1. 1 of 2
Efficacy and safety of high-dose daptomycin for complicated Gram-positive infections
Steinrucken J. ECCMID 2013 abs. P857
Single-centre retrospective study ( ): N=72 pts (median age: 67 yr) with severe/complicated infections caused by staphylococci/enterococci
Pts treated with high-dose daptomycin (>6 mg/kg) 1x/day as short infusion (renal insufficiency: dosing interval prolonged to 48h)
Median treatment duration: 17 days (range: 5-89 days)
Median follow-up: 21 months (range: 0 days- 3.5 yr)
Reporter comments:
These data indicate that fever or respiratory symptoms during high-dose daptomycin therapy should prompt search for possible eosinophilic pneumonia.
A weakness of this study is the limited number of patients.
pts: patients

2. 2 of 2
Efficacy and safety of high-dose daptomycin for complicated Gram-positive infections
Steinrucken J. ECCMID 2013 abs. P857
Efficacy: Clinical cure: 64 pts (89%)
Safety
Death during hospital stay: 5 pts (7%)
All AEs resolved after discontinuation of daptomycin
No correlation between daily or cumulative daptomycin dose and occurrence or severity of AEs
Reporter comments:
These data indicate that fever or respiratory symptoms during high-dose daptomycin therapy should prompt search for possible eosinophilic pneumonia.
A weakness of this study is the limited number of patients.
AE: adverse event
pts: patients
High-dose daptomycin seems to be highly efficacious for treatment of complicated Gram-pos. infections, but may also cause severe AEs

3. 1 of 3
Variability in plasma/target concentrations (conc.) of β-lactam antibiotics in critically ill patients
1Carlier M. ECCMID 2013 abs. P903
2Frey OR. ECCMID 2013 abs. P906
Study 11
N=16 adult critically ill patients without renal dysfunction (87% males; mean age: 57 yr; mean SOFA* score on day 1 was 5)
Treatment: Piperacillin/tazobactam: 30 min loading dose (4 g) + 4x 4g/day administered as 3h extended infusion
Analysis: 1 antibiotic trough sample/day during 7 consecutive days → validated ultra-high-performance liquid chromatography tandem mass spectometry analysis with coefficient of variation (CV) <15%
Results:
82 antibiotic conc. available
High intra- and interpatient variability in antibiotic trough conc.: Range: mg/l
Reporter comments:
A weakness of these studies is the lack of correlation of these data with clinical outcomes.
SOFA: Sequential Organ Failure Assessment
*SOFA: Sequential Organ Failure Assessment

4. 2 of 3
Variability in plasma/target concentrations (conc.) of β-lactam antibiotics in critically ill patients
1Carlier M. ECCMID 2013 abs. P903
2Frey OR. ECCMID 2013 abs. P906
Study 22
N=238 critically ill pts with severe infections due to Gram-negative bacteria (mean age: 71 yr; mean creatinine clearance: 49 ml/min; mean meropenem clearance: 6.3 l/h; renal replacement therapy: 32% of pts; acute renal failure: 25% of pts)
Treatment: Meropenem: 8 different dosing regimens; mean duration of therapy: 7.3 days (range: 2-23 days)
Analysis: Steady state concentrations (Css) of meropenem in serum
Definitions:
Target conc.:
Continuous infusion: Css 8-16 mg/l
Intermittent bolus injection: drug conc. >8 mg/l for 40% of time
Overdose: AUC24h >768 mg.h/l (reflecting meropenem dosage >12,000 mg/24h in normal subjects)
Results: 557 serum levels measured
Reporter comments:
A weakness of these studies is the lack of correlation of these data with clinical outcomes.
Data from poster

5. 3 of 3
Variability in plasma concentrations (conc.) of β-lactam antibiotics in critically ill patients
1Carlier M. ECCMID 2013 abs. P903
2Frey OR. ECCMID 2013 abs. P906
Reporter comments:
A weakness of these studies is the lack of correlation of these data with clinical outcomes.
pts: patients
Plasma antibiotic concentrations vary greatly within/between pts and also depend on the dosage regimen. Frequent therapeutic drug monitoring may be warranted to prevent underdosing
Data from poster

6. 1 of 2
Emergence of linezolid (LZD) resistance in coagulase-negative staphylococci (CNS) and Staphylococcus aureus
1Papadimitriou-Olivgeris M. ECCMID 2013 abs. O278 2Cafini F. ECCMID 2013 abs. O279 3Grare M. ECCMID 2013 abs. O280
Reporter comments:
In study 1, transmission of LZD-resistant strains via the staff from patient to patient was a very important risk factor for CNS colonisation. This was even more clear from the oral presentation, where it was said that in the Greek hospital, during nightshift, only 3 nurses were available for 10 patients in the ICU.
pts: patients

7. 2 of 2
Emergence of linezolid (LZD) resistance in coagulase-negative staphylococci (CNS) and Staphylococcus aureus
1Papadimitriou-Olivgeris M. ECCMID 2013 abs. O278 2Cafini F. ECCMID 2013 abs. O279 3Grare M. ECCMID 2013 abs. O280
Multivariable analysis1:
Reporter comments:
In study 1, transmission of LZD-resistant strains via the staff from patient to patient was a very important risk factor for CNS colonisation. This was even more clear from the oral presentation, where it was said that in the Greek hospital, during nightshift, only 3 nurses were available for 10 patients in the ICU.
pts: patients
The emergence of LZD-resistant S. aureus and CNS warrants cautious-ness about the use of LZD and the surveillance of LZD-treated pts

8. 1 of 2
Impact of selective oropharyngeal/digestive tract decontamination (SOD/SDD) on antimicrobial resistance in intensive care units (ICUs)
Houben AJM. ECCMID 2013 abs. O344
Multi-centre retrospective study ( )
Reporter comment:
The limitations of this study are the lack of background data on ICUs other than ICU level and the lack of correlation with patient survival. Its strengths are the fact that several pathogens and several types of antibiotics were included, in contrast to previous studies.
SC: standard of care
SDD: selective digestive tract decontamination
SOD: selective oropharyngeal decontamination

9. 2 of 2
Impact of selective oropharyngeal/digestive tract decontamination (SOD/SDD) on antimicrobial resistance in intensive care units (ICUs)
Houben AJM. ECCMID 2013 abs. O344
Average resistance rate per 100 beds per yr for gram-neg. bacteria:
All antimicrobial agents: decreasing time trend in rate of resistant isolates for SOD, SDD and standard of care (SC)
Tobramycin, ciprofloxacin, ceftazidime, cefotaxime/ceftriaxone: : no significant ≠ between SOD, SDD and SC
Colistin: :
SOD: 2.2x higher risk of resistance than SC (RR: 2.2; 95% CI: )
SDD: 1.5x higher risk of resistance than SC (RR: 1.5; 95% CI: )
2011 only: no significant ≠ between SOD, SDD and SC
Reporter comment:
The limitations of this study are the lack of background data on ICUs other than ICU level and the lack of correlation with patient survival. Its strengths are the fact that several pathogens and several types of antibiotics were included, in contrast to previous studies.
gram-neg: gram-negative
RR: rate ratio
SC: standard of care
SDD: selective digestive tract decontamination
SOD: selective oropharyngeal decontamination
Use of SOD or SDD does not seem to increase resistance over time in ICUs. Resistance rates do not seem to differ between ICUs using SOD, SDD or SC, except for resistance to colistin

10. 1 of 2
Efficacy of fosfomycin in infections caused by extensively drug-resistant (XDR) and pan-drug-resistant (PDR) Gram-negative pathogens in critically ill ICU patients
Pontikis K. ECCMID 2013 abs. P2112
Multi-centre prospective observational study (Greece; 12 intensive care units (ICUs); )
N=48 critically ill pts suffering from serious, microbiologically documented infections with XDR and PDR (but fosfomycin-susceptible) Gram-negative strains; treated with fosfomycin
Fosfomycin treatment regimen:
6 g iv 2h infusion every 6h
Median duration of treatment: 12 days
Reporter comments:
Weaknesses of this study are the lack of comparison group and the low number of patients. However, the current data are among the best available evidence so far, as it would be very difficult to conduct a comparative study with sufficient patients in both groups.
APACHE: Acute Physiology and Chronic Health Evaluation
iv: intravenously
pts: patients
SOFA: Sequential Organ Failure Assessment
Data from poster

11. 2 of 2
Efficacy of fosfomycin in infections caused by extensively drug-resistant (XDR) and pan-drug-resistant (PDR) Gram-negative pathogens in critically ill ICU patients
Pontikis K. ECCMID 2013 abs. P2112
Efficacy
14-day survival: 77.1% − 28-day survival: 62.5%
Microbiological outcomes
Safety
Most frequent adverse event: Severe hypokalaemia (reversible): N=10
Treatment termination due to adverse events: N=4
Reporter comments:
Weaknesses of this study are the lack of comparison group and the low number of patients. However, the current data are among the best available evidence so far, as it would be very difficult to conduct a comparative study with sufficient patients in both groups.
pts: patients
As fosfomycin seems to have a considerable efficacy and acceptable safety, and development of resistance occurs infrequently, it may be useful for treatment of PDR and XDR infections in critically ill pts
Data from poster

12. 1 of 2
Impact of colistin-induced nephrotoxicity on mortality in patients with extensively drug-resistant (XDR) Acinetobacter baumannii (Acb) infections
Andini R. ECCMID 2013 abs. O578
Single-centre prospective study (Italy): N=208 pts admitted to intensive care unit (ICU) with XDR Acb infection, treated with colistin (2x106 IU tid iv for days, adjusting doses according to renal function)
Renal function (RF) grading: according to Kidney/Disease Outcomes Quality Initiative (K/DOQI)
Renal toxicity grading: according to Risk, Injury, Failure, Loss, End Stage Kidney Disease (RIFLE) criteria
Reporter comments:
The colistin dosage used in this study might not be adequate: nowadays, 6x106 IU once daily, or even 9x106 IU first dosis followed by 4.5 x106 IU every 12h are used.
This study does not really prove a causal relationship between colistin use and nephrotoxicity (on-treatment renal impairment).
It is well known that patients with renal failure have a poorer prognosis than patients without renal dysfunction.
iv: intravenously
IU: international units
pts: patients
tid: three times a day

13. 2 of 2
Impact of colistin-induced nephrotoxicity on mortality in patients with extensively drug-resistant (XDR) Acinetobacter baumannii (Acb) infections
Andini R. ECCMID 2013 abs. O578
Hospital mortality among pts with renal replacement therapy at baseline: 69.4%
Multivariable analysis (adjusted for heart failure, diabetes mellitus, ischaemic heart disease, chronic obstructive pulmonary disease):
Baseline renal dysfunction is independent predictor of increased mortality: OR=2.47; 95% CI: ; P=0.004
Reporter comments:
The colistin dosage used in this study might not be adequate: nowadays, 6x106 IU once daily, or even 9x106 IU first dosis followed by 4.5 x106 IU every 12h are used.
This study does not really prove a causal relationship between colistin use and nephrotoxicity (on-treatment renal impairment).
It is well known that patients with renal failure have a poorer prognosis than patients without renal dysfunction.
Baseline renal dysfunction seems to be an independent predictor of increased hospital mortality in pts with XDR Acb infections treated with colistin, but not of colistin-induced renal toxicity

14. Impact of azithromycin on risk of cardiovascular (CV) death
Ray WA et al. N Engl J Med 2012;366:
Retrospective cohort study (Tennessee Medicaid cohort; ) in pts (30-74 yr) who had been prescribed azithromycin (excluding pts who had life-threatening non-CV illness, diagnosis of drug abuse, who were hospitalisated in prior 30 days or resided in nursing home during previous year)
Study group: Azithromycin: N=347,795 prescriptions*
Control groups:
No antibiotics: N=1,391,180 propensity-score-matched control periods (of similar length to the courses of antibiotic therapy)
Amoxicillin: N=1,348,672 prescriptions
Primary endpoints:
CV death
Death from any cause
Most common indications for azithromycin/amoxicillin prescription: infections of ear, nose, throat, bronchitis (62/63%)
Amoxicillin vs no antibiotics: no significant ≠ in risk of (CV) death
Reporter comments:
This publication was discussed during the ECCMID 2013 session ‘The year in infectious diseases’ by Ullmann AJ (S432) and Petrosillo N (S433).
In this observational study, 2 distinct control groups (i.e. no antibiotics and amoxicillin) were included to minimise the risk of confounding with factors associated with both azithromycin use and an increased risk of CV death.
This study could not establish a causal mechanism for the proarrhythmic effect of azithromycin.
pts: patients

15. Impact of azithromycin on risk of cardiovascular (CV) death
Ray WA et al. N Engl J Med 2012;366:
Reporter comments:
This publication was discussed during the ECCMID 2013 session ‘The year in infectious diseases’ by Ullmann AJ (S432) and Petrosillo N (S433).
In this observational study, 2 distinct control groups (i.e. no antibiotics and amoxicillin) were included to minimise the risk of confounding with factors associated with both azithromycin use and an increased risk of CV death.
This study could not establish a causal mechanism for the proarrhythmic effect of azithromycin.
CI: confidence interval
HR: hazard ratio
pts: patients
During the first 5 days of therapy, azithromycin seems to increase the risk of CV death compared with amoxicillin/no antibiotics, especially in pts with a high baseline risk of CV disease

16. 1 of 2
Predictors of mortality in bloodstream infections caused by Klebsiella pneumoniae carbapenemase-producing K. pneumoniae (KPC-Kp) during ICU stay
Papadimitriou-Olivgeris M. ECCMID 2013 abs. P1365
Single-centre retrospective study (Greece; 2-year period): N=273 intensive care unit (ICU) pts
+ 5 extra pts admitted to ICU due to bacteraemia
→ 53 pts with KPC-Kp BSI: 30-day mortality: 43.4%
Predictors of KPC-KP BSI during ICU stay (multivariable logistic regression)
Reporter comments:
Data on this topic from a multi-centre retrospective cohort study have been published: Tumbarello M et al. Clin Infect Dis 2012;55: The latter publication was discussed during the ECCMID 2013 session ‘The year in infectious diseases’ by Ullmann AJ (S432) and Petrosillo N (S433).
OR: odds ratio
pts: patients
Data from poster

17. 2 of 2
Predictors of mortality in bloodstream infections caused by Klebsiella pneumoniae carbapenemase-producing K. pneumoniae (KPC-Kp) during ICU stay
Papadimitriou-Olivgeris M. ECCMID 2013 abs. P1365
Independent predictors of 30-day mortality (multivariable logistic regression)
Reporter comments:
Data on this topic from a multi-centre retrospective cohort study have been published: Tumbarello M et al. Clin Infect Dis 2012;55: The latter publication was discussed during the ECCMID 2013 session ‘The year in infectious diseases’ by Ullmann AJ (S432) and Petrosillo N (S433).
CS: colistin
GENT: gentamicin
SAPS: Simplified Acute Physiology Score
SD: standard deviation
TIG: tigecycline
Tx: treatment
Septic shock, resistance to GENT/CS/TIG, high SAPS II score at onset and high age may predict higher 30-day mortality after KPC-Kp BSI, while combination therapy may predict lower mortality
Data from poster

18. 1 of 2
Predictors of mortality in bloodstream infections caused by Klebsiella pneumoniae carbapenemase-producing K. pneumoniae (KPC-Kp)
Tumbarello M et al. Clin Infect Dis 2012;55:943-50
Multi-centre retrospective cohort study (Italy; ): N=125 pts with bloodstream infection (BSIs) caused by KPC-Kp isolates
Primary outcome: Death within 30 days of 1st positive blood culture: 52/125 pts (41.6%)
Reporter comments:
This publication was discussed during the ECCMID 2013 session ‘The year in infectious diseases’ by Ullmann AJ (S432) and Petrosillo N (S433).
Data on this topic from a single-centre retrospective study were also presented at ECCMID 2013 abs. P1365.
pts: patients

19. 2 of 2
Predictors of mortality in bloodstream infections caused by Klebsiella pneumoniae carbapenemase-producing K. pneumoniae (KPC-Kp)
Tumbarello M et al. Clin Infect Dis 2012;55:943-50
Multivariable logistic regression:
Reporter comments:
This publication was discussed during the ECCMID 2013 session ‘The year in infectious diseases’ by Ullmann AJ (S432) and Petrosillo N (S433).
Data on this topic from a single-centre retrospective study were also presented at ECCMID 2013 abs. P1365.
pts: patients
Septic shock at BSI onset, inadequate initial antimicrobial therapy and high APACHE III score may predict higher 30-day mortality after KPC-Kp BSI, while combination therapy may predict lower mortality

20. 1 of 2
Predictors of colonisation by Klebsiella pneumoniae carbapenemase-producing K. pneumoniae (KPC-Kp) resistant to colistin (CS) during ICU stay
Papadimitriou-Olivgeris M. ECCMID 2013 abs. O343
Single-centre retrospective study (Greece; 2-year period): N=254 intensive care unit (ICU) pts hospitalised for ≥6 days;
Rectal samples taken upon ICU admission and 1x/week afterwards
During 2-year period: 305 KPC-Kp isolates collected (Enterotube IITM BDTM BBLTM; presence of blaKPC gene confirmed by PCR)
Antibiotic susceptibility (agar diffusion method according to CLSI guidelines):
Reporter comments:
Transmission of CS-resistant KPC-Kp via the staff from patient to patient was a very important risk factor for CNS colonisation. This was even more clear from the oral presentation, where it was said that in the Greek hospital, during nightshift, only 3 nurses were available for 10 patients in the ICU.
pts: patients

21. 2 of 2
Predictors of colonisation by Klebsiella pneumoniae carbapenemase-producing K. pneumoniae (KPC-Kp) resistant to colistin (CS) during ICU stay
Papadimitriou-Olivgeris M. ECCMID 2013 abs. O343
Multivariable analysis:
Reporter comments:
Transmission of CS-resistant KPC-Kp via the staff from patient to patient was a very important risk factor for CNS colonisation. This was even more clear from the oral presentation, where it was said that in the Greek hospital, during nightshift, only 3 nurses were available for 10 patients in the ICU.
pts: patients
The high rate of colonisation of ICU pts by KPC-Kp resistant to colistin warrants cautiousness about the surveillance of CS-treated pts, in order to avoid patient-patient transmission via the staff

22. 1 of 3
Impact of chlorhexidine gluconate (CHG) patient bathing on hospital-acquired and healthcare-associated infections
1Climo MW et al. N Engl J Med 2013;368:533-42
2Rupp ME et al. Infect Control Hosp Epidemiol 2012;33:
Reporter comment:
These publications were discussed during the ECCMID 2013 session ‘The year in infectious diseases’ by Ullmann AJ (S432) and Petrosillo N (S433).
mo: months
pts: patients

23. 2 of 3
Impact of chlorhexidine gluconate (CHG) patient bathing on hospital-acquired and healthcare-associated infections
1Climo MW et al. N Engl J Med 2013;368:533-42
2Rupp ME et al. Infect Control Hosp Epidemiol 2012;33:
Study 1
Overall incidence of skin reactions: CHG bathing: 2.0% - control: 3.4%
No skin reactions related to bathing; 85% of reactions: mild/moderate
Reporter comment:
These publications were discussed during the ECCMID 2013 session ‘The year in infectious diseases’ by Ullmann AJ (S432) and Petrosillo N (S433).

24. 3 of 3
Impact of chlorhexidine gluconate (CHG) patient bathing on hospital-acquired and healthcare-associated infections
1Climo MW et al. N Engl J Med 2013;368:533-42
2Rupp ME et al. Infect Control Hosp Epidemiol 2012;33:
Study 2
188,859 patient-days; 68,302 CHG baths
Adherence to CHG bathing: adult critical care units: 90% > other units: 57.7%
No consistent effect of CHG bathing on other healthcare-associated infections
No adverse events related to CHG bathing reported
Reporter comment:
These publications were discussed during the ECCMID 2013 session ‘The year in infectious diseases’ by Ullmann AJ (S432) and Petrosillo N (S433).
CDI: Clostridium difficile infection
ICU: intensive care unit
MDRO: multi-drug-resistant organism
pts: patients
Patient bathing with CHG not only reduces the risk of MDROs and hospital-acquired bloodstream infections in ICU populations, but may also reduce the risk of CDI in a broad range of hospitalised pts

25. 1 of 2
Response after combination antifungal therapy for invasive mucormycosis in pts with haematological diseases: data from SEIFEM and Fungiscope
Pagano L. ECCMID 2013 abs. P1006
Retrospective analysis of 2 large registries: SEIFEM/Fungiscope ( )
N=32 pts with haematological conditions (HC) and invasive mucormycosis (IM), treated with lipid formulations of amphotericin B + posaconazole (lip-AmB+POS)
Treatment response (after median follow-up of 3 months)
Reporter comments:
A weakness of this study is the lack of comparison group, i.e. patients with HC and IM treated with antifungal monotherapy. However, as the number of patients with HC and IM is very rare, it would be very difficult to obtain sufficient patients in both study groups. Therefore, this study represents the best available evidence on combination antifungal therapy for IM in patients with HC so far.
Data from the Fungiscope registry were also presented at ECCMID 2013 abs
pts: patients

26. 2 of 2
Response after combination antifungal therapy for invasive mucormycosis in pts with haematological diseases: data from SEIFEM and Fungiscope
Pagano L. ECCMID 2013 abs. P1006
Mortality (at day 90) 13 pts (41%) still alive 12 months after diagnosis without signs of active infection Univariable logistic regression analysis
Reporter comments:
A weakness of this study is the lack of comparison group, i.e. patients with HC and IM treated with antifungal monotherapy. However, as the number of patients with HC and IM is very rare, it would be very difficult to obtain sufficient patients in both study groups. Therefore, this study represents the best available evidence on combination antifungal therapy for IM in patients with HC so far.
Data from the Fungiscope registry were also presented at ECCMID 2013 abs
HC: haematological conditions
IM: invasive mucormycosis
Lip-AmB+POS: lipid formulations of amphotericin B + posaconazole
pts: patients
Combination antifungal therapy with Lip-AmB+POS seems to be efficacious in the treatment of IM in pts with haematological diseases
Data from poster