Inappropriate empirical antimicrobial Tx for coagulase-negative staphylococcal (CoNS) bacteraemia: impact on survival

• Single-centre retrospective cohort study + matched case-control study

(South Korea, 2010-2013)

• N=98 adult patients with true CoNS bacteraemia (≥2 blood cultures positive for

CoNS based on clinical presentation without apparent infection at another site):

– Appropriate empirical antimicrobial Tx (Tx given iv ≤48h after bacteraemia

onset, including ≥1 antibiotic to which isolate was susceptible): N=30 (‘cases’)

– Inappropriate empirical antimicrobial Tx (including Tx not administered ≤48h

after bacteraemia onset): N=68 (‘controls’)

Cases and controls matched for age, severity of underlying illness,

classification of main underlying diseases, prior hospital stay, severity of

sepsis, place of infection acquisition

Park S. ECCMID 2014 abs. eP220

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Data from poster

• Independent predictors of 30-day mortality (cohort study; multivariate analysis):

Inappropriate empirical antimicrobial Tx for coagulase-negative staphylococcal (CoNS) bacteraemia: impact on survival

Initial inappropriate antimicrobial Tx does not seem to increase mortality in pts with CoNS bacteraemia

Park S. ECCMID 2014 abs. eP220

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Data from poster

Fluconazole vs echinocandin/amphotericin B for initial Tx of Candida glabrata bloodstream infection (BSI): efficacy

• Multi-centre, population-based, observational study (Spain; 2010-2011): N=752 episodes of candidaemia in pts >16 yr

• N=96 (12.8%) episodes caused by C. glabrata (mixed candidaemia excluded)

• Annual C. glabrata incidence: 0.53 cases/103 admissions0.87/104 patient-days

• N=41 pts received antifungal Tx with fluconazole (FLC) or echinocandin/ amphotericin B (EC/AmB) within first 48h after collection of blood culture (excluding pts dying within first 48h, receiving delayed Tx or other antifungal agents)

• Fluconazole MIC50/MIC90 of Candida isolates (at 24h): 2/16 (EUCAST)

•

• Prior antifungal Tx: 25% of cases; for median time of 8.5 days

Puig-Asensio M. ECCMID 2014 abs. eP352

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Data from poster

Fluconazole vs echinocandin/amphotericin B for initial Tx of Candida glabrata bloodstream infection (BSI): efficacy

• Echinocandin/amphotericin B group: pts more severely ill:

Early mortality seems not to be affected by the use of fluconazole as initial Tx for C. glabrata BSIs

Puig-Asensio M. ECCMID 2014 abs. eP352

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Data from poster

*Pos. blood culture after ≥3 days of antifungal Tx

Fluconazole vs echinocandins for persistent candidaemia: mycological and clinical outcomes

• Single-centre retrospective analysis (Taiwan; 2011-2013): N=139 pts ≥18 yr with persistent candidaemia (i.e. persistence of the same Candida species ≥2 days after initiation of antifungal Tx) (only 1st candidaemia episode considered; mixed candidaemia excluded)

• Incidence of persistent candidaemia: 139/510 candidaemia episodes = 27.3%

• Eradication rate (i.e. no Candida species isolated from subsequent blood cultures): 48.9%

Lin KY. ECCMID 2014 abs. O237

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Data from oral presentation

Fluconazole vs echinocandins for persistent candidaemia: mycological and clinical outcomes

• Mycological outcome: median duration of persistence: 7 days

• Clinical outcome: 14-day mortality rate: 28.8%

Lin KY. ECCMID 2014 abs. O237

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Data from oral presentation

Potential predictorsMycological eradication 14-day mortality

OR 95% CI P OR 95% CI P

Echinocandin 0.31 0.01-13.89 0.543 0.10 0.01-2.06 0.135

CVC-free status 2.61 0.99-6.85 0.052 0.33 0.13-0.85 0.022

APACHE II score NS NS NS 1.09 1.02-1.16 0.010

Haematological malignancy 0.18 0.03-0.99 0.048 NS NS NS

Receipt of total parental nutrition 0.27 0.12-0.65 0.003 NS NS NS

C. tropicalis 0.28 0.09-0.83 0.021 NS NS NS

Fluconazole vs echinocandins for persistent candidaemia: mycological and clinical outcomes

Compared with fluconazole, echinocandins did not significantly improve eradication or 14-day mortality in pts with persistent candidaemia. Catheter removal and disease severity, but not echinocandin use,

may predict lower mortality

Lin KY. ECCMID 2014 abs. O237

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Data from oral presentation

NS: not significant

Multivariate analysis:

Candidaemia: epidemiology, species distribution, antifungal susceptibility and outcome

• Multi-centre study (2008-2010; pts included in database and prospectively followed; 5 tertiary teaching hospitals in Italy and Spain)

• N=995 episodes of candidaemia (only 1st episode per patient recorded)

• Overall candidaemia incidence: 1.55 cases/1,000 admissions; incidence remained stable during period 2008-2010

• Mean age: 66.2 yr; 57% males

• ≥1 comorbidity at time of candidaemia diagnosis: 93.1% of pts

Bassetti M et al. J Clin Microbiol 2013;51:4167-72

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Candidaemia: epidemiology, species distribution, antifungal susceptibility and outcome

• In vitro susceptibility to antifungal agents (CLSI breakpoints):

– Lowest MICs: amphotericin B

Almost 50% of candidaemia cases were found in IM wards. 30-day mortality rates were higher in HO and IM wards than in other wards

Bassetti M et al. J Clin Microbiol 2013;51:4167-72

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Combination Tx vs monotherapy for bloodstream infections (BSIs) caused by carbapenemase-producing Klebsiella pneumoniae (CP-Kp): impact on mortality

• 2-centre, retrospective, observational study (2009-2010; CP-Kp high-prevalence area, Greece): N=205 pts with CP-Kp BSI:VIM (zinc-dependent metallo-β-lactamase): 20.5% − KPC or KPC+VIM: 79.5%

• All-cause 28-day mortality: 40% (18 pts died ≤48h after bacteraemia onset)

Daikos GL et al. Antimicrob Agents Chemother 2014;58:2322-8

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†Carbapenem + tigecycline and/or aminoglycoside and/or colistin*8 pts infected with pan-resistant K. pneumoniae

Combination Tx vs monotherapy for bloodstream infections (BSIs) caused by carbapenemase-producing Klebsiella pneumoniae (CP-Kp): impact on mortality

Independent predictors of 28-day mortality (Cox proportional hazards model; N=175):

Compared with monoTx, combiTx may improve survival after CP-Kp BSI, mostly due to the efficacy of carbapenem-containing regimens

Daikos GL et al. Antimicrob Agents Chemother 2014;58:2322-8

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Adequate monotherapy vs combination Tx for P. aeruginosa (PA) bloodstream infections (BSIs): impact on mortality

• Post-hoc analysis of multi-centre, prospective cohort study* (Spain; 2008-2009): N=593 pts with single episode of monomicrobial PA BSI (MDR: 22%)

• 30-day mortality: 30% / Mortality within first 48h: 13%

Unadjusted 30-day survival (crude analysis):

Peña C et al. Clin Infect Dis 2013;57:208-16

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*Peña et al. Antimicrob Agents Chemother 2012;56:1256-72

Adequate monotherapy vs combination Tx for P. aeruginosa (PA) bloodstream infections (BSIs): impact on mortality

Multivariate analysis (Cox regression analysis, adjusted for high-risk bacteraemia, Pitt score, shock/multi-organ dysfunction at 48h, PA susceptibility):

Combination antimicrobial Tx may not reduce mortality risk compared with monotherapy in PA BSIs

Peña C et al. Clin Infect Dis 2013;57:208-16

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Albumin + crystalloids vs crystalloids alone in pts with severe sepsis: impact on mortality

• Albumin Italian Outcome Sepsis (ALBIOS): multi-centre, open-label, RCT (100 ICUs, Italy; 2008-2012): N=1,818 adult pts with severe sepsis:

– Group 1: Crystalloid solution (administered whenever clinically indicated): N=907

– Group 2: Crystalloid solution + 20% albumin (daily administration to maintain target serum albumin conc. ≥30 g/l): N=903

until discharge from ICU or 28 days after randomisation

• Day 1-7:

– Total daily amount of administered fluid: Group 2 ≈ group 1: P=0.10

– Mean arterial pressure: Group 2 > group 1: P=0.03

– Heart rate: Group 2 < group 1: P=0.002

– Daily net fluid balance: Albumin < crystalloids: P<0.001

Caironi P et al. N Engl J Med 2014;370:1412-21

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Albumin + crystalloids vs crystalloids alone in pts with severe sepsis: impact on mortality

Mortality

Length of stay (secondary endpoint)

Caironi P et al. N Engl J Med 2014;370:1412-21

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New organ failure (secondary endpoint)

SOFA (sub)score (secondary endpoint)

Albumin + crystalloids vs crystalloids alone in pts with severe sepsis: impact on mortality

In pts with severe sepsis, addition of albumin to crystalloids does not seem to improve survival after 28 and 90 days

Caironi P et al. N Engl J Med 2014;370:1412-21

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