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P099 Efficacy and safety of colistin for the treatment of infections caused by multidrug-resistant isolates of Pseudomonas aeruginosa sensitive to colistin in patients with haematological malignancy
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Poster Sessions
were rapidly thawed and infused without further processing. The granulocyte count, viability test and clonogenic assay were performed after thawing. Patients were monitored for vital signs and symptoms of the toxicity during and after infusion. Results: Overall incidence of side effects was 56.9%, but majority of reported complaints were mild and self limited. No life-threatening adverse effects were observed. Patients with lower body weight experienced significantly more side effects (p=0.006). Women experienced significantly more side-effects than men (p<0.0001). Patients who experienced side-effects received significantly higher (p=0.011) volume and more DMSO/kg BW (p><0.001). The median TNC and granulocyte content of the graft were found to be significantly higher in patients with side effects compared to the other group (p=0.041, p><0,0001) respectively. We performed logistic regression analysis to investigate multivariate relationship between occurrence of side effects as criterion and gender, body weight, diagnosis, volume of infused PBSC and DMSO per BW, number of TNC and granulocyte in graft as predictors. Female gender, diagnosis of multiple myeloma, and number of granulocytes infused per BW were significant predictors, respectively OR=0.41, 95% CI=0.22-0.77, OR=2.83, 95% CI=1.45-5.53 and OR=0.83, 95% CI=0.720.95.Patients treated for multiple myeloma had significantly more (p= 0.0099) side effects than other patients. Changes in blood pressure occurred in 41 (60.3%) patients with myeloma who experienced side effects what was significantly more then in patients with other diagnosis (p><0.0001). Thirty eight of fifty nine cases of hypertension and four of six cases of hypotension totally reported, occurred in patients with myeloma. This group of patients was significantly (p><0.0001) older then the other with median of age 55 years (range 36-68) vs. median of 44 (range 14-66). They received significantly more (p><0.0001) granulocytes with median of 3.12 × 108 /kg BW (range 0.2-11.47) vs. median of 2.42 × 108 /kg BW (range 0.14-18.2). Conclusion: Patients with multiple myeloma, women and recipients of graft with high number of granulocytes should be monitored for signs and symptoms of the infusion-toxicity. Our results indicate that the composition of graft is relevant and toxicity could be reduced by improvement of apheresis product quality and depletion of mature cells in graft wich are poorly preserved through the cryopreservation process.
P098 LightCycler Septifast assay as a tool for the rapid diagnosis of sepsis in patients during antimicrobial therapy A. Vince, S. Židovec-Lepej, D. Dušek, Z. Mitrovic, I. Grgi´c, R. Serventi-Seiwerth, B. Labar. University Hospital for Infectious Diseases “Dr. Fran Mihaljevi´c”, and Department of Medicine University Hospital Center, Zagreb, Croatia Aim: The aim of this study was to determine the additional diagnostic value of the first in vitro diagnostic multiplex realtime PCR assay (LightCycler SeptiFast test) for detection of
microorganisms in the blood of patients with suspected sepsis even during antimicrobial therapy. The newly-developed SeptiFast test detects up to 26 bacterial and fungal DNA(s) in whole blood. Patients and methods: The study enrolled 35 patients suspected of sepsis from the University Hospital for Infectious Diseases, Zagreb and Zagreb University Clinical Center. Patients were divided into 3 groups: sepsis in patients from intensive care unit (ICU) (n= 17), sepsis in patients outside ICU (n=9) and sepsis in hematological patients following bone marrow or peripheral blood stem cells transplantation (n=9). Fungal and bacterial DNA in the blood of the patients was detected by using LightCycler SeptiFast (Roche Diagnostics, USA). All patients enrolled in the study were treated with antimicrobial agents empirically at the time of testing. Blood cultures were taken from all patients as well. Results: Twelve of 38 (32%) samples were positive for bacterial/fungal DNA. Gram-positive bacterial DNA was detected in 10 of 12 samples (Klebsiella pneumoniae/oxitoca n=4; Escherichia coli n=3; Pseudomonas aeruginosa n=3). Grampositive bacterial DNA (Enterococcus faecium n=1 and Streptococcus pneumoniae n=2) were detected in two patients with polymicrobial sepsis (in combination with Klebsiella pneumoniae/oxitoca in both patients). Fungal DNA was detected in two patients (Aspergillus fumigatus in both samples). Clinical diagnosis in patients with positive results of the LightCycler SeptiFast included: sepsis in patients from intensive care unit (ICU) (n=4), sepsis in patients outside ICU (n=4) and sepsis in hematological patients (n=4). Additional SeptiFast-positive results (blood culture negative) were obtained in 8 of 35 patients. We detected one discordant result between SeptiFast test and cultivation (Enterobacter cloacae was detected by cultivation and Klebsiella pneumoniae/oxytoca by SeptiFast test). Due to the fact that SeptiFast test does not detect Actinobacillus sp. DNA, this microorganism was detected in 1 patient by using cultivation method only. Conclusion: The results of our study have shown that SeptiFast test is a valuable add-on to conventional cultivation methods for detection of gram-negative and gram-positive bacteria, as well as fungi in the blood of patients presenting with clinical picture of sepsis even during antimicrobial therapy.
P099 Efficacy and safety of colistin for the treatment of infections caused by multidrug-resistant isolates of Pseudomonas aeruginosa sensitive to colistin in patients with haematological malignancy N. Durakovic, A. Boban, M. Mrsi´c, D. Serti´c, R. Serventi-Seiwerth, D. Nemet, B. Labar. Department of Medicine, University Hospital Centre and School of Medicine, Zagreb, Croatia Aim: Infections due to multidrug-resistant (MDR) Gram-
Poster Sessions negative bacteria have been increasing and they are an important cause of nosocomial morbidity and mortality, especially in immunocompromised patients. Aim of this retrospective study was to determine the efficacy and safety of colistin (colistimethate sodium) use in the treatment of MDR Pseudomonas aeruginosa sensitive to colistin. Patients and methods: In the period between February 2002 and December 2006, 24 patients hospitalized in our institution had an infection caused by MDR P.aeruginosa and were treated with intravenous colistin. Patients were 46% male and 54% female; mean age was 35 years (range 16-60). All of the patients were treated for haematological malignancy, majority for AML (58%), followed by ALL (13%), NHL (12%), aplastic anemia (8%), CML and multiple myeloma (both 4%). Majority of patients were treated with intensive chemotherapy regimens (46%), 25% received allogeneic and 25% autologous transplants. All of the patients had clinical signs of sepsis; in 54% MDR P.aeruginosa was isolated from blood, in 13% from urine, 12% from skin lesions that had clinical presentation of echtyma gangrenosum, while others had MDR P.aeruginosa isolated from surveillance cultures. Patients received 3 MU of colistin every 8 hours for a mean (± SD) duration of 12.3 (± 5.6) days. Due to nature of their disease, and severity of infections, all of the patients received more than two other possibly nephrotoxic drugs; 79% were receiving vancomycin, 71% cefepime, 38% amikacine, 13% garamycine, and 46% received amphotericine B deoxycholate concurrently. Results: Of 24 patients receiving colistin, 18 patients (75%) had the drug discontinued after successful clearance of infection. In 2 patients (8%) drug was exchanged for another one due to lack of clinical imrovement, and 3 patients had a lethal outcome (all in multiorgan failure due to sepsis). Only one patient had displayed neurological toxicity (Jacksons attack with secondary generalisation), but the drug was not discontinued, dose was modified, patient had no further attacks. There was no statistically significant difference in the level of serum creatinine, creatinine clearance (calculated), or potassium levels between prior to colistin therapy and after colistin cessation. One patient developed renal failure and had to be subjected to continuous venovenous hemodiafiltration; of note is that at the time colistin introduction patient already had impaired renal function. In one patient drug had to be discontinued due to suspected allergic reaction. No other adverse events were noted. Conclusion: Colistin is an effective antimicrobial drug for the treatment of severe infections caused by MDR P.aeruginosa in haematological patients. The safety profile observed is acceptable in these severe life-threatening infections. Further studies are needed to better address the treatment of MDR P.aeruginosa., naimely the optimal dose and schedule, also route of administration of colistin, as well as drug-to-drug interactions.
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P100 Predictors of outcome for patients with haematological malignancies in ICU V. Gasparovic, I. Gornik, A. Oršuli´c, M. Ili´c. Division of Emergency and Intensive Care Medicine, University Hospital Rebro, General Hospital Nova Gradiška and General Hospital Dubrovnik, Dubrovnik, Croatia Introduction: Management of patients with haematological malignancies in intensive care units with neutropenic sepsis and/or organ failure is associated with high mortality caused by lack of cellular defences, ongoing inflammatory processes and other complications (e.g. intracranial bleeding). Patients and methods: During a period of five years (20012006) 45 patients with haematological malignancies were treated in our ICU because of respiratory failure, severe sepsis or septic shock. Respiratory failure was defined by alteration in blood gasses and/or tachypnea, circulatory failure was defined by hypotension and tachycardia and/or need for vasoactive treatment. Karnofsky performance index and SAPS score were determined at admission. Results: Incidence of haematological malignancies was: AML 18 (40%), NHL 16 (35,6%), ALL 3 (6,7%), MM 3 (6,7%), CLL 1 (2,2%), others 4 (8,9%). There were 20 male and 25 female patients, mean age was 49±15 years. Average SAPS score was 70±13 (Median 69), Karnofsky indeks 21±10 (Median 10). Six patients (13.3%) survived. Median ICU LOS was 3 days for non-survivors and 5 days for survivors. Average time from ICU admission to start of mechanical ventilation was 38,5±68,2 (Median 9) hours. Predictors of ICU outcome were: high SAPS score (P=0,037) and respiratory failure (P=0,024) at admission and thrombocytopenia (p=0,013). For our patients’ age, sex, haematological disease and type of previous treatment were not predictive of outcome. Discussion: Management of neutropenic patients with haematological malignancies and respiratory failure usually is a consequence of infection of respiratory tract. High mortality of such patients has compelled several investigations of prognostic markers for outcome. It has been established that respiratory status and haemodinamic parameters have predictive value, while age and underlying haematological condition do not [1]. These results are in concordance with our own. Main predictors of outcome were SAPS score, respiratory failure and thrombocytopenia. Higher SASP score and Karnofsky index can explain higher mortality of our patients compared with previous studies. Leukocyte count was not shown to be predictive for outcome in our study unlike thrombocytopenia. This can be explained by the fact that all neutropenic patients received granulocyte colony stimulating factor that does not influence thrombocytopoesis. Other authors concluded that main predictors of unfavourable outcome were neutropenia, use of vasopressors and high urea, while positive blood cultures were associated with survival [2]. Renal failure was not an outcome predictor in our patients. Our results show that management of respiratory failure and neutropenic sepsis in patients with haematological malignan-
Poster Sessions
were rapidly thawed and infused without further processing. The granulocyte count, viability test and clonogenic assay were performed after thawing. Patients were monitored for vital signs and symptoms of the toxicity during and after infusion. Results: Overall incidence of side effects was 56.9%, but majority of reported complaints were mild and self limited. No life-threatening adverse effects were observed. Patients with lower body weight experienced significantly more side effects (p=0.006). Women experienced significantly more side-effects than men (p<0.0001). Patients who experienced side-effects received significantly higher (p=0.011) volume and more DMSO/kg BW (p><0.001). The median TNC and granulocyte content of the graft were found to be significantly higher in patients with side effects compared to the other group (p=0.041, p><0,0001) respectively. We performed logistic regression analysis to investigate multivariate relationship between occurrence of side effects as criterion and gender, body weight, diagnosis, volume of infused PBSC and DMSO per BW, number of TNC and granulocyte in graft as predictors. Female gender, diagnosis of multiple myeloma, and number of granulocytes infused per BW were significant predictors, respectively OR=0.41, 95% CI=0.22-0.77, OR=2.83, 95% CI=1.45-5.53 and OR=0.83, 95% CI=0.720.95.Patients treated for multiple myeloma had significantly more (p= 0.0099) side effects than other patients. Changes in blood pressure occurred in 41 (60.3%) patients with myeloma who experienced side effects what was significantly more then in patients with other diagnosis (p><0.0001). Thirty eight of fifty nine cases of hypertension and four of six cases of hypotension totally reported, occurred in patients with myeloma. This group of patients was significantly (p><0.0001) older then the other with median of age 55 years (range 36-68) vs. median of 44 (range 14-66). They received significantly more (p><0.0001) granulocytes with median of 3.12 × 108 /kg BW (range 0.2-11.47) vs. median of 2.42 × 108 /kg BW (range 0.14-18.2). Conclusion: Patients with multiple myeloma, women and recipients of graft with high number of granulocytes should be monitored for signs and symptoms of the infusion-toxicity. Our results indicate that the composition of graft is relevant and toxicity could be reduced by improvement of apheresis product quality and depletion of mature cells in graft wich are poorly preserved through the cryopreservation process.
P098 LightCycler Septifast assay as a tool for the rapid diagnosis of sepsis in patients during antimicrobial therapy A. Vince, S. Židovec-Lepej, D. Dušek, Z. Mitrovic, I. Grgi´c, R. Serventi-Seiwerth, B. Labar. University Hospital for Infectious Diseases “Dr. Fran Mihaljevi´c”, and Department of Medicine University Hospital Center, Zagreb, Croatia Aim: The aim of this study was to determine the additional diagnostic value of the first in vitro diagnostic multiplex realtime PCR assay (LightCycler SeptiFast test) for detection of
microorganisms in the blood of patients with suspected sepsis even during antimicrobial therapy. The newly-developed SeptiFast test detects up to 26 bacterial and fungal DNA(s) in whole blood. Patients and methods: The study enrolled 35 patients suspected of sepsis from the University Hospital for Infectious Diseases, Zagreb and Zagreb University Clinical Center. Patients were divided into 3 groups: sepsis in patients from intensive care unit (ICU) (n= 17), sepsis in patients outside ICU (n=9) and sepsis in hematological patients following bone marrow or peripheral blood stem cells transplantation (n=9). Fungal and bacterial DNA in the blood of the patients was detected by using LightCycler SeptiFast (Roche Diagnostics, USA). All patients enrolled in the study were treated with antimicrobial agents empirically at the time of testing. Blood cultures were taken from all patients as well. Results: Twelve of 38 (32%) samples were positive for bacterial/fungal DNA. Gram-positive bacterial DNA was detected in 10 of 12 samples (Klebsiella pneumoniae/oxitoca n=4; Escherichia coli n=3; Pseudomonas aeruginosa n=3). Grampositive bacterial DNA (Enterococcus faecium n=1 and Streptococcus pneumoniae n=2) were detected in two patients with polymicrobial sepsis (in combination with Klebsiella pneumoniae/oxitoca in both patients). Fungal DNA was detected in two patients (Aspergillus fumigatus in both samples). Clinical diagnosis in patients with positive results of the LightCycler SeptiFast included: sepsis in patients from intensive care unit (ICU) (n=4), sepsis in patients outside ICU (n=4) and sepsis in hematological patients (n=4). Additional SeptiFast-positive results (blood culture negative) were obtained in 8 of 35 patients. We detected one discordant result between SeptiFast test and cultivation (Enterobacter cloacae was detected by cultivation and Klebsiella pneumoniae/oxytoca by SeptiFast test). Due to the fact that SeptiFast test does not detect Actinobacillus sp. DNA, this microorganism was detected in 1 patient by using cultivation method only. Conclusion: The results of our study have shown that SeptiFast test is a valuable add-on to conventional cultivation methods for detection of gram-negative and gram-positive bacteria, as well as fungi in the blood of patients presenting with clinical picture of sepsis even during antimicrobial therapy.
P099 Efficacy and safety of colistin for the treatment of infections caused by multidrug-resistant isolates of Pseudomonas aeruginosa sensitive to colistin in patients with haematological malignancy N. Durakovic, A. Boban, M. Mrsi´c, D. Serti´c, R. Serventi-Seiwerth, D. Nemet, B. Labar. Department of Medicine, University Hospital Centre and School of Medicine, Zagreb, Croatia Aim: Infections due to multidrug-resistant (MDR) Gram-
Poster Sessions negative bacteria have been increasing and they are an important cause of nosocomial morbidity and mortality, especially in immunocompromised patients. Aim of this retrospective study was to determine the efficacy and safety of colistin (colistimethate sodium) use in the treatment of MDR Pseudomonas aeruginosa sensitive to colistin. Patients and methods: In the period between February 2002 and December 2006, 24 patients hospitalized in our institution had an infection caused by MDR P.aeruginosa and were treated with intravenous colistin. Patients were 46% male and 54% female; mean age was 35 years (range 16-60). All of the patients were treated for haematological malignancy, majority for AML (58%), followed by ALL (13%), NHL (12%), aplastic anemia (8%), CML and multiple myeloma (both 4%). Majority of patients were treated with intensive chemotherapy regimens (46%), 25% received allogeneic and 25% autologous transplants. All of the patients had clinical signs of sepsis; in 54% MDR P.aeruginosa was isolated from blood, in 13% from urine, 12% from skin lesions that had clinical presentation of echtyma gangrenosum, while others had MDR P.aeruginosa isolated from surveillance cultures. Patients received 3 MU of colistin every 8 hours for a mean (± SD) duration of 12.3 (± 5.6) days. Due to nature of their disease, and severity of infections, all of the patients received more than two other possibly nephrotoxic drugs; 79% were receiving vancomycin, 71% cefepime, 38% amikacine, 13% garamycine, and 46% received amphotericine B deoxycholate concurrently. Results: Of 24 patients receiving colistin, 18 patients (75%) had the drug discontinued after successful clearance of infection. In 2 patients (8%) drug was exchanged for another one due to lack of clinical imrovement, and 3 patients had a lethal outcome (all in multiorgan failure due to sepsis). Only one patient had displayed neurological toxicity (Jacksons attack with secondary generalisation), but the drug was not discontinued, dose was modified, patient had no further attacks. There was no statistically significant difference in the level of serum creatinine, creatinine clearance (calculated), or potassium levels between prior to colistin therapy and after colistin cessation. One patient developed renal failure and had to be subjected to continuous venovenous hemodiafiltration; of note is that at the time colistin introduction patient already had impaired renal function. In one patient drug had to be discontinued due to suspected allergic reaction. No other adverse events were noted. Conclusion: Colistin is an effective antimicrobial drug for the treatment of severe infections caused by MDR P.aeruginosa in haematological patients. The safety profile observed is acceptable in these severe life-threatening infections. Further studies are needed to better address the treatment of MDR P.aeruginosa., naimely the optimal dose and schedule, also route of administration of colistin, as well as drug-to-drug interactions.
S109
P100 Predictors of outcome for patients with haematological malignancies in ICU V. Gasparovic, I. Gornik, A. Oršuli´c, M. Ili´c. Division of Emergency and Intensive Care Medicine, University Hospital Rebro, General Hospital Nova Gradiška and General Hospital Dubrovnik, Dubrovnik, Croatia Introduction: Management of patients with haematological malignancies in intensive care units with neutropenic sepsis and/or organ failure is associated with high mortality caused by lack of cellular defences, ongoing inflammatory processes and other complications (e.g. intracranial bleeding). Patients and methods: During a period of five years (20012006) 45 patients with haematological malignancies were treated in our ICU because of respiratory failure, severe sepsis or septic shock. Respiratory failure was defined by alteration in blood gasses and/or tachypnea, circulatory failure was defined by hypotension and tachycardia and/or need for vasoactive treatment. Karnofsky performance index and SAPS score were determined at admission. Results: Incidence of haematological malignancies was: AML 18 (40%), NHL 16 (35,6%), ALL 3 (6,7%), MM 3 (6,7%), CLL 1 (2,2%), others 4 (8,9%). There were 20 male and 25 female patients, mean age was 49±15 years. Average SAPS score was 70±13 (Median 69), Karnofsky indeks 21±10 (Median 10). Six patients (13.3%) survived. Median ICU LOS was 3 days for non-survivors and 5 days for survivors. Average time from ICU admission to start of mechanical ventilation was 38,5±68,2 (Median 9) hours. Predictors of ICU outcome were: high SAPS score (P=0,037) and respiratory failure (P=0,024) at admission and thrombocytopenia (p=0,013). For our patients’ age, sex, haematological disease and type of previous treatment were not predictive of outcome. Discussion: Management of neutropenic patients with haematological malignancies and respiratory failure usually is a consequence of infection of respiratory tract. High mortality of such patients has compelled several investigations of prognostic markers for outcome. It has been established that respiratory status and haemodinamic parameters have predictive value, while age and underlying haematological condition do not [1]. These results are in concordance with our own. Main predictors of outcome were SAPS score, respiratory failure and thrombocytopenia. Higher SASP score and Karnofsky index can explain higher mortality of our patients compared with previous studies. Leukocyte count was not shown to be predictive for outcome in our study unlike thrombocytopenia. This can be explained by the fact that all neutropenic patients received granulocyte colony stimulating factor that does not influence thrombocytopoesis. Other authors concluded that main predictors of unfavourable outcome were neutropenia, use of vasopressors and high urea, while positive blood cultures were associated with survival [2]. Renal failure was not an outcome predictor in our patients. Our results show that management of respiratory failure and neutropenic sepsis in patients with haematological malignan-