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: of 2

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 IRR conventional screening < IRR rapid 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: of 2 IRR 1: increase in acquisition; *P<0.05; † P≤0.01; ‡ P≤0.001 Change 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: –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: *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: of 2

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: of 2 *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 of 2 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 of 2 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/ /2012 Post-intervention period: 06/ /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 of 2 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 of 2

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

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: of 2 *No deaths considered to be related to study drug