Overview of By Mechanism PENICILLINS CEPHALOSPORINS FLUOROQUINOLONES AMINOGLYCOSIDES MONOBACTAMS CARBAPENEMS MACROLIDES OTHER Natural First generation Ciprofloxacin (Cipro)Levofloxacin (Levaguin) Moxifloxacin (Avelox)Norfloxacin AmikacinGentamicinKanamycinNeomycinTobramycin Aztreonam ErtapenemImienemMeropenem AzithromycinClarithromycinDirithromycinErythromycinClindamycin VancomycinRifampinDoxycyclineLinezolidTetracyclineTrimethoprim/ sulfamethoxacole Penicillin GPenicillin-VK CephalothinCefazolin (Ancef, Kefzol) CephapririnCephalexin (Keflex)other Penicillinase Resistant Second Generation MethicillinNafcillinOxacillinother CefacorCefotetan (Cefotan) other Aminopenicillins Third Generation Ampicillin Ceftriaxone (Rocephin) other Fourth Generation CefpiromeCefepime Antibiotic Grouping By Mechanism Cell Wall Synthesis PenicillinsCephalosporinsVancomycinBeta-lactamase InhibitorsCarbapenemsAztreonamPolymycinBacitracin Protein Synthesis Inhibitors Inhibit 30s SubunitAminoglycosides (gentamicin)TetracyclinesInhibit 50s SubunitMacrolidesChloramphenicolClindamycinLinezolid Streptogramins DNA Synthesis Inhibitors Fluoroquinolones Metronidazole RNA synthesis Inhibitors Rifampin Mycolic Acid synthesis inhibitors Isoniazid Folic Acid synthesis inhibitors SulfonamidesTrimethoprim Antibiotic Classification & Indications Inhibits Cell Wall Synthesis Penicillins(bactericidal: blocks cross linking via competitive inhibition of the transpeptidase enzyme) Class/Mechanism Drugs Indications (**Drug of Choice) Toxicity Penicillin Penicillin GAqueous penicillin GProcaine penicillin GBenzathine penicillin GPenicillin V Strep. pyogenes (Grp.A)**Step. agalactiae (Grp.B)**C. perfringens(Bacilli)** Hypersensitivity reactionHemolytic anemia Aminopenicillins AmpicillinAmoxicillin Above + ? Gram-negative:E. faecalis**E. Coli** Above Penicillinase-resistant-penicillins MethicillinNafcillinOxacillinCloxacillinDicloxacillin Above +PCNase-producingStaph. aureus Above + Interstitial nephritis Antipseudomonal penicillins CarbenicillinTicarcillinPiperacillin Above +Pseudomonas aeruginosa** Above Cephalosporins(bactericidal: inhibits bacterial cell wall synthesis via competitive inhibition of the transpeptidase enzyme) 1st generation CefazolinCephalexin Staph. aureus**Staph. epidermidis**Some Gram-negatives:E. ColiKlebsiella Allergic reactionCoombs-positive anemia (3%) 2nd generation CefoxitinCefaclorCefuroxime Above +? Gram-negative Allergic ReactionETOH Disulfiram reaction 3rd generation CeftriaxoneCefotaximeCeftazidimeCefepime (4th generation) Above +? Gram-negativePseudomonas Allergic ReactionETOH Disulfiram reaction Other Cell Wall Inhibitors Vancomycin (bactericidal: disrupts peptioglycan cross-linkage) Vancomycin MRSA**PCN/Ceph allegies**S. aureusS. epidermidis Red man syndromeNephrotoxicityOtotoxicity Beta-lactamase Inhibitors (bactericidal: blocking cross linking) Clavulanic AcidSulbactamTazobactam S aureus**S epidermis**E.Coli**Klebsiella** Hypersensitivity ReactionHemolytic anemia Carbapenems Imipenem (+ cilastatin)MeropenemDoripenemErtapenem Broadest activity of any antibiotic(except MRSA, Mycoplasma) Aztreonam Aztreonam Gram-negative rodsAerobesHospital-acquired infections Polymyxins Polymyxin BPolymyxin E Topical Gram-negative infections Bacitracin Bacitracin Topical Gram-positive infections Protein Synthesis Inhibition Anti-30S ribosomal subunit Aminoglycosides(bactericidal: irreversible binding to 30S) GentamicinNeomycinAmikacinTobramycinStreptomycin Aerobic Gram-negativesEnterobacteriaceae Pseudomonas NephrotoxicityOtotoxicity Tetracyclines(bacteriostatic: blocks tRNA) TetracyclineDoxycyclineMinocyclineDemeclocycline RickettsiaMycoplasmaSpirochetes (Lyme's disease) HepatotoxicityTooth discoloration Impaired growthAvoid in children < 12 years of age Anti-50S ribosomal subunit Macrolides(bacteriostatic: reversibly binds 50S) ErythromycinAzithromycinClarithromycin StreptococcusH. influenzaeMycoplamsa pneumonia Coumadin Interaction (cytochrome P450) Chloramphenicol(bacteriostatic) Chloramphenicol H influenzaeBacterial MeningitisBrain absces Aplastic AnemiaGray Baby Syndrome Lincosamide(bacteriostatic: inhibits peptidyl transferase by interfering with amino acyl-tRNA complex) Clindamycin Bacteroides fragilisS aureusCoagulase-negative Staph & StrepExcellent Bone Penetration Pseudomembranous colitisHypersensitivity Reaction Linezolid(variable) Linezolid Resistant Gram-positives Streptogramins QuinupristinDalfopristin VREGAS and S. aureus skin infections DNA Synthesis Inhibitors Fluoroquinolones(bactericidal: inhibit DNA gyrase enzyme, inhibiting DNA synthesis) 1st generation Nalidixic acid SteptococcusMycoplasmaAerobic Gram + PhototoxicityAchilles tendon ruptureImpaired fracture healing 2nd generation CiprofloxacinNorfloxacinEnoxacinOfloxacinLevofloxacin As Above +Pseudomonas as above 3rd generation Gatifloxacin As above + Gram-positives as above 4th generation MoxifloxacinGemifloxacin As above + Gram-positives + anaerobes as above Other DNA Inhibitors Metronidazole(bacteridical: metabolic biproducts disrupt DNA) Metronidazole (Flagyl) Anaerobics SeizuresCrebelar dysfunctionETOH disulfram reaction RNA Synthesis Inhibitors Rifampin(bactericidal: inhibits RNA transcription by inhibiting RNA polymerase) Rifampin StaphylococcusMycobacterium (TB) Body fluid discolorationHepatoxicity (with INH) Mycolic Acids Synthesis Inhibitors Isoniazid Isoniazidz TBLatent TB Folic acid Synthesis Inhibitors Trimethoprim/Sulfonamides(bacteriostatic: inhibition with PABA) Trimethoprim/Sulfamethoxazole (SMX)SulfisoxazoleSulfadiazine UTI organismsProteusEnterobacter ThrombocytopeniaAvoid in third trimester of pregnancy Pyrimethamine Pyrimethamine MalariaT. gondii Bacteria Overview Gram Postive Cocci Staphylococcus Staph. aureusMSSAMRSAStaph. epidermisStaph saprophyticus Streptococcus Strep pneumoniaeStrep pyogenes (Group A) Strep agalacticae (Group B) Strep viridansStrep Bovis (Group D) Enterococci E. faecalis (Group D strep) Gram Positive Bacilli Spore Forming Bacillus anthracisBacillus cereusClostridium tetaniClostridium botulinumClostridium perfringensClostridium difficile Non-Spore Forming Corynebacterium diphtheriaeListeria monocytogenes Gram Negative Cocci Neisseria Neisseria meningitidisNeisseria gonorrhoeae Gram Negative Bacilli Enterics Escherichia coliSalmonella typhiSalmonella enteridisShigella dysenteriaeKlebsiella pneumoniaeSerratiaProteusCampylobacter jejuniVibrio choleraeVibrio parahaemolyticus/vulnificusHelicobacter pyloriPseudomonas aeruginosaBacteroides fragilis Respiratory bacilli Haemophilus influenzaeHaemophilius ducreyiBordatella pertussis Zoonotic bacilli Yersinia enterocoliticaYersinia pestisBrucella Francisella tularensis Pasteurella multocida Bartonella henselae Other Gardnerella vaginalis Other Bacteria Mycobacteria Mycobacterium tuberculosisMycobacterium lepraeMOTTS Spirochetes Borrelia burgdorferiLeptospira interrogansTreponema pallidum Chlamydiaceae Chlamydia trachomatisChlamydophila RickettsiaEhrlichia Mycoplasmataceae Mycoplasma pneumoniaeUreaplasma urealyticum Fungus-like Bacteria Actinomyces israeliiNocardia Antibiotic Resistance Mechanisms Bacteria develop ability to hydrolyze these drugs using ß lactamase confers resistance to penicillin e.g. E. coli, Staph epidermidis, Pseudomonas aeruginosa, Klebsiella pneumoniae add ß lactamase inhibitor e.g. clavulanic acid in amoxicillin-clavulanate (Augmentin) Genetic mutation of mecA carried by Staphylococcal cassette chromosome (SCCmec) mobile genetic unit a bacterial gene encoding a penicillin-binding protein (PBP2a). PBP2a has reduced affinity for antibiotics confers resistance to methicillin, oxacillin, nafcillin e.g. MRSA SCCmec type IV has less genetic elements and is specific to CA-MRSA, making CA-MRSA less multi-drug resistant Altered cell wall permeability confers resistance to tetracyclines, quinolones, trimethoprim and ß 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 interferes 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)