Transcript Study 2 2 - Infectoforum

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Efficacy and safety of high-dose daptomycin for
complicated Gram-positive infections
Steinrucken J. ECCMID 2013 abs. P857
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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)
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Median treatment duration: 17 days (range: 5-89 days)
Median follow-up: 21 months (range: 0 days- 3.5 yr)
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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
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Death during hospital stay: 5 pts (7%)
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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
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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
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N=16 adult critically ill patients without renal dysfunction
(87% males; mean age: 57 yr; mean SOFA* score on day 1 was 5)
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*SOFA:
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
Sequential Organ Failure Assessment
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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
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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)
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Treatment: Meropenem: 8 different dosing regimens;
mean duration of therapy: 7.3 days (range: 2-23 days)
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Analysis: Steady state concentrations (Css) of meropenem in serum
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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)
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Results: 557 serum levels measured
Data from poster
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Variability in plasma concentrations (conc.) of βlactam 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
Emergence of linezolid (LZD) resistance in
coagulase-negative staphylococci (CNS) and
Staphylococcus aureus Papadimitriou-Olivgeris M. ECCMID 2013 abs. O278
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2Cafini
3Grare
F. ECCMID 2013 abs. O279
M. ECCMID 2013 abs. O280
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Emergence of linezolid (LZD) resistance in
coagulase-negative staphylococci (CNS) and
Staphylococcus aureus Papadimitriou-Olivgeris M. ECCMID 2013 abs. O278
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2Cafini
3Grare
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F. ECCMID 2013 abs. O279
M. ECCMID 2013 abs. O280
Multivariable analysis1:
The emergence of LZD-resistant S. aureus and CNS warrants cautious-ness
about the use of LZD and the surveillance of LZD-treated pts
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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 (2008-2011)
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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:
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
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Efficacy of fosfomycin in infections caused by extensively
drug-resistant (XDR) and pan-drug-resistant (PDR) Gramnegative pathogens in critically ill ICU patients
Pontikis K. ECCMID 2013 abs. P2112
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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
Data from poster
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Efficacy of fosfomycin in infections caused by extensively
drug-resistant (XDR) and pan-drug-resistant (PDR) Gramnegative 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
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
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Impact of colistin-induced nephrotoxicity on
mortality in patients with extensively drug-resistant
(XDR) Acinetobacter baumannii (Acb) infections
Andini R. ECCMID 2013 abs. O578
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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 1021 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
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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%
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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
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Impact of azithromycin on risk of
cardiovascular (CV) death
Ray WA et al. N Engl J Med 2012;366:1881-90
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Retrospective cohort study (Tennessee Medicaid cohort; 1992-2006) in pts
(30-74 yr) who had been prescribed azithromycin (excluding pts who had lifethreatening non-CV illness, diagnosis of drug abuse, who were hospitalisated in prior
30 days or resided in nursing home during previous year)
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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)
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– 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
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Impact of azithromycin on risk of
cardiovascular (CV) death
Ray WA et al. N Engl J Med 2012;366:1881-90
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
Predictors of mortality in bloodstream infections
caused by Klebsiella pneumoniae carbapenemaseproducing K. pneumoniae (KPC-Kp) during ICU stay
Papadimitriou-Olivgeris M. ECCMID 2013 abs. P1365
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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)
Data from poster
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Predictors of mortality in bloodstream infections
caused by Klebsiella pneumoniae carbapenemaseproducing K. pneumoniae (KPC-Kp) during ICU stay
Papadimitriou-Olivgeris M. ECCMID 2013 abs. P1365
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
Data from poster
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Predictors of mortality in bloodstream infections
caused by Klebsiella pneumoniae carbapenemaseproducing K. pneumoniae (KPC-Kp)
Tumbarello M et al. Clin Infect Dis 2012;55:943-50
• 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%)
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Predictors of mortality in bloodstream infections
caused by Klebsiella pneumoniae carbapenemaseproducing K. pneumoniae (KPC-Kp)
Tumbarello M et al. Clin Infect Dis 2012;55:943-50
• Multivariable logistic regression:
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
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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
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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
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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):
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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:
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
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Impact of chlorhexidine gluconate (CHG) patient 1 of 3
bathing on hospital-acquired and healthcareassociated infections
Climo MW et al. N Engl J Med 2013;368:533-42
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2Rupp
ME et al. Infect Control Hosp Epidemiol 2012;33:1094-100
Impact of chlorhexidine gluconate (CHG) patient 2 of 3
bathing on hospital-acquired and healthcareassociated infections
Climo MW et al. N Engl J Med 2013;368:533-42
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2Rupp
ME et al. Infect Control Hosp Epidemiol 2012;33:1094-100
Study 1
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Overall incidence of skin reactions: CHG bathing: 2.0% - control: 3.4%
No skin reactions related to bathing; 85% of reactions: mild/moderate
Impact of chlorhexidine gluconate (CHG) patient 3 of 3
bathing on hospital-acquired and healthcareassociated infections
Climo MW et al. N Engl J Med 2013;368:533-42
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2Rupp
ME et al. Infect Control Hosp Epidemiol 2012;33:1094-100
Study 2
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188,859 patient-days; 68,302 CHG baths
Adherence to CHG bathing: adult critical care units: 90% > other units: 57.7%
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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
Response after combination antifungal therapy for
invasive mucormycosis in pts with haematological
diseases: data from SEIFEM and Fungiscope
Pagano L. ECCMID 2013 abs. P1006
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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 (lipAmB+POS)
Treatment response (after median follow-up of 3 months)
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Response after combination antifungal therapy for
invasive mucormycosis in pts with haematological
diseases: data from SEIFEM and Fungiscope
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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
Combination antifungal therapy with Lip-AmB+POS seems to be efficacious in
the treatment of IM in pts with haematological diseases
Data from poster