The Pediatric Infectious Disease Journal Publish Ahead of Print DOI: 10.1097/INF.0000000000001743 Persistent Gram-Negative Neurosurgical Meningitis in a Neonate, Successfully Treated With Intraventricular Colistin: Case Report and Review of the Literature
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Laila S. Al Yazidi,1,2 MD, Brendan McMullan,1,2 MD, FRACP, FRCPA, Saeed Kohan,3 MBBS, FRACS, and Pamela Palasanthiran,1,2 MD, FRACP, PhD. 1
Department of Immunology and Infectious Diseases, Sydney Children's Hospital, Randwick,
New South Wales, Australia; 2
School of Women's and Children's Health, University of New South Wales, New South Wales,
Australia; 3
Department of Neurosurgery, Sydney Children’s Hospital, Randwick, New South Wales,
Australia.
Corresponding author: Dr Laila Al Yazidi
Department of Immunology and Infectious Diseases
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Sydney Children’s Hospital
High street, Randwick NSW 2031 Australia Telephone: +61 2 9382 1111; Fax: +61 2 9382 1580 E-mail: [email protected]; [email protected]
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Abbreviated Title/Running Head: IVT Colistin in a Neonate with Meningitis Source of support: None Conflicts of interest: None to declare
1
Copyright © 2017 Wolters Kluwer Health, Inc. Unauthorized reproduction of this article is prohibited.
Abstract: We present a case of Gram-negative neurosurgical meningitis in a neonate, refractory to optimal intravenous therapy and removal of ventriculo-peritoneal shunt. Cerebrospinal fluid was sterilized within 24 hours using intraventricular colistin. This is the first report of intraventricular
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colistin use in neonatal meningitis caused by Enterobacter cloacae. Keywords: colistin, polymyxins, intraventricular/intrathecal, gram-negative neurosurgical
A
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meningitis, children
2
Copyright © 2017 Wolters Kluwer Health, Inc. Unauthorized reproduction of this article is prohibited.
Introduction: In this article, we present a case of successful sterilization of the CSF in a difficult case of Gram negative neurosurgical meningitis and summarize the literature on IVT colistin use in neonates. Case:
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A male neonate (twin 1) born prematurely at 35 weeks of gestation required ventriculoperitoneal (VP) shunt insertion on day 4 of life for severe hydrocephalus, associated with spina bifida, diagnosed antenatally. On day 18 of life, the infant developed fever and irritability. He was investigated for sepsis, including examination of cerebrospinal fluid (CSF) from the VP shunt. The CSF white cell count (WCC) was 2250 x106 /L, with 91% polymorphonuclear
leukocytes and 9% mononuclear leukocytes. CSF glucose concentration was 3-4 weeks, but higher mortality courses of treatment (< 1week). In critically ill patients, however, death may be due to other underlying conditions before completion of scheduled therapy5. In our case, administration of polymyxin via the IVT/ITH route was an effective and welltolerated treatment of EVD-related meningitis/ventriculitis in a neonate. Although scant,
6
Copyright © 2017 Wolters Kluwer Health, Inc. Unauthorized reproduction of this article is prohibited.
available literature supports this option for meningitis/ventriculitis caused by multidrug-resistant gram-negative bacteria in children and neonates, particularly in setting of meningitis complicating neurosurgery. Further studies are needed to evaluate criteria for initiation of IVT/ITH polymyxins, the optimal dosages for neonates and children, and the role of combined
A
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systemic and local therapy. (Word count 1146/1500)
7
Copyright © 2017 Wolters Kluwer Health, Inc. Unauthorized reproduction of this article is prohibited.
References 1- Bell SM, Gatus BJ, Pham JN, Rafferty DL, Allerton JK, Antibiotic susceptability testing by the CDS methods. A manual for medical and veterinary laboratories 2016, 8th edition. Available at: http://cdstest.net/wordpress/wp-content/uploads/Antibiotic-Susceptibility-
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Testing-by-the-CDS-Method-8th-Edition.pdf. Last accessed 21/12/2016. 2- Tunkel A, Hartman B, Kaplan S, Kaufman B, Roos K, Scheld M, Whitley R (2004)
Practice guidelines for the management of bacterial meningitis. Clin Infect Dis 39:1267– 1284
3- Santos AS, Iraneta A, Matos M, Brito M. Intraventricular colistin in Gram-negative
ventriculoperitoneal shunt infection in two paediatric patients. Acta Neurochir ,2015; 157: 2219-2220
4- Drew RJ, Cole TS, Lee MK, Paulus S, Mallucci CL, Riordan A. Antimicrobial treatment options for neurosurgical ventricular shunt infections in children from 1993 to 2012: a syestmatic review. Childs Nerv Syst, 2014; 30:841-850.
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5- Bargiacchi O, Rossati A, Car P, Brustia D, Brondolo R, Rosa F,et al.
Intrathecal/intraventricular colistin in external ventricular device-related infections by multi-drug resistant Gram negative bacteria: case reports and review. Infection, 2014; 42:801-809.
A
6- Alaoui SY, Nejmi SE, Chakir AA, Hmamouchi B, Chlilek A. Intraventricular colistin use in neonatal meningitis caused by Acinetobacter baumannii. Ann Fr Anesth Reanim 2011;30:854-5.
7- Tekgunduz KS, Kara M, Caner I, Demirelli Y. Safety and efficacy of intraventricular colistin in neonates with culture proven sepsis. Iran J Pediatr.2015; 25 (4): e453.
8
Copyright © 2017 Wolters Kluwer Health, Inc. Unauthorized reproduction of this article is prohibited.
8- Karaiskos I, Galani L, Baziaka F, Giamarellou H (2013) Intraventricular and intrathecal colistin as the last therapeutic resort for the treatment of multidrug-resistant and extensively drug resistance Acinetobacter baumannii ventriculitis and meningitis: a literature review. Int J Antimicrob Agent 41:499–508
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9- Kaye KS, Kaye D (2012). Polymyxins (Polymyxin B and Colistin). Mandell GL, Bennet JE, Dolin R. Mandell, Douglas, and Bennett's Principles and Practice of Infectious Diseases, 7th edition. (pp 469 – 470). Philadelphia: Churchill Livingstone.
10- Falagas ME, Bliziotis IA, Tam VH. Intraventricular or intrathecal use of polymyxins in patients with Gram-negative meningitis: a systematic review of the available evidence. Int J Antimicrob Agents 2007; 29:9–25.
11- Markantonis SL, Markou N, Fousteri M, Sakellaridis N, Karatzas S, Alamanos I,
Dimopoulou E, Baltopoulos G (2009) Penetration of colistin into cerebrospinal fluid. Antimicrob Agent Chemother 53:4907–10
12- Karaiskos I, Galani L, Baziaka F, Katsouda E, Ioannidis I, Andreou A,et al. Successful
C C
treatment of extensively drug-resistant (XDR) Acinetobacter baumannii meningitis with
intraventricular colistin after application of a loading dose: a case series. Int J Antimicrob Agents,2013; 41: 480-483.
13- Ng J, Gosbell IB, Kelly JA, Boyle MJ, Ferguson JK. Cure of multiresistant
A
Acinetobacter baumannii central nervous system infections with intraventricular or intrathecal colistin: case series and literature review. J Antimicrob Chemother 2006;58:1078–1081.
9
Copyright © 2017 Wolters Kluwer Health, Inc. Unauthorized reproduction of this article is prohibited.
14- Eljaaly K, Dose and duration of intraventricular antibiotics therapy in meningitis. Clinical Microbiology and Infection; 2016; Available at: http://dx.doi.org/10.1016/j.cmi.2016.05.019. Accessed 17 August 2016. 15- Imberti R, Cusato M, Accetta G, et al. Pharmacokinetics of colistin in cerebrospinal fluid
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after intraventricular administration of colistin methanesulfonate. Antimicrob Agents Chemother 2012;56:4416e21.
16- Fotakopoulos G, Makris D, Chatzi M, Tsimitrea E, Zakynthinos E, Fountas K. Outcomes in meningitis/ventriculitis treated with intravenous or intraventricular plus intravenous
A
C C
colistin. Acta Neurochir 2016;158:603e10.
10
Copyright © 2017 Wolters Kluwer Health, Inc. Unauthorized reproduction of this article is prohibited.
Figure 1: Summary of the patient CSF cultures and the antibiotics used for treatment during the course of his disease: VP: ventriculoperitoneal, CSF: Cerebrospinal fluid, IVT: Intraventricular, IV: intravenous. Plus sign: Growth in CSF culture. Minus sign: no growth.
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Table 1: Summary of neonates treated for neurosurgical meningitis with IVT colistin from the
A
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case reports published in the literature.
11
Copyright © 2017 Wolters Kluwer Health, Inc. Unauthorized reproduction of this article is prohibited.
Table 1: Summary of neonates treated for neurosurgic meningitis with IVT colistin from the case reports published in the literature.
Age
1
4d (term)
2
21 (33/40) 18d (35/40)
Isolated microorganism
Dose of IVTx colistin
days to sterilize CSF (day)
Duration of Intraventricular colistin (days)
Toxicity
Outcome
Myelomeningocele, hydrocephalus Hydrocephalus
Myelomeningocele, hydrocephalus
Acinetobacter baumannii Acinetobacter baumannii Enterobacter cloacae
1.6mg/day
7
NR
None
Cure
10mg/day
4
21
None
Cure
5mg/day
1
9
None
Cure
A
C C
3 (our patient)
Underlying disease(s)
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Patient
12
Copyright © 2017 Wolters Kluwer Health, Inc. Unauthorized reproduction of this article is prohibited.
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Copyright © 2017 Wolters Kluwer Health, Inc. Unauthorized reproduction of this article is prohibited.
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Laila S. Al Yazidi,1,2 MD, Brendan McMullan,1,2 MD, FRACP, FRCPA, Saeed Kohan,3 MBBS, FRACS, and Pamela Palasanthiran,1,2 MD, FRACP, PhD. 1
Department of Immunology and Infectious Diseases, Sydney Children's Hospital, Randwick,
New South Wales, Australia; 2
School of Women's and Children's Health, University of New South Wales, New South Wales,
Australia; 3
Department of Neurosurgery, Sydney Children’s Hospital, Randwick, New South Wales,
Australia.
Corresponding author: Dr Laila Al Yazidi
Department of Immunology and Infectious Diseases
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Sydney Children’s Hospital
High street, Randwick NSW 2031 Australia Telephone: +61 2 9382 1111; Fax: +61 2 9382 1580 E-mail: [email protected]; [email protected]
A
Abbreviated Title/Running Head: IVT Colistin in a Neonate with Meningitis Source of support: None Conflicts of interest: None to declare
1
Copyright © 2017 Wolters Kluwer Health, Inc. Unauthorized reproduction of this article is prohibited.
Abstract: We present a case of Gram-negative neurosurgical meningitis in a neonate, refractory to optimal intravenous therapy and removal of ventriculo-peritoneal shunt. Cerebrospinal fluid was sterilized within 24 hours using intraventricular colistin. This is the first report of intraventricular
EP TE D
colistin use in neonatal meningitis caused by Enterobacter cloacae. Keywords: colistin, polymyxins, intraventricular/intrathecal, gram-negative neurosurgical
A
C C
meningitis, children
2
Copyright © 2017 Wolters Kluwer Health, Inc. Unauthorized reproduction of this article is prohibited.
Introduction: In this article, we present a case of successful sterilization of the CSF in a difficult case of Gram negative neurosurgical meningitis and summarize the literature on IVT colistin use in neonates. Case:
EP TE D
A male neonate (twin 1) born prematurely at 35 weeks of gestation required ventriculoperitoneal (VP) shunt insertion on day 4 of life for severe hydrocephalus, associated with spina bifida, diagnosed antenatally. On day 18 of life, the infant developed fever and irritability. He was investigated for sepsis, including examination of cerebrospinal fluid (CSF) from the VP shunt. The CSF white cell count (WCC) was 2250 x106 /L, with 91% polymorphonuclear
leukocytes and 9% mononuclear leukocytes. CSF glucose concentration was 3-4 weeks, but higher mortality courses of treatment (< 1week). In critically ill patients, however, death may be due to other underlying conditions before completion of scheduled therapy5. In our case, administration of polymyxin via the IVT/ITH route was an effective and welltolerated treatment of EVD-related meningitis/ventriculitis in a neonate. Although scant,
6
Copyright © 2017 Wolters Kluwer Health, Inc. Unauthorized reproduction of this article is prohibited.
available literature supports this option for meningitis/ventriculitis caused by multidrug-resistant gram-negative bacteria in children and neonates, particularly in setting of meningitis complicating neurosurgery. Further studies are needed to evaluate criteria for initiation of IVT/ITH polymyxins, the optimal dosages for neonates and children, and the role of combined
A
C C
EP TE D
systemic and local therapy. (Word count 1146/1500)
7
Copyright © 2017 Wolters Kluwer Health, Inc. Unauthorized reproduction of this article is prohibited.
References 1- Bell SM, Gatus BJ, Pham JN, Rafferty DL, Allerton JK, Antibiotic susceptability testing by the CDS methods. A manual for medical and veterinary laboratories 2016, 8th edition. Available at: http://cdstest.net/wordpress/wp-content/uploads/Antibiotic-Susceptibility-
EP TE D
Testing-by-the-CDS-Method-8th-Edition.pdf. Last accessed 21/12/2016. 2- Tunkel A, Hartman B, Kaplan S, Kaufman B, Roos K, Scheld M, Whitley R (2004)
Practice guidelines for the management of bacterial meningitis. Clin Infect Dis 39:1267– 1284
3- Santos AS, Iraneta A, Matos M, Brito M. Intraventricular colistin in Gram-negative
ventriculoperitoneal shunt infection in two paediatric patients. Acta Neurochir ,2015; 157: 2219-2220
4- Drew RJ, Cole TS, Lee MK, Paulus S, Mallucci CL, Riordan A. Antimicrobial treatment options for neurosurgical ventricular shunt infections in children from 1993 to 2012: a syestmatic review. Childs Nerv Syst, 2014; 30:841-850.
C C
5- Bargiacchi O, Rossati A, Car P, Brustia D, Brondolo R, Rosa F,et al.
Intrathecal/intraventricular colistin in external ventricular device-related infections by multi-drug resistant Gram negative bacteria: case reports and review. Infection, 2014; 42:801-809.
A
6- Alaoui SY, Nejmi SE, Chakir AA, Hmamouchi B, Chlilek A. Intraventricular colistin use in neonatal meningitis caused by Acinetobacter baumannii. Ann Fr Anesth Reanim 2011;30:854-5.
7- Tekgunduz KS, Kara M, Caner I, Demirelli Y. Safety and efficacy of intraventricular colistin in neonates with culture proven sepsis. Iran J Pediatr.2015; 25 (4): e453.
8
Copyright © 2017 Wolters Kluwer Health, Inc. Unauthorized reproduction of this article is prohibited.
8- Karaiskos I, Galani L, Baziaka F, Giamarellou H (2013) Intraventricular and intrathecal colistin as the last therapeutic resort for the treatment of multidrug-resistant and extensively drug resistance Acinetobacter baumannii ventriculitis and meningitis: a literature review. Int J Antimicrob Agent 41:499–508
EP TE D
9- Kaye KS, Kaye D (2012). Polymyxins (Polymyxin B and Colistin). Mandell GL, Bennet JE, Dolin R. Mandell, Douglas, and Bennett's Principles and Practice of Infectious Diseases, 7th edition. (pp 469 – 470). Philadelphia: Churchill Livingstone.
10- Falagas ME, Bliziotis IA, Tam VH. Intraventricular or intrathecal use of polymyxins in patients with Gram-negative meningitis: a systematic review of the available evidence. Int J Antimicrob Agents 2007; 29:9–25.
11- Markantonis SL, Markou N, Fousteri M, Sakellaridis N, Karatzas S, Alamanos I,
Dimopoulou E, Baltopoulos G (2009) Penetration of colistin into cerebrospinal fluid. Antimicrob Agent Chemother 53:4907–10
12- Karaiskos I, Galani L, Baziaka F, Katsouda E, Ioannidis I, Andreou A,et al. Successful
C C
treatment of extensively drug-resistant (XDR) Acinetobacter baumannii meningitis with
intraventricular colistin after application of a loading dose: a case series. Int J Antimicrob Agents,2013; 41: 480-483.
13- Ng J, Gosbell IB, Kelly JA, Boyle MJ, Ferguson JK. Cure of multiresistant
A
Acinetobacter baumannii central nervous system infections with intraventricular or intrathecal colistin: case series and literature review. J Antimicrob Chemother 2006;58:1078–1081.
9
Copyright © 2017 Wolters Kluwer Health, Inc. Unauthorized reproduction of this article is prohibited.
14- Eljaaly K, Dose and duration of intraventricular antibiotics therapy in meningitis. Clinical Microbiology and Infection; 2016; Available at: http://dx.doi.org/10.1016/j.cmi.2016.05.019. Accessed 17 August 2016. 15- Imberti R, Cusato M, Accetta G, et al. Pharmacokinetics of colistin in cerebrospinal fluid
EP TE D
after intraventricular administration of colistin methanesulfonate. Antimicrob Agents Chemother 2012;56:4416e21.
16- Fotakopoulos G, Makris D, Chatzi M, Tsimitrea E, Zakynthinos E, Fountas K. Outcomes in meningitis/ventriculitis treated with intravenous or intraventricular plus intravenous
A
C C
colistin. Acta Neurochir 2016;158:603e10.
10
Copyright © 2017 Wolters Kluwer Health, Inc. Unauthorized reproduction of this article is prohibited.
Figure 1: Summary of the patient CSF cultures and the antibiotics used for treatment during the course of his disease: VP: ventriculoperitoneal, CSF: Cerebrospinal fluid, IVT: Intraventricular, IV: intravenous. Plus sign: Growth in CSF culture. Minus sign: no growth.
EP TE D
Table 1: Summary of neonates treated for neurosurgical meningitis with IVT colistin from the
A
C C
case reports published in the literature.
11
Copyright © 2017 Wolters Kluwer Health, Inc. Unauthorized reproduction of this article is prohibited.
Table 1: Summary of neonates treated for neurosurgic meningitis with IVT colistin from the case reports published in the literature.
Age
1
4d (term)
2
21 (33/40) 18d (35/40)
Isolated microorganism
Dose of IVTx colistin
days to sterilize CSF (day)
Duration of Intraventricular colistin (days)
Toxicity
Outcome
Myelomeningocele, hydrocephalus Hydrocephalus
Myelomeningocele, hydrocephalus
Acinetobacter baumannii Acinetobacter baumannii Enterobacter cloacae
1.6mg/day
7
NR
None
Cure
10mg/day
4
21
None
Cure
5mg/day
1
9
None
Cure
A
C C
3 (our patient)
Underlying disease(s)
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Patient
12
Copyright © 2017 Wolters Kluwer Health, Inc. Unauthorized reproduction of this article is prohibited.
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Copyright © 2017 Wolters Kluwer Health, Inc. Unauthorized reproduction of this article is prohibited.
