New antibiotics – antibiotics belonging to an existing class of antibiotics but is not used clincially.
Novel antibiotics – has an action mechanism not used against bacteria.
MRSA infection treatment – majority of the strains are resistant to antibiotics but a few.
The classical antibiotic for MRSA is vancomycin. The novelantibiotics used are linezolid, synercid and daptomycin.
Linezolid – it is effective against MRSA and VRE infections. Protein synthesisinhibition as it affects the bindingsite of the initiator – tRNA.
The gram negativebacteria is resistant due to the efflux mechanisms.
Synercid – used intravenously to treat VRE and skin/skin structure infections caused by Staphylocccus aureus and streptococcus pyogenes.
The combination inhibits protein synthesis by binding to the same place on the 70S ribosome.
Daptomycin – it is a lipopeptide which is used intravenously for gram positive infections. Causes depolarization of cell membranes by bidning to it. It also interrupts DNA, RNA and protein synthesis.
MRSA antibiotics and mode of actions:
vancomycin - blockssubstrate
Linezoid - proteinsynthesisinhibition (50S sub particle)
Enterococci – it is a pathogen found in patients who are at the hospital for a long time and are getting adminstered many antibiotic courses.
There are 2 types E.faecalis and E.faecium.
E.Faecium most difficult to treat. Highervancomycin resistance.
UTI and endocarditits are the most commoninfections by the enterococci.
Vancomycin – it is a glycopeptide antibiotic. It inhibits cell wall synthesis.
Penicillin blocks enzyme and vancomycin blocks susbstrate.
Bacteria gets resistance to vancomycin when there is a loss in a hydrogen bond which leads to a drop in the drug binding affinity.
Clostridium difficile – it is a spore forming, anaerobic, gram positive bacterium. Causes nosocomialdiarrhea due to antibiotic therapy. Toxigenicstrains lead to damage of colonicmucosa due to toxinA and Bsynergisticactivity.
Majority if these disease occurs before or afterantibiotictherapy.
CDAD treatment – antibiotic discontinued.
Specific antibiotics are given orally (vancomycin and metronidazole)
Metronidazole – nitroaryl compound. Prodrug is activated by anaerobicenzymes which reduce the nitro group to hydroxylamine.
During the reduction, reactive products are made that destroybacterialcellcomponents – DNA, proteins and membranes.
Helps to reservevancomycin for MRSAinfection.
Disrupts nucleic acidsynthesis.
Vancomycin replaces metronidazole if there is no drug response, pregnancy and lactation, drug intolerance, critically ill patients and metronidazole resistant organism.
HAI caused by gram negative – blood stream infections, pneumonia, UTI.
UTI caused by urinary catheters. Caused by uropathogenic E.coli.
Gramnegative bacteria uses the enzymeBlactamase to be resistant against Blactamantibiotics.
Penicillin – Blactamasesresistant
Cephalosporins and monobactams – Blactamaseextendedspectrumresistance.
Carbapenems – carbapenemasesresistance (can deactivateall types of B lactamantibiotics and are resistant to inhibition from these enzymes)
Antibiotictreatment of HAI by gram negative bacteria – carbapenems for pathogenexpressingextendedBlactamasespectrum
Colistin or tigecycline for pathogensexpressingcarbapenemases.
Meropenem – carbapenemBlactamantibiotic.
Similar to penicillinstructure.Bicyclicring with oneBlactamring and a 5memberedring.
Sulphurattached as a sidechain to 5memberedring despite not being part of the ring.
There is 1C=C in 5memberedring.
Colistin – it is a polymyxinantibiotic and produces colistinA and B. It is made up of cyclic peptides. It is used as a last resort to gram negativebacteria that are resistant to other antibiotics.
Colistin sticks to the phosphate of the lipid group in the cell membrane.Breaks the membrane down and kills the bacteria.
Tigecycline – inhibits bacterial protein synthesis. Binds to 30S subunit and blocks entry of amino acylt-RNA into ribosome. It is a broadd spectrumantibiotic.
penicillin can inhibit cell wall synthesis by binding to the penicillinbindingprotein.Bacteria developed resistance forming beta lactumase which will destroy penicillin before it bind.
Penicillin was modified to methicillin which again led to bacteria resistance but the bacteria changed the binding protein, preventing the methicillin to bind. Therefore penicillin and methicillin are not effective antibiotics.