1. Systematic review + meta-analysis: 69 (quasi-)randomised trials: N=7,863 pts with sepsis: any BL monoTx vs any combination of BL + AG: N (studies) : same BL in both arms: 22; broader-spectrum BL in monoTx arm: 47 β-lactam (BL) monotherapy (monoTx) vs BL/ aminoglycoside (AG) combination therapy for sepsis β-lactam/AG combination Tx does not seem to provide an advantage over β-lactam monoTx in septic pts, but increases nephrotoxicity Paul M et al. Cochrane Database Syst Rev 2014;1:CD003344

2. Impact of time to initiation of antibiotic Tx on in-hospital mortality in pts with severe sepsis or septic shock Multi-centre, retrospective study (2005-2010; Surviving Sepsis Campaign): 165 ICUs in Europe, USA, South-America N=17,990 pts receiving antibiotics after severe sepsis or septic shock In-hospital mortality: total cohort: 29.7% Logistic regression model: OR for hospital mortality: adjusted for Sepsis Severity Score, ICU admission source (emergency department, ward vs ICU) and geographic region Ferrer R et al. Crit Care Med 2014;42:1749-55 1 of 2

3. Impact of time to initiation of antibiotic Tx on in-hospital mortality in pts with severe sepsis or septic shock Risk of hospital mortality ( based on generalised estimating equation population averaged logistic regression model) Assumed patient: from USA, admitted via the emergency department, with Sepsis Severity Score of 52 (median of all observations) Results similar in pts with severe sepsis and septic shock, regardless of number of organ failure(s) In patients with severe sepsis or septic shock, the risk of in-hospital mortality shows a linear increase with each hour delay in initiation of antibiotic Tx during the first 6 hours after patient identification Ferrer R et al. Crit Care Med 2014;42:1749-55 2 of 2

4. Impact of medical education on risk of developing and dying from severe sepsis Matched cohort study (2000-2008, Taiwan’s National Health Insurance Research Database): 29,697 physicians + 29,697 demographically and socioeconomically matched controls without medical education/background Primary outcome: Development of severe sepsis: Secondary outcome: 90-day mortality following severe sepsis: lower for physicians; HR (adjusted for baseline/additional covariates)= 0.82; 95% CI: 0.71-0.95 Compared with matched controls, physicians seem to have a lower risk of developing and dying from severe sepsis Shen HN et al. Crit Care Med 2014;42:816-23 *Adjusted for age, sex, income level, urbanisation status, geographic region, Charlson comorbidity score

5. Clinical risk factors and outcomes associated with FKS mutations in pts with Candida glabrata candidaemia Single-centre retrospective study (2009-2012; USA): N=72 pts with C. glabrata bloodstream infection (BSI) → N=13 pts (18%) with FKS mutation N=57 pts treated with micafungin 100 mg iv every 24h Beyda ND et al. Clin Infect Dis 2014;59:819-25 1 of 2 * caspofungin susceptibility test: Sensititre YeastOne, Trek Diagnostic systems, USA; MIC: minimum inhibitory concentration; NPV: negative predictive value; PPV: positive predictive value; Sens.: sensitivity; Spec.: specificity Tx failure: assessed at day 14 using consensus definitions of outcomes for antifungal therapy or as a breakthrough infection while receiving an echinocandin for ≥3 days as empiric therapy

6. Clinical risk factors and outcomes associated with FKS mutations in pts with Candida glabrata candidaemia Independent predictor of FKS mutant C. glabrata BSI (multivariate analysis): Independent predictor(s) of echinocandin Tx failure (multivariate analysis): Previous echinocandin exposure seems to be a risk factor for FKS mutant C. glabrata BSI and may predict echinocandin Tx failure Beyda ND et al. Clin Infect Dis 2014;59:819-25 2 of 2

7. Role of FKS mutations in Candida glabrata: MIC values, echinocandin resistance and multi-drug-resistance (MDR) Multi-centre, population-based surveillance study (2008-2013; USA): N=1,380 C. glabrata bloodstream isolates Antifungal susceptibility testing 2008-2013: decrease in absolute # of C. glabrata isolates/study centre BUT % of isolates resistant to any echinocandin remains constant Pham CD et al. Antimicrob Agents Chemother 2014;58:4690-6 1 of 2 MIC: minimum inhibitory concentration

8. Role of FKS mutations in Candida glabrata: MIC values, echinocandin resistance and multi-drug resistance (MDR) Identification of mutations in FKS genes 1,302 isolates screened for mutations, including all 77 isolates with resistant or intermediate MIC value for ≥1 echinocandin: FKS1 HS1 (hot spot 1): 15 mutations / FKS2 HS1: 35 mutations All isolates with FKS mutation, except for 1: resistant to ≥1 echinocandin FKS mutation detected in 81% of isolates resistant to ≥1 echinocandin Only 1 isolate resistant to all 3 echinocandins did not have FKS mutation Echinocandin resistance among US C. glabrata is a concern, especially since 36% of echinocandin-resistant isolates may be MDR Pham CD et al. Antimicrob Agents Chemother 2014;58:4690-6 2 of 2

9. De-escalation vs continuation of empirical antimicrobial Tx for severe sepsis Multi-centre, non-blinded, randomised non-inferiority study (2012-2013; France; 9 ICUs; N=116 pts with severe sepsis Randomised to: De-escalation (N=59): after antibiogram, empirical Tx switched to appropriate antibiotic with a narrower spectrum or Continuation of empirical antimicrobial Tx (N=57) FU: 90 days Primary outcome: Duration of ICU stay Leone M et al. Intensive Care Med 2014;40:1399-408 1 of 2 98

10. De-escalation vs continuation of empirical antimicrobial Tx for severe sepsis Compared with continuation of empirical antimicrobial Tx, de-escalation seems to increase duration of ICU stay and # of superinfections, but may not increase mortality rate or # of organ failures Leone M et al. Intensive Care Med 2014;40:1399-408 2 of 2 *From inclusion to day 28; D-SOFA: changes in Sequential Organ Failure Assessment score

11. Impact of mandatory infectious disease consultation (IDC) on management of S. aureus (SA) bacteraemia Single-centre, before-after study in adult pt with documented blood cultures positive for SA, surviving >48h from index culture: Mandatory IDC implemented in August 2012: comparison ±1-yr period before/after implementation Mandatory IDC may positively impact management of SA bacteraemia Salazar D. IDWeek 2014 abs. 134