Jpn. J. Infect. Dis., 68, 318–320, 2015
Original Article
Incidence and Risk Factors for Colistin-Associated Nephrotoxicity Fatih Temocin1*, Sebnem Erdinc2, Necla Tulek2, Meryem Demirelli2, Cemal Bulut2, and Gunay Ertem2 1Department 2Infectious
of Infectious Diseases and Clinical Microbiology, Yozgat State Hospital, Yozgat; and Diseases and Clinical Microbiology, Ankara Training and Research Hospital, Ankara, Turkey
SUMMARY: Polymyxins have recently reemerged as a treatment option in response to the increasing number of resistant bacterial infections seen in recent years. Therefore, the current study aimed to determine the rate of and risk factors related to colistin-associated nephrotoxicity. All adult patients who had received colistimethate sodium (CMS) between 2010 and 2012 and met the inclusion criteria were included in the study. RIFLE (Risk, Injury, Failure, Loss of renal function and End stage of renal disease) criteria were used to evaluate nephrotoxicity. Age, sex, underlying diseases presences, daily and total CMS doses, daily blood urea and creatinine levels, as well as concurrent drug use were recorded for each patient. Nephrotoxicity occurred in 48z of patients. There was a significant difference in the baseline serum urea levels of patients who experienced nephrotoxicity and those who did not (P value (P) ＝ 0.015). Furthermore, the multivariate analysis showed that advanced age and concomitant aminoglycoside-class antibiotic use were significantly associated with nephrotoxicity. In conclusion, colistin should be used carefully, and all patients should be monitored closely for renal nephrotoxicity.
INTRODUCTION
MATERIALS AND METHODS
Colistin is a polymyxin-class antimicrobial agent. Polymyxins were first produced in 1947, and were used regularly between 1950 and 1980. However, because of the emergence of nephrotoxic side effects (which reached ～50z) associated with their use, polymyxins were replaced with different therapeutic agents. Since then colistin has been used primarily for the treatment of patients with cystic fibrosis (1). However, with the increasing number of resistant bacterial infections in recent years and the limited number of antibiotics that can be used for treating these infections, polymyxins have re-emerged as a preferred treatment option. In particular, polymyxins are especially used as compulsory antibiotics for the treatment of infections caused by multi-drug resistant Pseudomonas aeruginosa (P. aeruginosa) and Acinetobacter baumannii (A. baumannii ) as well as infections caused by carbapenamaseproducing enteric bacteria (2). Colistin is available in two forms: colistin sulfate and colistimethate sodium (CMS). CMS has a lower therapeutic efficacy, and it has a lower nephrotoxic effect (2,3). However, recent studies with colistin have reported lower nephrotoxicity rates compared to those in previous studies (4,5). In recent years, there has been an increase in the incidence of multi-drug resistant gram-negative bacilli and accordingly, a parallel increase in colistin use. The current study aimed to determine the incidence and risk factors of colistin-associated nephrotoxicity in patients who received CMS therapy.
Patients: Adult patients who received CMS at the Ankara Training and Research Hospital between December 2010 and December 2012 were retrospectively included in this study. The hospital has a 600-bed capacity and is located in the capital city of Turkey. The infection control committee performs active patient- and laboratory-based surveillance in high-priority departments such as the intensive care units. The decision to use colistin was made by infectious disease and clinical microbiology physicians. Patients included in this study were contacted through the pharmacy database and clinical records. Patients with chronic renal disease (regardless of the need for hemodialysis), who were treated for less than 72 h, were younger than 16 years-old, required an initial dose adjustment, or were taking a recurrent course of colistin therapy, were excluded from this study. The daily dose of colistin was recorded in milligrams and analyzed accordingly. Individual patient information was recorded separately on the relevant forms. CMS (Kocak Farma, Istanbul, Turkey) equivalent to 300 mg/ day (2 × 150 mg/day) colistin basal activity was the standard initial dose, however, adjustments were applied when needed. Variables and definitions: The RIFLE (Risk, Injury, Failure, Loss of kidney function, and End stage of renal disease) criteria were used to evaluate nephrotoxicity (Table 1) (6). Age, sex, underlying diseases, daily CMS Table 1. RIFLE1) criteria used for nephrotoxicity Risk Injury Failure Loss ESRD
Received May 23, 2014. Accepted October 29, 2014. J-STAGE Advance Publication February 13, 2015. DOI: 10.7883/yoken.JJID.2014.223 *Corresponding author: Mailing address: Department of Infectious Diseases and Clinical Microbiology, Yozgat State Hospital, 66100, Yozgat, Turkey. E-mail: ftemucin ＠yahoo.com.tr
1): 2):
318
Serum creatinine × 1.5 or GFR2) decrease ＞25z Serum creatinine × 2 or GFR decrease ＞50z Serum creatinine × 3 or GFR decrease ＞75z Persistent acute renal failure or function loss ＞4 weeks End-stage renal disease ＞3 months
Adapted from reference (6). Glomerular Filtration Rate.
Colistin-Associated Nephrotoxicity
Nephrotoxicity, as defined by the RIFLE criteria, occurred in 62 patients (48.1z); however, the majority of these patients were in the ``Risk'' group (53.2z) (Table 3). Hemodialysis was required for 1 patient who developed renal failure. Furthermore, colistin had to be discontinued in 4 patients because their creatinine levels continued to increase despite dosage adjustment. In patients who experienced nephrotoxicity, the mean and median values of the total colistin dose received prior to renal damage were 1591.9 ± 751 mg and 1350 mg, respectively. Deterioration in renal functioning was observed as early as on the 3rd day of therapy and as late as the 14th day of therapy (mean 5.4 ± 2.4 days, median 5.0 days). While we adjusted the dose immediately upon detection of deterioration in renal functioning, the patients with normal renal functionings continued to receive maintenance dosages; therefore, a comparison between the dosages could not be performed.
dose, total CMS dose received immediately before renal failure developed, daily blood urea and creatinine levels, as well as concurrent drug use (i.e., aminoglycoside, vancomycin, carbapenem, diuretics, acetylcysteine, non-steroid anti-inflammatory drugs, and other drug uses) were also included in the record. Statistical analysis: SPSS ver.15.0 software was used for the statistical analyses. The change in creatinine levels over time was analyzed using a repeated-measures analysis of variance, with pairwise comparisons using a paired t test. The Fisher's exact test and the Wilcoxon rank-sum were used to determine the differences between patients with and patients without evidence of renal failure. A P value (P) ＜ 0.05 was considered statistically significant. RESULTS Of the 149 patients who used colistin, 15 were excluded prior to the treatment because of renal failure, 3 were excluded for drug use within the past 72 h, and 2 were excluded based on age (＜16 years). The remaining 129 patients were included in the study. Of these, 70 (54.3z) received treatment for pneumonia; 25 (19.4z), for a urinary tract infection; 18 (14z), for a bloodstream infection; 10 (7.8z), for a soft tissue infection; 4 (3.2z), for a central nervous system infection; and 2 (1.6z), for another types of infection. A. baumannii was the cause of infection in the majority of the patients (84.5z), followed by P. aeruginosa (10.9z) and Expanded Spectrum b Lactamase-positive Escherichia coli (3.1z). Colistin use in these patients was required because of multi-drug resistance, including resistance to carbapenems. Empirical treatment was administered to two patients. Table 2 shows the demographic and clinical characteristics of the patients in this study. Advanced age was a risk factor for nephrotoxicity in the univariate analysis (P ＜ 0.001). There was no significant difference in baseline creatinine levels between patients who experienced nephrotoxicity and those who did not. On the other hand, there was a significant difference in baseline serum urea levels in patients who experienced nephrotoxicity and those who did not (P ＝ 0.015). In addition, the concomitant use of aminoglycoside-class antibiotics significantly increased the occurrence of nephrotoxicity (P ＝ 0.047) (data not shown). Both advanced age and use of antibiotics belonging to the aminoglycoside-class antibiotics remained significant in multivariate analysis (OR 3.1, P ＝ 0.007; 95z CI, [1.361–7.025]), (OR 2.8, P ＝ 0.01; 95z CI [1.281–6.214]), respectively.
DISCUSSION The current study examined patients who used colistin during a 2-year period and identified risk factors related to nephrotoxicity rates. The results showed that nephrotoxicity occurred in 48z of the patients. Two recent studies using the same colistin dosages reported similar results nephrotoxicity rates of 45z and 43z, respectively (7,8). This study also showed that advanced age was a significant risk factor for colistin-associated nephrotoxicity. The incidence of nephrotoxicity development was significantly higher in patients who had high urea levels at the beginning of treatment compared to patients who had normal levels. Although other studies have not examined blood urea levels as a risk factor (9,10), our findings underline the importance of focusing on patient urea levels at the beginning of treatment, even if GFR and serum creatinine levels are normal. Table 3. Distribution of patients with nephrotoxicity according to RIFLE criteria except ``Loss'' and ``End-stage renal disease'' Criteria
No. of patient (total)
z
No nephrotoxicity Nephrotoxicity
67 (129) 62 (129)
51.9 48.1
33 13 16
53.2 21.0 25.8
R (Risk) I (Injury) F (Failure)
Table 2. Demographic and clinical features of patients under CMS therapy Characteristic
All patient (n ＝ 129)
Patient with nephrotoxicity outcome (n ＝ 62)
Patient without nephrotoxicity outcome (n ＝ 67)
P value
Sex (Female/Male) Mean age (years) Older than 65 years Baseline creatinine level (mg/dL) Baseline urea level (mg/dL) Mean treatment duration (days)
62/67 61.7 ± 18.1 69 (53.5z) 0.865 ± 0.488 53.8 ± 37.2 9.5 ± 3.4
28/34 67.5 ± 14.7 41 (66.1z) 0.922 ± 0.446 62.1 ± 37.5 9.5 ± 3.3
34/33 56.2 ± 19.3 28 (41.8z) 0.811 ± 0.522 46.09 ± 35.6 9.5 ± 3.4
0.526 ＜0.001 0.006 0.199 0.015 0.122
319
In this study, vancomycin, carbapenems, and aminoglycoside-class antibiotics were also analyzed as risk factors, however, only aminoglycoside-class antibiotics had a significant effect on nephrotoxicity (P ＜ 0.05). This indicates that antibiotics that will be combined with colistin should be carefully selected. This study also investigated the use of N-acetylcysteine, which is recommended to prevent contrast substance nephropathy because of its antioxidant properties (11–13). However, N-acetylcysteine had no effect on the prevention of colistin nephrotoxicity in this study (P ＝ 0.584, data not shown). In addition the majority of patients who experienced nephrotoxicity due to colistin were categorized in the RIFLE criteria ``Risk'' group. This could be related to close monitoring, daily renal tests, and prompt dosage adjustments. On the other hand, given that long-term follow-up of patients was not performed, the long-term effects of colistin on renal functions could not be assessed. Further studies are needed to assess the longterm effects of colistin nephrotoxicity. The first case of colistin nephrotoxicity occurred on the 3rd day at a cumulative dose of 600 mg. Therefore, as suggested by Falagas et al. (14), both the duration of use as well as the cumulative dose of colistin should be taken into account when predicting colistin nephrotoxicity. In conclusion, colistin should be used carefully in older patients, patients using concurrent mediations, and patients with high blood urea levels. In addition, all patients should be closely monitored for renal nephrotoxicity.
2. 3.
4.
5. 6. 7. 8. 9. 10. 11. 12.
13.
Conflict of interest None to declare.
14.
REFERENCES 1. Falagas ME, Kasiakou SK. Toxicity of polymyxins: a systematic
320
review of the evidence from old and recent studies. Crit Care. 2006;10:R27. Kwa A, Kasiakou SK, Tam VH, et al. Polymyxin B: similarities to and differences from colistin (polymyxin E). Expert Rev Anti Infect Ther. 2007;5:811-21. Li J, Turnidge J, Milne R, et al. In vitro pharmacodynamic properties of colistin and colistin methanesulfonate against Pseudomonas aeruginosa isolates from patients with cystic fibrosis. Antimicrob Agents Chemother. 2001;45:781-5. Falagas ME, Rafailidis PI, Loannidou E, et al. Colistin therapy for microbiologically documented multidrug-resistant gram-negative bacterial infections: a retrospective cohort study of 258 patients. Int J Antimicrob Agents. 2010;35:194-9. Paul M, Bishara J, Levcovich A, et al. Effectiveness and safety of colistin: prospective comparative cohort study. J Antimicrob Chemother. 2010;65:1019-27. Kellum JA, Bellomo R, Ronco C. Definition and classification of acute kidney injury. Nephron Clin Pract. 2008;109:c182-7. Hartzell JD, Neff R, Ake J, et al. Nephrotoxicity associated with intravenous colistin (colistimethate sodium) treatment at a tertiary care medical center. Clin Infect Dis. 2009;48:1724-8. Pogue JM, Lee J, Marchaim D, et al. Incidence of and risk factors for colistin-associated nephrotoxicity in a large academic health system. Clin Infect Dis. 2011;53:879-84. Deryke CA, Crawford AJ, Uddin N, et al. Colistin dosing and nephrotoxicity in a large community teaching hospital. Antimicrob Agents Chemother. 2010;54:4503-5. Sorli L, Luque S, Grau S, et al. Trough colistin plasma level is an independent risk factor for nephrotoxicity: a prospective observational cohort study. BMC Infect Dis. 2013;13:380. Briguori C, Manganelli F, Scarpato P, et al. Acetylcysteine and contrast agent-associated nephrotoxicity. J Am Coll Cardiol. 2002;40:298-303. Tadros GM, Mouhayar EN, Akinwande AO, et al. Prevention of radiocontrast-induced nephropathy with N-acetylcysteine in patients undergoing coronary angiography. J Invasive Cardiol. 2003;15:311-4. Tepel M, Van der Giet M, Schwarzfeld C, et al. Prevention of radiographic-contrast-agent-induced reductions in renal function by acetylcysteine. N Engl J Med. 2000;343:180-4. Falagas ME, Fragoulis KN, Kasiakou SK, et al. Nephrotoxicity of intravenous colistin: a prospective evaluation. Int J Antimicrob Agents. 2005;26:504-7.
Original Article
Incidence and Risk Factors for Colistin-Associated Nephrotoxicity Fatih Temocin1*, Sebnem Erdinc2, Necla Tulek2, Meryem Demirelli2, Cemal Bulut2, and Gunay Ertem2 1Department 2Infectious
of Infectious Diseases and Clinical Microbiology, Yozgat State Hospital, Yozgat; and Diseases and Clinical Microbiology, Ankara Training and Research Hospital, Ankara, Turkey
SUMMARY: Polymyxins have recently reemerged as a treatment option in response to the increasing number of resistant bacterial infections seen in recent years. Therefore, the current study aimed to determine the rate of and risk factors related to colistin-associated nephrotoxicity. All adult patients who had received colistimethate sodium (CMS) between 2010 and 2012 and met the inclusion criteria were included in the study. RIFLE (Risk, Injury, Failure, Loss of renal function and End stage of renal disease) criteria were used to evaluate nephrotoxicity. Age, sex, underlying diseases presences, daily and total CMS doses, daily blood urea and creatinine levels, as well as concurrent drug use were recorded for each patient. Nephrotoxicity occurred in 48z of patients. There was a significant difference in the baseline serum urea levels of patients who experienced nephrotoxicity and those who did not (P value (P) ＝ 0.015). Furthermore, the multivariate analysis showed that advanced age and concomitant aminoglycoside-class antibiotic use were significantly associated with nephrotoxicity. In conclusion, colistin should be used carefully, and all patients should be monitored closely for renal nephrotoxicity.
INTRODUCTION
MATERIALS AND METHODS
Colistin is a polymyxin-class antimicrobial agent. Polymyxins were first produced in 1947, and were used regularly between 1950 and 1980. However, because of the emergence of nephrotoxic side effects (which reached ～50z) associated with their use, polymyxins were replaced with different therapeutic agents. Since then colistin has been used primarily for the treatment of patients with cystic fibrosis (1). However, with the increasing number of resistant bacterial infections in recent years and the limited number of antibiotics that can be used for treating these infections, polymyxins have re-emerged as a preferred treatment option. In particular, polymyxins are especially used as compulsory antibiotics for the treatment of infections caused by multi-drug resistant Pseudomonas aeruginosa (P. aeruginosa) and Acinetobacter baumannii (A. baumannii ) as well as infections caused by carbapenamaseproducing enteric bacteria (2). Colistin is available in two forms: colistin sulfate and colistimethate sodium (CMS). CMS has a lower therapeutic efficacy, and it has a lower nephrotoxic effect (2,3). However, recent studies with colistin have reported lower nephrotoxicity rates compared to those in previous studies (4,5). In recent years, there has been an increase in the incidence of multi-drug resistant gram-negative bacilli and accordingly, a parallel increase in colistin use. The current study aimed to determine the incidence and risk factors of colistin-associated nephrotoxicity in patients who received CMS therapy.
Patients: Adult patients who received CMS at the Ankara Training and Research Hospital between December 2010 and December 2012 were retrospectively included in this study. The hospital has a 600-bed capacity and is located in the capital city of Turkey. The infection control committee performs active patient- and laboratory-based surveillance in high-priority departments such as the intensive care units. The decision to use colistin was made by infectious disease and clinical microbiology physicians. Patients included in this study were contacted through the pharmacy database and clinical records. Patients with chronic renal disease (regardless of the need for hemodialysis), who were treated for less than 72 h, were younger than 16 years-old, required an initial dose adjustment, or were taking a recurrent course of colistin therapy, were excluded from this study. The daily dose of colistin was recorded in milligrams and analyzed accordingly. Individual patient information was recorded separately on the relevant forms. CMS (Kocak Farma, Istanbul, Turkey) equivalent to 300 mg/ day (2 × 150 mg/day) colistin basal activity was the standard initial dose, however, adjustments were applied when needed. Variables and definitions: The RIFLE (Risk, Injury, Failure, Loss of kidney function, and End stage of renal disease) criteria were used to evaluate nephrotoxicity (Table 1) (6). Age, sex, underlying diseases, daily CMS Table 1. RIFLE1) criteria used for nephrotoxicity Risk Injury Failure Loss ESRD
Received May 23, 2014. Accepted October 29, 2014. J-STAGE Advance Publication February 13, 2015. DOI: 10.7883/yoken.JJID.2014.223 *Corresponding author: Mailing address: Department of Infectious Diseases and Clinical Microbiology, Yozgat State Hospital, 66100, Yozgat, Turkey. E-mail: ftemucin ＠yahoo.com.tr
1): 2):
318
Serum creatinine × 1.5 or GFR2) decrease ＞25z Serum creatinine × 2 or GFR decrease ＞50z Serum creatinine × 3 or GFR decrease ＞75z Persistent acute renal failure or function loss ＞4 weeks End-stage renal disease ＞3 months
Adapted from reference (6). Glomerular Filtration Rate.
Colistin-Associated Nephrotoxicity
Nephrotoxicity, as defined by the RIFLE criteria, occurred in 62 patients (48.1z); however, the majority of these patients were in the ``Risk'' group (53.2z) (Table 3). Hemodialysis was required for 1 patient who developed renal failure. Furthermore, colistin had to be discontinued in 4 patients because their creatinine levels continued to increase despite dosage adjustment. In patients who experienced nephrotoxicity, the mean and median values of the total colistin dose received prior to renal damage were 1591.9 ± 751 mg and 1350 mg, respectively. Deterioration in renal functioning was observed as early as on the 3rd day of therapy and as late as the 14th day of therapy (mean 5.4 ± 2.4 days, median 5.0 days). While we adjusted the dose immediately upon detection of deterioration in renal functioning, the patients with normal renal functionings continued to receive maintenance dosages; therefore, a comparison between the dosages could not be performed.
dose, total CMS dose received immediately before renal failure developed, daily blood urea and creatinine levels, as well as concurrent drug use (i.e., aminoglycoside, vancomycin, carbapenem, diuretics, acetylcysteine, non-steroid anti-inflammatory drugs, and other drug uses) were also included in the record. Statistical analysis: SPSS ver.15.0 software was used for the statistical analyses. The change in creatinine levels over time was analyzed using a repeated-measures analysis of variance, with pairwise comparisons using a paired t test. The Fisher's exact test and the Wilcoxon rank-sum were used to determine the differences between patients with and patients without evidence of renal failure. A P value (P) ＜ 0.05 was considered statistically significant. RESULTS Of the 149 patients who used colistin, 15 were excluded prior to the treatment because of renal failure, 3 were excluded for drug use within the past 72 h, and 2 were excluded based on age (＜16 years). The remaining 129 patients were included in the study. Of these, 70 (54.3z) received treatment for pneumonia; 25 (19.4z), for a urinary tract infection; 18 (14z), for a bloodstream infection; 10 (7.8z), for a soft tissue infection; 4 (3.2z), for a central nervous system infection; and 2 (1.6z), for another types of infection. A. baumannii was the cause of infection in the majority of the patients (84.5z), followed by P. aeruginosa (10.9z) and Expanded Spectrum b Lactamase-positive Escherichia coli (3.1z). Colistin use in these patients was required because of multi-drug resistance, including resistance to carbapenems. Empirical treatment was administered to two patients. Table 2 shows the demographic and clinical characteristics of the patients in this study. Advanced age was a risk factor for nephrotoxicity in the univariate analysis (P ＜ 0.001). There was no significant difference in baseline creatinine levels between patients who experienced nephrotoxicity and those who did not. On the other hand, there was a significant difference in baseline serum urea levels in patients who experienced nephrotoxicity and those who did not (P ＝ 0.015). In addition, the concomitant use of aminoglycoside-class antibiotics significantly increased the occurrence of nephrotoxicity (P ＝ 0.047) (data not shown). Both advanced age and use of antibiotics belonging to the aminoglycoside-class antibiotics remained significant in multivariate analysis (OR 3.1, P ＝ 0.007; 95z CI, [1.361–7.025]), (OR 2.8, P ＝ 0.01; 95z CI [1.281–6.214]), respectively.
DISCUSSION The current study examined patients who used colistin during a 2-year period and identified risk factors related to nephrotoxicity rates. The results showed that nephrotoxicity occurred in 48z of the patients. Two recent studies using the same colistin dosages reported similar results nephrotoxicity rates of 45z and 43z, respectively (7,8). This study also showed that advanced age was a significant risk factor for colistin-associated nephrotoxicity. The incidence of nephrotoxicity development was significantly higher in patients who had high urea levels at the beginning of treatment compared to patients who had normal levels. Although other studies have not examined blood urea levels as a risk factor (9,10), our findings underline the importance of focusing on patient urea levels at the beginning of treatment, even if GFR and serum creatinine levels are normal. Table 3. Distribution of patients with nephrotoxicity according to RIFLE criteria except ``Loss'' and ``End-stage renal disease'' Criteria
No. of patient (total)
z
No nephrotoxicity Nephrotoxicity
67 (129) 62 (129)
51.9 48.1
33 13 16
53.2 21.0 25.8
R (Risk) I (Injury) F (Failure)
Table 2. Demographic and clinical features of patients under CMS therapy Characteristic
All patient (n ＝ 129)
Patient with nephrotoxicity outcome (n ＝ 62)
Patient without nephrotoxicity outcome (n ＝ 67)
P value
Sex (Female/Male) Mean age (years) Older than 65 years Baseline creatinine level (mg/dL) Baseline urea level (mg/dL) Mean treatment duration (days)
62/67 61.7 ± 18.1 69 (53.5z) 0.865 ± 0.488 53.8 ± 37.2 9.5 ± 3.4
28/34 67.5 ± 14.7 41 (66.1z) 0.922 ± 0.446 62.1 ± 37.5 9.5 ± 3.3
34/33 56.2 ± 19.3 28 (41.8z) 0.811 ± 0.522 46.09 ± 35.6 9.5 ± 3.4
0.526 ＜0.001 0.006 0.199 0.015 0.122
319
In this study, vancomycin, carbapenems, and aminoglycoside-class antibiotics were also analyzed as risk factors, however, only aminoglycoside-class antibiotics had a significant effect on nephrotoxicity (P ＜ 0.05). This indicates that antibiotics that will be combined with colistin should be carefully selected. This study also investigated the use of N-acetylcysteine, which is recommended to prevent contrast substance nephropathy because of its antioxidant properties (11–13). However, N-acetylcysteine had no effect on the prevention of colistin nephrotoxicity in this study (P ＝ 0.584, data not shown). In addition the majority of patients who experienced nephrotoxicity due to colistin were categorized in the RIFLE criteria ``Risk'' group. This could be related to close monitoring, daily renal tests, and prompt dosage adjustments. On the other hand, given that long-term follow-up of patients was not performed, the long-term effects of colistin on renal functions could not be assessed. Further studies are needed to assess the longterm effects of colistin nephrotoxicity. The first case of colistin nephrotoxicity occurred on the 3rd day at a cumulative dose of 600 mg. Therefore, as suggested by Falagas et al. (14), both the duration of use as well as the cumulative dose of colistin should be taken into account when predicting colistin nephrotoxicity. In conclusion, colistin should be used carefully in older patients, patients using concurrent mediations, and patients with high blood urea levels. In addition, all patients should be closely monitored for renal nephrotoxicity.
2. 3.
4.
5. 6. 7. 8. 9. 10. 11. 12.
13.
Conflict of interest None to declare.
14.
REFERENCES 1. Falagas ME, Kasiakou SK. Toxicity of polymyxins: a systematic
320
review of the evidence from old and recent studies. Crit Care. 2006;10:R27. Kwa A, Kasiakou SK, Tam VH, et al. Polymyxin B: similarities to and differences from colistin (polymyxin E). Expert Rev Anti Infect Ther. 2007;5:811-21. Li J, Turnidge J, Milne R, et al. In vitro pharmacodynamic properties of colistin and colistin methanesulfonate against Pseudomonas aeruginosa isolates from patients with cystic fibrosis. Antimicrob Agents Chemother. 2001;45:781-5. Falagas ME, Rafailidis PI, Loannidou E, et al. Colistin therapy for microbiologically documented multidrug-resistant gram-negative bacterial infections: a retrospective cohort study of 258 patients. Int J Antimicrob Agents. 2010;35:194-9. Paul M, Bishara J, Levcovich A, et al. Effectiveness and safety of colistin: prospective comparative cohort study. J Antimicrob Chemother. 2010;65:1019-27. Kellum JA, Bellomo R, Ronco C. Definition and classification of acute kidney injury. Nephron Clin Pract. 2008;109:c182-7. Hartzell JD, Neff R, Ake J, et al. Nephrotoxicity associated with intravenous colistin (colistimethate sodium) treatment at a tertiary care medical center. Clin Infect Dis. 2009;48:1724-8. Pogue JM, Lee J, Marchaim D, et al. Incidence of and risk factors for colistin-associated nephrotoxicity in a large academic health system. Clin Infect Dis. 2011;53:879-84. Deryke CA, Crawford AJ, Uddin N, et al. Colistin dosing and nephrotoxicity in a large community teaching hospital. Antimicrob Agents Chemother. 2010;54:4503-5. Sorli L, Luque S, Grau S, et al. Trough colistin plasma level is an independent risk factor for nephrotoxicity: a prospective observational cohort study. BMC Infect Dis. 2013;13:380. Briguori C, Manganelli F, Scarpato P, et al. Acetylcysteine and contrast agent-associated nephrotoxicity. J Am Coll Cardiol. 2002;40:298-303. Tadros GM, Mouhayar EN, Akinwande AO, et al. Prevention of radiocontrast-induced nephropathy with N-acetylcysteine in patients undergoing coronary angiography. J Invasive Cardiol. 2003;15:311-4. Tepel M, Van der Giet M, Schwarzfeld C, et al. Prevention of radiographic-contrast-agent-induced reductions in renal function by acetylcysteine. N Engl J Med. 2000;343:180-4. Falagas ME, Fragoulis KN, Kasiakou SK, et al. Nephrotoxicity of intravenous colistin: a prospective evaluation. Int J Antimicrob Agents. 2005;26:504-7.
