Intensive Care Med DOI 10.1007/s00134-015-4010-z
LETTER
survival showed no significant diftigecycline versus colistin– ferences between the two groups imipenem/cilastatin. [HR = 0.52; 95 % CI 0.20–1.34; Between 1 January 2009 and 30 p = 0.166] (Fig. 1). The inverse September 2014, 79 adult patients admitted in the ICU of Habib Bour- probability of treatment weighted guiba University Hospital developed (IPTW) Cox proportional hazards Ab VAP and were treated either with model adjusted for variables found to colistin–tigecycline [Tige(?) group; be significantly associated with death n = 19] or colistin–imipenem/cilas- 28 days after VAP diagnosis showed no significant difference between tatin [Tige(-) group; n = 60]. Tige(?) and Tige(-) groups Colistin–tigecycline regimen was [HR = 0.76, 95 % CI 0.44–1.33; used only when Ab isolated strains p = 0.34]. were resistant to imipenem. Colistin Colistin–tigecycline Unlike Freire et al.’s study [3], our was given at 2 MIU (million interversus colistin–imipenem– findings show the colistin–tigecycline national units) every 8 h without a cilastatin combinations loading dose. Tigecycline was given regimen to be as effective as colistin– at 100 mg twice a day during the first imipenem/cilastatin in patients with for the treatment 48 h and then at 50 mg twice a day. Ab VAP. This difference can be of Acinetobacter baumannii was given at 500 mg every related to two major factors: first, ventilator-acquired pneumonia: Imipenem tigecycline and imipenem were both 6 h. Median [interquartile range a prognosis study used in combination with colistin; (IQR)] age was 42 [27–60] years. second, our patients received highMedian [IQR] SOFA score was 7 Accepted: 3 August 2015 [5–10]. Median [IQR] from the initi- dose tigecycline regimen during the first 48 h. In fact, Burkhardt et al. [4] ation of mechanical ventilation to Ó Springer-Verlag Berlin Heidelberg and reported that the concentration of VAP onset was 7 [5–10] days. SubESICM 2015 tigecycline in the intracellular sequent Ab bloodstream infections were recorded in 10 patients and were epithelial lining fluid was particularly high, whereas it was significantly significantly more frequent in the lower in the extracellular fluid. Tige(?) group (26.3 versus 8.3 %; Dear Editor, Hence, using tigecycline with a high p = 0.04). Median [IQR] MIC of Ventilator-acquired pneumonia tigecycline in the Tige(?) group was dosage may improve its efficacy in (VAP) still remains a major issue in 1 [0.4–1.8] mg/l. Crude ICU mortal- VAP patients. Moreover, these 48 h intensive care units (ICUs). Several ity was significantly lower in the represent the time needed to achieve studies highlighted that Pseudomonas Tige(?) group (26.3 versus 53.3 %; an effective concentration of colistin aeruginosa or Acinetobacter bauat the infection site [5]. The major p = 0.04). The Kaplan–Meier estimannii (Ab) are two leading causes of mates of the probability of day 28 limitations of our study are its mortality in this setting [1]. Multidrug resistance is one of the hallmarks of Ab infections. Hence, a renewed interest in colistin as a salvage therapy has emerged in the last few decades. More recently, experimental studies testing the susceptibility of Ab to tigecycline gave promising results [2]. However, a phase 3, multicenter, randomized, double-blind study has shown that tigecycline use was associated with higher mortality in the subgroup of patients with VAP when compared to imipenem/cilastatin [3]. The aim of our study was to compare two regimens for the treatment of Fig. 1 Survival Kaplan–Meier curve by day 28 comparing tigecycline–colistin versus imipenem–colistin regimens patients with Ab VAP: colistin– Anis Chaari Ta`i Pham Basma Mnif Kamilia Chtara Fatma Medhioub Najeh Baccouche Mabrouk Bahloul Adne`ne Hammami Mounir Bouaziz
3. Freire AT, Melnyk V, Kim MJ, Datsenko O, Dzyublik O, Glumcher F, Chuang YC, Maroko RT, Dukart G, Cooper CA et al (2010) Comparison of tigecycline with imipenem/cilastatin for the Compliance with ethical standards treatment of hospital-acquired pneumonia. Diagn Microbiol Infect Dis Conflicts of interest None. 68(2):140–151 4. Burkhardt O, Rauch K, Kaever V, Hadem J, Kielstein JT, Welte T (2009) Tigecycline possibly underdosed for the treatment of pneumonia: a References pharmacokinetic viewpoint. Int J Antimicrob Agents 34(1):101–102 1. Bassetti M, De Waele JJ, Eggimann P, 5. Plachouras D, Karvanen M, Friberg LE, Garnacho-Montero J, Kahlmeter G, Papadomichelakis E, Antoniadou A, Menichetti F, Nicolau DP, Paiva JA, Tsangaris I, Karaiskos I, Poulakou G, Tumbarello M, Welte T et al (2015) Kontopidou F, Armaganidis A et al Preventive and therapeutic strategies in (2009) Population pharmacokinetic critically ill patients with highly resistant analysis of colistin methanesulfonate and bacteria. Intensive Care Med colistin after intravenous administration 41(5):776–795 in critically ill patients with infections 2. Scheetz MH, Qi C, Warren JR, caused by gram-negative bacteria. Postelnick MJ, Zembower T, Obias A, Antimicrob Agents Chemother Noskin GA (2007) In vitro activities of 53(8):3430–3436 various antimicrobials alone and in combination with tigecycline against carbapenem-intermediate or -resistant A. Chaari ()) K. Chtara F. Medhioub Acinetobacter baumannii. Antimicrob N. Baccouche M. Bahloul M. Bouaziz Agents Chemother 51(5):1621–1626 Department of Intensive Care, Habib Bourguiba University Hospital, Faculty of Medicine, Road El Ain km 0.5, 3029 Sfax, Tunisia e-mail: [email protected] Tel.: (?216) 26349334
retrospective design and the small sample size. Further studies are needed to confirm our findings.
T. Pham AP-HP, Hoˆpital Tenon, Unite´ de Re´animation me´dico-chirurgicale, Poˆle Thorax Voies ae´riennes, Groupe hospitalier des Hoˆpitaux Universitaires de L’Est Parisien, Hoˆpital Tenon, 4 rue de la Chine, 75020 Paris Cedex 20, France T. Pham UMR 1153, Inserm, Sorbonne Paris Cite´, ECSTRA Team, Universite´ Paris Diderot, Paris, France T. Pham UMR 915, Inserm, Universite´ Paris Est Cre´teil, Cre´teil, France B. Mnif A. Hammami Department of Microbiology, Habib Bourguiba University Hospital, Faculty of Medicine, Sfax, Tunisia
LETTER
survival showed no significant diftigecycline versus colistin– ferences between the two groups imipenem/cilastatin. [HR = 0.52; 95 % CI 0.20–1.34; Between 1 January 2009 and 30 p = 0.166] (Fig. 1). The inverse September 2014, 79 adult patients admitted in the ICU of Habib Bour- probability of treatment weighted guiba University Hospital developed (IPTW) Cox proportional hazards Ab VAP and were treated either with model adjusted for variables found to colistin–tigecycline [Tige(?) group; be significantly associated with death n = 19] or colistin–imipenem/cilas- 28 days after VAP diagnosis showed no significant difference between tatin [Tige(-) group; n = 60]. Tige(?) and Tige(-) groups Colistin–tigecycline regimen was [HR = 0.76, 95 % CI 0.44–1.33; used only when Ab isolated strains p = 0.34]. were resistant to imipenem. Colistin Colistin–tigecycline Unlike Freire et al.’s study [3], our was given at 2 MIU (million interversus colistin–imipenem– findings show the colistin–tigecycline national units) every 8 h without a cilastatin combinations loading dose. Tigecycline was given regimen to be as effective as colistin– at 100 mg twice a day during the first imipenem/cilastatin in patients with for the treatment 48 h and then at 50 mg twice a day. Ab VAP. This difference can be of Acinetobacter baumannii was given at 500 mg every related to two major factors: first, ventilator-acquired pneumonia: Imipenem tigecycline and imipenem were both 6 h. Median [interquartile range a prognosis study used in combination with colistin; (IQR)] age was 42 [27–60] years. second, our patients received highMedian [IQR] SOFA score was 7 Accepted: 3 August 2015 [5–10]. Median [IQR] from the initi- dose tigecycline regimen during the first 48 h. In fact, Burkhardt et al. [4] ation of mechanical ventilation to Ó Springer-Verlag Berlin Heidelberg and reported that the concentration of VAP onset was 7 [5–10] days. SubESICM 2015 tigecycline in the intracellular sequent Ab bloodstream infections were recorded in 10 patients and were epithelial lining fluid was particularly high, whereas it was significantly significantly more frequent in the lower in the extracellular fluid. Tige(?) group (26.3 versus 8.3 %; Dear Editor, Hence, using tigecycline with a high p = 0.04). Median [IQR] MIC of Ventilator-acquired pneumonia tigecycline in the Tige(?) group was dosage may improve its efficacy in (VAP) still remains a major issue in 1 [0.4–1.8] mg/l. Crude ICU mortal- VAP patients. Moreover, these 48 h intensive care units (ICUs). Several ity was significantly lower in the represent the time needed to achieve studies highlighted that Pseudomonas Tige(?) group (26.3 versus 53.3 %; an effective concentration of colistin aeruginosa or Acinetobacter bauat the infection site [5]. The major p = 0.04). The Kaplan–Meier estimannii (Ab) are two leading causes of mates of the probability of day 28 limitations of our study are its mortality in this setting [1]. Multidrug resistance is one of the hallmarks of Ab infections. Hence, a renewed interest in colistin as a salvage therapy has emerged in the last few decades. More recently, experimental studies testing the susceptibility of Ab to tigecycline gave promising results [2]. However, a phase 3, multicenter, randomized, double-blind study has shown that tigecycline use was associated with higher mortality in the subgroup of patients with VAP when compared to imipenem/cilastatin [3]. The aim of our study was to compare two regimens for the treatment of Fig. 1 Survival Kaplan–Meier curve by day 28 comparing tigecycline–colistin versus imipenem–colistin regimens patients with Ab VAP: colistin– Anis Chaari Ta`i Pham Basma Mnif Kamilia Chtara Fatma Medhioub Najeh Baccouche Mabrouk Bahloul Adne`ne Hammami Mounir Bouaziz
3. Freire AT, Melnyk V, Kim MJ, Datsenko O, Dzyublik O, Glumcher F, Chuang YC, Maroko RT, Dukart G, Cooper CA et al (2010) Comparison of tigecycline with imipenem/cilastatin for the Compliance with ethical standards treatment of hospital-acquired pneumonia. Diagn Microbiol Infect Dis Conflicts of interest None. 68(2):140–151 4. Burkhardt O, Rauch K, Kaever V, Hadem J, Kielstein JT, Welte T (2009) Tigecycline possibly underdosed for the treatment of pneumonia: a References pharmacokinetic viewpoint. Int J Antimicrob Agents 34(1):101–102 1. Bassetti M, De Waele JJ, Eggimann P, 5. Plachouras D, Karvanen M, Friberg LE, Garnacho-Montero J, Kahlmeter G, Papadomichelakis E, Antoniadou A, Menichetti F, Nicolau DP, Paiva JA, Tsangaris I, Karaiskos I, Poulakou G, Tumbarello M, Welte T et al (2015) Kontopidou F, Armaganidis A et al Preventive and therapeutic strategies in (2009) Population pharmacokinetic critically ill patients with highly resistant analysis of colistin methanesulfonate and bacteria. Intensive Care Med colistin after intravenous administration 41(5):776–795 in critically ill patients with infections 2. Scheetz MH, Qi C, Warren JR, caused by gram-negative bacteria. Postelnick MJ, Zembower T, Obias A, Antimicrob Agents Chemother Noskin GA (2007) In vitro activities of 53(8):3430–3436 various antimicrobials alone and in combination with tigecycline against carbapenem-intermediate or -resistant A. Chaari ()) K. Chtara F. Medhioub Acinetobacter baumannii. Antimicrob N. Baccouche M. Bahloul M. Bouaziz Agents Chemother 51(5):1621–1626 Department of Intensive Care, Habib Bourguiba University Hospital, Faculty of Medicine, Road El Ain km 0.5, 3029 Sfax, Tunisia e-mail: [email protected] Tel.: (?216) 26349334
retrospective design and the small sample size. Further studies are needed to confirm our findings.
T. Pham AP-HP, Hoˆpital Tenon, Unite´ de Re´animation me´dico-chirurgicale, Poˆle Thorax Voies ae´riennes, Groupe hospitalier des Hoˆpitaux Universitaires de L’Est Parisien, Hoˆpital Tenon, 4 rue de la Chine, 75020 Paris Cedex 20, France T. Pham UMR 1153, Inserm, Sorbonne Paris Cite´, ECSTRA Team, Universite´ Paris Diderot, Paris, France T. Pham UMR 915, Inserm, Universite´ Paris Est Cre´teil, Cre´teil, France B. Mnif A. Hammami Department of Microbiology, Habib Bourguiba University Hospital, Faculty of Medicine, Sfax, Tunisia
