AntibioticsThings to keep in your lab coat.The Sanford Guide to Antimicrobial TherapyJohns Hopkins Abx Guide (not free any more!almoiSilo programo"pocratesTips for the boardsStudy hard and efficiently. #on$t %aste time on a resource that isn$t making sense.Get the landscape first then the landmarks.#on$t be afraid to study outside of the re&ie% books.Think like a 'uestion %riter. Anticipate 'uestions for each topic.(orget about learning e&erything because the gaps in your kno%ledge %ill be random.Gram)positi&esGram)negati&esAminoglycosidesTetracyclines(luoro'uinolines*ifampinSulfonamides+acrolides,lindamycin-ine.olid/ancomycinA.treonamAnti)staph !,0$s(nafcillin1 methicillin1 oxacillins!enicillin G2/ Anti)pseudomonal !,0$s(pipercillin1 ticarcillin1 carbenicillin,ephalosporins 3st Generation4rd Generation5nd GenerationAmoxicillinAmpicillin6mipenem+eropenemHo% to approach the daunting task of learning antibiotics ,reate a general rule and kno% the exception to the rule.*ule7 All cell)%all inhibitors are beta)lactams1 except &ancomycin.8eta)lactam A89o!enicillinso,ephalosporinsoA.treonamo,arbapenems"xceptiono/ancomycin8eta)lactam structureGram)positi&e &s. Gram)negati&e+echanism of Action3.All beta)lactams bind penicillin)binding proteins (!8!$s5.All beta)lactams block transpeptidase cross)linking of cell %all4.Acti&ate autolytic en.ymes1 causing osmotic damage (bactericidal8eta)lactams73st mechanism of resistance8eta)lactamase production (i.e. S. aureus:e can get around this mode of resistance by making beta)lactamase resistant penicillins (i.e. nafcillin8eta)lactams75nd mechanism of resistance,hange the structure of !8!$s (i.e. +ethicillin)*esistant S. Aureus;nce bugs ha&e changed their !8!$s1 %e only ha&e one drug that %ill %ork1 &ancomycin.8eta)lactams74rd mechanism of resistance"fflux pump or change in porin structure7*ele&ant for gram)negati&e bacteriaSummary of resistances to beta)lactamases3st beta)lactamase production (S. aureus5nd change in !8! (+*SA4rd efflux pump or change in porin structure (gram)negati&es i.e. pseudomonas3st Generation#rugso!enicillin G and / ,linical useo0arro% spectrum (mainly gram)positi&esSensiti&e to beta)lactamaseso+eans7 on an exam1 penicillin G or / is ne&er the ans%er for treating Staph"xam 'uestions7o#;, for syphillis (ben.athine penicillin1 o#;, in strep infections1 especially to pre&ent rheumatic fe&ero#;, for susceptible pneumococci5nd Generation#rugso0afcillin1 +ethicillin1 ;xacillin1 ,loxacillin1 #iclaxicillinTo o&ercome the beta)lactamase resistance1 these drugs %ere de&eloped but they became so narro% spectrum that they only clinically are used for Staph.These drugs created the superbug +*SAo8eta)lactamaseoAltered !8!$s4rd Generation#rugsoAminopenicillins AmpicillinAmoxicillin,linical use o8road spectrum (gram positi&e and gram negati&es1 but 0;T beta)lactamase resistant(amous for treating7 H. flu and -isteria (ampicillin -yme #isease (amox #;, in peds and pregnancy"nterococcio#rug companies made body guards1 cla&ulanic acid and sulbactam1 to protect the aminopenicillins from beta)lactamases. )3?A cross)allergenicity %ith cephalosporinsToxicityJarisch)Herxheimer reaction in *x of syphiliso(e&er1 chills1 headache1 myalgias1 and exacerbation of syphilitic cutaneous lesions Ampicillin causes a famous maculopapular rash %hen gi&en to patients %ith infectious mono ("8/.,ephalosporins+echanism of action and resistance7 osame as penicillins3st Generation ,ephalosporins#rugsoAny drug %ith BphC in name b2c from "urope,ephalexin1 cephradine"xcept cefa.olin (famous for surgical prophylaxis b2c of long half)life,linical useoGram positi&esAnd a fe% gram negati&es !"cD (!roteus1 ". coli1 Dlebsiella!harmacokineticso#o not enter ,0S5nd Generation ,ephalosporins#rugso,efoxitin1 cefaclor1 cefuroxime,linical useoGram negati&es7 H"0 !"cDS (H. flu1 "nterobacter1 0eisseria1 !roteus1 ". coli1 Dlebsiella1 Serratia!harmacokineticso#o not enter ,0S1 except cefuroxime4rd Generation ,ephalosporins#rugso,eftriaxone1 cefotaxime1 cefta.idimeonotice the Bt$sC,linical useo3st generation E 5nd generation F 4rd generation (gram positi&e and negati&e Eanaerobes!harmacokineticso,eftriaxone is lipid soluble+eans good entry into ,0S+eans metaboli.ed and excreted into bo%el,an cause sludge in gallbladder8oards7o,eftazidime for pseudomonazo,eftriaxone for gonorrhea and meningitis?S ribosomal subunit (resistance is through methylation at binding site+acrolides,linical useoSame broad co&erage as tetracyclinesoG*6$s and atypical pneumonias (+ycoplasma1 -egionella1 ,hlamydiao0eisseriaoAlternati&e for penicillin allergic patientsToxicitiesoStimulate motilin receptor (erythromycin causing G6 upseto-ipid soluble1 except a.ithromycin+eans !? interactions (erythromycin is a famous inhibitor and li&er problems (acute cholestatic hepatitis,lindamycin+echanismo8locks peptide bond formation at >?S ribosomal subunit (bacteriostatic,linical useoGram)positi&es and anaerobes+eans can easily cause ,. diff colitisoGood penetration into bones+eans can be used for S. aureus osteomyelitis-ine.olid+echanismo-ine.olid binds on the 54S portion of the >?S subunit close to the peptidyl transferase and chloramphenicol binding sites. ,linicalo(amous for treating gram)positi&e drug resistant bugs (+*SA1 and multidrug resistant pneumococcusToxicityoGsually %ell toleratedoThrombocytopeniao+A;6 (a&oid tyramine containing foodHuinupristin2#alfopristin +echanismo!rotein synthesis inhibitors that bind the >?S ribosomal subunit ,linical useo/*"Toxicityo!)? inhibitor6nhibitors of #0A synthesis(luoro'uinolones*ifampinSulfonamides(luoro'uinolones#rugso,iprofloxacinoGatifloxacino-e&ofloxacino+oxifloxacino;floxacin+echanismo6nhibits #0A gyrase (topoisomerase 66 (8actericidal(luoro'uinolones,linical useoGram)negati&e rods of GT6 and diarrheao:ere 3st oral treatment of gram)negati&e sepsis+eans %ere o&erused1 leading to resistanceo#istributes into all tissues and fluids (including bones+eans can inhibit cartilage and tendon damage leading to tendonitis and tendon rupture in adults+eans can be used for Salmonella osteomyelitis+eans contraindicated in pregnancy and in children o*espiratory fluoro'uinolones (le&ofloxacin for drug resistant pneumococcusoAnthrax (ciprofloxacinToxicityoHT prolongation and arrhythmiasoHypo2hyperglycemiaoAchilles tendon rupture or tendinitis has occurred rarely *ifampin+echanismo6nhibits #0A)dependent *0A polymerase,linical useoT8 (in combo and in prophylaxiso(amous for prophylaxis of meningococcus and H. fluToxicityoHepatotoxico*e&s up !)?o*$s7*0A polymerase inhibitor*e&s up !)?*ed2orange body fluidsSulfonamides and TrimethoprimSulfonamides+echanismo6nhibits bacterial dihydropteroate synthase by competing for binding sites %ith p)aminoben.oic acid (!A8A1 a precursor re'uired for bacterial synthesis of folic acid.oTrimethoprim binds tightly to bacterial dihydrofolate reductase. Synergistic %ith sulfonamides.Sulfonamides,linical useo*esistance to sulfonamides is commono!,! prophylaxis (!; and treatment (6/TrimethoprimKSulfamethoxa.ole1 (T+!)S+96f sulfa allergy use pentamidine (antiproto.oal agentoToxoplasmosis (!yrimethamine E Sulfadia.ineToxicityoAllergies (sulfa allergies1 hemolytic anemia1 SJSo,arried by albumin+eans can cause kernicteruso,rystalluriao(olic acid can be gi&en to a&oid some toxicities+etronida.ole+echanismoToxic metabolites+eans causes G6 disturbance1 glossitis (metallic taste in mouth1 urethritis,linical useoAnaerobesoBG.".T. on the +etroC (Giardia1 "ntamoeba1 Trichomonaso,. diff colitis (!;Toxicityo+etronidazole #isulfiram)like reaction %2 ethanol+echanisms of *esistanceHo% to approach antibiotic co&erage*ule7 "&ery bacteria is gram negati&e1 except for the gram)positi&es and oddballs."xceptions to e&erything is gram)negati&eGram)positi&esoStaph2Strepo-isteriao8acilluso,lostridiumo,orynebacterium;ddballso+ycoplasma (no cell %alloGreaplasma (no cell %allo-egionella (sil&er staino,hlamydia (obligate intracellularo*ickettsia (obligate intracellularo+ycobacterium (acid)fastoTreponema (spirocheteo8orrelia (spirochete,ell :allGram)positi&esGram)negati&es4?s ribosome0ucleus>?s ribosome,ell :allGram)positi&esGram)negati&es4?s ribosome0ucleus>?s ribosome/ancomycinA.treonam,ell :allGram)positi&esGram)negati&es4?s ribosome0ucleus>?s ribosome/ancomycinA.treonamAnti)staph !,0$s(nafcillin1 methicillin1 oxacillins!enicillin G2/ Anti)pseudomonal !,0$s(pipercillin1 ticarcillin1 carbenicillin,ell :allGram)positi&esGram)negati&es4?s ribosome0ucleus>?s ribosome/ancomycinA.treonamAnti)staph !,0$s(nafcillin1 methicillin1 oxacillins!enicillin G2/ Anti)pseudomonal !,0$s(pipercillin1 ticarcillin1 carbenicillin,ephalosporins 3st Generation4rd Generation5nd GenerationGram)positi&esGram)negati&es4?s ribosome0ucleus>?s ribosome/ancomycinA.treonamAnti)staph !,0$s(nafcillin1 methicillin1 oxacillins!enicillin G2/ Anti)pseudomonal !,0$s(pipercillin1 ticarcillin1 carbenicillin,ephalosporins 3st Generation4rd Generation5nd GenerationAmoxicillinAmpicillinGram)positi&esGram)negati&es4?s ribosome0ucleus>?s ribosome/ancomycinA.treonamAnti)staph !,0$s(nafcillin1 methicillin1 oxacillins!enicillin G2/ Anti)pseudomonal !,0$s(pipercillin1 ticarcillin1 carbenicillin,ephalosporins 3st Generation4rd Generation5nd GenerationAmoxicillinAmpicillin6mipenem+eropenemGram)positi&esGram)negati&esAminoglycosidesTetracyclines0ucleus+acrolides,lindamycin-ine.olid/ancomycinA.treonamAnti)staph !,0$s(nafcillin1 methicillin1 oxacillins!enicillin G2/ Anti)pseudomonal !,0$s(pipercillin1 ticarcillin1 carbenicillin,ephalosporins 3st Generation4rd Generation5nd GenerationAmoxicillinAmpicillin6mipenem+eropenemGram)positi&esGram)negati&esAminoglycosidesTetracyclines(luoro'uinolines*ifampinSulfonamides+acrolides,lindamycin-ine.olid/ancomycinA.treonamAnti)staph !,0$s(nafcillin1 methicillin1 oxacillins!enicillin G2/ Anti)pseudomonal !,0$s(pipercillin1 ticarcillin1 carbenicillin,ephalosporins 3st Generation4rd Generation5nd GenerationAmoxicillinAmpicillin6mipenem+eropenem+y rules for antibiotics 'uestions.6s the bug gram)positi&e or gram)negati&eLoGse the chart %e =ust made for %hat antibiotic to use-ook for contraindications to using your antibiotic. 6s the patient too young or too pregnantLo#on$t use tetracyclines1 aminoglycosides1 fluoro'uinolones1 sulfonamides.6s the bug intracellularoGse a tetracycline or macrolideAntibacterial #rugs in !regnancy,aution Gnkno%n/ancomycin,ontraindicated Tooth discoloration1 inhibition of bone gro%th in fetusI hepatotoxicityTetracyclines,autionI contraindicated at termHemolysis in ne%born %ith GM!#b deficiencyI kernicterus in ne%born Sulfonamides,aution Gnkno%nHuinupristin2dalfopristin,autionI contraindicated at termHemolytic anemia in ne%borns0itrofurantoin,aution 0one kno%n1 but carcinogenic in rats+etronida.ole,aution Gnkno%n+eropenem,aution "mbryonic and fetal toxicity in rats-ine.olid,aution Toxicity in some pregnant animals6mipenem2cilastatin ,ontraindicated ,holestatic hepatitis"rythromycin estolate ,aution #ecreased %eight in animals"rtapenem,ontraindicated Teratogenicity in animals,larithromycin,aution Arthropathy in immature animals(luoro'uinolones,aution at term Gray syndrome in ne%born,hloramphenicol,autiona !ossible Nth ner&e toxicityAminoglycosidesRecommendation Toxicity in PregnancyAntibacterial DrugG8S1 ". coli1 H. flu1 -isteria1 +eningococcus1 !neumococcus0e%bornAdult!ractice HuestionA 3M)year)old high school cheerleader presents %ith lo% grade fe&er1 pleuritic pain and a non)producti&e cough. A sample tube of her blood %as placed in ice1 and Ograins of sandO appeared in the glass portion of the tube. Therapy should include %hich of the follo%ingLA. Ampicillin8. "rythromycin,. ;xygen and external cooling#. !enicillin G". *iba&irin!ractice HuestionA >N)year)old alcoholic man %ith multiple dental caries de&elops a pulmonary abscess and is treated %ith antibiotics. Se&eral days later1 he de&elops nausea1 &omiting1 abdominal pain1 and &oluminous green diarrhea. :hich of the follo%ing antibiotics is most likely responsible for this patientPs symptomsLA. ,hloramphenicol8. ,lindamycin,. Gentamicin#. +etronida.ole". /ancomycin!ractice Huestion:hich of the follo%ing organisms is most likely to be implicated as a cause of urethritis that persists after antibiotic therapy for gonorrheaLA. Actinomyces8. ,hlamydia,. +ycobacteria#. 0ocardia". *ickettsia!ractice HuestionA 44)year)old %oman presents %ith fe&er1 &omiting1 se&ere irritati&e &oiding symptoms1 and pronounced costo&ertebral angle tenderness. -aboratory e&aluation re&eals leukocytosis %ith a left shiftI blood cultures indicate bacteremia. Grinalysis sho%s pyuria1 mild hematuria1 and gram)negati&e bacteria. :hich of the follo%ing drugs %ould best treat this patientPs infectionLA. Ampicillin and gentamicin8. "rythromycin,. Gentamicin and &ancomycin#. Tetracycline!ractice HuestionA 4>)year)old male undergoes an appendectomy. Se&eral days later1 an abscess has formed at the surgical site. 6t does not impro&e %ith administration of a cephalosporin1 but does respond to nafcillin. The infecting organism most likely produced an en.yme that %ould hydroly.e %hich bond in the abo&e moleculeL A. A8. 8,. ,#. #