Journal of Hospital Infection (I992) 22 (Supplement A), 69-74
Comparative clinical and m i c r o b i o l o g i c a l study of a m o x y c i l l i n - c l a v u l a n i c acid and ciprofloxacin in acute purulent exacerbations of chronic bronchitis D. L e g n a n i , V. M. L o m b a r d o , G. G. N e g r e t t o , G. B e g h i a n d O. C a r a t o z z o l o
Institute of Respiratory Diseases, University of Milan, Milan, Italy Summary: In a retrospective study, the clinical and microbiological efficacy of amoxycillin-clavulanic acid and ciprofloxacin were evaluated in outpatients observed within the previous year who were affected by acute purulent exacerbations of chronic bronchitis. Of the 95 patients included in the trial, 50 received amoxycillin 875 mg-clavulanic acid 125 mg 8-hourly for 10 days and 45 received ciprofloxacin 500 mg 12-hourly before meals for 10 days. Of the amoxycillin-clavulanic acid-treated patients, 90% showed clear clinical improvement and in 10% treatment failed. In the ciprofloxacin group, 75.5% of patients showed improvement and in 24.5% treatment failed. All pathogens isolated prior to therapy were susceptible to the antibiotic used for therapy. At the end of treatment, in the amoxycitlin-clavulanic acid-treated group, 84% of strains were eradicated and 8% persisted; others were superinfections. In the ciprofloxacin group, 57"7% of strains were eradicated, 26.6% persisted and 15-5% were superinfections. No clinically significant side effects were observed in either group. Overall, amoxycillin-clavulanic acid demonstrated superior clinical and microbiological efficacy to ciprofloxacin, although this might be attributable to the higher proportion of aerobic Gram-negative pathogens in the ciprofloxacin group.
Keywords: Chronic bronchitis; antimicrobial therapy. Introduction
In bacterial exacerbations of chronic bronchitis, characterized by an increase in cough, d y s p n o e a and the quantity and purulence of the s p u t u m , the principal isolated pathogens are usually Haemophilus influenzae and Streptococcus pneumoniae, and less frequently Moraxella catarrhalis, Staphylococcus aureus, Klebsiella pneumoniae and Pseudomonas aeruginosa. 1,2 T h e incidence of the various isolated pathogens during a bacterial exacerbation of chronic bronchitis varies greatly for different case histories. This may in part be due to the different geographical distribution of the various pathogens but most probably it is due to the m e t h o d used to obtain s p u t u m samples, the treatment of the samples thereafter, and the care taken by the assigned microbiology laboratories to search for the various Correspondence to: Dr D. Legnani, Institute of Respiratory Diseases, University of Milan, Milan, Italy. 0195-6701/92/0A0069 + 06 $ 0 8 00]0
@ 1992 "rht: H~,spital Infectir
69
%t,t lely
70
D. Legnani e t al.
pathogens. 2 T h e currently available antibiotics, macrolides, ~-lactams, tetracyclines and quinolones, which have a broad s p e c t r u m of action, are usually e m p l o y e d in the treatment of such bacterial infections with satisfactory results. However, there is a continual evolution of bacterial resistance with wide geographical differences; 3 although it is secondary to the use of certain antibiotics instead of others, it does cause difficulty in choosing the correct antibiotic during episodes of bacterial exacerbation of chronic bronchitis. ~7 In our study we have retrospectively evaluated the clinical and microbiological efficacy of two antibiotics whose characteristics--spectrum of action, non-susceptibility to the c o m m o n bacterial resistance mechanisms, favourable pharmacokinetics, manageability and tolerability--represent first choice drugs in the treatment of exacerbations of chronic bronchitis. Amoxycillin has for years been regarded as the first choice antibiotic for treating exacerbations of chronic bronchitis, s'9 b u t its efficacy has progressively diminished because of the increasing incidence of ~-lactamase-producing pathogens. T h e association of clavulanic acid, which is a potent [3-1actamase inhibitor, with amoxycillin has enhanced amoxycillin's efficacy and has widened its bactericidal spectrum of action, u>14 Ciprofloxacin, a newer fluoroquinolone, presents a spectrum of action which includes difficult pathogens and it is not, as yet, affected by significant drug resistance, ls'16 Schmidt et a l J 7 compared the clinical and microbiological efficacy of these two antibiotics in the treatment of chronic bronchitis. T h e i r study demonstrated the superior efficacy of amoxycillin-clavulanic acid against Gram-positive organisms compared with ciprofloxacin, which was more effective against Gram-negative organisms. Materials and methods
All outpatients observed as being affected by bacterial exacerbations of chronic bronchitis were subjected to standard diagnostic investigations consisting of a chest X-ray (to exclude concomitant acute or chronic disease), biochemical laboratory examinations (to evaluate indices of inflammation, renal and hepatic function), trials of respiratory function, arterial blood gas analysis, as well as bacteriological examination of s p u t u m (by positioning five orthodontal swabs at the opening of salivary gland ducts after a washing of the oral cavity with sterile saline solution to avoid oral contamination). S p u t u m samples were immediately delivered to the microbiology laboratory for culture and standard antibiotic susceptibility tests. 18 Only those s p u t u m samples selected by the Bartlett m e t h o d were analysed. 19 Antibiotic therapy was started immediately and subsequently maintained or modified, on the basis of sensitivity results. T h e treatment period, regardless of the antibiotic chosen, was not less than 8 days.
A m o x y c i l l i n - c l a v u l a n i c acid and ciprofloxacin in chronic bronchitis
71
At the end of treatment, 48 h after the last antibiotic administration, patients were subjected to biochemical investigations, trials of respiratory function, arterial blood gas analysis as well as bacteriological examination of sputum. From retrospective analyses of all patients monitored during the past year, all those who had received ciprofloxacin or amoxycillin-clavulanic acid were selected. Patients were excluded where there was a need to modify the dosage of bronchodilators and anti-inflammatory agents usually taken or if antibiotic therapy had been administered during the 2 weeks preceding the exacerbation. No patients were taking H2-receptor antagonist drugs concomitantly. Data was obtained from 95 patients. T h e clinical characteristics of the patients were similar: 50 patients, 33 males and 17 females b e t w e e n the ages of 27 and 82 years (average age being 58"8) received amoxycillin-clavulanic acid (875 m g of amoxycillin and 125 mg of clavulanic acid) 8-hourly for 10 days; while 45 patients, 31 males and 14 females b e t w e e n the ages of 28 and 80 years (average age being 58) received 500 mg ciprofloxacin (taken on an e m p t y stomach, 30 min before meals) 12-hourly for 10 days. At the end of the antibiotic treatment, patients were considered cured if they demonstrated an i m p r o v e m e n t of cough, s p u t u m production, purulence and chest examination, and eradication of the pathogen responsible for the exacerbation. Patients were considered improved if there was clinical response even if there was a reappearance of pathogens in the s p u t u m sample at the end of therapy.
Results
Clinical findings A m o n g the 50 patients treated with amoxycillin-clavulanic acid, 32 patients (64%) were cured, 13 patients (26%) showed improvement, and in five cases (10%) treatment proved to be ineffective. A m o n g the 45 patients treated with ciprofloxacin, 26 (57"7%) were cured, eight (17"7%) showed i m p r o v e m e n t and in 11 cases (24"4%) treatment proved to be ineffective (Table I).
Microbiological findings In the 50 patients treated with amoxycillin-clavulanic acid, 69 organisms were isolated (59 Gram-positive and 10 Gram-negative) (Table II). Eradication of the organism from s p u t u m occurred at the end of treatment in 42 patients (84%); in three patients (6%) elimination of the initially isolated pathogen with a superinfection sustained by a second pathogen occurred; in four patients (8%), persistence of the initially isolated pathogen occurred; and in one patient a clear reduction of colony count of the isolated pathogenic species occurred. Mixed pathogens were isolated from 18
72
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Table I. Clinical results for amoxycillin-clavulanic acid vs. ciprofloxacin therapy
Cured* Improved Failed Clinical success (cured + improved)
Amoxycillin-clavulanic acid (total patients: 50)
Ciprofloxacin (total patients: 45)
32 (64%) 13 (26%) 5 (10%) 90%
26 (57"7%) 8 (177%) 11 (24.4%) 75.4%
* For definitions see Methods.
patients before treatment and three patients after treatment. At the end of t r e a t m e n t , t h e t o t a l n u m b e r o f i s o l a t e d p a t h o g e n s w a s 12 ( s i x G r a m - p o s i t i v e o r g a n i s m s a n d six G r a m - n e g a t i v e o r g a n i s m s ) . I n t h e 45 p a t i e n t s t r e a t e d w i t h c i p r o f l o x a c i n , 73 o r g a n i s m s w e r e i s o l a t e d (42 G r a m - p o s i t i v e o r g a n i s m s a n d 31 G r a m - n e g a t i v e o r g a n i s m s ) ( T a b l e I I ) . B a c t e r i a l e r a d i c a t i o n at t h e e n d o f t r e a t m e n t w a s a c h i e v e d in 26 p a t i e n t s
Table II. Isolated pathogens before and after therapy with amoxycillin clavulanic acid and before and after therapy with ciprofloxacin Before
After
No.
%
59 32 11
6 2 1
8.7 2.9 1.4
8 7
85.5 46-4 15.9 1.4 11-6 10.1
1 1
1.4 1.4
10 4 3 2
14.5 5.8 4.3 2-9
6 2 2 1
8.7 2.9 2.9 1-4
1
1-4
1
1.4
Ciprofloxacin Gram-positive organisms Streptococcus pneumoniae Staphylococcus aureus Staphylococcus epidermidis Enterococcus spp. Other Gram-positive
42 12 14 2 10 4
57.5 16.4 19.2 2.7 13.7 5.5
18 9 6
24-7 12-3 8.2
3
4.1
Gram-negative organisms Haemophilus influenzae Pseudomonas aeruginosa Escherichia coli Mcinetobacter spp. Other Gram-negative
31 13 5 6 2 5
42-5 17.8 6.8 8.2 2-7 6-8
10 1 5 1 2 1
13.7 1.4 6.8 1.4 2.7 1-4
Amoxycillin-clavulanic acid Gram-positive organisms Streptococcus pneumoniae Staphylococcus aureus Staphylococcus epidermidis Enterococcus spp. Other Gram-positive Gram-negative organisms Haemophilus influenzae Klebsiella pneumoniae Escherichia coh" Other Gram-negative
1
No.
%
-
A m o x y c i l l i n - c l a v u l a n i c acid and ciprofloxacin in chronic bronchitis
73
(57"7%), persistence occurred in 12 (26"6%) of the patients and superinfection occurred in seven (15"5%) of the patients. In 25 patients, the infection was sustained by other organisms. At the end of treatment, 48 h after the last dose of antibiotic, the total n u m b e r of organisms isolated was 28 (18 Gram-positive and 10 Gram-negative). N o n e of the isolated pathogens at the beginning of treatment was resistant to the antibiotics studied. At the end of treatment, none of the persistent pathogens isolated from patients that had received either antibiotic had become resistant. Discussion
It is difficult to evaluate the effectiveness of an antibiotic on the basis of a small n u m b e r of treated cases, since n u m e r o u s variables may lead to incorrect conclusions. Evaluation of our data appears to show amoxycillin-clavulanic acid to be more efficacious from both a clinical and a microbiological point of view compared with ciprofloxacin, even though the latter has a broader s p e c t r u m of action. However, there were appreciable differences between the pathogens isolated in the two groups. Even though both antibiotics have a broad spectrum of action, it is known that ciprofloxacin is not highly active against S. pneumoniae, while amoxycillin-clavulanic acid has no activity against Pseudomonas spp. In this study, only two of 32 S. pneumoniae persisted after amoxycillin clavulanic acid, but nine of 12 after ciprofloxacin. Therefore, the difference in the observed results in the two groups of patients m a y be due to the fact that in the patients treated with amoxycillin-clavulanic acid, a large n u m b e r of Gram-positive pathogens was encountered (59 of the 69 isolated; 85"5%); the Gram-negatives represented 10 out of 69; 14"5%. In the patients treated with ciprofloxacin, there was lower percentage of Gram-positive (42 out of 73; 57"5%) and higher of G r a m - n e g a t i v e pathogens (31 out of 73; 42"5%). T h e percentage of Gram-positive bacterial pathogens eradicated from s p u t u m was 90"2% for amoxycillin-clavulanic acid and 40% for Gram-negative organisms. Ciprofloxacin eradicated 57"3 % of Gram-positive organisms and 67-8% of G r a m - n e g a t i v e organisms. T h i s study shows that ciprofloxacin has greater activity against Gram-negative organisms than Gram-positives. T h e different distribution of bacterial species in the two groups under study may, in part, explain the different clinical efficacy b e t w e e n the two antibiotics in this study. Considering the wide spectrum of action of both amoxycillin-clavulanic acid and ciprofloxacin, which includes most of those pathogens usually encountered in the course of a bacterial exacerbation of chronic bronchitis, coupled with the absence of side effects and their manageability, these two drugs should both be considered suitable for the first line empirical treatment of such infections. It is perhaps not surprising that neither agent
74
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was u n i f o r m l y s u c c e s s f u l i n p a t i e n t s w i t h u n d e r l y i n g tract disease.
chronic respiratory
This study was supported by a grant from SmithKline Beecham.
References 1. Simon C, Stille W. Antibiotika Therapie in Klinik und Praxis. 7th edn. Stuttgart, New York: Schattauer-Verlag. 2. Krasemann C, Koch RC. Microorganismi patogeni nella bronchite cronica. In: Fass RJ, Ed. Simposium Lausanne, June 1990. 3. Ling J, Chau PY, Leung YK et al. Antibiotic susceptibility of pneumococci and Haemophilus influenzae isolated from patients with acute exacerbation of chronic bronchitis; prevalence of tetracycline-resistant strains in Hong Kong. J Infect, 1983; 6: 33 37. 4. Philpott-Howard J, Williams JD. Increase in antibiotic resistance in Haemophilus influenzae in the United Kingdom since 1977: report of a study group. Br M e d J , 1982; 284: 1597-1604. 5. Jorgensen JH, Doern GV, Thornsberry PC et al. National prevalence of antimicrobial resistance in Haemophilus influenzae: a collaborative study. Communication at the Annual Meeting of the American Society for Microbiology; 5 March 1985. 6. Nelson JD. The increasing frequency of [3-1actamase-producing Haemophilus influenzae. J Am Med Assoc, 1980; 244: 239. 7. May JR, Davies J. Resistance of Haemophilus influenzae to trimethoprin. Br Med J, 1972; 3:376 379. 8. May JR, Ingold A. Amoxycillin in the treatment of chronic non-tuberculous bronchial infections. Br J Dis Chest, 1972; 66:185-189. 9. Burgi H. Klinisch-experimentelle. Erfahrungen mit amoxycillin bei chronischer bronchitis. Chemotherapy, 1973; 19 (Supp.): 19 25. 10. Beeuwks H, Rutgers VH. A combination of amoxycillin and clavulanic acid in the treatment of respiratory infection caused by amoxycillin-resistant Haemophilus influenzae. Infection 1981; 9: 244-248. 11. Pines A, Raafat H, Khorasani MH et al. Experience with amoxycillin plus potassium clavulanate in lower respiratory tract infections. In: Robinson GN, Watson A, Eds. Proceedings of the first Augmentin ( Clavulanate-potentiated Amoxycillin ) Symposium, 3-4 July 1980, 277-282. Amsterdam: Excerpta Medica 1980: 277-282. 12. Methar S. Respiratory tract infections caused by [3-1actamase-producing organisms treated with Augmentin. In: Robinson GN, Watson A, Eds. Proceedings of the first Augmentin ( Clavulanate-Potentiated Amoxycillin ) Symposium, 3-4 July 1980 Amsterdam: Excerpta Medica 1980; 259 264. 13. Wallace RJ Jr, Steele LC, Brooks DL et al. Amoxycillin/clavulanicacid in the treatment of lower respiratory tract infections caused by ~-lactamase-positive Haemophilus influenzae and Branhamella catarrhalis. Antimicrob Agents Chemother, 1985; 27: 912-915. 14. Maesen FP, Davies BI, Baur C et al. Amoxycillin/clavulanate in exacerbations of chronic bronchitis. J Antimicrob Chemother, 1987; 19: 373-383. 15. Neu HC. Ciprofloxacin; a major advance in quinolone chemotherapy. A m J M e d , 1987; 82: (Suppl. 4A): 1 - 11. 16. Hooper DC, Wolfson JS, Ng EY et al. Mechanisms of action and resistance to ciprofloxacin. Am J Med, 1987; 82 (Suppl. 4A): 12-20. 17. Schmidt EW, Zimmermann I, Ritzerfeld W e t al. Controlled prospective study of oral amoxycillin/clavulanate versus ciprofloxacin in acute exacerbations of chronic bronchitis. J Antimicrob Chemother, 1989; 24 (Suppl. B): 185 193. 18. Bauer AW, Kirby WMM, Sherris JC et al. Antibiotic susceptibility testing by standardized single desk method. Am J Clin Pathol, 1966; 45: 493496. 19. Bartlett RC. Medical Microbiology: Quality, Cost and Clinical Relevance. New York: J. Wiley & Sons 1974.
Comparative clinical and m i c r o b i o l o g i c a l study of a m o x y c i l l i n - c l a v u l a n i c acid and ciprofloxacin in acute purulent exacerbations of chronic bronchitis D. L e g n a n i , V. M. L o m b a r d o , G. G. N e g r e t t o , G. B e g h i a n d O. C a r a t o z z o l o
Institute of Respiratory Diseases, University of Milan, Milan, Italy Summary: In a retrospective study, the clinical and microbiological efficacy of amoxycillin-clavulanic acid and ciprofloxacin were evaluated in outpatients observed within the previous year who were affected by acute purulent exacerbations of chronic bronchitis. Of the 95 patients included in the trial, 50 received amoxycillin 875 mg-clavulanic acid 125 mg 8-hourly for 10 days and 45 received ciprofloxacin 500 mg 12-hourly before meals for 10 days. Of the amoxycillin-clavulanic acid-treated patients, 90% showed clear clinical improvement and in 10% treatment failed. In the ciprofloxacin group, 75.5% of patients showed improvement and in 24.5% treatment failed. All pathogens isolated prior to therapy were susceptible to the antibiotic used for therapy. At the end of treatment, in the amoxycitlin-clavulanic acid-treated group, 84% of strains were eradicated and 8% persisted; others were superinfections. In the ciprofloxacin group, 57"7% of strains were eradicated, 26.6% persisted and 15-5% were superinfections. No clinically significant side effects were observed in either group. Overall, amoxycillin-clavulanic acid demonstrated superior clinical and microbiological efficacy to ciprofloxacin, although this might be attributable to the higher proportion of aerobic Gram-negative pathogens in the ciprofloxacin group.
Keywords: Chronic bronchitis; antimicrobial therapy. Introduction
In bacterial exacerbations of chronic bronchitis, characterized by an increase in cough, d y s p n o e a and the quantity and purulence of the s p u t u m , the principal isolated pathogens are usually Haemophilus influenzae and Streptococcus pneumoniae, and less frequently Moraxella catarrhalis, Staphylococcus aureus, Klebsiella pneumoniae and Pseudomonas aeruginosa. 1,2 T h e incidence of the various isolated pathogens during a bacterial exacerbation of chronic bronchitis varies greatly for different case histories. This may in part be due to the different geographical distribution of the various pathogens but most probably it is due to the m e t h o d used to obtain s p u t u m samples, the treatment of the samples thereafter, and the care taken by the assigned microbiology laboratories to search for the various Correspondence to: Dr D. Legnani, Institute of Respiratory Diseases, University of Milan, Milan, Italy. 0195-6701/92/0A0069 + 06 $ 0 8 00]0
@ 1992 "rht: H~,spital Infectir
69
%t,t lely
70
D. Legnani e t al.
pathogens. 2 T h e currently available antibiotics, macrolides, ~-lactams, tetracyclines and quinolones, which have a broad s p e c t r u m of action, are usually e m p l o y e d in the treatment of such bacterial infections with satisfactory results. However, there is a continual evolution of bacterial resistance with wide geographical differences; 3 although it is secondary to the use of certain antibiotics instead of others, it does cause difficulty in choosing the correct antibiotic during episodes of bacterial exacerbation of chronic bronchitis. ~7 In our study we have retrospectively evaluated the clinical and microbiological efficacy of two antibiotics whose characteristics--spectrum of action, non-susceptibility to the c o m m o n bacterial resistance mechanisms, favourable pharmacokinetics, manageability and tolerability--represent first choice drugs in the treatment of exacerbations of chronic bronchitis. Amoxycillin has for years been regarded as the first choice antibiotic for treating exacerbations of chronic bronchitis, s'9 b u t its efficacy has progressively diminished because of the increasing incidence of ~-lactamase-producing pathogens. T h e association of clavulanic acid, which is a potent [3-1actamase inhibitor, with amoxycillin has enhanced amoxycillin's efficacy and has widened its bactericidal spectrum of action, u>14 Ciprofloxacin, a newer fluoroquinolone, presents a spectrum of action which includes difficult pathogens and it is not, as yet, affected by significant drug resistance, ls'16 Schmidt et a l J 7 compared the clinical and microbiological efficacy of these two antibiotics in the treatment of chronic bronchitis. T h e i r study demonstrated the superior efficacy of amoxycillin-clavulanic acid against Gram-positive organisms compared with ciprofloxacin, which was more effective against Gram-negative organisms. Materials and methods
All outpatients observed as being affected by bacterial exacerbations of chronic bronchitis were subjected to standard diagnostic investigations consisting of a chest X-ray (to exclude concomitant acute or chronic disease), biochemical laboratory examinations (to evaluate indices of inflammation, renal and hepatic function), trials of respiratory function, arterial blood gas analysis, as well as bacteriological examination of s p u t u m (by positioning five orthodontal swabs at the opening of salivary gland ducts after a washing of the oral cavity with sterile saline solution to avoid oral contamination). S p u t u m samples were immediately delivered to the microbiology laboratory for culture and standard antibiotic susceptibility tests. 18 Only those s p u t u m samples selected by the Bartlett m e t h o d were analysed. 19 Antibiotic therapy was started immediately and subsequently maintained or modified, on the basis of sensitivity results. T h e treatment period, regardless of the antibiotic chosen, was not less than 8 days.
A m o x y c i l l i n - c l a v u l a n i c acid and ciprofloxacin in chronic bronchitis
71
At the end of treatment, 48 h after the last antibiotic administration, patients were subjected to biochemical investigations, trials of respiratory function, arterial blood gas analysis as well as bacteriological examination of sputum. From retrospective analyses of all patients monitored during the past year, all those who had received ciprofloxacin or amoxycillin-clavulanic acid were selected. Patients were excluded where there was a need to modify the dosage of bronchodilators and anti-inflammatory agents usually taken or if antibiotic therapy had been administered during the 2 weeks preceding the exacerbation. No patients were taking H2-receptor antagonist drugs concomitantly. Data was obtained from 95 patients. T h e clinical characteristics of the patients were similar: 50 patients, 33 males and 17 females b e t w e e n the ages of 27 and 82 years (average age being 58"8) received amoxycillin-clavulanic acid (875 m g of amoxycillin and 125 mg of clavulanic acid) 8-hourly for 10 days; while 45 patients, 31 males and 14 females b e t w e e n the ages of 28 and 80 years (average age being 58) received 500 mg ciprofloxacin (taken on an e m p t y stomach, 30 min before meals) 12-hourly for 10 days. At the end of the antibiotic treatment, patients were considered cured if they demonstrated an i m p r o v e m e n t of cough, s p u t u m production, purulence and chest examination, and eradication of the pathogen responsible for the exacerbation. Patients were considered improved if there was clinical response even if there was a reappearance of pathogens in the s p u t u m sample at the end of therapy.
Results
Clinical findings A m o n g the 50 patients treated with amoxycillin-clavulanic acid, 32 patients (64%) were cured, 13 patients (26%) showed improvement, and in five cases (10%) treatment proved to be ineffective. A m o n g the 45 patients treated with ciprofloxacin, 26 (57"7%) were cured, eight (17"7%) showed i m p r o v e m e n t and in 11 cases (24"4%) treatment proved to be ineffective (Table I).
Microbiological findings In the 50 patients treated with amoxycillin-clavulanic acid, 69 organisms were isolated (59 Gram-positive and 10 Gram-negative) (Table II). Eradication of the organism from s p u t u m occurred at the end of treatment in 42 patients (84%); in three patients (6%) elimination of the initially isolated pathogen with a superinfection sustained by a second pathogen occurred; in four patients (8%), persistence of the initially isolated pathogen occurred; and in one patient a clear reduction of colony count of the isolated pathogenic species occurred. Mixed pathogens were isolated from 18
72
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Table I. Clinical results for amoxycillin-clavulanic acid vs. ciprofloxacin therapy
Cured* Improved Failed Clinical success (cured + improved)
Amoxycillin-clavulanic acid (total patients: 50)
Ciprofloxacin (total patients: 45)
32 (64%) 13 (26%) 5 (10%) 90%
26 (57"7%) 8 (177%) 11 (24.4%) 75.4%
* For definitions see Methods.
patients before treatment and three patients after treatment. At the end of t r e a t m e n t , t h e t o t a l n u m b e r o f i s o l a t e d p a t h o g e n s w a s 12 ( s i x G r a m - p o s i t i v e o r g a n i s m s a n d six G r a m - n e g a t i v e o r g a n i s m s ) . I n t h e 45 p a t i e n t s t r e a t e d w i t h c i p r o f l o x a c i n , 73 o r g a n i s m s w e r e i s o l a t e d (42 G r a m - p o s i t i v e o r g a n i s m s a n d 31 G r a m - n e g a t i v e o r g a n i s m s ) ( T a b l e I I ) . B a c t e r i a l e r a d i c a t i o n at t h e e n d o f t r e a t m e n t w a s a c h i e v e d in 26 p a t i e n t s
Table II. Isolated pathogens before and after therapy with amoxycillin clavulanic acid and before and after therapy with ciprofloxacin Before
After
No.
%
59 32 11
6 2 1
8.7 2.9 1.4
8 7
85.5 46-4 15.9 1.4 11-6 10.1
1 1
1.4 1.4
10 4 3 2
14.5 5.8 4.3 2-9
6 2 2 1
8.7 2.9 2.9 1-4
1
1-4
1
1.4
Ciprofloxacin Gram-positive organisms Streptococcus pneumoniae Staphylococcus aureus Staphylococcus epidermidis Enterococcus spp. Other Gram-positive
42 12 14 2 10 4
57.5 16.4 19.2 2.7 13.7 5.5
18 9 6
24-7 12-3 8.2
3
4.1
Gram-negative organisms Haemophilus influenzae Pseudomonas aeruginosa Escherichia coli Mcinetobacter spp. Other Gram-negative
31 13 5 6 2 5
42-5 17.8 6.8 8.2 2-7 6-8
10 1 5 1 2 1
13.7 1.4 6.8 1.4 2.7 1-4
Amoxycillin-clavulanic acid Gram-positive organisms Streptococcus pneumoniae Staphylococcus aureus Staphylococcus epidermidis Enterococcus spp. Other Gram-positive Gram-negative organisms Haemophilus influenzae Klebsiella pneumoniae Escherichia coh" Other Gram-negative
1
No.
%
-
A m o x y c i l l i n - c l a v u l a n i c acid and ciprofloxacin in chronic bronchitis
73
(57"7%), persistence occurred in 12 (26"6%) of the patients and superinfection occurred in seven (15"5%) of the patients. In 25 patients, the infection was sustained by other organisms. At the end of treatment, 48 h after the last dose of antibiotic, the total n u m b e r of organisms isolated was 28 (18 Gram-positive and 10 Gram-negative). N o n e of the isolated pathogens at the beginning of treatment was resistant to the antibiotics studied. At the end of treatment, none of the persistent pathogens isolated from patients that had received either antibiotic had become resistant. Discussion
It is difficult to evaluate the effectiveness of an antibiotic on the basis of a small n u m b e r of treated cases, since n u m e r o u s variables may lead to incorrect conclusions. Evaluation of our data appears to show amoxycillin-clavulanic acid to be more efficacious from both a clinical and a microbiological point of view compared with ciprofloxacin, even though the latter has a broader s p e c t r u m of action. However, there were appreciable differences between the pathogens isolated in the two groups. Even though both antibiotics have a broad spectrum of action, it is known that ciprofloxacin is not highly active against S. pneumoniae, while amoxycillin-clavulanic acid has no activity against Pseudomonas spp. In this study, only two of 32 S. pneumoniae persisted after amoxycillin clavulanic acid, but nine of 12 after ciprofloxacin. Therefore, the difference in the observed results in the two groups of patients m a y be due to the fact that in the patients treated with amoxycillin-clavulanic acid, a large n u m b e r of Gram-positive pathogens was encountered (59 of the 69 isolated; 85"5%); the Gram-negatives represented 10 out of 69; 14"5%. In the patients treated with ciprofloxacin, there was lower percentage of Gram-positive (42 out of 73; 57"5%) and higher of G r a m - n e g a t i v e pathogens (31 out of 73; 42"5%). T h e percentage of Gram-positive bacterial pathogens eradicated from s p u t u m was 90"2% for amoxycillin-clavulanic acid and 40% for Gram-negative organisms. Ciprofloxacin eradicated 57"3 % of Gram-positive organisms and 67-8% of G r a m - n e g a t i v e organisms. T h i s study shows that ciprofloxacin has greater activity against Gram-negative organisms than Gram-positives. T h e different distribution of bacterial species in the two groups under study may, in part, explain the different clinical efficacy b e t w e e n the two antibiotics in this study. Considering the wide spectrum of action of both amoxycillin-clavulanic acid and ciprofloxacin, which includes most of those pathogens usually encountered in the course of a bacterial exacerbation of chronic bronchitis, coupled with the absence of side effects and their manageability, these two drugs should both be considered suitable for the first line empirical treatment of such infections. It is perhaps not surprising that neither agent
74
D. Legnani e t aL
was u n i f o r m l y s u c c e s s f u l i n p a t i e n t s w i t h u n d e r l y i n g tract disease.
chronic respiratory
This study was supported by a grant from SmithKline Beecham.
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