ࡱ>  ` 2bjbj 4, ,4444l l l D***8bdb2VVVVVqV,      $/hp.l lmqll.44VV%%%lJ 4|Vl V%l%%xM l PVJ p:e/*jN"St;͐0N DPl P %y   ..%   llllbbb}&Gbbb&G T444444  THE NEED-TO-KNOW ANTIMICROBIALS Yearly update by Rho Chi Class of 2008 University of Washington School of Pharmacy Autumn Quarter, 2006 Generic nameAMOXICILLIN Proprietary nameAmoxil, Polymox Class (generation)Aminopenicillin MOA (bactericidal/bacteriostatic)Binds to PBPs to inhibit cell wall synthesis, bactericidal Spectrum (Gm+, Gm-, anaerobes)Gram +: streptococci, Enterococcus, but NOT S. aureus Gram - : only a few (E. coli, Proteus spp, a few others)lots of resistance No below-the-diaphragm anaerobic activity DOC for which diseasesAOM, ABS, prophylaxis of endocarditis before dental, esophageal, and upper respiratory procedures Absorption, distribution, metabolism, excretionAbsorbed well from GI tract; widely distributed in tissues (especially inflamed tissue); renal excretion PD (time vs. concentration dependent killing)Time-dependent Side effects (what, how common, monitoring)Diarrhea--common, call MD if excessive, blood in stool or abdominal cramping AllergiesPossible anaphylaxis or rash Drug interactionsNot common Dose (renal/hepatic failure, obesity)AOM: 90mg/kg/day, div BID x 10 days ABS mild/moderate, w/out recent abx: 1 g TID x 10 days Endocarditis prophylaxis: 2 g po x 1 hr before appt. CrCl 10-50 mL/min: Give q8-12h <10 mL/min: Give q24h Pregnancy, pediatrics issuesPregnancy B, ok in pediatrics Relative costGeneric and very inexpensive  Generic nameAMOXICILLIN/CLAVULANIC ACID Proprietary nameAugmentin Class (generation)-lactam/-lactamase inhibitor combination MOA (bactericidal/bacteriostatic)Amox: binds to penicillin binding proteins (PBPs) to inhibit protein synthesis (bactericidal) Clavulanic acid: inhibits -lactamases Spectrum (Gm+, Gm-, anaerobes)Gram + (S. aureus, Enterococcus, streptococci) enteric gram -, H.flu, M.cat anaerobes below the diaphragm Very similar to amp/sulbactam in activityDOC for which diseasesRefractory otitis media, acute/severe bacterial sinusitis, dog/cat bites, aspiration CAP Absorption, distribution, metabolism, excretionAbsorption: 75%, Distribution: inflammation-mediated, gets to most tissues Excretion: Renal PD (time vs. concentration dependent killing)Time-dependent Side effects (what, how common, monitoring)Common: N/V, antibiotic associated diarrhea Rare: thrombocytopenia AllergiesPenicillin allergy rash: 5-10%, anaphylaxis: 0.001% Drug interactionsAllopurinol may increase incidence or rash Dose (renal/hepatic failure, obesity)Normal Doses: Refractory otitis media: 90mg/kg/day div q12hX10d (Pediatric) Acute/severe bact. Sinusitis & aspiration CAP: augmentin XR 2 tabs po BID X10-14d Dog/cat bites: 875 mg BID X 3-5d (prophylaxis) or 10-14d (infected wound) Renal failure: adjustment may be required Pregnancy, pediatrics issuesPregnancy cat B, safe in pediatrics Relative costModerately expensive  Generic nameAMPICILLIN Proprietary nameOmipen, Polycillin Class (generation)Aminopenicillin MOA (bactericidal/bacteriostatic)CIDAL, acid unstable antibiotic that inhibits the biosynthesis of cell wall mucopeptide (peptidoglycan). Most effective when bacteria are growing (subject to the inoculum effect). Spectrum (Gm+, Gm-, anaerobes)Alone: covers streptococci and Enterococcus, but not S. aureus Gm- is ok for a few organisms, but watch out for resistance. No Pseudomonas coverage. Anaerobe coverage is poor because of -lactamases below the diaphragm With sulbactam: modest Gm- improvement, but much better gm+ (including S. aureus) and anaerobe improvement DOC for which diseasesMeningitis (for Listeria monocytogenes) Gastroenteritis (for Listeria monocytogenes) Complicated UTI/catheters (alternative choice) Pneumonia (not reliable for H. influenzae) Absorption, distribution, metabolism, excretionGood GI absorption Distribution: bound to plasma proteins, diffuses readily into most tissues with inflammation. Excretion: Largely unchanged in the urine PD (time vs. concentration dependent killing)Time dependent killing Side effects (what, how common, monitoring)Fever, rash fairly common, diarrhea is a serious problem Allergies0.7-10% Rash and anaphylaxis. X-sensitivity to all PCNs, and varying X-sensitivity to cephalosporins Drug interactionsAllopurinol (increases frequency of rash) Oral contraceptives (the general warning) Dose (renal/hepatic failure, obesity)Normal: 250-500 mg po q6h OR 150-200 mg/kg/d IV Max IV dose in adults: 2 gm IV q4h Renal Failure: CrCl >50-90 same, CrCl 10-50: q6-12h, CrCl <10: q12-24h Pregnancy, pediatrics issuesPregnancy category B, excreted in breast milk, may lead to sensitization Relative costOral 500 mg ~ 35 cents (CHEAP); IV modestly priced Generic nameAMPICILLIN/SULBACTAMProprietary nameUnasynClass (generation)Aminopenicillin/-lactamase inhibitor combinationMOA (bactericidal/bacteriostatic)Bactericidal. Inhibits cell wall synthesis by binding to PBPs; sulbactam is a  lactamase inhibitor Spectrum (Gm+, Gm-, anaerobes)G+: streptococci, S. aureus, Enterococcus G-: E. coli, Klebsiella, Proteus, H. influenzae Anaerobes: good for below-diaphragm The sulbactam improves the S. aureus and anaerobic coverage of ampicillin, but only modestly improves G- coverage DOC for which diseasesIntra-abdominal infections With advanced macrolide (azithromycin) for CAP treated on inpatient basis, non ICU (especially if aspiration pneumonia is a concern) Absorption, distribution, metabolism, excretion A-IV only D-to bile, blister, tissue fluids, CSF (inflamed). M-not particularly significant E-75-85% excreted unchanged in urine in 8 hrs. Half-life 1.3 hours. PD (time vs. concentration dependent killing)Time dependent killingSide effects (what, how common, monitoring)Rash, diarrheaAllergiesContraindicated in patients with penicillin and (true) cephalosporin allergies (about 20-40% chance the latter will be allergic to penicillins) Drug interactionsAmpicillin levels can be increased by probenecid. Penicillins may increase methotrexate exposure during concurrent therapy. Monitor MTX levels. Dose (renal/hepatic failure, obesity)1.5-3 g IV q6h Adjust for renal dysfunction Pregnancy, pediatrics issuesSafe in pediatric and pregnant patients (B) Relative costModerately expensive Generic nameAZITHROMYCIN Proprietary nameZithromax, Zmax Class (generation)Azalide (advanced-generation macrolide) MOA (bactericidal/bacteriostatic)Inhibits bacterial growth by suppressing RNA-dependent protein synthesis, bacteriostatic Spectrum (Gm+, Gm-, anaerobes)Gram pos: S. pneumoniae (lots of resistance, though), other streptococci; not a good staph drug (no MRSA) Gram neg: H. influenzae, M. catarrhalis (not really a good Gram-negative drug) Atypicals (Legionella, Mycoplasma, Chlamydia): good coverage No useful anaerobic activity below diaphragm DOC for which diseasesPenicillin allergic AOM, CAP w/ no previous antibiotics, Chlamydia STD Absorption, distribution, metabolism, excretionAbsorption:good (newest data suggest no reason to avoid antacids), bioavailability 37% Tissue half-life: 2-4 days Distribution: especially good into lungs PD (time vs. concentration dependent killing)AUC/MIC correlates best with activity Side effects (what, how common, monitoring)N/V, antibiotic associated diarrhea (rare) Prolong QTc interval (generally minor) Very well-tolerated drug in generalAllergiesRare Drug interactionsDigoxin: increases serum levels of digoxin? Dose (renal/hepatic failure, obesity)Normal Doses: Pen-allergic AOM: 30 mg/kg/day (single dose, or divided over 3-5 days) Pharyngitis: 60 mg/kg/day (divided over 5 days) CAP: 500 mg day 1, then 250 mg day 2-5 (adult) Chlamydia: 1 gm x1 Pregnancy, pediatrics issuesPregnancy category B, safe in pediatrics Relative costModerate  Generic nameAZTREONAMProprietary nameAzactamClass (generation)MonobactamMOA (bactericidal/bacteriostatic)Bactericidal. Inhibits cell wall synthesis by binding to PBPs. Spectrum (Gm+, Gm-, anaerobes)Gram (-) including Pseudomonas; no G+, no anaerobes. Not a drug that is commonly used. DOC for which diseasesUseful in patients with a history of severe allergy to penicillin (extremely low rate of cross-allergenicity). Used with metronidazole in secondary peritonitis. Absorption, distribution, metabolism, excretionGiven IV/ IM. Half life approx 1.7 hrs. Distributes throughout body. Mainly excreted in the urine. 12% fecal. PD (time vs. concentration dependent killing)Time dependentSide effects (what, how common, monitoring)Pain at injection site, G.I upset, Drug-induced eosinophilia (all somewhat rare) AllergiesVirtually no cross reactivity with other -lactamsDrug interactionsMonitor renal function if used with aminoglycosidesDose (renal/hepatic failure, obesity)1-2 gm IV q6-8h. However, dose adjustments needed for renal dysfunction. The liver plays a minor role in elimination. Pregnancy, pediatrics issuesPregnancy category B, safety/effectiveness under 9 months not established Relative costExpensive- no generic available Generic nameCEFAZOLINProprietary nameAncef, KefzolClass (generation)1st generation cephalosporin (IV drug)MOA (bactericidal/bacteriostatic)Bactericidal. Inhibits cell wall synthesis by binding to PBPs. Spectrum (Gm+, Gm-, anaerobes)Mainly gram +, a few enteric GNRs. No anaerobes below the diaphragm. DOC for which diseasesSurgical prophylaxis, occasional skin infections.Absorption, distribution, metabolism, excretionDistributes into bone well. Does not distribute into CSF in useful concentrations, even if inflamed. Excreted mainly unchanged in urine. PD (time vs. concentration dependent killing)Time dependent killing.Side effects (what, how common, monitoring)GI upsetAllergiesCross reactivity possible for those with penicillin allergies (under 5%) Drug interactionsNothing significantDose (renal/hepatic failure, obesity)1-2 gm IV q8h Decrease dose in renal insufficiencyPregnancy, pediatrics issuesPregnancy category BRelative costRelatively cheap- generic available. Generic nameCEFDINIRProprietary nameOmnicefClass (generation)3rd generation oral cephalosporinMOA (bactericidal/bacteriostatic)Bactericidal. Inhibits cell wall synthesis by binding to PBPs. Spectrum (Gm+, Gm-, anaerobes)Gram (+) cocci like Strep. Might work for S. aureus (not MRSA). Like all cephalosporins it is ineffective for Enterococcus. DOC for which diseasesSome pediatricians favor cefdinir for AOM because of its relatively pleasant taste Absorption, distribution, metabolism, excretionAbsorption independent of food. Half life approx 1.7 hrs. Distributes into tissue. Excreted renally. PD (time vs. concentration dependent killing)Time dependentSide effects (what, how common, monitoring)GI upset, headacheAllergiesCross reactivity possible for those with penicillin allergies (but chance is <1%) Drug interactionsAntacids may decrease absorptionDose (renal/hepatic failure, obesity)AOM: 14 mg/kg/day Decrease dose for renal dysfunctionPregnancy, pediatrics issuesPregnancy category BRelative costModerately expensive- no generic available. Generic nameCEFEPIMEProprietary nameMaxipimeClass (generation)4th generation cephalosporinMOA (bactericidal/bacteriostatic)BactericidalSpectrum (Gm+, Gm-, anaerobes)Summary: Best of ceftriaxone + best of ceftazidime Gm+ Gm- lacks anaerobes Pseudomonas  lactamase stable DOC for which diseasesICU monotherapy, maybe better than imipenem because it lacks anaerobe coverage In combination with ciprofloxacin for ICU treatment of CAP, 1-2 g IV q 12h x 10 days Absorption, distribution, metabolism, excretionA: IV, IM D: 20% protein bound, CSF concentrations decent M: Liver metabolism minor E: 85% unchanged in the urine PD (time vs. concentration dependent killing)Time-dependent Side effects (what, how common, monitoring)headache, confusion (rare) bleeding and bruising (rare, monitor PT) Mild diarrhea, more common AllergiesLess than 1% cross-reactivity if PCN allergy (rash) Drug interactionsNothing significant Dose (renal/hepatic failure, obesity)1-2 gm IV q8-12h Adjust for renal dysfunction Pregnancy, pediatrics issuesPregnancy category B Relative cost2g = $35-40 Generic nameCEFOTAXIMEProprietary nameClaforanClass (generation)3rd generation cephalosporinMOA (bactericidal/bacteriostatic)BactericidalSpectrum (Gm+, Gm-, anaerobes)Gm+ Gm- (bacilli), but not Pseudomonas No below diaphragm anaerobes DOC for which diseasesSBP: 2g IV q 8h x 5 days Bacterial meningitis for 0-1 month old along with ampicillin, 75 mg/kg q 6h Absorption, distribution, metabolism, excretionA: IV only D: 30-51% protein bound, CSF penetration good M: Liver converts it to active metabolite E: Renal 50-85%, biliary 15-75% PD (time vs. concentration dependent killing)Time-dependent Side effects (what, how common, monitoring)Agranulocytosis (rare) Steven-Johnson syndrome (rare) Mild diarrhea, nausea (more common) AllergiesLess than 1% cross-reactivity if PCN allergy (rash) Drug interactionsNothing significant Dose (renal/hepatic failure, obesity)1-2 gm IV q8-12h (adults) Adjust for renal dysfunction Pregnancy, pediatrics issuesPregnancy category B Safe in pediatrics Relative cost2g = $22 Generic nameCEFPODOXIME PROXETILProprietary nameVantinClass (generation)3rd generation oral cephalosporin MOA (bactericidal/bacteriostatic)Bactericidal inhibits cell wall synthesis Spectrum (Gm+, Gm-, anaerobes)Some Gram + and Gram bacteria (stable against -lactamases) NOT: MRSA, Enterococcus, Pseudomonas, Enterobacter DOC for which diseasesCan be used in AOM if recent antibiotic use Can be used in ABS if recent antibiotic use Absorption, distribution, metabolism, excretionBioavailability 46% Minimal metabolism PD (time vs. concentration dependent killing)Time-dependentSide effects (what, how common, monitoring)Diarrhea, nausea common AllergiesWatch for penicillin allergy (but cross-allergenicity is probably less than 1%) Drug interactionsAntacids Dose (renal/hepatic failure, obesity)10 mg/kg/day (AOM) 200 mg po bid (ABS) Pregnancy, pediatrics issuesPregnancy category B Relative costModerate Generic nameCEFTAZIDIMEProprietary nameFortaz, Tazicef, TazidimeClass (generation)Third generation cephalosporinMOA (bactericidal/bacteriostatic)BactericidalSpectrum (Gm+, Gm-, anaerobes)Gm+: limited; dont trust for these Gm-: Pseudomonas, most Enterobacteriaceae Anaerobes: not useful for below-the-diaphragm DOC for which diseases1. Pseudomonas pneumonia in CF patients 2. Other diseases due to Gram-negative bacteria: life-threatening, susceptible Gram-negative organisms including Pseudomonas and Enterobacteriaceae 3. Gram-negative osteomyelitis, especially due to Pseudomonas 4. Hospital acquired peritonitis (in combination with an antianaerobic drug) 5. Meningitis due to Pseudomonas 6. Nosocomially-acquired UTI Absorption, distribution, metabolism, excretionA: Parenteral only D: widely throughout the body including bone, bile, skin, CSF, endometrium, heart, pleural and lymphatic fluids M: minimally metabolized E: 90-96% renal PD (time vs. concentration dependent killing)Time dependent killing Side effects (what, how common, monitoring)Hypersensitivity (rash), transient eosinophilia, increased liver function tests AllergiesHypersensitivity to ceftazidime Drug interactionsNothing significant Dose (renal/hepatic failure, obesity)1-2 gm IVq8h Adjust for renal dysfunction Pregnancy, pediatrics issuesCategory B; OK to use in pediatrics Relative costModerately expensive  Generic nameCEFTRIAXONE Proprietary nameRocephin Class (generation)3rd generation cephalosporin MOA (bactericidal/bacteriostatic)Binds to PBPs to inhibit cell wall synthesis, bactericidal Spectrum (Gm+, Gm-, anaerobes)Gram (no Pseudomonas), Gram +, no below diaphragm anaerobes DOC for which diseasesCAP, inpatient, when Pseudomonas not an issue; bacterial meningitis for 1 mo-50 yrs; necrotizing fasciitis; NVE caused by HACEK group, gonorrhea (urethral, cervical, rectal, pharyngeal, and DGI) Absorption, distribution, metabolism, excretion100% absorption w/IM or IV administration; widely distributed in tissues including CSF, synovial fluid; minimally metabolized; biliary excretion PD (time vs. concentration dependent killing)Time-dependent Side effects (what, how common, monitoring)Rash, diarrhea, eosinophilia, increase in LFTs, all uncommon, monitor for severity AllergiesRash and anaphylaxis uncommon Drug interactionsNot common Dose (renal/hepatic failure, obesity)CAP, inpatient, when Pseudomonas not an issue: 2 g IV Q24h (+adv. macrolide) Bacterial meningitis for 1 mo-50 yrs: 2 g IV q12h (+vanco+dex) Necrotizing fasciitis: 2 g q12h (+ clindamycin) NVE caused by HACEK group: 2 g IV Q24h x4 wks Gonorrhea (urethral, cervical, rectal, pharyngeal): 125 mg IM x 1 DGI: 1 g IM/IV q24h x 7 days No dose adjustment necessary for renal disease, but possibly for severe hepatic impairment Pregnancy, pediatrics issuesPregnancy B, safe in pediatrics Relative cost$40-50 per gram  Generic nameCEFUROXIME AXETIL Proprietary nameCeftin Class (generation)Cephalosporin (oral, second generation) MOA (bactericidal/bacteriostatic)CIDAL, inhibit mucopeptide synthesis (peptidoglycan) in the bacterial cell wall making it unstable; more effective against rapidly growing bacteria (subject to the inoculum effect) Spectrum (Gm+, Gm-, anaerobes)Ok Gm+ (not as potent as 1st gen) Better Gm- than 1st gen (not Pseudomonas) Anaerobic coverage not especially good Better -lactamase resistance than 1st gen, therefore better for resistant strains than 1st gen DOC for which diseasesAOM, ABS (one of a number of options) Absorption, distribution, metabolism, excretionAbsorption: absorbed from GI and rapidly hydrolyzed in intestinal mucosa and blood, take with food Distribution: widely distributed to most tissues and fluids including CSF (not used for meningitis, though) Metabolism: metabolized to free cefuroxime plus acetaldehyde and acetic acid Excretion: primarily excreted renally PD (time vs. concentration dependent killing)Time-dependent killing Side effects (what, how common, monitoring)Anemia, eosinophilia, neutropenia (very rare) AllergiesCross-sensitivity to penicillins probably on the order of 1-2% Drug interactionsNone to speak of Oral contraceptivesthe general warning with antibiotics Dose (renal/hepatic failure, obesity)PO: 250-500 mg q12h Oral suspension for AOM: 30 mg/kg day divided q12h Adjust for renal dysfunction Pregnancy, pediatrics issuesCategory B, excreted in breast milk in small quantities Relative costOral moderately priced  Generic nameCEPHALEXINProprietary nameVelosefClass (generation)1st generation cephalosporinMOA (bactericidal/bacteriostatic)Bactericidal. Inhibits cell wall synthesis.Spectrum (Gm+, Gm-, anaerobes) Better Gm + than Gm -. Gm+: S. aureus (not MRSA); S. pneumoniae Gm-: E.coli; Klebsiella sp; Proteus mirabilis Anaerobic activity: not good DOC for which diseasesSkin infections caused by Gm + organismsAbsorption, distribution, metabolism, excretionWell absorbed from the GI tract and widely distributed throughout the body and many tissues. Primarily eliminated by kidney excretion. PD (time vs. concentration dependent killing)Time dependent killingSide effects (what, how common, monitoring)May cause mild diarrhea. AllergiesNot given to patient with a history of anaphylaxis to penicilin or known cephalosporin hypersensitivity. Probably OK to give to a patient with a history of penicillin rash (cross-allergenicity <5%, if that high) Drug interactionsNone of significance Dose (renal/hepatic failure, obesity)Normal: 250-500mg po q6h Renal failure: increase dosing interval to q12h Pregnancy, pediatrics issuesPregnancy category B; safe in pediatricsRelative cost500 mg generic $0.44 Generic nameCIPROFLOXACIN Proprietary nameCipro Class (generation)FQ, early 2nd generation, non-respiratory MOA (bactericidal/bacteriostatic)Binds to DNA gyrase and/or topoisomerase IV to inhibit DNA replication and repair. Bactericidal. Spectrum (Gm+, Gm-, anaerobes)Gram-, limited Gram +, no anaerobic coverage DOC for which diseasesAcute uncomplicated cystitis (when TMP/SMX resistance ~20% and for elderly patients), acute uncomplicated pyelonephritis Absorption, distribution, metabolism, excretionBioavailability 70%; widely distributed in most tissues, including synovial and prostatic fluids; eliminated by both renal and nonrenal mechanisms. Half-life 4 hours. PD (time vs. concentration dependent killing)Concentration-dependent Side effects (what, how common, monitoring)Nausea, CNS toxicity, tendon toxicity (rare). All uncommon, monitor for severity. AllergiesRash uncommon, anaphylaxis rare Drug interactionsCYP1A2 inhibitor Dose (renal/hepatic failure, obesity)Acute uncomplicated cystitis: 250 mg po BID x 3 days for non-elderly, 7-10 days for elderly Acute uncomplicated pyelonephritis: 500 mg po BID x 10-14 days or 200-400 mg IV q12h x 7-14 days CrCl 10-50 mL/min: decrease dose by 50-75% CrCl <10 mL/min: decrease dose by 50% Pregnancy, pediatrics issuesPregnancy category C, not FDA-approved in pediatrics except for treatment of anthrax and complicated pyelonephritis Relative costGeneric and relatively inexpensive  Generic nameCLARITHROMYCIN Proprietary nameBiaxin Class (generation)Advanced macrolide MOA (bactericidal/bacteriostatic)Bacteriostatic Spectrum (Gm+, Gm-, anaerobes)Gm+: Group A,B,C, and G streptococci; S. pneumoniae; MSSA Gm-: M. catarrhalis, H. influenzae Atypicals: Mycoplasma, Chlamydophila, Legionella No usable antianaerobic activity DOC for which diseases Acute exacerbation of chronic bronchitis Acute otitis media (alternative) Community acquired pneumonia (alternative in certain patients) Maxillary sinusitis, acute (alternative) Tonsillitis/pharyngitis H. pylori Absorption, distribution, metabolism, excretionBioavailability: 50% Vd 4 L/kg, protein binding 42-50% Metabolized in liver (active metabolite) Mixed renal and nonrenal elimination, half life 5-7 hr PD (time vs. concentration dependent killing)Time-dependent killing Side effects (what, how common, monitoring)Common: nausea and vomiting, diarrhea, headache. Metallic taste is particularly bothersome to patients. AllergiesTrue allergy to clarithromycin is rare Drug interactionsInhibitor and substrate of CYP3A4 Dose (renal/hepatic failure, obesity)Normal:500 mg q12h po or ER 1 gm po qd Renal dosing: CrCl 10-50: 75% of the dose CrCl<10: 50 % of the dose or extend the dosing interval. Pregnancy, pediatrics issuesCategory C Can be used in pediatric patients Relative cost500mg About 5 dollar per tab ER: also about 5 dollar per tab  Generic nameCLINDAMYCINProprietary nameCleocinClass (generation)Lincosamide (the only one on the US market)MOA (bactericidal/bacteriostatic)Bstatic: binds to 50S ribosomal subunit, inhibiting protein synthesis. Bcidal in high concentrations (but still generally viewed as a static drug) Side benefit: appears to decrease toxin synthesis by certain organisms Spectrum (Gm+, Gm-, anaerobes)Anaerobes (B. fragilis group). Gm (+) cocci [including streptococci and community-associated-MRSA]. No aerobic G- activity. DOC for which diseasesNecrotizing faciitis [in combination with a -lactam  ceftriaxone or Pen G if GABS]. Also a popular choice for a lung abscess. Absorption, distribution, metabolism, excretionBA: 90% T1/2: 1.5-6.5hrs, hepatic metabolism Distribution: High concentrations in bone and urine; no significant levels in CSF, even with inflamed meninges; crosses placenta; enters breast milk Eliminated in feces and bile Excretion: Urine (10%) and feces (~4%) as active drug and metabolites PD (time vs. concentration dependent killing)Time dependentSide effects (what, how common, monitoring)Diarrhea (20-30%) Pseudomembranous colitis due to C. difficile overgrowth (discontinue if significant diarrhea, cramps, or passage of blood and mucus occur) AllergiesNo major issues.Drug interactionsIncreased duration of neuromuscular blockade from tubocurarine, pancuronium (contraindicated in botulism cases) .Dose (renal/hepatic failure, obesity)Usual dose: Oral: 150-450 mg q6h (max: 1.8 g/day) IM, IV: 600-900mg q8h (max: 4.8 g/day) Adjustment is recommended in patients with severe hepatic disease. Pregnancy, pediatrics issuesPregnancy Category B, safe in kids Relative cost$8.00/600mg IV ($24-$36/day) Generic nameCOLISTIN (POLYMYXIN E), administered as the prodrug COLISTIMETHATE Proprietary nameColy-Mycin M Parenteral Class (generation)Polymyxin (a cyclic polypeptide) MOA (bactericidal/bacteriostatic)Bactericidal. Binds to lipopolysaccharide and alters cell membrane permeability, leading to spillage of cytoplasmic content and cell death Spectrum (Gm+, Gm-, anaerobes)Many Gram-negative bacilli including P. aeruginosa and Acinetobacter. However, Gram-positive organisms, anaerobes, and a few common Gram-negatives are resistant. DOC for which diseasesNone. Useful for serious infections caused by Gram-negative bacilli resistant to everything else. Used in inhaled form in patients with cystic fibrosis. Absorption, distribution, metabolism, excretionNot absorbed PO. CSF concentrations uncertain (can be directly instilled). A small fraction of administered colistimethate is hydrolyzed to colistin, which is mostly eliminated nonrenally. Half-lives: colistimethate 2 hours, colistin 4 hours. PD (time vs. concentration dependent killing)Concentration-dependent, limited postantibiotic effect Side effects (what, how common, monitoring)Nephrotoxicity (10-15%); neurotoxicity (7%) Allergies2% incidence of hypersensitivity Drug interactionsNot well studied Dose (renal/hepatic failure, obesity)Supplied in vials labeled with colistin base activity (150 mg each, equivalent to 400 mg colistimethate sodium). IV Dose: 2.5-5.0 mg/kg/day of colistin base activity, divided 2-4 times a day. Duration depends on indication. Adjust for renal dysfunction. Inhaled dose of colistimethate sodium: 40-60 mg, 2-3 times a day. Better tolerated than inhaled colistin. Pregnancy, pediatrics issuesCategory C Relative costAbout $100/day (IV) Generic nameDAPTOMYCIN Proprietary nameCubicin Class (generation)Cyclic lipopeptide MOA (bactericidal/bacteriostatic)Binds to bacterial membranes and causes rapid depolarization of membrane potential, leading to inhibition of protein, DNA, and RNA synthesis and cell death. Rapidly bactericidal. Spectrum (Gm+, Gm-, anaerobes)Vancomycin-like spectrum (includes VRE, MRSA,GISA, PRSP). No useful G- activity, no anaerobic coverage. DOC for which diseasesApproved for skin infections, but not likely to be a big use for this drug, Good use: endocarditis due to VRE Also an for endocarditis due to MRSA and non-MRSA S. aureus Absorption, distribution, metabolism, excretionA: IV only D: thought to have limited tissue penetration; binds to lung surfactant so must never be used for pulmonary infections M: Minimal metabolism E: Renally excreted PD (time vs. concentration dependent killing)Concentration-dependent killing Side effects (what, how common, monitoring)Increased CPKmonitor for muscle pain or weakness; potential to cause muscle damage still uncertain AllergiesHypersensitivity reactions possible Drug interactionsHMG-CoA reductase inhibitorsCubist recommends discontinuing them during daptomycin therapy Dose (renal/hepatic failure, obesity)Usual dose for skin infections: 4 mg/kg q24h If CrCl < 30: 4 mg/kg q 48 h Endocarditis dose (unapproved) 6 mg/kg q24h Pregnancy, pediatrics issuesPregnancy: B Pediatrics: Not approved in patients under 18 Relative cost$135 per 500mg vial Generic nameDICLOXACILLIN Proprietary nameVarious Class (generation)Penicillinase-resistant penicillin MOA (bactericidal/bacteriostatic)Bactericidal; inhibits cell wall synthesis Spectrum (Gm+, Gm-, anaerobes)S. aureus (MSSA), streptococci NOT ACTIVE FOR MRSA or coagulase-negative staphylococci DOC for which diseasesImpetigo (especially bullous) Ecthyma In general, a reasonable choice for a skin infection due to S. aureus or S. pyogenes Absorption, distribution, metabolism, excretionA: Oral - 60-80% D: volume of dist: 0.16 L/kg M: Hepatic E: Mainly by the liver PD (time vs. concentration dependent killing)Time-dependent killing Side effects (what, how common, monitoring)Diarrhea (dont expect a lot) Rash AllergiesHypersensitivity reaction possible Drug interactionsNothing special Dose (renal/hepatic failure, obesity)No specific adjustment necessary in renal failurePregnancy, pediatrics issuesPregnancy: B Pediatric: OK Relative cost500 mg generic = $1.20  Generic nameDOXYCYCLINE Proprietary nameVibramycin Class (generation)Tetracycline MOA (bactericidal/bacteriostatic)Bacteriostatic, binds to bacterial ribosome Spectrum (Gm+, Gm-, anaerobes)Gram (+) and Gram (-) (resistance is a problem with tetracyclines) Atypical pathogens (for CAP) DOC for which diseasesPossible for CAP (healthy, no recent antibiotics) Possible for cat bite in penicillin-allergic patient Absorption, distribution, metabolism, excretionA: oral, almost complete D: wide M/E: feces 30%, urine 23% PD (time vs. concentration dependent killing)Concentration-dependent killing Side effects (what, how common, monitoring)Nauseaa common problem with this drug Bad taste Diarrhea Less phototoxicity than with tetracycline AllergiesNot common Drug interactionsIncreases activity of warfarin Cations (aluminum, iron, magnesium) decrease absorption of doxycycline Dose (renal/hepatic failure, obesity)100 mg po q12h No specific adjustments necessary in renal failure Pregnancy, pediatrics issuesPregnancy: D Not in children under 8 Relative costInexpensive  Generic nameERTAPENEMProprietary nameInvanzClass (generation)CarbapenemMOA (bactericidal/bacteriostatic)Bactericidal. Inhibits cell wall synthesis by binding to PBPs. Excellent -lactamase stability (typical of a carbapenem). Spectrum (Gm+, Gm-, anaerobes)More active than imipenem against Enterobacteriaceae, but not clinically useful for P. aeruginosa. A bit less active than imipenem against gram-positive aerobic organisms and anaerobes. Poor activity against Enterococcus, Stenotrophomonas, and Acinetobacter. DOC for which diseasesNot DOC for anything, but a useful alternative for mild-to-moderate intraabdominal infection, and also CAP Absorption, distribution, metabolism, excretionParenteral only. 85-95% protein bound, Vd 8L at steady state. Renal excretion 80% of total drug (40% unchanged, 40% ring-opened form). Elimination half-life 4 hours, prolonged in renal insufficiency. PD (time vs. concentration dependent killing)Time-dependent (like all -lactams)Side effects (what, how common, monitoring)Typical of a -lactam (GI, dermatologic). Seizures not a problem (as they were initially with imipenem). May cause LFT and hematologic abnormalities (rare). AllergiesAvoid in patients with history of penicillin-induced anaphylaxis Drug interactionsNone significantDose (renal/hepatic failure, obesity)1 gm IV/IM q24h. Decrease to 500 mg IV/IM q24h if CrCl less than 30. Duration of treatment depends on specific infection. Pediatric (3 mon-12 years): 15 mg/kg IV/IM bid, maximum 1 gram/day. Pregnancy, pediatrics issuesCategory BRelative cost$40-50 per gram depending on the institution Generic nameERYTHROMYCINProprietary nameVariousClass (generation)MacrolideMOA (bactericidal/bacteriostatic)Bacteriostatic. Inhibits bacterial growth by suppressing RNA-dependent protein synthesis. Spectrum (Gm+, Gm-, anaerobes)Gm+ aerobes and atypicals (Mycoplasma, Chlamydophila, Legionella) No good for MRSA Poor for most Gram-negatives, no good for anaerobes DOC for which diseasesAtypical pneumonia; diphtheria; pertussis; Alternative to amoxicillin for preventing bacterial endocarditis Absorption, distribution, metabolism, excretionAbsorbed well from the fasting GI tract, distributed readily into most tissues except brain and CSF, excreted primarily in bile. PD (time vs. concentration dependent killing)Time-dependent killingSide effects (what, how common, monitoring)N/V/D, abdominal cramps (due to hemiketal metabolites formed in the gut); may prolong QTc interval (questionable significance) AllergiesRareDrug interactionsCYP 3A4 inhibitor. Increases blood levels of benzodiazepines, carbamazepine, cyclosporine, ergot alkaloids, lovastatin, simvastatin, tacrolimus, pimozide Dose (renal/hepatic failure, obesity)Normal: 250-500mg po (or IV) q6h Possibly adjust dose for CrCl <10 Orally available as salt form and esters (be careful with doses) Pregnancy, pediatrics issuesPregnancy category B Pediatrics: safe Relative costGenerally inexpensive Generic nameETHAMBUTOLProprietary nameMyambutolClass (generation)Antimycobacterial agentMOA (bactericidal/bacteriostatic)Bacteriostatic Spectrum (Gm+, Gm-, anaerobes)Mycobacterium spp.DOC for which diseasesInitial treatment of active TB (to cover resistance) Removed from therapy as soon as susceptibility to INH and RIF are confirmed Absorption, distribution, metabolism, excretionPoor CNS penetration regardless of inflammation Renal elimination PD (time vs. concentration dependent killing)UnknownSide effects (what, how common, monitoring)Most frequent toxicity: optic neuritis (dose-related). May result in changes in red-green color perception. AllergiesNot commonDrug interactionsNo significant interactionsDose (renal/hepatic failure, obesity)15-25 mg/kg/day Must adjust dose in renal dysfunction Pregnancy, pediatrics issuesCDC says safe in pregnancy Relative costInexpensive Generic nameGENTAMICINProprietary nameGaramycinClass (generation)aminoglycosideMOA (bactericidal/bacteriostatic)Bactericidal, inhibits protein synthesis by binding with 30S ribosomal subunit. Spectrum (Gm+, Gm-, anaerobes)Aerobic gram-negative bacilli, Pseudomonas aeruginosa. Synergistic with cell-wall active drugs for G+ organisms. No anaerobic coverage. DOC for which diseasesHAP (w/antipseudomonal -lactam)Absorption, distribution, metabolism, excretionPoor oral absorption Vd = 0.26 L/kg; does not cross blood-brain barrier Relatively low concentrations in lung secretions Renally eliminated, T1/2 = 2-3 hours PD (time vs. concentration dependent killing)Concentration dependent killingSide effects (what, how common, monitoring)Nephrotoxicity (reversible), ototoxicity (irreversible), neuromuscular blockade at high concentrations AllergiesNoneDrug interactionsIncreased nephrotoxicity with amphotericin B, cisplatin, cyclosporine, NSAIDs, vancomycin, radiographic contrast. Increased ototoxicity with cisplatin and loop diuretics. Increased apnea or respiratory paralysis with neuromuscular blocking agents. Dose (renal/hepatic failure, obesity)2 mg/kg load, then 1.7 mg/kg IV q8h Sarubbi-Hull dosing nomogram is very useful Peak = 5-8 mcg/ml (10-12 for pneumonia, <3 for G+) Trough = <1 mcg/ml Renal failure: adjust dose based on CrCl Obesity: Dose based on IBW + 0.4(TBW-IBW) Pregnancy, pediatrics issuesPregnancy Category D, may be used in pediatrics, Breastfeeding: infant risk minimal Relative costInexpensive Generic nameIMIPENEM/CILASTATINProprietary namePrimaxinClass (generation)CarbapenemMOA (bactericidal/bacteriostatic)Bactericidal, interferes with last stage of bacterial cell wall synthesis. Excellent -lactamase resistance. Spectrum (Gm+, Gm-, anaerobes)Very broad spectrum: most gram positive, gram negative (including Pseudomonas), and anaerobes. Not Coag(-) staph or MRSA. DOC for which diseasesHospital acquired infections: high severity intraabdominal infections, hospital-acquired pneumonia  Absorption, distribution, metabolism, excretionNot absorbed by GI tract. Given IV or IM. Hydrolyzed by dihydropeptidases present in brush border of renal proximal tubule to a toxic metabolite; therefore given with cilastatin, an inhibitor of these enzymes, to prevent breakdown. 70% excreted in urine as active drug. Half-life 1 hour. PD (time vs. concentration dependent killing)Time-dependent killingSide effects (what, how common, monitoring)N/V if infused too quickly. Increased potential for seizures if recommended doses exceeded in patients with CrCl less than 20 ml/min. AllergiesIncidence of hypersensitivity is low. Potential for cross-reactivity with other -lactams is about 50% for immediate hypersensitivity, 10% or less for accelerated hypersensitivity Drug interactionsNoneDose (renal/hepatic failure, obesity)500 mg q6h IV  adjust for renal failure. CrCl>50-90: 250-500 mg q6-8h CrCl 10-50: 250 mg q6-12h CrCl<10: 125-250 mg q12h Pregnancy, pediatrics issuesPregnancy category C, well tolerated in adults and children. Safety and efficacy of IM product not established in children under 12. Relative cost500 mg Primaxin: $33.10. One of the more expensive antimicrobials.  Generic nameISONIAZIDProprietary nameINH (abbreviation for isonicotinic acid hydrazide)Class (generation)Antituberculous agent, first lineMOA (bactericidal/bacteriostatic)Bactericidal, mechanism unknown--possibly via inhibition of mycolic acid synthesis resulting in disruption of the cell wall Spectrum (Gm+, Gm-, anaerobes)Mycobacterium tuberculosisDOC for which diseasesTBAbsorption, distribution, metabolism, excretion CYP 2E1 inhibitor MAO inhibitor (weak)A-Rapid and complete; slowed with food D-distributes widely to all body tissues and fluids, including CSF; crosses placenta; enters breast milk M-mostly hepatic by acetylation E-Half-life: Fast acetylators:30-100 minutes Slow acetylators: 2-5 hours 75-95% excreted in urine; also in feces and saliva PD (time vs. concentration dependent killing)Not knownSide effects (what, how common, monitoring)Hepatitis (monitor LFT baseline, 1, 3, and 6 months). Avoid ethanol. Peripheral neuropathy (give pyridoxine 25-50 mg qd). AllergiesNot commonDrug interactionsMetabolic enzyme inhibitor (CYP2C19, CYP3A4). Significance uncertain, dont fret too much about this. Dose (renal/hepatic failure, obesity)5 mg/kg/day (max 300 mg qd). Duration depends on clinical situation. Pregnancy, pediatrics issuesPregnancy category C. Enters breast milk, compatible with lactation Relative costCheap: 300 mg tablets, 30/$9.84 Generic nameLEVOFLOXACIN Proprietary nameLevaquin Class (generation)Fluoroquinolone MOA (bactericidal/bacteriostatic)Inhibits DNA gyrase and/or topoisomerase IV in susceptible organisms thereby inhibits relaxation of DNA and promote breakage. Bactericidal. Spectrum (Gm+, Gm-, anaerobes)Very good coverage of almost all Gram negatives; borderline for Pseudomonas. Decent Streptococcus coverage and non-resistant S. aureus. Active vs. Enterococcus if in the urine. Poor anaerobic coverage, not reliable for MRSA. DOC for which diseasesCAP/HAP; UTI in elderly and where E. coli is >20% TMP/SMX resistant; bacterial sinusitis if exposed to antibiotics one month prior Absorption, distribution, metabolism, excretionOral: bioavailability=99% Distribution: Vd:1.25L/kg, CSF conc. about 15% of serum levels, high concentrations in prostate, lung, gynecological tissues, sinus, saliva Metabolism: minimal Excretion: primarily urine as unchanged drug, half-life 6-8 hours PD (time vs. concentration dependent killing)Concentration dependent (AUC/MIC correlates best) Side effects (what, how common, monitoring)Gastrointestinal: diarrhea, nausea Neurologic: confusion, headache Cardiovascular: QTc prolongation (rare) Endocrine: hypoglycemia (in diabetic patients, rare) Musculoskeletal: rupture of tendon (rare) Acute interstitial nephritis (rare) AllergiesSkin rashes occur now and then (generally uncommon) Drug interactionsAvoid use of metal cations (e.g. aluminum, magnesium) Dose (renal/hepatic failure, obesity)Normal: 500 mg IV/PO qd (UTI: 250 mg PO qd) CrCl between 10-50: 500 mg x1, then 250 mg q24-48h CrCl <10: 500 mg x1 then 250 mg q48h Depending on the situation, 750 mg levofloxacin qd x5 days can be used (CAP, ABS) Pregnancy, pediatrics issuesNot approved for pediatric use; pregnancy category C Relative costModerately priced  Generic nameLINEZOLID Proprietary nameZyvox Class (generation)Oxazolidinone MOA (bactericidal/bacteriostatic)Inhibits bacterial growth by preventing formation of 70s initiation complex, which inhibits protein synthesis, Bacteriostatic. Spectrum (Gm+, Gm-, anaerobes)Gram +: yes, including MRSA, PNSP, and VRE Gram -: not useful Anaerobes: some, not especially useful here DOC for which diseasesVRE In addition, linezolid is looking better and better for certain MRSA infections, especially pneumonia Absorption, distribution, metabolism, excretionAbsorption: very good Metabolism: 2 major metabolites Excretion: mostly in urine (~80%) PD (time vs. concentration dependent killing)Time-dependent killing Side effects (what, how common, monitoring)N/V, diarrhea, headache Reversible thrombocytopenia, anemia, neutropenia (the blood dyscrasias mainly occur in patients who receive >2 weeks of treatment) AllergiesRare Drug interactionsWeakly and reversibly inhibits monoamine oxidase (MAO); may interact with dietary tyramine and SSRIs (possible serotonin syndrome) Adrenergic agents: risk of hypertension Dose (renal/hepatic failure, obesity)600 mg PO (or IV) BID X10-14d (adult) 10 mg/kg q8h (pediatric) Renal failure: no adjustment necessary Pregnancy, pediatrics issuesPregnancy category C, safe in pediatrics Relative costExpensive! Generic nameMEROPENEM Proprietary nameMerrem Class (generation)Carbapenem MOA (bactericidal/bacteriostatic)CIDAL, inhibition of cell wall synthesis; readily penetrates the cell wall of most Gm+ and Gm- bacteria to reach PBP targets Spectrum (Gm+, Gm-, anaerobes)Good Gm+, good Gm-, Good anaerobic coverage No MRSA coverage, Pseudomonas YES In general, a bit more potent than imipenem for Gm- but a bit less potent than imipenem for Gm+ DOC for which diseasesHAP (empiric) Severe diverticulitis, perirectal abscess, peritonitis Sinusitis (hospitalized + intubation-related) Malignant otitis externa BOTTOM LINE: can be used for anything imipenem can be used for Absorption, distribution, metabolism, excretionPenetrates well into most tissues including CSF Largely eliminated unchanged in the urine Half-life 1 hour PD (time vs. concentration dependent killing)Time-dependent Side effects (what, how common, monitoring)Rash, thrombocytopenia, nausea/vomiting, diarrhea, headache (all less than imipenem) AllergiesHave occurred in patients with hypersensitivities to  lactam antibiotics (the pattern is assumed to be like imipenem) Drug interactionsProbenecid (inhibits renal excretion of meropenem) Oral contraceptives (the usual antibiotic-OC risk) Dose (renal/hepatic failure, obesity)Normal dose is 0.5-1.0 gm IV q8h 2 gm IV q8h for meningitis Adjust in renal insufficiency Pregnancy, pediatrics issuesPregnancy category B Lactation: unknown if excreted in breast milk (probably isnt) Relative costComparable to imipenem  Generic nameMETRONIDAZOLEProprietary nameFlagylClass (generation)NitroimidazoleMOA (bactericidal/bacteriostatic)Bactericidal; causes disruption of DNA helix and strand breakage leading to inhibition of protein synthesis and cell death Spectrum (Gm+, Gm-, anaerobes)Anaerobes, protozoa, H. pylori. No activity against aerobic bacteria. DOC for which diseasesTrichomoniasis, C. difficile colitis, bacterial vaginosis, anaerobic infections Absorption, distribution, metabolism, excretionA-Well absorbed D-distributes to saliva, bile, seminal fluid, breast milk, bone, liver, lung and vaginal secretions, crosses placenta, and BBB. M-30-60% hepatic E-Half-life: 6-8 hr 20-40% excreted unchanged in urine; 6-15% in feces PD (time vs. concentration dependent killing)UnclearSide effects (what, how common, monitoring)Nausea, vomiting, metallic taste Disulfiram reaction (alcohol) AllergiesVery rareDrug interactions2C9 inhibitor--potential interactions with warfarin and phenytoin Dose (renal/hepatic failure, obesity)500 mg PO tid x 10-14 days (C. difficile colitis) 2 g PO x 1 (Trichomonas) 500 mg po bid x 7 days (bacterial vaginosis) 500 mg IV q8h (serious anaerobic infection) Dose reduction recommended if CrCl <10Pregnancy, pediatrics issuesSafe in pregnancy (B)Relative costCheap Generic nameMOXIFLOXACINProprietary nameAveloxClass (generation)3rd generation fluoroquinoloneMOA (bactericidal/bacteriostatic)Bactericidal inhibits topoisomerase II (DNA gyrase) and topoisomerase IV Attacking dual targets with roughly equal affinity may give moxifloxacin an advantage over levofloxacin in terms of causing resistance Bulky C-7 group helps to avoid bacterial efflux Spectrum (Gm+, Gm-, anaerobes)Excellent gram-positive coverage Not as great gram-negative coverage Anaerobe coverage is good (unproven though)DOC for which diseasesCan be used in ABS if recent antibiotic use CAP patients with co-morbid conditions Absorption, distribution, metabolism, excretion90% bioavailability Absorbed in the gut Widely distributed throughout body Mainly eliminated by the liver (conjugation) PD (time vs. concentration dependent killing)Concentration-dependent (AUC/MIC correlates best) Side effects (what, how common, monitoring)Can prolong the QT interval (usually insignificant); has other typical FQ side effects; overall well tolerated AllergiesRareDrug interactionsAvoid antacids Dose (renal/hepatic failure, obesity)400 mg PO qd (no adjustment in renal insufficiency)Pregnancy, pediatrics issuesPregnancy category C Not approved in pediatric patients Relative costMore expensive compared to ciprofloxacin and levofloxacin  Generic nameNAFCILLIN Proprietary nameUnipen Class (generation)Penicillinase-resistant penicillin MOA (bactericidal/bacteriostatic)CIDAL. Penicillinase-resistant inhibitor of biosynthesis of mucopeptide (peptidoglycan). Most effective when bacteria are growing (subject to the inoculum effect) Spectrum (Gm+, Gm-, anaerobes)Ok Gm+, but really no Gm- or anaerobic coverage (NO MRSA) DOC for which diseasesOsteomyelitis (MSSA) Brain abscess Mastoiditis (outpatient) Staphylococcal endocarditis (MSSA) Anything S. aureus that is MSSA Cellulitis, erysipelas Toxic shock syndrome Absorption, distribution, metabolism, excretionDistributes to most tissues readily where there is inflammation Excretion: metabolized. NO ADJUSTMENT FOR RENAL DYSFUNCTION. PD (time vs. concentration dependent killing)Time-dependent killing Side effects (what, how common, monitoring)Fever, rash, neutropenia (monitor WBC); all relatively rare AllergiesPatients who are truly penicillin-allergic should be assumed nafcillin-allergic Drug interactionsDecreases the anticoagulant effect of warfarin (mechanism unclear; CYP3A induction suggested, although CYP3A catalyzes only a minor R-warfarin metabolic pathway) Dose (renal/hepatic failure, obesity)Normal: 1-2 gm q4h IV, IM Renal failure: no reduction generally needed Hepatic failure: adjust empirically if dysfunction is severe Pregnancy, pediatrics issuesPregnancy category B Excreted into breast milk in small quantities (not clinically significant) Relative cost1 gm ~$5.63  Generic nameNITROFURANTOINProprietary nameMacrobid, MacrodantinClass (generation)Synthetic nitrofuranMOA (bactericidal/bacteriostatic)Bactericidal at high conc, bacteriostatic at low conc. Inhibition of bacterial acetylcoenzyme A and subsequent disruption of the carbohydrate metabolism. Spectrum (Gm+, Gm-, anaerobes)Gm+: S. aureus, Enterococcus Gm-: E. coli; be careful, many Gram-negatives are relatively resistant, e.g. Proteus, Enterobacter, Klebsiella Anaerobes: no useful activity DOC for which diseasesAlternative therapy for UTI (x7days) Occasionally used for longterm prophylaxis Absorption, distribution, metabolism, excretionIncreased absorption with meal; highly protein bound and distributed throughout tissues; readily metabolized in tissues, renally excreted. USE ONLY FOR URINARY TRACT INFECTION! PD (time vs. concentration dependent killing)Concentration-dependent killingSide effects (what, how common, monitoring)N/V, pulmonary fibrosis, peripheral neuropathy, pseudotumor cerebri, intrahepatic cholestasis, hepatitis, and hemolytic anemia in G6PD deficiency. When given long-term, monitor for pulmonary, hepatic, and neurologic toxicity. These toxicities arent necessarily common, but nevertheless physicians like to avoid them by choosing other agents. AllergiesRareDrug interactionsAntacids can decrease the absorption of nitrofurantoinDose (renal/hepatic failure, obesity)Macrodantin: 100 mg q6h x 7 days Macrobid: 100 mg bid x7 days Longterm UTI prophylaxis: 50-100 mg po qd Contraindicated in renal failure (CrCl <50) Pregnancy, pediatrics issuesPregnancy category B (but not for use in G6PD-deficient mothers) Relative costMacrodantin:100mg generic $1.21 Macrobid: 100mg generic $2.26  Generic namePENICILLIN GProprietary nameVariousClass (generation)Natural penicillin (susceptible to penicillinase)MOA (bactericidal/bacteriostatic)Bactericidal. Inhibits cell wall synthesis by binding to PBPs. Spectrum (Gm+, Gm-, anaerobes)Gram +: good for Streptococcus pyogenes (GABS) but not active against Staphylococcus (neither MSSA nor MRSA). PNSP prevalence about 40% in the US. Gram -: useful for nonpenicillinase-producing species of Neisseria Usually effective for above-diaphragm anaerobes but not for below-diaphragm anaerobes DOC for which diseasesAcute pharyngitis ARF prophylaxis Syphilis, neurosyphilis Absorption, distribution, metabolism, excretionPen G: IV only 65% protein bound Crosses BBB if meninges are inflamed >80% excreted unchanged via kidneys Half-life: 30 minutes PD (time vs. concentration dependent killing)Time dependentSide effects (what, how common, monitoring)Diarrhea, serum sickness (rare) AllergiesImmediate allergy: anaphylaxis (rare) Accelerated: urticarial rash Late: maculopapular rashDrug interactionsProbenecid inhibits tubular secretion of penicillin which results in increased blood levels Dose (renal/hepatic failure, obesity)Acute pharyngitis: Bicillin LA 0.6 or 1.2 million units x1, depending on patient weight Neurosyphilis: Pen G 3-4 MU IV q4h x10-14d Dose reduction in renal failure Pregnancy, pediatrics issuesSafe in pregnancy and pediatricsRelative costPen G: 5MU about $5-6 Generic namePENICILLIN VKProprietary nameVariousClass (generation)Natural penicillin (susceptible to penicillinase)MOA (bactericidal/bacteriostatic)Bactericidal. Inhibits cell wall synthesis by binding to PBPs. Spectrum (Gm+, Gm-, anaerobes)Gram +: good for Streptococcus pyogenes (GABS) but not active against Staphylococcus (neither MSSA nor MRSA). PNSP prevalence about 40% in the US. DOC for which diseasesAcute pharyngitisAbsorption, distribution, metabolism, excretion60-70% absorbed 65% protein bound >80% excreted unchanged via kidneys Half-life: 30 minutesPD (time vs. concentration dependent killing)Time dependentSide effects (what, how common, monitoring)Diarrhea, serum sickness (rare) AllergiesImmediate allergy: anaphylaxis (rare) Accelerated: urticarial rash Late: maculopapular rashDrug interactionsProbenecid inhibits tubular secretion of penicillin which results in increased blood levels Dose (renal/hepatic failure, obesity)Acute pharyngitis: 250 mg PO bid or tid (25-50 mg/kg/day) x10d Pregnancy, pediatrics issuesSafe in pregnancy and pediatricsRelative costInexpensive Generic namePIPERACILLIN/TAZOBACTAMProprietary nameZosynClass-lactam/-lactamase inhibitorMOA (bactericidal/bacteriostatic)Bactericidal. Inhibits cell wall synthesis. Tazobactam is a -lactamase inhibitor that inhibits some -lactamases (such as Bush class 2b enzymes, or the ESBLs) but NOT class 1 enzymes (from SPICE organisms) Spectrum (Gm+, Gm-, anaerobes)Broad: gram (+) and (-) including Pseudomonas, plus anaerobes DOC for which diseasesCAP: with cipro for ICU pts at risk for Pseudomonas HAP: combined with gentamicin Secondary peritonitis (all by itself) Osteomyelitis in diabetes Absorption, distribution, metabolism, excretionWidely distributed throughout body Excreted mostly unchanged via kidneys Half-life of piperacillin: 1 hour PD (time vs. concentration dependent killing)Time dependentSide effects (what, how common, monitoring)Drug fever, rash, diarrhea AllergiesImmediate allergy: anaphylaxis (rare) Accelerated: urticarial rash Late: maculopapular rashDrug interactionsNothing significantDose (renal/hepatic failure, obesity)Standard dose: 3.375 g IV q6h (can also use 4.5 g q8h). This dose is not reliable for Pseudomonas, however, so be careful. Reduce dose in renal failure IMPORTANT: 16-18 grams/day of piperacillin must be used whenever Pseudomonas is a concern (i.e. 3.375 g IV q4h or 4.5 gm IV q6h) Pregnancy, pediatrics issuesCategory BRelative cost~$50 per day (standard dose) Generic namePYRAZINAMIDEProprietary namePZA (abbreviation)Class (generation)Antituberculous agentMOA (bactericidal/bacteriostatic)Bactericidal in acid pH of macrophagesSpectrum (Gm+, Gm-, anaerobes)Mycobacterium tuberculosisDOC for which diseasesActive TB, first line (only used in combination with other drugs) Absorption, distribution, metabolism, excretionA: almost completely absorbed from GI tract D: 5-10% protein bound, Vd 0.75-1.65 L/kg, distributes into CSF well M: 15-30% E: Renal 70% Half-life: 9 hours PD (time vs. concentration dependent killing)UnclearSide effects (what, how common, monitoring)N/V, Hyperuricemia, arthralgia (40%), severe liver injury Monitor LFTs, serum uric acid levels AllergiesNot commonly reportedDrug interactionsNot well defined Dose (renal/hepatic failure, obesity)TB: 25-30 mg/kg/day Renal dosing: consider decreasing dose by 50% if CrCl less than 10 Pregnancy, pediatrics issuesPregnancy category C, safe in pediatricsRelative costInexpensive Generic nameRIFAMPINProprietary nameRimactaneClass (generation)RifamycinMOA (bactericidal/bacteriostatic)Bactericidal drug Binds to bacterial DNA-dependent RNA polymerase Spectrum (Gm+, Gm-, anaerobes)M. tuberculosis Excellent for S. aureus (including MRSA) and S. epidermidis but only in combination with another drug DOC for which diseasesFirst line for TB PVE Chemoprophylaxis for N. meningitidis meningitis Absorption, distribution, metabolism, excretionA: 90-95% GI absorbed, delayed by food D: 60-90% protein bound, rapidly distributed into tissues, penetrate abscesses and CSF (if inflamed) Vd: 0.9 L/kg M: Liver 60-80%, enterohepatic circulation E: Renal 15-30%, Bile, Feces 60% PD (time vs. concentration dependent killing)Not establishedSide effects (what, how common, monitoring)GI upset is common, colors body fluids orange; routinely causes hyperbilirubinemia (usually transient); hemolytic anemia, renal failure, thrombocytopenia (1%) especially in patients who receive intermittent therapy (get baseline CBC, liver enzymes, SCr) AllergiesUncommonDrug interactionsMakes oral contraceptives unreliable Potent inducer of CYP 1A2, 2C9, 2C19, 3A4 Dose (renal/hepatic failure, obesity)TB dose: 10 mg/kg/day (maximum 600 mg qd) Meningococcus prophylaxis: 600 mg PO bid x2 days PVE: 300 mg PO q8h Adjunct drug for S. aureus: 300 mg PO q8-12h Renal: consider a dosage change if CrCl <50 Hepatic: decrease dose if severe dysfunction Pregnancy, pediatrics issuesPregnancy category C, ok in pediatricsRelative costInexpensive Generic nameTELITHROMYCINProprietary nameKetekClass (generation)KetolideMOA (bactericidal/bacteriostatic)Bacteriostatic; binds to 2 sites on 23S ribosome (macrolides bind to only one); also avoids drug efflux Spectrum (Gm+, Gm-, anaerobes)G+: especially good for drug resistant S. pneumoniae, S pyogenes G-: M cat and H flu Unreliable for MRSA Not good for anaerobes SUMMARY: the best of azithro plus the best of clarithro rolled into one drug, with the added advantage of covering drug-resistant S. pneumoniae DOC for which diseasesIndicated for CAP, AECB, sinusitisAbsorption, distribution, metabolism, excretionA: oral 57% bioavailability, unaffected by food D: 60-70% protein bound, penetrates lung tissues well, Vd=2.9 L/kg M: 37% in liver (50% CYP metabolized) E: 75% feces, Renal 12-14%. Half-life 10 hours. PD (time vs. concentration dependent killing)Concentration dependent, prolonged post antibiotic effect Side effects (what, how common, monitoring)Diarrhea (10%), nausea (7%), headache (5%), dizziness (4%), vomiting (3%) Liver dysfunction (rare) Visual disturbances can be serious AllergiesHypersensitivity to ketolide or macrolide antibiotics Drug interactionsCompetitive inhibitor of CYP 3A4 and 2D6Dose (renal/hepatic failure, obesity)Usual: 800 mg PO qd x5 days (7-10 days for CAP) Renal dosing: 400 mg PO qd if CrCl <30 Pregnancy, pediatrics issuesPregnancy category C Pediatrics safety not yet established (no suspension form available) Relative costExpensive, overpriced (at least initially) Generic nameTIGECYCLINEProprietary nameTygacilClass (generation)Glycylcycline (derived from minocycline)MOA (bactericidal/bacteriostatic)Bacteriostatic: inhibits protein translation by binding to the 30S ribosomal subunit Spectrum (Gm+, Gm-, anaerobes)Most Gm+ (including MRSA, VRE, PNSP) Many Gm- (not 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d$IfgdTzkdZK$$Ifl0,"&r t0644 ladev~xx d$IfgdTzkdK$$Ifl0,"5c t0644 la~{{ d$IfzkdL$$Ifl0,"5c t0644 la34{uu$If d$Ifzkd,M$$Ifl0,"5c t0644 la2345?RX @ A B C e       !!!!("5"?"I"K"Y"u"w"""""v#w#x#y#ιιvh&ich!CJaJh&ichcy]5CJ\aJhhCJaJh!CJaJhcy]CJ\aJUh&ichcy]6CJ\]aJh&ichcy]CJ\aJh,J55CJaJh&ichcy]5CJaJh&ichOaCJaJhcy]CJaJhOaCJaJh&ichcy]CJaJ.45T{A B {uuuuuu$If d$IfzkdM$$Ifl0,"5c t0644 laracycline resistance mechanisms: ribosomal protection and efflux DOC for which diseasesAlternative treatment for complicated skin and skin structure infections as well as intraabdominal infections Absorption, distribution, metabolism, excretionMetabolism / Excretion: not extensively metabolized. 59% of the dose is eliminated by biliary/fecal excretion, and 33% is excreted in urine. Approximately 22% of the total dose is excreted as unchanged tigecycline in urine. Half-life LONG: 30-36 hours. PD (time vs. concentration dependent killing)Concentration-dependent (AUC/MIC)Side effects (what, how common, monitoring)Significant nausea, vomiting and diarrhea. Tooth discoloration: the use of tigecycline during tooth development (last half of pregnancy, infancy, and childhood until the age of 8 years) may cause permanent discoloration of the teeth (yellow-gray-brown). AllergiesNo major issuesDrug interactionsMay decrease warfarin clearance (significance unclear) Dose (renal/hepatic failure, obesity)100 mg IV x1, then 50 mg IV q12 hours (x10-14 days) NO adjustment in renal dysfunction In severe hepatic impairment, the initial dose of tigecycline should be 100 mg, then 25 gm IV q12h Pregnancy, pediatrics issuesPregnancy Category D; safety in pediatrics has not been established Relative costAbout $90/day (similar to linezolid) Generic nameTRIMETHOPRIM/SULFAMETHOXAZOLE (TMP/SMX) Proprietary nameBactrim, Septra Class (generation)Sulfonamide plus DHFR inhibitor MOA (bactericidal/bacteriostatic)Bacteriostatic: SMX inhibits dihydropteroate synthetase, TMP inhibits dihydrofolate reductase Spectrum (Gm+, Gm-, anaerobes)Gm+: good for CA-MRSA, but usually does not work for PNSP and does not cover Enterococcus, S. epidermidis, or GABS Gm-: generally effective for enteric GNR, H. influenzae; does not cover Pseudomonas Anaerobes: inactive DOC for which diseasesUTI (unless E. coli resistance is >20%) SBP prophylaxis PCP in AIDS patients Absorption, distribution, metabolism, excretionAbsorption: 90-100% Vd: TMP 2.0 L/kg; SMX 360 mL/kg; penetrates CSF Half-life: 10-12 hr (each component) Metabolism: extensive liver metabolism Renal excretion: SMX 10-30%; TMP 50-75% PD (time- or concentration-dependent killing)Unclear Side effects (what, how common, monitoring)10% of patients: N/V/GI upset; skin problems (rash, urticaria, photosensitivity); hyperkalemia Less common: Stevens-Johnson syndrome, toxic epidermal necrolysis. Can cause blood dyscrasias, especially in AIDS patients. Commonly suspected cause of aseptic meningitis. AllergiesSulfonamide allergy is common Drug interactionsSMX is a CYP2C9 inhibitor Dose (renal/hepatic failure, obesity)UTI: 1 DS tablet BID PCP: 5 mg/kg q6-8h (based on TMP component) Reduce dose by 50% if CrCl <50 ml/min Pregnancy, pediatrics issuesPregnancy category C but do not use near term; safe for use in pediatrics but do not use in children < 2 months old due to possibility of kernicterus Relative costVery inexpensive  Generic nameVANCOMYCIN Proprietary nameVancocin Class (generation)Glycopeptide MOA (bactericidal/bacteriostatic)Bactericidal: inhibits cell wall synthesis by binding to D-ala-D-ala dipeptides Spectrum (Gm+, Gm-, anaerobes)Gm+: active against most genera (should be combined with an aminoglycoside to treat E. faecalis) No Gm- activity Anaerobic activity: C. difficile (oral only) DOC for which diseasesMRSA infections Bacterial meningitis (combined with ceftriaxone) Vascular catheter infections due to S. epidermidis Endocarditis (second line) Antibiotic-associated diarrhea (second line) Absorption, distribution, metabolism, excretionA: not orally absorbed D: wide, including CSF if meninges are inflamed; Vd 0.7 L/kg M: not metabolized E: excreted unchanged in the urine (half-life 6 hours) PD (time vs. concentration dependent killing)Time-dependent killing Side effects (what, how common, monitoring)Rapid infusion can cause red man syndrome (flushed skin, edema) Neutropenia (rare) Rash (rare) Ototoxicity and nephrotoxicity (rare) AllergiesNot a particular issue with this drug Drug interactionsIncreased frequency of nephrotoxicity with aminoglycosides Dose (renal/hepatic failure, obesity)Normal dose: 1 gm IV q12h Obesity: daily dose correlates with actual body weight Renal dysfunction: increase dosing interval as CrCl decreases Pregnancy, pediatrics issuesPregnancy category C, safe to use in pediatrics Relative costSomewhat expensive      B C Z   {uu$If d$IfzkdPN$$Ifl0,"5c t0644 la   !!~~~$IfzkdN$$Ifl0,"5c t0644 la!!("J"~u d$If$IfzkdtO$$Ifl0,"5c 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