Pharmacology II: Cell Wall Inhibitors II PDF

Pharmacology II CELL WALL INHIBITORS II Dr. Sheryar Afzal College of veterinary Medicine King Faisal University  3 Cephalosporins Similar to penicillins (same MOA and resistance...

Pharmacology II CELL WALL INHIBITORS II Dr. Sheryar Afzal College of veterinary Medicine King Faisal University  3 Cephalosporins Similar to penicillins (same MOA and resistance mechanism), but more stable to bacterial lactamases. Note: Cephalosporins are ineffective against MRSA, L. monocytogenes, Clostridium difficile, and the enterococci.  5 Cephalosporins 1st-generation (cefazolin, Cephalexin, Cefadroxil and etc) Resistant to the staphylococcal penicillinase (including MSSA) 2nd-generation (Cefuroxime, cefotetan, cefoxitin, cefprozil, cefaclor and etc)  10 Cephalosporins eneration (Cefotaxime, ceftriaxone, ceftazidime) Less potent than first-generation cephalosporins against MSSA, but with enhanced activity against gram- negative bacilli as well as most other enteric organisms plus Serratia marcescens. Ceftriaxone and cefotaxime are agents of choice for meningitis caused by pneumococci, meningococci, H influenzae, and susceptible enteric gram- negative rods, but not by L monocytogenes. Ceftazidime has activity against P. aeruginosa (but resistance is increasing) Third-generation cephalosporins are associated with significant collateral damage (induction and spread of  13 Cephalosporins h-generation (Cefepime) Wide antibacterial spectrum (active against streptococci and staphylococci, but only those that are methicillin susceptible). Effective against aerobic gram-negative organisms, such as Enterobacter species, E. coli, K. pneumoniae, P. mirabilis, P. aeruginosa. Advanced generation (Ceftaroline) Broad-spectrum, has anti-gram-negative activity similar to 3rd gen ceftriaxone (Administered IV as a prodrug) Against MRSA and treat complicated skin and skin structure infections and community-acquired pneumonia Important gaps in coverage include P. aeruginosa, extended-spectrum β- lactamase (ESBL)-producing Enterobacteriaceae, and Acinetobacter baumannii.  15 Cephalosporins  16 Cephalosporins Resistanc e Same as those described for the penicillins. Cephalosporins may be susceptible to extended-spectrum β-lactamases (ESBLs) by E. coli and K. pneumoniae. Adverse effects Hypersensitivity including anaphylaxis, fever, skin rashes, nephritis, granulocytopenia, and hemolytic anemia Cross-sensitivity is common between penicillin and 1st gen cephalosporins  24 Carbapenems Imipenem, Meropenem, Doripenem, Ertapenem - synthetic β-lactam antibiotics Imipenem resists hydrolysis by most β-lactamases (For empiric therapy because it is Imipenem, Meropenem active against β-lactamase– Doripenem producing gram-positive and gram-negative organisms, anaerobes, and P. aeruginosa)  26 Carbapenems Imipenem/cilastatin and meropenem penetrate well into body tissues and fluids Including CSF. Meropenem is known to reach therapeutic levels in bacterial meningitis even without inflammation. Adverse effects Imipenem/cilastatin can cause nausea, vomiting, and diarrhoea. Eosinophilia and neutropenia are less common than with other β-lactams. High levels of imipenem may provoke seizures; other carbapenems are less likely to do so.  29 Monobactams Aztreonam (IV or IM) β-lactam ring is not fused to another ring. Against gram-negative pathogens, including the Enterobacteriaceae and P. aeruginosa (lacks activity against gram-positive & anaerobes). Resistant to most β-lactamases except for ESBLs. Nontoxic (may cause phlebitis, skin rash and abnormal liver function tests). Little cross-reactivity with antibodies induced by other β-lactams (An alternative for patients who are allergic to other penicillins, cephalosporins, or carbapenems).  35 T H A N  K O U ;)