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Efficacy and safety of high-dose daptomycin for complicated Gram-positive infections

1 of 2. Efficacy and safety of high-dose daptomycin for complicated Gram-positive infections. Single-centre retrospective study (2009-2012) : N=72 pts (median age: 67 yr) with severe/complicated infections caused by staphylococci/enterococci

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Efficacy and safety of high-dose daptomycin for complicated Gram-positive infections

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  1. 1 of 2 Efficacy and safety of high-dose daptomycin for complicated Gram-positive infections Single-centre retrospective study (2009-2012): 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) Steinrucken J. ECCMID 2013 abs. P857

  2. 2 of 2 Efficacy and safety of high-dose daptomycin for complicated Gram-positive infections 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 High-dose daptomycin seems to be highly efficacious for treatment of complicated Gram-pos. infections, but may also cause severe AEs Steinrucken J. ECCMID 2013 abs. P857

  3. 1 of 3 Variability in plasma/target concentrations (conc.) of β-lactam antibiotics in critically ill patients 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: 4-155 mg/l 1Carlier M. ECCMID 2013 abs. P903 2Frey OR. ECCMID 2013 abs. P906 *SOFA: Sequential Organ Failure Assessment

  4. 2 of 3 Variability in plasma/target concentrations (conc.) of β-lactam antibiotics in critically ill patients 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 1Carlier M. ECCMID 2013 abs. P903 2Frey OR. ECCMID 2013 abs. P906 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 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. O2782Cafini F. ECCMID 2013 abs. O2793Grare M. ECCMID 2013 abs. O280

  7. 2 of 2 Emergence of linezolid (LZD) resistance in coagulase-negative staphylococci (CNS) and Staphylococcus aureus • Multivariable analysis1: 1Papadimitriou-Olivgeris M. ECCMID 2013 abs. O2782Cafini F. ECCMID 2013 abs. O2793Grare M. ECCMID 2013 abs. O280 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) Multi-centre retrospective study (2008-2011) Houben AJM. ECCMID 2013 abs. O344

  9. 2 of 2 Impact of selective oropharyngeal/digestive tract decontamination (SOD/SDD) on antimicrobial resistance in intensive care units (ICUs) • 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:2008-2011: no significant ≠ between SOD, SDD and SC • Colistin: • 2008-2011: • SOD: 2.2x higher risk of resistance than SC(RR: 2.2; 95% CI: 1.4-3.5) • SDD: 1.5x higher risk of resistance than SC(RR: 1.5; 95% CI: 1.0-2.4) • 2011 only: no significant ≠ between SOD, SDD and SC 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 Houben AJM. ECCMID 2013 abs. O344

  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 Multi-centre prospective observational study (Greece; 12 intensive care units (ICUs); 2010-2012) 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 Pontikis K. ECCMID 2013 abs. P2112 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 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 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 Pontikis K. ECCMID 2013 abs. P2112 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 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 10-21 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 Andini R. ECCMID 2013 abs. O578

  13. 2 of 2 Impact of colistin-induced nephrotoxicity on mortality in patients with extensively drug-resistant (XDR) Acinetobacter baumannii (Acb) infections 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: 1.33-4.57; P=0.004 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 Andini R. ECCMID 2013 abs. O578

  14. 1 of 2 Impact of azithromycin on risk of cardiovascular (CV) death Retrospective cohort study (Tennessee Medicaid cohort; 1992-2006) 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 Ray WA et al. N Engl J Med 2012;366:1881-90

  15. 2 of 2 Impact of azithromycin on risk of cardiovascular (CV) death 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 Ray WA et al. N Engl J Med 2012;366:1881-90

  16. 1 of 2 Predictors of mortality in bloodstream infections caused by Klebsiella pneumoniae carbapenemase-producing K. pneumoniae (KPC-Kp) during ICU stay 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) Papadimitriou-Olivgeris M. ECCMID 2013 abs. P1365 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 Independent predictors of 30-day mortality (multivariable logistic regression) 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 Papadimitriou-Olivgeris M. ECCMID 2013 abs. P1365 Data from poster

  18. 1 of 2 Predictors of mortality in bloodstream infections caused by Klebsiella pneumoniae carbapenemase-producing K. pneumoniae (KPC-Kp) Multi-centre retrospective cohort study (Italy; 2010-2011): 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%) Tumbarello M et al. Clin Infect Dis 2012;55:943-50

  19. 2 of 2 Predictors of mortality in bloodstream infections caused by Klebsiella pneumoniae carbapenemase-producing K. pneumoniae (KPC-Kp) • Multivariable logistic regression: Tumbarello M et al. Clin Infect Dis 2012;55:943-50 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 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): Papadimitriou-Olivgeris M. ECCMID 2013 abs. O343

  21. 2 of 2 Predictors of colonisation by Klebsiella pneumoniae carbapenemase-producing K. pneumoniae (KPC-Kp) resistant to colistin (CS) during ICU stay Multivariable analysis: 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 Papadimitriou-Olivgeris M. ECCMID 2013 abs. O343

  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;33:1094-100

  23. 2 of 3 Impact of chlorhexidine gluconate (CHG) patient bathing on hospital-acquired and healthcare-associated infections 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 1Climo MW et al. N Engl J Med 2013;368:533-42 2Rupp ME et al. Infect Control Hosp Epidemiol 2012;33:1094-100

  24. 3 of 3 Impact of chlorhexidine gluconate (CHG) patient bathing on hospital-acquired and healthcare-associated infections 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 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 1Climo MW et al. N Engl J Med 2013;368:533-42 2Rupp ME et al. Infect Control Hosp Epidemiol 2012;33:1094-100

  25. 1 of 2 Response after combination antifungal therapy for invasive mucormycosis in pts with haematological diseases: data from SEIFEM and Fungiscope Retrospective analysis of 2 large registries: SEIFEM/Fungiscope (2007-2012) 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) Pagano L. ECCMID 2013 abs. P1006

  26. 2 of 2 Response after combination antifungal therapy for invasive mucormycosis in pts with haematological diseases: data from SEIFEM and Fungiscope Mortality (at day 90) 13 pts (41%) still alive 12 months after diagnosis without signs of active infection Univariable logistic regression analysis Combination antifungal therapy with Lip-AmB+POS seems to be efficacious in the treatment of IM in pts with haematological diseases Pagano L. ECCMID 2013 abs. P1006 Data from poster

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