3/20/2011. Code 215 of Hammurabi: If a physician performed a major operation on

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1 The Good Antibiotics: the Good, the Bad and the Ugly John P. Cello, MD Professor of Medicine and Surgery, University of California, San Francisco Most organisms can be readily identified by culture, special histologic stains, or PCR techniques Decompression of locculated fluid and resection of necrotic tissue are the primary mechanisms for infection control Nearly all identifiable organism are responsive to antibiotic therapy (at least partially so) Surgical Debridement or Abscess Drainage Ten shekels would pay for carpenter s labor for 450 days Code 215 of Hammurabi: If a physician performed a major operation on a seignior with a bronze lancet and has saved the seignior s life...he shall receive ten shekels of silver Code of Hammurabi If a physician performed a major operation on a seignior with a bronze lancet and has caused the seignior s death. they shall cut off his hand. 1

2 First Natural Antibiotic turpentine resin Antibiotics The term antibiotic (Greek anti against, bios life ) was coined by Paul Vuillemin, pupil of Louis Pasteur Many non-biotics tried during 18 th, 19 th and early 20 th century limited impact. First truly effective antibiotic - penicillin Sir Alexander Fleming Born, 1881 Ayrshire, Scotland St. Mary s Medical School, London University 1928 noted mold on S. aureus plate that created bacteriafree zone 1940 s IV penicillin given for serious infections, harvested from patient s urine 2

3 Penicillin Beta-lactam ring tazobactam Carbapenem Beta lactamase clavulanic acid Cephalosporin sulbactam Antibiotic Nomenclature Translation & Dosing Antibiotic Nomenclature Translation & Dosing (cont.) Piperacillin-tazobactam Ticarcillin-clavulanic clavulanic acid Doripenem Ertapenem Imipenem-cilastatin Meropenem Cefazolin Cefepime Cefotaxime Cefoxitin Zosyn g q. 6 h. Timentin 3.1 g q. 6 h. Doribax 500 mg q. 8 h. Ivanz 1 g q. 24 h. Primaxin 500 mg q 6 h. Generic 1 g 8 h. Ancef 1-2 g q 8 h. Maxipime 2 g q 8-12 h. Claforan 1-2 g q. 6-8 h. Mefoxin 2 g q 6 h. Ceftazidime Ceftriaxone Cefuroxime Tigecycline Ciprofloxacin Levofloxacin Moxifloxacin Metronidazole Gentamicin (or tobra.) Amikacin Azetreonam Vancomycin Fortaz 2 g q 8 h. Rocephin 1-2 g q h. Zinacef 1.5 g q 8 h. Tygacil 100mg then 50mg q 12 h Cipro 400 mg q 12 h. Levaquin 750 mg q 24 h. Avelox 400 mg q 24 h. Flagyl 500 mg q 8-12 h. Generic 5-7 mg/kg q 24 h. Generic mg/kg q 24h. Azactam 1-2 g q 6-8 h. Generic mg/kg q 8-12 h. 3

4 Organisms in Intra-Abdominal Infections Organisms in Complicated Intra-abdominal Infections Randomized Controlled Trials From: Lopez et al. World J. Emer Surg 2011;6:7. Solomkin JS et al. Clin Inf Dis 50:133,2010. Antibiotic Coverage Ticarcillin-clavulanic clavulanic acid (Timentin) or ertapenem (Ivanz) good coverage for mild to moderate intra-abdominal abdominal infections (where it is unlikely anerobes play a significant role). Would need to add metronidazole if substantial anaerobes present. Piperacillin-tazobactam (Zosyn) or imipenem-cilastatin (Primaxim) or meropenem all excellent for moderate to severe intra-abdominal abdominal infections - no need to add metronidazole (all have excellent anaerobic coverage) Vancomycin needed if MRSA suspected (complicated post-surgical surgical infections) Pieracci FM et al. Scand J Surg 96:184,

5 Initial Empiric Treatment for Adult Non- Biliary Abdominal Infections Initial Empiric Antibiotics Adult Community-Acquired Biliary Infections Solomkin JS et al. Clin Inf Dis 50:133,2010. Solomkin JS et al. Clin Inf Dis 50:133,2010. The Bad Natural selection encourages the growth of organisms resistant to initiated treatments Antibiotic over-usage has lead to the evolution of highly resistant organisms Resistant organisms have colonized most healthcare and even many community environments Why Antibiotic Treatment Fails? Solomkin JS et al. Clin Inf Dis 50:133,

6 Risk Factors for Drug Resistance When to limit Antibiotic Therapy Pieracci FM et al. Scand J Surg 96:184,2007. Pieracci FM et al. Scand J Surg 96:184,2007. The Ugly Commencel organism destruction in natural environments (e.g. the GI tract) has created disastrous consequences highly resistant Clostridia MRSA organism have become the routine rather than the exception in hospital-acquired acquired and even in some community-acquired infections The emergence of resistant organisms has propelled the rush to more evolved antibiotics Disappointing number of antibacterial in phase 2 or 3 trials - a lean pipeline Escape Pathogens now cause majority of nosocomial infections Organism Enterococcus faecium Staphylococcus aureus Klebsiella pneumoniae Acinetobacter baumanii Pseudomonas aeruginosa Enterobacter species Current Feature Vancomycin resistance MRSA Carbapenem resistance Multidrug resistance Fluoroquinolone resistance Multidrug resistance Boucher HW et al Clinical Infect Dis 48: 1-12,

7 Current and Future Strategies for Combating Clostridium difficile C. Difficile Treatments - Standard Gerding DN and Johnson S Gerding DN and Johnson S C. Difficile Treatments Non-Antibiotic Antibiotic Rescue - Definitions Prebiotic: non-digestible food ingredient that stimulates the growth or activity of bacteria in the gut which are beneficial to health Probiotic: live organisms which when administered in adequate quantities confer a health benefit to the host. Gerding DN and Johnson S 7

8 Probiotics - Single Organisms Probiotic Combinations Verna EC and Lucak S Verna EC and Lucak S Response Rifaximin 400mg TID X 14 d, pts. Not responding to Metronidazole 1500 mg/d. Rifaximin controlled trial. Basu PP et al. Thera Adv Gastroenterol 3:221,