Beta-lactamase

From the very beginning of my student life, I loved biology. When I was in my lower secondary school, I still remember that day when my science teacher told me the story of microbes and the day after showed and taught applications of microscope, my interest in microbiology started to take its shape. I became even intensely interested when he told us that bacteria and virus are invisible to your naked eyes, however they can cause you disease and some might kill you. After the completion of my high

REVIEW OF LITRATURE The term “sepsis” has been around since prehistoric times. Hippocrates presented the word sepsis 2400 years ago to represent a condition where an overwhelming infection leads to tissue breakdown with rotting, foul odour, and disease. The ancient Roman scholar and writer (116 BC–27 BC), Marcus Terentius Varro mentioned that “small creatures, invisible to the eye, fill the atmosphere, and breathed through the nose cause dangerous diseases.” In the early 1990s at a conference convened

The term “sepsis” has been around since prehistoric times. Hippocrates presented the word sepsis 2400 years ago to represent a condition where an overwhelming infection leads to tissue breakdown with rotting, foul odour, and disease. The ancient Roman scholar and writer (116 BC–27 BC), Marcus Terentius Varro mentioned that “small creatures, invisible to the eye, fill the atmosphere, and breathed through the nose cause dangerous diseases.” In the early 1990s at a conference convened by the American

become unbeatable to some of today’s most potent antibiotics. An alarming statistic that was recently released, “23,000 people are killed every year out of the 2 million who are be infected by these superbugs” (NIH Feb. 2014). Extended Spectrum Beta-Lactamases (ESBLs) are currently one of the leading superbugs in the world; with a skyrocketing mortality rate and plummeting choices of antibiotics to treat the infections caused by this bacterium, the clock is ticking to find this superbug’s Achilles tendon

newly approved combination drug Avycaz is composed of Ceftazidime and Avibactam. Ceftazidime is a 3rd generation cephalosporin. It inhibits bacterial cell wall synthesis by binding to the penicillin binding protein. Avibactam is a non- Beta lactam Beta Lactamase Inhibitor. It is essential in increasing the

neonatal septicemia caused by Gram negative bacilli (GNB) has increased in the past decade and it is often associated with higher mortality rate.(3) The emergence of multi-drug resistant among gram negative bacilli specifically Extended spectrum β-lactamase (ESBL) producing GNB deserves particular concerns, as the treatment options available for multiple drug resistant (MDR) strain is often limited. Inappropriate initial antibiotics predispose these neonates to severe sepsis and poor outcome (4). Sepsis

(59/171) of MICU and 57.1% (24/42) of PICU isolates were detected with CTX alone suggesting CTX-M–type. Whereas none of the isolates were detected by CAZ/CLA combined disc alone. Among the 213 ESBL positive isolates, 66 also tested positive for AmpC β-lactamase. Of those, 16 (24.2%) isolates were proved to be ESBL only by FEP/CLA combined disc test. Thus 16 isolates would have been missed by using only CLSI recommended method (Table

1.6.1 Classification of β-lactamases Two major schemes for classification of β-lactamases are currently in use. The molecular classification of β-lactamases is based on the amino acid sequence homology dividing them into four classes A through D. The enzymes belonging to class A, C and D utilize serine residue for substrate hydrolysis while class B enzymes (metallo-β-lactamases) utilize divalent zinc ions for β-lactam hydrolysis [Ambler R. P. et al, 1991]. The functional classification is based

natural products from microorganisms like penicillin, cephalosporin and other β lactam based antibiotics (Figure 1). 1,2 However, soon after its commercialization and widespread usage, β lactamase secreting penicillin resistant strains of Staphylococcus aureus were isolated.3 The introduction of methicillin (a β lactamase-insensitive semi-synthetic penicillin), to curb the resistance problem resulted in the evolution of another resistant strain known as methicillin-resistant Staphylococcus aureus (MRSA)

1.7.2.3 CTX-M β-lactamases Most of the early ESBLs were mainly ceftazidimases with little or no hydrolytic activity against cefotaxime. ESBLs often showed variable substrate preference with some enzymes hydrolyzing one cephalosporin type better than the others. The first enzyme with the capability of cefotaxime hydrolysis but unable to hydrolyze ceftazidime was reported from an E. coli strain isolated from a dog that was used as a model to study cephalosporin pharmacokinetics in Japan in 1986. It