Indian J Pediatr DOI 10.1007/s12098-016-2033-2
SCIENTIFIC LETTER
Intravenous Colistimethate Sodium in Neonatal Sepsis Shankha Subhra Nag 1 & Abhijit Dutta 1 & Piyali Mitra 2 & Rahul Majumdar 1 & Mridula Chatterjee 1
Received: 3 September 2015 / Accepted: 11 January 2016 # Dr. K C Chaudhuri Foundation 2016
To the Editor: Colistin is a re-emerging antibiotic in the last few years owing to increase in Gram negative multi drug resistant (MDR) nosocomial infections. Effect of the drug on the immature renal system of neonates has not been studied extensively yet. In this retrospective descriptive study, we have tried to evaluate the safety and efficacy of colistimethate sodium (CMS) in MDR neonatal infections. Medical records of all the neonates treated with intravenous CMS for MDR sepsis in neonatal care units between September 2013 and February 2015 were retrieved and analyzed. Twenty eight neonates with mean gestational age of 35.57 wk (range 28–43 wk), and mean birth weight of 2048 g (range 990–3780 g) received CMS during the study period. Mean postnatal age at initiation of CMS therapy was 8.46 d (range 5–12 d), and mean duration of CMS therapy was 16.1 d (range 14–24 d) in surviving cases. CMS was used in the doses of 50,000–75,000 IU/ kg/d. Empirical antimicrobials were continued despite known resistance to them owing to lack of data on
* Shankha Subhra Nag [email protected]
1
2
Department of Pediatric Medicine, North Bengal Medical College, Sushruta Nagar 734012, West Bengal, India Department of Pathology, North Bengal Medical College, Sushruta Nagar, West Bengal, India
efficacy of colistin. Following CMS therapy, 22 neonates (78.6 %) survived. Death in the remaining 6 neonates (21.4 %) was unrelated to adverse effects of CMS. There were no significant statistical differences between baseline and post CMS values of blood urea, serum creatinine, and estimated creatinine clearance (Table 1). Nephrotoxicity was noted in 3 neonates (10.7 %) on 4– 6 d of therapy. However, those neonates were on netilmicin therapy in addition to CMS; and renal functions returned to normal after discontinuation of netilmicin. Moreover, urine examination of the study population revealed no significant abnormality. In some related studies, the efficacy of CMS was 72.2 % to 81 % and nephrotoxicity was noted among 5.1 % to 19 % neonates [1–3]. CMS was used in dose of 50,000–1,20,000 IU/kg/d or 2–5 mg/kg/d in their study subjects. Although electrolyte imbalance was observed in some studies [2, 4], we did not find such changes in our cohort.
Table 1 Renal function parameters of the subjects before and after CMS therapy Parameters
Baseline value Post CMS value p value Mean ± SD Mean ± SD
Blood urea (mg/dl)
39.41 ± 20.88
35.66 ± 20.05
Serum creatinine (mg/dl)
0.72 ± 0.25
0.61 ± 0.25
0.087
37.30 ± 21.28
0.283
Estimated creatinine clearance 29.56 ± 14.21 (ml/min/1.73m2)
0.517
Indian J Pediatr
Observation of the present study shows that intravenous CMS has an acceptable safety profile in neonates and is quite efficacious in treatment of MDR Gram negative sepsis. Concomitant use of other nephrotoxic drugs should be avoided and frequent monitoring of renal function is essential. Acknowledgment The authors thank Dr. Nilanjana Gosh, Department of Community Medicine, North Bengal Medical College, Sushruta Nagar, West Bengal, India, for helping in statistical analysis.
Contributions SSN was responsible for conception of the study, acquisition of data and drafting the manuscript. AD was responsible for design of the study, acquisition of data and revising the manuscript for important intellectual content. PM was responsible for analysis and interpretation of data, literature search, and revising the manuscript for important intellectual content. RM was responsible for collection of data and drafting the manuscript. MC was responsible for revising the manuscript critically, and for overall guidance. All the authors approved the version to be published and agreed to be accountable for all aspects of the work ensuring that questions related to the accuracy or integrity of any part of the work are appropriately investigated and resolved.
Compliance with Ethical Standards Conflict of Interest None. Source of Funding None.
References 1. 2.
3. 4.
Jajoo M, Kumar V, Jain M, Kumari S, Manchanda V. Intravenous colistin administration in neonates. Pediatr Infect Dis J. 2011;30:218–21. Alan S, Yildiz D, Erdevo O, et al. Efficacy and safety of intravenous colistin in preterm infants with nosocomial sepsis caused by Acinetobacter baumannii. Am J Perinatol. 2014;31: 1079–86. Kumar PP, Giri SR, Shaikh FA, Panigrahy N, Chirla D. Safety and efficacy of intravenous colistin in children. Indian Pediatr. 2015;52:129–30. Tekgunduz KS, Kara M, Caner I, Demirelli Y. Safety and efficacy of intravenous colistin in neonates with culture proven sepsis. Iran J Pediatr. 2015;25:e453.
SCIENTIFIC LETTER
Intravenous Colistimethate Sodium in Neonatal Sepsis Shankha Subhra Nag 1 & Abhijit Dutta 1 & Piyali Mitra 2 & Rahul Majumdar 1 & Mridula Chatterjee 1
Received: 3 September 2015 / Accepted: 11 January 2016 # Dr. K C Chaudhuri Foundation 2016
To the Editor: Colistin is a re-emerging antibiotic in the last few years owing to increase in Gram negative multi drug resistant (MDR) nosocomial infections. Effect of the drug on the immature renal system of neonates has not been studied extensively yet. In this retrospective descriptive study, we have tried to evaluate the safety and efficacy of colistimethate sodium (CMS) in MDR neonatal infections. Medical records of all the neonates treated with intravenous CMS for MDR sepsis in neonatal care units between September 2013 and February 2015 were retrieved and analyzed. Twenty eight neonates with mean gestational age of 35.57 wk (range 28–43 wk), and mean birth weight of 2048 g (range 990–3780 g) received CMS during the study period. Mean postnatal age at initiation of CMS therapy was 8.46 d (range 5–12 d), and mean duration of CMS therapy was 16.1 d (range 14–24 d) in surviving cases. CMS was used in the doses of 50,000–75,000 IU/ kg/d. Empirical antimicrobials were continued despite known resistance to them owing to lack of data on
* Shankha Subhra Nag [email protected]
1
2
Department of Pediatric Medicine, North Bengal Medical College, Sushruta Nagar 734012, West Bengal, India Department of Pathology, North Bengal Medical College, Sushruta Nagar, West Bengal, India
efficacy of colistin. Following CMS therapy, 22 neonates (78.6 %) survived. Death in the remaining 6 neonates (21.4 %) was unrelated to adverse effects of CMS. There were no significant statistical differences between baseline and post CMS values of blood urea, serum creatinine, and estimated creatinine clearance (Table 1). Nephrotoxicity was noted in 3 neonates (10.7 %) on 4– 6 d of therapy. However, those neonates were on netilmicin therapy in addition to CMS; and renal functions returned to normal after discontinuation of netilmicin. Moreover, urine examination of the study population revealed no significant abnormality. In some related studies, the efficacy of CMS was 72.2 % to 81 % and nephrotoxicity was noted among 5.1 % to 19 % neonates [1–3]. CMS was used in dose of 50,000–1,20,000 IU/kg/d or 2–5 mg/kg/d in their study subjects. Although electrolyte imbalance was observed in some studies [2, 4], we did not find such changes in our cohort.
Table 1 Renal function parameters of the subjects before and after CMS therapy Parameters
Baseline value Post CMS value p value Mean ± SD Mean ± SD
Blood urea (mg/dl)
39.41 ± 20.88
35.66 ± 20.05
Serum creatinine (mg/dl)
0.72 ± 0.25
0.61 ± 0.25
0.087
37.30 ± 21.28
0.283
Estimated creatinine clearance 29.56 ± 14.21 (ml/min/1.73m2)
0.517
Indian J Pediatr
Observation of the present study shows that intravenous CMS has an acceptable safety profile in neonates and is quite efficacious in treatment of MDR Gram negative sepsis. Concomitant use of other nephrotoxic drugs should be avoided and frequent monitoring of renal function is essential. Acknowledgment The authors thank Dr. Nilanjana Gosh, Department of Community Medicine, North Bengal Medical College, Sushruta Nagar, West Bengal, India, for helping in statistical analysis.
Contributions SSN was responsible for conception of the study, acquisition of data and drafting the manuscript. AD was responsible for design of the study, acquisition of data and revising the manuscript for important intellectual content. PM was responsible for analysis and interpretation of data, literature search, and revising the manuscript for important intellectual content. RM was responsible for collection of data and drafting the manuscript. MC was responsible for revising the manuscript critically, and for overall guidance. All the authors approved the version to be published and agreed to be accountable for all aspects of the work ensuring that questions related to the accuracy or integrity of any part of the work are appropriately investigated and resolved.
Compliance with Ethical Standards Conflict of Interest None. Source of Funding None.
References 1. 2.
3. 4.
Jajoo M, Kumar V, Jain M, Kumari S, Manchanda V. Intravenous colistin administration in neonates. Pediatr Infect Dis J. 2011;30:218–21. Alan S, Yildiz D, Erdevo O, et al. Efficacy and safety of intravenous colistin in preterm infants with nosocomial sepsis caused by Acinetobacter baumannii. Am J Perinatol. 2014;31: 1079–86. Kumar PP, Giri SR, Shaikh FA, Panigrahy N, Chirla D. Safety and efficacy of intravenous colistin in children. Indian Pediatr. 2015;52:129–30. Tekgunduz KS, Kara M, Caner I, Demirelli Y. Safety and efficacy of intravenous colistin in neonates with culture proven sepsis. Iran J Pediatr. 2015;25:e453.
