1 / 61

Resistant Organisms and Nosocomial Infections: MRSA and CRBSI

Resistant Organisms and Nosocomial Infections: MRSA and CRBSI. Jim Pile, MD, FACP Divisions of Hospital Medicine and Infectious Diseases CWRU/MetroHealth Medical Center. Disclosures. Advisory Boards: -- Baxter -- Ortho-McNeil -- Pfizer. What We'll Cover. MRSA - Epidemiology

wilmet
Télécharger la présentation

Resistant Organisms and Nosocomial Infections: MRSA and CRBSI

An Image/Link below is provided (as is) to download presentation Download Policy: Content on the Website is provided to you AS IS for your information and personal use and may not be sold / licensed / shared on other websites without getting consent from its author. Content is provided to you AS IS for your information and personal use only. Download presentation by click this link. While downloading, if for some reason you are not able to download a presentation, the publisher may have deleted the file from their server. During download, if you can't get a presentation, the file might be deleted by the publisher.

E N D

Presentation Transcript

  1. Resistant Organisms and Nosocomial Infections: MRSA and CRBSI Jim Pile, MD, FACP Divisions of Hospital Medicine and Infectious Diseases CWRU/MetroHealth Medical Center

  2. Disclosures • Advisory Boards: -- Baxter -- Ortho-McNeil -- Pfizer

  3. What We'll Cover • MRSA - Epidemiology - Clinical aspects - Controversies surrounding vancomycin - Alternative agents • Catheter-related bloodstream infection (CRBSI) - Diagnosis - Prevention - Treatment

  4. A 35 Year Old Man . . . . • Is admitted with a several day history of a "boil" on his right upper arm. The area has become increasingly tender, and "feels like it has pus in it." He noted chills and subjective fever last night, and states he has had 2 similar episodes in the past 6 months. On exam, he has a T of 38.0º C, with BP of 138/84, HR 94. A 6 cm abscess is present on the lateral aspect of his R upper arm, with modest surrounding cellulitis. Exam is o/w normal.

  5. A 35 Year Old Man . . . . He reports throat swelling with vancomycin, and hives with sulfa drugs • Does he need antibiotic therapy, or will drainage suffice? • If "yes," which antibiotic will you choose? • Should he be cultured for MRSA colonization, and if + should decolonization be attempted?

  6. MRSA • Arose from single clone • Carry mecA gene, located on SCC • 5 types of SCCmec, which code for antibiotic resistance • Spread of SCCmec from MRSA to MSSA isolates well-documented • > 50% of Staph aureus isolates from U.S. hospitals

  7. The Emergence of CA-MRSA

  8. Community-Associated MRSA (CA-MRSA) • Most U.S. isolates are SCCmec-IV • Majority stem from single clone: USA300 strain • Almost all have Panton-Valentine leukocidin (PVL) - Purulent SSTIs - Necrotizing fasciitis - Necrotizing pneumonia

  9. 422 patients with acute, purulent SSTIs MRSA in 59% (range, 15-74%) 97% of MRSA USA300 100/175 antibiotic courses were 'wrong' Moran, NEJM 2006;355:666 Antibiotic Sensitivities: TMP/SMX: 100% Rifampin: 100% Clindamycin: 95% Tetracycline: 92% Quinolones: 60% Erythomycin: 6% Extent of the Problem: 8/04

  10. Moran et al, NEJM 2006;355:666

  11. Harbor-UCLA study found CA-MRSA made up increasing proportion of nosocomial MRSA infxs Stroger/Cook County: % of nosocomial MRSA BSI due to CA-MRSA rose from 24% in 2000-03 to 49% in 2003-06 Maree, EID 2007;13:236 Popovich, CID 2008;46:787 Changing Epidemiology of Nosocomial MRSA Infection

  12. Retrospective study of CA-MRSA from SF hospitals, SF/Boston clinics MDR CA-MRSA highly associated with MSM Raises ? of epidemic of difficult-to-treat CA-MRSA Diep, Ann Intern Med 2008;148:249 Multi-Drug Resistant CA-MRSA:More Bad News

  13. 2003 meta-analysis suggested worse outcome for MRSA Pooled hazard ratio of 1.93 for MRSA Appeared to hold up even when co-morbidities and severity of underlying illness controlled for Cosgrove, CID 2003;36:53 MRSA vs MSSA Bacteremia: Does it Matter?

  14. CA-MRSA vs CA-MSSA: Not So Much? • Single-center Taiwanese study examined outcome in pts admitted with CA-MRSA vs CA-MSSA bacteremia 2001-2006 • More SSTI and pneumonia in MRSA group, more endovascular infection in MSSA • 30-day survival: 90% (MRSA) vs 87% (MSSA); p=0.62 Wang, CID 2008;46:799

  15. Does Our Patient Require Antibiotic Therapy? • Several studies have suggested that CA-MRSA skin infections may not require abts after adequate drainage (all small/flawed) • 492 patients, 531 episodes of CA-MRSA SSTIs • 41% received inactive antibiotics • 8.5% treatment failure: 5% with active abt, 13% with inactive (OR 2.80, p=.001) Ruhe, CID 2007;44:777

  16. MRSA Colonization • Colonization typically precedes infection • Is eradication of colonization possible? • Does eradication of colonized state prevent infection? • Mupirocin + chlorhexidine + rifampin + doxycycline vs no treatment -74% vs 32% MRSA-free at 3 months -54% MRSA-free at 8 months Simor, CID 2007;44:178

  17. Should Decolonization be Attempted in Our Patient? • Criteria for attempting decolonization not well defined • Importance of CA-MRSA at extranasal sites • If attempted: -Consider multi-modality therapy -Be cognizant of AEs -Remember decay of results

  18. Whither Vancomycin (Wither Vancomycin)?

  19. Isolated in early 1950s, from S. orientalis Early preparations markedly impure Little used, due to A. advent of antistaph B- lactams B. oto, nephrotoxicity Dosing/monitoring issues Vancomycin: A Short History

  20. Vancomycin Use, 1975-1996 (Levine, CID 2006;42:S5)

  21. Vancomycin: A Suboptimal Agent for Staph aureus • Recent case-control study of MSSA bacteremia: mortality 37% with vanco, 11% with B-lactams (p<0.01) • 54 cases of MSSA bacteremic pneumonia treated with vancomycin or cloxacillin: mortality 47% vs 0% • 123 ESRD pts with MSSA bacteremia treated with vanco or cefazolin: 31% vs 13% failed treatment, OR 3.5 Kim, AAC 2008;52:192; Gonzalez CID 1999;29:1171; Stryjewski, CID 2007;44:190

  22. Time-Kill Curves for MSSA (from Stevens, CID 2006;42:S51)

  23. Mounting Concerns Over Vancomycin Effectiveness • Growing sense that efficacy against MRSA may be lessening • Emergence of VISA, VRSA --VISA: MIC 4-8 mcg/ml; VRSA: ≥ 16 mcg/ml • Phenomenon of heteroresistance (hVISA) a much bigger problem at present --Heterogeneous population of MRSA, with a sub-population unresponsive to vancomycin despite reported sensitivity

  24. MIC Uncertainties • Based on mounting data, MRSA susceptibility breakpoint for vanco changed from ≤ 4 mcg/ml to ≤ 2 mcg/ml in 2006 • Many labs have difficulty with MRSA MICs • ≤ 2 mcg/ml, however, still does not confirm true susceptibility • 15% of strains with very low MIC by reliable testing still vanco tolerant!

  25. MRSA MIC vs Vancomycin Failure Rate (Stevens, CID 2006;42:S51)

  26. agr gene cluster regulates a variety of key virulence and metabolic pathways Down-regulated function appears to confer tolerance to vancomycin; MIC may still be very low Have low vanco levels in past driven emergence? Sakoulas, CID 2006;42:S40 agr Polymorphism: Still More Trouble?

  27. MRSA Pneumonia Issues • Evidence suggests that a vancomycin trough of 4-5X the MIC may be optimal for serious MRSA infections • Penetration of vancomycin into lung only 20-30% of that achieved in serum • It may be difficult to achieve adequate concentrations of vancomycin in the lung, particularly if the MIC of the organism is relatively higher

  28. Will High-dose Vancomycin Overcome These Concerns? • 95 pts with nosocomial MRSA infections (low vs high MIC: ie, ≤ 1 mcg/ml or > 1 mcg/ml) • Study targeted aggressive vancomycin trough levels • Even with achievement of high trough levels, outcome worse in high MIC group: 62% vs 85% response (p=.02) • Uncertain whether benefit associated with high troughs Hidayat, Arch Intern Med 2006;166:2138

  29. "There is an antibiotic called mud That's proving to be quite a dud. Its provenance is jungle Its use is a bungle It just won't get rid of your crud" -Stan Deresinski, MD CID 2007;44:1543

  30. 1992 study of 101 IVDU pts with serious Staph aureus infxs: 86% cured with TMP/SMX, 98% (!) with vancomycin No failures in either group with MRSA (47%). Authors concluded vanco superior, but TMP/SMX a valuable alternative Markowitz, Ann Int Med 1992;117-390; Proctor, CID 2008;46:584 Trimethoprim/Sulfa and MRSA

  31. Retrospective study of 24 pts with MRSA infxs treated with long-acting tetracyclines: 83% cured Review of world literature: 85% of 85 pts treated with TCNs responded well Ruhe, CID 2005;40:1429 Clindamycin: most MRSA strains remain sensitive Some data suggest efficacy in children with serious MRSA infx Very limited data in adults Tetracycline and Clindamycin Treatment of MRSA

  32. Daptomycin • Cyclic lipopeptide, rapidly bactericidal against S. aureus • 2006 study of daptomycin vs standard therapy for MRSA, MSSA bacteremia -Daptomycin "not inferior" to standard treatment • 2004 cSSTI trial, dapto vs standard tx: -83% vs 84% cure • Daptomycin NOT appropriate for pneumonia Fowler, NEJM 2006;355:653 Arbeit, CID 2004;38:1673

  33. Linezolid vs Vancomycin in Nosocomial Pneumonia • RCT comparing linezolid + aztreonam to vanco + aztreonam for nosocomial pneumonia --204 evaluable pts: clinical cure (66% linezolid, 68% vanco), mortality equivalent • Continuation study: 345 patients evaluable, clinical efficacy/mortality again equivalent (cure in 68% vs 65%; mortality 20% both arms) Rubinstein, CID 2001;32:402; Wunderink, Clin Ther 2003:25:980

  34. Wunderink, RG. Linezolid vs vancomycin: analysis of 2 double-blind studies of patients with MRSA nosocomial pneumonia. Chest 2003;124:1789

  35. Other Existing Agents • Quinupristin/Dalfopristin • Tigecycline

  36. In the Pipeline • Dalbavancin • Ceftobiprole • Iclaprim • Oritavancin • Telavancin

  37. Summary • The epidemiology of MRSA continues to evolve, with CA-MRSA moving into the hospital • Most CA-MRSA strains remain sensitive to multiple antibiotics--for the moment • Vancomycin MAY still be the drug of choice for serious MRSA infections, but leaves much to be desired • Multiple alternatives exist, with more coming

  38. CRBSI: Diagnosis, Prevention and Management

  39. A 54 Year Old Woman with an Entero-cutaneous Fistula . . . . After colo-rectal surgery and receiving TPN via a Hickman catheter presents with 2 days of fever to 102° F and no other symptoms. Her T on presentation is 38.8° C, her BP/HR are essentially normal, and her catheter exit site and tunnel are not inflamed. The remainder of her physical exam is unrevealing.

  40. A 54 y.o. with an ECF . . . . • Should the catheter be removed on arrival? • If not, how will you decide whether it is the culprit? • If you decide the catheter is infected, will the offending pathogen influence your decision to remove it? • If the catheter is retained, how will you treat the infection?

  41. Scope of the Problem • > 5 million catheter-related infxs in US annually • ? 200K infections • 80K CRBSI in U.S. ICUs, estimated 28,000 deaths • CRBSI cost estimates/episode $3K-$50K • ? > $2 billion per year Raad, Lancet ID 2007;7:645; Pronovost, NEJM 2006;355:2725

  42. Pathogenesis of CRBSI • Non-tunneled CVCs: 1. Extraluminal colonization 2. Colonization of hub and catheter lumen 3. Hematogenous seeding of catheter • Tunneled CVCS: -Hub contamination/intraluminal colonization

  43. Diagnosis of CRBSI • Frequently not straightforward • Exit site inflammation: relatively specific, but very insensitive • Catheters frequently not the culprit in pts with unexplained fever (and may not be source of bacteremia) • How can non-infected CVCs be distinguished?

  44. Quantitative Blood Cultures • Blood Cxs drawn simultaneously from CVC and peripherally • ≥ 5-fold higher colony count from CVC considered diagnostic of CRBSI • Non-tunneled CVCs: sensitivity 82%, specificity 89% • Tunneled (long-term) CVCs: S/S 83%/97% • Both expensive and laborious Safdar, Ann Intern Med 2005;142:451

  45. Differential Time to Positivity • Blood cultures obtained simultaneously from CVC and peripherally • CVC culture reported + at least 2 hours before peripheral considered diagnostic for CRBSI • Sens/specif 89%/87% for short-term catheters; 90%/72% for tunneled catheters • Simple and widely available • More cost-effective than quantitative techniques Mermel CID 2001;32:1249; Safdar Ann Intern Med 2005;142:451

  46. Hand hygiene HCW education Regular surveillance of catheter site Maximum sterile barriers 2% chlorhexidine skin prep Removal of unnecessary catheters Don't routinely replace non-tunneled CVCs Use subclavian vein when possible MMWR 2002;51/RR-10 CRBSI Prevention: Antiseptic Practice

  47. MHA Keystone ICU Project • 103 ICUs in Michigan, 375K CVC days • Comprehensive unit-based education, daily goals sheet, and VAP intervention as well • Included 5 key measures: hand hygiene, full sterile barriers, chlorhexidine use, avoidance of femoral site, removing unnecessary CVCs • Central line carts created, nurses empowered, checklists used to increase compliance Pronovost NEJM 2006;355:2725

More Related