- Email: [email protected]
clavulanic acid in the treatment of elderly patients with acute exacerbations of chronic bronchitis and pneumonia
CURRENT THERAPEUTIC RESEARCH” VOL. 57, SUPPL. A, 1996
COMPARISON OF CEFPODOXIME PROXETIL AND AMOXICILLIN~~LAVULANIC ACID IN THE TREATMENT 0F ELDERLY PATIENTS WITH ACUTE EXACERBATIONS OF CHRONIC BRONCHITIS AND PNEUMONIA MIGUEL ANGEL SALAZAR
LEZAMA
Clinical Service No. 2, National Institute of Respiratory Diseases, Mexico City, Mexico
ABSTRACT
The efficacy and tolerability of cefpodoxime proxetil were evaluated in 29 patients over 65 years of age with a diagnosis of acute exacerbation of chronic bronchitis or community-acquired pneumonia. In this open, comparative, randomized study, patients were treated with cefpodoxime proxetil200 mg twice daily or a combination of amoxicillin/ clavulanic acid 500/125 mg three times daily for 5 to 10 days. The patients were evaluated at the beginning and end of the treatment period and 25 to 40 days after the treatment ended. The causative organism was isolated in 17 (59%) of the 29 patients. No statistically significant differences were reported between the two groups regarding the number of isolates, bacterial sensitivity, or inhibition halo diameter. The percentages of satisfactory clinical responses at the end of the treatment were 100% for the cefpodoxime proxetil group and 73% for the amoxicillinklavulanic acid group. This difference was statistically significant (P = 0.05). There were no therapeutic failures in the cefpodoxime proxetil group, but 27% of the patients in the amoxicillinklavulanic acid group experienced therapeutic failure (P = 0.04). Thus cefpodoxime proxetil was shown to be superior to amoxicillinlclavulanic acid in the treatment of acute exacerbations of chronic bronchitis or pneumonia in elderly patients. INTRODUCTION
Community-acquired respiratory tract infections are a public health problem. In elderly patients, these infections are a significant cause of morbidity and mortality.’ In Mexico, they are the number one cause of morbidity and mortality in persons older than age 6L2 In 1991, chronic obstructive pulmonary diseases and pneumonias were the cause of 44.9% of deaths at the Mexican National Institute of Respiratory Diseases (INER).3 Over the last 10 to 15 years, a gradual change has been observed in the pathogenetic profile of the organisms that cause respiratory tract infections. Together with the appearance of beta-lactamase-producing strains, these changes have decreased the efficacy of many beta-lactamase antibiotics, including ampicillin and amoxicillin.4T5 Thus, to effectively treat respiratory tract infections, we must administer an antimicrobial agent, preferably orally, that has high bactericidal action against gram-positive 91
0011-393x’96/%3.50
CEFPODOXIME
PROXETIL
VERSUS
AMOXICILLINKLAVULANIC
ACID
and gram-negative respiratory tract pathogens and is resistant to the destructive action of the beta-lactamases. The third-generation cephalosporin cefpodoxime proxetil has a wide spectrum of antibacterial activity and is highly resistant to hydrolysis by the beta-lactamases. It has bactericidal action against the most important gram-positive and gram-negative organisms from a clinical point of view and against the most important causative agents of lower respiratory tract infections, such as Streptococcus pneumoniae and Haemophilus infZuenzae.6
The purpose of our study was to compare the efficacy and safety of cefpodoxime proxetil with that of amoxicillinklavulanic acid in the treatment of acute exacerbations of chronic bronchitis and community-acquired pneumonia of bacterial etiology in elderly patients. PATIENTS AND METHODS
A total of 29 outpatients older than age 65 were enrolled in this open, comparative, randomized study from August 1, 1991 through May 30, 1992. All patients were diagnosed with pneumonia and atypical bronchitis of bacterial origin or with type 1 or type 2 chronic bronchitis, according to the Anthonisen classification.7 Demographic data and pathology per treatment group are shown in the table. Patients with severe infections that required parenteral treatment; those with pulmonary tuberculosis, asthma, or cystic fibrosis; and those with a history of hypersensitivity to beta-lactam antibiotics were excluded. Patients with significant immunosuppression and those who could not be monitored according to protocol procedures also were excluded. Patients who had previously received antibiotic treatment during the days before
Table. Patient demographic characteristics. Pneumonia
No. of patients Age (Y) Mean + SD Sex Male Female Weight (kg) Mean 2 SD Height(cm) Mean 2 SD
Bronchitis
Overall
CPO
AMICV
CPD
AMICV
CPD
AWCV
4
4
10
11
14
15
75.8 -t 8.8
79.3 ? 9.5 70.9 t 14.7 70.3 ? 6.1 100% 0%
75% 25%
zr: OrJ
55% 45%
72.3 2 13.2 72.7 -t 7.9 :z00
KY00
60.8 rt 13.2 57.8 2 3.9 58.2 ? 10.9 63.0 * 22.2 59.0 2 11.2 61.6 ? 19.0 162 ? 10.7
CPD = cefpodoxime; AMXV
163 * 6.2
158 2 13.5
= amoxicillin/clavulanic acid.
98
158 * 10.0
159 2 12.3
159 2 9.0
M. A. SALAZAR LEZAMA
the beginning of the study were not eligible, unless documented resistance to the antibiotic or clinical failure was observed. The patients enrolled in the study were randomly assigned to receive two lOO-mg tablets of cefpodoxime proxetil twice daily or a 500/125-mg dose of amoxicillinklavulanic acid three times a day for a treatment period of 5 to 10 days, according to the clinical response. The patients were evaluated at the beginning and end of the treatment period and 25 to 40 days after the treatment ended. To control patient compliance and to closely monitor the clinical evolution during treatment, the patients were hospitalized. The sputum samples were considered valid in establishing the etiologic diagnosis only if they met the 1984 standards established by the National Committee for Clinical Laboratory Standards.’ The direct test had to show more than 25 polymorphonuclear cells per field, and the isolated pathogen had to grow with a count equal to or higher than 10 colonyforming units per milliliter. Sputum samples were collected within the 24 hours before antimicrobial treatment was begun. The bacterial sensitivity to cefpodoxime proxetil and amoxicillin/ clavulanic acid was determined for each isolated bacteria, irrespective of the treatment group assigned. The organisms were considered sensitive to cefpodoxime proxetil when the inhibition halo was equal to or greater than 22 mm and sensitive to amoxicillinklavulanic acid when the halo was equal to or greater than 20 mm for Staphylococcus and Haemophilus species and greater than or equal to 18 mm for other bacteria. The bacteriologic response was considered satisfactory if, in the posttreatment cultures, the causative organism had been eradicated or, in cases in which no samples were obtained for culture, there was a positive clinical response. Results were analyzed according to the protocol, or explanatory, analysis and according to the intent-to-treat analysis. The study protocol was approved by the Ethical Research Committee of the National Institute of Respiratory Diseases. All patients provided informed consent to participating in the study. RESULTS
Fourteen patients were randomly assigned to the cefpodoxime proxetil group and 15 to the amoxicillinklavulanic acid group. One patient from the cefpodoxime proxetil group was excluded from the explanatory analysis because this patient received a single dose of trimethoprim/ sulfamethoxazole a few hours before starting the study. Nevertheless, this patient was included in management analysis. One patient from the cefpodoxime proxetil group and one from the amoxicillinklavulanic acid group died a few hours after the treatment 99
CEFPODOXIME
PROXETIL
VERSUS
AMOXICILLIN/CLAVULANIC
ACID
concluded. The first patient died of a massive myocardial infarction, which was confirmed in the postmortem examination. The second patient died of a pulmonary thromboembolism. No deaths were attributed to the drug administered. The presumed causative agent was isolated in 17 (59%) patients. The organisms isolated were Klebsiella oxytoca (l), Klebsiella pneumoniue (l), Staphylococcus aureus (l), ikforaxella catarrhalis (6), Streptococcus pneumonk (2), Escherichia coli (2), and Haemophilus species (4). All the organisms isolated at the beginning of the study were sensitive to cefpodoxime proxetil, including those isolated in the amoxicillinklavulanic acid group. The cefpodoxime proxetil inhibition halo range was 22 to 32 mm (average, 25.3 mm). Ninety-two percent of the isolated organisms were sensitive to amoxicillinklavulanic acid; Kpneumoniae, which was isolated from one patient with pneumonia, was resistant to this combination. The amoxicillinklavulanic acid inhibition halos fluctuated between 19 and 35 mm (average, 24.4 mm). No statistically significant differences in isolates, bacterial sensitivity, or inhibition halo diameter were reported in the two treatment groups. The average duration of treatment was 6.8 days in the cefpodoxime proxetil group and 7.5 days in the amoxicillinklavulanic acid group. Fever receded during the first day of treatment in both groups. Disappearance or lessening of cough was observed on the fifth day in patients treated with cefpodoxime proxetil and on the sixth day in those receiving amoxicillin clavulanic acid. Sputum production disappeared or became hyaline 3.2 days after treatment with cefpodoxime proxetil and 5.2 days after treatment with amoxicillinklavulanic acid; this difference was statistically significant (P = 0.02). A satisfactory clinical response at the end of treatment was achieved in all patients (14/14) in the cefpodoxime proxetil group and in 73% (11115) of those in the amoxicillinklavulanic acid group; this difference was statistically significant (P = 0.05). On the follow-up visit, 25 to 40 days after the end of treatment, the clinical response was satisfactory in all patients (14/14) treated with cefpodoxime proxetil and in 86% (13115) of those treated with amoxicillinklavulanic acid (P = 0.3). No patient in the cefpodoxime proxetil group experienced a therapeutic failure, while 27% (4/15) of the patients in the amoxicillinklavulanic acid group were considered therapeutic failures P = 0.05). In the follow-up visit, the therapeutic response was considered successful in all patients (14/14) in the cefpodoxime proxetil group and unsuccessful in 14% (2/15) of the patients in the amoxicillinklavulanic acid group. At the end of treatment, bacteriologic eradication was obtained in all patients in the cefpodoxime proxetil group; the causative pathogen also was isolated in all patients in this group at the beginning of the study. In contrast, the bacteriologic cure was obtained in only 73% (11/15) of the 100
M.A.SALAZARLRZAMA
patients in the amoxicillin/clavulanic acid group. In the follow-up visit, the percentage of satisfactory bacteriologic responses remained at 100% (14/ 14) in the ceEpodoxime proxetil group and improved to 86% (13/15) in the amoxicillin/clavulanic acid group. Two patients in the amoxicilliticlavulanic acid group reported mild diarrhea, which did not merit discontinuation of treatment. None of the patients in the cefpodoxime proxetil group reported adverse effects considered to be related to treatment. DISCUSSION
Respiratory tract infections continue to be a serious health problem throughout the world, especially in very old and very young patients. In elderly patients, diagnosis and treatment often are complicated by agerelated immunologic alterations. The clinical picture in elderly patients can be further confused by the absence of cough, sputum, and fever. The radiologic densities may be long in disappearing, and leukocytes may not be present. In addition, the bacteria may change during treatment,g making it difficult to isolate the causative microorganism from the sputum.lOT1l Although S pneumoniae is reported in many studies as the most common pathogen in community-acquired pneumonia, this may vary when the patient has underlying diseases, such as alcoholism or diabetes.” For this reason, empiric treatment may be necessary, using an antibiotic with a spectrum of activity that includes the microorganisms pathogenic for the lower respiratory tract. Bacterial infections of the bronchial area are one of the most frequent pathogenic factors in chronic bronchitis. Thus one of the most important points in the treatment of acute respiratory tract infections is to eradicate the causative pathogens from bronchial secretions with an antibiotic that is resistant to beta-lactamases. l2 In our study, the most frequently isolated organism was M caturrhalis, which has acquired an extraordinary resistance to beta-lactams in more than 80% of its strains.13 All the microorganisms that we isolated were sensitive to cefpodoxime proxetil; the clinical efficacy of this drug was greater than that of the combination of amoxicillin and clavulanic acid. The percentage of bacterial isolates that were presumably the cause of the infection at the beginning of the study was the same or even higher than that reported in the medical literature or by INER.10,11*‘4 The results of our study show that cefpodoxime proxetil is an effective and well-tolerated oral antibiotic treatment in the management of acute exacerbations of chronic bronchitis and community-acquired pneumonia in vulnerable patients with high risk factors and in the elderly. Cefpodoxime proxetil may be used as an alternative to injectable therapy. 101
CEFPODOXIME
PROXETIL
VERSUS
AMOXICILLINiCLAVULANIC
ACID
Acknowledgment This study was sponsored by Grupo Roussel, S.A. de C.V. References: 1. MacFarlane
J. Community-acquired
pneumoniae.
Br J Dis Chest. 1987;81:116-127.
2. Kumate J, Canedo L, Pedrota 0. La salud de 10s mexicanos y la medicina en Mkcico. Mexico, D.F: Editorial de1 Colegio National, 1977:173-222. 3. Instituto National de Enfermedades Respiratorias. Znforme de Labores. Mexico City: Instituto National de Enfermedades Respiratorias, 1991:28. 4. Alvarez S, Jones M, Holtsclaw-Berck S, et al. In vitro susceptibility and betalactamase production of 53 isolates of Branhamella catarrhalis. Antimicrob Agents Chemother. 1985;27:646-647. 5. Istre G, Conner JS, Glode MP, Hopkins RS. Increasing resistance rates in Haemophilus influenzae meningitis. Am J Dis Child. 1984;138:366-369. 6. Wise R, Andrews JM, Ashby JP, Thronber D. The in vitro activity comparison with other oral cephalosporins. J Antimicrob Chemother.
of cefpodoxime: A 1990;25:541-550.
7. Anthonisen NR, Manfreda J, Warren CPW, et al. Antibiotic therapy in exacerbations chronic obstructive pulmonary disease. Ann Zntern Med. 1987;106:196-204.
of
8. National Committee for Clinical Laboratory Standards Subcommittee for antimicrobial susceptibility test. Approved standard M2 A3. Performance standards for antimicrobic disk susceptibility test for bacteria which grow aerobically. Villanova, PA: National Committee for Clinical Laboratory Standards, 1984;369-383. 9. Katsunuma H. Clinical evaluation of the effect of cefotaxime in senile pneumonia caused by gram-positive and gram-negative bacteria. Infection. 1985;13(Suppl l):S18-S24. 10. Davidson M, Tempest B, Palmer DL. Bacteriologic diagnosis of acute pneumonia. Comparison of sputum transtracheal aspirates and lung aspirates. JAMA. 1976;235:158-163. 11. Woodhead MA, MacFarlane JT, MacCracken JS, et al. Prospective study of the aetiology and outcome of pneumonia in the community. Lancet. 1987;1:671-674. 12. Periti P, Novelli A, Schildwatcher G, et al. Efficacy and tolerance of cefpodoxime proxetil compared with co-amoxiclav in the treatment of exacerbations of chronic bronchitis. J Antimicrob Chemother. 1990;26(Suppl E):63-69. 13. Verghese A, Berck SL. Moroxella 1991;5:523-537.
(Branhamella)
catarrhalis. Znfect Dis Clin North Am.
14. Garza R, Sada E, Carrillo C. Moraxella catarrhnlis y exacerbaci6n ica. Znfectologia. 1991;11:63-67.
102
de la bronquitis
c&n-
COMPARISON OF CEFPODOXIME PROXETIL AND AMOXICILLIN~~LAVULANIC ACID IN THE TREATMENT 0F ELDERLY PATIENTS WITH ACUTE EXACERBATIONS OF CHRONIC BRONCHITIS AND PNEUMONIA MIGUEL ANGEL SALAZAR
LEZAMA
Clinical Service No. 2, National Institute of Respiratory Diseases, Mexico City, Mexico
ABSTRACT
The efficacy and tolerability of cefpodoxime proxetil were evaluated in 29 patients over 65 years of age with a diagnosis of acute exacerbation of chronic bronchitis or community-acquired pneumonia. In this open, comparative, randomized study, patients were treated with cefpodoxime proxetil200 mg twice daily or a combination of amoxicillin/ clavulanic acid 500/125 mg three times daily for 5 to 10 days. The patients were evaluated at the beginning and end of the treatment period and 25 to 40 days after the treatment ended. The causative organism was isolated in 17 (59%) of the 29 patients. No statistically significant differences were reported between the two groups regarding the number of isolates, bacterial sensitivity, or inhibition halo diameter. The percentages of satisfactory clinical responses at the end of the treatment were 100% for the cefpodoxime proxetil group and 73% for the amoxicillinklavulanic acid group. This difference was statistically significant (P = 0.05). There were no therapeutic failures in the cefpodoxime proxetil group, but 27% of the patients in the amoxicillinklavulanic acid group experienced therapeutic failure (P = 0.04). Thus cefpodoxime proxetil was shown to be superior to amoxicillinlclavulanic acid in the treatment of acute exacerbations of chronic bronchitis or pneumonia in elderly patients. INTRODUCTION
Community-acquired respiratory tract infections are a public health problem. In elderly patients, these infections are a significant cause of morbidity and mortality.’ In Mexico, they are the number one cause of morbidity and mortality in persons older than age 6L2 In 1991, chronic obstructive pulmonary diseases and pneumonias were the cause of 44.9% of deaths at the Mexican National Institute of Respiratory Diseases (INER).3 Over the last 10 to 15 years, a gradual change has been observed in the pathogenetic profile of the organisms that cause respiratory tract infections. Together with the appearance of beta-lactamase-producing strains, these changes have decreased the efficacy of many beta-lactamase antibiotics, including ampicillin and amoxicillin.4T5 Thus, to effectively treat respiratory tract infections, we must administer an antimicrobial agent, preferably orally, that has high bactericidal action against gram-positive 91
0011-393x’96/%3.50
CEFPODOXIME
PROXETIL
VERSUS
AMOXICILLINKLAVULANIC
ACID
and gram-negative respiratory tract pathogens and is resistant to the destructive action of the beta-lactamases. The third-generation cephalosporin cefpodoxime proxetil has a wide spectrum of antibacterial activity and is highly resistant to hydrolysis by the beta-lactamases. It has bactericidal action against the most important gram-positive and gram-negative organisms from a clinical point of view and against the most important causative agents of lower respiratory tract infections, such as Streptococcus pneumoniae and Haemophilus infZuenzae.6
The purpose of our study was to compare the efficacy and safety of cefpodoxime proxetil with that of amoxicillinklavulanic acid in the treatment of acute exacerbations of chronic bronchitis and community-acquired pneumonia of bacterial etiology in elderly patients. PATIENTS AND METHODS
A total of 29 outpatients older than age 65 were enrolled in this open, comparative, randomized study from August 1, 1991 through May 30, 1992. All patients were diagnosed with pneumonia and atypical bronchitis of bacterial origin or with type 1 or type 2 chronic bronchitis, according to the Anthonisen classification.7 Demographic data and pathology per treatment group are shown in the table. Patients with severe infections that required parenteral treatment; those with pulmonary tuberculosis, asthma, or cystic fibrosis; and those with a history of hypersensitivity to beta-lactam antibiotics were excluded. Patients with significant immunosuppression and those who could not be monitored according to protocol procedures also were excluded. Patients who had previously received antibiotic treatment during the days before
Table. Patient demographic characteristics. Pneumonia
No. of patients Age (Y) Mean + SD Sex Male Female Weight (kg) Mean 2 SD Height(cm) Mean 2 SD
Bronchitis
Overall
CPO
AMICV
CPD
AMICV
CPD
AWCV
4
4
10
11
14
15
75.8 -t 8.8
79.3 ? 9.5 70.9 t 14.7 70.3 ? 6.1 100% 0%
75% 25%
zr: OrJ
55% 45%
72.3 2 13.2 72.7 -t 7.9 :z00
KY00
60.8 rt 13.2 57.8 2 3.9 58.2 ? 10.9 63.0 * 22.2 59.0 2 11.2 61.6 ? 19.0 162 ? 10.7
CPD = cefpodoxime; AMXV
163 * 6.2
158 2 13.5
= amoxicillin/clavulanic acid.
98
158 * 10.0
159 2 12.3
159 2 9.0
M. A. SALAZAR LEZAMA
the beginning of the study were not eligible, unless documented resistance to the antibiotic or clinical failure was observed. The patients enrolled in the study were randomly assigned to receive two lOO-mg tablets of cefpodoxime proxetil twice daily or a 500/125-mg dose of amoxicillinklavulanic acid three times a day for a treatment period of 5 to 10 days, according to the clinical response. The patients were evaluated at the beginning and end of the treatment period and 25 to 40 days after the treatment ended. To control patient compliance and to closely monitor the clinical evolution during treatment, the patients were hospitalized. The sputum samples were considered valid in establishing the etiologic diagnosis only if they met the 1984 standards established by the National Committee for Clinical Laboratory Standards.’ The direct test had to show more than 25 polymorphonuclear cells per field, and the isolated pathogen had to grow with a count equal to or higher than 10 colonyforming units per milliliter. Sputum samples were collected within the 24 hours before antimicrobial treatment was begun. The bacterial sensitivity to cefpodoxime proxetil and amoxicillin/ clavulanic acid was determined for each isolated bacteria, irrespective of the treatment group assigned. The organisms were considered sensitive to cefpodoxime proxetil when the inhibition halo was equal to or greater than 22 mm and sensitive to amoxicillinklavulanic acid when the halo was equal to or greater than 20 mm for Staphylococcus and Haemophilus species and greater than or equal to 18 mm for other bacteria. The bacteriologic response was considered satisfactory if, in the posttreatment cultures, the causative organism had been eradicated or, in cases in which no samples were obtained for culture, there was a positive clinical response. Results were analyzed according to the protocol, or explanatory, analysis and according to the intent-to-treat analysis. The study protocol was approved by the Ethical Research Committee of the National Institute of Respiratory Diseases. All patients provided informed consent to participating in the study. RESULTS
Fourteen patients were randomly assigned to the cefpodoxime proxetil group and 15 to the amoxicillinklavulanic acid group. One patient from the cefpodoxime proxetil group was excluded from the explanatory analysis because this patient received a single dose of trimethoprim/ sulfamethoxazole a few hours before starting the study. Nevertheless, this patient was included in management analysis. One patient from the cefpodoxime proxetil group and one from the amoxicillinklavulanic acid group died a few hours after the treatment 99
CEFPODOXIME
PROXETIL
VERSUS
AMOXICILLIN/CLAVULANIC
ACID
concluded. The first patient died of a massive myocardial infarction, which was confirmed in the postmortem examination. The second patient died of a pulmonary thromboembolism. No deaths were attributed to the drug administered. The presumed causative agent was isolated in 17 (59%) patients. The organisms isolated were Klebsiella oxytoca (l), Klebsiella pneumoniue (l), Staphylococcus aureus (l), ikforaxella catarrhalis (6), Streptococcus pneumonk (2), Escherichia coli (2), and Haemophilus species (4). All the organisms isolated at the beginning of the study were sensitive to cefpodoxime proxetil, including those isolated in the amoxicillinklavulanic acid group. The cefpodoxime proxetil inhibition halo range was 22 to 32 mm (average, 25.3 mm). Ninety-two percent of the isolated organisms were sensitive to amoxicillinklavulanic acid; Kpneumoniae, which was isolated from one patient with pneumonia, was resistant to this combination. The amoxicillinklavulanic acid inhibition halos fluctuated between 19 and 35 mm (average, 24.4 mm). No statistically significant differences in isolates, bacterial sensitivity, or inhibition halo diameter were reported in the two treatment groups. The average duration of treatment was 6.8 days in the cefpodoxime proxetil group and 7.5 days in the amoxicillinklavulanic acid group. Fever receded during the first day of treatment in both groups. Disappearance or lessening of cough was observed on the fifth day in patients treated with cefpodoxime proxetil and on the sixth day in those receiving amoxicillin clavulanic acid. Sputum production disappeared or became hyaline 3.2 days after treatment with cefpodoxime proxetil and 5.2 days after treatment with amoxicillinklavulanic acid; this difference was statistically significant (P = 0.02). A satisfactory clinical response at the end of treatment was achieved in all patients (14/14) in the cefpodoxime proxetil group and in 73% (11115) of those in the amoxicillinklavulanic acid group; this difference was statistically significant (P = 0.05). On the follow-up visit, 25 to 40 days after the end of treatment, the clinical response was satisfactory in all patients (14/14) treated with cefpodoxime proxetil and in 86% (13115) of those treated with amoxicillinklavulanic acid (P = 0.3). No patient in the cefpodoxime proxetil group experienced a therapeutic failure, while 27% (4/15) of the patients in the amoxicillinklavulanic acid group were considered therapeutic failures P = 0.05). In the follow-up visit, the therapeutic response was considered successful in all patients (14/14) in the cefpodoxime proxetil group and unsuccessful in 14% (2/15) of the patients in the amoxicillinklavulanic acid group. At the end of treatment, bacteriologic eradication was obtained in all patients in the cefpodoxime proxetil group; the causative pathogen also was isolated in all patients in this group at the beginning of the study. In contrast, the bacteriologic cure was obtained in only 73% (11/15) of the 100
M.A.SALAZARLRZAMA
patients in the amoxicillin/clavulanic acid group. In the follow-up visit, the percentage of satisfactory bacteriologic responses remained at 100% (14/ 14) in the ceEpodoxime proxetil group and improved to 86% (13/15) in the amoxicillin/clavulanic acid group. Two patients in the amoxicilliticlavulanic acid group reported mild diarrhea, which did not merit discontinuation of treatment. None of the patients in the cefpodoxime proxetil group reported adverse effects considered to be related to treatment. DISCUSSION
Respiratory tract infections continue to be a serious health problem throughout the world, especially in very old and very young patients. In elderly patients, diagnosis and treatment often are complicated by agerelated immunologic alterations. The clinical picture in elderly patients can be further confused by the absence of cough, sputum, and fever. The radiologic densities may be long in disappearing, and leukocytes may not be present. In addition, the bacteria may change during treatment,g making it difficult to isolate the causative microorganism from the sputum.lOT1l Although S pneumoniae is reported in many studies as the most common pathogen in community-acquired pneumonia, this may vary when the patient has underlying diseases, such as alcoholism or diabetes.” For this reason, empiric treatment may be necessary, using an antibiotic with a spectrum of activity that includes the microorganisms pathogenic for the lower respiratory tract. Bacterial infections of the bronchial area are one of the most frequent pathogenic factors in chronic bronchitis. Thus one of the most important points in the treatment of acute respiratory tract infections is to eradicate the causative pathogens from bronchial secretions with an antibiotic that is resistant to beta-lactamases. l2 In our study, the most frequently isolated organism was M caturrhalis, which has acquired an extraordinary resistance to beta-lactams in more than 80% of its strains.13 All the microorganisms that we isolated were sensitive to cefpodoxime proxetil; the clinical efficacy of this drug was greater than that of the combination of amoxicillin and clavulanic acid. The percentage of bacterial isolates that were presumably the cause of the infection at the beginning of the study was the same or even higher than that reported in the medical literature or by INER.10,11*‘4 The results of our study show that cefpodoxime proxetil is an effective and well-tolerated oral antibiotic treatment in the management of acute exacerbations of chronic bronchitis and community-acquired pneumonia in vulnerable patients with high risk factors and in the elderly. Cefpodoxime proxetil may be used as an alternative to injectable therapy. 101
CEFPODOXIME
PROXETIL
VERSUS
AMOXICILLINiCLAVULANIC
ACID
Acknowledgment This study was sponsored by Grupo Roussel, S.A. de C.V. References: 1. MacFarlane
J. Community-acquired
pneumoniae.
Br J Dis Chest. 1987;81:116-127.
2. Kumate J, Canedo L, Pedrota 0. La salud de 10s mexicanos y la medicina en Mkcico. Mexico, D.F: Editorial de1 Colegio National, 1977:173-222. 3. Instituto National de Enfermedades Respiratorias. Znforme de Labores. Mexico City: Instituto National de Enfermedades Respiratorias, 1991:28. 4. Alvarez S, Jones M, Holtsclaw-Berck S, et al. In vitro susceptibility and betalactamase production of 53 isolates of Branhamella catarrhalis. Antimicrob Agents Chemother. 1985;27:646-647. 5. Istre G, Conner JS, Glode MP, Hopkins RS. Increasing resistance rates in Haemophilus influenzae meningitis. Am J Dis Child. 1984;138:366-369. 6. Wise R, Andrews JM, Ashby JP, Thronber D. The in vitro activity comparison with other oral cephalosporins. J Antimicrob Chemother.
of cefpodoxime: A 1990;25:541-550.
7. Anthonisen NR, Manfreda J, Warren CPW, et al. Antibiotic therapy in exacerbations chronic obstructive pulmonary disease. Ann Zntern Med. 1987;106:196-204.
of
8. National Committee for Clinical Laboratory Standards Subcommittee for antimicrobial susceptibility test. Approved standard M2 A3. Performance standards for antimicrobic disk susceptibility test for bacteria which grow aerobically. Villanova, PA: National Committee for Clinical Laboratory Standards, 1984;369-383. 9. Katsunuma H. Clinical evaluation of the effect of cefotaxime in senile pneumonia caused by gram-positive and gram-negative bacteria. Infection. 1985;13(Suppl l):S18-S24. 10. Davidson M, Tempest B, Palmer DL. Bacteriologic diagnosis of acute pneumonia. Comparison of sputum transtracheal aspirates and lung aspirates. JAMA. 1976;235:158-163. 11. Woodhead MA, MacFarlane JT, MacCracken JS, et al. Prospective study of the aetiology and outcome of pneumonia in the community. Lancet. 1987;1:671-674. 12. Periti P, Novelli A, Schildwatcher G, et al. Efficacy and tolerance of cefpodoxime proxetil compared with co-amoxiclav in the treatment of exacerbations of chronic bronchitis. J Antimicrob Chemother. 1990;26(Suppl E):63-69. 13. Verghese A, Berck SL. Moroxella 1991;5:523-537.
(Branhamella)
catarrhalis. Znfect Dis Clin North Am.
14. Garza R, Sada E, Carrillo C. Moraxella catarrhnlis y exacerbaci6n ica. Znfectologia. 1991;11:63-67.
102
de la bronquitis
c&n-