J Pediatr Infect Dis
DOI: 10.1055/s-0043-1778121
Review Article

Challenges in Diagnosis and Treatment of Neonatal Ventriculitis: A Case Report and Systematic Review of Difficult-to-Treat Central Nervous System Infection Resistant to Conventional Therapy

1   Department Neonatology, Akdeniz University Faculty of Medicine, Antalya, Turkey
,
1   Department Neonatology, Akdeniz University Faculty of Medicine, Antalya, Turkey
,
1   Department Neonatology, Akdeniz University Faculty of Medicine, Antalya, Turkey
,
2   Department of Clinical Microbiology, Akdeniz University Faculty of Medicine, Antalya, Turkey
,
3   Department of Pediatric Infectious Disease, Akdeniz University Faculty of Medicine, Antalya, Turkey
,
1   Department Neonatology, Akdeniz University Faculty of Medicine, Antalya, Turkey
,
1   Department Neonatology, Akdeniz University Faculty of Medicine, Antalya, Turkey
› Author Affiliations
Funding None.

Abstract

Objective Ventriculitis is an example of the increasing global trend in difficult-to-treat infections in neonates caused by pathogens resistant to conventional therapies. This article describes the first use of intravenous and intraventricular tigecycline to treat ventriculitis caused by vancomycin-resistant enterococci in a preterm neonate and systematically review the literature on challenges posed by the definitions, diagnosis, and treatment of neonatal ventriculitis

Methods The authors searched PubMed and Internet search engines for “ventriculitis” in the period from 2003 to 2023 restricting the research to “Newborn,” “Human,” “English language,” and “full-text availability.”

Results Thirty-seven publications (20 case reports, 6 case series, and 11 research articles) were extracted upon research. Preterm birth, posthemorrhagic ventricular dilatation requiring placement of ventricular access devices, and sepsis preceded neonatal ventriculitis. Infections caused by rare microorganisms, in particular gram-negative bacteria resistant to conventional therapies, predominated in the publications describing the need for a combination of intravenous (IV) and intraventricular (IVT) therapies. Survivors of neonatal ventriculitis developed neurodevelopmental impairments such as hydrocephalus, seizures, motor function, hearing, and vision impairment.

Conclusion Clinical suspicion of ventriculitis indicated by subtle signs is key for prompt diagnosis. Effective IV and IVT antibiotics are essential to prevent serious sequelae and mortality. The drug delivery method should be changed if there is no clinical response. This study emphasizes the urgent need for pediatric trials of antibiotics against organisms resistant to other drugs.



Publication History

Received: 16 July 2023

Accepted: 04 December 2023

Article published online:
02 February 2024

© 2024. Thieme. All rights reserved.

Georg Thieme Verlag KG
Rüdigerstraße 14, 70469 Stuttgart, Germany

 
  • References

  • 1 Williams PC, Qazi SA, Agarwal R. et al. Antibiotics needed to treat multidrug-resistant infections in neonates. Bull World Health Organ 2022; 100 (12) 797-807
  • 2 Guillén-Pinto D, Málaga-Espinoza B, Ye-Tay J. et al. Neonatal meningitis: a multicenter study in Lima, Peru. Rev Peru Med Exp Salud Publica 2020; 37 (02) 210-219
  • 3 Peros T, van Schuppen J, Bohte A, Hodiamont C, Aronica E, de Haan T. Neonatal bacterial meningitis versus ventriculitis: a cohort-based overview of clinical characteristics, microbiology and imaging. Eur J Pediatr 2020; 179 (12) 1969-1977
  • 4 Harris L, Munakomi S. Ventriculitis. Treasure Island, FL: StatPearls Publishing;; 2023
  • 5 Ouchenir L, Renaud C, Khan S. et al. The epidemiology, management, and outcomes of bacterial meningitis in infants. Pediatrics 2017; 140 (01) e20170476
  • 6 Hussain K, Sohail Salat M, Ambreen G, Iqbal J. Neurodevelopment outcome of neonates treated with intraventricular colistin for ventriculitis caused by multiple drug-resistant pathogens: a case series. Front Pediatr 2021; 8: 582375
  • 7 Parasuraman JM, Albur M, Fellows G, Heep A. Monitoring intraventricular vancomycin for ventriculostomy access device infection in preterm infants. Childs Nerv Syst 2018; 34 (03) 473-479
  • 8 Shah SS, Ohlsson A, Shah VS. Intraventricular antibiotics for bacterial meningitis in neonates. Cochrane Database Syst Rev 2012; 2012 (07) CD004496
  • 9 Ray S, Mukhopadhyay K, Ray P, Suthar R, Angrup A. Neurodevelopmental outcome in neonates with Acinetobacter sepsis with meningitis and/or ventriculitis at 2-5 years. Indian J Pediatr 2021; 88 (04) 400-401
  • 10 de Louvois J, Halket S, Harvey D. Neonatal meningitis in England and Wales: sequelae at 5 years of age. Eur J Pediatr 2005; 164 (12) 730-734
  • 11 Ramanan M, Shorr A, Lipman J. Ventriculitis: infection or inflammation. Antibiotics (Basel) 2021; 10 (10) 1246
  • 12 Kumar R, Singhi P, Dekate P, Singh M, Singhi S. Meningitis related ventriculitis: experience from a tertiary care centre in northern India. Indian J Pediatr 2015; 82 (04) 315-320
  • 13 Tunkel AR, Hasbun R, Bhimraj A. et al. 2017 Infectious Diseases Society of America's Clinical Practice Guidelines for healthcare-associated ventriculitis and meningitis. Clin Infect Dis 2017; 64 (06) e34-e65
  • 14 Helgason EA, Oskarsdottir T, Brynjarsson H, Olafsson IH, Thors V. Intraventricular vancomycin treatment for shunt-related ventriculitis caused by methicillin-resistant Staphylococcus aureus in a preterm infant: a case report. Pediatr Infect Dis J 2022; 41 (04) 340-342
  • 15 Honavar AG, David A, Amladi A, Thomas L. Multidrug-resistant Elizabethkingia anophelis septicemia, meningitis, ventriculitis, and hydrocephalus in a preterm neonate: a rare complication of an emerging pathogen. J Pediatr Neurosci 2021; 16 (01) 79-81
  • 16 Kara TT, Kocaoglu M. A ventriculoperitoneal shunt infection successfully treated with intraventricular coadministration of tigecycline and colistin. Klin Padiatr 2020; 232 (02) 70-72
  • 17 Bhat RR, Batra P, Sachan R, Singh G. Neonatal ventriculitis: a case series and review of literature. Trop Doct 2020; 50 (03) 266-270
  • 18 Honda A, Nakao H, Shoji K, Kubota M, Ishiguro A. Neonatal group B streptococcal ventriculitis without red flags for meningitis. Pediatr Int 2020; 62 (08) 996-998
  • 19 Furudate A, Hirose S, Abe K. et al. Infantile Aspergillus fumigatus ventriculitis successfully treated with monitoring of plasma and cerebrospinal fluid voriconazole concentration level. J Infect Chemother 2020; 26 (01) 132-135
  • 20 Pratheep R, Ray S, Mukhopadhyay K. et al. First case report of intraventricular tigecycline in a neonate with extensively drug-resistant Acinetobacter baumannii ventriculitis. Pediatr Infect Dis J 2019; 38 (08) e172-e174
  • 21 Scaggs Huang FA, Mortensen J, Skoch J. et al. Successful whole genome sequencing-guided treatment of Mycoplasma hominis ventriculitis in a preterm infant. Pediatr Infect Dis J 2019; 38 (07) 749-751
  • 22 Joshi P, Shah B, Joshi V, Kumar A, Singhal T. Treatment of Elizabethkingia meningoseptica neonatal meningitis with combination systemic and intraventricular therapy. Indian J Pediatr 2019; 86 (04) 379-381
  • 23 Yamamura Y, Mihara Y, Nakatani K, Nishiguchi T, Ikebe T. Unexpected ventriculitis complication of neonatal meningitis caused by Streptococcus gallolyticus subsp. pasteurianus: a case report. Jpn J Infect Dis 2018; 71 (01) 68-71
  • 24 Mahabeer P, Mzimela BW, Lawler MA. et al. Colistin-resistant Acinetobacter baumannii as a cause of neonatal ventriculitis. S Afr J Infect Dis 2018; 33 (05) a141
  • 25 Lubián-López SP, Galán-Sánchez F, Rodriguez-Iglesias M, Benavente-Fernández I. Pyogenic intraventricular empyema owing to Veillonella parvula in a preterm infant. Enferm Infecc Microbiol Clin 2017; 35 (08) 541-542
  • 26 Preuß M, Thome U, Kluge J, Hirsch FW, Viehweger A, Nestler U. Retroclival arachnoid cyst in a preterm infant after ventriculitis and intraventricular hemorrhage: a case report. Childs Nerv Syst 2015; 31 (02) 347-350
  • 27 Sadarangani SP, Batdorf R, Buchhalter LC. et al. Clostridium septicum brain abscesses in a premature neonate. Pediatr Infect Dis J 2014; 33 (05) 538-540
  • 28 Özlü F, Yapicioglu H, Ozcan K. et al. Evaluation of neonates with ventriculitis. Cukurova Med J 2013; 38 (04) 553-558
  • 29 Piparsania S, Rajput N, Bhatambare G. Intraventricular polymyxin B for the treatment of neonatal meningo-ventriculitis caused by multi-resistant Acinetobacter baumannii: case report and review of literature. Turk J Pediatr 2012; 54 (05) 548-554
  • 30 Mehar V, Zade P, Joshi M. et al. Neonatal ventriculitis with multi drug resistant Acinetobactor baumanii: a case report and review of literature. Pediatr Therapeut 2012; 2: 131
  • 31 Hartmann C, Peter C, Hermann E. et al. Successful treatment of vancomycin-resistant Enterococcus faecium ventriculitis with combined intravenous and intraventricular chloramphenicol in a newborn. J Med Microbiol 2010; 59 (Pt 11): 1371-1374
  • 32 Kumar S, Kohlhoff S, Valencia G, Hammerschlag MR, Sharma R. Treatment of vancomycin-resistant Enterococcus faecium ventriculitis in a neonate. Int J Antimicrob Agents 2007; 29 (06) 740-741
  • 33 Chen SY, Lu FL, Lee PI. et al. Neonatal listeriosis. J Formos Med Assoc 2007; 106 (02) 161-164
  • 34 Miyairi I, Causey KT, DeVincenzo JP, Buckingham SC. Group B streptococcal ventriculitis: a report of three cases and literature review. Pediatr Neurol 2006; 34 (05) 395-399
  • 35 Nava-Ocampo AA, Mojica-Madera JA, Villanueva-García D, Caltenco-Serrano R. Antimicrobial therapy and local toxicity of intraventricular administration of vancomycin in a neonate with ventriculitis. Ther Drug Monit 2006; 28 (03) 474-476
  • 36 Wong KK, Gruenewald SM, Larcos G, Jamali M. Neonatal fungal ventriculitis. J Clin Ultrasound 2006; 34 (08) 402-406
  • 37 Laborada G, Cruz F, Nesin M. Serial cytokine profiles in shunt-related ventriculitis treated with intraventricular vancomycin. Chemotherapy 2005; 51 (06) 363-365
  • 38 Çay Ü, Alabaz D, Özgür Gündeşlioğlu Ö, Kibar F, Çetin C, Oktay K. Experience with enterococcal meningitis/ventriculitis in children. Pediatr Int 2022; 65 (01) e15398
  • 39 Singh BK, Maria A, Bandyopadhyay T, Choudhary SK. Clinico-epidemiological profile and outcomes of babies with neural tube defects in a tertiary care center in Northern India. J Matern Fetal Neonatal Med 2022; 35 (25) 7052-7057
  • 40 Parasuraman JM, Kloprogge F, Standing JF, Albur M, Heep A. Population pharmacokinetics of intraventricular vancomycin in neonatal ventriculitis, a preterm pilot study. Eur J Pharm Sci 2021; 158: 105643
  • 41 Ochi F, Tauchi H, Nagai K. et al. Therapeutic effect of linezolid in children with health care-associated meningitis or ventriculitis. Clin Pediatr (Phila) 2018; 57 (14) 1672-1676
  • 42 Vallejo JG, Cain AN, Mason EO, Kaplan SL, Hultén KG. Staphylococcus aureus central nervous system infections in children. Pediatr Infect Dis J 2017; 36 (10) 947-951
  • 43 Akturk H, Sutcu M, Somer A. et al. Carbapenem-resistant Klebsiella pneumoniae colonization in pediatric and neonatal intensive care units: risk factors for progression to infection. Braz J Infect Dis 2016; 20 (02) 134-140
  • 44 Chu SM, Hsu JF, Lee CW. et al. Neurological complications after neonatal bacteremia: the clinical characteristics, risk factors, and outcomes. PLoS One 2014; 9 (11) e105294
  • 45 Bentlin MR, Ferreira GL, Rugolo LM, Silva GH, Mondelli AL, Rugolo Júnior A. Neonatal meningitis according to the microbiological diagnosis: a decade of experience in a tertiary center. Arq Neuropsiquiatr 2010; 68 (06) 882-887
  • 46 Giske CG, Turnidge J, Cantón R, Kahlmeter G. EUCAST Steering Committee. Update from the European Committee on Antimicrobial Susceptibility Testing (EUCAST). J Clin Microbiol 2022; 60 (03) e0027621
  • 47 Garcia-Prat M, Álvarez-Sierra D, Aguiló-Cucurull A. et al. Extended immunophenotyping reference values in a healthy pediatric population. Cytometry B Clin Cytom 2019; 96 (03) 223-233
  • 48 Garcia-Prat M, Álvarez-Sierra D, Aguiló-Cucurull A. et al. Extended immunophenotyping reference values in a healthy pediatric population. Cytometry B Clin Cytom 2019; 96 (03) 223-233
  • 49 Schretlen E, Muytjens H, Slooff J. Neonatale meningitis, ventriculitis, wel of geen intraventriculaire therapie? [Neonatal meningitis, ventriculitis, intraventricular therapy or not?]. Tijdschr Kindergeneeskd 1985; 53 (04) 136-141
  • 50 De Angelis LC, Parodi A, Sebastiani M. et al. External ventricular drainage for posthemorrhagic ventricular dilatation in preterm infants: insights on efficacy and failure. J Neurosurg Pediatr 2021; 28 (05) 563-571
  • 51 Wellons III JC, Shannon CN, Holubkov R. et al; Hydrocephalus Clinical Research Network. Shunting outcomes in posthemorrhagic hydrocephalus: results of a Hydrocephalus Clinical Research Network prospective cohort study. J Neurosurg Pediatr 2017; 20 (01) 19-29
  • 52 National Center for Emerging and Zoonotic Infectious Diseases (U.S.). Division of Healthcare Quality Promotion. CDC/NHSN surveillance definitions for specific types of infections. 2023 . Accessed July 10, 2023 at: https://stacks.cdc.gov/view/cdc/127235
  • 53 Edwards MS, Baker CJ, Kaplan SL. et al. Bacterial Meningitis in the Neonate: Clinical Features and Diagnosis. Waltham, MA: UpToDate. 2023 . Accessed July 11, 2023: https://www.uptodate.com/contents/bacterial-meningitis-in-the-neonate-clinical-features-and-diagnosis
  • 54 Zimmermann P, Curtis N. Normal values for cerebrospinal fluid in neonates: a systematic review. Neonatology 2021; 118 (06) 629-638
  • 55 van der Hoeven A, van der Beek MT, Bekker V. et al. Improved diagnostics in bacterial neonatal meningitis using a next-generation sequencing platform. Infect Dis Ther 2023; 12 (07) 1921-1933
  • 56 Graf EH, Farquharson MV, Cárdenas AM. Comparative evaluation of the FilmArray meningitis/encephalitis molecular panel in a pediatric population. Diagn Microbiol Infect Dis 2017; 87 (01) 92-94
  • 57 Arora HS, Asmar BI, Salimnia H, Agarwal P, Chawla S, Abdel-Haq N. Enhanced identification of group B Streptococcus and Escherichia coli in young infants with meningitis using the BioFire FilmArray meningitis/encephalitis panel. Pediatr Infect Dis J 2017; 36 (07) 685-687
  • 58 Gupta N, Grover H, Bansal I. et al. Neonatal cranial sonography: ultrasound findings in neonatal meningitis: a pictorial review. Quant Imaging Med Surg 2017; 7 (01) 123-131
  • 59 Likeman M. MRI brain imaging in neonates. Paediatr Child Health 2014; 24 (09) 407-412
  • 60 Thatrimontrichai A, Janjindamai W, Dissaneevate S, Maneenil G. Neonatal multidrug-resistant bacterial meningitis: a 29-year study from a tertiary hospital in Thailand. J Infect Dev Ctries 2021; 15 (07) 1021-1026
  • 61 Hallmaier-Wacker LK, Andrews A, Nsonwu O. et al. Incidence and aetiology of infant Gram-negative bacteraemia and meningitis: systematic review and meta-analysis. Arch Dis Child 2022; 107 (11) 988-994
  • 62 Turner PJ, Greenhalgh JM. MYSTIC Study Group (Europe). The activity of meropenem and comparators against Acinetobacter strains isolated from European hospitals, 1997-2000. Clin Microbiol Infect 2003; 9 (06) 563-567
  • 63 Chase MNJ. Enterococcal and viridans streptococcal infections. Enterococcal infections. In: Cherry JD, Kaplan SL, Steinbach WJ, Hotez PJ. eds. Feigin and Cherry's Textbook of Pediatric Infectious Diseases. 8th ed. Philadelphia, PA:: Elsevier; 2018: 835-850
  • 64 Li X, Fan S, Lin X. et al. The first case report of Enterococcus gallinarum meningitis in neonate: a literature review. Medicine (Baltimore) 2018; 97 (07) e9875
  • 65 Who publishes list of bacteria for which new antibiotics are urgently needed. Saudi Med J 2017; 38 (04) 445-445
  • 66 Şahin A, Dalgic N. Intraventricular plus intravenous tigecycline for the treatment of daptomycin nonsusceptible vancomycin-resistant enterococci in an infant with ventriculoperitoneal shunt infection. World Neurosurg 2019; 130: 470-473
  • 67 Curebal B, Dalgic N, Bayraktar B. Intraventricular tigecycline for the treatment of shunt infection: a case in pediatrics. J Neurosurg Pediatr 2018; 23 (02) 247-250
  • 68 Iosifidis E, Violaki A, Michalopoulou E. et al. Use of tigecycline in pediatric patients with infections predominantly due to extensively drug-resistant gram-negative bacteria. J Pediatric Infect Dis Soc 2017; 6 (02) 123-128
  • 69 Sharland M, Rodvold KA, Tucker HR. et al. Safety and efficacy of tigecycline to treat multidrug-resistant infections in pediatrics: an evidence synthesis. Pediatr Infect Dis J 2019; 38 (07) 710-715
  • 70 Jaspan HB, Brothers AW, Campbell AJ. et al. Multidrug-resistant Enterococcus faecium meningitis in a toddler: characterization of the organism and successful treatment with intraventricular daptomycin and intravenous tigecycline. Pediatr Infect Dis J 2010; 29 (04) 379-381
  • 71 Fried HI, Nathan BR, Rowe AS. et al. The Insertion and management of external ventricular drains: an evidence-based consensus statement—a statement for healthcare professionals from the Neurocritical Care Society. Neurocrit Care 2016; 24 (01) 61-81
  • 72 Chu J, Jensen H, Holubkov R. et al; Hydrocephalus Clinical Research Network, Hydrocephalus Clinical Research Network Members. The Hydrocephalus Clinical Research Network quality improvement initiative: the role of antibiotic-impregnated catheters and vancomycin wound irrigation. J Neurosurg Pediatr 2022; 29 (06) 711-718
  • 73 Edwards M, Baker C, Nordli Jr DR. et al. Bacterial meningitis in the neonate: neurologic complications. Waltam, MA: UpToDate Inc. 2015 . Available from Accessed: September 16, 2023 at: https://www.uptodate.com
  • 74 Brumbaugh JE, Bell EF, Do BT. et al; Eunice Kennedy Shriver National Institute of Child Health and Human Development Neonatal Research Network. Incidence of and neurodevelopmental outcomes after late-onset meningitis among children born extremely preterm. JAMA Netw Open 2022; 5 (12) e2245826