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• 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 novel antibiotics used are linezolid, synercid and daptomycin.
• Linezolid – it is effective against MRSA and VRE infections. Protein synthesis inhibition as it affects the binding site of the initiator – tRNA.

  The gram negative bacteria 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 - blocks substrate

  Linezoid - protein synthesis inhibition (50S sub particle)

  Synercid - protein synthesis inhibition (70s subparticle)

  Daptomycin - cell membrane depolarization
• 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. Higher vancomycin resistance.

  UTI and endocarditits are the most common infections 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 nosocomial diarrhea due to antibiotic therapy. Toxigenic strains lead to damage of colonic mucosa due to toxin A and B synergistic activity.

  Majority if these disease occurs before or after antibiotic therapy.
• CDAD treatment – antibiotic discontinued.

  Specific antibiotics are given orally (vancomycin and metronidazole)
• Metronidazole – nitroaryl compound. Prodrug is activated by anaerobic enzymes which reduce the nitro group to hydroxylamine.

  During the reduction, reactive products are made that destroy bacterial cell components – DNA, proteins and membranes.

  Helps to reserve vancomycin for MRSA infection.

  Disrupts nucleic acid synthesis.
• 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.
• Gram negative bacteria uses the enzyme B lactamase to be resistant against B lactam antibiotics.

  Penicillin – B lactamases resistant

  Cephalosporins and monobactams – B lactamase extended spectrum resistance.

  Carbapenems – carbapenemases resistance (can deactivate all types of B lactam antibiotics and are resistant to inhibition from these enzymes)
• Antibiotic treatment of HAI by gram negative bacteria – carbapenems for pathogen expressing extended B lactamase spectrum

  Colistin or tigecycline for pathogens expressing carbapenemases.
• Meropenem – carbapenem B lactam antibiotic.

  Similar to penicillin structure. Bicyclic ring with one B lactam ring and a 5 membered ring.

  Sulphur attached as a side chain to 5 membered ring despite not being part of the ring.

  There is 1 C=C in 5 membered ring.
• Colistin – it is a polymyxin antibiotic and produces colistin A and B. It is made up of cyclic peptides. It is used as a last resort to gram negative bacteria 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 acyl t-RNA into ribosome. It is a broadd spectrum antibiotic.
• penicillin can inhibit cell wall synthesis by binding to the penicillin binding protein. 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.