Overview of By Mechanism PENICILLINSCEPHALOSPORINSFLUOROQUINOLONESAMINOGLYCOSIDESMONOBACTAMSCARBAPENEMSMACROLIDESOTHERNaturalFirst generationCiprofloxacin (Cipro)Levofloxacin (Levaguin)Moxifloxacin (Avelox)Norfloxacin AmikacinGentamicinKanamycinNeomycinTobramycin AztreonamErtapenemImienemMeropenemAzithromycinClarithromycinDirithromycinErythromycinClindamycinVancomycinRifampinDoxycyclineLinezolidTetracyclineTrimethoprim/ sulfamethoxacolePenicillin GPenicillinCephalothinCefazolin (Ancef, Kefzol)CephapririnCephalexin (Keflex)Penicillinase ResistantSecond GenerationMethicillinNafcillinOxacillinotherCefacorCefotetan (Cefotan)otherAminopenicillinsThird GenerationAmpicillinCeftriaxone (Rocephin)otherFourth GenerationCefpiromeCefepime Antibiotic Grouping By MechanismCell Wall SynthesisPenicillinsCephalosporinsVancomycinBeta-lactamase InhibitorsCarbapenemsAztreonamPolymycinBacitracinProtein Synthesis InhibitorsInhibit 30s SubunitAminoglycosides (gentamicin)TetracyclinesInhibit 50s SubunitMacrolidesChloramphenicolClindamycinLinezolidStreptograminsDNA Synthesis InhibitorsFluoroquinolonesMetronidazoleRNA synthesis InhibitorsRifampinMycolic Acid synthesis inhibitorsIsoniazidFolic Acid synthesis inhibitorsSulfonamidesTrimethoprim Antibiotic Classification & Indications Inhibits Cell Wall SynthesisPenicillins(bactericidal: blocks cross linking via competitive inhibition of the transpeptidase enzyme)Class/MechanismDrugsIndications (**Drug of Choice)ToxicityPenicillinPenicillin GAqueous penicillin GProcaine penicillin GBenzathine penicillin GPenicillin VStrep. pyogenes (Grp.A)**Step. agalactiae (Grp.B)**C. perfringens(Bacilli)**Hypersensitivity reactionHemolytic anemiaAminopenicillinsAmpicillinAmoxicillinAbove +? Gram-negative:E. faecalis**E. Coli** AbovePenicillinase-resistant-penicillinsMethicillinNafcillinOxacillinCloxacillinDicloxacillinAbove +PCNase-producingStaph. aureusAbove +Interstitial nephritisAntipseudomonal penicillinsCarbenicillinTicarcillinPiperacillinAbove +Pseudomonas aeruginosa** AboveCephalosporins(bactericidal: inhibits bacterial cell wall synthesis via competitive inhibition of the transpeptidase enzyme)1st generationCefazolinCephalexinStaph. aureus**Staph. epidermidis**Some Gram-negatives:E. ColiKlebsiellaAllergic reactionCoombs-positive anemia (3%)2nd generationCefoxitinCefaclorCefuroximeAbove +? Gram-negativeAllergic ReactionETOH Disulfiram reaction3rd generationCeftriaxoneCefotaximeCeftazidimeCefepime (4th generation)Above +? Gram-negativePseudomonasAllergic ReactionETOH Disulfiram reactionOther Cell Wall InhibitorsVancomycin(bactericidal: disrupts peptioglycan cross-linkage) VancomycinMRSA**PCN/Ceph allegies**S. aureusS. epidermidisRed man syndromeNephrotoxicityOtotoxicityBeta-lactamase Inhibitors(bactericidal: blocking cross linking)Clavulanic AcidSulbactamTazobactamS aureus**S epidermis**E.Coli**Klebsiella**Hypersensitivity ReactionHemolytic anemiaCarbapenemsImipenem (+ cilastatin)MeropenemDoripenemErtapenemBroadest activity of any antibiotic(except MRSA, Mycoplasma)AztreonamAztreonamGram-negative rodsAerobesHospital-acquired infectionsPolymyxinsPolymyxin BPolymyxin ETopical Gram-negative infectionsBacitracinBacitracinTopical Gram-positive infectionsProtein Synthesis InhibitionAnti-30S ribosomal subunitAminoglycosides(bactericidal: irreversible binding to 30S)GentamicinNeomycinAmikacinTobramycinStreptomycinAerobic Gram-negativesEnterobacteriaceaePseudomonasNephrotoxicityOtotoxicityTetracyclines(bacteriostatic: blocks tRNA)TetracyclineDoxycyclineMinocyclineDemeclocyclineRickettsiaMycoplasmaSpirochetes(Lyme's disease)HepatotoxicityTooth discoloration Impaired growthAvoid in children < 12 years of ageAnti-50S ribosomal subunitMacrolides(bacteriostatic: reversibly binds 50S)ErythromycinAzithromycinClarithromycinStreptococcusH. influenzaeMycoplamsa pneumoniaCoumadin Interaction (cytochrome P450)Chloramphenicol(bacteriostatic)ChloramphenicolH influenzaeBacterial MeningitisBrain abscesAplastic AnemiaGray Baby SyndromeLincosamide(bacteriostatic: inhibits peptidyl transferase by interfering with amino acyl-tRNA complex)ClindamycinBacteroides fragilisS aureusCoagulase-negative Staph & StrepExcellent Bone PenetrationPseudomembranous colitisHypersensitivity ReactionLinezolid(variable)LinezolidResistant Gram-positivesStreptograminsQuinupristinDalfopristinVREGAS and S. aureus skin infectionsDNA Synthesis InhibitorsFluoroquinolones(bactericidal: inhibit DNA gyrase enzyme, inhibiting DNA synthesis)1st generationNalidixic acidSteptococcusMycoplasmaAerobic Gram +PhototoxicityAchilles tendon ruptureImpaired fracture healing2nd generationCiprofloxacinNorfloxacinEnoxacinOfloxacinLevofloxacinAs Above +Pseudomonasas above3rd generationGatifloxacinAs above + Gram-positivesas above4th generationMoxifloxacinGemifloxacinAs above + Gram-positives + anaerobesas aboveOther DNA InhibitorsMetronidazole(bacteridical: metabolic biproducts disrupt DNA)Metronidazole (Flagyl)AnaerobicsSeizuresCrebelar dysfunctionETOH disulfram reactionRNA Synthesis InhibitorsRifampin(bactericidal: inhibits RNA transcription by inhibiting RNA polymerase)RifampinStaphylococcusMycobacterium(TB)Body fluid discolorationHepatoxicity (with INH)Mycolic Acids Synthesis InhibitorsIsoniazidIsoniazidzTBLatent TBFolic acid SynthesisInhibitorsTrimethoprim/Sulfonamides(bacteriostatic: inhibition with PABA)Trimethoprim/Sulfamethoxazole (SMX)SulfisoxazoleSulfadiazineUTI organismsProteusEnterobacterThrombocytopeniaAvoid in third trimester of pregnancyPyrimethaminePyrimethamineMalariaT. gondii Bacteria Overview Gram Postive CocciStaphylococcusStaph. aureusMSSAMRSAStaph. epidermisStaph saprophyticusStreptococcusStrep pneumoniaeStrep pyogenes (Group A)Strep agalacticae (Group B)Strep viridansStrep Bovis (Group D)EnterococciE. faecalis (Group D strep)Gram Positive BacilliSpore FormingBacillus anthracisBacillus cereusClostridium tetaniClostridium botulinumClostridium perfringensClostridium difficileNon-Spore FormingCorynebacterium diphtheriaeListeria monocytogenesGram Negative CocciNeisseriaNeisseria meningitidisNeisseria gonorrhoeaeGram Negative BacilliEntericsEscherichia coliSalmonella typhiSalmonella enteridisShigella dysenteriaeKlebsiella pneumoniaeSerratiaProteusCampylobacter jejuniVibrio choleraeVibrio parahaemolyticus/vulnificusHelicobacter pyloriPseudomonas aeruginosaBacteroides fragilisRespiratory bacilliHaemophilus influenzaeHaemophilius ducreyiBordatella pertussisZoonotic bacilliYersinia enterocoliticaYersinia pestisBrucellaFrancisella tularensisPasteurella multocidaBartonella henselaeOtherGardnerella vaginalisOther BacteriaMycobacteriaMycobacterium tuberculosisMycobacterium lepraeMOTTSSpirochetesBorrelia burgdorferiLeptospira interrogansTreponema pallidumChlamydiaceaeChlamydia trachomatisChlamydophilaRickettsiaEhrlichiaMycoplasmataceaeMycoplasma pneumoniaeUreaplasma urealyticumFungus-like BacteriaActinomyces 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)