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Indian Pediatr 2015;52: 129 -130 |
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Safety and Efficacy of Intravenous Colistin
in Children
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Poddutoor Preetham Kumar, Swapnil Rameshwar Giri,
Farhan AR Shaikh,
Nalinikant Panigrahy and Dinesh Chirla
From Department of Intensive Care, Rainbow
Children’s Hospital, Banjara Hills, Hyderabad, India.
Correspondence to: Dr P Preetham Kumar C/o Rainbow
Children’s Hospital, Banjara Hills, Hyderabad. 500034.
Email: [email protected]
Received: July 30, 2014;
Initial review: October 21, 2014;
Accepted: December 05, 2014.
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Objective: To observe the safety and efficacy of
Colistimethate sodium in children infected with gram-negative bacteria,
susceptible only to colistimethate sodium. Methods: This
prospective observational study done over 2 years observed children who
received colistin for >48 h, for renal failure as defined by p-RIFLE
criteria. Results: Out of 68 children, 52 (76.5%) survived. There
were three children with evidence of acute kidney injury and none had
neurotoxicity. Serum creatinine significantly decreased at 48 h and at
end of treatment, from that at beginning of therapy (P=0.007).
Conclusion: Colistimethate sodium is effective against carbapenem-resistant
Gram-negative bacteria, and is safe in children.
Keywords: Acute kidney injury, Antimicrobial resistance,
Colistin.
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G ram-negative bacteria around the world are
becoming increasingly resistant to conventional antibiotics including
carbapenems [2] this has led to a renewed interest in antibiotics like
Colistimethate sodium, which were abandoned in 1980s because of
nephrotoxicity and neurotoxicity [3].
Documentation of pediatric usage of colistin has been
limited to only few case reports or small retrospective studies [4-7].
We planned this prospective study to observe the safety profile and
efficacy of colistimethate sodium for treatment of infections caused by
multi drug resistant gram-negative bacteria in children.
Methods
This prospective descriptive study was conducted from
January 1, 2010 to December 31, 2011. The study was approved by hospital
Ethical Committee. All children in whom gram-negative bacteria
susceptible only to colistimethate sodium were isolated from sterile
fluids and/or children who had ventilator associated pneumonia with
positive tracheal cultures were studied. All children who received
colistimethate sodium for <48 hours were excluded from the study. The
dosage of colistimethate sodium was 75,000 to 120,000 IU/kg/d in three
divided doses; acute kidney injury (AKI) was defined according to
p-RIFLE criteria [2].
Serum creatinine and blood urea were monitored at
pre-therapy, 48 hours, 96 hours, and at the end of treatment. Urine
output was measured 6 hourly for the first five days of therapy.
Cultures were only repeated if clinical cure was not achieved. Data were
filled into a proforma by the respective registrar/fellow and the data
was analyzed at the end of the study for survival and toxicity of
colistimethate sodium. Statistical analysis was done using paired t-test
and repeated measures of analysis of variance; P value <0.05 was
considered statistically significant.
Results
A total of 68 patients (47 males) were included in
this study. Out of 39 neonates, 18 were preterm and 35 received
ventilation. Out of 29 patients aged more than 4 weeks, 25 were
ventilated. Median age of patient was 16 days (range 3 d–14y), and mean
duration of therapy was 11.6 days. Two patients required more than one
course of colistimethate sodium for microbiological clearance and
clinical recovery. Acinetobacter was the commonest organism
isolated (blood 17, trachea 36, CSF 3, central line 1 and peritoneum 1),
followed by Klebsiella (blood 3, trachea 8, CSF 1 and urine 1),
followed by Pseudomonas (blood 3, trachea 1), Yersinia
(blood 1) and E. coli (blood 1, trachea 1).
Fifty two (76.5%) patients survived and death in 18
(23.5) was attributed to persistence of sepsis and multi-organ
dysfunction. Out of the 16 children who died, five received less than
five days of colistimethate sodium.
Three patients (2 preterm neonates) had acute kidney
injury (AKI) as per p-RIFLE criteria [2]. All these patients who
developed AKI died; one of them was also receiving concomitant
nephrotoxic drugs.
Serum creatinine at 48 hours of therapy and at the
end of the treatment decreased significantly (P=0.007) from
baseline. The other biochemical parameters also showed improvement on
therapy (Table I). No other toxic effects of
colistimethate sodium therapy were observed, except for apnea on third
and twelfth day of colistimethate sodium therapy in two preterm
neonates.
Table I Biochemical Characteristics of Study Subjects.
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Pre-therapy |
Post-therapy |
P |
|
mean( SD) |
mean( SD) |
Value |
Serum creatinine (mg/dL) |
0.5(0.2) |
0.5(0.17) |
0.145 |
Blood urea (mg/dL) |
36.7(22.9) |
31.6(19.6) |
0.133 |
Platelets (lakhs/cumm) |
1.7(1.70) |
2.9(1.92) |
<0.001 |
C-reactive protein (mg/L) |
33.8(27.3) |
14.7(22.2) |
<0.001 |
Discussion
In our series of 68 children with multi drug
resistant gram-negative sepsis, survival rates use 76% with intravenous
colistin therapy; only 3 children developed AKI. Though creatinine
estimation is considered a gold marker [9] for renal function
estimation, in neonates it is influenced by prematurity and maternal
creatinine levels. With a predominant neonatal population, it can be
considered as a limitation of our study. Considering the fact that there
was only one neonate who was started colistimethate sodium in the first
week of life, the effect of maternal creatinin levels would have been
negligible.
The survival rate in our study is broadly in
agreement with other case series [4,6,7,10] where survival of 75-84% has
been reported. Renal toxicity in other studies varied from 0-22%
[4,11-13]. Paradoxically, the creatinine values in our study were
significantly better after 48 hours and at the end of therapy, probably
because of improvement in sepsis. Larger controlled trials are needed to
study the safety of colistimethate sodium, particularly in the setting
of multi organ dysfunction.
Contributors: DC, FS: conceived and designed the
study. DC: acts as guarantor; SRG, NP: was responsible for collection of
data; PPK: was responsible for analysis of the data and drafting the
paper; NP: participated in protocol development and helped in drafting
the paper. The final manuscript was approved by all the authors.
Funding: None; Competing interests: None
stated.
What this study adds?
• Colistimethate sodium is safe and efficacious in children
having multi drug resistant gram negative sepsis.
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