| Abstract |
Colistin, an antibiotic almost abandoned for intravenous
administration for many years, due to its reported toxicity, has been
recently reintroduced in clinical practice due to the emergence of
multidrug-resistant Gram-negative bacteria and the lack of
development of new antibiotics to combat them. However, new data
about its safety and effectiveness in the treatment of serious
hospital-acquired infections in patients without cystic fibrosis are
lacking. Thus, the objective of this study was to re-evaluate the use
of colistin for the treatment of infections mainly due to strains of
Acinetobacter baumannii, Pseudomonas aeruginosa, and Klebsiella
pneumonia.
A retrospective cohort study was performed at “Henry Dunant”
hospital, a 450-bed tertiary-care hospital. Patients who were
hospitalized from 1/October/2000 to 31/January/2004 and received
intravenous colistin for more than 72 hours were further analyzed.
Primary outcome measure was the in-hospital mortality; secondary
end points were the clinical outcome of the infections and the
occurrence of colistin-induced nephrotoxicity.
Fifty patients received intravenous colistin with a mean (median)
daily dose of 4,5 (3) million IU for 21,3 (16,5) days for the
management of 54 episodes of infections due to multidrug-resistant
Gram-negative bacteria. The predominant infections were
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pneumonia (33,3%), bacteremia (27,8%), urinary tract infection
(11,1%), and intra-abdominal infection (11,1%). The responsible
pathogens were Acinetobacter baumannii (51,9%), Pseudomonas
aeruginosa (42,6%), and Klebsiella pneumonia (3,7%); no
pathogen was isolated from one case. In-hospital mortality was
24% (12/50 patients). Clinical response (cure and improvement) of
the infection was observed in 66,7% of episodes (36/54 episodes of
infection). In the studied group, serum creatinine levels were
decreased, at the end of colistin treatment, by an average (± SD)
of 0,2 (±1,3) mg/dl compared to baseline levels. Deterioration of
renal function during CMS therapy was observed in 4/50 patients
(8%). Multivariable analysis showed that age (OR= 1,059, 95%CI=
1,004 – 1,118) and temperature on admission to the hospital (OR=
0,383, 95%CI = 0,148 – 0,991) were independent predictors of inhospital
mortality.
We further analyzed data for 19 courses of prolonged (more than 4
weeks) intravenous colistin administration [mean (±SD) duration of
administration 43,4 (±14,6) days, mean daily dosage (±SD) 4,4
(±2,1) million IU, mean cumulative dosage (±SD) 190,4 (±91)
million IU] in 17 patients. The median creatinine value increased by
0,25 mg/dl during the treatment compared to the baseline (p<
0,001) but returned close to the baseline at the end of treatment
(higher by 0,1 mg/dl, p= 0,67).
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A prospective cohort study was also performed at “Henry Dunant”
Hospital to further clarify the issue of colistin induced
nephrotoxicity. Patients who received intravenous colistin at least 7
days for the treatment of multidrug resistant Gram-negative
bacterial infections were included in the study. The development of
nephrotoxicity through evaluations of serum creatinine, blood urea,
serum electrolytes, urinalysis, and creatinine and sodium in 24-hour
urine collection during intravenous colistin therapy was the primary
end point of the study.
Twenty one patients were included in this prospective evaluation.
The mean (± SD)/median daily dose of colistin administered
intravenously to the patients was 5,5 (±1,9)/6 million IU and the
mean (±SD)/median cumulative dose of the medication was 90,2
(±52,0)/72 million IU. The range of the duration of intravenous
colistin treatment was 7 - 54 days; the mean (± SD)/median
duration was 17,7 (±11,7)/15 days. Three of the 21 evaluable
patients (14,3%) developed nephrotoxicity during the intravenous
treatment with colistin. The cumulative dose of the administered
colistin was statistically correlated with the difference between
baseline and end of treatment values of serum creatinine (r= 0,6,
p= 0,004 by Spearman’s test). No other toxic events were noted
during the intravenous administration of colistin.
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In conclusion, the use of intravenous colistin for the treatment of
infections due to multidrug-resistant Gram-negative bacteria
appears to be safe and effective. Colistin should be considered as a
possible therapeutic option for these patients.
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