Surgical infection ผ.ศ. น.พ. กำธร มำลำธรรม หน วยโรคต ดเช อ ภำคว ชำอำย รศำสตร คณะแพทยศำสตร โรงพยำบำลรำมำธ บด

Transcription

1 Surgical infection ผ.ศ. น.พ. กำธร มำลำธรรม หน วยโรคต ดเช อ ภำคว ชำอำย รศำสตร คณะแพทยศำสตร โรงพยำบำลรำมำธ บด 1

2 Scope Surgical prophylaxis: Pharmacologic approach to prevent SSI Antimicrobial therapy for surgical infections 2

3 Surgical prophylaxis 3

4 Principles of Antimicrobial Prophylaxis Use an AMP agent for all operations or classes of operations in which its use has been shown to reduce SSI rates based on evidence from clinical trials or for those operations after which incisional or organ/space SSI would represent a catastrophe. 4

5 Principles of Antimicrobial Prophylaxis Use an AMP agent that is safe, inexpensive, and bactericidal with an in vitro spectrum that covers the most probable intra-operative contaminants for the operation. 5

6 Principles of Antimicrobial Prophylaxis Time the infusion of the initial dose of antimicrobial agent so that a bactericidal concentration of the drug is established in serum and tissues by the time the skin is incised. 6

7 Principles of Antimicrobial Prophylaxis Maintain therapeutic levels of the antimicrobial agent in both serum and tissues throughout the operation and until, at most, a few hours after the incision is closed in the operating room. 7

8 Choice of antimicrobial agents Cefazolin: most surgery AMC, AMS, cefoxitin: GI and urogenital tract Cefuroxime: GI and urogenital tract 8

9 Modification of Antimicrobial Prophylaxis Based on Rectal Culture to Prevent Fluoroquinolone- Resistant Escherichia coli Infections after Prostate Biopsy Suwantarat N et al Infect Control Hosp Epidemiol 2013;34(9):

10 Suwantarat N et al Infect Control Hosp Epidemiol 2013;34(9):

11 Effect of Preoperative Antibiotic Prophylaxis on Surgical Site Infections Complicating Cardiac Surgery Finkelstein R et al Infect Control Hosp Epidemiol 2014;35(1):

12 Results 2,637 patients Overall SSI rate was 8.4%. Superficial and deep/organ space infection rates were 7.9% vs 10.0%; 4.7% vs 6.8%; and 3.3% vs 3.3%, respectively for patients receiving cefazolin or vancomycin. 12

13 Suppurative thrombophlebitis 13

14 Factors to consider in intra-abdominal infection Primary & secondary peritonitis Community-type organism Unusual presentation, e.g. TB Tertiary peritonitis Nosocomial pathogens: MRSA, MDR A. baumannii, P. aeruginosa 14

15 Antimicrobial agents for intraabdominal infection Ceftriaxone + metronidazole Lowest cot, convenience Lac coverage for enterococci Ampicillin/sulbactam or amoxicillin/clavulanate aminoglycoside Others: 15

16 Acute necrotizing pancreatitis 16

17 Etiologic agents: pancreatic abscess Gram-negative enteric bacilli E. coli, Klebsiella spp., Enterobacteriaceae Anaerobes Anaerobic GPC, Bacteroides spp., Actinomyces spp. Gram-positive cocci Streptococci, Staphylococci, Enterococci 17

18 Antibiotic prophylaxis in acute necrotizing pancreatitis Lack of consistent benefit Variable inclusion criteria & methodological quality Different regimens Potential for harm Change pancreatic isolates (Gram-ve to fungi and Gram+ve organisms) Nathens AB., et al Crit Care Med 2004; 32: ) 18

19 No reduction in mortality (RR,.76; 95% CI, ) No protection against infected necrosis (RR,.79; 95% CI, ) or surgical intervention (RR,.88; 95% CI, ). Jafri NS. et al. The American Journal of Surgery (2009) 197,

20 Post-operative infections Surgical site Tracheobronchitis/Pneumonia: A. baumannii Urinary tract infection: E. coli Catheter-associated infection 20

21 Post-operative fever Atelectasis Blood transfusion Phlebitis Chemical Infectious Pseudogout/gout 21

22 Ramabio: Antibiogram in your hand 22

23 Ramabio: Antibiogram in your hand 23

24 Ramabio: Antibiogram in your hand 24

25 Risk factors for MDR Previous hospitalization in the past 3 months History of exposure to antibiotics Indwelling medical devices ICU or other areas with high incidence of MDR stay 25

26 Susceptibility of E. coli AMOX/CLAV CFR CRO CAZ NFX AMK GEN TMP/SMX National Antimicrobial Resistance Surveillance Center, Thailand 26

27 Susceptibility of P. aeruginosa CAZ Cefepime IMP PIP CPX AMK GEN National Antimicrobial Resistance Surveillance Center, Thailand 27

28 Susceptibility of A. baumannii CPZ/SUL IMP National Antimicrobial Resistance Surveillance Center, Thailand 28

29 Available antimicrobial agents Beta-lactam Penicillin: Amp/sulb, Amox/clav, Pip/tazo Cephalosporins: cefoxitin, ceftriaxone, ceftazidime, cefoperazone/sulbactam, cefepime, cefpirome Carbapenems: imipenem, meropenem, doripenem ertapenem Fluoroquinolones: ciprofloxacin, ofloxacin, levofloxacin, moxifloxacin Aminoglycosides: amikacin, gentamicin Miscellaneous: metronidazole, clindamycin 29

30 b-lactam/b-lactamase inhibitor Ampicillin/sulbactam Amoxycillin/clavulanate Piperacillin/tazobactam Cefoperazone/sulbactam Better anti gram ve and anaerobic bacteria except P. aeruginosa 30

31 Classification of Carbapenems GROUP 1 Carbapenems (community acquired infections) Ertapenem GROUP 2 Carbapenems (hospital acquired infections Pseudomonas and Acinetobacter activity) Imipenem Meropenem Panipenem Biapenem Doripenem GROUP 3 Carbapenems (hospital acquired infections Pseudomonas and MRSA activity) CS-023 (investigational) Not all carbapenems are the same Shah PM and Isaacs RD. J Antimicrob Chemother 2003; 52:

32 Comparison of Carbapenems Nicolau DP. Pharmacochemother 2008;9:

33 In vitro activities of carbapenems Organism MIC (mg/ml) Meropenem Imipenem Ertapenem S. aureus S. pneumoniae PS S. pneumoniae PR S. pyogenes <0.06 < E. faecalis Norrby SR Infect Dis Clin Practice 1997;6 :

34 Imipenem/cilastatin Warnings and Precautions Seizures Patients at risk: Pre-existing CNS disorders Impaired renal function Hemodialysis patients Low body weight Drug Interactions Ganciclovir (increased seizures) 34

35 Meta-analysis Clinical Response in Severe Infections Meropenem vs. Imipenem Imipenem Favors meropenem Edwards SJ et al. Curr Med Res Opin 2005;21:

36 Ertapenem Pharmacokinetics Absorption: IM bioavailability = 90%; Cmax ~ 2.3h Distribution: Serum concentrations 1G IV: h 1G IM: 67 2 h Non-linear PK due to concentration-dependent protein binding 95% protein bound at conc < 100 ug/ml 85% protein bound at conc ~ 300 ug/ml Metabolism: hydrolysis of beta-lactam ring Elimination: t 1/2 = 4 hours in adults and peds > 12 yo t 1/2 = 2.5 hours in peds 3 months - 12 years old 80% excreted in urine, 10% in feces 36

37 Ertapenem Dosing and Administration Usual dosing: Adults and peds > 12 yo: 1G IM/IV qd < 3 months - 12 years: 15 mg/kg IM/IV BID (not to exceed 1G/d) Dosage adjustment in renal dysfunction (adults): Clcr </= 30 ml/min or ESRD: 500 mg IM/IV qd HD: if dose given < 6 hours prior to HD, give 125mg supplemental dose following HD. There is no data in pediatric patients with renal dysfunction 37

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50 Ceftazidime & Cefepime Ceftazidime Anti-pseudomonal 3 rd generation cephalosporin, no anti-staph activity Cefepime 4 th generation cephalosporin Anti-pseudomonal Anti-staph 50

51 Piperacillin/tazobactam Activity against gram-positive species (streptococcus) Neisseria Haemophilus Enterobacteriaceae spp. Anaerobes Acts synergistically against Pseudomonas and some Enterobactericeae species when it is combined with an aminoglycoside 51

52 Cefoperazone-sulbactam Enhanced potency against Escherichia coli, Klebsiella pneumoniae, and Proteus mirabilis Another third generation cephalosporin with modest activity against P. aeruginosa Used to treat intra-abdominal, biliary and gynecologic infections 52

53 Cefoperazone-sulbactam Usual Adult Dose Mild-moderately severe 1 2 g q12h Severe Disease 2 4 g q8h Peak serum concentration (1g): 153ug/mL t 1/2: hrs Serum protein binding: 90% Route of excretion : hepatic 80%; renal 20% 53

54 Fluoroquinolones Ciprofloxacin: +ve anti-pseudomonal activity Ofloxacin, levofloxacin Moxifloxacin (some antianaerobic/gm +ve bacteria) 54

55 Effective use of antimicrobial agents Ascertain the diagnosis Lower resp. tract infection: Symptoms and signs: O 2 requirement, amount and character of resp. secretion, VS, breath sound Lab: CXR, Gram stain and culture 55

56 Effective use of antimicrobial agents Ascertain the diagnosis Surgical site infection Symptoms and signs: vital signs, inflamed site, purulent drainage Lab: Gram stain and culture 56

57 Effective use of antimicrobial agents Ascertain the diagnosis UTI Symptoms and signs: vital signs Lab: Urinalysis, culture 57

58 Effective use of antimicrobial agents Ascertain the diagnosis Bloodstream infection Symptoms and signs: vital signs Lab: blood culture Paired simultaneous peripheral and central venous blood 58

59 Thank you for your attention 59