Universal vs targeted decolonisation to prevent ICU infections: data from REDUCE MRSA trial

• Multi-centre, cluster-randomised study: N=74,256 pts from 74 ICUs: 3 strategy groups:

1. MRSA screening + isolation

2. Targeted decolonisation: MRSA screening + isolation + decolonisation of MRSA carriers (intranasal mupirocin 2x/day for 5 days + daily bathing with chlorhexidine-impregnated cloths)

3. Universal decolonisation: no MRSA screening; decolonisation of all pts (intranasal mupirocin 2x/day for 5 days + daily bathing with

chlorhexidine-impregnated cloths for entire ICU stay)

Huang SS et al. N Engl J Med 2013;368:2255-65

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MRSA-pos. clinical culture MRSA BSI BSI with any pathogen

•54 pts need to undergo universal decolonisation to prevent 1 BSI from any pathogen•AEs occurred in 7 pts: mild and related to chlorhexidine

Universal vs targeted decolonisation to prevent ICU infections: data from REDUCE MRSA trial

In ICU pts, universal decolonisation seems to be more effective than targeted decolonisation, or screening and isolation, in reducing rates

of MRSA clinical isolates and BSI from any pathogen

Huang SS et al. N Engl J Med 2013;368:2255-65

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Continuous infusion vs intermittent bolus dosing of β-lactam antibiotics in severe sepsis

• Multi-centre, prospective, double-blind RCT (Australia, Hong Kong)

• N=60 ICU pts with severe sepsis in previous 48h, receiving continuous infusion (N=30) or intermittent bolus dosing (N=30) of piperacillin-tazobactam, meropenem and ticarcillin-clavulanate

Primary endpoint (pharmacokinetic)

Dulhunty JM et al. Clin Infect Dis 2013;56:236-44

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Continuous infusion vs intermittent bolus dosing of β-lactam antibiotics in severe sepsis

Secondary endpoints (clinical)

In critically ill pts with severe sepsis, continuous infusion of β-lactam antibiotics may lead to higher plasma antibiotic concentrations and

higher clinical cure rates than intermittent bolus dosing

Dulhunty JM et al. Clin Infect Dis 2013;56:236-44

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Extended or continuous vs short-term infusion of β-lactam antibiotics: systematic review and meta-analysis of clinical outcomes

• Systematic literature review (January 2012) + meta-analysis: articles reporting on comparative outcomes of pts treated with extended (≥3h) or continuous (24h) vs short-term (20-60 min) iv infusion of carbapenems or piperacillin/tazobactam: 14 studies on 1,229 patients included:

Falagas ME et al. Clin Infect Dis 2013;56:272-82

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Extended or continuous vs short-term infusion of β-lactam antibiotics: systematic review and meta-analysis of clinical outcomes

• Clinical cure: no statistical difference between extended/continuous and short-term infusions: Risk ratio=1.13; 95% CI: 0.99-1.28; P=0.08

Mortality seems to be lower for extended or continuous infusion of carbapenems or piperacillin/tazobactam than for short-term infusion

Falagas ME et al. Clin Infect Dis 2013;56:272-82

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Extended infusion of doripenem vs standard infusion of doripenem and meropenem: clinical outcomes

• Single-centre, retrospective analysis (pharmacy database; USA) in hospitalised pts with moderate-to-severe infections:– 2009-2010: N=134 pts treated with meropenem:

standard infusion (30 min)– 2011-2012: N=129 pts treated with doripenem:

• Extended infusion (4h): N=58 (45%)• Standard infusion (30 min): N=71 (55%)

• Main clinical outcomes: mortality or transfer to hospice care (vs discharge to home, long-term care or rehab facility)

Jogi V. IDWeek 2013 abs. 784

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Extended infusion of doripenem vs standard infusion of doripenem and meropenem: clinical outcomes

Odd ratio (OR) for mortality or transfer to hospice care:

•Doripenem extended infusion vs doripenem standard infusion:

OR=4.5; 95% CI:1.5-13; P<0.01

•Meropenem standard infusion vs doripenem standard + extended

infusion:

OR=2.2; 95% CI: 1.2-4; P<0.01

Mortality seems to be higher for extended infusion of doripenem than for standard infusion. However, compared to meropenem standard

infusion, mortality may be lower in the total doripenem group (extended + standard infusion)

Jogi V. IDWeek 2013 abs. 784

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• Multi-centre, open-label, phase III RCT (Italy; 2008-2011)

• N=210 ICU pts with life-threatening nosocomial infection due to XDR A. baumannii susceptible to colistin (MIC ≤2 mg/l), randomised to:

– Colistin alone (2.106 U every 8h iv): N=105

– Colistin (2.106 U every 8h iv) + rifampicin (600 mg every 12 h iv): N=105

• Median treatment duration: 12.5 days

Safety

Impact of addition of rifampicin to colistin on mortality due to extensively drug-resistant (XDR) Acinetobacter baumannii infections

Durante-Mangoni E et al. Clin Infect Dis 2013;57:349-58

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Efficacy

•Multivariable logistic regression: Treatment arm is NOT an independent predictor of 30-day mortality: OR=0.88; 95% CI: 0.46-1.69; P=0.71

Impact of addition of rifampicin to colistin on mortality due to extensively drug-resistant (XDR) Acinetobacter baumannii infections

Rifampicin should not be combined with colistin in routine clinical practice, as it does not seem to reduce 30-day mortality in serious

XDR A. baumannii infections compared with colistin alone

Durante-Mangoni E et al. Clin Infect Dis 2013;57:349-58

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Aggressive vs conservative initiation of antimicrobial treatment for suspected ICU-acquired infections (IAI)

• Single-centre, 2-year, quasi-experimental, before-after observational cohort study (USA) in adult pts admitted to surgical ICU:

– Sep 2008 − Aug 2009: Aggressive strategy:Antimicrobial treatment (Tx) started if clinical suspicion of infection

– Sep 2009 − Aug 2010: Conservative strategy: Antimicrobial Tx started only after objective confirmation of infection

Hranjec T et al. Lancet Infect Dis 2012;12:774-80

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• Aggressive strategy is a predictor of mortality (univariate analysis, adjusted for age,

sex, trauma involvement, acute physiology, APACHE II score and site of infection):Aggressive vs conservative strategy: OR=2.5; 95% CI: 1.5-4.0; P<0.0001

Aggressive vs conservative initiation of antimicrobial treatment for suspected ICU-acquired infections (IAI)

Delaying antimicrobial Tx for suspected ICU-acquired infections until objective evidence of infection may not worsen patient mortality

Hranjec T et al. Lancet Infect Dis 2012;12:774-80

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Use of minocycline against methicillin-resistant Staphylococcus aureus (MRSA) and multi-drug-resistant gram-negative organisms (MDRO)

• Single-centre, retrospective study (USA; 2009-2012)

• N=21 pts (22 infections) (25-83 yr) treated with iv minocycline 100 mg every 12h for ≥24h

• No adverse events attributed to minocycline in any treated patient

Bishburg E et al. Infect Dis Clin Practice 2013;doi:10.1097/IPC.0b013e31828bbb82

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Use of minocycline against methicillin-resistant Staphylococcus aureus (MRSA) and multi-drug-resistant gram-negative organisms (MDRO)

†Death: 1 patient with neutropenia and severe sepsis: initial Tx: imipenem/ cilastatin → changed to amikacin/minocycline due to persistent fever and KPC-producing K. pneumoniae, sensitive to minocycline

Bishburg E et al. Infect Dis Clin Practice 2013;doi:10.1097/IPC.0b013e31828bbb82

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Iv minocyclin may be used for MRSA and MDRO infections if other Tx options are scarce. Minocycline has a favourable pharmacokinetic

profile and allows for completion of Tx with an oral formulation

Impact of vancomycin minimum inhibitory concentration (MIC) on mortality in Staphylococcus aureus bacteraemia (SAB)

• Systematic literature review, meta-analysis and meta-regression: 38 studies reporting on mortality and vancomycin MIC in pts with SAB

• N=8,039 SAB episodes (mean age: 63 yr)

• Overall mortality: 25.3%

Van Schooneveld TC. IDWeek 2013 abs. 376

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Impact of vancomycin minimum inhibitory concentration (MIC) on mortality in Staphylococcus aureus bacteraemia (SAB)

Higher vancomycin MIC values do not seem to be associated with increased mortality in pts with SAB

Van Schooneveld TC. IDWeek 2013 abs. 376

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In vitro activity of ceftolozane/tazobactam (TOL/TAZ) against aerobic Gram-negative organisms causing intra-abdominal infections (IAIs)

• Program to Assess TOL/TAZ Susceptibility (PACTS): Multi-centre surveillance study (Europe, USA; 2012): N=809 isolates of aerobic Gram-negative bacilli from hospitalised pts with diagnosis of IAI

Sader H. IDWeek 2013 abs. 698

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Data from poster

In vitro activity of ceftolozane/tazobactam (TOL/TAZ) against aerobic Gram-negative organisms causing intra-abdominal infections (IAIs)

TOL/TAZ demonstrated potent activity against aerobic Gram-neg. IAI-causing pathogens, including ESBL-phenotypes and P. aeruginosa

Sader H. IDWeek 2013 abs. 698

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Data from poster

In vitro activity of ceftazidime-avibactam (CAZ-AVI) against Gram-negative pathogens causing bloodstream infections (BSIs)

• Avibactam: novel non-β-lactam β-lactamase inhibitor

• Multi-centre study (USA; 2012): N=1,462 Gram-negative organisms from hospitalised pts with BSIs

• Enterobacteriaceae: N=1,269

At CAZ-AVI MIC ≤4 µg/ml (i.e. CLSI susceptible breakpoint for CAZ): 99.8% of strains inhibited → only 2 strains with CAZ-AVI MIC >4 µg/ml: Providencia spp. (8 µg/ml) − E. aerogenes (16 µg/ml)

Sader H. IDWeek 2013 abs. 700

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Data from poster

In vitro activity of ceftazidime-avibactam (CAZ-AVI) against Gram-negative pathogens causing bloodstream infections (BSIs)

CAZ/AVI demonstrated potent activity against Gram-neg. BSI-causing organisms, including those resistant to most currently used agents

Sader H. IDWeek 2013 abs. 700

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Data from poster