Presentation on theme: "Surgical Site Infection: New Solutions to a Continuing Problem R. Lawrence Reed, II, MD, FACS, FCCM Professor of Surgery Loyola University Medical Center."— Presentation transcript:
Surgical Site Infection: New Solutions to a Continuing Problem R. Lawrence Reed, II, MD, FACS, FCCM Professor of Surgery Loyola University Medical Center Director, SICU, Hines VA Medical Center Maywood, IL
Surgical Site Infections (SSI) Third most common nosocomial infection (14%–16%) Most common nosocomial infection among surgical patients (38%) –2/3 incisional –1/3 organs or spaces accessed during surgery 7.3 additional postoperative days at cost of $3,152 in extra charges Mangram AJ et al. Infect Control Hosp Epidemiol. 1999;20:
Colonization vs Contamination – Definitions Colonization –Bacteria present in a wound with no signs or symptoms of systemic inflammation –Usually less than 10 5 cfu/mL Contamination –Transient exposure of a wound to bacteria –Varying concentrations of bacteria possible –Time of exposure suggested to be < 6 hours –SSI prophylaxis best strategy
SSI – Definitions Infection –Systemic and local signs of inflammation –Bacterial counts 10 5 cfu/mL –Purulent versus nonpurulent –LOS effect –Economic effect Surgical wound infection is SSI LOS=length of stay.
Superficial Incisional SSI Infection occurs within 30 days after the operation and involves only skin or subcutaneous tissue of the incision Mangram AJ et al. Infect Control Hosp Epidemiol. 1999;20: Subcutaneous tissue Skin Superficial incisional SSI
Deep Incisional SSI Infection occurs within 30 days after the operation if no implant is left in place or within 1 year if implant is in place and the infection appears to be related to the operation and the infection involves the deep soft tissue (e.g., fascia and muscle layers) Deep soft tissue (fascia & muscle) Deep incisional SSI Superficial incisional SSI Mangram AJ et al. Infect Control Hosp Epidemiol. 1999;20:
Organ/Space SSI Infection occurs within 30 days after the operation if no implant is left in place or within 1 year if implant is in place and the infection appears to be related to the operation and the infection involves any part of the anatomy, other than the incision, which was opened or manipulated during the operation Deep incisional SSI Superficial incisional SSI Organ/space SSI Organ/space Mangram AJ et al. Infect Control Hosp Epidemiol. 1999;20:
SSI – Risk Factors Operation Factors Duration of surgical scrub Maintain body temp Skin antisepsis Preoperative shaving Duration of operation Antimicrobial prophylaxis Operating room ventilation Inadequate sterilization of instruments Mangram AJ et al. Infect Control Hosp Epidemiol. 1999;20: Foreign material at surgical site Surgical drains Surgical technique –Poor hemostasis –Failure to obliterate dead space –Tissue trauma
SSI – Risk Factors Patient Characteristics Age Diabetes –HbA 1C and SSI –Glucose > 200 mg/dL postoperative period (<48 hours) Nicotine use: delays primary wound healing Steroid use: controversial Malnutrition: no epidemiological association Obesity: 20% over ideal body weight Mangram AJ et al. Infect Control Hosp Epidemiol. 1999;20: Prolonged preoperative stay: surrogate of the severity of illness and comorbid conditions Preoperative nares colonization with Staphylococcus aureus: significant association Perioperative transfusion: controversial Coexistent infections at a remote body site Altered immune response
Bacterial dose Virulence Impaired host resistance Risk of Infection
Bacterial doseVirulence Impaired host resistance Risk of Infection
Bacterial doseVirulence Impaired host resistance Virulence Impaired host resistance Risk of InfectionRisk of Surgical Infection Bacterial dose
SSI – Wound Classification Class 1 = Clean Class 2 = Clean contaminated Class 3 = Contaminated Class 4 = Dirty infected Mangram AJ et al. Infect Control Hosp Epidemiol. 1999;20: Prophylactic antibiotics indicated Therapeutic antibiotics
SSI – Risk Stratification NNIS Project 3 independent variables associated with SSI risk –Contaminated or dirty/infected wound classification –ASA > 2 –Length of operation > 75th percentile of the specific operation being performed NNIS=National Nosocomial Infections Surveillance. NNIS. CDC. Am J Infect Control. 2001;29:
Campaign to Prevent Antimicrobial Resistance Centers for Disease Control and Prevention National Center for Infectious Diseases Division of Healthcare Quality Promotion Link to: Campaign to Prevent Antimicrobial Resistance OnlineCampaign to Prevent Antimicrobial Resistance Online Link to: Federal Action Plan to Combat Antimicrobial ResistanceFederal Action Plan to Combat Antimicrobial Resistance Clinicians hold the solution!
12 Steps to Prevent Antimicrobial Resistance Among Surgical Patients Step 1 – Prevent SSIs – Monitor and maintain normal glycemia – Maintain normothermia – Perform proper skin preparation using appropriate antiseptic agent and, when necessary, hair removal techniques – Think outside the wound to stop surgical site infections CDC. Available at Accessed July 16, 2004.
Opportunity to Prevent SSI An estimated 40%–60% of SSIs are preventable Overuse, underuse, improper timing, and misuse of antibiotics occurs in 25%–50% of operations Mangram AJ et al. Infect Control Hosp Epidemiol. 1999;20:
Principles of Antibiotic Prophylaxis Mangram AJ et al. Infect Control Hosp Epidemiol. 1999;20: Preop administration, serum levels adequate throughout procedure with a drug active against expected microorganisms. High Serum Levels 1.Preop timing 2.IV route 3.Highest dose of drug During Procedure 1.Long half-life 2.Long procedure– redose 3.Large blood loss– redose Duration 1.None after wound closed 2.24 hours maximum
Surgical Site Infection (SSI) Mangram AJ et al. Infect Control Hosp Epidemiol. 1999;20:
National Data Collection State-level baseline description from random sample of 788 cases per state Data collected from records by two professional clinical data abstraction centers Abstraction tool for hospitals is available….Is JCAHO compatible
Surgical Infection Prevention Preliminary Results 34,133 (87.3)Cases eligible for analysis 205 (0.52) 1,817 (4.7) 2 (0.01) 1,461 (3.74) 1,432 (3.66) 36 (0.09) General Exclusions Surgery of interest not performed Infection present pre-operatively Missing antibiotic dates and times Patient on antibiotics prior to admission Patient on antibiotics for more than 24 hours pre-op Other 39,086 (100)Number of cases reviewed N (%)
Discontinuation of Antibiotics Patients were excluded from the denominator of this performance measure if there was any documentation of an infection during surgery or in the first 48 hours after surgery.
Most Common Pathogens Associated With Nosocomial Infections (NNIS 1989–1998) Medical & Surgical Combined PathogenAll Sites BSI Pneumonia SSI n=235,758n=50,091n=64,056n=22,043 Coag-neg Staph S aureus Enterococci spp P aeruginosa Enterobacter spp E coli C albicans K pneumoniae Others Relative Percentage by Site of Infection BSI=bloodstream infection; SSI=surgical site infection. Fridkin SK et al. Clin Chest Med. 1999;20:
Predominance of S aureus in Skin and Skin Structure Infections (SSSIs) SENTRY – US and Canada 2000 Rennie RP et al. Diagn Microbiol Infect Dis. 2003;45: N=1,404 isolates S aureus 45.9% 10.8% P aeruginosa Enterococci8.2% E coli 7.0% Enterobacter 5.8% Other 17.3% MSSA 30.9% MRSA ~15% Klebsiella 5.1%
CDC. MMWR. 1997;46: , 635. (1975 data); Lowy FD. N Engl J Med. 1998;339: ( data); CDC. NNIS System Report, January–November (1998 data); CDC. NNIS System Report, January 1990–May 1999, issued June Am J Infect Control. 1999;27: (1999 data); CDC. NNIS System Report, January 1992–June Am J Infect Control. 2001;29: (2000 data); NNIS. CDC. Am J Infect Control. 2003;31: Progression of Methicillin Resistant S aureus – United States 13%
Impact of MRSA on SSI N=479 patients MRSA greater 90-d mortality vs MSSA (adjusted odds ratio, 3.4; 95% CI: 1.5–7.2) MRSA longer LOS after infection (median additional days=5; P<0.001) MRSA associated with greater hospital charges (1.19-fold increase in hospital charges, P=0.03) Engemann JJ et al. Clin Infect Dis. 2003;36: ,455 52,971 92, ,000 20,000 30,000 40,000 50,000 60,000 70,000 80,000 90, ,000 Control MSSA MRSA Median Hospital Charges
Vascular SSI Retrospective review (1993–2000) –Leicester Royal Infirmary, United Kingdom –172 patients MRSA-positive (4.4% of total) –75 infected, 97 colonized Proportion of wound/graft infections caused by MRSA has increased –4% in 1994, increased to 63% in 2000 All patients with aortic graft infection died All patients with infected prosthetic infrainguinal bypass required amputations Nasim A et al. Eur J Vasc Endovasc Surg. 2001;22:
MRSA in Orthopedic SSI Prospective study, London, United Kingdom 12-month study, January through December 2000 Total of 1,879 patients admitted, 121 screened 1.6% of total with MRSA infection/colonization Higher risk for MRSA infection –Hip surgery –Emergency surgery for femoral neck fracture –Presence of wound MRSA infection – increased hospital LOS (88 vs 11 days) 41% of positive patients still carried MRSA on discharge Tai CC et al. Int Orthop. 2004;28:32-35.
MRSA in Cardiac Surgery 3,443 CABG patients, all received antimicrobial prophylaxis June 1997 through December 2000 Sternal SSI developed in 122 (3.5%) –71 (58.2%) were superficial SSI –51 (41.8%) were deep SSI Gram-positive cocci were most frequently recovered (81%) S aureus was the most frequently isolated pathogen (49%) S aureus bacteremia occurred in 18% and was significantly associated with deep SSI (P=0.002) CABG=coronary artery bypass grafting. Sharma M et al. Infect Control Hosp Epidemiol. 2004;25:
Impact of MRSA in Cardiac Surgery Retrospective review (41 patients) –Poststernotomy S aureus mediastinitis –MRSA: 15 patients –MSSA: 26 patients Logistic regression analysis: MRSA was the only independent risk factor for increased mortality, P=0.04 Mekontso-Dessap A et al. Clin Infect Dis. 2001;32: Survival Rates
Nasal Mupirocin and SSI 4,030 patients enrolled, 3,864 ITT patients PRDBPCT, intranasal mupirocin 891 patients (23.1%) had S aureus in anterior nares –444 mupirocin, –447 placebo S aureus SSI: –2.3% mupirocin –2.4% placebo ITT=intent-to-treat; PRDBPCT=prospective, randomized, double-blind placebo-controlled trial. Perl TM et al. N Engl J Med. 2002;346: Percent of patients with S aureus (%) MupirocinPlacebo P=0.02 All postoperative S aureus Infections
Surgical Wound Management SSI Prophylaxis in MRSA-Colonized Patient Must use same principles Drug choice difference MRSA drugs –Vancomycin –Quinupristin/dalfopristin* –Linezolid –Daptomycin *Not FDA approved for MRSA.
Vancomycin Bactericidal glycopeptide –Discovered in 1956 –Produced by Streptococcus orientalis, an actinomycete isolated from soil samples from Indonesia & India Introduced clinically in 1958 Quickly overshadowed by less toxic anti- staphylococcal penicillins and cephalosporins Re-emergence as an important antibiotic in 1980s & 1990s
Historical Yearly Usage of Vancomycin Kirst HA et al. Antimicrob Agents Chemother. 1998;42: ; NNIS. Am J Infect Control. 2001;29: : 1.8 million courses of vancomycin annually in U.S. 30 million doses of vancomycin estimated
12 Steps to Prevent Antimicrobial Resistance Among Surgical Patients Step 9. Know when to say no to vanco –Vanco should be used to treat known infections, not for routine prophylaxis –Treat staphylococcal infection, not contaminants or colonization –Consider other antimicrobials in treating MRSA CDC. Available at Accessed July 16, 2004.
Vancomycin Tissue Penetration 33 open-heart surgery patients, mean vancomycin concentrations after 15 mg/kg IV dose –Below the mean MICs for many strains of staphylococci MIC=minimum inhibitory concentration. Daschner FD et al. J Antimicrob Chemother. 1987;19:
Bone 5 : 7%–13 % Vancomycin Penetration Sternal Bone 1 : 57% Heart Valve 4 : 12% CNS: <10% Fat 4 : 14% Muscle 4 : 9% Epithelial lining fluid 3 : 18% Lung tissue 2 : 17%–24% 1. Massias L et al. Antimicrob Agents Chemother. 1992;36: ; 2. Cruciani M et al. J Antimicrob Chemother. 1996;38: Lamer C et al. Antimicrob Agents Chemother. 1993;37: ; 4. Daschner FD et al. J Antimicrob Chemother. 1987;19: ; 5. Graziani AL et al. Antimicrob Agents Chemother. 1988;32:
Quinupristin/Dalfopristin (Synercid ® ) Streptogramin class related to macrolide-lincosamides –Quinupristin is a Group B streptogramin –Dalfopristin is a Group A streptogramin Activity against: –MSSA – potently bactericidal –Streptococcus pneumoniae (including PRSP) – potently bactericidal –MRSA – moderately active –E faecium – moderately active against most E faecium strains –NO activity against E faecalis PRSP=penicillin-resistant Streptococcus pneumoniae. Synercid ® IV (quinupristin/dalfopristin for injection) [package insert]. Bristol, Tenn: Monarch Pharmaceuticals, Inc; 2002.
Quinupristin/Dalfopristin (Synercid ® ) Central line access used to decrease incidence of infusion-related venous irritation 3%–30% incidence of severe myalgias and arthralgias Resistance has already been reported Bacteriostatic Does not have indication for pneumonia –Did not perform as well as vancomycin Synercid ® IV (quinupristin/dalfopristin for injection) [package insert]. Bristol, Tenn: Monarch Pharmaceuticals, Inc; 2002.
Daptomycin (Cubicin) Lipopeptide natural product Activity in Gram-positive organisms Distinct mechanism of action Rapidly bactericidal in vitro and in vivo No mechanisms of resistance identified No cross-resistance with other antibiotics Safety profile similar to comparators Once-daily IV dosing Cubicin (daptomycin for injection) [prescribing information]. Lexington, MA: Cubist Pharmaceuticals; September 2003.
Linezolid (ZYVOX ® ) An oxazolidinone: a novel antimicrobial class 100% oral bioavailability Equivalent dosing oral/IV No dose adjustment in renal failure Bacteriostatic No cross-resistance with other antibiotics Reversible thrombocytopenia with prolonged use Binds selectively to the 50S ribosomal subunit –Inhibits the formation of a functional initiation complex ZYVOX ® (linezolid injection, tablets, and oral suspension) [package insert]. Kalamazoo, Mich: Pharmacia & Upjohn, a Pfizer Company; revised June 2004.
Average Steady-State Plasma Linezolid Concentrations After Oral Administration of 400 or 600 mg Twice Daily Linezolid concentration (μg/mL) Time After Last Dose (hours) 600 mg BID 400 mg BID MIC-90 Staph MIC-90 Entero MIC-90 Strep Linezolid Research Update. Denver, Colo: Infectious Diseases Society of America; November 13, 1998.
1. Graziani AL et al. Antimicrob Agents Chemother. 1988;32: ; 2. Matzke et al. Clin Pharmacokinet. 1986;11: ; 3. Albanese J et al. Antimicrob Agents Chemother. 2000;44: ; 4. Georges H et al. Eur J Clin Microbiol Infect Dis. 1997;16: ; 5. Lamer C et al. Antimicrob Agents Chemother. 1993;37: ; 6. Daschner FD et al. J Antimicrob Chemother. 1987;20: ; 7. Blevins RD et al. Antimicrob Agents Chemother. 1984;25: ; 8. Lovering AM et al. J Antimicrob Chemother. 2002;50:73-77; 9. Conte JE et al. Antimicrob Agents Chemother. 2002;46: ; 10. Gee T et al. Antimicrob Agents Chemother. 2001;45: ; 11. Gendjar SR et al ASN/ISN World Congress of Nephrology; 2001; San Francisco, Calif. Abstract Comparison of Tissue Concentrations (% Tissue/Serum) TissueVancomycinLinezolid Bone7%–13% 1 60% 8 Cerebral Spinal Fluid0%–18% 2,3 70% 9 Epithelial Lining Fluid (Lung)11%–17% 4,5 450% 9 Inflammatory Blister Fluid % 10 Muscle~30% 6 94% 8 Peritoneal dialysis fluid~20% 7 61% 11
Complicated Skin and Soft Tissue Infection (cSSTI) Treatment Staph most common cause Staph resistance continues to increase –57.1% in 2002 Treatment for MRSA cSSTI prior to 2000 –Vancomycin –Quinupristin/dalfopristin* New alternatives for treatment of MRSA cSSTI –Linezolid –Daptomycin NNIS. CDC. Am J Infect Control. 2003;31: *Not FDA approved for MRSA.
Quinupristin/Dalfopristin (Q/D) Efficacy Design: 2 randomized, open-label, controlled clinical trials in cSSSI –Study 1: Q/D (7.5 mg/kg q12h IV) vs oxacillin (2 g q6h IV)* –Study 2: Q/D (7.5 mg/kg q12h IV) vs cefazolin (1 g q8h IV)* Q/D (n=450) Comparator (n=443) Study 1 (US)49.5%51.9% Study 2 (International)66.4%64.2% Postoperative infections 14/38 (36.8%)24/42 (57.1%) Traumatic wound infections 33/55 (60.0%) *Vancomycin 1 g q12h IV could be substituted if the pathogen was suspected or confirmed methicillin-resistant Staphylococcus or the patient was allergic to penicillin, cephalosporins, or carbapenems. Patients cured or improved. Results are combined from the 2 clinical trials. Statistical conclusions could not be reached due to the small number of patients in the subsets. Efficacy in the Clinically Evaluable Population Synercid ® IV (quinupristin/dalfopristin for injection) [package insert]. Bristol, Tenn: Monarch Pharmaceuticals, Inc; Not FDA approved for MRSA.
Quinupristin/Dalfopristin (Q/D) Efficacy Design: 2 randomized, open-label, controlled clinical trials in cSSSI Summary of Clinical and Microbiologic Results* Q/D (n=450) Comparator (n=443) Clinical efficacy 68.2%70.7% Microbiologic eradication 66.6%77.7% MSSA64.3%76.6% MRSA77.8%50.0% Gram-positive cocci only56.3%69.7% *Results are combined from the 2 clinical trials. Patients cured or improved in the clinically evaluable population. Overall and by-pathogen bacteriologic eradication rates in the microbiologically evaluable population. cSSSIs=complicated skin and skin structure infections. Nichols RL et al. J Antimicrob Chemother. 1999;44: Not FDA approved for MRSA.
Study design: Open-label, randomized, comparator- controlled, multicenter, multinational clinical study Population: 1,200 hospitalized adult patients with cSSTI Treatment arms: Vancomycin (IV only) 1 g every 12 hours Linezolid (oral or IV) 600 mg every 12 hours OR Linezolid vs Vancomycin for cSSTI Presumed or Known to Be Caused by MRSA Weigelt JA et al. Infectious Diseases Society of America, 2003, poster 314. San Diego, CA. If MSSA, vancomycin could be switched to oxacillin/nafcillin/flucloxacillin (IV only) 1–2 g q6h or dicloxacillin (oral) 500 mg q6h 4- to 14-day treatment duration
Linezolid vs Vancomycin for cSSTI Clinical Cure Rates in Clinically Evaluable Subset P=0.023 Weigelt JA et al. Infectious Diseases Society of America, 2003, poster 314. San Diego, CA.
Linezolid vs Vancomycin for cSSTI Clinical Cure Rates in MRSA Subgroup *P= / /134 Weigelt JA et al. Infectious Diseases Society of America, 2003, poster 314. San Diego, CA.
Linezolid Reduces LOS vs Vancomycin in cSSTI due to MRSA Study Sample (linezolid/vancomycin) LinezolidVancomycinP Value ITT (592/588)7.49.8< CE (491/472)7.49.9< ME (349/334)7.69.8< MRSA (143/146) Mean LOS (days) CE=clinically evaluable; ITT=intent-to-treat; LOS=length of stay; ME=microbiologically evaluable. Weigelt JA et al. Infectious Diseases Society of America; 2003, poster 315. San Diego, CA.
CE=clinically evaluable; ITT=intent-to-treat; ME=microbiologically evaluable; MITT=modified intent-to-treat. Linezolid vs Vancomycin for cSSTI IV Antibiotic Treatment Days Duration of IV treatment (days) Weigelt JA et al. Infectious Diseases Society of America, 2003, poster 315. San Diego, CA.
Cost Effectiveness of Linezolid vs Vancomycin in cSSTI C O S T ($) $4,143 CI (3,750–4,576) $5,187 CI (4,691–5,714) 2003 Per diem hospital cost, administration of IV therapy, wholesale acquisition cost LinezolidVancomycin Fleming T, ed. Red Book edition. Montvale NJ: Thompson PDR;2004.
Linezolid vs Vancomycin for Surgical Site Infection (SSI ) Total Patients With cSSTI 1,200 Total Patients With SSI 135 Linezolid 66 Vancomycin 69 -Weigelt J et al.: Am J Surg 2004;188:
Linezolid vs Vancomycin in SSI Study Population Study PopulationLinezolid (n, %) Vancomycin (n, %) All patients66 (100)69 (100) MRSA34 (52)31 (45) Baseline demographics: No significant difference Baseline comorbidities/MRSA risk factors: No significant difference -Weigelt J et al.: Am J Surg 2004;188:
Linezolid vs Vancomycin in SSI: Clinical Cure Rates at TOC P=0.06 -Weigelt J et al.: Am J Surg 2004;188:
Linezolid vs Vancomycin in SSI: Microbiological Cure Rates at TOC P= Weigelt J et al.: Am J Surg 2004;188:
Linezolid vs Vancomycin in SSI: Microbiological Cure Rates at TOC in MRSA Pts. P= Weigelt J et al.: Am J Surg 2004;188:
Daptomycin for cSSSIs Phase III: 2 international, multicenter, randomized, double-blind (evaluator blinded) studies (Studies 9801 & 9901): –Daptomycin (4 mg/kg IV qd) vs 1 of 2 comparators: Vancomycin (1 g q12h) Synthetic penicillin (4–12 g/d in 4 daily doses) Primary endpoint was safety and efficacy Both studies demonstrated equivalence of daptomycin to the comparator Arbeit RD et al. Clin Infect Dis. 2004;38:
Daptomycin Efficacy Design: 2 randomized, multinational, multicenter investigator-blinded studies Daptomycin 4 mg/kg IV q24h or vancomycin 1 g IV q12h or a semisynthetic penicillin (nafcillin, oxacillin, cloxacillin, flucloxacillin) Type of InfectionDaptomycin No. of Pts (Success rate %) Comparator* No. of Pts (Success rate %) Wound infection169 (84%)180 (87%) Major abscess102 (92%)92 (88%) Ulcer infection47 (66%)56 (70%) Other infection 47 (79%)58 (83%) *Comparator was vancomycin or a semisynthetic penicillin. Other infections included complicated cellulitis, major abscess, or traumatic wound infection. Clinical Success Rate: CE Population Arbeit RD et al. Clin Infect Dis. 2004;38:
Comparison of MRSA Antimicrobials Unfamiliarity and cost, reversible hematologic abnormalities, resistance (ie, VRE with prolonged use) Limited indications, acquisition cost, myalgia, not effective for pneumonia Infusion site inflammation, myalgias, arthralgias, and resistance Toxicity, resistance (VRE, VISA, VRSA) Disadvantages Potential for less resistance Faster cure (rapidly cidal) QD Parenteral cSSSI Daptomycin Oral dosing removal of catheters, early discharge, evidence of superiority to vancomycin in cSSTI Alternative to vancomycin FamiliarityAdvantages Gets patients homeWorks when vancomycin wont CheapSales pitch BIDq8-12hVariable depending upon renal function Dosing Parenteral, oralParenteral (central?)ParenteralRoute(s) cSSSI and pneumoniacSSSI (not MRSA)MultipleFDA approved for MRSA LinezolidQuinupristin/ Dalfopristin Vancomycin
Summary SSI is a preventable morbidity Gram-positive organisms are the primary pathogens –MRSA increasing Treatment alternatives in MRSA SSIs and cSSTIs –Vancomycin –Linezolid –Daptomycin –Quinupristin/dalfopristin* *Not FDA approved for MRSA.