Successful Treatment of Multidrug-Resistant Central Nervous System Infections with Colistin

Successful Treatment of
Multidrug-Resistant Acinetobacter
baumannii Central Nervous System
Infections with Colistin
Aspasia Katragkou and Emmanuel Roilides
J. Clin. Microbiol. 2005, 43(9):4916. DOI:
10.1128/JCM.43.9.4916-4917.2005.
These include:
REFERENCES
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JOURNAL OF CLINICAL MICROBIOLOGY, Sept. 2005, p. 4916–4917
0095-1137/05/$08.00⫹0 doi:10.1128/JCM.43.9.4916–4917.2005
Copyright © 2005, American Society for Microbiology. All Rights Reserved.
Vol. 43, No. 9
Successful Treatment of Multidrug-Resistant Acinetobacter baumannii
Central Nervous System Infections with Colistin
infection (meningitis or ventriculitis) due to multidrug-resistant A. baumannii and were treated with colistin intravenously
and/or either intrathecally or intraventricularly (Table 1).
In none of these cases was treatment discontinued due to
adverse effects; however, some authors emphasized the need of
dose modification, especially in patients with renal insufficiency
(11). Although nephrotoxicity, neurotoxicity, and neuromuscular blockage have been described in association with systemic
use of colistin (5), in the reports reviewed here intrathecal or
intraventricular administration exhibited a safe profile even
after prolonged use. Generally, intrathecal or intraventricular
administration of colistin alone or in combination with systematic administration was well tolerated and could be an effective
salvage therapy in patients with CNS infections due to A.
baumannii strains resistant to conventional antibiotics. It is of
note that sterilization of cerebrospinal fluid (CSF) was
achieved in all reported cases within a median of 4.5 days
(range 1 to 6 days). Moreover, cure was achieved in all but one
case reported (13 out of 14 cases; cure rate, 93%).
By using a broth dilution assay of polymyxins, Jimenez-Mejias et al. determined that about 25% of colistin penetrated the
CSF and reached bactericidal concentrations for the entire
dosing period. Colistin produced a peak of 5 ␮g/ml in serum
and a peak of 1.25 ␮g/ml in CSF 1 h after intravenous administration (8, 9). To date it is well known that colistin methanesulfonate, once administered, is hydrolyzed to a mixture of
TABLE 1. Reported cases of multidrug-resistant A. baumannii CNS infections treated with colistin
Data from reference no.:
Characteristic
11
8
9
13
2
4
6
6
10
No. of patients
Age (yr)/sex
Underlying
condition
CNS infection
Ventricular tubeb
MIC (␮g/ml)
Colistin methanesulfonate dosage, in
mg/kg of body
wt/day (route)
Duration of colistin
treatment, in days
Antibiotic(s)
coadministeredc
5
NRa
NR
1
55/F
MEN
1
14/Male
CT
1
41/F
SH
1
49/F
MEN
2
NR
NR
1
16/Male
HEM
1
34/F
SH
1
28/Male
CT
M, V
NR
NR
2.5–5 (i.v.)
M
Yes (20)
1
5 (i.v.)
M
Yes (42)
0.3
5 (i.v.)
M
Yes (8)
0.5
5–10 (ith)e
M
NR
NR
3.2 (ith)e
NR
NR
NR
4 (i.v.)
⫹ 20
(ith)e
V
Yes (16)
ⱕ4
5–10 mg/
12 h
(iventr)
V
Yes (7)
ⱕ4
5–10 mg/
12 h
(iventr)
NR
15
30
22
17
NR
19
17
M
NR
NR
80 mg/8 h (i.v.)
⫹ 1.6–3.2
mg/d
(iventr)
63
No
No
No
No
SAM ⫹
VAN
(i.v.)
NR
TOB (17
days)
(i.v.)
AMK ⫹ TEC
(63 days)
(i.v. ⫹
iventr)
CSF sterilizationd
(days)
Levels of colistin
Infection outcome
NR
4
5
1
6
NR
SAM (3
days)
⫹ TOB
(19 days)
(i.v.)
2
6
NR
No
4 of 5
Cured
Yes
Cured
Yes
Cured
Titers
Cured
No
Cured
No
Cured
Titers
Cured
Titers
Cured
No
Cured
a
NR, not reported; MEN, meningioma; CT, cranial trauma; SH, subarachnoid hemorrhage; HEM, hemangioblastoma; M, meningitis; V, ventriculitis; F, female; i.v.,
intravenous; ith, intrathecal; iventr, intraventricular.
b
In parentheses is the number of days from catheter insertion to diagnosis of infection.
c
SAM, ampicillin-sulbactam; VAN, vancomycin; TOB, tobramycin; AMK, amikacin; TEC, teicoplanin. The numbers in parentheses are the duration of treatment.
d
Time after initiation of colistin treatment.
e
Milligrams per day.
4916
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Acinetobacter baumannii may cause severe central nervous
system (CNS) infections, such as meningitis and ventriculitis,
especially in patients undergoing neurosurgical procedures or
head trauma. Mortality ranges from 20% to 27% in different
case series (3). Carbapenems have been considered the treatment of choice for severe infections. However, increasing numbers of carbapenem-resistant Acinetobacter isolates have been
reported worldwide, dramatically reducing the existing therapeutic options (1).
Over the past 30 years, colistin use has been limited due to
concerns regarding its toxicity along with the development of
newer antibiotics with better safety profiles (5, 7). However,
the increasing incidence of multidrug-resistant A. baumannii in
addition to a lack of new antimicrobial agents has reawakened
interest in the utilization of colistin due to its good activity
against this organism (7).
Although of particular interest, reports on the management
of CNS infections due to multidrug-resistant A. baumannii
with colistin are relatively scarce. In order to build on this
experience, we reviewed the literature and summarized the
up-to-date data. Reports for this review were found through a
search of PubMed and of references cited in relevant articles.
To the best of our knowledge, eight reports (one prospective
nonrandomized study [11], one retrospective study [4], and six
case reports [2, 6, 8–10, 13]) overall have been published.
These include a total of 14 patients who suffered from CNS
VOL. 43, 2005
products (colistin sulfate or base, which is more microbiologically active, and its partially sulfomethylated derivatives).
Therefore, microbiological assays lack specificity, since the
concentrations quantified are apparent values for the combined antibacterial activity of the mixture of hydrolytic products of colistin methanesulfonate (12).
From this analysis it becomes evident that, indeed, experience in multidrug-resistant Acinetobacter CNS infections is
scattered. Besides, some of the existing reports provide inadequate information to come to safe conclusions. Consequently,
more extensive pharmacokinetic and pharmacodynamic studies as well as randomized controlled trials are needed to evaluate the clinical use of colistin and the desirable concentrations in CSF after intravenous administration.
4917
7. Jain, R., and L. H. Danziger. 2004. Multidrug-resistant Acinetobacter infections: an emerging challenge to clinicians. Ann. Pharmacother. 38:1449–
1459.
8. Jimenez-Mejias, M. E., B. Becerril, F. J. Marquez-Rivas, C. Pichardo, L.
Cuberos, and J. Pachon. 2000. Successful treatment of multidrug-resistant
Acinetobacter baumannii meningitis with intravenous colistin sulfomethate
sodium. Eur. J. Clin. Microbiol. Infect. Dis. 19:970–971.
9. Jimenez-Mejias, M. E., C. Pichardo-Guerrero, F. J. Marquez-Rivas, D. Martin-Lozano, T. Prados, and J. Pachon. 2002. Cerebrospinal fluid penetration
and pharmacokinetic/pharmacodynamic parameters of intravenously administered colistin in a case of multidrug-resistant Acinetobacter baumannii meningitis. Eur. J. Clin. Microbiol. Infect. Dis. 21:212–214.
10. Kasiakou, S. K., P. I. Rafailidis, K. Liaropoulos, and M. E. Falagas. 2005.
Cure of post-traumatic recurrent multiresistant gram-negative rod meningitis with intraventricular colistin. J. Infect. 50:348–352.
11. Levin, A. S., A. A. Barone, J. Penco, M. V. Santos, I. S. Marinho, E. A.
Arruda, E. I. Manrique, and S. F. Costa. 1999. Intravenous colistin as
therapy for nosocomial infections caused by multidrug-resistant Pseudomonas aeruginosa and Acinetobacter baumannii. Clin. Infect. Dis. 28:1008–1011.
12. Li, J., R. L. Nation, R. W. Milne, J. D. Turnidge, and K. Coulthard. 2005.
Evaluation of colistin as an agent against multi-resistant gram-negative bacteria. Int. J. Antimicrob. Agents 25:11–25.
13. Vasen, W., P. Desmery, S. Ilutovich, and A. Di Martino. 2000. Intrathecal use
of colistin. J. Clin. Microbiol. 38:3523.
Aspasia Katragkou
Emmanuel Roilides*
Laboratory of Infectious Diseases
3rd Department of Pediatrics
Aristotle University
Hippokration Hospital
Thessaloniki 54642, Greece
*Phone: 30-2310-892444
Fax: 30-2310-992983
E-mail: roilides@med.auth.gr
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