• Multi-centre study in 13 European ICUs: N=8,519 pts admitted to ICU for ≥3 days and ≥1 nasal, rectal or wound swab during ICU admission:

• 3 phases:

1. Phase 1: Baseline (6 mo): N=1,962

2. Phase 2: Interrupted time series study (6 mo): daily chlorhexidine gluconate (CHG) body washing + hand hygiene improvement: N=1,926

3. Phase 3: Cluster-randomised trial (12-15 mo): continuation of phase 2 interventions + ICUs randomised to:

• Conventional screening (chromogenic screening for MRSA and VRE) + contact precautions for identified carriers: N=2,280 OR

• Rapid screening (PCR for MRSA and VRE; chromogenic screening for highly resistant

Enterobacteriaceae (HRE)) + contact precautions for identified carriers: N=2,351

Impact of infection control and prevention measures on acquisition of resistant bacteria in ICUs

Derde LP et al. Lancet Infect Dis 2014;14:31-9

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Impact of infection control and prevention measures on acquisition of resistant bacteria in ICUs

• Primary endpoint: Acquisition of resistant bacteria/100 patient-days at risk

• IRRconventional screening < IRRrapid screening, but no significant ≠ (P=0.06)

Screening and isolation of carriers may not further reduce acquisition rates of resistant bacteria (particularly MRSA) compared with

improved hand hygiene + unit-wide CHG body washing

Derde LP et al. Lancet Infect Dis 2014;14:31-9

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IRR<1: decrease in acquisition; IRR >1: increase in acquisition; *P<0.05; †P≤0.01; ‡P≤0.001Change in trend = rate of change of the log weekly acquisition rate; accounted for cluster effects and potential confounding factors fitted as covariates; HRE: highly resistant Enterobacteriaceae

• Systematic review + meta-analysis (2012): 9 studies comparing impact of interventions to prevent VRE spread in 30,949 adult hospitalised pts:

– 1 cluster RCT; 3 controlled clinical trials; 5 interrupted time series

– USA: N=7; UK: N=1; Canada: N=1

– Publication date: 1996-2011

– University hospitals: surgical/medical ICU, surgical unit, haematology unit

– VRE colonisation at hospital admission: 0.5%-58%

– Overall quality of studies: poor

Impact of infection control and prevention measures on transmission of hospital-acquired vancomycin-resistant enterococci (VRE)

Contact precautions may not significantly reduce VRE acquisition rate among hospitalised pts, while hand hygiene measures may do so

De Angelis G et al. J Antimicrob Chemother 2014;69:1185-92

*Pooled risk ratio

Combination Tx vs monotherapy for carbapenemase-producing Enterobacteriaceae

• Systematic review (2013): 20 non-randomised studies: N=692 pts receiving definitive Tx for infections caused by:

– Carbapenemase-producing Enterobacteriaceae: 15 studies OR

– Carbapenem-resistant Enterobacteriaceae (CRE): 5 studies

• Predominant causative pathogen: 19 studies: Klebsiella spp. − 1 study: Enterobacter cloacae

• Predominant type of infections (>50% of included infections): Bacteraemia: 8 studies − Pneumonia/urinary tract infections: 12 studies

• Critically ill pts: 10/20 studies (50%)

• Primary outcome: 30-day mortality / Secondary outcome: Tx failure

• Synthesis of available evidence using statistical analyses, including meta-analysis: not possible due to methodological issues, including clinical heterogeneity → only descriptive analysis

• 3 studies: 194 critically ill pts with bloodstream infections (BSIs) due to carbapenemase-producing Klebsiella spp.: significantly lower mortality with combination Tx than with monotherapy

Falagas ME et al. Antimicrob Agents Chemother 2014;58:654-63

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Combination Tx vs monotherapy for carbapenemase-producing Enterobacteriaceae

In most studies, combination Tx did not significantly reduce mortality vs monotherapy, except for 3 studies reporting on BSIs in critically ill pts

Falagas ME et al. Antimicrob Agents Chemother 2014;58:654-63

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*Infections due to VIM-1-producing isolates; AMK: amikacin; CS: colistin; FOS: fosfomycin; GENT: gentamicin; PoB: polymyxin B; TIG: tigecycline; TZP: piperacillin-tazobactam

Impact of antibiotic stewardship (ASP) and infectious disease (ID) consultation on antibiotic use in the emergency department (ED)

• Single-centre study (USA; Jan-June 2014): collaborative ED, ASP and ID management pilot programme:

– ID specialist formally evaluated pts presenting in ED with infectious conditions and offered recommendations regarding antibiotic selection, dosing, duration and additional testing

– Pts were offered appropriate in- or outpatient FU

• N=331 pts evaluated by ID consultant over 6 mo: ±3 pts/day

• Additional time spent by ID consultant on evaluating pts in ED, coordinating care and communicating with other providers: 4 h/day

• Number of additional FU visits/pt after initial consultation: ≥1

• Most common reasons for ID consultation in ED:Pneumonia (30.5%), sepsis (16.9%), skin and soft tissue infections (11.2%), urinary tract infections and pyelonephritis (11.2%), CNS infections (5.4%), osteomyelitis or joint infections (5.4%), intraabdominal infections (5.1%), other (14.3%)

Madaline T. IDWeek 2014 abs. 228

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Data from poster

Impact of antibiotic stewardship (ASP) and infectious disease (ID) consultation on antibiotic use in the emergency department (ED)

• Antibiotic recommendation accepted by ED staff: 92%

Early ID/ASP consultation in the ED seems to improve initial antibiotic prescribing, reduce unnecessary antibiotic use, improve patient

safety and avert unnecessary admissions

Madaline T. IDWeek 2014 abs. 228

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Data from poster

Impact of accountability campaign among healthcare workers (HCW) on hand hygiene (HH) compliance

Single-centre before-after study (35 units, including 8 ICUs; USA): ±800 stan-dardised HH observations collected monthly by 4 trained covert monitors (CoM)

•Pre-intervention period: 03/2008-05/2012

•Post-intervention period: 06/2012-08/2014: ‘Just Culture’ (JC) campaign:HCWs held accountable for conscious disregard for safety, but not for system failures:

– Progressive discipline: if non-compliance with HH (CoM observation): verbal warning → written warning → final written warning → termination

– Education/communication:

• Annual education of >2,000 employees; biannual CoM training

• Online promotional material, electronic communication, screensavers

• Non-compliance observations by anyone other than CoM: considered as teaching moments

– Environment: ongoing inspection of availability of alcohol hand sanitiser and chlorhexidine gluconate soap

– System change to reliably support HH practices: leadership, case reviews

Querry A. IDWeek 2014 abs. 1499

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Data from poster

Impact of accountability campaign among healthcare workers (HCW) on hand hygiene (HH) compliance

• Post-intervention period: 117 HCW went through JC progressive disciplinary process:

– Verbal warning: 112

– Written warning: 1

– Terminated: 2

– Cases dismissed: 2 (events secondary to system failure)

A HH campaign with accountability and potential disciplinary action for HCWs may lead to sustainable near perfect HH compliance

Querry A. IDWeek 2014 abs. 1499

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Bedaquiline vs placebo for newly diagnosed, smear-positive, multi-drug-resistant (MDR) tuberculosis (TBC)

• Bedaquiline: diarylquinoline that inhibits mycobacterial ATP synthase

• TMC207-C208: multi-centre, double-blind, phase IIb RCT: N=160 pts with newly diagnosed, smear-positive MDR TBC, randomised to:

– Bedaquiline: 400 mg od for 2 wk, followed by 200 mg 3x/wk for 22 wk+ preferred 5-drug, 2nd-line anti-TBC background regimen

– Placebo + preferred 5-drug, 2nd-line anti-TBC background regimen

• FU: 120 wk

• Primary endpoint: Median time to sputum-culture conversion in liquid broth

Diacon AH et al. New Engl J Med 2014;371:723-32

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Bedaquiline vs placebo for newly diagnosed, smear-positive, multi-drug-resistant (MDR) tuberculosis (TBC)

• Safety:

The addition of bedaquiline to a preferred background regimen for 24 wk resulted in faster culture conversion and higher conversion rate

than placebo. This effect remained significant for 120 wk

Diacon AH et al. New Engl J Med 2014;371:723-32

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*No deaths considered to be related to study drug