Penicillin and gentamicin therapy vs amoxicillin/clavulanate in severe hypoxemic pneumonia
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《美国医学杂志》
Department of Pediatrics, Advanced Pediatrics Center, Post Graduate Institute of Medical Education and Research Center, Chandigarh, India
Abstract
Objective : To compare the efficacy of sequential injectable crystalline penicillin (C.pen) and gentamicin combination followed by oral amoxicillin with sequential IV and oral amoxicillin-clavulanate (amox-clav) in treatment of severe or very severe hypoxemic pneumonia. Methods : Children aged 2-59 months with WHO-defined severe or very severe pneumonia with hypoxemia (SpO 2 <90%) were included in the study. Patients with fever > 10 days, bacterial meningitis, prior antibiotic therapy > 24 hours, stridor, heart disease and allergy to any of the study drugs were excluded. They were randomly allocated to two groups - Group A and Group B. Group A received C. pen and gentamicin intravenously (IV), followed by oral amoxicillin and group B got amox-clav IV, followed by oral amox-clav. Minimum duration of IV therapy was 3 days and total 7 days. Respiratory rate, oxygen saturation and chest wall indrawing were monitored 6 hourly. Results : 71 patients were included. There were two (5.2%) blood cultures positive in group A and three (9%) in group B. Organisms isolated were S. pneumoniae (n=3) and H. influenzae-b (n=2). There was only one treatment failure in each of the groups. One was due to penicillin resistant H. influenzae -b and the other was due to worsening of pneumonia. The mean time taken for normalization of tachypnea, hypoxia, chest wall indrawing and inability to feed was similar (P-N.S). Mean duration of IV therapy in group A was 76±25 hrs and group B was 75±24 hrs (p>0.1). Conclusion : In children of 2-59 months, sequential injectable C. pen and gentamicin combination, followed by oral amoxicillin or sequential IV and oral amox-clav were equally effective for the treatment of severe or very severe hypoxemic community acquired pneumonia.
Keywords: Acute respiratory infections; Community acquired pneumonia; Penicillin; Gentamicin; Amoxicillin/clavulanate
Acute Respiratory Infections (ARI) kill four million children every year, and most of these deaths are caused by pneumonia. Of these, developing countries are responsible for a disproportionate 90% of the deaths.[1] Standard case management guidelines of World Health Organization (WHO) recommend hospitalization, oxygen and injectable antibiotics in severe and very severe pneumonia patients which contributes to majority of pneumonia case fatality.[2] The most frequently isolated pathogens are S. pneumoniae and H. influenzae ; staphylococcus aureus and gram negative organisms account for a small proportion.[2],[3],[4] WHO has given simple guidelines for early detection and rational antibiotic treatment of pneumonia and recommend penicillin and gentamicin combination or chloramphenicol as first line therapy in patients with very severe pneumonia and severe pneumonia.[3] This provides adequate coverage against the common pathogens involved.[3] Streptococcus pneumoniae and H . influenzae cause most fatal pneumonia in children, and these bacteria can be killed by several inexpensive antibiotics such as penicillin and ampicillin.[5] The objective of this study was to compare the efficacy of sequential injectable crystalline penicillin (C.pen) and gentamicin, combination followed by oral amoxicillin, with sequential IV and oral amoxicillin-clavulanate (amox-clav) in treatment of severe or very severe hypoxemic pneumonia.
Materials and Methods
This study was an open label randomized controlled trial conducted at Advanced Pediatrics Center, Post Graduate Institute and Medical Education and Research, during July 1999 to June 2000. Institute Ethics Committee approved the study. Informed written consent was obtained from the parents.
Inclusion criteria: Two months to 59 months old patients who had fever (temperature > 38 0sub c) and with history of cough or rapid or difficult breathing were screened for their eligibility for inclusion in the study. Those with tachypnea, chest wall indrawing, hypoxemia in room air and X-ray chest showing alveolar infiltrates, segmental or lobar consolidation were included in the study. Tachypnea was defined as respiratory rate 3 50/min in 2-11 months and 3 40/min in 12-59 month old child.[3] Chest wall indrawing was defined as inward movement of lower chest wall on breathing in.[3] Hypoxemia was defined as oxygen saturation less then 90% in room air.[3] Severe pneumonia was defined as tachypnea and chest wall indrawing.[3] Very severe pneumonia was defined as tachypnea, chest wall indrawing and either central cyanosis or inability to drink.[3]
Exclusion criteria: Patients were excluded if they had fever >10 days, intravenous antibiotic>24 hrs, heart disease, stridor when calm, audible wheeze, bacterial meningitis, history of recurrent cough, previously diagnosed asthma, diphtheria, pertusis, measles, allergy to study drugs and renal failure.
Enrolment of subjects, baseline examination and laboratory data: The baseline history and examination was obtained in each case. It included description of symptoms prior to admission and their duration, treatment for the illness prior to admission, respiratory rate, heart rate, temperature, level of consciousness, weight, height, respiratory, cardiovascular and neurological findings. Oxygen saturation (SpO 2 ) was measured with the help of a pulse oximeter (Nellcore ) using a finger probe or ear lobe probe whichever was appropriate. Complete blood counts, arterial blood gases, blood glucose and bacterial culture were obtained.
Randomization: Patients were randomly allocated to group A or B. The randomization was done in blocks of 6 patients and stratified in 2 age groups- 2 months to 11 months and 12 months to 59 months. Randomization list was prepared before starting the study and random treatment assignment was placed in serially - labeled sealed envelopes. The assignment was opened when patient had met all the inclusion and exclusion criteria and written consent was available.
Patients in Group A received Crystalline penicillin (benzyl penicillin) - 50,000 IU/kg IV, q6h and g entamicin 2.5 mg/kg, IV, q8h for at least 3 days. After that, oral amoxicillin 15 mg/kg 8 hourly was substituted for C.pen. Group B patients were given Amoxicillin- Clavulanate 30 mg/kg IV q12h for at least 3 days and were changed to oral amox-clav when able to feed.
Supportive therapy was given as per the standard case management guidelines prepared by WHO programme for the control of ARI[3]. After enrolment, patients were followed up every 6 hour, to record respiratory rate, chest wall indrawing, and oxygen saturation were recorded.
Outcome Variables: Outcome variables were treatment failure and length of time (in hours) taken for recovery from tachypnea, hypoxemia and chest-wall indrawing.
Treatment failure was defined as any change, modification, or discontinuation of allocated antibiotic therapy because of deterioration in patient's condition, development of serious intercurrent illness or complications such as refractory septic shock, acute renal failure, meningitis etc., persistence of danger signs such as inability to drink after 48 hrs of treatment, or relapse of the hypoxemic pneumonia during the following 2 weeks.
Statistical Analysis: Patient's characteristics across the groups were compared by analysis of variance or Student 't' test and chi-square test. The outcome analysis was on 'intention to treat' basis.
Results
Seventy-one patients were enroled in the study, of which 38 were randomized to receive C. pen/gentamicin (group A) and 33 patients to receive amox-clav (group B).
Clinical characteristics, respiratory rate, heart rate, and oxygen saturation were similar in both the groups table1. Blood culture was positive in two patients in group A and three in group B. Group A had one each of S . pneumoniae and H . influenzae b, while group B had two S . pneumoniae and one H . influenzae-b isolated in blood culture. None of the S. pneumoniae showed resistance to penicillin, amoxicillin, erythromycin and gentamicin, while one of two H . influenzae-b was resistant to all of above (it was sensitive to ciprofloxacin, cefotaxime and chloramphenicol).
Outcome: Only 2 patients, one in each group had treatment failure. The one in group A had H. influenzae-b in blood culture that was resistant to penicillin and required change of antibiotics. The patient in group B continued to worsen and required change in antibiotics and was put on mechanical ventilation.
Mean time taken for recovery of various signs of respiratory distress was comparable in both the groups table2 as also the pattern of time taken (in hours) for recovery from tachypnea, chest wall indrawing, hypoxia and inability to feed Figure1. Mean duration of IV antibiotics was 76±24 hrs in group A and 75±24 hrs in group B. (P - n.s.)
Discussion
This study shows that the sequential injectable and oral regimens using C. pen and gentamicin combination followed by oral amoxicillin and sequential IV and oral amox-clav for the treatment of severe or very severe hypoxemic community - acquired pneumonia were equally effective. There was one instances of treatment failure in one in each group. One case of treatment failure was because of penicillin resistant H . influenzae-b . The other patient had worsening respiratory distress requiring ventilatory support and change of antibiotics.
Five (7.0%) blood cultures were positive in this study. This is in accordance with the various studies that have found the very low positivity rate of blood cultures in pneumonia[6], [7]. Moreover, other studies, which have investigated for bacteria and viruses, have shown that in more than 12-58% of lower respiratory tract illnesses, the organism is not isolated[8]. The organisms isolated were Streptococcus pneumoniae and Hemophillus influenzae-b. This is compatible with the published data[9], [10],[11]. In developing countries, H . influenzae-b has been implicated to be important cause of pneumonia [12]. Indian data on H. influenzae strain is scarce; it has been found in only 10-15% of severe lower respiratory tract illness in India[12].
Only one culture in our study was resistant; that was H. influenzae-b. S . Pneumoniae did not show resistance to penicillin. This is in contrast to the concern of increasing resistance observed in pneumococcus in various studies[13],[14],[15].
We have not looked for the viral etiologies of pneumonia in the present study. Viral infection alone has been implicated in approximately 20-25% of community-acquired pneumonia[16], [17]. Hence, it is possible that some of the present cases that were culture negative may be of viral etiology.
The groups were well-matched with respect to age, weight and height. There was a male preponderance in our study. Similar overall male predominance has been reported from our center for all other diseases.[18] This could be a reflection of male bias seen in hospital studies in India and in many other countries. Thirty nine percent of our children were malnourished according to IAP guidelines. Malnutrition was common in our patients, which is similar to that reported elsewhere.[19]
Penicillin and gentamicin combination provides comprehensive broad spectrum coverage against S. pneumoniae , H. influenzae , gram-negative organisms and community acquired Staphylococcus aureus.[8], [11] Penicillin and ampicillin are very active against S . pyogenes and S . pneumonia , and moderately effective against H . influenzae.[11] Gentamicin is active against all the enteric gram-negative bacilli, S. aureus , S . epidermidis and pseudomonas by virtue of its synergistic effect with penicillin. The combination is therefore expected to be effective against most of the organisms causing pneumonia. Further, it may still be effective against penicillin-resistant pneumococcal pneumonia as there is no good evidence that in vitro penicillin-resistance of S . pneumoniae translates into treatment failure, even if microbial sensitivity tests are carried out in high quality laboratories.[20]
Amox-clav is a combination of a broad-spectrum beta-lactam antibiotic (amoxicillin) and the potent beta-lactamase enzyme inhibitor, clavulanic acid, an agent that has only weak antibacterial activity on its own. Clavulanic acid protects amoxicillin from hydrolysis by beta-lactamase and thus extends the spectrum of activity of amoxicillin to cover a wide range of gram-positive and gram-negative, and aerobic and anaerobic bacteria, including those isolates resistant to other beta lactam antibiotics because of beta lactamase production.[21] It is therefore likely to be effective against almost all the common bacterial organisms causing pneumonia. It is further supported by very low treatment failure rate in this study.
To treat a 10 kg old child, the cost of therapy of 3 days for amox-clav works out to be Rs. 230 in comparison to Rs. 120 for penicillin and gentamicin, i.e. it is twice more costly. But, the numbers of injections required in 3 days were 15 in C.pen and gentamicin combination whereas six in amox-clav. This may increase the rate of hospital-acquired infections, burden on hospital staff, and indirect costs involved.
To conclude, treatment failure rates were very low with both sequential injectable and oral regimens using C.pen and gentamicin combination followed by oral amoxicillin and sequential IV and oral amox-clav for the treatment of severe or very severe hypoxemic community-acquired pneumonia.
References
1. Cherian T. Acute respiratory infections in developing countries: current status and future directions. Indian Pediatr 1997; 34: 877-884.
2. Shann F. Etiology of severe pneumonia in children in developing countries. Pediatr Infect Dis J 1986; 5: 247-252.
3. WHO. Programme for control of acute respiratory infections. Acute Respiratory Infections in Children: Case Management in a Small Hospital in Developing Countries - A Manual for Doctors and Senior Health Workers. Geneva WHO/ARI/90.5.
4. Vuori-Holopainen E, Peltola H. Reappraisal of lung tap: Review of an old method for better etiologic diagnosis of childhood pneumonia. Clin Infect Dis 2001; 32 : 715-726.
5. World Health Organization. Acute respiratory infections: The forgotten pandemic. Bull WHO 1998; 76: 101-103.
6. McCracken GH Jr. Etiology and treatment of pneumonia. Pediatr Infect Dis J 2000; 19 : 373-377.
7. McCracken GH Jr. Diagnosis and management of pneumonia in children. Pediatr Infect Dis J 2000; 19: 924-928.
8. Korppi M. Community acquired pneumonia in children. Pediatr Drugs 2003; 5 : 821-832.
9. Juven T, Mertsola J, Waris M et al. Etiology of community acquired pneumonia in 254 hospitalized children. Pediatr Infect Dis J 2000; 19 : 293-98.
10. Kosma H, Korppi T, Jokinen M et al. Etiology of childhood pneumonia: Serologic results of a prospective, population based study. Pediatr Infect Dis J 1998; 17: 986-991.
11. McIntosh K. Community acquired pneumonia in children. N Engl J Med 2002; 346: 429-437.
12. Kumar L. Severe acute lower respiratory tract infection. Etiology and management. Indian J Pediatr 1987; 54 : 189-98.
13. Tan TQ, Mason EO Jr., Barson WJ et al. Clinical characteristics and outcome of children with pneumonia attributable to penicillin susceptible and penicillin-non-susceptible Streptococcus pneumoniae. Pediatrics 1998; 102: 1369-1375.
14. Pallares R, Linare J, Vakillo M et al. Resistance to Penicillin and cephalosporin and mortality from severe pneumococcal pneumonia in Barcelona, Spain. New Eng J Med 1995; 333: 474-480.
15. MC Gowan JE Jr and Metchock BG. Penicillin-resistant pneumococci-an emerging threat to successful therapy. J Hosp Infection 1995; 30 (suppl): 472-482.
16. Wubbel L, Muniz L, Ahmed A et al. Aetiology and treatment of community acquired pneumonia in ambulatory children. Pediatr Infect Dis J 1999; 18: 98-104.
17. Heiskanen-Kosma T, Korppi M, Tokinen C et al. Aetiology of childhood pneumonias: serologic results of prospective, population-based study. Pediatr Infect Dis J 1998; 17: 986-991.
18. Singhi S, Jain V and Gupta G. Pediatric emergencies at a tertiary care hospital in India. J Trop Ped 2003; 49: 207-211.
19. Kumar L, Kumar V, Mitra SK et al. Staphylococcal lung disease in children. Indian Pediatr 1974; 11 : 793-797.
20. Rasmussen Z, Pio A and Enarson P. Case management of childhood pneumonia in developing countries: recent relevant research and current initiatives. Int J Tuberc Lung Dis 2000; 4: 807-826.
21. Easton J, Noble S and Perry CM. Amoxicillin/Clavulanic acid: A review of its use in the management of pediatric patients with acute otitis media. Drugs 2003; 63 : 311-340.(Bansal Arun, Singhi Sunit)
Abstract
Objective : To compare the efficacy of sequential injectable crystalline penicillin (C.pen) and gentamicin combination followed by oral amoxicillin with sequential IV and oral amoxicillin-clavulanate (amox-clav) in treatment of severe or very severe hypoxemic pneumonia. Methods : Children aged 2-59 months with WHO-defined severe or very severe pneumonia with hypoxemia (SpO 2 <90%) were included in the study. Patients with fever > 10 days, bacterial meningitis, prior antibiotic therapy > 24 hours, stridor, heart disease and allergy to any of the study drugs were excluded. They were randomly allocated to two groups - Group A and Group B. Group A received C. pen and gentamicin intravenously (IV), followed by oral amoxicillin and group B got amox-clav IV, followed by oral amox-clav. Minimum duration of IV therapy was 3 days and total 7 days. Respiratory rate, oxygen saturation and chest wall indrawing were monitored 6 hourly. Results : 71 patients were included. There were two (5.2%) blood cultures positive in group A and three (9%) in group B. Organisms isolated were S. pneumoniae (n=3) and H. influenzae-b (n=2). There was only one treatment failure in each of the groups. One was due to penicillin resistant H. influenzae -b and the other was due to worsening of pneumonia. The mean time taken for normalization of tachypnea, hypoxia, chest wall indrawing and inability to feed was similar (P-N.S). Mean duration of IV therapy in group A was 76±25 hrs and group B was 75±24 hrs (p>0.1). Conclusion : In children of 2-59 months, sequential injectable C. pen and gentamicin combination, followed by oral amoxicillin or sequential IV and oral amox-clav were equally effective for the treatment of severe or very severe hypoxemic community acquired pneumonia.
Keywords: Acute respiratory infections; Community acquired pneumonia; Penicillin; Gentamicin; Amoxicillin/clavulanate
Acute Respiratory Infections (ARI) kill four million children every year, and most of these deaths are caused by pneumonia. Of these, developing countries are responsible for a disproportionate 90% of the deaths.[1] Standard case management guidelines of World Health Organization (WHO) recommend hospitalization, oxygen and injectable antibiotics in severe and very severe pneumonia patients which contributes to majority of pneumonia case fatality.[2] The most frequently isolated pathogens are S. pneumoniae and H. influenzae ; staphylococcus aureus and gram negative organisms account for a small proportion.[2],[3],[4] WHO has given simple guidelines for early detection and rational antibiotic treatment of pneumonia and recommend penicillin and gentamicin combination or chloramphenicol as first line therapy in patients with very severe pneumonia and severe pneumonia.[3] This provides adequate coverage against the common pathogens involved.[3] Streptococcus pneumoniae and H . influenzae cause most fatal pneumonia in children, and these bacteria can be killed by several inexpensive antibiotics such as penicillin and ampicillin.[5] The objective of this study was to compare the efficacy of sequential injectable crystalline penicillin (C.pen) and gentamicin, combination followed by oral amoxicillin, with sequential IV and oral amoxicillin-clavulanate (amox-clav) in treatment of severe or very severe hypoxemic pneumonia.
Materials and Methods
This study was an open label randomized controlled trial conducted at Advanced Pediatrics Center, Post Graduate Institute and Medical Education and Research, during July 1999 to June 2000. Institute Ethics Committee approved the study. Informed written consent was obtained from the parents.
Inclusion criteria: Two months to 59 months old patients who had fever (temperature > 38 0sub c) and with history of cough or rapid or difficult breathing were screened for their eligibility for inclusion in the study. Those with tachypnea, chest wall indrawing, hypoxemia in room air and X-ray chest showing alveolar infiltrates, segmental or lobar consolidation were included in the study. Tachypnea was defined as respiratory rate 3 50/min in 2-11 months and 3 40/min in 12-59 month old child.[3] Chest wall indrawing was defined as inward movement of lower chest wall on breathing in.[3] Hypoxemia was defined as oxygen saturation less then 90% in room air.[3] Severe pneumonia was defined as tachypnea and chest wall indrawing.[3] Very severe pneumonia was defined as tachypnea, chest wall indrawing and either central cyanosis or inability to drink.[3]
Exclusion criteria: Patients were excluded if they had fever >10 days, intravenous antibiotic>24 hrs, heart disease, stridor when calm, audible wheeze, bacterial meningitis, history of recurrent cough, previously diagnosed asthma, diphtheria, pertusis, measles, allergy to study drugs and renal failure.
Enrolment of subjects, baseline examination and laboratory data: The baseline history and examination was obtained in each case. It included description of symptoms prior to admission and their duration, treatment for the illness prior to admission, respiratory rate, heart rate, temperature, level of consciousness, weight, height, respiratory, cardiovascular and neurological findings. Oxygen saturation (SpO 2 ) was measured with the help of a pulse oximeter (Nellcore ) using a finger probe or ear lobe probe whichever was appropriate. Complete blood counts, arterial blood gases, blood glucose and bacterial culture were obtained.
Randomization: Patients were randomly allocated to group A or B. The randomization was done in blocks of 6 patients and stratified in 2 age groups- 2 months to 11 months and 12 months to 59 months. Randomization list was prepared before starting the study and random treatment assignment was placed in serially - labeled sealed envelopes. The assignment was opened when patient had met all the inclusion and exclusion criteria and written consent was available.
Patients in Group A received Crystalline penicillin (benzyl penicillin) - 50,000 IU/kg IV, q6h and g entamicin 2.5 mg/kg, IV, q8h for at least 3 days. After that, oral amoxicillin 15 mg/kg 8 hourly was substituted for C.pen. Group B patients were given Amoxicillin- Clavulanate 30 mg/kg IV q12h for at least 3 days and were changed to oral amox-clav when able to feed.
Supportive therapy was given as per the standard case management guidelines prepared by WHO programme for the control of ARI[3]. After enrolment, patients were followed up every 6 hour, to record respiratory rate, chest wall indrawing, and oxygen saturation were recorded.
Outcome Variables: Outcome variables were treatment failure and length of time (in hours) taken for recovery from tachypnea, hypoxemia and chest-wall indrawing.
Treatment failure was defined as any change, modification, or discontinuation of allocated antibiotic therapy because of deterioration in patient's condition, development of serious intercurrent illness or complications such as refractory septic shock, acute renal failure, meningitis etc., persistence of danger signs such as inability to drink after 48 hrs of treatment, or relapse of the hypoxemic pneumonia during the following 2 weeks.
Statistical Analysis: Patient's characteristics across the groups were compared by analysis of variance or Student 't' test and chi-square test. The outcome analysis was on 'intention to treat' basis.
Results
Seventy-one patients were enroled in the study, of which 38 were randomized to receive C. pen/gentamicin (group A) and 33 patients to receive amox-clav (group B).
Clinical characteristics, respiratory rate, heart rate, and oxygen saturation were similar in both the groups table1. Blood culture was positive in two patients in group A and three in group B. Group A had one each of S . pneumoniae and H . influenzae b, while group B had two S . pneumoniae and one H . influenzae-b isolated in blood culture. None of the S. pneumoniae showed resistance to penicillin, amoxicillin, erythromycin and gentamicin, while one of two H . influenzae-b was resistant to all of above (it was sensitive to ciprofloxacin, cefotaxime and chloramphenicol).
Outcome: Only 2 patients, one in each group had treatment failure. The one in group A had H. influenzae-b in blood culture that was resistant to penicillin and required change of antibiotics. The patient in group B continued to worsen and required change in antibiotics and was put on mechanical ventilation.
Mean time taken for recovery of various signs of respiratory distress was comparable in both the groups table2 as also the pattern of time taken (in hours) for recovery from tachypnea, chest wall indrawing, hypoxia and inability to feed Figure1. Mean duration of IV antibiotics was 76±24 hrs in group A and 75±24 hrs in group B. (P - n.s.)
Discussion
This study shows that the sequential injectable and oral regimens using C. pen and gentamicin combination followed by oral amoxicillin and sequential IV and oral amox-clav for the treatment of severe or very severe hypoxemic community - acquired pneumonia were equally effective. There was one instances of treatment failure in one in each group. One case of treatment failure was because of penicillin resistant H . influenzae-b . The other patient had worsening respiratory distress requiring ventilatory support and change of antibiotics.
Five (7.0%) blood cultures were positive in this study. This is in accordance with the various studies that have found the very low positivity rate of blood cultures in pneumonia[6], [7]. Moreover, other studies, which have investigated for bacteria and viruses, have shown that in more than 12-58% of lower respiratory tract illnesses, the organism is not isolated[8]. The organisms isolated were Streptococcus pneumoniae and Hemophillus influenzae-b. This is compatible with the published data[9], [10],[11]. In developing countries, H . influenzae-b has been implicated to be important cause of pneumonia [12]. Indian data on H. influenzae strain is scarce; it has been found in only 10-15% of severe lower respiratory tract illness in India[12].
Only one culture in our study was resistant; that was H. influenzae-b. S . Pneumoniae did not show resistance to penicillin. This is in contrast to the concern of increasing resistance observed in pneumococcus in various studies[13],[14],[15].
We have not looked for the viral etiologies of pneumonia in the present study. Viral infection alone has been implicated in approximately 20-25% of community-acquired pneumonia[16], [17]. Hence, it is possible that some of the present cases that were culture negative may be of viral etiology.
The groups were well-matched with respect to age, weight and height. There was a male preponderance in our study. Similar overall male predominance has been reported from our center for all other diseases.[18] This could be a reflection of male bias seen in hospital studies in India and in many other countries. Thirty nine percent of our children were malnourished according to IAP guidelines. Malnutrition was common in our patients, which is similar to that reported elsewhere.[19]
Penicillin and gentamicin combination provides comprehensive broad spectrum coverage against S. pneumoniae , H. influenzae , gram-negative organisms and community acquired Staphylococcus aureus.[8], [11] Penicillin and ampicillin are very active against S . pyogenes and S . pneumonia , and moderately effective against H . influenzae.[11] Gentamicin is active against all the enteric gram-negative bacilli, S. aureus , S . epidermidis and pseudomonas by virtue of its synergistic effect with penicillin. The combination is therefore expected to be effective against most of the organisms causing pneumonia. Further, it may still be effective against penicillin-resistant pneumococcal pneumonia as there is no good evidence that in vitro penicillin-resistance of S . pneumoniae translates into treatment failure, even if microbial sensitivity tests are carried out in high quality laboratories.[20]
Amox-clav is a combination of a broad-spectrum beta-lactam antibiotic (amoxicillin) and the potent beta-lactamase enzyme inhibitor, clavulanic acid, an agent that has only weak antibacterial activity on its own. Clavulanic acid protects amoxicillin from hydrolysis by beta-lactamase and thus extends the spectrum of activity of amoxicillin to cover a wide range of gram-positive and gram-negative, and aerobic and anaerobic bacteria, including those isolates resistant to other beta lactam antibiotics because of beta lactamase production.[21] It is therefore likely to be effective against almost all the common bacterial organisms causing pneumonia. It is further supported by very low treatment failure rate in this study.
To treat a 10 kg old child, the cost of therapy of 3 days for amox-clav works out to be Rs. 230 in comparison to Rs. 120 for penicillin and gentamicin, i.e. it is twice more costly. But, the numbers of injections required in 3 days were 15 in C.pen and gentamicin combination whereas six in amox-clav. This may increase the rate of hospital-acquired infections, burden on hospital staff, and indirect costs involved.
To conclude, treatment failure rates were very low with both sequential injectable and oral regimens using C.pen and gentamicin combination followed by oral amoxicillin and sequential IV and oral amox-clav for the treatment of severe or very severe hypoxemic community-acquired pneumonia.
References
1. Cherian T. Acute respiratory infections in developing countries: current status and future directions. Indian Pediatr 1997; 34: 877-884.
2. Shann F. Etiology of severe pneumonia in children in developing countries. Pediatr Infect Dis J 1986; 5: 247-252.
3. WHO. Programme for control of acute respiratory infections. Acute Respiratory Infections in Children: Case Management in a Small Hospital in Developing Countries - A Manual for Doctors and Senior Health Workers. Geneva WHO/ARI/90.5.
4. Vuori-Holopainen E, Peltola H. Reappraisal of lung tap: Review of an old method for better etiologic diagnosis of childhood pneumonia. Clin Infect Dis 2001; 32 : 715-726.
5. World Health Organization. Acute respiratory infections: The forgotten pandemic. Bull WHO 1998; 76: 101-103.
6. McCracken GH Jr. Etiology and treatment of pneumonia. Pediatr Infect Dis J 2000; 19 : 373-377.
7. McCracken GH Jr. Diagnosis and management of pneumonia in children. Pediatr Infect Dis J 2000; 19: 924-928.
8. Korppi M. Community acquired pneumonia in children. Pediatr Drugs 2003; 5 : 821-832.
9. Juven T, Mertsola J, Waris M et al. Etiology of community acquired pneumonia in 254 hospitalized children. Pediatr Infect Dis J 2000; 19 : 293-98.
10. Kosma H, Korppi T, Jokinen M et al. Etiology of childhood pneumonia: Serologic results of a prospective, population based study. Pediatr Infect Dis J 1998; 17: 986-991.
11. McIntosh K. Community acquired pneumonia in children. N Engl J Med 2002; 346: 429-437.
12. Kumar L. Severe acute lower respiratory tract infection. Etiology and management. Indian J Pediatr 1987; 54 : 189-98.
13. Tan TQ, Mason EO Jr., Barson WJ et al. Clinical characteristics and outcome of children with pneumonia attributable to penicillin susceptible and penicillin-non-susceptible Streptococcus pneumoniae. Pediatrics 1998; 102: 1369-1375.
14. Pallares R, Linare J, Vakillo M et al. Resistance to Penicillin and cephalosporin and mortality from severe pneumococcal pneumonia in Barcelona, Spain. New Eng J Med 1995; 333: 474-480.
15. MC Gowan JE Jr and Metchock BG. Penicillin-resistant pneumococci-an emerging threat to successful therapy. J Hosp Infection 1995; 30 (suppl): 472-482.
16. Wubbel L, Muniz L, Ahmed A et al. Aetiology and treatment of community acquired pneumonia in ambulatory children. Pediatr Infect Dis J 1999; 18: 98-104.
17. Heiskanen-Kosma T, Korppi M, Tokinen C et al. Aetiology of childhood pneumonias: serologic results of prospective, population-based study. Pediatr Infect Dis J 1998; 17: 986-991.
18. Singhi S, Jain V and Gupta G. Pediatric emergencies at a tertiary care hospital in India. J Trop Ped 2003; 49: 207-211.
19. Kumar L, Kumar V, Mitra SK et al. Staphylococcal lung disease in children. Indian Pediatr 1974; 11 : 793-797.
20. Rasmussen Z, Pio A and Enarson P. Case management of childhood pneumonia in developing countries: recent relevant research and current initiatives. Int J Tuberc Lung Dis 2000; 4: 807-826.
21. Easton J, Noble S and Perry CM. Amoxicillin/Clavulanic acid: A review of its use in the management of pediatric patients with acute otitis media. Drugs 2003; 63 : 311-340.(Bansal Arun, Singhi Sunit)