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 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%

Cephalosporins Gram + Gram + Coverage plus: 1 st GenerationEcoli AncefProteus Keflex Klebsiella

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

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

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

Penicillins Penicillin AmpicillinCloxacillin AmoxillinOxacillin Nafcillin Methicillin ®

Penicillins Coverage AmpicillinEnterococcus AmoxicillinEcoli Klebsiella Proteus H. Flu Clavulin®=amoxicillin+clavulinic acid

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

+ RRRR

Penicillins Cloxacillin Oxacillin Nafcillin Methicillin

Carbapenems Imipenem + Cilastatin (Primaxin) Meropenem (Merrem) Ertapenem (Invanz)

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

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

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

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-??

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

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

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

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

Aminoglycosides Gentamicin Tobramycin Amikacin

Aminoglycosides MIC Serratia(Pseudomonas a.) Gentamicin.5 2 Tobramycin2.5

Others Vancomycin Linezolid Septra

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

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

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

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: Pugin J. Minerva Anestesiol. 2002;68(4): Next Back

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: Next Back

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

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) 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: Next Back

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

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: Next Back

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

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

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

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