Methicillin-Resistant Staphylcccus aureus Infectin in a Tertiary Care Hspital in Rural British Clumbia: A Retrspective Study f Resistance Patterns and Empiric Antibitic Therapy STUDY PROTOCOL Nicle Bruchet, B.Sc., B.Sc.(Pharm), ACPR Dctr f Pharmacy Student, Faculty f Pharmaceutical Sciences, University f British Clumbia, Vancuver, British Clumbia, Canada. Dawn Dalen, BSP, ACPR, PharmD Clinical Pharmacist Specialist Emergency Medicine, Kelwna General Hspital, Kelwna, British Clumbia, Canada. Clinical Assistant Prfessr, Faculty f Pharmaceutical Sciences, University f British Clumbia, Vancuver, British Clumbia, Canada. Denise Sprague, BSc. (Pharm), ACPR, PharmD Clinical Pharmacist Specialist Infectius Diseases, Kelwna General Hspital, Kelwna, British Clumbia, Canada. June 15, 2009
Intrductin Methicillin-resistant Staphylcccus aureus (MRSA) is an increasingly cmmn human pathgen and an imprtant cause f infectin in bth hspitalized patients and patients in the cmmunity. MRSA refers t the Staphylcccus aureus strains that are resistant t beta-lactam antibitics, including penicillins, cephalsprins, mnbactams and carbapenems (1,2). MRSA first emerged in the 1960s after the intrductin f the semi-synthetic penicillins, methicillin, xacillin and clxacillin, and has since becme a cmmn nscmial pathgen (2). In the United States, it is estimated that 40% f hspital Staphylcccus aureus strains are methicillin resistant. In Canada, the rates f nscmial MRSA are lwer than in the United States, with an estimated hspital MRSA rate f 10.4% in 2003 (2). MRSA is ften thught f as a hspital-assciated infectin, hwever ver the past ten years there has been an emergence f genetically distinct MRSA strains in the cmmunity setting. These infectins have been seen in patients withut recent hspitalizatins, and are capable f causing infectins ranging frm mild t life-threatening (2). Thus, regardless f whether the MRSA infectin is hspital-assciated (HA) r cmmunity-assciated (CA), it represents an imprtant cause f mrbidity and mrtality in bth the hspital and cmmunity settings. HA-MRSA and CA-MRSA are genetically distinct frms f MRSA and they als differ in terms f the ppulatins they infect and their susceptibility t antibitics. There are n standardized definitins f HA-MRSA and CA-MRSA. Despite this, hwever, HA-MRSA is typically defined as MRSA strains that are transmitted t patients within health care facilities (2). There are a number f factrs assciated with an increased risk f HA-MRSA infectin and these include: previus islatin f MRSA, islatin f MRSA mre than 48 hurs after hspital admissin, the presence f an indwelling catheter r percutaneus device at the time f culture, histry f hspitalizatin, surgery, dialysis r residence in a lng-term care facility within ne year f the MRSA culture date (2). CA-MRSA is typically defined as MRSA islates btained frm patients in the cmmunity wh have nt had recent expsure t the health care system and wh have nne f the risk factrs assciated with HA-MRSA (2). In additin, CA-MRSA als refers t an MRSA infectin in patients in health care 2
facilities that was present r incubating at the time f admissin (2). Certain ppulatins f patients are at higher risk f develping CA-MRSA and these include: yung peple, Abriginal r African American individuals, athletes wh play cntact sprts, intravenus drug users, men wh have sex with men, thse f lwer sciecnmic class r living in situatins f vercrwding, thse with a chrnic skin disrder and thse with recurrent r recent antibitic use (2). Despite the definitins f CA-MRSA and HA-MRSA and the knwn risk factrs fr their ccurrence, it can ften be difficult t determine whether a MRSA infectin in a given patient is due t a cmmunity r hspital assciated pathgen using epidemilgic infrmatin alne. This is because hspital strains f MRSA are ften fund in patients in the cmmunity and cmmunity strains are ften fund in hspitalized patients. As such, genetic and antibitic susceptibility testing are required t definitively determine if a MRSA strain is cmmunity r hspital assciated. MRSA cnfers resistance t beta-lactam antibitics thrugh mutatins in the gene that cdes fr the penicillin binding prtein 2a, lcated in the rganism (2,3). There are five different alleles f this gene and each cntain different mutatins resulting in resistance t beta-lactam antibitics (2). CA-MRSA and HA-MRSA differ in terms f the genetic mutatins fund in the gene cding fr the penicillin binding prtein 2a. CA-MRSA and HA- MRSA als differ in terms f their susceptibility t ther classes f antibitics, aside frm beta-lactam antibitics. In general, CA-MRSA is mre susceptible t ther types f antibitics, such as clindamycin, sulfamethxazle-trimethprim, flurquinlne antibitics and tetracyclines, where as HA-MRSA is resistant t these antibitics (1,2). Regardless f whether it is cmmunity r hspital-assciated, MRSA can result in infectins ranging frm mild t life-threatening. Cmmn infectins caused by MRSA include: skin and sft tissue infectins, skin abscesses, stemyelitis, wund infectins, catheter-related infectins, pneumnia and bacteremia. The chice f empiric antibitic therapy in a patient suspected f having an infectin caused by MRSA depends n many factrs, including the site and severity f the infectin, clinical status f the patient, whether the patient develped the infectin in the cmmunity r in hspital and whether the patient has risk factrs fr the develpment f a cmmunity-assciated r hspital-assciated MRSA infectin. In general, fr mild r mderate infectins, such as sme skin and sft tissue infectins, 3
suspected t be caused by CA-MRSA, clindamycin, sulfamethxazle-trimethprim r a tetracycline antibitic are reasnable therapeutic alternatives fr empiric antibitic therapy (2,4,5). In thse with mre severe infectins and in patients with risk factrs fr HA-MRSA, vancmycin is generally indicated (2). In additin t cnsidering the site and severity f the infectin, the patient demgraphics and clinical characteristics, lcal antibitic resistance patterns fr MRSA are als imprtant t cnsider when deciding n empiric antibitic therapy as they can help guide the chice f antibitic. HA-MRSA strains are typically resistant t multiple classes f antibitics, whereas CA-MRSA strains are ften nly resistant t beta-lactam and macrlide antibitics (2). As such, mre therapeutic ptins are available fr the management f CA-MRSA infectins. Despite this, hwever, resistance t the cmmnly used antibitics fr the management f CA-MRSA infectins can ccur and this has the ability t influence the chice f empiric antibitic therapy fr the management f patients suspected f having a CA-MRSA infectin. A study by Mran et al. (6) assessed the susceptibility patterns f MRSA infectins in patients presenting the emergency departments in the United States in August f 2004 fr skin and sft tissue infectins. This study fund that fr the MRSA islates, 95% were susceptible t clindamycin, 6% were susceptible t erythrmycin, 60% t flurquinlnes, 100% t rifampin, 100% t sulphamethxazletrimethprim and 92% t tetracycline. This study was cnducted at University-affiliated hspitals in eleven cities in the United States and due t differences in the prevalence rates f MRSA, the antibitics used t treat MRSA and the patient ppulatins, the results f this study may nt be transferable t centres in Canada and t nn-urban centres. Anther study cnducted at 57 military hspitals and clinics in the United States cmpared the susceptibility f MRSA cultures btained frm children in 2001-2002 t thse btained frm children in 2003-2004 and demnstrated an increase in clindamycin resistance amng MRSA cultures frm 0.48% in 2001-2002 t 3.97% in 2003-2004 (7). A study by Szumwski et al. (8) assessed the treatment ptins, clinical utcmes and susceptibility data fr MRSA skin and sft tissue infectins in an ambulatry clinic in Bstn. This study demnstrated that 48.2% f the MRSA cultures were resistant t clindamycin, whereas nly 0.5% were resistant t sulfamethxazletrimethprim. These studies prvide infrmatin n the resistance patterns f MRSA in the hspital and cmmunity settings and als highlight sme f the differences in resistance patterns at different health 4
care sites. MRSA resistance t empiric antibitic therapy depends n antibitic patterns f use at that health care site, patient clinical and demgraphic characteristics and micrbilgic characteristics f the rganism. Therefre, lcal data n antibitic patterns f resistance is required t determine the mst apprpriate empiric antibitic chice fr the management f MRSA infectin. Study Ratinale In British Clumbia in 2008, ne in five Staphylcccus aureus islates frm British Clumbia labratries were methicillin resistant (9). Of these MRSA islates, 36.2% f them were resistant t clindamycin, 84.8% were resistant t erythrmycin, 6.4% were resistant t sulfamethxazle-trimethprim and 7.8% were resistant t dxycycline (9). It is unclear frm this data, hwever, hw many f these MRSA islates had the genetic mutatins characteristic f CA-MRSA and hw many had the genetic mutatins characteristic f HA-MRSA. Kelwna General Hspital serves the city f Kelwna and is als a majr referral centre fr rural cmmunities in the interir f British Clumbia. The incidence f MRSA infectins at Kelwna General Hspital is currently nt knwn. In additin, the resistance patterns f MRSA infectins at Kelwna General Hspital are als nt knwn. Due t the diverse patient ppulatin served by this hspital, it is unclear if the prvince-wide MRSA susceptibility data can be applied t MRSA infectins in Kelwna. As such, a study is required t characterize the susceptibility patterns f MRSA cultures at Kelwna General Hspital and the chice f empiric antibitic regimens used t treat MRSA infectins in this hspital. The purpse f this study will be t prvide valuable infrmatin n the patterns f resistance fr MRSA infectins in Kelwna and the demgraphics and clinical characteristics f the patients infected with MRSA in the interir f British Clumbia. In additin, we wuld like t characterize the current empiric antibitic chice used fr suspected MRSA infectins at Kelwna General Hspital. Study Objectives Primary Objective T characterize the susceptibility patterns f MRSA cultures at Kelwna General Hspital ver a ne year perid 5
Secndary Objectives T characterize the types f infectins caused by MRSA at Kelwna General Hspital T describe the patient-specific MRSA risk factrs, if present, fr patients diagnsed with a MRSA infectin at Kelwna General Hspital T characterize the empiric antibitic regimens used t treat patients with suspected MRSA infectin at Kelwna General Hspital Study Design Overview This study will be a retrspective chart review and will assess the susceptibility patterns and empiric antibitic therapy fr MRSA infectins at Kelwna General Hspital frm June 1, 2008 t May 31, 2009. The investigatrs fr this study, wh are respnsible fr designing the study and develping the study methdlgy, include a Dctr f Pharmacy Student, Clinical Pharmacy Specialist in Emergency Medicine, a Clinical Pharmacy Specialist in Infectius Diseases and a Medical Micrbilgist. A University f British Clumbia undergraduate pharmacy student will be respnsible fr cllecting the study data. Patient Selectin Patients will be cnsidered fr inclusin int this study if they had a psitive culture fr a suspected infectin r a psitive screening culture fr MRSA btained at Kelwna General Hspital between June 1, 2008 and May 31, 2009. Inclusin Criteria Males and females 18 years f age r lder Exclusin Criteria Males and females less than 18 years f age 6
Outcme Measures The primary utcme f this study is the percentage f MRSA cultures resistant t different antibitics, including clindamycin, sulfamethxazle-trimethprim, ciprflxacin, mxiflxacin, tetracycline, erythrmycin, linezlid r vancmycin. The secndary utcmes include the incidence f each type f MRSA infectin, the incidence f identified MRSA risk factrs and the percent f each empiric antibitic chsen in this patient ppulatin. Study Prcedures A list cntaining patient names, medical recrd numbers, patient ages, date(s) f MRSA culture and lcatin f culture will be btained frm the micrbilgy labratry database fr all patients with a psitive MRSA culture between June 1, 2008 and May 31 2009. Upn review f the btained list, patients meeting the exclusin criteria will be excluded frm the study. Patients meeting the study inclusin criteria will be included in the study. The hspital charts f included patients will be btained frm health recrds and will be reviewed t btain patient demgraphic, clinical and scial histry infrmatin fr the hspital visit in which the psitive MRSA culture was btained. In additin, the micrbilgy labratry cmputer system will be accessed t btain resistance patterns fr each MRSA culture. The data cllectin frm that will be used t cllect the data is prvided in Appendix I. Once all data is cllected, it will be entered int a Micrsft Excel spreadsheet fr analysis. The fllwing infrmatin, if available, will be btained frm each patient chart: Patient medical recrd number Patient demgraphic data Date f admissin r visit t hspital Gender Age Lcatin in hspital at time f culture Emergency department Hspital ward 7
Intensive care unit Patient clinical data and scial histry Cmrbid diseases Any risk factrs fr MRSA (2) Abriginal Athlete invlved in a cntact sprt Injectin drug user Hmelessness Recent hspitalizatin in the past year In Interir Health Authrity In British Clumbia In Canada Outside f Canada Immuncmprmised Underging hemdialysis Recent trauma in the past year Indwelling catheter in time f culture Percutaneus device at the time f culture Site f infectin Name(s) f empiric antibitic(s) The fllwing infrmatin, if available, will be btained frm the Micrbilgy Labratry cmputer system: Date f MRSA culture Site(s) f MRSA culture Whether the rganism was sensitive, intermediately sensitive r resistant t Clindamycin Sulfamethxazle-trimethprim Ciprflxacin Mxiflxacin 8
Tetracycline Erythrmycin Linezlid Vancmycin Minimum Inhibitry Cncentratin (MIC) <0.5 0.5-1.0 1.1-1.5 1.6-2.0 >2 Evaluatin f Study Outcmes and Statistical Analysis All data btained frm the patient charts and the Micrbilgy Labratry system will be entered int a Micrsft Excel Spreadsheet fr analysis. Micrsft excel will be used t determine the number and percent f MRSA cultures resistant t the pre-specified antibitics and t categrize and calculate the number and percent f MRSA infectin type, risk factrs fr MRSA infectin and type f empiric antibitic therapy given. Descriptive statistics, specifically the mean, standard deviatin and percent will be used when analyzing the patient demgraphic, clinical and micrbilgic characteristics. 9
References 1. Niclle L. Cmmunity-acquired MRSA: a practitiner s guide. CMAJ 2006;175(2):145-46. 2. Bartn M, Hawkes M, Mre D, et al. Guidelines fr the preventin and management f cmmunityassciated methicillin-resistant Staphylcccus aureus: A perspective fr Canadian health care practitiners. Can J Infect Dis Med Micrbil 2006;17(Suppl C):4C 3. Zetla N, Francis JS, Nuerrnberg EL, Bishai WR. Cmmunity acquired methicillin-resistant Staphylcccus aureus: an emerging threat. Lancet Infect Dis 2005;5:275-86. 4. Stevens DL, Bisn AL, Chambers HF, et al. Practice guidelines fr the diagnsis and management f skin and sft-tissue infectins. Clin Infect Diseases 2005;41:1373-406. 5. Abrahamian FM, Talan DA, Faaem F, et al. Management f skin and sft tissue infectins in the emergency department. Infect Dis Clin N Am 2008;22:89-116. 6. EMERGEncy ID Net Study Grup. Methicillin-resistant S. aureus infectins amng patients in the emergency department. NEJM 2006;355:666-74. 7. Braun L, Craft D, Williams R, Tuamkum F, et al. Increasing clindamycin resistance amng methicillin-resistant Staphylcccus aureus in 57 Nrtheast United States military treatment facilities. Ped Infec Dis J 2005;24:622-626. 8. Szumwski JD, Chen DE, Kanaya F, et al. Treatment and utcmes f infectins by methicillinresistant Staphylcccus aureus in an ambulatry clinic. Antimicr Agent and Chem 2007;Feb:423-28. 9. Epidemilgy Services, British Clumbia Centre fr Disease Cntrl. Antimicrbial resistance trends in the Prvince f British Clumbia. August 2008. 10
Appendix I: Study Data Cllectin Frm 11
MRSA Study Data Cllectin Frm Versin 1_June17, 2009 Patient Name: Patient ID: Age: Gender: Weight (kg): Date f Admissin/Visit: Lcatin in Hspital in Time f Culture EMERG Ward ICU Type f Culture Screen Culture fr Infectin Bth Cmrbid Diseases (check all that apply) COPD Diabetes Rheumatid Arthritis Ostearthritis Heart Failure Asthma Hypertensin Other MRSA Risk Factrs (check all that are present) Site(s) f Infectin Athlete IVDU Abriginal Hmeless Immuncmprmised Hemdialysis Skin and Sft Tissue Skin Abscess Buttcks Abscess Surgical Wund Traumatic Wund Bne/Jint/Hardware Diabetic Ft Pneumnia Bacteremia Urinary Tract CNS Other Trauma in last year Indwelling catheter (at time f culture) Percutaneus device (at time f culture) Hspitalizatin in last year In Interir Health In BC In Canada Outside Canada Nt available Susceptibility t Antibitics (S,I,R) Clinda Septra Cipr Lev Mxi Tetra Erythr Vancmycin MIC <0.5 1.1-1.5 >2 Linezlid 0.6-1.0 1.6-2 Nt available Date f Culture Site(s) f Culture Bld Sputum Urine Brnchscpy Wund CSF Nasal swab Rectal Swab Other Incisin/Drainage Perfrmed Empiric Antibitics Yes N Yes N Empiric Antibitics Cefazlin Cefazlin and prbenicid Clinda iv Clinda p Cipr Mxi Clx iv clx p cephalexin amxicillin/clavulanate dxycycline vancmycin linezlid Septra Other Is culture susceptible t empiric antibitic chice? Yes N Nt Available Empiric Abx nt tested