2: 10s cfu/ml) during, at the termination or following therapy, and 5) Superinfection= 2: 10s cfu/ml of the original organism plus a new pathogen at any time during or after therapy. After cessation of therapy, each patient with a bacteriologic response of eradication at the infection site returned in 5 to 9 days for evaluation, and the responders (with continuously negative cultures at the above period) returned again for a follow-up evaluation 4 -to 6 weeks after therapy.
Statistics. Statistical significance was determined by the use of the chi-square analysis, Student's t-test and Fisher's exact test, whenever expected frequencies were less than about 5. RESULTS
The causative pathogens in each patientgroup are shown in Table 2. Four patients had more than one type of organism (mixed infection). Escherichia coli was the organism isolated most frequently in all3 groups (in 47.5% of the total population). Pseudomonas aeruginosa (22.5%), Klebsiella species (9%), Proteus species (7.5%) and Enterobacter species (6%) were isolated in a lower incidence in each group . Fifty-six per cent (n= 14) of the aztreonamtreated patients, 63% (n= 16) of the ceftazidime and 54% (n = 13) of the amikacin had an operative procedure during or in the immediate proximity to study treatment. Forty-four per cent of the patients in group A, 44% of those in group B and 50% of the patients in group C had an indwelling catheter for 3 or more days during therapy. In all cases, however, in which an indwelling catheter was used, the latter was removed at least 24 hours before termination of study drug treatment. The therapeutic results were determined ac-
TABLE 2 -
Distribution of urine infecting organisms. Aztreonam
Escherichia coli Pseudomonas aeruginosa Proteus mirabilis Proteus vulgaris Klebsiella pneumoniae Klebsiella oxytoca Enterobacter cloacae En terobacter aerogenes Serratia marcescens Morganella morganil Providencia stuartii K. pneumonlae +E. cloacae E.coll + Citrobacter freundii Ps. aeruglnosa + P. mirabilis E. coli+ Ps. aeruginosa
12
Totals
27
5
Ceftazidime Amikacin 13 6
11
5
2
1 2
1
2
2 2
1 1
28
25
379
A COMPARATIVE STUDY ON AZTREONAM, CEFfAZIDIME AND AMIKACIN, ETC.
cording to clinical and urine bacteriologic response and are shown in Tables 3 and 4. Clinical response: In the group of patients treated with aztreonam 16 (84%) had clinical resolution of symptoms and signs at 5 to 9 days following therapy while 2 (10.5%) failed to respond. Six were not evaluable since they were either asymptomatic prior to treatment or had TABLE
3 - Clinical and bacteriologic response.
Aztreonam (n = 25) No.( % )
Downloaded by [Australian Catholic University] at 09:51 25 August 2017
symptoms before and after treatment due to nephrolithiasis, post-irradiation or lower urinary tract obstruction. In the ceftazidime-treated group the rates of resolution and persistence of symptoms were 82% and 9%, respectively, while in the amikacin group 85% and 10%, respectively (chi-square test, p > 0.05). Overall, 15 patients out of 76 in the present study were
Ceftazidime (n = 27) No.( % )
Am ikacin (n = 24) No.(%)
Clinical response at day 5 to 9 after cessation of therapy Resolution * Improvement Failure
16 (84.2) 1 (5.3) 2 (10.5)
18 (81.8) 2 (9 .1) 2 (9.1)
17 (85) 1 (5) 2 (10)
Tot a I
19
22
20
6
5
4
Not evaluable Bacteriologic response Day 3 of therapy Eradication * Persistence Reinfection/Superinfection
20 (80) 5 (20) 0
23 (85.2) 4 (14.8) 0
20 (83.3) 4 (16.7) 0
Tot a I
25
27
24
Eradication * Persistence Reinfection/Superinfection
22 (88) 2 (8) 1 (4)
23 (85 .2) 2 (7.4) 2 (7.4)
21 (87 .5) 2 (8.3) 1 (4.2)
Tot a I
25
27
24
20 (90.9) 1 (4.6) 1 (4.5)
22 (95 .7) 1 (4.3) 0
19 (90 .5) 1 (4 .8) 1 (4.7)
22
23
21
Eradication * Relapse Reinfection/Superinfection
18 (90) 1 (5) 1 (5)
20 (90.9) 2 (9.1) 0
17 (98 .5) 2 (10.5) 0
Tot a I
20
22
19
Eradication * Persistence Relapse Reinfection Superinfection
18 (72) 3 (12) 1 (4) 2 (8) (4)
20 (74.1) 3 (11.1) 2 (7 .4) (3.7) (3 .7)
17 (70 .8) 3 (12 .5) 2 (8.3) 1 (4.2) 1 (4.2)
Tot a I
25
27
24
End of therapy
5 to 9 days after therapy Eradication * Persistence Reinfection/Superinfection Tot a I 4 to 6-week follow-up
Overall bacteriologic response
* There were no statistically significant differences among groups (chi-square test, p> 0.05) .
Downloaded by [Australian Catholic University] at 09:51 25 August 2017
380
M.D. MELEKOS • A. SKOUTEUS • C. CHRYSSANTHOPOULOS • H .P. BASSARlS
not evaluable for clinical response due to pretreatment lack of signs and symptoms or the existence of symptoms before and after treatment because of nephrolithiasis, cancer, postirradiation or lower urinary tract obstruction. Bacteriologic response: At the end of therapy, the bacteriologic response at the site of urinary tract infection was eradication for 88% of the patients in the aztreonam group, 85% in the ceftazidime and 87.5% in the amikacin. Among the 66 patients who initially responded successfully to therapy, 91% of those in the aztreonam group, 96% in the ceftazidime and 90% in the amikacin group demonstrated negative cultures. When patients with bacteriologic responses of eradication at the above period returned again for a follow-up evaluation 4 to 6 weeks after treatment, the responses were graded as eradication at 18 sites m the aztreonam group (90%), at 20 sites (91%) in the ceftazidime and at 17 sites (89%) in the amikacin group. Overall, that is including culture evaluations at the end of therapy, 5 to 9 days after cessation of therapy and at 4 to 6-week follow-up, the bacteriologic response was eradication for 18 patients (72%) in the aztreonam group, for 20 patients (74%) in the ceftazidime and for 17 patients (71%) in the amikacin group (Table 3). All the above differences were remarkably comparable (chi-square test, p > 0.05). The bacteriologic responses for each causative organism correlated well in those for each site of infection, i.e . 20 of the 27 pathogens in the aztreonam group were eradicated, compared to 21 of the 28 in the ceftazidime group and 18 of the 25 in the amikacin group (Table 4). The 14 persisted (in 9 patients) or relapsed (in 5) infections included 5 Escherichia coli, 3 Pseudomonas aeruginosa, 2 Enterobacter cloacae and 4 other organisms: Proteus mirabilis, Serratia marcescens, Klebsiella pneumoniae and Citrobacter freundii (one patient with each). Two patients m the aztreonam group and one in each of the ceftazidime and amikacin groups were considered as failures due to reinfection with: Streptococcus faecalis and Enterobacter cloacae in group A, Streptococcus faecalis in group B and Escherichia coli in group C. Superinfection occurred in 3 patients (one in each group) due to: Pseudomonas aeruginosa in group A, Streptococcus faecalis in group B and Staphylococcus epidermidis in group C.
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