Resistant Organisms and Nosocomial Resistant Organisms and Nosocomial Infections: MRSA and CRBSIInfections: MRSA and CRBSI

Jim Pile, MD, FACPJim Pile, MD, FACP

Divisions of Hospital Medicine and Divisions of Hospital Medicine and Infectious DiseasesInfectious Diseases

CWRU/MetroHealth Medical CenterCWRU/MetroHealth Medical Center

DisclosuresDisclosures

Advisory Boards:Advisory Boards:

-- Baxter-- Baxter

-- Ortho-McNeil-- Ortho-McNeil

-- Pfizer-- Pfizer

What We'll CoverWhat We'll Cover

MRSAMRSA

-- EpidemiologyEpidemiology

-- Clinical aspectsClinical aspects

-- Controversies surrounding vancomycinControversies surrounding vancomycin

-- Alternative agentsAlternative agents

Catheter-related bloodstream infection (CRBSI)Catheter-related bloodstream infection (CRBSI)

-- DiagnosisDiagnosis

-- PreventionPrevention

-- TreatmentTreatment

A 35 Year Old Man . . . .A 35 Year Old Man . . . .

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

A 35 Year Old Man . . . .A 35 Year Old Man . . . .

He reports throat swelling with vancomycin, and He reports throat swelling with vancomycin, and hives with sulfa drugshives with sulfa drugs

Does he need antibiotic therapy, or will drainage Does he need antibiotic therapy, or will drainage suffice?suffice?

If "yes," which antibiotic will you choose?If "yes," which antibiotic will you choose?

Should he be cultured for MRSA colonization, and Should he be cultured for MRSA colonization, and if + should decolonization be attempted?if + should decolonization be attempted?

MRSAMRSA

Arose from single cloneArose from single clone

Carry mecA gene, located on SCCCarry mecA gene, located on SCC

5 types of SCCmec, which code for antibiotic 5 types of SCCmec, which code for antibiotic resistanceresistance

Spread of SCCmec from MRSA to MSSA isolates Spread of SCCmec from MRSA to MSSA isolates well-documentedwell-documented

> 50% of > 50% of Staph aureusStaph aureus isolates from U.S. hospitals isolates from U.S. hospitals

The Emergence of CA-MRSAThe Emergence of CA-MRSA

Community-Associated MRSACommunity-Associated MRSA(CA-MRSA)(CA-MRSA)

Most U.S. isolates are SCCmec-IVMost U.S. isolates are SCCmec-IV

Majority stem from single clone: USA300 strainMajority stem from single clone: USA300 strain

Almost all have Panton-Valentine leukocidin Almost all have Panton-Valentine leukocidin (PVL)(PVL)

- Purulent SSTIs- Purulent SSTIs

- Necrotizing fasciitis- Necrotizing fasciitis

- Necrotizing pneumonia- Necrotizing pneumonia

Extent of the Problem: 8/04Extent of the Problem: 8/04

422 patients with acute, 422 patients with acute, purulent SSTIspurulent SSTIs

MRSA in 59% (range, 15-MRSA in 59% (range, 15-74%)74%)

97% of MRSA USA30097% of MRSA USA300

100/175 antibiotic courses 100/175 antibiotic courses were 'wrong'were 'wrong'

Moran, NEJM 2006;355:666Moran, NEJM 2006;355:666

Antibiotic Antibiotic SensitivitiesSensitivities::

TMP/SMX: 100%TMP/SMX: 100%

Rifampin: 100%Rifampin: 100%

Clindamycin: 95%Clindamycin: 95%

Tetracycline: 92%Tetracycline: 92%

Quinolones: 60%Quinolones: 60%

Erythomycin: 6%Erythomycin: 6%

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

Changing Epidemiology of Changing Epidemiology of Nosocomial MRSA InfectionNosocomial MRSA Infection

Harbor-UCLA study found Harbor-UCLA study found CA-MRSA made up CA-MRSA made up increasing proportion of increasing proportion of nosocomial MRSA infxsnosocomial MRSA infxs

Stroger/Cook County: % of Stroger/Cook County: % of nosocomial MRSA BSI due nosocomial MRSA BSI due to CA-MRSA rose from 24% to CA-MRSA rose from 24% in 2000-03 to 49% in 2003-06in 2000-03 to 49% in 2003-06

Maree, EID 2007;13:236Maree, EID 2007;13:236

Popovich, CID 2008;46:787Popovich, CID 2008;46:787

Multi-Drug Resistant CA-MRSA:Multi-Drug Resistant CA-MRSA:More Bad NewsMore Bad News

Retrospective study of CA-Retrospective study of CA-MRSA from SF hospitals, MRSA from SF hospitals, SF/Boston clinicsSF/Boston clinics

MDR CA-MRSA highly MDR CA-MRSA highly associated with MSMassociated with MSM

Raises ? of epidemic of Raises ? of epidemic of difficult-to-treat CA-MRSAdifficult-to-treat CA-MRSA

Diep, Ann Intern Med 2008;148:249Diep, Ann Intern Med 2008;148:249

MRSA vs MSSA Bacteremia: MRSA vs MSSA Bacteremia: Does it Matter?Does it Matter?

2003 meta-analysis 2003 meta-analysis suggested worse outcome suggested worse outcome for MRSAfor MRSA

Pooled hazard ratio of 1.93 Pooled hazard ratio of 1.93 for MRSAfor MRSA

Appeared to hold up even Appeared to hold up even when co-morbidities and when co-morbidities and severity of underlying severity of underlying illness controlled forillness controlled for

Cosgrove, CID 2003;36:53Cosgrove, CID 2003;36:53

CA-MRSA vs CA-MSSA: Not CA-MRSA vs CA-MSSA: Not So Much?So Much?

Single-center Taiwanese study examined outcome Single-center Taiwanese study examined outcome in pts admitted with CA-MRSA vs CA-MSSA in pts admitted with CA-MRSA vs CA-MSSA bacteremia 2001-2006bacteremia 2001-2006

More SSTI and pneumonia in MRSA group, more More SSTI and pneumonia in MRSA group, more endovascular infection in MSSAendovascular infection in MSSA

30-day survival: 90% (MRSA) vs 87% (MSSA); 30-day survival: 90% (MRSA) vs 87% (MSSA); p=0.62p=0.62

Wang, CID 2008;46:799Wang, CID 2008;46:799

Does Our Patient Require Does Our Patient Require Antibiotic Therapy?Antibiotic Therapy?

Several studies have suggested that CA-MRSA Several studies have suggested that CA-MRSA skin infections may not require abts after skin infections may not require abts after adequate drainage (all small/flawed)adequate drainage (all small/flawed)

492 patients, 531 episodes of CA-MRSA SSTIs492 patients, 531 episodes of CA-MRSA SSTIs

41% received inactive antibiotics41% received inactive antibiotics

8.5% treatment failure: 5% with active abt, 13% 8.5% treatment failure: 5% with active abt, 13% with inactive (OR 2.80, p=.001)with inactive (OR 2.80, p=.001)

Ruhe, CID 2007;44:777Ruhe, CID 2007;44:777

MRSA ColonizationMRSA Colonization

Colonization typically precedes infectionColonization typically precedes infection

Is eradication of colonization possible?Is eradication of colonization possible?

Does eradication of colonized state prevent infection?Does eradication of colonized state prevent infection?

Mupirocin + chlorhexidine + rifampin + doxycycline vs Mupirocin + chlorhexidine + rifampin + doxycycline vs no treatmentno treatment

-74% vs 32% MRSA-free at 3 months-74% vs 32% MRSA-free at 3 months

-54% MRSA-free at 8 months-54% MRSA-free at 8 months

Simor, CID 2007;44:178Simor, CID 2007;44:178

Should Decolonization be Should Decolonization be Attempted in Our Patient?Attempted in Our Patient?

Criteria for attempting decolonization not well Criteria for attempting decolonization not well defineddefined

Importance of CA-MRSA at extranasal sites Importance of CA-MRSA at extranasal sites

If attempted:If attempted:

-Consider multi-modality therapy-Consider multi-modality therapy

-Be cognizant of AEs-Be cognizant of AEs

-Remember decay of results-Remember decay of results

Whither Vancomycin (Wither Whither Vancomycin (Wither Vancomycin)?Vancomycin)?

Vancomycin: A Short HistoryVancomycin: A Short History

Isolated in early 1950s, Isolated in early 1950s, from from S. orientalisS. orientalis

Early preparations Early preparations markedly impuremarkedly impure

Little used, due to Little used, due to

A. advent of antistaph A. advent of antistaph

B-B- lactamslactams

B. oto, nephrotoxicityB. oto, nephrotoxicity

Dosing/monitoring issuesDosing/monitoring issues

Vancomycin Use, 1975-1996 (Vancomycin Use, 1975-1996 (Levine, Levine,

CID 2006;42:S5CID 2006;42:S5))

Vancomycin: A Suboptimal Vancomycin: A Suboptimal Agent for Agent for Staph aureusStaph aureus

Recent case-control study of MSSA bacteremia: Recent case-control study of MSSA bacteremia: mortality 37% with vanco, 11% with B-lactams (p<0.01)mortality 37% with vanco, 11% with B-lactams (p<0.01)

54 cases of MSSA bacteremic pneumonia treated with 54 cases of MSSA bacteremic pneumonia treated with vancomycin or cloxacillin: mortality 47% vs 0%vancomycin or cloxacillin: mortality 47% vs 0%

123 ESRD pts with MSSA bacteremia treated with vanco 123 ESRD pts with MSSA bacteremia treated with vanco or cefazolin: 31% vs 13% failed treatment, OR 3.5or cefazolin: 31% vs 13% failed treatment, OR 3.5

Kim, AAC 2008;52:192; Gonzalez CID 1999;29:1171; Stryjewski, CID Kim, AAC 2008;52:192; Gonzalez CID 1999;29:1171; Stryjewski, CID 2007;44:1902007;44:190

Time-Kill Curves for MSSA (Time-Kill Curves for MSSA (from from

Stevens, CID 2006;42:S51Stevens, CID 2006;42:S51))

Mounting Concerns Over Mounting Concerns Over Vancomycin EffectivenessVancomycin Effectiveness

Growing sense that efficacy against MRSA may be Growing sense that efficacy against MRSA may be lesseninglessening

Emergence of VISA, VRSAEmergence of VISA, VRSA

--VISA: MIC 4-8 mcg/ml; VRSA: --VISA: MIC 4-8 mcg/ml; VRSA: ≥ 16 mcg/ml≥ 16 mcg/ml

Phenomenon of heteroresistance (hVISA) a much Phenomenon of heteroresistance (hVISA) a much bigger problem at present bigger problem at present

----Heterogeneous population of MRSA, with a Heterogeneous population of MRSA, with a sub-sub-

population unresponsive to vancomycin despite population unresponsive to vancomycin despite reported reported sensitivitysensitivity

MIC UncertaintiesMIC Uncertainties

Based on mounting data, MRSA susceptibility Based on mounting data, MRSA susceptibility breakpoint for vanco changed from breakpoint for vanco changed from ≤ 4 mcg/ml to ≤ 4 mcg/ml to ≤ 2 mcg/ml in 2006≤ 2 mcg/ml in 2006

Many labs have difficulty with MRSA MICsMany labs have difficulty with MRSA MICs

≤ ≤ 2 mcg/ml, however, still does not confirm true 2 mcg/ml, however, still does not confirm true susceptibilitysusceptibility

15% of strains with very low MIC by reliable 15% of strains with very low MIC by reliable testing still vanco tolerant!testing still vanco tolerant!

MRSA MIC vs Vancomycin MRSA MIC vs Vancomycin Failure Rate (Failure Rate (Stevens, CID 2006;42:S51Stevens, CID 2006;42:S51))

agragr Polymorphism: Still More Polymorphism: Still More Trouble?Trouble?

agr agr gene cluster regulates gene cluster regulates a variety of key virulence a variety of key virulence and metabolic pathwaysand metabolic pathways

Down-regulated function Down-regulated function appears to confer tolerance appears to confer tolerance to vancomycin; MIC may to vancomycin; MIC may still be very lowstill be very low

Have low vanco levels in Have low vanco levels in past driven emergence?past driven emergence?

Sakoulas, CID 2006;42:S40Sakoulas, CID 2006;42:S40

MRSA Pneumonia IssuesMRSA Pneumonia Issues

Evidence suggests that a vancomycin trough of 4-5X Evidence suggests that a vancomycin trough of 4-5X the MIC may be optimal for serious MRSA infectionsthe MIC may be optimal for serious MRSA infections

Penetration of vancomycin into lung only 20-30% of Penetration of vancomycin into lung only 20-30% of that achieved in serumthat achieved in serum

It may be difficult to achieve adequate It may be difficult to achieve adequate concentrations of vancomycin in the lung, concentrations of vancomycin in the lung, particularly if the MIC of the organism is relatively particularly if the MIC of the organism is relatively higherhigher

Will High-dose Vancomycin Will High-dose Vancomycin Overcome These Concerns?Overcome These Concerns?

95 pts with nosocomial MRSA infections (low vs high 95 pts with nosocomial MRSA infections (low vs high MIC: ie, MIC: ie, ≤ 1 mcg/ml or > 1 mcg/ml)≤ 1 mcg/ml or > 1 mcg/ml)

Study targeted aggressive vancomycin trough levelsStudy targeted aggressive vancomycin trough levels

Even with achievement of high trough levels, Even with achievement of high trough levels, outcome worse in high MIC group: 62% vs 85% outcome worse in high MIC group: 62% vs 85% response (p=.02)response (p=.02)

Uncertain whether benefit associated with high Uncertain whether benefit associated with high troughstroughs Hidayat, Arch Intern Med 2006;166:2138Hidayat, Arch Intern Med 2006;166:2138

"There is an antibiotic called mud"There is an antibiotic called mud

That's proving to be quite a dud.That's proving to be quite a dud.

Its provenance is jungleIts provenance is jungle

Its use is a bungleIts use is a bungle

It just won't get rid of your crud"It just won't get rid of your crud"

-Stan Deresinski, MD-Stan Deresinski, MD

CID 2007;44:1543CID 2007;44:1543

Trimethoprim/Sulfa Trimethoprim/Sulfa and MRSAand MRSA

1992 study of 101 IVDU pts with 1992 study of 101 IVDU pts with serious Staph aureus infxs: serious Staph aureus infxs: 86% cured with TMP/SMX, 98% 86% cured with TMP/SMX, 98% (!) with vancomycin(!) with vancomycin

No failures in either group with No failures in either group with MRSA (47%). Authors MRSA (47%). Authors concluded vanco superior, but concluded vanco superior, but TMP/SMX a valuable alternativeTMP/SMX a valuable alternative

Markowitz, Ann Int Med 1992;117-Markowitz, Ann Int Med 1992;117-390; Proctor, CID 2008;46:584390; Proctor, CID 2008;46:584

Tetracycline and Clindamycin Tetracycline and Clindamycin Treatment of MRSATreatment of MRSA

Retrospective study of 24 Retrospective study of 24 pts with MRSA infxs pts with MRSA infxs treated with long-acting treated with long-acting tetracyclines: 83% cured tetracyclines: 83% cured

Review of world literature: Review of world literature: 85% of 85 pts treated with 85% of 85 pts treated with TCNs responded wellTCNs responded well

Ruhe, CID 2005;40:1429Ruhe, CID 2005;40:1429

Clindamycin: most MRSA Clindamycin: most MRSA strains remain sensitivestrains remain sensitive

Some data suggest Some data suggest efficacy in children with efficacy in children with serious MRSA infxserious MRSA infx

Very limited data in Very limited data in adults adults

DaptomycinDaptomycin

Cyclic lipopeptide, rapidly bactericidal against Cyclic lipopeptide, rapidly bactericidal against S. S. aureusaureus

2006 study of daptomycin vs standard therapy for 2006 study of daptomycin vs standard therapy for MRSA, MSSA bacteremiaMRSA, MSSA bacteremia

-Daptomycin "not inferior" to standard treatment-Daptomycin "not inferior" to standard treatment

2004 cSSTI trial, dapto vs standard tx: 2004 cSSTI trial, dapto vs standard tx:

-83% vs 84% cure-83% vs 84% cure

Daptomycin NOT appropriate for pneumonia Daptomycin NOT appropriate for pneumonia Fowler, NEJM 2006;355:653Fowler, NEJM 2006;355:653 Arbeit, CID 2004;38:1673Arbeit, CID 2004;38:1673

Linezolid vs Vancomycin in Linezolid vs Vancomycin in Nosocomial PneumoniaNosocomial Pneumonia

RCT comparing linezolid + aztreonam to vanco + RCT comparing linezolid + aztreonam to vanco + aztreonam for nosocomial pneumoniaaztreonam for nosocomial pneumonia

--204 evaluable pts: clinical cure (66% --204 evaluable pts: clinical cure (66% linezolid, 68% vanco), mortality equivalentlinezolid, 68% vanco), mortality equivalent

Continuation study: 345 patients evaluable, Continuation study: 345 patients evaluable, clinical efficacy/mortality again equivalent (cure clinical efficacy/mortality again equivalent (cure in 68% vs 65%; mortality 20% both arms)in 68% vs 65%; mortality 20% both arms)

Rubinstein, CID 2001;32:402; Wunderink, Clin Ther 2003:25:980Rubinstein, CID 2001;32:402; Wunderink, Clin Ther 2003:25:980

Wunderink, RG. Linezolid vs vancomycin: Wunderink, RG. Linezolid vs vancomycin: analysis of 2 double-blind studies of patients analysis of 2 double-blind studies of patients with MRSA nosocomial pneumonia. Chest with MRSA nosocomial pneumonia. Chest 2003;124:17892003;124:1789

Other Existing AgentsOther Existing Agents

Quinupristin/DalfopristinQuinupristin/Dalfopristin

TigecyclineTigecycline

In the PipelineIn the Pipeline

DalbavancinDalbavancin

CeftobiproleCeftobiprole

IclaprimIclaprim

OritavancinOritavancin

TelavancinTelavancin

SummarySummary

The epidemiology of MRSA continues to evolve, The epidemiology of MRSA continues to evolve, with CA-MRSA moving into the hospital with CA-MRSA moving into the hospital

Most CA-MRSA strains remain sensitive to Most CA-MRSA strains remain sensitive to multiple antibiotics--for the momentmultiple antibiotics--for the moment

Vancomycin MAY still be the drug of choice for Vancomycin MAY still be the drug of choice for serious MRSA infections, but leaves much to be serious MRSA infections, but leaves much to be desireddesired

Multiple alternatives exist, with more comingMultiple alternatives exist, with more coming

CRBSI: Diagnosis, Prevention CRBSI: Diagnosis, Prevention and Managementand Management

A 54 Year Old Woman with an A 54 Year Old Woman with an Entero-cutaneous Fistula . . . .Entero-cutaneous Fistula . . . .

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

A 54 y.o. with an ECF . . . .A 54 y.o. with an ECF . . . .

Should the catheter be removed on arrival?Should the catheter be removed on arrival?

If not, how will you decide whether it is the If not, how will you decide whether it is the culprit?culprit?

If you decide the catheter is infected, will the If you decide the catheter is infected, will the offending pathogen influence your decision to offending pathogen influence your decision to remove it?remove it?

If the catheter is retained, how will you treat the If the catheter is retained, how will you treat the infection?infection?

Scope of the ProblemScope of the Problem

> 5 million catheter-related infxs in US annually> 5 million catheter-related infxs in US annually

? 200K infections? 200K infections

80K CRBSI in U.S. ICUs, estimated 28,000 80K CRBSI in U.S. ICUs, estimated 28,000 deathsdeaths

CRBSI cost estimates/episode $3K-$50KCRBSI cost estimates/episode $3K-$50K

? > $2 billion per year? > $2 billion per year

Raad, Lancet ID 2007;7:645; Pronovost, NEJM 2006;355:2725Raad, Lancet ID 2007;7:645; Pronovost, NEJM 2006;355:2725

Pathogenesis of CRBSIPathogenesis of CRBSI

Non-tunneled CVCs:Non-tunneled CVCs:

1. Extraluminal colonization1. Extraluminal colonization

2. Colonization of hub and catheter lumen2. Colonization of hub and catheter lumen

3. Hematogenous seeding of catheter3. Hematogenous seeding of catheter

Tunneled CVCS:Tunneled CVCS:

-Hub contamination/intraluminal colonization-Hub contamination/intraluminal colonization

Diagnosis of CRBSIDiagnosis of CRBSI

Frequently not straightforwardFrequently not straightforward

Exit site inflammation: relatively specific, but Exit site inflammation: relatively specific, but very insensitivevery insensitive

Catheters frequently not the culprit in pts with Catheters frequently not the culprit in pts with unexplained fever (and may not be source of unexplained fever (and may not be source of bacteremia)bacteremia)

How can non-infected CVCs be distinguished?How can non-infected CVCs be distinguished?

Quantitative Blood CulturesQuantitative Blood Cultures

Blood Cxs drawn simultaneously from CVC and Blood Cxs drawn simultaneously from CVC and peripherallyperipherally

≥ ≥ 5-fold higher colony count from CVC considered 5-fold higher colony count from CVC considered diagnostic of CRBSIdiagnostic of CRBSI

Non-tunneled CVCs: sensitivity 82%, specificity 89%Non-tunneled CVCs: sensitivity 82%, specificity 89%

Tunneled (long-term) CVCs: S/S 83%/97%Tunneled (long-term) CVCs: S/S 83%/97%

Both expensive and laboriousBoth expensive and laborious

Safdar, Ann Intern Med 2005;142:451Safdar, Ann Intern Med 2005;142:451

Differential Time to PositivityDifferential Time to Positivity

Blood cultures obtained Blood cultures obtained simultaneouslysimultaneously from CVC and from CVC and peripherallyperipherally

CVC culture reported + at least 2 hours before peripheral CVC culture reported + at least 2 hours before peripheral considered diagnostic for CRBSIconsidered diagnostic for CRBSI

Sens/specif 89%/87% for short-term catheters; 90%/72% Sens/specif 89%/87% for short-term catheters; 90%/72% for tunneled cathetersfor tunneled catheters

Simple and widely availableSimple and widely available

More cost-effective than quantitative techniquesMore cost-effective than quantitative techniques

Mermel CID 2001;32:1249; Safdar Ann Intern Med 2005;142:451Mermel CID 2001;32:1249; Safdar Ann Intern Med 2005;142:451

CRBSI Prevention: Antiseptic CRBSI Prevention: Antiseptic PracticePractice

Hand hygieneHand hygiene

HCW educationHCW education

Regular surveillance of Regular surveillance of catheter sitecatheter site

Maximum sterile barriersMaximum sterile barriers

2% chlorhexidine skin 2% chlorhexidine skin prepprep

Removal of unnecessary Removal of unnecessary catheterscatheters

Don't routinely replace Don't routinely replace non-tunneled CVCsnon-tunneled CVCs

Use subclavian vein Use subclavian vein when possiblewhen possible

MMWR 2002;51/RR-10MMWR 2002;51/RR-10

MHA Keystone ICU ProjectMHA Keystone ICU Project

103 ICUs in Michigan, 375K CVC days103 ICUs in Michigan, 375K CVC days

Comprehensive unit-based education, daily goals sheet, Comprehensive unit-based education, daily goals sheet, and VAP intervention as welland VAP intervention as well

Included 5 key measures: hand hygiene, full sterile Included 5 key measures: hand hygiene, full sterile barriers, chlorhexidine use, avoidance of femoral site, barriers, chlorhexidine use, avoidance of femoral site, removing unnecessary CVCsremoving unnecessary CVCs

Central line carts created, nurses empowered, checklists Central line carts created, nurses empowered, checklists used to increase complianceused to increase compliance

Pronovost NEJM 2006;355:2725Pronovost NEJM 2006;355:2725

Keystone ICU StudyKeystone ICU Study

Significant reduction in Significant reduction in rate of CRBSI in quarter rate of CRBSI in quarter of implementationof implementation

Results sustained over Results sustained over duration of studyduration of study

CRBSI fell from mean of CRBSI fell from mean of 7.7 to 1.4 infections per 7.7 to 1.4 infections per catheter daycatheter day

"The structure of the intervention involved daily "The structure of the intervention involved daily commitment to a culture of safety . . . . We can no commitment to a culture of safety . . . . We can no longer accept the variations in safety culture, longer accept the variations in safety culture, behavior, or systems of practice that have plagued behavior, or systems of practice that have plagued medical care for decades. Imagine the effect if all medical care for decades. Imagine the effect if all 6000 acute care hospitals in the US were to show a 6000 acute care hospitals in the US were to show a similar commitment and discipline."similar commitment and discipline."

-Richard Wenzel, MD-Richard Wenzel, MD

Antimicrobial CathetersAntimicrobial Catheters

Silver-impregnated Silver-impregnated catheterscatheters

Antiseptic cathetersAntiseptic catheters

Antibiotic-coated catheterAntibiotic-coated catheter

CDC: "consider" use of CDC: "consider" use of impregnated catheter impregnated catheter when expected to be in when expected to be in place > 5 daysplace > 5 days

CRBSI Management: Key CRBSI Management: Key QuestionsQuestions

1. Is the catheter truly the culprit?1. Is the catheter truly the culprit?

2. Does the catheter need to be removed?2. Does the catheter need to be removed?

3. What type of antibiotic therapy?3. What type of antibiotic therapy?

4. How long should the infection be treated?4. How long should the infection be treated?

Deciding When to Remove the Deciding When to Remove the CatheterCatheter

Tunneled vs non-tunneled CVCTunneled vs non-tunneled CVC

Hemodynamic instabilityHemodynamic instability

Identity of pathogenIdentity of pathogen

Complicated infectionComplicated infection

Tunnel/port pocket infectionsTunnel/port pocket infections

Antibiotic Lock TherapyAntibiotic Lock Therapy

Failure appears to frequently relate to inability to kill Failure appears to frequently relate to inability to kill organisms in luminal biofilmorganisms in luminal biofilm

Antibiotic concentration may need to be 100-1000X Antibiotic concentration may need to be 100-1000X greater to kill bacteria in biofilmgreater to kill bacteria in biofilm

ALT: 2-5 cc of antibiotic solution instilled into ALT: 2-5 cc of antibiotic solution instilled into lumen(s) and "locked"lumen(s) and "locked"

83% cure rate vs 67% with conventional therapy only 83% cure rate vs 67% with conventional therapy only

Mermel CID 2001;32:1249Mermel CID 2001;32:1249

Coagulase Negative StaphCoagulase Negative Staph

Leading cause of CRBSI in most seriesLeading cause of CRBSI in most series

Up to 80% of catheters salvageableUp to 80% of catheters salvageable

If catheter retained: 7 days systemic therapy, If catheter retained: 7 days systemic therapy, 10-14 days lock therapy (ALT)10-14 days lock therapy (ALT)

Catheter removed: 5-7 days systemic therapyCatheter removed: 5-7 days systemic therapy

Weekly dalbavancin therapy promisingWeekly dalbavancin therapy promising

Mermel CID 2001;32:1249; Raad CID 2005;40:374Mermel CID 2001;32:1249; Raad CID 2005;40:374

Staph aureusStaph aureus

Strong association with metastatic infectionStrong association with metastatic infection

23% of S. aureus CRBSI had endocarditis in 1 23% of S. aureus CRBSI had endocarditis in 1 studystudy

Faster sx resolution/less relapse with CVC Faster sx resolution/less relapse with CVC removalremoval

Uncomplicated infxs with catheter retention: 14 Uncomplicated infxs with catheter retention: 14 days systemic + abt lock therapydays systemic + abt lock therapy

Fowler JACC 1997;30:1072; Mermel CID 2001;32:1249Fowler JACC 1997;30:1072; Mermel CID 2001;32:1249

Gram Negative BacilliGram Negative Bacilli

Recent study reported cure in 13/15 HD catheter infxs Recent study reported cure in 13/15 HD catheter infxs (87%) with systemic + lock tx(87%) with systemic + lock tx

"Tough" pathogens ("Tough" pathogens (S. maltophilia, B. cepacia, S. maltophilia, B. cepacia, Acinetobacter, Acinetobacter, non-non-aeruginosa Pseudomonasaeruginosa Pseudomonas) appear ) appear less likely to respondless likely to respond

Catheter removed: 7-14 days systemic abtsCatheter removed: 7-14 days systemic abts

Catheter retained: 14 days systemic + ALT txCatheter retained: 14 days systemic + ALT tx

Poole, Nephrol Dial Transplant 2004;19:1237; Raad Lancet ID 2007;7:645;Poole, Nephrol Dial Transplant 2004;19:1237; Raad Lancet ID 2007;7:645;

Mermel CID 2001;32:1249Mermel CID 2001;32:1249

Candida sppCandida spp

Multiple prospective studies support worse Multiple prospective studies support worse outcome with attempted CVC salvageoutcome with attempted CVC salvage

70% failure rate even with systemic + lock tx70% failure rate even with systemic + lock tx

IDSA guidelines suggest amphotericin B for IDSA guidelines suggest amphotericin B for unstable patientsunstable patients

Echinocandin for Echinocandin for C. glabrata C. glabrata oror krusei krusei

Treat for 2 weeks after last + BCxTreat for 2 weeks after last + BCx

SummarySummary

Decision to attempt CVC salvage should be Decision to attempt CVC salvage should be made case-by-case, but many can be savedmade case-by-case, but many can be saved

Many (most?) Many (most?) S. aureus S. aureus and virtually all Candida and virtually all Candida infections mandate CVC removalinfections mandate CVC removal

Antibiotic lock therapy is promising, and Antibiotic lock therapy is promising, and probably still underutilizedprobably still underutilized

Revised guidelines in progress! Revised guidelines in progress!