Cellulitis Treatment Where and How

Cellulitis & Associated SSTI Avenues of TreatmentOutlineBackgroundWhen should patients go home (PO), come back (IV) or go upstairs (admit)?And when do we get it wrong?OPAT rationaleOPAT at St Pauls now and futureTake home lessonsEpidemiologyCellulitis and associated SSTI (erysipelas, abscess-associated cellulitis) are a common presenting complaint to physician offices, outpatient hospital clinics and EDsIncreasing prevalence, correlated with increases in community MRSA especially in the early 21st century

Increasing ED visits for cellulitis in early 21st century(Palin, AEM 2008) analysis of US NHAMCS (1993-2005)% of all ED visits with SSTI increased from 1.35% to 2.98%Associated increase in MRSA coverage with antibiotics(Talan, CID 2008) Rates of MRSA SSTI in 12 US EDs in 2004 vs 200859% prevalence of MRSA unchanged with increasing appropriate MRSA coverage (57% in 2004 vs 97% in 2008)

NHAMCS US National Hospital Ambulatory Care Medical Survey samples EDs from all 50 states and DC, except federal/military/VA Eds. 374891 ED visits14.2 million visits in 2005 overall9.6 million visits for cellulitis/abscess

Talan 2004 n=422, 2008 n=6194Special local concerns(Binswanger, CID 2000) survey of 169 IVUs in San FranciscoOver 50% had active untreated abscess or cellulitis(Kerr, JPH 2006) prospective cohort study of 883 IVUs in Vancouver60% accessed SPH ER services in the last 12-24 monthsMost common reason was SSTI (18%)Kerr & Grafstein - SPH5Special local concerns(Lloyd-Smith, OIDJ 2013) 4-year study of 1083 Insite users, tracking incidence of St Pauls ED use for cutaneous injection-related infections (CIRI cellulitis & abscess)Predictors of ED use based on IVU patterns/demographics (not clinical)Female incidence 23.8 per 100 person-yearsDTES residence AHR 2.06 (1.13-3.78)Hospital referral AHR 4.48 (2.76-7.30)Male incidence 19.2 per 100 person-yearsRequire assistance injecting AHR 1.38 (1.01-1.90)HIV+ AHR 1.85 (1.34-2.55)Hospital referral AHR 2.97 (1.93-4.57)GrafsteinCox progression hazard regression: 100 person followed over 1 year, 50 people followed over 2 years

age, sex (female vs male), currently residing in the DTES (yes vs no), requiringassistance with injection (yes vs no), living in unstable housing (yes vs no), daily cocaineinjection (yes vs no), daily heroin injection (yes vs no), daily crack injection (yes vs no),daily speedball injection (yes vs no) and being HIV-positive (yes vs no). Variables refer tobehaviour during the last six months unless otherwise specified.6

Mild vs moderate cellulitisIDSA 2014Mild no systemic signs of infectionOutpatient oral antibiotics for patients who do not have SIRS, altered mental status, or hemodynamic instabilityModerate systemic signs of infection (? but not meeting SIRS)Severe failed oral antibiotic treatment, SIRS criteria, immunocompromisedCREST 2005Class I systemically well, no uncontrolled comorbiditiesClass II systemically ill OR systemically well + higher-risk comorbidity (PVD, chronic venous insufficiency, obesity)(Class III & IV) SIRS -> severe sepsis/life threateningPotential regimensSpectrum of regimens choice of regimen based on clinical judgement of severity and resource availabilityTopical antibioticsPO antibioticsED IV dose + home POED IV dose + return to ED for IV dosingED IV dose + outpatient IV antibiotics (OPAT clinic)ED IV with observation x 24-48 hours - SSU / DTU / CDUAdmit to wardAdmit to ICU / OR10

Outpatient treatment(Heather, CJEM 2005) prospective convenience sample of 75 patients (2 ED sites Ontario) with uncomplicated cellulitis treated with PO Keflex or IV ancef/probenecid or IV ceftriaxone (based on clinical judgement)39% treated with oral antibiotics, 7% failure rate61% treated with IV antibiotics, 26% failure rateTreatment failure = admission to hospital (7%), speciality consult (1%), change in antibiotics (8%), I&D (4%) overall rate of 20%Significant differences in treatment failure group:Older (46 vs 59, p = 0.02)More previous antibiotic treatment (16% vs 50%, p = 0.01)Subset interobserver agreement - kappa 0.39 (fair agreement) for assessment of severity

Traditional risk factors (IVDU, diabetes, peripheral vascular disease, clinical factors fever, systemic symptoms, size of lesion, location of lesion no difference)12Outpatient treatment(Peterson, AEM 2014) Prospective cohort study of 497 patients diagnosed with cellulitis (2 EDs in London, ON) treated with outpatient PO or IV antibiotics (RT ED), variable regimens based on ERP discretionTreatment failure = change in antibiotics (not including step-down from IV to PO), hospitalization overall rate 21%majority (17%) due to change in antibiotics4% due to admission to hospital13

Risk factors like comorbidities, IVDU, location of infection not affected** low risk of fever overall14

15ED observation unitMay be a sicker patient population unclear initial disposition as to home vs admissionOften RTED for daily IV ABx or OPAT not availableAssociated with cost savings managed by ED doctors during shift(Schrock, IJEM 2008) retrospective cohort review of 183 patients admitted to ED observation unit for 24 hours for abscess/cellulitis38% from EDOU required admission5.6% returned within 7 days of discharge for admission5% (!!) mortality

Risk factorOR (95% C.I.)Gender (female)2.34 (1.06-5.16)WBC > 154.06 (1.53-10.74)Traditional risk factors diabetes, immunocompromised, IVDU, MRSA not associated1.5% ED visit for SSTI, 57% discharged home, 35% admitted directly, 8% for ED OU16

ED observation unit(Volz, 2012 AJEM) single-site retrospective cohort study of 377 patients with cellulitis admitted to an ED observation unit for IV antibiotics and to assess response to treatmentDecision within 24 hours of admission to hospital vs discharge with PO antibioticsOverall treatment failure / admission rate 29.2%Caveats: not everyone had bloodwork or lactate. HR > 100, WBC > 11 trending. IVDU, immunocompromised, diabetes no differece17Which patients need admission?(Sabaj, AJEM 2009) single-site retrospective cohort study of 674 ED patients presenting with soft tissue infectionprimary outcome hospital stay > 24 hours81% discharged with PO antibiotics 1% returned requiring admission8% admitted to EDOU all remained > 24 hours, 50% hospitalized11% referred for hospital admission 78% of those hospitalizedWhich patients need admission?In this study, initial ED temp > 37.8% was 30.9% sensitivity and 94.8% specific for outcome

(Talan, WJEM 2015) prospective multi-site study (12 US EDs) of 619 adults presenting with a SSTIED physicians surveyed on clinical reasons for admissionPatient risk factors analyzed to look for independent predictors of admission15.2% hospitalization rate (13% to ward, 0.5% to ICU, 1.8% to EDOU)0% overall mortalityNeeds IV Abx sole reason in 42% of admitted patients (no availability of outpatient therapy)

Which patients need admission?Independent risk factor for admission% in admitted patients% in discharged patientsHistory of fever43.6%10.5%Maximal length of erythema > 10cm43.6%11.3%History of failed treatment16.1%6%Any co-morbidity61.7%27.2%Age > 65 years5.4%1.3%At least one risk factor present in 89 of 94 patients (95% sensitivity)All risk factors absent in 291 of 525 patients (45% specificity)While EPs tended to hospitalize patients who had fever, larger lesions, failed treatment, co-morbidities and advanced age, of 94 admitted patients, none had subsequent ICU transfer or died, and only two had amputations, both of whom had soft tissue gas on their initial radiographs21

OPAT Outpatient Parental Antibiotic Therapy(Seaton, EJIM 2013) the administration of a parenteral antimicrobial in a non inpatient or ambulatory setting (clinic, office, home) with the explicit aim of facilitating admission avoidance or early dischargearound for decades, well established clinical literatureinfections managed via OPAT should have a predictable course, a consistent response to a well-defined antimicrobial therapy and a low likelihood of acute deteriorationtends to be run by ID, sometimes by internistswhen we bring patients back to the ED for repeat IV antibiotics and reassessment, we are practicing a version of OPAT23

OPAT review of the evidence(Barr, IJAA 2012) 10-year cohort study of 2233 OPAT clinic patients53% for SSTI92.4% cure or improvement, 9.1% admission rate(Chapman, JAC 2009) 2-year cohort study of 334 OPAT clinic patients59% for SSTI87% cure or improvement, 6.3% admission rate, 39-59% estimated cost savings (versus inpatient treatment)OPAT review of the evidence(Esposito, IJAA 2004) analysis of International OPAT Registry of 9826 US patients, 981 UK patients, 620 Italian patientsUSA cure or improvement in 92.5%UK cure or improvement in 96.8%Italy cure or improvement in 95.1%(Wai, Pharmacoeconomics 2000) Cost-analysis of OPAT program at VGH (?UBC) hospital based on 117 patients over a 3-year periodEstimated cost per patient from hospital - $1910Estimated cost per patient from MOH - $6326Estimated 55-87% cost savings per patient compared to hospital stay26

(Esposito, IJAA 2004)OPAT rationale for specialist care in cellulitisPresentation by Dr. Richard Bachand (PharmD) Director of Antimicrobial Stewardship at VIHAOPAT data from RJH in 2006

OPAT rationale for specialist care in cellulitis(Levell, BJD 2011) UK single site, 635 patients referred from GPs to dermatologists for lower limb cellulitis 33% had other diagnoses(David, DOJ 2011) two US sites - 145 patients referred from ERPs for admission for cellulitis, 28% had other diagnoses as reviewed by ID or dermatology(Previous pilot study showed 100% concordance between ID & dermatology)Most common misdiagnosis stasis dermatitis

St. Pauls OPAT programStarted Jan 19, 2015Patients requiring more than 1 day of IV antibioticsManaged by Infectious Diseases specialistsOpen 7 days a week (11am-7pm, in flux)Currently main source of patients is SSTI referred by SPH ED doctorsUncomplicated cellulitis or abscess-associated cellulitis (I&Dd)Also take any uncomplicated infection requiring IV AbxUTI/pyelonephritis, dental infections, osteomyelitis,St. Pauls OPAT program feedback for usDiscussions with Dr. Philip Peters and Dr. Tom HaveyThings ED doctors do wellGenerally appropriate referralsGenerally appropriate choice of antibioticsUseful items for the OPAT clinicBaseline bloodwork on patients, including a CRP+/- blood cultures when clinically appropriate (not most SSTI, consider in pyelonephritis)+ wound cultures if I&D or needle aspiration of associated abscess+ HIV statusSome challenges related to patient populationTake home lessonsWe are generally better at predicting who has mild cellulitis needing PO antibiotics than the disposition for those who have moderate cellulitisNo clear guidelinesBeware the history or presence of fever consistent risk factor for admission and failed outpatient therapy in larger studiesClinic-based OPAT is effective (comparable to or better than returning to ED for IV therapy), and cost-effective when compared to inpatient admissionSpecialist care available in OPAT may reduce duration or intensity of antibiotic regimen and in identification of alternative diagnosesReferencesWai AO, et al. Cost Analysis of an Adult Outpatient Parenteral Antibiotic Therapy (OPAT) Programme. Pharmacoeconomics 2000; 18(5):451-7Palin DJ, et al. Increased US Emergency Department Visits for Skin and Soft Tissue Infections, and Changes in Antibiotic Choices, During the Emergence of Community-Associated Methicillin-Resistant Staphylococcus aureus. Ann Emerg Med 2008; 51(3): 291-8. Talan DA, et al. Comparison of Staphylococcus aureus from skin and soft-tissue infections in US emergency department patients, 2004 and 2008. Clin Infect Dis. 2011; 53(2):144-9Binswanger IA, et al. High prevalence of abscesses and cellulitis among community-recruited injection drug users in San Francisco. Clin Infect Dis. 2000;30(3):579-81.Kerr T, et al. High rates of primary care and emergency department use among injection drug users in Vancouver. J Public Health (Oxf). 2005;27(1):62-6.Lloyd-Smith E, et al. DETERMINANTS OF CUTANEOUS INJECTION-RELATED INFECTIONS AMONG INJECTION DRUG USERS AT AN EMERGENCY DEPARTMENT. Open Infect Dis J. 2012;6.Stevens DL, et al. Practice guidelines for the diagnosis and management of skin and soft tissue infections: 2014 update by the Infectious Diseases Society of America. Clin Infect Dis. 2014 Jul 15;59(2):e10-52.Clinical Resource Efficiency Support Team (CREST) Guidelines on the Management of Cellulitis in Adults. Belfast, Ireland; 2005.Murray H, Stiell I, Wells G. Treatment failure in emergency department patients with cellulitis. CJEM. 2005 Jul;7(4):228-34.Peterson D, et al. Predictors of failure of empiric outpatient antibiotic therapy in emergency department patients with uncomplicated cellulitis. Acad Emerg Med. 2014 May;21(5):526-31.Schrock JW, Laskey S, Cydulka RK. Predicting observation unit treatment failures in patients with skin and soft tissue infections. Int J Emerg Med. 2008 Jun;1(2):85-90.Volz KA, et al. Identifying patients with cellulitis who are likely to require inpatient admission after a stay in an ED observation unit. Am J Emerg Med. 2013 Feb;31(2):360-4.Sabbaj A, et al. Soft tissue infections and emergency department disposition: predicting the need for inpatient admission. Acad Emerg Med. 2009 Dec;16(12):1290-7.Talan DA, et al. Factors associated with decision to hospitalize emergency department patients with skin and soft tissue infection. West J Emerg Med. 2015 Jan;16(1):89-97.Seaton RA, Barr DA. Outpatient parenteral antibiotic therapy: principles and practice. Eur J Intern Med. 2013 Oct;24(7):617-23.Barr DA, Semple L, Seaton RA. Outpatient parenteral antimicrobial therapy (OPAT) in a teaching hospital-based practice: a retrospective cohort study describing experience and evolution over 10 years. Int J Antimicrob Agents. 2012 May;39(5):407-13.Chapman AL, et al. Clinical efficacy and cost-effectiveness of outpatient parenteral antibiotic therapy (OPAT): a UK perspective. J Antimicrob Chemother. 2009 Dec;64(6):1316-24.Esposito S, et al. Outpatient parenteral antibiotic therapy (OPAT) in different countries: a comparison. Int J Antimicrob Agents. 2004 Nov;24(5):473-8.David CV, et al. Diagnostic accuracy in patients admitted to hospitals with cellulitis. Dermatol Online J. 2011 Mar 15;17(3):1.Levell NJ, Wingfield CG, Garioch JJ. Severe lower limb cellulitis is best diagnosed by dermatologists and managed with shared care between primary and secondary care. Br J Dermatol. 2011 Jun;164(6):1326-8.Thank you!