Nosocomial (Healthcare Associated) Infections

Daniel J. Diekema, MD, FACP

• Financial disclosure: Research funding received from Merck, Pfizer, Astellas, Cerexa, PurThread Technologies, bioMerieux, Innovative Biosensors, Inc.

No products manufactured by the above companies will be discussed during this presentation.

Nosocomial (Healthcare Associated) Infections

Clinical Questions: • What are the most common hospital or healthcare-associated infections?

• What prevention measures can be used to prevent these infections?

• What basic infection control procedures are relevant to the hospital-based physician?

Focus will be on prevention, with most time devoted to infections with the greatest morbidity and mortality.

Nosocomial Infection Definition

h Acquired in a hospital or healthcare facility (“healthcare-associated”)

h Not present or incubating at admission h for most bacterial infections, onset of

symptoms >48 hours after admission h symptoms may not present until after

discharge

Nosocomial Infections: An ongoing epidemic

h 5-10% of all inpatients acquire infection during hospitalization:  Up to 2 million persons infected annually  Responsible for up to 90K deaths/year   Increase length of stay, increase costs →24 days, up to $28K per nosocomial ICU

bloodstream infection →$30 billion in direct costs to US hospitals

–  Pittet D, et al. JAMA 1994;271:1598-1601. –  http://www.cdc.gov/ncidod/dhqp/pdf/Scott_CostPaper.pdf

Nosocomial Infections Distribution by site of infection

Urinary Tract

Surgical Site

Lung

Bloodstream

Other: C. difficile

Nosocomial Bloodstream Infection h CDC: 31K deaths annually from nosocomial BSI h Most (>85%) are associated with CVCs h 15 million CVC days/year in US ICUs h If rate of BSI is 5.3 per 1000 CVC days:

h 80,000 catheter-associated BSI (CA-BSI) h If attributable mortality is 12-25%:

h 10K-20K deaths per year from CA-BSI

Mermel L. Ann Intern Med 2000;132:391. CDC. MMWR 51;RR-101 Klevens, et al. Pub Health Rep 2007;122:160-6

Sources of Central-Line Associated Bloodstream Infections (CLABSI)

h Migration of organisms from the catheter-skin interface over the external surface of the catheter

h Migration of organisms from the catheter hub down the internal surface of the catheter

h Hematogenous seeding of the catheter tip

h Contamination on insertion h Contaminated infusates

Prevention strategies focus on controlling bacterial flora at the insertion site…

CLABSI: Prevention “bundles”

h Institute for Healthcare Improvement, VA ICU collaborative, Canadian ICU collaborative, etc….

h Incorporate five practices for which the evidence strongly supports reduction in CA-BSI: h Daily review of need for central line h Hand hygiene h Use of maximal sterile barriers for insertion h Chlorhexidine for skin antisepsis h Use subclavian or IJ as preferred insertion site

CLABSI: Prevention “bundles”

h Keystone Project, over 100 Michigan ICUs h ↓ mean CA-BSI rate from 7.7 to 1.4 per

1000 catheter-days (66% reduction) h Reduced median to “zero” h Reduction persisted out to 18 months

•  Quasi-experimental design, Hawthorne effect, incomplete data collection, little process information

•  But still………

Pronovost P, et al. NEJM 2006;355:2725-32.

Keystone Project: 36 month follow up

Pronovost, et al. BMJ 2010;340:c309

Preventing CLABSI: Where do we go from here?

h Unanswered questions: h How to sustain a BSI reduction? h What is the role of new technologies

and approaches? •  Antimicrobial devices/dressings, antimicrobial

lock solutions, etc.

h How should we move the reduction outside of the ICU environment?

Preventing CLABSI: Sustaining a reduction

h Short term, education-based interventions extinguish over time!

h A durable change in process and culture is required (↓ complexity) h Checklists, process measures h Empower staff to stop insertion h Unit leadership and buy-in h Support from hospital leadership

CLABSI: New approaches for prevention

h Where can we put more antimicrobials? h Catheters

•  Antimicrobial impregnated catheters •  Antimicrobial lock solutions

h Dressings •  CHG impregnated dressings

h Patients •  CHG bathing (“source control”)

CHG impregnated dressings: A randomized, controlled trial

Timsit, et al. JAMA 2009;301:1231-41.

h Randomized controlled trial of CHG impregnated sponge dressing vs. standard dressings

h Outcomes: catheter colonization, CA-BSI, “clinical sepsis”

h 1653 pts from 7 ICUs randomized h 4 groups, stratified by dressing type and

3 vs. 7 day dressing changes

CHG impregnated dressings: A randomized, controlled trial

Timsit, et al. JAMA 2009;301:1231-41.

Incidence/1000 catheter days ITT analysis

Outcome Control CHG HR [95% CI]

Catheter colonization

15.8 6.3 0.4 [0.3-0.5]

CA-BSI 1.3 0.4 0.2 [0.1-0.7]

New approaches for prevention: CHG bathing (“Source Control”) h Multicenter study (5 centers, 6 ICUs)

Montecalvo et al. Am J Med 2012;125:505-511.

Monitored CHG bathing

Unmonitored CHG bathing

CLABSI: Applying prevention methods

?

Hand hygiene Daily CVC review Optimal insertion site MSB for insertion 2% CHG for skin prep CHG bathing

CHG dressings AM impreg CVC AM lock prophylaxis

CA-BSI rate

Time

Pressures will increase to address this fraction:

Are all infections preventable?

h One day prevalence survey of central venous catheter use at 6 large academic healthcare centers h 29% of 2459 patients had CVCs h 43-80% of ICU patients h 7-39% of non-ICU patients

h 70% of CVCs were in non-ICU patients

CLABSI: Moving prevention out of the ICU

Climo M, et al. Infect Cont Hosp Epidemiol 2003;24:942-5.

h Start with a bundle of 5 proven practices h Culture of safety, unit leadership

•  Empower nursing staff

h ↓ complexity, ↑ redundancy •  Line placement kits/carts, checklists

h Apply newer approaches as needed h CHG dressings, bathing

h Move prevention out of the ICU h Line placement and care teams

Preventing CLABSI: Summary

Ventilator Associated Pneumonia h Most common nosocomial infection in the ICU

h 25% of all NI reported from Med-Surg ICUs h Affects between 9-27% of intubated patients

h Increased morbidity, mortality and LOS h Increases LOS by 7-9 days h Increases hospital costs by $11- 40K h Attributable mortality from 10-25%

Hidron AI, et al. Infect Cont Hosp Epidemiol 2008;29:996. Safdar N, et al. Crit Care Med 2005;33:2184-93. Rello J, et al. Chest 2002;122:2115-2121. Rello J, et al. Chest 1991;100:439-444.

Limitations of VAP Definitions

h One third with VAP have no autopsy evidence h One fourth without VAP have autopsy evidence h Aspects of definition are subjective h Conditions with similar clinical findings:

h atelectasis, pulmonary edema, thromboembolic dz, ARDS, alveolar hemorrhage, hypersensitivity pneumonitis, pulmonary contusion, combinations of disorders (e.g. BSI + pulmonary edema)

Klompas M. JAMA 2007;297:1583.

“The wards and the post-mortem room show a very striking contrast in their pneumonia statistics…”

Sir William Osler, 1907

h Lower VAP rates could mean: h Excellent care, fewer actual infections h Change in application of definition or

diagnostic practices

Klompas M, Platt R. Ann Intern Med 2007;147:803-805. Klompas M. Thorax 2009;64:463-65

“Subjectivity and inaccuracy in the VAP definition allow hospitals to undertake practices that will markedly decrease their VAP rates and yet do little or nothing to improve patient outcomes.”

Pathogenesis of VAP h Entry of pathogens into lower respiratory

tract → colonization → infection h Leakage/aspiration around ET tube

• Biofilm adherent to ET tube h Inhalation of contaminated aerosols h Direct inoculation h Hematogenous spread

h Infection often multifocal h Sampling issues?

Niederman, Craven, et al. Am J Resp Crit Care Med 2005;171:388-416.

h Facilitate/accelerate weaning h Protocols require adequate staffing h Reintubation also increases VAP risk

h Use non-invasive ventilation when possible h Positive pressure ventilation/facemask h COPD exacerbations, acute hypoxemic

respiratory failure, immunocompromise with inflitrates and respiratory failure

Preventing VAP: ↓ use of mechanical ventilation

Niederman, Craven, et al. Am J Resp Crit Care Med 2005;171:388-416.

Multifactorial Interventions: The “ventilator bundle”

h Implementation of those interventions with the supporting evidence/feasibility h Hand Hygiene h Elevation of HOB h “Sedation vacation” each day h Assessment of readiness to wean h PUD and DVT prophylaxis h Chlorhexidine oral care (new)

www.ihi.org

Spontaneous awakening trial + spontaneous breathing trial

Girard et al. Lancet 2008;371:126-34.

h Intervention arm had fewer: h Vent days h ICU days h Hospital days h Deaths

h No difference in reintubation rates

Reducing aspiration risk: Continuous subglottic suctioning

h Meta-analysis, 13 studies, 2442 pts h VAP RR = 0.55;

95% CI 0.46-0.66 h Decreased ICU

LOS by ~1.5 days, MV by ~1 day

Muscedere et al. Crit Care Med 2011;39:1985-91.

VAP rates appear to be declining across the country….

Courtesy of Shelley Magill, MD, PhD (CDC/NHSN)

h VAP is common, and increases LOS, hospital costs, and mortality

h Better diagnostics for VAP are needed to reduce misclassification

h VAP prevention literature is murky, but: h IHI bundle + oral care with chlorhexidine h Continuous subglottic suctioning h Other approaches (silver coated ET tubes,

selective DD, etc.) if rate remains high

VAP Prevention: Summary

Clostridium difficile h Anaerobic, spore-

forming bacillus

h Gram-positive

h Present in soil and environment

h Hospitals are major reservoirs

C. difficile associated disease (CDAD)

Asymptomatic colonization

Diarrhea (mild to severe)

Colitis +/- pseudomembranes

Toxic megacolon

Colonic perforation/peritonitis

Sepsis & acute abdomen without diarrhea

Low severity

High severity

Main Risk Factors for CDAD

h Antimicrobial use h Advanced age h Use of PPIs or H2 blockers h Infected roommate h Prolonged hospital stay h Multiple, severe underlying conditions h Immunosuppressive therapy

Events leading to CDAD:

h Intact microbiota of colon h Humoral immune response

Main Host Defenses against CDAD

h Antimicrobial use h C. difficile exposure/carriage h ? Defect in humoral immunity

CDAD risk lasts for at least 3 months after receipt of antibiotics

Hensgens, et al. J Antimicrob Chemother 2012;67:742-48.

Importance of serum antibody response to Toxin A

h Baseline serum antibodies do not predict who will develop CDAD

h Increase in toxin A IgG (anamnestic response) predicts asymptomatic carriage (P <.001) h A low (or absent) Ab response in pts with CDAD

h New data suggest efficacy of monoclonal antibodies to prevent CDAD recurrence (7% vs 25%)

Kyne et al. NEJM 2000;342:390 Lowy et al. NEJM 2010;362:197

Changing Epidemiology of CDAD

h Increasing rates world-wide h More severe disease

h More treatment failures h More colectomies h More CDAD-related deaths

h Community-acquired cases

Incidence of C. difficile-related Hospitalization in U.S.

Zilberberg MD, et al. Emerg Infect Dis. 2008;14:929-31.

More CDAD, more deaths

BI/NAP 1 Strain Epidemic Strain

Black SR et al. Infect Control Hosp Epidemiol 2011;32(9):897-902

h Great geographic variability in rates of BI/NAP1 h Accounts for 61% of CDAD isolates from recent

multicenter sample of acute care CDAD in Chicago

Transmission h Transmitted via fecal-oral route h Spread via healthcare workers’ hands and

contaminated environments h Hand Hygiene

h Alcohol-based hand cleaners do not eliminate spores.

h Must wash hands with soap and water

Risk Factors - Environment h Spores can persist in rooms up to 40 days after

infected patient is discharged h Spores have been recovered from:

h Hospital toilets h Metal bedpans h Commodes h Thermometers h Floors

h Resistant to many commonly used cleaning agents. h Detergents may not eliminate C. difficile spores

C. difficile Transmission & Relationship to Prior Room Occupants

Shaugnessey et al. Infect Control Hosp Epidemiol 2011;32:201.

110% Increased risk

Prevention and Control Strategies

h Preventing patient to patient spread h Hand hygiene (handwashing) h Gowns, gloves, isolating, cohorting h Dedicating items to patient h Room cleaning and disinfection

•  Dilute bleach on units with higher rates

h Decreasing antimicrobial use

www.cdc.gov

CDAD Primary Treatment

h D/C antibiotics alone relieves symptoms in 10-20% of mild cases

h Oral metronidazole or vancomycin relieves symptoms in > 95% of cases

h Problem: Up to 20-30% of patients have recurrences

Adjuvant Therapies Described for Severe or Relapsing CDAD

h Prolonged po vanco taper h Rifaximin “chaser” h Probiotics h Intestinal microbiota transplant* h Immunotherapy

h IVIG h Monoclonal antibodies

*Gough et al. Clin Infect Dis 2011;53:994-1002

Reducing C. difficile: Summary h Our greatest HAI challenge at this time h Requires increased, intensive attention to:

h Antimicrobial stewardship •  Every hosptial must have an active program •  Tackles the key risk factor for C. difficile disease

h Early accurate detection + isolation/HH h Environmental cleaning and disinfection

•  C. difficile forms spores that are difficult to eradicate •  Monitoring of cleaning process necessary •  Bleach based cleaning may be required •  New technologies also in the works

–  E.g. Hydrogen peroxide vapor, other touchless methods

Surgical Site Infections h 2nd most common nosocomial infection h Over half present after discharge h Organism distribution--percent

h Staphylococcus aureus 20 h Coagulase negative staph 14 h Enterococcus spp. 12 h Escherichia coli 8 h Pseudomonas aeruginosa 8

Surgical Site Infections Risk Factors: Only some can be modified

h Infection at another site → treat infections pre-operatively h Duration of procedure → surgical technique and asepsis h Diabetes, hyperglycemia → careful glucose control h Shaving operative site preoperatively → clip, don’t shave! h Hypothermia intraoperatively → normothermia (warm pt) h S. aureus carrier state → S. aureus decolonization h Low oxygen tension? → high flow oxygen? (conflicting data) h Advanced age h Obesity h Length of postoperative stay h Surgical wound classification

Surgical Site Infections Other Methods of Prevention

h Perioperative antibiotic prophylaxis h Published guidelines exist h Timing of administration is critical

•  Initiate within 1 hour prior to incision h Decolonize patients who carry S. aureus?

h For S. aureus carriers, some studies show benefit to decolonization

h Consider first for major cardiothoracic or orthopedic procedures (e.g. Prosthetic jts)

Bode et al. N Engl J Med 2010;362:9-17

Surgical Site Infections S. aureus screening

h S. aureus decolonization

Bode et al. N Engl J Med 2010;362:9-17

Catheter-associated urinary tract infection (CA-UTI)

h Urinary tract is most common HAI site h Associated with urinary tract catheters h Though less morbid than other HAIs,

sheer number contributes substantially to LOS, cost, morbidity/mortality, abx use h 17% of hospital BSI of urinary source h Majority of CA-UTI may be preventable

http://www.cdc.gov/hicpac/pdf/CAUTI/CAUTIguideline2009final.pdf

http://www.cdc.gov/hicpac/pdf/CAUTI/CAUTIguideline2009final.pdf http://www.cdc.gov/ncidod/dhqp/HAI_shea_idsa.html

Catheter-associated urinary tract infection (CA-UTI)

h Principles of prevention, divided into 3 modules for implementation: h Appropriate catheter use (I)

•  Proper indications, remove ASAP

h Aseptic placement (II) •  Appropriately trained personnel only

h Proper maintenance (III) •  Closed drainage system •  Unobstructed urine flow

Nosocomial Infections Summary

h NIs affect 5-10% of hospitalized pts and cause significant morbidity and mortality

h Evidence-based interventions can greatly ↓ infection rates, save lives

h Challenges: moving prevention outside of the ICU environment, sustaining gains, pushing rates to irreducible minimum…….and hand hygiene!

Additional data slides for Q&A……

CLABSI: Prevention Strategies

h Anatomic site of catheter insertion h Density of skin flora at insertion site is a risk factor

h Data suggest infection rates differ by site: FEMORAL > IJ > SUBCLAVIAN

Complication category

Femoral (n, 134)

Subclavian (n, 136)

p-value

Contamination 26 (19%) 6 (4%) <0.001

Clinical sepsis 4 1

Bloodstream infxn 2 1 0.07

Merrer, et al. JAMA 2001;286: 700-707. Mermel, et al. Am J Med 1991;91:197-205.

h Hand hygiene h Hospital-wide hand

hygiene campaign with alcohol product led to ↓ in over nosocomial infection and in MRSA BSI

CLABSI: Prevention Strategies

Pittet D, et al. Lancet 2000;356:1307.

h Maximal Sterile Barrier Precautions • Prospective randomized trial of MSB during

catheter insertion • CA-BSI rate 6-fold higher in control group

– Raad II, et al. ICHE 1994;15:231-238. • Educational program for catheter insertion •  Increase maximal barrier use 44% → 65% • Decrease CA-BSI 4.5 → 2.9 per 1000 pt days

– Sherertz R, et al. Ann Intern Med 2000;132:641

CLABSI: Prevention Strategies

CLABSI: Prevention Strategies

h Skin antisepsis h Chlorhexidine (2%) is now preferred

• 2.3 (chlorhex) vs. 7.1 (EtOH) vs. 9.3 (P-I) bloodstream infections per 100 catheters

– Maki DG, et al. Lancet 1991;338:339-43. • Metanalysis: 7 studies of CHG versus P-I • Pooled RR 0.5 (0.3-0.9), favored CHG

– Ann Int Med 2002;136:792-801.

h Chlorhexidine/silver sulfadiazine: h Meta-analysis: OR 0.56 (0.37-0.84, p=0.005)

vs. placebo •  Veenstra DL, et al. JAMA 1999;281:261-7

h Minocycline/rifampin: h Several randomized trials demonstrate

reduction in CA-BSI compared with placebo •  Raad I, et al. Ann Int Med 1997;128:267-74 •  Darouiche R, et al. NEJM 1999;340:1-8 •  Chatzinikolaou I, et al. Am J Med 2003;115:352-57. •  Hanna H, et al. J Clin Onc 2004;22:3163-71 •  Darouiche R, et al. Ann Surg 2005;242:192-200.

New approaches for prevention: Antimicrobial impregnated catheters

h Instillation of antimicrobials into lumen h Meta-analysis of 7 trials of vancomycin lock

solution, mostly cancer pts with long term CVCs h CA-BSI RR = 0.49 [0.26-0.95], p=0.03

•  Safdar N, Maki D. Clin Infect Dis 2006;43:474-84. h Practices vary widely

h <20% of EIN members have used •  Recurrent BSI and limited access options •  <1% use routinely •  Vancomycin (68%), EtOH (9%) most common

Polgreen et al. Infect Cont Hosp Epidemiol 2010;31:554-57.

New approaches for prevention: Antimicrobial lock solutions

Reducing aspiration risk: Semi-recumbent positioning

Alexiou, et al. J Crit Care 2009;24:515-522

• One of three RCTs demonstrated significant ↓ in VAP • Overall trend favors semirecumbent position • Patients should not be completely supine.

Preventing VAP: The “sedation vacation”

h Daily interruption of sedation: h 128 patients on mechanical ventilation

randomized to daily interruption of sedation until awake

h Duration of ventilation 4.9 vs. 7.3 days (p=0.004)

Kress JP et al. N Engl J Med 2000;342:1471-77.

h Recent meta-analyses of oral antisepsis • 12 CHG RCTs → RR 0.7 [95% CI, 0.5-0.9]1

–  Effect most pronounced for 2% (vs. 0.12%)

Preventing VAP: Chlorhexidine oral care

(1) Labeau, et al. Lancet ID 2011;11:845 (2) Kola et al. J Hosp Inf 2007;66:207.

S-DD for VAP Prevention h Pro:

h Accumulated trials data support efficacy in reducing VAP and mortality

h Cons: h Impact of systemic + oral antimicrobials

on resistance emergence h Can oral decontamination with

chlorhexidine provide similar benefit?

h 2003 pts randomized h Among those intubated

> 24 hrs: h 4.8 vs. 7.5% micro-

confirmed VAP, p=0.03

h No diff in vent days, LOS, mortality, MD suspicion of VAP

h Reducing VAP, or reducing colonizers?

Preventing VAP: Antmicrobial (silver) coated ET tubes

Kollef et al. JAMA 2008;300:805.

Ventilator Associated Pneumonia: Risk Factors (partial list)

h Mechanical ventilation h Recumbent position h Increased gastric pH h Enteral feeding h ↓ level of consciousness h Advanced age h Male sex h Pre-existing pulmonary disease http://www.cdc.gov/mmwr/preview/mmwrhtml/rr5303a1.htm Niederman et al. Am J Resp Crit Care Med 2005;171:388-416.

aspiration

The IHI Ventilator Bundle: Meta-analysis

h Only four studies met inclusion criteria h All had methodologic problems

•  All were “before-after” study designs •  Little information re diagnostic approach before and after •  Selection/publication bias, confounding?

h 38-60% reduction in VAP post-intervention •  Resar et al. Jt Comm J Qual Pt Saf 2005;31:243. •  Berriel-Cass et al. Jt Comm J Qual Pt Saf 2006;32:612. •  Youngquist et al. Jt Comm J Qual Pt Saf 2007;33:219. •  Unahalekhaka et al. Jt Comm J Qual Pt Saf 2007;33:387.

h Is the bundle cost-effective? Which aspects are most important? Should new elements be added?

Zilberberg et al. Crit Care Med 2009;37:305.

h RCT in 12 Italian ICUs, N = 600 adults h Early trach (6-8 d) vs. late (13-15 d) h VAP: 14% early vs. 21% late (p=0.07) h ↓ risk for VAP (HR, 0.66 [0.42-1.04],

remaining on vent (HR, 0.7 [0.56-0.87]), remaining in ICU (HR, 0.7 [0.55-0.97]),

h ↓ Mortality risk, but NS (HR, 0.8) Terragni, et al. JAMA 2010;303:1483

Major issues with CLABSI definition

h Designed to be sensitive, not specific h Does pos blood cx + CVC = CLABSI? h Many infections that meet CLABSI

criteria may be from gut translocation h Enterococcus, Candida, Gram negs

h CDC has working group assembled to consider changes to CLABSI definition

Am J Infect Cont 2011, Sept 22 (Epub ahead of print)

h Interpret clinical signs as strictly as possible h Interpret CXRs as strictly as possible h Require consensus between 2 or more IPs h Seek intensivist endorsement before accepting case h Require BAL for diagnosis h Set quantitative growth thresholds for diagnosis h Transfer patients who require prolonged ventilation h Expand surveillance to include uncomplicated post-

op patients