1 / 40

Bugs and Drugs: Solving the Antibiotic Dilemma

Bugs and Drugs: Solving the Antibiotic Dilemma. Catherine Davis, Pharm.D. Exempla Saint Joseph Hospital. Presentation Overview. Briefly review sensitivity testing Review advantages/disadvantages of commonly prescribed antibiotics

len
Download Presentation

Bugs and Drugs: Solving the Antibiotic Dilemma

An Image/Link below is provided (as is) to download presentation Download Policy: Content on the Website is provided to you AS IS for your information and personal use and may not be sold / licensed / shared on other websites without getting consent from its author. Content is provided to you AS IS for your information and personal use only. Download presentation by click this link. While downloading, if for some reason you are not able to download a presentation, the publisher may have deleted the file from their server. During download, if you can't get a presentation, the file might be deleted by the publisher.

E N D

Presentation Transcript


  1. Bugs and Drugs:Solving the Antibiotic Dilemma Catherine Davis, Pharm.D. Exempla Saint Joseph Hospital

  2. Presentation Overview • Briefly review sensitivity testing • Review advantages/disadvantages of commonly prescribed antibiotics • Provide recommendations for appropriate indications for various antibiotics

  3. Drug Expenditures - 2001

  4. Challenges in Antimicrobial Selection • Changing resistance patterns • New antibiotics from which to select • National Backorders!!! • Piperacillin/tazobactam • Cefotaxime • Cefotetan • Penicillin • Cefazolin

  5. Sensitivity TestingMinimum Inhibitory Concentration • MIC - concentration at which the growth of the organism is inhibited • “breakpoint” is determined based on serum/tissue levels of respective agent • optimum therapy is for peak to achieve > 8 times the MIC • CANNOT compare actual #’s between different classes of antibiotics

  6. MIC Interpretation • If the sensitivity report indicates an MIC less than a specific concentration (i.e. <8), antibiotic in question should achieve adequate concentrations to inhibit growth • Review all agents listed as susceptible and select the most narrow spectrum/cost effective agent that will cover the organism

  7. Antibiotic Selection:The Right Agent for the Right Patient • Infecting organism • Susceptibility data/local resistance patterns • Site of infection • Duration of hospitalization/prior antibiotics • Allergy history • Age • Renal/Hepatic status • Immunologic status • Pregnancy

  8. Beta-Lactams penicillins cephalosporins carbapenems monobactams Quinolones Aminoglycosides Glycopeptides Macrolides Miscellaneous VRE Antibiotics Antibiotic Classes

  9. Advantages good oral absorption good gram + coverage Enterococcus Streptococcus inexpensive Disadvantages frequent dosing increasing resistance gram negatives Strep pneumo inactivates aminoglycosides Penicillins:Pen VK, Ampicillin, Amoxicillin

  10. Penicillin, Ampicillin, Amoxicillin:Indications for Use • Strep infections known to be PCN sensitive • Enterococcus infections (dose 2 Gms q4h for ampicillin + gentamicin synergy dosed) • Necrotizing fasciitis - PCN 24 MU/day + Clinda 600mg q8h • Renal adjust for CrCl <30 mL/min

  11. Advantages excellent Staph aureus coverage best treatment option for serious MSSA infections narrow spectrum (no gram negative coverage) Diclox for Staph Disadvantages frequent dosing (2 Gms q4-6h) increasing incidence of MRSA (35% at ESJH) no Enterococcus coverage AntiStaphylococcal PCN’sNafcillin, Oxacillin, Dicloxacillin

  12. Beta-Lactamase Inhibitors • Amoxicillin/Clavulanate (Augmentin®) • Ampicillin/Sulbactam (Unasyn®) • Piperacillin/Tazobactam (Zosyn®) • Ticarcillin/Clavulanate (Timentin®)

  13. Advantages stabilization against beta-lactamases excellent broad coverage, including anaerobes Zosyn > Timentin for Pseudomonas Enterococcus coverage (not Timentin) Disadvantages GI intolerance (Augmentin) Superinfections High cost frequent dosing E. coli resistance increasing with Unasyn Beta-Lactamase InhibitorsAugmentin, Unasyn, Timentin, Zosyn

  14. Intraabdominal prophylaxis + gentamicin for E. coli Mixed infection including Enterococcus 1.5-3 Gms q6h Severe mixed infection workhorse ICU drug Ventilator associated pneumonia +/- AG Severe diabetic foot infection suspected of involving mixed flora Narrow as soon as possible 3.375 Gms q6h Unasyn, Zosyn IndicationsUnasyn Zosyn

  15. Cephalosporins:General Similarities • excellent penetration to tissues, including BBB (ceftriaxone, cefotaxime) • coverage based on “generation” • NO ENTEROCOCCUS ACTIVITY • wide therapeutic index • wide range of uses • *historically comprises one of the largest portions of antibiotic budget

  16. Cephalosporins:First Generations • most active against gram positives • cellulitis • good coverage against selected gram negatives (E. coli, Proteus, Klebsiella) • Good option for pyelonephritis • excellent for surgical prophylaxis (cefazolin) • Cefazolin (Ancef®) 1 Gm q8h • Cephalexin (Keflex®) higher MIC’s to Staph

  17. Cephalosporins:Second Generations • less gram positive coverage • additional gram negative coverage, respiratory pathogens (Hemophilus, Moraxella) - cefuroxime (Zinacef®, Ceftin®) • anaerobes (anti-anaerobic agents - cefotetan, cefoxitin, cefmetazole) • ~ 75% anaerobic coverage • intraabdominal, GYN prophylaxis

  18. Cefotetan (Cefotan®) , Cefoxitin (Mefoxin®):Indications for Use • Surgical Prophylaxis for intraabdominal infections (Cefotan 1 Gm q12h) • Intraabdominal infections from community (no Enterococcus coverage) • Diabetic foot infections (E. coli, anaerobes)

  19. Cephalosporins:Third+ Generations • additional gram negative (nosocomial) coverage, some gram positive, anaerobic coverage • Pseudomonas coverage (ceftazidime, cefepime) • excellent BBB penetration (ceftriaxone, cefotaxime and others) • Good coverage against Strep and Staph (except ceftazidime)

  20. Third Generation Ceph’s:Indication for Use • Cefepime (Maxipime®), ceftazidime (Fortaz®) • Neutropenic Fever (cefepime 2 Gms q12h) • Pseudomonas infections • Cefotaxime (Claforan®), ceftriaxone (Rocephin®) • Meningitis (cefotaxime 2 Gms q8h) • CAP (cefotaxime 1 Gm q8-12h) • Endocarditis with HACEK organisms or PCN intermediate Strep (cefotaxime 2 Gms q8h)

  21. Oral Cephalosporins • 1st Generation: cephalexin (Keflex®) • 500 mg TID-QID • UTI • 2nd Generation: None Formulary • Ceftin®, Cefzil®, Lorabid® • 3rd Generation: cefpodoxime (Vantin®) • Oral transition for CAP, STD’s • 100 - 200 mg BID

  22. Carbapenems • Imipenem/Cilastatin (Primaxin®) • excellent broad spectrum coverage but increasing Pseudomonas resistance • reserve for resistant organisms, seriously ill patients or PCN allergy • potential for seizures - adjust for renal status • beta-lactamase inducer • 500 mg q6-8h • Meropenem (Merrem®) • less seizure risk • fewer indications

  23. Carbapenems: Ertapenem (Invanz®) • Recently approved agent for community infections • Intraabdominal or complicated skin and skin structure infections • No Enterococcus or Pseudomonas coverage • 1 Gm IV q24h • Adjust for CrCl <30 mL/min (500 mg qd)

  24. Monobactam:Aztreonam (Azactam®) • ONLY gram-negative coverage • moderate Pseudomonas activity • safe to use in PCN allergic patients • excellent safety profile • 1 -2 Gms q8h • Adjust for CrCl <30 mL/min

  25. QuinolonesAnother Class with Generations • excellent tissue penetration • excellent bioavailabilty • convenient dosing • some resistance to Pseudomonas developing • potential for overuse due to many factors • avoid with sucralfate, separate from antacids

  26. Quinolones:“First Generations” • Norfloxacin, Ciprofloxacin • primarily gram negative, including Pseudomonas • some atypical • poor gram positive, no anaerobic • Cipro - interactions with theophylline, warfarin, phenytoin

  27. Quinolones:“Second Generations” • Levofloxacin, Lomefloxacin, Gatifloxacin, Moxifloxacin • additional gram positive and atypical coverage, including Strep pneumoniae • moderate gram negative • excellent bioavailability • Levofloxacin - warfarin interactions • Moxifloxacin - no Pseudomonas coverage, good anaerobic coverage (KP formulary)

  28. Levofloxacin (Levaquin®)Indications for Use • CAP, especially patients with comorbidities • Doxycycline for pts with no comorbidities • Complicated UTI infections (resistant to first generation ceph’s, sulfa) • Gram negative infections in patient allergic to PCN (+/- AG or anaerobic coverage) • Not preferred for cellulitis (750 mg dose) • 500 mg IV/PO qd (adjust for CrCl < 50) • Add metronidazole for anaerobes

  29. Aminoglycosides:Gentamicin, Tobramycin, Amikacin • excellent gram negative coverage • amikacin > tobramycin > gentamicin • synergistic activity • low levels for gram positive synergy (1 mg/kg) • therapeutic levels for gram negative synergy • (5-7mg/kg once daily) • NO Anaerobes - requires 02 to get into cell • dosing strategies dependent on indication • toxicities well defined

  30. Glycopeptides:Vancomycin • excellent gram positive • reserve for resistant organisms, PCN/Ceph allergic patients • VRE • GISA?? • nephrotoxicity no longer a real concern • only monitor trough’s except for select situations • oral ONLY for Flagyl failures

  31. Macrolides:erythro-, clarithro-, azithromycin • moderate gram positives (Strep developing resistance - now up to 35%) • good atypical • use for lower respiratory tract infections • erythro and clarithro interactions • theophylline, warfarin (+ azithro) • azithromycin - STD coverage (1 Gm x1) • CAP: 250 - 500 mg qd x 5-7 days

  32. Antianaerobic Agents • Metronidazole (Flagyl®) • excellent anaerobic, first line C. difficile • 500 mg q12h except C. diff and bowel preps • half-life = 8 hours • Excellent bioavailability • warfarin interaction, disulfiram reactions • Clindamycin (Cleocin®) • gram positive, anaerobic (600 mg IV q8h max) • Use with PCN for nec fasciitis (Gp A Strep) • ? Pseudomembranous colitic

  33. Miscellaneous • SMX/TMP (Septra®, Bactrim®) • excellent tissue penetration, broad uses • gram positive and “easy” gram negative • warfarin interaction • Some GI intolerance in elderly

  34. Antifungals: Fluconazole • Not effective against non-albicans strains • Indications for use • C. albicans from sterile body site • C. albicans from multiple non-sterile sites (urine, wound, sputum) • Prophylaxis for recurrent intraabdominal rupture or anastomotic leak • Systemic infections: 800 mg load, 400 mg qd • UTI: 100 mg qd x5 days • Excellent bioavailability

  35. Antibiotic Costs

  36. New Agents for VRE: • Quinupristin/Dalfopristin (Synercid®) • Streptogramin antibiotics • Effective against VREF (not E. faecalis), Staph aureus (MRSA and MSSA) • Dosing: 7.5 mg/kg q8h • Infusion related ADR’s - central line preferred • Potential to elevate liver enzymes • Cyt P450 3A4 interaction • Non-Formulary

  37. New Agents for VRELinezolid (Zyvox®) • Oxazolidinone antibiotic • Effective against E. faecalis & E. faecium, MRSA, MSSA, Strep pneumo • IV, PO, Suspension - 100% absorption • 600 mg BID • Thrombocytopenia (> 2 weeks duration of therapy), GI intolerance • MAOI - weak inhibitor • Dopamine, epinephrine - adjust dose down

  38. Cost Comparison

  39. Linezolid (Zyvox®):Indications for Use • VREF • likely will be considered preferred therapy in place of Synercid® • need to carefully evaluate for potential colonization • MRSA Infections ONLY for Vanco intolerant patients • after trial of continuous infusion +/- Benadryl if possible • ID Consult

  40. Resistance: A National Concern • Often result of inappropriate or overuse of antibiotics • Significant financial impact on healthcare • Selecting out multi-drug resistance • Narrow coverage as soon as possible • ? Rotation of preferred classes of antibiotics • Don’t treat colonizations or contaminations

More Related