Successful use of intrathecal colistin in the treatment of Pseudomonas aeruginosa ventriculitis
Publication: Official Journal of the Association of Medical Microbiology and Infectious Disease Canada
Volume 2, Number 1
Abstract
Abstract
This case report describes a 56-year-old woman with multi-drug-resistant Pseudomonas aeruginosa ventriculitis secondary to external ventricular drain insertion who was successfully treated with intrathecal colistin, intravenous colistin, and intravenous meropenem. A review of the English-language literature found six similar cases. While the patient did not experience side effects, self-limited paresthesias of the arm were noted in one case report. Intrathecal colistin should be considered as a therapy for ventriculitis when antibiotic choices are limited by resistant organisms. Patients should be monitored for neurological side effects during therapy.
Résumé
Le présent rapport décrit le cas d’une femme de 56 ans atteinte d’une ventriculite à Pseudomonas aeruginosa multirésistante secondaire à l’insertion d’un drain ventriculaire externe dont le traitement de colistine par voie intrathécale, de colistine par voie intraveineuse, et méropénem par voie intraveineuse. Une analyse des publications anglophones a permis de recenser six cas similaires. Les patients n’avaient pas souffert d’effets secondaires, mais l’un des rapports faisait état d’une paresthésie du bras spontanément résolutive. Il faut envisager la colistine par voie intrathécale pour traiter la ventriculite lorsque les choix d’antibiotiques sont limités par des organismes résistants et surveiller les effets secondaires neurologiques pendant le traitement.
Introduction
The use of intrathecal antibiotics in central nervous system (CNS) infections is generally reserved for antibiotic-resistant organisms or treatment failures (1). Here we present a case in which intrathecal colistin was used successfully to treat a multi-drug-resistant (MDR) Pseudomonas aeruginosa ventriculitis, with a brief review of the associated literature.
Case presentation
A 56-year-old, previously well woman was admitted to hospital with subarachnoid and intraventricular hemorrhage, hydrocephalus, and a middle cerebral artery aneurysm. She underwent emergency surgical intervention, at which time an external ventricular drain (EVD) was inserted. Cerebrospinal fluid (CSF) sampling was unremarkable at the time of insertion.
On day 14 of admission, the patient’s neurological status worsened. CSF and blood cultures grew P. aeruginosa, and IV ceftazidime and meropenem were started empirically. Subsequently, the isolates were found to be susceptible to amikacin and colistin; as a result, ceftazidime and meropenem were discontinued, and therapy with IV colistin was started (150 mg IV every 8 hours).
The patient’s level of consciousness improved in the following days, and her EVD was removed. A lumbar puncture was performed after 1 week of colistin therapy; cell count showed 20 leukocytes and 1 erythrocyte, and gram stain and culture were negative.
On day 25 of admission, however, the patient developed hydrocephalus, and a new EVD was inserted. CSF showed 485 leukocytes, with 93% neutrophils; culture was negative. Because recurrent infection was suspected, IV meropenem and intrathecal colistin (10 mg in 2 mL of normal saline daily) were added to the existing regimen of IV colistin.
The patient completed a 4-week course of IV meropenem, 40 days of IV colistin, and 18 days of intrathecal colistin. Renal function remained within normal limits throughout. A lumbar puncture after antibiotic completion and EVD removal was sterile, with a normal cell count.
The patient was discharged to a rehabilitation program with right-sided hemiparesis and short-term memory impairment. By 18-month follow-up, she was independent in her activities of daily living, although deficits in taste and smell remained.
Discussion
EVDs and other CNS shunts are a mainstay in the management of hydrocephalus secondary to neurological injury; unfortunately, they may become infected. While skin flora predominate, infection with gram-negative bacilli can occur as well, possibly by introduction during surgery or via retrograde infection in the case of ventriculo-peritoneal shunts (1).
Hospital-acquired P. aeruginosa is difficult to treat because of its resistance to many common antibiotics. An increase in MDR Pseudomonas has prompted the revival of older antibiotics such as colistin, a polymyxin derivative. While the use of intrathecal colistin is not approved by the US Food and Drug Administration, the Infectious Disease Society of America guidelines include it as an option for the treatment of bacterial meningitis, suggesting a dose of 10 mg, with subsequent dose adjustment based on CSF colistin levels (2). Because this testing was not available at our hospital, we opted for the recommended dose alone.
A search of PubMed using the terms intrathecal + colistin+Pseudomonas produced 10 articles; however, some of these addressed infections with other resistant gram-negative organisms (e.g., Acinetobacter baumannii), and some were not available in English. Here we summarize 6 case reports from the 5 remaining articles specifically addressing the treatment of P. aeruginosa shunt infections.Table 1: Cases of Pseudomonas aeruginosa ventriculitis treated with intrathecal colistin
| Case report | Patient demographics | Details of therapy with colistin | Additional relevant therapies | Outcome | Side effects of intrathecal colistin |
|---|---|---|---|---|---|
| Gump and Walsh (2005), USA(3) | 51yo F with subarachnoid hemorrhage, VPS | Concomitant IV colistin (no dose or duration given) and intrathecal colistin (20 mg in 3 mL × 1 dose, then 10 mg daily to complete 10 days). | Initial therapy with IV and intrathecal amikacin; additional doses of IV imipenem, piperacillin-tazobactam, and levofloxacin. VPS externalized. | CSF cultures negative by day 3 of colistin; CSF remained sterile. | None reported |
| Karagoz et al (2013), Turkey(4) | 24yo F with epidermoid tumour resection, VPS | Concomitant IV colistin (4 mg/kg/day) and intrathecal colistin (10 mg/day) × 21 days. | No additional antibiotic therapy. VPS externalized. | CSF cultures negative by day 2 of colistin and remained sterile; CSF WBC drop from 584 to 0. | None reported |
| Schina et al (2005), Greece(5) | 35yo F with SLE, subarachnoid hemorrhage, ‘intrathecal catheter’ | IV colistin (no dose given) × 30 days and intrathecal colistin (daily × 16 days, then every 48 hrs to complete 26 days; dose varied). | Additional doses of IV ceftazidime, gentamicin, and amikacin, as well as methylprednisolone and cyclophosphamide. Intrathecal catheter replaced. | CSF culture negative at ~day 4 of colistin. Subsequent Enterococcus faecalis intrathecal catheter infection. | Left arm numbness on day 4 of intrathecal colistin (resolved with dose reduction) |
| Quinn et al (2005), case #1, USA (6) | 69yo F with subarachnoid hemorrhage, VPS | IV colistin (5 mg/kg/day) × 8 days, replaced by intrathecal colistin (5–10 mg daily) × 14 days | IV cefepime and amikacin empirically. VPS externalized. | CSF culture sterile by day 4 of IV colistin but elevated CSF WBC; CSF sterile and 0 WBC at completion of intrathecal colistin | None reported |
| Quinn et al (2005), case #2, USA (6) | 69yo F w subarachnoid hemorrhage, VPS | IV colistin (5 mg/kg/day) × 10 days; addition of intrathecal colistin from day 14–21 | VPS externalized. | CSF cultures positive after 7 days of IV colistin, sterile after 2 days of intrathecal colistin. 2 WBC at completion of intrathecal colistin. | None reported |
| Yagmur and Esen (2006), Turkey (7) | 16yo M in motor vehicle accident with decompressive craniectomy, VAS | Intrathecal colistin (5 mg/day) × 21 days. No mention of use of concomitant IV colistin. | Initial IV amikacin. VAS externalized. | Decrease in CSF WBC count and sterilization of culture reported | None reported |
VPS=ventriculo-peritoneal shunt; CSF=cerebro-spinal fluid; WBC=white blood cells; VAS=ventriculo-atrial shunt; SLE=systemic lupus erythematosus
In all of the cases, intrathecal therapy was used in conjunction with systemic antibiotic therapy and removal or externalization of the infected catheter. In 2 cases, the renal side effects of IV colistin prompted a switch to intrathecal colistin (6). Only 1 study reported side effects with intrathecal colistin, in the form of self-limited paresthesias of the arm (5). However, a 2009 review of 24 cases of A. baumannii shunt infections treated with intrathecal colistin describes chemical ventriculitis in 3 cases and dose-related seizures in 1 case, and a case of cauda equina syndrome after intraventricular colistin administration has also been described (8,9).
In our patient, CSF was sterile by 7 days of IV colistin alone, but a subsequent rise in CSF leukocytes and clinical deterioration suggested persistent infection, prompting the addition of intrathecal therapy. While the lack of persistently positive cultures in our case is a limitation in demonstrating ongoing infection, culture sensitivity from CSF is low, and our patient responded clinically to intrathecal therapy, with an associated drop in CSF leukocytes. It is also difficult to attribute the improvement in our case to the addition of intrathecal colistin alone, since IV meropenem was restarted simultaneously and has been shown to act synergistically with IV colistin in the treatment of resistant gram-negative pathogens (10). However, 2 other case reports demonstrated culture clearance when colistin was the only IV antibiotic used, suggesting that intrathecal therapy was a vital intervention (4,6).
Summary
Above we describe a case of MDR Pseudomonas ventriculitis successfully treated with intrathecal colistin, IV colistin, IV meropenem, and EVD replacement. Intrathecal colistin has been successfully employed in other cases of CNS shunt infections with P. aeruginosa, resulting in rapid CSF sterilization, and physicians should be aware of this potential strategy. Patients should be monitored for neurological side effects during therapy.
Competing Interests:
The authors have nothing to disclose.
Contributors:
All authors participated in conceiving the article and collecting the data. Dr Whellams drafted the manuscript. All authors critically revised the manuscript and approved the final version submitted for publication
Ethics Approval:
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Animal Studies:
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Funding:
No funding was received for this work.
Peer Review:
This article has been peer reviewed.
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Khawcharoenporn T, Apisarnthanarak A, Mundy LM. Intrathecal colistin for drug-resistant Acinetobacter baumannii central nervous system infection: a case series and systematic review. Clin Microbiol Infect. 2010;16(7):888–94. Medline:
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Official Journal of the Association of Medical Microbiology and Infectious Disease Canada
Volume 2 • Number 1 • September 2017
Pages: 93 - 96
Copyright
Copyright © 2017, Association of Medical Microbiology and Infectious Disease Canada (AMMI Canada). This article is free to read to all interested readers, immediately upon publication. For their own personal use, users may read, download, print, search, or link to the full text. Manuscripts published in the Official Journal of the Association of Medical Microbiology and Infectious Disease Canada are copyrighted to the Association of Medical Microbiology and Infectious Disease Canada (AMMI Canada). Requests for permission to reproduce this article should be made to the University of Toronto Press using the Permission Request Form: https://jammi.utpjournals.press/journal-policies#_copyright
History
Published ahead of print: 1 September 2017
Published online: 29 September 2017
Published in print: September 2017
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Journal of the Association of Medical Microbiology and Infectious Disease Canada 2017 2:1, 93-96
Journal of the Association of Medical Microbiology and Infectious Disease Canada 2017 2:1, 93-96