TY - JOUR
T1 - Combination therapy with ampicillin and azithromycin in an experimental pneumococcal pneumonia is bactericidal and effective in down regulating inflammation in mice
AU - Majhi, Arnab
AU - Kundu, Kiran
AU - Adhikary, Rana
AU - Banerjee, Madhubanti
AU - Mahanti, Sayantika
AU - Basu, Anirban
AU - Bishayi, Biswadev
N1 - Funding Information:
The author (Biswadev Bishayi) thanks the University Grants Commission, Government of India, New Delhi, India for providing fellowship to Mr. Arnab Majhi (sanction number: UGC/561/Jr. Fellow. SC. Dated: 22.07.2010) and also to the Department of Science and Technology, Govt. of India for additional support under DST-PURSE programme to the Department of Physiology, University of Calcutta. The author (Biswadev Bishayi) is indebted to Dr. Sunil Kumar Manna, Scientist and Head, Immunology Division, Centre for DNA Fingerprinting and Diagnostics, Hyderabad, India for providing us with the primers for pneumolysin and autolysin.
PY - 2014/2/24
Y1 - 2014/2/24
N2 - Objectives. Emergence of multidrug resistance among Streptococcus pneumoniae (SP), has limited the available options used to treat infections caused by this organism. The objective of this study was to compare the role of monotherapy and combination therapy with ampicillin (AMP) and azithromycin (AZM) in eradicating bacterial burden and down regulating lung inflammation in a murine experimental pneumococcal infection model. Methods. Balb/C mice were infected with 10§ssup§6§esup§ CFU of SP. Treatments with intravenous ampicillin (200 mg/kg) and azithromycin (50 mg/kg) either alone or in combination was initiated 18 h post infection, animals were sacrificed from 0 - 6 h after initiation of treatment. AMP and AZM were quantified in serum by microbiological assay. Levels of TNF-α, IFN-γ IL-6, and IL-10 in serum and in lungs, along with myeloperoxidase, inflammatory cell count in broncho alveolar lavage fluid, COX-2 and histopathological changes in lungs were estimated. Results: Combination therapy down regulated lung inflammation and accelerated bacterial clearance. This approach also significantly decreased TNF-α, IFN-γ, IL-6 and increased IL-10 level in serum and lungs along with decreased myeloperoxidase, pulmonary vascular permeability, inflammatory cell numbers and COX-2 levels in lungs. Conclusions: Combinatorial therapy resulted in comparable bactericidal activity against the multi-drug resistant isolate and may represent an alternative dosing strategy, which may help to alleviate problems with pneumococcal pneumonia.
AB - Objectives. Emergence of multidrug resistance among Streptococcus pneumoniae (SP), has limited the available options used to treat infections caused by this organism. The objective of this study was to compare the role of monotherapy and combination therapy with ampicillin (AMP) and azithromycin (AZM) in eradicating bacterial burden and down regulating lung inflammation in a murine experimental pneumococcal infection model. Methods. Balb/C mice were infected with 10§ssup§6§esup§ CFU of SP. Treatments with intravenous ampicillin (200 mg/kg) and azithromycin (50 mg/kg) either alone or in combination was initiated 18 h post infection, animals were sacrificed from 0 - 6 h after initiation of treatment. AMP and AZM were quantified in serum by microbiological assay. Levels of TNF-α, IFN-γ IL-6, and IL-10 in serum and in lungs, along with myeloperoxidase, inflammatory cell count in broncho alveolar lavage fluid, COX-2 and histopathological changes in lungs were estimated. Results: Combination therapy down regulated lung inflammation and accelerated bacterial clearance. This approach also significantly decreased TNF-α, IFN-γ, IL-6 and increased IL-10 level in serum and lungs along with decreased myeloperoxidase, pulmonary vascular permeability, inflammatory cell numbers and COX-2 levels in lungs. Conclusions: Combinatorial therapy resulted in comparable bactericidal activity against the multi-drug resistant isolate and may represent an alternative dosing strategy, which may help to alleviate problems with pneumococcal pneumonia.
KW - Ampicillin
KW - Azihromycin
KW - Combination therapy
KW - Inflammation
KW - Multiple drug resistance
KW - Streptococcus pneumoniae
UR - http://www.scopus.com/inward/record.url?scp=84895462067&partnerID=8YFLogxK
U2 - 10.1186/1476-9255-11-5
DO - 10.1186/1476-9255-11-5
M3 - Article
AN - SCOPUS:84895462067
SN - 1476-9255
VL - 11
JO - Journal of Inflammation (United Kingdom)
JF - Journal of Inflammation (United Kingdom)
IS - 1
M1 - 5
ER -