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Review of Antibiotics

Review of Antibiotics. Zagorka Popovski, Pharm.D. Clinical Pharmacist, Intensive Care. Cephalosporins. Gram + 1 st Generation •Ancef •Keflex . LESS IS MORE!!!. Timing of pre op antibiotic is key. POPOVSKI and TEOH SCCM 1993 SAN DIEGO CA.

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Review of Antibiotics

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  1. Review of Antibiotics Zagorka Popovski, Pharm.D. Clinical Pharmacist, Intensive Care

  2. Cephalosporins Gram + 1st Generation •Ancef •Keflex

  3. LESS IS MORE!!! • Timing of pre op antibiotic is key

  4. POPOVSKI and TEOHSCCM 1993 SAN DIEGO CA • REDUCTION OF POST-OP ANTIBIOTICS FROM 72 HR TO 48HR • ADMINISTER PRE-OP ANTIBIOTIC IN OR • WOUND INFECTION RATE REDUCED FROM 2% TO 0.6%

  5. Cephalosporins Gram + Gram + Coverage plus: 1st Generation •Ecoli •Ancef •Proteus •Keflex •Klebsiella

  6. Cephalosporins Gram + 1st Generation 2nd Generation •Ancef •Cefuroxime •Keflex •Cefamandole •Cefotetan +/- anaerobe •Cefoxitin H Flu

  7. Cephalosporins Gram + Gram - 1st Generation 2nd Generation 3rd Generation •Ancef •Cefuroxime •Ceftriaxone •Keflex •Cefamandole •Cefotaxime •Cefotetan •Ceftazidime •Cefoxitin

  8. Cephalosporins Gram - Gram - Coverage *3rd Generation Acinetobacter Serratia •Ceftriaxone (CNS penetration, gram neg. alternative to amnioglycosides) •Cefotaxime •Ceftazidime •Pseudomonas Aeruginosa *not for enterobacter

  9. Penicillins ® Penicillin Ampicillin Cloxacillin Amoxillin Oxacillin Nafcillin Methicillin

  10. Penicillins Coverage •Ampicillin •Enterococcus •Amoxicillin •Ecoli •Klebsiella •Proteus •H. Flu Clavulin®=amoxicillin+clavulinic acid

  11. Antipseudomonal Penicillins • Piperacillin (Pipracil) • Piperacillin/Tazobactam (Tazocin) • Ticarcillin (Ticar) • Ticarcillin/Clavulante (Timentin) Gram +/- (including Pseudomonas a.) *anaerobic coverage

  12. + R R

  13. Penicillins • Cloxacillin • Oxacillin • Nafcillin • Methicillin

  14. Carbapenems • Imipenem + Cilastatin (Primaxin) • Meropenem (Merrem) • Ertapenem (Invanz)

  15. Meropenem • Very broad spectrum • Gram negative including pseudomonas • gram positive including staph and enterococcus • Anaerobes • Indicated for “high-severity” intra-abdominal infections • Replaced imipenem//cilastatin at HHS

  16. Christou & Solomkin, 1990 (Intra-abdominal sepsis) F A I L U R E AA + AMG Imipenem 5 7 15 30 A.P.A.C.H.E.

  17. Activity of Study Agents Against Facultative Gram-Negative Bacteria

  18. Activity of Study Agents Against Common Anaerobic Bacteria

  19. CONDITIONS FOR WHICH THERAPEUTIC ANTIBIOTICS (24h) ARE NOT RECOMMENDED • Traumatic and iatrogenic enteric perf’n operated on within 12h • Gastroduodenal perf’n operated on within 24h • Acute/gangrenous appendicitis without perf’n • Acute/gangrenous cholecyswtitis without perf’n • Transmural bowel necrosis from embolic,thrombotic or obsstructive vascular occlusion without perf’n or established peritonitis or abcess

  20. Fluoroquinolones • Nalidixic acid (NegGram) • Ciprofloxacin (Cipro) • Norfloxacin (Noroxin) • Levofloxacin (Levaquin) • Gatifloxacin (Tequin) • Moxifloxacin (Avelox)

  21. Fluoroquinolones • Ciprofloxacin (Cipro) - Ps. a. • Norfloxacin (Noroxin) • Levofloxacin (Levaquin) • Gatifloxacin (Tequin) • Moxifloxacin (Avelox) CAP Strep. + other gram neg atypicals

  22. Fluoroquinolones • Advantages (Bioavailability, IV/PO, tissue penetration) • Drug Interactions (Calcium, Iron, Magnesium) (Theophylline,Methylxanthines) • Side Effects

  23. Aminoglycosides • Gentamicin • Tobramycin • Amikacin

  24. Aminoglycosides MIC Serratia (Pseudomonas a.) Gentamicin .5 2 Tobramycin 2 .5

  25. Others • Vancomycin • Linezolid • Septra

  26. SAVING ANTIBIOTICS SAVES LIVES!!! PRINCIPLES: • For empiric therapy, reassess at day 4, consult ID • Narrow spectrum when bacteria identified • Convert to oral therapy when possible

  27. SAVING ANTIBIOTICS SAVES LIVES!!! • Clinical Pulmonary Infection Score (CPIS) • Takes into account temperature,wbc,secretions,ventilation,xray • </- 6 ( treat with 3 days levofloxacin or cefotaxime) • >6 ( bronch and treat with 8 days

  28. SAVING ANTIBIOTICS SAVES LIVES!!! • BENEFITS: • Reduced use of broad spectrum agents • Reduced resistance • Reduced LOS • Reduced fungal infections • Reduced costs >$200,000

  29. CPIS Use for Non-invasive Diagnosis of HAP/VAP Calculate CPIS CPIS≤6 CPIS>6 Consider treatment Gram stain of Tracheobronchial (TB) secretions Recalculate CPIS daily, examine Gram stain Treatment according to Gram stain Pugin J. Am Rev Respir Dis. 1991;143:1121-9. Pugin J. Minerva Anestesiol. 2002;68(4):261-5. 1 2 3 4 5 6 7 Back Next

  30. CPIS Antibiotic Study • Inclusion Criteria: • Clinical Pulmonary infection score (CPIS) 6 • Ventilated or non-ventilated • Exclusion Criteria: • Infected with HIV • 18 years of age Singh N, et al. Am J Respir Crit Care Med. 2000;162:505-511. 1 2 3 4 5 6 7 Back Next

  31. CPIS Antibiotic Study: Trial Design CPIS≤6 Standard Therapy (antibiotics for 10-21 days) Experimental Therapy Ciprofloxacin for 3 days CPIS calculated at 3 days CPIS ≤6 CPIS >6 Discontinue treatment Treat as pneumonia Singh N, et al. Am J Respir Crit Care Med. 2000;162:505-11. 1 2 3 4 5 6 7 Back Next

  32. CPIS Antibiotic Study: Outcomes • Data for patients with entry CPIS 6 subject to standard and experimental therapy Singh N, et al. Am J Respir Crit Care Med. 2000;162:505-511. 1 2 3 4 5 6 7 Back Next

  33. CPIS Antibiotic Study: Outcomes • Data for patients with CPIS 6 at the 3-day evaluation point and no extrapulmonary infections Singh N, et al. Am J Respir Crit Care Med. 2000;162:505-511. 1 2 3 4 5 6 7 Back Next

  34. CPIS Antibiotic Study: Conclusions • Prolonged (i.e. >3 days) use of antibiotics in patients with an initial CPIS ≤6 may be unnecessary and inappropriate Singh N, et al. Am J Respir Crit Care Med. 2000;162:505-511. 1 2 3 4 5 6 7 Back Next

  35. FUNGAL INFECTIONS • RISK FACTORS • TPN • Steroids • Broad spectrum antibiotics • Abdominal involvement • Immunosuppression

  36. ANTIFUNGAL AGENTS • Polyenes: Amphotericin B (binds to sterols and disrupts barrier resulting in leakage of intracellular contents • For hemodynamically unstable, systemic infections • Adverse effects may limit treatment

  37. ANTIFUNGAL AGENTS cont’d • Azoles: Fluconazole, voriconazole, itraconazole (inhibit p450-mediated 14-alpha demethylase in the sterol) • Good activity vs C. albicans, resistance to Krusei, Glabrata • Numerous drug interactions

  38. ANTIFUNGAL AGENTS cont’d • Echinocandins: Caspofungen (inhibit fungal cell wall synthesis) • Active against C. albicans, krusei, glabrata • cost

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