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LAC Outbreak Investigations in the 21st Century “Disease Detectives”

LAC Outbreak Investigations in the 21st Century “Disease Detectives”. Laurene Mascola, M.D., M.P.H., F.A.A.P. Chief, Acute Communicable Disease Control Program Los Angeles County Department of Public Health. Eastern Virginia Medical School of Public Health April 16, 2008. OBJECTIVES.

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LAC Outbreak Investigations in the 21st Century “Disease Detectives”

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  1. LAC Outbreak Investigations in the 21st Century“Disease Detectives” Laurene Mascola, M.D., M.P.H., F.A.A.P. Chief, Acute Communicable Disease Control Program Los Angeles County Department of Public Health Eastern Virginia Medical School of Public Health April 16, 2008 DPH Acute Communicable Disease Control Program

  2. OBJECTIVES • To describe how the Los Angeles County Public Health Department investigates: • Nosocomial infections (hospital acquired) • Skin infections (contact transmission) • Vectorborne infections―trigger bioterrorism alarms! • Demonstrate how local investigations lead to national policy issues DPH Acute Communicable Disease Control Program

  3. NOSOCOMIAL INFECTIONS Beware of being sick and then being hospitalized DPH Acute Communicable Disease Control Program

  4. Serratia marcescens Outbreak Investigation Los Angeles CountyJanuary 2005 DPH Acute Communicable Disease Control Program

  5. BACKGROUND AND INTRODUCTION • January 2005, ICP notified LAC health department of 6 cases of Serratia marcescens (SM) blood stream infections (BSIs) after cardiac procedures within 11 day period; surgery unit closed • Serratia marcescens is a gram negative bacteria that thrives in moist environments; frequently causes hospital infections Terashita D, M.D. DPH Acute Communicable Disease Control Program

  6. HOW DOES ONE PERFORMAN INVESTIGATION • Confirm there is an outbreak • Define wrt to person, time and place • Make hypothesis • Design statistical tests to analyze above • Use results and decide on biologic plausibility • Make recommendations and control outbreak • Maybe lead to more investigations/studies • And don’t forget the politics Terashita D, M.D. DPH Acute Communicable Disease Control Program

  7. METHODS-LAC OUTBREAK (1) • Lab inpatient records/medical charts reviewed to confirm outbreak; compared infection rates of last year • Case-control study initiated • Site visit/environmental sampling done • Isolates obtained for pulsed field electrophoresis (PFGE) Terashita D, M.D. DPH Acute Communicable Disease Control Program

  8. METHODS-LAC OUTBREAK (2) • Case defined as patient in CSU in January 2005 with culture confirmed SM and PFGE match • Control patients in CSU (cardio/surgical unit) within 4 hours of matched cases (used three controls/case) • Environmental samples after site visit; meds used at time of outbreak no longer available for culture Terashita D, M.D. DPH Acute Communicable Disease Control Program

  9. RESULTS (1) LABORATORY: REPORTED POSITIVE INPATIENT S. MARCESCENS CULTURES BY MONTH AND CULTURE SITE, JANUARY 2004–JANUARY 2005 Terashita D, M.D. DPH Acute Communicable Disease Control Program

  10. S. MARCESCENS BACTEREMIA BY DAY JANUARY 1–16, 2005 X= CT patient, different PFGE pattern Terashita D, M.D. DPH Acute Communicable Disease Control Program

  11. RESULTS OF OPERATING ROOM INVESTIGATION LAC AND HOSPITAL INFECTION CONTROL (1) • Percentage of all SM blood culture results from blood samples increased significantly from 11% in 2004 to 60% in January 2005 • Case and control patients were similar with respect to age, sex • All 6 cases received MgSO4 during 24 hrs from compounding pharmacy X compared to 39% (7) controls; matched OR 6.4; 95% CI 1.1-38.3 Terashita D, M.D. DPH Acute Communicable Disease Control Program

  12. Environmental Cultures Multi-dose medication vials Ice and water from perfusion room Surfaces in OR Cleaning disinfectant from EVS ALL NEGATIVE Cohort Investigation No association with staff members No association with operating rooms No association with specific medications or equipment RESULTS OF OPERATING ROOM INVESTIGATION LAC AND HOSPITAL INFECTION CONTROL (2) Terashita D, M.D. DPH Acute Communicable Disease Control Program

  13. RESULTS OF OPERATING ROOM INVESTIGATION LAC AND HOSPITAL INFECTION CONTROL (3) • Although odds ratio, epi data supported Mg SO4, no conclusive proof • CDC notified of 2nd outbreak of SM BSIs among 3 patients in New Jersey cardiac/pulmonary hospital March 05 • Serendipitously, one patient became septic while receiving infusion of MgSO4 Terashita D, M.D. DPH Acute Communicable Disease Control Program

  14. OUTBREAK 2: NEW JERSEY • LAC and NJ Serratia isolatesmatched by PFGE • All NJ patients received IV MgSO4 within 48 hours prior to onset of BSI • Cultures of sample infusion and unopened bag of MgSo4 in same lot revealed SM • Multistate investigation begun Terashita D, M.D. DPH Acute Communicable Disease Control Program

  15. TO MAKE A LONG STORY SHORT… • Case-finding done across the nation with PFGE matching done • CDC interviewed compounding pharmacy X to find distribution of contaminated lots and to learn about infection control practices during MgSO4 compounding • Worked with FDA and State Board of Pharmacy Terashita D, M.D. DPH Acute Communicable Disease Control Program

  16. NATIONAL RESULTS • 50 total suspect cases in 11 states; 18 confirmed from Jan 5-March 26, 2005 in 5 states • Lot A of MgSO4 grew SM, same PFGE • Made in compounding pharmacy that has limited regulations compared to pharmaceutical manufacturers • Did not test or retain samples of each lot for sterility; no definitive source identified Terashita D, M..D. DPH Acute Communicable Disease Control Program

  17. SOURCE OF OUTBREAK ? • Hypothesized to be hands of compounding pharmacist(s) • Only small bags involved which necessitated touching entry port • Also another lot was contaminated with multiple gram negative species; several of which were environmental organisms Terashita D, M.D. DPH Acute Communicable Disease Control Program

  18. CONCLUSION AND DISCUSSION (1) • National health-care associated outbreak of SM BSIs due to contaminated IV medicine produced by compounding pharmacy • Has different oversight and regulations than pharmaceutical (pharm) companies • Hospitals often unaware of difference when order product Terashita D, M.D. DPH Acute Communicable Disease Control Program

  19. CONCLUSION AND DISCUSSION (2) • Delayed suspicions that product was source of LA outbreak • Is similar product—same dose—from pharm company in use in hospital that only differed by volume (for preg women etc.) • Major difference between quality control—compounding pharmacies do not need to hold product or test for sterility vs. pharm manufacturers Terashita D, M.D. DPH Acute Communicable Disease Control Program

  20. SOCO AND POLICY IMPLICATIONS • Compounding pharmacies are increasingly used by hospitals as source of IV medicines as are less costly • Hospital administrators should be aware of risks associated with compounded sterile medicines vs. others • Investigators need to take these risks into account when doing BSIs outbreaks Terashita D, M.D. DPH Acute Communicable Disease Control Program

  21. An Outbreak of Community-Associated Methicillin Resistant Staphylococcus aureus in a Football Team-Los Angeles, August-September, 2003 DPH Acute Communicable Disease Control Program

  22. INFECTIONS CAUSED BY CONTACT…. • “Always have clean underwear on” • “Wash your hands” • “Don’t put that in your mouth” • “Protect yourself and stay healthy” Nguyen DM, M.D. DPH Acute Communicable Disease Control Program

  23. BACKGROUND • Causes of skin infections among athletes • Fungal, viral, parasitic, bacterial • Community-Associated MRSA (CA-MRSA) infections increasingly more common • Teams with reports of CA-MRSA infections • Close-contact sports: football, wrestling, rugby • Others: fencing, soccer, canoers, diving Nguyen DM, M.D. DPH Acute Communicable Disease Control Program

  24. AUGUST 25, 2003 LAC DHS notified… • Two football players hospitalized for skin infections • Cellulitis and pre-patellar bursitis knee • Abscess elbow • Two additional hospitalized players reported • Infected “insect bite” foot • Abscess elbow • Failed outpatient antibiotic therapy • Had MRSA positive wound cultures Nguyen DM, M.D. DPH Acute Communicable Disease Control Program

  25. TEAM CHARACTERISTICS • Competitive university football program • 107 players on roster • Season starts with training camp • August 5-18 • Close-knit, isolated living conditions Nguyen DM, M.D. DPH Acute Communicable Disease Control Program

  26. OBJECTIVES OF INVESTIGATION • Describe the outbreak • Determine potential risk factors for CA-MRSA infection and nasal carriage among players • Control outbreak and prevent disease Nguyen DM, M.D. DPH Acute Communicable Disease Control Program

  27. METHODS • Literature Review • Consultations • Case-Finding • Case-Control Study • Nasal Carriage Study • Laboratory Study • Site Visits Nguyen DM, M.D. DPH Acute Communicable Disease Control Program

  28. CASE DEFINITIONS • Case-Patient • Player with a skin or soft tissue infection, either culture-confirmed or clinically diagnosed as CA-MRSA, from August 15–September 3, 2003 • Control • Teammate, randomly selected • Carrier • Asymptomatic teammate with positive MRSA nasal culture during same period Nguyen DM, M.D. DPH Acute Communicable Disease Control Program

  29. CASE FINDING • Review of athletic trainer’s treatment log • Active surveillance including skin inspection • Encourage players to report skin lesions • Query of student health service Nguyen DM, M.D. DPH Acute Communicable Disease Control Program

  30. EPIDEMIC CURVE Infection Control Measures Infection Control Measures (hexachlorophene) 3 Training Camp 8/5-18 Game #1 2 Number Case-Patients Training camp 8/5-18 Game #1 Case-Patients 1 0 8/5 8/10 8/15 8/20 8/25 8/30 9/4 Date of Diagnosis (2003) Nguyen DM, M.D. DPH Acute Communicable Disease Control Program

  31. TEAM-INITIATED INFECTION CONTROL MEASURES Prior to our involvement: • Increased frequency of locker room cleaning • Drained and disinfected whirlpool tubs • Instructed players on hygiene education • Provided more towels • Initiated hexachlorophene showers (8/26) Nguyen DM, M.D. DPH Acute Communicable Disease Control Program

  32. POTENTIAL SOURCE As soon as current outbreak recognized… • Trainer identified a potential source • Returning player • CA-MRSA skin infection in 2002 • Allergic rhinitis, poor hygiene habits • MRSA positive nasal culture (8/25/03) • Locker directly across from the first case-patient in current outbreak • Roommate during camp with third case-patient Nguyen DM, M.D. DPH Acute Communicable Disease Control Program

  33. CASE-CONTROL STUDY • Design • Unmatched, three controls per case-patient • Data gathering • Standardized questionnaire, administered in person • Data analysis • MS Access database • Epi Info version 3, released 10/31/03 • Univariate analysis using Fisher’s Exact Test • Odds ratio (OR), 95% confidence interval (95% CI) Nguyen DM, M.D. DPH Acute Communicable Disease Control Program

  34. ADDITIONAL INVESTIGATIONS • Nasal carriage study • Cultures from anterior nares of all available football team members • Laboratory investigation • Pulsed-field gel electrophoresis (PFGE) of MRSA isolates • SmaI, EagI restriction enzymes digestion • Antibiotic resistance pattern Nguyen DM, M.D. DPH Acute Communicable Disease Control Program

  35. CASE-PATIENTS • 11 case-patients identified • Attack rate 10% overall (N=107 players) • Attack rate 20% linemen (6 out of 30) • Highest attack rate of any position • Over-represented 55% case-patients (linemen make up 28% of team) • Seven culture-confirmed • Four hospitalized • Nine required surgical incision and drainage Nguyen DM, M.D. DPH Acute Communicable Disease Control Program

  36. CHARACTERISTICS OF INFECTIONS • Presenting Signs • Boils (64%) • “Insect bites” (18%) and folliculitis (18%) • Infection Sites • Elbow (46%) • Forearm (18%) and knee (18%) • Leg (9%) and foot (9%) • No multiple site infection • Infection not at current skin trauma site Nguyen DM, M.D. DPH Acute Communicable Disease Control Program

  37. CARRIERS • Eight (8%) MRSA positive carriers • 99 (93%) of 107 players cultured • One case-patient later identified with carriage • Only counted as case-patient in risk analysis Nguyen DM, M.D. DPH Acute Communicable Disease Control Program

  38. LABORATORY RESULTS • Outbreak strain • Genotype A: USA300 • Indistinguishable from infected players 2002 • Case-patients • Four of seven isolates available for PFGE • Indistinguishable from outbreak strain • Identical antibiotic resistance pattern Nguyen DM, M.D. DPH Acute Communicable Disease Control Program

  39. ADDITIONAL LABORATORY RESULTS • Carriers • Six of eight isolates available for PFGE • Four indistinguishable from outbreak strain • Two had different genotypes (B, C) • MRSA isolate from potential source player not available for PFGE • Identical antibiotic resistance pattern as the outbreak strain Nguyen DM, M.D. DPH Acute Communicable Disease Control Program

  40. PLAYERS’ INTERVIEWS • 10 (91%) of 11 case-patients • All enrolled in study • 6 (75%) of 8 carriers • 4 enrolled in study • 2 excluded due to different MRSA genotypes than outbreak strain • 32 controls • All enrolled in study Nguyen DM, M.D. DPH Acute Communicable Disease Control Program

  41. CASE-CONTROL STUDYRISK FACTORS FOR INFECTION Nguyen DM, M.D. DPH Acute Communicable Disease Control Program

  42. CASE-CONTROL STUDYRISK FACTORS FOR CARRIAGE Nguyen DM, M.D. DPH Acute Communicable Disease Control Program

  43. LOCKER ROOM DISTRIBUTION OF CASE-PATIENTS AND CARRIERS Training Room Field Showers Showers CASE-PATIENTS 1 S CARRIERS S=Potential Source 1=1st Case-patient Nguyen DM, M.D. DPH Acute Communicable Disease Control Program

  44. INTERIM FINDINGS • Site visit observations (9/3/03) • Delayed wound care • Sharing of equipment and towels • Sleeping players in locker room • Environmental health inspection (9/3/03) • Whirlpool tubs not properly cleaned • Laundry procedures may be inadequate Nguyen DM, M.D. DPH Acute Communicable Disease Control Program

  45. SURVEILLANCE RESULTS • Hexachlorophene showers daily x 3 weeks • No infection for four weeks after discontinuation • Three new players with CA-MRSA infections • Boil elbow (CA-MRSA infection in 2002) • Abscess chin • Folliculitis leg • Two weeks thereafter, one additional player with skin infection • Boil gluteus • Shared soap at home with roommate (case-patient) Nguyen DM, M.D. DPH Acute Communicable Disease Control Program

  46. NOVEMBER 22, 2003 • Observed real-game situation • Student trainers reusing towels between players • Players were sharing towels on sidelines • Used towels left on benches • Outcome intervention: • Team switched to disposable towels on sidelines • No new infections since, including the final two games Nguyen DM, M.D. DPH Acute Communicable Disease Control Program

  47. IMPRESSIONS • CA-MRSA may have been introduced into the team by previously infected player • Players may be at increased risk for CA-MRSA infections during training camp • Close-knit living conditions facilitate transmission • Soap sharing marker poor hygiene practices • High carriage rate • Linemen at increased risk Nguyen DM, M.D. DPH Acute Communicable Disease Control Program

  48. FURTHERMORE • Eradication of CA-MRSA may be difficult • First reported recurrence of CA-MRSA in a football team • Enforcement of proper hygiene practices may be impossible • In locker room, on the field, home • Hexachlorophene showers may decrease CA-MRSA infection on short-term basis Nguyen DM, M.D. DPH Acute Communicable Disease Control Program

  49. MRSA SKIN INFECTION Nguyen DM, M.D. DPH Acute Communicable Disease Control Program

  50. MRSA SKIN INFECTION Nguyen DM, M.D. DPH Acute Communicable Disease Control Program

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