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Before going into the macrolides topic let’s first discuss about protein synthesis and bacterial bacterial protein synthesis for bacteria to survive it requires protein for reproduction growth repair and regulation of metabolism which are coded by unique generate code present in dna there are two main steps in bacterial protein synthesis transcription and
Translation first let’s talk about transcription for the bacteria to begin protein synthesis the double stranded dna molecule must unwind and separate in the region which codes for the specific protein only one strand of dna serves as a template transcription is carried out by rna polymerase which results in the formation of messenger rna which is an exact copy
Of the dna segment now in translation when the strand of messenger rna is complete it detaches from the dna template and ribosomes get attached to messenger rna bacterial ribosomes are made of a small 30 s and a large 50s subunit after the two subunits join together around a strand of messenger rna the polypeptide chain synthesis begins during this death along
The messenger rna alignment of p rna molecules occur in sequence each trna carries a unique amino acid determined by the sequence of messenger rna and when aligned along the messenger rna and ribosomal joins together to form a polypeptide chain the ribosomes will keep adding amino acids to the growing polypeptide chain until it comes across a point along the
Messenger rna known as the stop codon it is a nucleotide triplet present in the messenger rna which signals a termination of translation into proteins and at this point it releases the finished protein molecule collides macrolide antibiotics example azithromycin clarithromycin and talero myosin are used in the treatment of community-acquired respiratory infection
Particularly pneumonia they are derivatives of old macrolide antibiotic erythromycin mechanism of action of macrolides antibacterial mechanism of action of newer macrolides is similar to that of erythromycin that they bind to 50 subunit of bacterial ribosome leading to inhibition or transpeptidase translocation chain elongation and ultimately bacterial protein
Synthesis mechanism of resistance of macrolides acquired macrolide resistance is an increased problem there are two main mechanisms of acquired macrolide resistance that have been identified me delays encoded by the erm genes earng gene alter the macrolide binding site on the bacterial ribosomal rna usually conferring a high degree of macrolide resistance
Changes to the 50’s ribosomal subunit which is the target binding site for macrolide antibiotics will lead to resistance to the macrolides this mechanism of resistance is mediated by the erythromycin ribosome methylation gene which is found on plasmids or transposon transposons are small genetic elements that are capable of moving from one bacterium to another
And integrating into the host chromosomal dna copies of the aritaum – ribosome methylation gene are transported to other bacteria by plasmids or transposons through polite channels and the era through myosin ribosome methylation gene is incorporated into the new bacterial genome during protein synthesis this bacterium will transcribe and translate the genetic
Code of the era through meissen ribosome methylation gene which results in the production of a protein enzyme that is capable of methylating the 50s subunit at a specific position the altered 50s subunit results in decreased binding affinity for the macro lights and other antibiotics such as wrinkles amides and strep – grameen type b this pattern of resistance
Is referred to as the mls phenotype because the macro light is unable to bind to the 50s ribosomal subunit it is not able to inhibit protein synthesis and thus the bacteria itself is not harmed and continues to produce polypeptide chains of amino acids active macro light efflux pumps encoded by mes ms ra and msrb genes this mechanism confers a low to moderate
Degree of macrolide resistance ‘if lux pumps are coded by the mi fa gene ‘if lux pumps develop resistance to only macro lights and not blink olamide’s and strep to graham and type b they are referred to as m phenotype the eve lux pumps are energy dependent these pumps traverse the cell membrane off the bacteria and function by pumping out the macrolide antibiotic
After it has entered the bacterium even though the efflux pumps are present micro light antibiotics continue to enter the bacteria once they are inside the cytoplasm of the bacteria these efj lux pumps actively remove the macrolide antibiotics before they have a chance to reach their target 50s ribosomal subunit and the bacterial protein synthesis is unaffected
In north america a flex pump resistance mechanisms are more common whereas ribosomal mechanism is more common in europe and asia these mechanisms are responsible for error through mice and resistance in most gram positive cocci example staphylococcus aureus streptococcus pneumonia and other streptococci mechanism of resistance to azithromycin or clarithromycin
Are the same or similar to those of aritaum ison as it’s from ison clarithromycin and toledo myosin have enhanced gram-negative tivity compared with erythromycin as a result erythromycin resistance gram negative organisms may be sensitive to the newer drug as it roman is more effective in vitro against most strains of haemophilus influenzae and has more rapid
Killing and a longer post antibiotic effect than clarithromycin for this reason as it roman is preferred over clarithromycin in outpatients with community acquired pneumonia to have comorbidities such as chronic obstructive pulmonary disease erythromycin does not have activity against haemophilus influenzae these antibiotics are also usually active against other
Gram positive organisms including steppe locust aureus and group a b c and g streptococcus metabolism and pharmacokinetics newer macrolides are stable at gastric ph as a result their bioavailability is better than that of erythromycin and enteric coding is not required in contrast azithromycin extended-release suspension should be taken on an empty stomach and
Clarithromycin extended-release tablets should be administered with food tissue and intracellular penetration all macrolides distribute and concentrate well in most body tissues and phagocytic cells tell Γͺtre meissen is the most highly concentrated in tissue followed by other macrolides adverse reactions the newer macrolides are generally better tolerated than
Aritaum isen because of its most frequent gastrointestinal side effects risk of qt prolongation and sudden death era through meissen is now rarely recommended some of the major adverse effects associated with these drugs are as follows hepatotoxicity in which abnormal lfp hepatitis cholestatic jaundice hepatic necrosis and hepatic failure are seen gastrointestinal
Toxicity in which nausea diarrhea and abdominal pain may be seen qt prolongation is especially associated with erythromycin
Transcribed from video
Macrolides Antibiotics Animated presentation- Mechanism of action , Kinetics , Resistance By Dr.G Bhanu Prakash Animated Medical Videos