Skin and Soft tissue Infections: new bugs, old drugs Disclosure Statement Sponsor: Goodman Photographic Presented by: Dr. Kristopher Wiebe, MD, CCFP (EM) Presented to: BC Chapter, Canadian Society of Hospital Pharmacists April 19, 2007 Dr. Wiebe has not received funding from, nor profits from in any way, any pharmaceuticals and/or pharmaceutical companies mentioned in this lecture. Outline Cases History of Staph Aureus and the evolution of MRSA Epidemiology/Prevalence of MRSA THE RISE OF MRSA Empiric treatment of skin and soft tissue infections New Antibiotics Cases Revisited Summary Cases Nov 2004. A 47 year old male presents to CGH ER with a red crusted lesion to his (L) arm with mild surrounding cellulitis. PMHx: superbug infection Case 1 con t Assuming that the patient does not need Incision and Drainage or IV antibiotics, what antibiotic do you choose?? A: Keflex B: Clindamycin C: Erythromycin D: Septra E: Cipro F: Cloxacillin G: None of the above Case 1 con t: Any other important management strategies? Swab? Topical antibiotics? 1

Case 2 A 24 year old female IV drug user presents with an abscess to her (R) antecubital fossa: What is the most likely inciting organism: A: MRSA B: Group A Strep C: Other Strep D: Staph aureus (MSSA) E: Coliforms Case 2 (con t) Which is the most appropriate initial management strategy? A: IV antibiotics alone B: Oral antibiotics alone C: I and D alone D: I and D plus antibiotics E: It depends Case 3 A 48 year old lawyer and his wife present to the ER each with multiple small abscesses The lawyer says this is the 3 rd time this has happened in the last year The pair are otherwise healthy and have no history of hospitalization, hospital visits, incarceration or IV drug use Case 3 (con t) Are there any historical factors in this case that make MRSA more or less likely as the causative pathogen? Is there any further information necessary? What is the most appropriate empiric treatment?? A: I and D of all lesions but no antibiotics B: IV Vancomycin C: IV Ancef D: Oral Keflex E: None of the above Case 4 Background: Staph Aureus 38 year old female with (R) leg abscess and sepsis. Most appropriate treatment? A: IV ANCEF B: IV VANCOMYCIN D: IV CLINDAMYCIN E: I and D plus iv Ancef F: I and D plus iv Clinda G: I and D plus iv Vanco E: None of the above Gram (+) cocci in clusters Frequent skin commensal organism (50%) Frequent cause of skin and soft tissue infections Initially sensitive to Penicillin but soon became resistant (B-lactamase) By the 1970 s Staph Aureus uniformly resistant to Penicillin Antimicrobial selection caused gradual replacement of Penicillin sensitive to Penicillin resistant strains. 2

Cloxacillin, Cephalosporins and Clavulinic Acid Inherently resistant to B-lactamase Therefore have been the drugs of choice for treating Staph Aureus for decades. They also cover Group A Strep; ; therefore are ideal drugs for skin and soft tissue infections! But wait.!!!! MRSA: Methicillin Resistant Staph Aureus MRSA 1 st identified in late 60 s By mid-80 s became a common nosocomial infection/colonizer Resistant to all B-lactams by virtue of alterations in transpeptidase (Penicillin binding protein). Rare in the non-hospitalized patients.but wait.!!!!! CA_MRSA: Community Acquired MRSA Late 90 s early 2000 s: sporadic outbreaks of MRSA in non-hospitalized patients identified CA-MRSA: case definition MRSA isolated from an individual who has not recently been in contact with a health facility. These outbreaks were labelled Community Acquired MRSA based on the lack contact with health care facilities. CA-MRSA: cytogenetic definition CA-MRSA is a genetically distinct organism from HA-MRSA. 99% of CA-MRSA comes from a single clone (USA 300 Clone) CA-MRSA possesses virulence factors not possessed by HA-MRSA, making it a particularly aggressive organism Panton-Valentine Leukocydin factor (PVL gene) Damages the cell membranes of Neutrophils, Macrophages and Monocytes, ultimately lysing them Spider Bites and MRSA A 47 year old Male presents with a spider bite. What kind of a spider produces this characteristic bite? Brown Recluse Black widow Violin Back MRSA spider 3

Risk Factors for CA-MRSA (traditional/sporadic outbreak) SPIDER BITE (pt identified) IV Drug Use Homeless / indigent Incarceration Sports teams Poverty Multiple Abscesses Known Contact with MRSA Recent Antibiotic Use and / or failure (ie Keflex failure = MRSA until proven otherwise!!) MRSA: new risk factor The single biggest predictor of MRSA infection? Abscess (likelihood ratio 20-30) Aug 17, 2006 All traditional risk factors of secondary importance CA-MRSA : who cares?!? You should! WHY? CA-MRSA: prevalence Texas: 1990: 2.3% 2001: 40.3% 2005: 78% California: 51% of all skin and soft tissue infections were MRSA at the infection site! Annals of Emergency Medicine, 2005 CA-MRSA: Prevalence CA-MRSA: prevalence New England Journal of Medicine Talon Et Al 2006 Multi-Center Trial (11 centres across continental US) 2004 59% of all infection site isolates were MRSA Conclusions: MRSA is the most common identifiable cause of skin and soft-tissue tissue infections among patients presenting to emergency departments in 11 U.S. cities. When antimicrobial therapy is indicated for the treatment of skin and soft-tissue tissue infections, clinicians should consider obtaining cultures and modifying empirical therapy to provide MRSA coverage. 4

Implications: Clinicians should consider modifying their practice to empirically cover MRSA and obtain wound cultures in ALL skin and soft tissue infections CA-MRSA: implications for Fraser Health So does this all apply to us??? YES!!! CA-MRSA: Local Prevalence MRSA local prevalence Guesses?? K. Wiebe Case Series (Aug 27 2006 - Dec 11 2006) CGH ER / Walk In Clinic 13/18 skin infections MRSA = 72 % 4/18 MSSA = 28% 4/18 MIXED (MRSA/MSSA + STREP)= 28% 72% of ALL skin infections 100% of abscesses 100% 5

Chilliwack ER data (2006): Bottom Line: 153 Staph. Aureus isolates 88 MRSA = 57.5 % (courtesy Dr. B Mack) MRSA is the most common isolate from skin and soft tissue infections in the US. MRSA is probably the most common isolate from skin and soft tissue infections in Chilliwack, and this likely extrapolates to all of Fraser Health. MRSA will replace MSSA over the next 10-20 years just as Pen resistant SA replaced Pen Sensitive SA 30 years ago. Bottom Line: Clinicians should empirically cover MRSA in all complicated and/or severe skin and soft-tissue tissue infections. Clinicians should empirically cover MRSA in any infection likely to be caused by staph aureus (eg/osteomyelitis/endocarditis/necrotizing pneumonia) Bottom Line: Hospital Pharmacists should recommend antimicrobial coverage with activity against MRSA for seriously ill patients with skin and soft tissue infections. So do I need to throw out the Ancef/Keflex??? Not Yet, Orthopedic surgeons! Ancef is probably still useful in PURE cellulitis. Why? Cellulitis vs Abscess Limitation of aforementioned data is ability to culture the wound. Abscesses = easy, cellulitis = hard Therefore, the above data applies to wounds with purulent exudate Pure cellulitis is more likely to be Group A Strep (Abrahamian, 2006) 6

What if it looks like this? So: if it looks like this you can still use Ancef, Provided it is not a life-threatening infection Is it likely to be MRSA? Yes: the presence of pus indicates @ least a 50% likelihood of MRSA based on all available data. So how do you treat suspected MRSA?? MRSA susceptibilities CA-MRSA is predictably susceptible to several common antibiotics: Septra (100%) Rifampin (100%) Doxycycline (86-92%) Clindamycin (94-95%) 95%) Universally resistant to cephalosporins/penicillins/macrolides/quinolones Local Susceptibilities Caveats Rapid resistance to Rifampin Therefore not used as monotherapy Inducible Clindamycin resistance Estimated @ 2-10% in US trials Possibly up to 47% in Fraser East Clinical significance uncertain: treatment failures reported Probably excludes Clindamycin monotherapy 7

What About Septra?? Probably not a good empiric monotherpay agent: why? No Group A Streptococcal coverage Doxycycline, likewise, has imperfect strep coverage. Recommendations: minor infections, possible CA-MRSA requiring antibiotics Empiric therapy = combination therapy Septra + Clinda or Rifampin or Keflex Clinda + Septra or Doxy or Rifampin Combination therapy ensures coverage of both strep and staph, and limits emergence of resistance. Serious/Life threatening Infections potentially due to MRSA Vancomycin + Ancef/Clinda/Clox Addition of 2 nd agent needed as some evidence to suggest Vanco not as good for MSSA. Other options = IV Septra / IV Linezolid Minor Abscess: no surrounding cellulitis, no systemic features Incision and Drainage only Does not apply to multiple abscesses 8

New Antibiotics Cases revisted DAPTOMYCIN (CUBICIN) Acitve against MRSA MSSA STREP Cyclic lipopeptide Tigecyclin (Tigacyl) 1 st glycylcycline Active against mrsa mssa strep and gram negs Both FDA approved: Health Canada pending 1.) 48 year old Male, history of superbug : treatment? Swab plus 2 of: Clinda/Septra/Doxy/Rifampin 2.) 26 year old Female, IV drug user, antecubital abscess: Organism? Treatment? Organism = MRSA! Treatment = I and D +/- combo therapy Cases revisited Husband and Wife, abscesses More info? Treated with keflex 3 times for previous episodes Almost certainly MRSA based on multiple abscesses and multiple courses of Keflex even though no other identifiable risk factors Treatment? I and D, Swab, Combination therapy Summary CA-MRSA is highly prevalent as a cause of skin and soft tissue infections CA-MRSA = virulent/aggressive CA-MRSA will replace MSSA in a matter of years Abscess/purulent skin infection = MRSA until proven otherwise Serious/life threatening skin and soft tissue infections must be treated with antibiotics active against both MRSA/MSSA and strep Summary QUESTIONS?!?! Septra, Doxy, Rifampin and Clinda can be used in combination when oral therapy is indicated. Vancomycin remains the agent of choice when iv therapy is indicated New antimicrobials may soon be available Small uncomplicated abscesses can still be treated with primary I and D alone. 9

Thank You 10