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P836 Efficacy and safety of colistin
Clinical trials of antibiotics
S213
Conclusion: Empiric meropenem monotherapy of severe infections in ICU appears to be more adequate and more cost-effective than conventional combination therapy with broad-spectrum antibiotics. P836 Efficacy and safety of colistin A. Levcovich, Y. Lischenski, P. Leon, S. Lev, R. Hazzan, M. Chowers, J. Bishara, L. Leibovici, M. Paul (Petah Tikva, Kfar Saba, IL) Objectives: The use of colistin decreased substantially in the 1970s following reports of renal failure and neuropathy. The appearance of highly resistant Gram-negative bacteria in hospitals, such as Acinetobacter baumannii, Pseudomonas spp. and Klebsiella spp., rendered colistin a drug of last resort for patients infected with these bacteria. The objectives of this study were to establish the safety and efficacy profile of colistin, in comparison to carbapenems and ampicillinsulbactam. Methods: Prospective observational cohort study including all adult patients treated with colistin, imipenem, meropenem or ampicillin/ sulbactam with bacteraemia or fulfilling CDC diagnostic criteria for pneumonia, urinary tract infection, meningitis, catheter-related or catheter-associated infections. We compared outcomes for colistin vs. comparator antibiotics. Data were collected at the time of infection presentation with follow-up of 30 days. Mortality was defined as 30day all-cause mortality. Renal failure was defined as 50% increase of creatinine levels from baseline and above 1.4 mg/dL at 2 weeks followup.
Baseline patient characteristics Colistin
Comparators
P-value
No patients Female gender Age (mean, SD) Service Internal medicine Surgery ICU Baseline functional status (full activity) Central line Mechanical ventilation Recent invasive procedure Charison score (median, range) McCabe score 1 2 3 SOFA score (median, range) Chronic renal failure Albumin g/dL (mean, SD) WBC K/micl (mean, SD) Bacteraemia
31 14 (45.2%) 68 (±16)
44 19 (43.2%) 57 (±20)
0.86 0.029
12 (38.7%) 4 (12.9%) 15 (48.4%) 17 (54.8%)
14 14 16 31
(31.8%) (31.8%) (36.4%) (70.5%)
0.17
10 (32.3%) 18 (58.1%) 18 (58.1%) 2 (1−6)
19 (43.2%) 25 (56.8%) 29 (65.9%) 1 (1−7)
0.34 0.91 0.49 0.31
17 (54.8%) 7 7 4 (1−14) 10 (32.3%) 2.2 (±0.46) 16.587 (±9.6) 12 (38.7%)
32 (72.7%) 8 4 4 (1−14) 11 (25%) 2.4 (±0.66) 14.294 (±8.4) 13 (29.5%)
0.11b
a For
ICU vs. others;
b for
0.29a
0.68 0.49 0.33 0.28 0.41
1 vs. others.
only to colistin in 23/3. Baseline patient characteristics and outcomes are shown in the table. Mortality was significantly higher with colistin vs. comparators, 48% vs. 20%, p = 0.01. A multivariate analysis including 75 patients and the variables age, McCabe score, independent functional status and treatment arm as covariates, revealed that colistin remained significantly associated with 30-day mortality (p = 0.03). Conclusions: Treatment with colistin was associated with a significantly higher mortality rate at 30 days and a non-significantly higher rate of renal failure development. Higher-risk patients were treated with colistin. P837 Clinical factors associated with daptomycin outcomes in skin and soft-tissue infections K. Lamp, L. Friedrich, K. Lindfield (Lexington, US) Objectives: To examine the impact of multiple clinical factors on daptomycin (DAP) clinical outcomes in patients (pts) with skin and softtissue infections (SSTI). Methods: The Cubicin® Outcomes Registry and Experience (CORE^sm 2005) is a multicentre (52 US institutions), retrospective study evaluating DAP outcomes. Pts unevaluable for outcome were excluded. Factors that may impact clinical outcomes (initial creatinine clearance [CrCl] <30 mL/min, dialysis, complicated SSTI [cSSTI], bacteraemia, methicillin-resistant Staphylococcus aureus [MRSA], sepsis, ICU stay, diabetes, cancer history, chronic kidney disease, age 66 yrs, concomitant antibiotic (abx) use, community location, prior abx category) were investigated in a multivariate logistic regression analysis (MV). Prior abx categories were defined as: no prior abx (DAP first line, FL), DAP after vancomycin (VAN) failure (VF), after VAN without VAN failure (VNF), after non-VAN failure (NVF), and after non-VAN without non-VAN failure (NVNF). Prior abx failure was determined by the investigator. Results: There were 486 evaluable pts with SSTI including noncatheterrelated bacteraemia. The number of pts in prior abx categories were FL (n = 127, 26%), VF (n = 56, 12%), VNF (n = 121, 25%), NVF (n = 86, 18%), NVNF (n = 96, 20%). Pts were 51% female, 21% 66 yrs, 12% with CrCl <30 mL/min or dialysis, 57% were in the community 2 days prior to DAP. The population consisted of 70% cSSTI, 30% uncomplicated SSTI and 5% of all pts had bacteraemia. The most common pathogen cultured was MRSA, 52%. The median DAP dose (4 mg/kg) and duration (12 days) did not differ by prior abx category. Overall, 94% of pts achieved clinical success after DAP therapy. By logistic regression DAP success rates were higher for FL than VF (98% vs. 88%, P = 0.018). The presence of an initial low CrCl (P = 0.015), ICU stay (P = 0.007) and sepsis (P = 0.009) were significant predictors of lower DAP success in MV. There was a trend that VF (P = 0.07) or NVF (P = 0.07) were associated with lower DAP success. Conclusion: In almost 500 SSTI pts treated with DAP, clinical success rates exceeded 90%. In the MV, a low initial CrCl, ICU stay or presence of sepsis were associated with lower DAP success which is consistent for markers of severity of illness. Prior abx category, in the presence of other patient factors, in MV resulted in the observation that DAP success was independent of the prior abx. Further studies are needed to confirm these findings. P838 Clinical experience trends with daptomycin in the first two years: report from a registry K. Lamp, L. Friedrich (Lexington, US)
Results: Data were collected between March to October 2006 in 2 medical centres in Israel; 31 patients were treated with colistin and 44 with comparator antibiotics (meropenem 12, imipenem 15, ampicillin-sulbactam 17). All infections were healthcare associated (median time in hospital before infection 17 days, 0−34). Prior antibiotic treatment was administered to 27 patients with colistin vs. 38 patients with comparator antibiotics. Treatment was administered for microbiologically documented infections in all but 2 patients. Acinetobacter, Klebsiella and Pseudomonas spp. were implicated in 56%, 56% and 31% of infections, respectively. Colistin was administered as single drug to 27/31 colistin-treated patients; bacteria were susceptible
Objectives: To describe trends in the use of daptomycin (DAP) in the United States during the first two years on the market. Methods: The Cubicin® Outcomes Registry and Experience (CORESM ) collected data in 2004 and 2005 at 45 and 52 US institutions, respectively. CORESM is a retrospective, observational chart review evaluating outcomes of DAP patients (pts). Investigators collected demographic, disease state, clinical and microbiological data; outcomes were assessed using standard definitions. Results: There were 1160 and 1172 pts enrolled in CORESM 2004 and 2005, respectively. Pts with more than one infection type were
S213
Conclusion: Empiric meropenem monotherapy of severe infections in ICU appears to be more adequate and more cost-effective than conventional combination therapy with broad-spectrum antibiotics. P836 Efficacy and safety of colistin A. Levcovich, Y. Lischenski, P. Leon, S. Lev, R. Hazzan, M. Chowers, J. Bishara, L. Leibovici, M. Paul (Petah Tikva, Kfar Saba, IL) Objectives: The use of colistin decreased substantially in the 1970s following reports of renal failure and neuropathy. The appearance of highly resistant Gram-negative bacteria in hospitals, such as Acinetobacter baumannii, Pseudomonas spp. and Klebsiella spp., rendered colistin a drug of last resort for patients infected with these bacteria. The objectives of this study were to establish the safety and efficacy profile of colistin, in comparison to carbapenems and ampicillinsulbactam. Methods: Prospective observational cohort study including all adult patients treated with colistin, imipenem, meropenem or ampicillin/ sulbactam with bacteraemia or fulfilling CDC diagnostic criteria for pneumonia, urinary tract infection, meningitis, catheter-related or catheter-associated infections. We compared outcomes for colistin vs. comparator antibiotics. Data were collected at the time of infection presentation with follow-up of 30 days. Mortality was defined as 30day all-cause mortality. Renal failure was defined as 50% increase of creatinine levels from baseline and above 1.4 mg/dL at 2 weeks followup.
Baseline patient characteristics Colistin
Comparators
P-value
No patients Female gender Age (mean, SD) Service Internal medicine Surgery ICU Baseline functional status (full activity) Central line Mechanical ventilation Recent invasive procedure Charison score (median, range) McCabe score 1 2 3 SOFA score (median, range) Chronic renal failure Albumin g/dL (mean, SD) WBC K/micl (mean, SD) Bacteraemia
31 14 (45.2%) 68 (±16)
44 19 (43.2%) 57 (±20)
0.86 0.029
12 (38.7%) 4 (12.9%) 15 (48.4%) 17 (54.8%)
14 14 16 31
(31.8%) (31.8%) (36.4%) (70.5%)
0.17
10 (32.3%) 18 (58.1%) 18 (58.1%) 2 (1−6)
19 (43.2%) 25 (56.8%) 29 (65.9%) 1 (1−7)
0.34 0.91 0.49 0.31
17 (54.8%) 7 7 4 (1−14) 10 (32.3%) 2.2 (±0.46) 16.587 (±9.6) 12 (38.7%)
32 (72.7%) 8 4 4 (1−14) 11 (25%) 2.4 (±0.66) 14.294 (±8.4) 13 (29.5%)
0.11b
a For
ICU vs. others;
b for
0.29a
0.68 0.49 0.33 0.28 0.41
1 vs. others.
only to colistin in 23/3. Baseline patient characteristics and outcomes are shown in the table. Mortality was significantly higher with colistin vs. comparators, 48% vs. 20%, p = 0.01. A multivariate analysis including 75 patients and the variables age, McCabe score, independent functional status and treatment arm as covariates, revealed that colistin remained significantly associated with 30-day mortality (p = 0.03). Conclusions: Treatment with colistin was associated with a significantly higher mortality rate at 30 days and a non-significantly higher rate of renal failure development. Higher-risk patients were treated with colistin. P837 Clinical factors associated with daptomycin outcomes in skin and soft-tissue infections K. Lamp, L. Friedrich, K. Lindfield (Lexington, US) Objectives: To examine the impact of multiple clinical factors on daptomycin (DAP) clinical outcomes in patients (pts) with skin and softtissue infections (SSTI). Methods: The Cubicin® Outcomes Registry and Experience (CORE^sm 2005) is a multicentre (52 US institutions), retrospective study evaluating DAP outcomes. Pts unevaluable for outcome were excluded. Factors that may impact clinical outcomes (initial creatinine clearance [CrCl] <30 mL/min, dialysis, complicated SSTI [cSSTI], bacteraemia, methicillin-resistant Staphylococcus aureus [MRSA], sepsis, ICU stay, diabetes, cancer history, chronic kidney disease, age 66 yrs, concomitant antibiotic (abx) use, community location, prior abx category) were investigated in a multivariate logistic regression analysis (MV). Prior abx categories were defined as: no prior abx (DAP first line, FL), DAP after vancomycin (VAN) failure (VF), after VAN without VAN failure (VNF), after non-VAN failure (NVF), and after non-VAN without non-VAN failure (NVNF). Prior abx failure was determined by the investigator. Results: There were 486 evaluable pts with SSTI including noncatheterrelated bacteraemia. The number of pts in prior abx categories were FL (n = 127, 26%), VF (n = 56, 12%), VNF (n = 121, 25%), NVF (n = 86, 18%), NVNF (n = 96, 20%). Pts were 51% female, 21% 66 yrs, 12% with CrCl <30 mL/min or dialysis, 57% were in the community 2 days prior to DAP. The population consisted of 70% cSSTI, 30% uncomplicated SSTI and 5% of all pts had bacteraemia. The most common pathogen cultured was MRSA, 52%. The median DAP dose (4 mg/kg) and duration (12 days) did not differ by prior abx category. Overall, 94% of pts achieved clinical success after DAP therapy. By logistic regression DAP success rates were higher for FL than VF (98% vs. 88%, P = 0.018). The presence of an initial low CrCl (P = 0.015), ICU stay (P = 0.007) and sepsis (P = 0.009) were significant predictors of lower DAP success in MV. There was a trend that VF (P = 0.07) or NVF (P = 0.07) were associated with lower DAP success. Conclusion: In almost 500 SSTI pts treated with DAP, clinical success rates exceeded 90%. In the MV, a low initial CrCl, ICU stay or presence of sepsis were associated with lower DAP success which is consistent for markers of severity of illness. Prior abx category, in the presence of other patient factors, in MV resulted in the observation that DAP success was independent of the prior abx. Further studies are needed to confirm these findings. P838 Clinical experience trends with daptomycin in the first two years: report from a registry K. Lamp, L. Friedrich (Lexington, US)
Results: Data were collected between March to October 2006 in 2 medical centres in Israel; 31 patients were treated with colistin and 44 with comparator antibiotics (meropenem 12, imipenem 15, ampicillin-sulbactam 17). All infections were healthcare associated (median time in hospital before infection 17 days, 0−34). Prior antibiotic treatment was administered to 27 patients with colistin vs. 38 patients with comparator antibiotics. Treatment was administered for microbiologically documented infections in all but 2 patients. Acinetobacter, Klebsiella and Pseudomonas spp. were implicated in 56%, 56% and 31% of infections, respectively. Colistin was administered as single drug to 27/31 colistin-treated patients; bacteria were susceptible
Objectives: To describe trends in the use of daptomycin (DAP) in the United States during the first two years on the market. Methods: The Cubicin® Outcomes Registry and Experience (CORESM ) collected data in 2004 and 2005 at 45 and 52 US institutions, respectively. CORESM is a retrospective, observational chart review evaluating outcomes of DAP patients (pts). Investigators collected demographic, disease state, clinical and microbiological data; outcomes were assessed using standard definitions. Results: There were 1160 and 1172 pts enrolled in CORESM 2004 and 2005, respectively. Pts with more than one infection type were