Fight against Resistance to Beta lactam antibiotics

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The Fight Against Resistance -to ß lactam antibiotics:

The Fight Against Resistance -to ß lactam antibiotics Exam Roll: 2119 Session: 2012-13 Department of Microbiology University Of Dhaka.

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β-Lactam antibiotics (beta-lactam antibiotics) are a broad class of  antibiotics , consisting of all antibiotic agents that contains a  β-lactam  ring in their molecular structures. The B-lactam structure of penicillin was detected by Ernest Chain in 1942. share similar • features of chemistry, • mechanism of action, • pharmacologic and clinical effects

Cell Wall Assembly:

Cell Wall Assembly Layer of cell wall with cross links of 5 glycines (gray) Second layer of cell wall cross-linked to the lower layer Transpeptidase (PBP) forms a 5-glycine bridge between peptides A subunit is added to the growing chain

Transpeptidase, or PBP (orange sunburst) is bound by beta-lactam antibiotic (light blue) and its activity is inhibited (turns gray):

Transpeptidase, or PBP (orange sunburst) is bound by beta-lactam antibiotic (light blue) and its activity is inhibited ( turns gray)

5-glycine crosslinking bridges cannot form in the presence of a beta-lactam, and the cell wall is deformed and weakened:

5-glycine crosslinking bridges cannot form in the presence of a beta-lactam, and the cell wall is deformed and weakened

PowerPoint Presentation:

Antibacterial agents do not cause bacteria to become resistant but their use preferentially selects resistant populations of bacteria.

Antibiotic resistance mechanisms:

Antibiotic resistance mechanisms Enzyme-Based Resistance: Aminoglycoside Disruption

Mechanisms of beta-lactam resistance:

Mechanisms of beta-lactam resistance Drug-modifying enzymes (beta-lactamases) Gram-positives(e.g., S. aureus ) excrete the enzyme Gram-negative (e.g., E. coli ) retain the enzyme in the periplasm Overexpression of cell wall synthetic enzymes Alteration of the PBPs so antibiotic cannot bind e.g., S. pneumoniae , gonococcus Exclusion from the site of cell wall synthesis Porin mutations in the outer membrane of Gram-negative bacteria only (e.g., Ps. aeruginosa )

Beta-lactamases (darkorange) bind to the antibiotics (lightblue) and cleave the beta-lactam ring. The antibiotic is no longer able to inhibit the function of PBP (orange sunburst):

Beta-lactamases (darkorange) bind to the antibiotics (lightblue) and cleave the beta-lactam ring. The antibiotic is no longer able to inhibit the function of PBP (orange sunburst) Beta-lactamases

Beta-lactamase activity:

Beta-lactamase activity

PowerPoint Presentation:

Numbers of unique β-lactamase enzymes identified since the introduction of the first β-lactam antibiotics. Source: Davies et al, 2010

Antibiotic misuse:

Antibiotic misuse Antibiotic Irrational and blind prescription Animal and Aquaculture feed Dumping of unused and residual antibiotic Consequence Environmen t Altered microbial community Antibiotic in food chain Antibiotic resistance develop

Fight against resistance to beta lactam antibiotics:

Fight against resistance to beta lactam antibiotics Fight against resistance microbes prophylactic Preventive

PowerPoint Presentation:

Fight to the beta lactam resistance microbes to get cure Beta lactamase inhibitor and efflux pump inhibitor Clavulanic acid Sulbactam Tazobactam ( ̶ )

Fight to the beta lactam resistance microbes to get cure :

Fight to the beta lactam resistance microbes to get cure Augmentin is combination of amoxicillin and clavulanate (clavulanate has s structure similar penicilline) it is B-lactamase inhibitor. Sulbactam – another B-lactamase Inhibitor. Combination Sulbactam + Ampicillin = Unasyn.

Penicillinase (beta lactamase)-resistant penicillins :

Penicillinase (beta lactamase)-resistant penicillins Methicillin and isoxazolyl penicillins (e.g. oxacillin, cloxacillin and dicloxacillin) They are the drugs of first choice for treating infections of the penicillase-productive microbes .

Cephalosporins & Cephamycins: :

Cephalosporins & Cephamycins : They have a betalactam ring. They are relatively stable in dilute acid and are highly resistant to penicillinase . Carbapenems The antimicrobial spectrum of imipenem is the broadest one of all the beta-lactam antibiotics. Imipenem is easily hydrolized by dehydropeptidase in the body, so the clinical preparation is the mixture made by imipenem and peptidase inhibitor named cilastatin.

PowerPoint Presentation:

Although some bacteria can produce a beta-lactamase called cephalosporinase that acts on the cephalosporin nucleus to destroy its antibacterial activity. Today Real Scenario is Carbapenems are highly resistant to hydrolysis by penicillinases and cephalosporinases but they are hydrolyzed by metallo -beta-lactamase and carbapenemases . Extended-spectrum beta-lactamases(ESBLs) are mutant enzymes that can Hydrolyze 3 rd and 4 th gen cephalosporins and aztreonam

PowerPoint Presentation:

Prevention is better than cure Antibiotics effective use :

How Does We Manage This Crisis?:

How Does We Manage This Crisis?

Ten Wonders for Infection Control (How to Prevent Resistance and Lower Cost):

Ten Wonders for Infection Control (How to Prevent Resistance and Lower Cost) Source: CDC, 2010

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Prevention is better than cure The World Health Organization’s policy package to combat antimicrobial resistance: Making the best of currently available antimicrobial agents Determining microbiological etiology of infections Empirical therapy based on most probable etiology Early de-escalation of antimicrobial therapy Knowledge of local and regional antimicrobial resistance rates Stratifying patients at risk of infections due to resistant organisms Utilizing tools to determine severity of illness scores

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