Abstract
Pneumonia caused by Klebsiella pneumoniae is important due to its high morbidity and mortality. This infection causes acute inflammation in the lung due to characterized by increased activity of neutrophils, generate oxy free radical and decreased the endogenous anti oxidant defense system. CSE1034 is a novel fixed dose combination drug of ceftriaxone plus sulbactam with VRP1034. The aim of this investigation was to compare the efficacy study of CSE1034 drug vs ceftriaxone alone in pneumonia induced rat model. For pneumonia infection in animal model, doses were standardized at concentration 102 to 106 CFU/ml of Klebsiella pneumoniae. Total thirty two male rats (150 ± 5 g) were randomely selected and divided into four groups of eight animals each. Group I was normal saline treated; group II was pneumonia infected; group III was infected plus ceftriaxone treated and group IV was infected plus CSE1034 treated. Pneumonia infection was induced in all group except group I via intranasal instillation, at concentration (log 106 CFU/ml) for 15 days. Infection was confirmed by raised body temperature, bacterial count, cell count and cytokine (TNF-α, IL-6) parameters in blood. After conformation of infection, CSE1034 and ceftriaxone drugs treatment were stared for 15 days. At the end experiment, blood and lung tissue were collected and measured the biochemical and enzymatic parameters in all group. The finding showed that a significant decrease lactate dehydrogenase activity, malonaldialdehyde, total protein, albumin, nitrate, tumor necrosis factor-α, interlukin-6 levels and bacterial count along with increase reduced glutathione level in lung homogenate of CSE1034 treated group as compared to pneumonia induced and ceftriaxone treated groups. These findings suggested that CSE1034 is effective than ceftriaxone which reduced bacterial count and enhanced endogenous antioxidant status along with reduces, inflammatory response during pneumonia infection.
Highlights
Klebsiella pneumoniae is an important cause of both communityacquired as well as nocosomial lung infection
The finding showed that a significant decrease lactate dehydrogenase activity, malonaldialdehyde, total protein, albumin, nitrate, tumor necrosis factor-α, interlukin-6 levels and bacterial count along with increase reduced glutathione level in lung homogenate of CSE1034 treated group as compared to pneumonia induced and ceftriaxone treated groups. These findings suggested that CSE1034 is effective than ceftriaxone which reduced bacterial count and enhanced endogenous antioxidant status along with reduces, inflammatory response during pneumonia infection
Bacterial count was found almost equal in 104,105 CFU/ml at 12 hours whereas at 18 hours, the bacterial count was slightly reduced at dose 105 CFU/ml but at 24 hours, the count was increased at dose 105 CFU/ml
Summary
Klebsiella pneumoniae is an important cause of both communityacquired as well as nocosomial lung infection. Ceftriaxone is a third generation cephalosporin class of betalactam drug with potent bactericidal activity against a wide range of gram positive and gram negative bacteria [7]. Sulbactam is potent and highly specific inhibitors of a wide range variety of beta lactamase produced by common gram positive and gram negative aerobes and anaerobes [9]. It is a molecule which inhibits beta lactamase, an enzymes produced by bacteria that destroys the antibiotics. VRP1034 (under patent) used as a third vector for their syngestic effect and play a significant role for reduction of toxicity It is having a antimicrobial, chelating and antioxidant properties. The aim of this study was to determined the comparative efficacy CSE1034 vs ceftriaxone alone drugs in Klebsiella pneumoniae induced pneumonia induced rat model
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