Antibiotic Summary

ANTIBACTERIALS
CELL WALL SYNTHESIS INHIBITORS (BACTERICIDAL) BETA-LACTAMS
Mode of Action beta-lactam ring competitively inhibits penicillin binding proteins (PBPs) and prevents cross linking of peptidoglycan strands normally needed for cell wall integrity: osmotic lysis of the bacterium PENICILLINS benzyl penicillin (narrow spectrum, not penicillinase resistant) e.g. penicillin G (IV or IM), penicillin V (PO) effective against Streptococci, most anaerobes (no\B. fragilis),Neisseria,and Tpallidum (syphilis) isoxazoyl penicillin (narrow spectrum, penicillinase resistant)) e.g. methicillin, cloxacillin, oxacillin, nafcillin effective against Staphylococci and some Streptococci; drug of choice for penicillin-resistant S. aureus (PRSA) aminopenicillins (broad spectrum, penicillinase sensitive) e.g. ampicillin, amoxicillin effective against most Gram positives including Enterococci, some Gram negatives amoxicillin first line therapy for acute cystitis or asymptomatic UTI in pregnant women ampicillin combined with gentamicin first line therapy for pyelonephritis combine with clavulanic acid (penicillinase inhibitor) to enhance spectrum (i.e. increase activity vs. beta-lactamase producers) ureidopenicillins (broad spectrum, penicillinase sensitive) e.g. piperacillin, carbenicillin, ticarcillin effective againstGram positives, Pseudomonas, Gram negatives (e.g. Enterobacter), and anaerobes (e.g. Bacteroides fragilis) combine tazobactam with piperacillin to enhance spectrum of activity especially against the penicillinase producing organisms CEPHALOSPORINS Clinical Use 1st generation e.g. cefazolin IV/IM (Ancef); cephalexin po (Keflex) Gram positive cocci (except MRSA and Enterococci), Gram negative bacilli (ma in ly coli, Klebsiella, P. mirabilis) 2nd generation e.g. cefuroxime IV/IM (Kefurox); cefuroxime axetil po (CeftirT), Cefotetan po (CefotarT) less Gram positive activity but more Gram negative coverage than 1st generation U influenzae, coli, Klebsiella, Proteus) cefotetan has anaerobic activity and is used in intra-abdominal and pelvic infections 3rd generation e.g. cefotaxime IV/IM, ceftriaxone IV/IM, ceftazidime IV/IM broad spectrum activity against enteric Gram negatives, less Gram positive coverage than 1st generation crosses blood-brain barrier (unlike 1st and 2nd generation) ceftazidime should be used if Pseudomonas coverage is required 4th generation e.g. cefepime, cefpirome broad spectrum activity against Gram negatives (including P. aeruginosa) and good coverage of Gram positive cocci (MRSA and S. pneumoniae) useful in severe hospital or community-acquired infections (pneumonia, bacteremia) CARBAPENEMS (e.g. Imipenem, Meropenem) Clinical Use broadest spectrum of activity against anaerobes, Gram positives (exceptEnterococcus faecium and MRSA), and Gram negatives, including P. aeruginosa imipenem drug of choice for drug-resistant Enterobacter always administered with cilastin (inhibitor of renal dihydropeptidase I) to decrease inactivation in renal tubules GLYCOPEPTIDES (e.g. Vancomycin) Mechanism of action blocks cell wall peptidoglycan polymerization (synthesis) resulting in loss of cell wall integrity and osmotic rupture of the bacterium Clinical Use oniy active against Gram positive organisms true major penicillin allergic patients (e.g. anaphylaxis, exfoliative dermatitis, vasculitis, or severe urticaria) MRSA infection coagulase-negative Staphylococcus (e.g. S. epidermidis) in patients with prosthetic valves with joint or line infections oral formulation is 2nd line treatment for antibiotic-associated pseudomembranous colitis (C. difficile)

ribosomal BOS subunit, which prevents translocation of polypeptide chain Clinical Use Mycoplasma, Legionella, Chlamydia, Treponema, Helicobacter pylori Urinary Tract infections, Gram positive cocci (streptococcal infections in patients allergic to penicillin) first line therapy for community-acquired pneumonia as an outpatient LINCOSAMIDES(e.g. Clindamycin) Mechanism of Action inhibit protein synthesis by binding to BOS ribosomal subunit, which prevents peptide bond formation Clinical Use Gram positives anaerobic infections (S fragilis, C. perfringens) LINEZOLID Mechanism of Action binds 23S ribosomal area of the BOS subunit, prevents funtional 70S initiation complex Clinical Use Enterococci, Staphylococci (basteriostatic): use in VRE Streptococci (bactericidal)

folic acid production and thus inhibits nucleic acid synthesis and bacterial growth SMX competes with paraaminobenzoic acid for dihydropteroate synthase to prevent folic acid production and thus inhibit nucleic acid synthesis and bacterial growth Clinical Use SMX alone: Nocardia combination: Pneumocystis carinii, Toxoplasma, Shigella, Salmonella, commoniy used for urinary tract infections

DNA GYRASE INHIBITORS (BACTERICIDAL)

QUINOLONES e.g. ciprofloxacin, levofloxacin, moxifloxacin, norfloxacin, ofloxacin, gatifloxacin, nalidixic acid Mechanism of Action prevents supercoiling of nucleic acids by inhibiting DNA gyrase to block DNA replication Clinical Use enteric Gram negative bacilli of urinary and Gl tracts, limited Gram positive coverage (twith levo, moxi, gati) ciprofloxacin first line therapy for uncomplicated and complicated cystitis in adults use if Pseudomonas suspected levofloxacin, moxifloxacin, gatifloxacin useful against respiratory pathogens {Legionella, Chlamydia, Mycoplasma) first line therapy for community acquired pneumonia as an outpatient moxifloxacin and gatifloxacin have some anaerobic coverage

VIA 30S RIBOSOME (BACTERICIDAL)

AMINOGLYCOSIDES (e.g. Gentamicin, Tobramycin, Amikacin, Streptomycin, Neomycin) Mechanism of Action inhibit protein synthesis initiation by binding to the 30S ribosomal subunit, thereby causing misreading of mRNA Clinical Use primarily Gram negative aerobes and mycobacteria tobramycin used for Pseudomonas aeruginosa infections requires oxygen for uptake, therefore, ineffective against anaerobes

DNA-DEPENDENT RNA POLYMERASE INHIBITORS (BACTERICIDAL)

RIFAMPIN Mechanism of action inhibits bacterial protein synthesis by inhibiting DNA-dependent RNA polymerase Clinical Use Gram positive cocci, many Gram negative bacilli, most Mycobacterium species always used in combination to reduce resistance prophylaxis against meningococcus

VIA 30S RIBOSOME (BACTERIOSTATIC)

TETRACYCLINES (e.g. Tetracycline, Doxycycline) Mechanism of Action inhibit protein synthesis by binding to the 30S ribosomal subunit, thereby blocking amino acid linked tRNA from binding to the A site of the ribosome Clinical Use Chlamydia, Mycoplasma, Rickettsia, Borrelia burgdoferi (Lyme disease) doxycycline used for malaria prophylaxis and treatment tetracycline used to treat acne Side-effects Gl upset, hepatotoxicity Fanconi's syndrome discolors teeth and inhibits bone growth in children (contraindicated in pregnancy, neonates, children)

PROTEIN SYNTHESIS INHIBITORS

VIA 50S RIBOSOME (BACTERIOSTATIC)
CHLORAMPHENICOL Mechanism of Action inhibits protein synthesis by binding to the ribosomal BOS subunit, which prevents the aminoacyl end of tRNA from associating with peptidyl transferase Clinical Use 2nd line treatment for meningitis U influenzae, fl meningitides, S. pneumoniae) MACROUDES (e.g. Erythromycin, Clarithromycin, Azithromycin) Mechanism of Action inhibit protein synthesis by binding to the P site of the

DNA COMPLEX DAMAGING AGENTS (BACTERICIDAL)

METRONIDAZOLE Mechanism of Action forms toxic metabolites in the bacterial cell which damage the microbial DNA Clinical Use anaerobic bacteria (first line therapy for pseudomembranous colitis) several protozoan parasites (Trichomoniasis, amebiasis, used in combination with omeprazole and clarithromycin in patients with penicillin allergy for triple therapy against H. pylori Crohn's disease, hepatic encephalopathy

FOLIC ACID METABOLISM INHIBITORS (BACTERIOSTATIC)

TRIMETHOPRIM-SULFAMETHOXAZOLE (TMP-SMX) Mechanism of Action TMP inhibits dihydrofolate reductase which prevents