Antibiotic Resistance Mechanisms

Bacteria develop ability to hydrolyze these drugs using β lactamase confers resistance to penicillin e.g. E. coli, Staph epidermidis, Pseudomonas aeruginosa, Klebsiella pneumoniae add β lactamase inhibitor e.g. clavulanic acid in amoxicillin-clavulanate (Augmentin) Genetic mutation of mecA a bacterial gene encoding a penicillin-binding protein. New PBP has reduced affinity for antibiotics confers resistance to methicillin, oxacillin, nafcillin e.g. MRSA Altered cell wall permeability confers resistance to tetracyclines, quinolones, trimethoprim and β lactam antibiotics Creation of biofilm barrier provides an environment where offending bacteria can multiply safe from the hoste immune system Salmonella Staph epidermidis Active efflux pumps confers resistance to erythromycin and tetracycline e.g. msrA gene in Staph Altered peptidoglycan subunit (altered D-alanyl-D-alanine of NAM/NAG-peptide)  confers resistance to vancomycin e.g. vancomycin resistant enterococcus (VRE)  Ribosome alteration erm gene confer inducible resistance to MLS (macrolide lincosamide streptogranin) agents via methylation of 23s rRNA demonstrate using D zone test    for inducible clindamycin resistance in Staph and beta hemolytic Strep Penicillins Mechanism interfer with bacterial cell wall synthesis Subclassification and tested examples natural penicillin G penicillinase-resistant methicillin (Staphcillin) aminopenicillins ampicillin (Omnipen, Polycillin) Cephalosporins Overview bactericidal Mechanism disrupts the synthesis of the peptidoglycan layer of bacterial cell walls   does so through competitive inhibition on PCB (penicllin binding proteins) peptidoglycan layer is important for cell wall structural integrity. same mechanicsm of action as beta-lactam antibiotics (such as penicillins) Subclassification and tested examples first generation cefazolin (Ancef, Kefzol) second generation cefaclor (Ceclor) third generation cefriazone (Rocephin) fourth generation cefepime (Maxipime) Fluoroquinolones Mechanism blocks DNA replication via inhibition of DNA gyrase  Side effects inhibit early fracture healing through toxic effects on chondrocytes  increased rates of tendinitis, with special predilection for the Achilles tendon.  tenocytes in the Achilles tendon have exhibited degenerative changes when viewed microscopically after fluoroquinolone administration. recent clinical studies have shown an increased relative risk of Achilles tendon rupture of 3.7.  Subclassification and tested examples ciprofloxacin (Cipro) levofloxacin (Levaquin) Aminoglycosides Mechanism bactericidal inhibition of bacterial protein synthesis  work by binding to the 30s ribosome subunit, leading to the misreading of mRNA. This misreading results in the synthesis of abnormal peptides that accumulate intracellularly and eventually lead to cell death. These antibiotics arebactericidal. Subclassification and tested examples gentamicin (Garamycin) Vancomycin Coverage gram-positive bacteria Mechanism bactericidal an inhibitor of cell wall synthesis  Resistance increasing emergence of vancomycin-resistant enterococci has resulted in the development of guidelines for use by the  (CDC)  indications for vancomycin  serious allergies to penicillins or beta-lactam antimicrobials  serious infections caused by susceptible organisms resistant to penicillins (MRSA, MRSE) surgical prophylaxis for major procedures involving implantation of prostheses in institutions with a high rate of MRSA or MRSE Rifampin Most effective against intracellular phagocytized Staphylococcus aureus in macrophages  Linezolid Linezolid binds to the 23S portion of the 50S subunit and acts by preventing the formation of the initiation complex between the the 30S and 50S subunits of the ribosome. Splenectomy Splenectomy patients or patients with functional hyposplenism require the following vaccines and/or antibiotics  Pneumococcal immunization Haemophilus influenza type B vaccine Meningococcal group C conjugate vaccine Influenza immunization Lifelong prophylactic antibiotics (oral phenoxymethylpenicillin or erythromycin)