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

2. Cephalosporins Gram + 1 st Generation Ancef Keflex

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

4. POPOVSKI and TEOH SCCM 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: 1 st GenerationEcoli AncefProteus Keflex Klebsiella

6. Cephalosporins Gram + 1 st Generation2 nd Generation AncefCefuroxime Keflex Cefamandole Cefotetan+/- anaerobe Cefoxitin H Flu

7. Cephalosporins Gram + Gram - 1 st Generation2 nd Generation3 rd Generation AncefCefuroximeCeftriaxone Keflex CefamandoleCefotaxime CefotetanCeftazidime Cefoxitin

8. Cephalosporins Gram -Gram - Coverage *3 rd GenerationAcinetobacter Serratia Ceftriaxone (CNS penetration, gram neg. alternative to amnioglycosides) Cefotaxime CeftazidimePseudomonas Aeruginosa *not for enterobacter

9. Penicillins Penicillin AmpicillinCloxacillin AmoxillinOxacillin Nafcillin Methicillin ®

10. Penicillins Coverage AmpicillinEnterococcus AmoxicillinEcoli 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. + RRRR

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. 5 7 15 30 FAILUREFAILURE A.P.A.C.H.E. Imipenem AA + AMG Christou & Solomkin, 1990 (Intra-abdominal sepsis)

17. Activity of Study Agents Against Facultative Gram-Negative Bacteria Bacteria Tobramycin MIC Imipenem MIC 90Resistant 90Resistant E.Coli Enterobacter Klebsiella Proteus Pseudomonas a. Citrobacter sp. Other Gram Negative Breakpoint…Tobramycin 4 Imipeneim 4 4.0 1.0 4.0 16.0 2.0 50001205000120 0.25 1.0 4.0 2.0 0.5 4.0 00010000001000

18. Activity of Study Agents Against Common Anaerobic Bacteria Bacteria Clindamycin MIC Imipenem MIC 90Resistant 90Resistant ß. Fragilis Bacteroides sp. Clostridia sp. Enterococci Breakpint…Clindamycin 2 Imipenem 4 16.0 4.0 - ??4-??4- 0.50 2.0 4.0 00000000

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 Tobramycin2.5

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 CPIS≤6CPIS≤6 Consider treatment Calculate CPIS Calculate CPIS CPIS>6CPIS>6 Gram stain of Tracheobronchial (TB) secretions Gram stain of Tracheobronchial (TB) secretions Treatment according to Gram stain to Gram stain Treatment according to Gram stain to Gram stain Recalculate CPIS daily, examine Gram stain Pugin J. Am Rev Respir Dis. 1991;143:1121-9. Pugin J. Minerva Anestesiol. 2002;68(4):261-5. 1234567 Next Back

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. 1234567 Next Back

31. CPIS Antibiotic Study: Trial Design CPIS≤6 Standard Therapy (antibiotics for 10-21 days) Standard Therapy (antibiotics for 10-21 days) Experimental Therapy Ciprofloxacin for 3 days CPIS >6 Treat as pneumonia Singh N, et al. Am J Respir Crit Care Med. 2000;162:505-11. CPIS ≤6 Discontinue treatment CPIS calculated at 3 days 1234567 Next Back

32. CPIS Antibiotic Study: Outcomes Experimental Therapy (n=39) Standard Therapy (n=42) p Value Deaths at 3 days0% (0/39)7% (3/42)NS CPIS >6 at 3 days21% (8/39)23% (9/39)NS Extrapulmonary infections 18% (7/39)15% (6/39)NS Antibiotic continuation >3 days 28% (11/39)97% (38/39)0.0001 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. 1234567 Next Back

33. CPIS Antibiotic Study: Outcomes Experimental Therapy (n=39) Standard Therapy (n=42) p Value Antibiotic continuation > 3 days 0% (0/25)96% (24/25)0.0001 Mean duration of antibiotics, day 39.80.0001 Mean cost$259$6400.0001 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. 1234567 Next Back

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. 1234567 Next Back

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