[go: up one dir, main page]
More Web Proxy on the site http://driver.im/
Next Article in Journal
Therapeutic Drug Monitoring-Guided Linezolid Therapy for the Treatment of Multiple Staphylococcal Brain Abscesses in a 3-Month-Old Infant
Previous Article in Journal
Intratumoral Fusobacterium nucleatum in Pancreatic Cancer: Current and Future Perspectives
Previous Article in Special Issue
Emergence of Carbapenem-Resistant Uropathogenic Escherichia coli (ST405 and ST167) Strains Carrying blaCTX-M-15, blaNDM-5 and Diverse Virulence Factors in Hospitalized Patients
You seem to have javascript disabled. Please note that many of the page functionalities won't work as expected without javascript enabled.
 
 
Search for Articles:
Title / Keyword
Author / Affiliation / Email
Journal
Article Type
 
 
Advanced Search
 
Section
Special Issue
Volume
Issue
Number
Page
 
Journals
Pathogens
Volume 14
Issue 1
10.3390/pathogens14010003
pathogens-logo
Submit to this Journal Review for this Journal Propose a Special Issue
► Article Menu

Article Menu

share Share announcement Help format_quote Cite question_answer Discuss in SciProfiles thumb_up
...
Endorse textsms
...
Comment
first_page
settings
Order Article Reprints
Font Type:
Arial Georgia Verdana
Font Size:
Aa Aa Aa
Line Spacing:
Column Width:
Background:
Case Report

Treatment Options for Nosocomial Ventriculitis/Meningitis: A Case Report and Review of the Literature

by
Marios Karvouniaris
*,
Zoi Aidoni
,
Eleni Gkeka
,
Stella Niki Primikyri
,
Konstantinos Pagioulas
and
Elena Argiriadou
Intensive Care Unit, Department of Anesthesiology and Critical Care, AHEPA University Hospital, Aristotle University of Thessaloniki, 54636 Thessaloniki, Greece
*
Author to whom correspondence should be addressed.
Pathogens 2025, 14(1), 3; https://doi.org/10.3390/pathogens14010003
Submission received: 1 December 2024 / Revised: 23 December 2024 / Accepted: 25 December 2024 / Published: 26 December 2024
(This article belongs to the Special Issue Hospital-Acquired Infections and Multidrug-Resistant (MDR) Pathogens)
Versions Notes

Abstract

:
Ventriculo-meningitis or nosocomial meningitis/ventriculitis is a severe nosocomial infection that is associated with devastating neurological sequelae. The cerebrospinal fluid isolates associated with the infection can be Gram-positive or -negative, while the Enterococcus spp. is rarely identified. We report a case of a 68-year-old woman with a past medical history of insulin-dependent diabetes mellitus, hypertension, and coronary artery disease. She was admitted to the intensive care unit following a scheduled sphenoid wing meningioma resection. Her course was complicated with left middle cerebral artery pseudoaneurysm and hemispheric hemorrhage, and an arterial stent and external ventricular drainage catheter were placed. Neurological evaluation showed a minimal conscious state. She presented high fever on the 35th intensive care unit day. Cerebrospinal fluid was sampled and the external ventricular catheter was removed. Enterococcus faecalis was isolated from the culture specimen. The patient received targeted treatment with an ampicillin plus ceftriaxone combination, and a follow-up culture confirmed the pathogen’s eradication. Although she was considered cured, she had a prolonged intensive care unit stay and finally died in the ward two months after the completion of treatment. This case highlights the first reported use of this combination in a severe, non-endocarditis, invasive enterococcal infection, while the review discusses treatment options for nosocomial ventriculitis/meningitis.

1. Introduction

Ventriculo-meningitis (VM), or nosocomial or post-operative meningitis/ventriculitis, is a severe infection that complicates neurosurgical surgery, external ventricular (or lumbar) drainage, and ventriculoperitoneal shunts [1]. The incidence of this infection varies from 0 to 22%, and it is due to either Gram-negative or Gram-positive bacteria [1,2,3]. Members of the genus Enterococcus are resilient to the healthcare environment, intrinsically resistant to many antimicrobial agents, and can cause device-associated infections [4]. Enterococcus faecalis, which causes about two-thirds of enterococcal infections, was the fifth most frequent pathogen isolated from bloodstream infections worldwide [5,6]. In contrast to Staphylococcus spp., Enterococcus spp. strains are less commonly isolated from cerebrospinal fluid cultures of nosocomial VM patients. In a case series from Spain, the authors estimated the occurrence rate of enterococcal meningitis, community-acquired and nosocomial, at 0.3–4% [7]. Clinical or epidemiological criteria cannot be used to distinguish enterococcal VM (EVM) from VM because of the presence of other bacteria [8,9].
The species and presence of resistance mechanisms determine the suggested antimicrobial chemotherapy [10,11]. Most E. faecalis isolates are susceptible to aminopenicillins, while most Enterococcus faecium isolates are not. Aminopenicillins such as ampicillin and amoxicillin are the preferred antimicrobials for treating susceptible enterococcal infections in non-allergic patients [11]. Apart from aminopenicillins, available active antimicrobial agents are linezolid, imipenem, vancomycin, teicoplanin, and fosfomycin; however, antimicrobial resistant rates vary across countries around the world [12]. E. faecium is one of the most common pathogens responsible for nosocomial infections and is multi-resistant to antibacterial action [13]. The recommended treatment is vancomycin or, in the presence of the vancomycin-resistant phenotype, linezolid or daptomycin [11]. Combining ampicillin or vancomycin with an aminoglycoside to enhance bactericidal action is the routine treatment for more invasive infections such as endocarditis and meningitis [4].
Nonetheless, the treating physician must consider that the central nervous system’s barriers hinder antibacterials from entering the cerebrospinal fluid compartment following their systematic administration [14]. Meanwhile, the current Infectious Diseases Society of America guidelines for healthcare-associated ventriculitis and meningitis do not provide suggestions for treating EVM [15]. However, clinicians can draw expertise from invasive enterococcal infections at other sites, such as infective endocarditis, where ampicillin is combined with an aminoglycoside or ceftriaxone [10,16,17]. Ceftriaxone is a standard meningitis therapy, as it is a poor ligand for the transporters (primarily located in the choroid plexuses) that actively carry away from the central nervous system and many other members of the beta-lactam class [18]. Meanwhile, daily ampicillin dosing for VM may be as high as 15 g or even more, particularly in the critical care setting, where its volume of distribution is increased and renal clearance is augmented [14,19]. An ampicillin–ceftriaxone treatment for complicated bacteremia and endocarditis was associated with fewer relapses than ampicillin monotherapy [10,20].
The objective of the present report is to discuss the therapeutic management of nosocomial enterococcal VM considering there are limited data on the subject. Notably, we present a successful bacterial eradication in an E. faecalis VM case with a combination of ampicillin and ceftriaxone.

2. Description

A 68-year-old woman was admitted to the neurosurgical department for a scheduled resection of a left sphenoid wing meningioma. She presented with a medical history of insulin-dependent diabetes mellitus, hypertension, and coronary artery disease, and had no allergies. She developed right upper and lower arm weakness and was unable to walk. After the surgery, she was transferred to the intensive care unit. The following day, she remained unconscious after sedation withdrawal, and a repeat computerized tomography scan revealed hemispheric hemorrhage and a left middle cerebral artery pseudoaneurysm. The latter was stented and an external ventricular drainage catheter was placed. During the following weeks, neurological evaluation showed a minimally conscious state.
On the 35th day in the intensive care unit, she developed a high fever after the removal of the external ventricular catheter the day before. Cerebrospinal fluid (CSF) specimens were sent for culture and routine analysis (Table 1).
The following day, a Gram-positive microorganism was isolated from the CSF culture. On day 22 of drainage, the external ventricular drainage catheter was suspected to be the primary source of the VM, but the two craniotomies could not be ruled out as contributing causes of the infection. The removal of the catheter was considered the initial therapeutic step. Regarding antimicrobial treatment, linezolid (Demo Pharmaceuticals, Athens, Greece) was started, pending further laboratory input. E. faecalis was identified by matrix-assisted laser desorption ionization performed by the MALDI Biotyper® Sirius System (Bruker, Bremen, Germany). Antimicrobial susceptibility testing performed by the Vitek®2 automated system (bioMerieux, Marcy-l;Etoile, France) showed susceptibility to ampicillin and high-level gentamycin resistance. Ampicillin 16 g daily (Cooper Pharmaceuticals, Athens, Greece) by continuous infusion plus ceftriaxone 2 g (Anfarm Pharmaceuticals, Athens, Greece) twice daily were substituted for linezolid. Meanwhile, creatinine clearance, measured after 24 h urine collection, was augmented at 190 mL/min. The patient’s fever subsided in 4 days, following treatment. A follow-up CSF culture and routine fluid examination on treatment day 13 confirmed bacterial eradication (Table 1). The treatment lasted for 14 days. Following the pathogen clearance, the patient remained afebrile, and her neurological status failed to improve. Ventilator weaning was prolonged, lasting five weeks. She was then transferred to a neurosurgical ward, where she died three weeks later, and two months after the completion of treatment, without showing any signs of infection.

3. Discussion

The literature on nosocomial EVM is summarized in Table S1 [7,8,9,21,22,23,24,25,26,27,28,29,30,31,32,33,34,35,36,37,38,39,40,41,42,43,44,45,46]. Previous studies were usually small case series and case reports, while there were only four series with at least ten cases each. Of 138 reported cases, a species was identified in 128. E. faecalis was most commonly identified (59.4%), followed by E. faecium (26.1%). Almost all E. faecalis isolates retained susceptibility to ampicillin, whereas vancomycin-resistant Enterococcus (VRE) was isolated in 23.2% of patients. Finally, there were 55 (39.9%) pediatric patients. Regarding treatment options, there are antimicrobials considered more efficacious that present favorable pharmacokinetic profiles, i.e., adequate penetration into the CSF after intravenous delivery. However, when one of the above agents cannot be administered, there are less optimal alternatives (Table 2).
Among the most commonly used agents, linezolid is a suitable empirical treatment for nosocomial Gram-positive VM as it retains activity against VRE and methicillin-resistant Staphylococcus and sufficiently enters the CSF following its intravenous (IV) administration [47,48,49,50]. Moreover, limited efficacy data further support its use for treating EVM (Table 2).
The gold standard for enterococcal infections is ampicillin whenever susceptible strains are involved [10,11]. Concerning the management of EVM, it was often combined with aminoglycosides and only once with cefotaxime (Table 2 and Table S1). Regarding dosing, a high IV ampicillin dose of 200 mg/kg/day or an adult daily dose of approximately 15 g should suffice [7,14]. The presence of high-level gentamycin resistance in our case made us consider using ceftriaxone as the companion drug. This is, as far as we are aware, the first reported co-administration of ampicillin and ceftriaxone for treating EVM.
Vancomycin, in combination with a beta-lactam class antipseudomonal drug, is recommended for empirically treating VM [15]. However, the current guidelines recommend the use of vancomycin in the context of staphylococcal infections, particularly if they are methicillin-resistant. The drug dose should be adjusted to maintain trough levels of 15–20 mcg/mL [15]. Data on vancomycin use in EVM are limited to case series and case reports (Table S1). Although IV vancomycin demonstrated unpredictable CSF penetration, most patients were cured [51]. Teicoplanin showed similar efficacy to vancomycin for managing methicillin-resistant Staphylococcus aureus infection [52]. However, its role in treating EVM is not defined.
Regarding less common options, daptomycin can be used to manage bloodstream VRE infections; concerning EVM, daptomycin poorly penetrates the CSF and is rarely used [1,37,53,54,55,56]. The efficacy of tigecycline has been questioned, as it demonstrated increased mortality compared with other antimicrobials; moreover, it poorly enters the CSF following IV delivery [57,58]. Thus, it can be combined with other active drugs as salvage therapy [57]. It has been used for treating VM, due to extensively drug resistant Gram-negative pathogens, via both IV and IT/IVT routes [1,59,60]. Currently, there are no available data for tigecycline treatment for EVM. In vitro data showed that chloramphenicol often retains activity against E. faecium regardless of vancomycin resistance, although enterococcal resistance rates to the drug vary widely between countries and have increased over time [12,61]. Meanwhile, this drug demonstrated favorable penetration into the CSF (approximately 50%) and had comparable efficacy to beta-lactams in meningitis treatment [1,62]. However, adding IT/IVT to IV chloramphenicol may improve efficacy (Table 2), while toxicities, particularly hematological, are a major concern [11]. Fosfomycin adequately penetrates the CSF, and has been used to treat mostly non-enterococcal central nervous system infections with a companion antimicrobial in 87% of patients [63,64]. This combination regimen achieved a cure rate as high as 90% and a CSF sterilization rate of 97% [63]. It is active against enterococci, including VRE, and could be a valuable therapeutic option for EVM, given its favorable CSF entry profile. Quinupristin/dalfopristin is inactive against E. faecalis, but retains activity against most E. faecium strains [11]. Regrettably, it was associated with higher mortality than linezolid and its indication for treating VRE bloodstream infections was withdrawn. It presents severe adverse effects and should be used, if available, as a complementary drug to a combination regimen [11]. Nonetheless, it minimally enters the CSF and should seldom be considered a suitable treatment option [65].
There are novel antimicrobials that include enterococci in their antimicrobial spectrum that might be used in the management of EVM [66]. Eravacycline, a tetracycline related to tigecycline, does not sufficiently enter the CSF. Similarly, the novel glycopeptides, either dalbavancin or telavancin, or oritavancin, are poorly transferred to the CSF after IV administration. Finally, tedizolid, although closely related to linezolid, penetrated the CSF less than linezolid, lacking the latter’s excellent pharmacokinetic profile for treating CNS infections [66].
Finally, adjunct IT/IVT therapy is directly delivered to the CSF compartment, bypassing the blood–brain and blood–CSF barriers. Regarding EVM, there are limited literature data on adjunct IT/IVT treatment with vancomycin or aminoglycoside, or, more recently, daptomycin (Table S1).

4. Summary

In line with previous reports on EVM treatment, which described the use of ampicillin either as the sole antimicrobial or complemented with an aminoglycoside, we found that the combination of ampicillin and ceftriaxone eradicated the pathogen in the CSF. The literature on EVM mostly includes small case series and case reports on various antimicrobial options for treating enterococcal strains. Enterococci are endogenously resistant to a plethora of antimicrobial agents, while available in vitro active drugs should penetrate the blood–brain and blood–CSF barriers to reach the infection site. In addition to E. faecalis, which usually remains susceptible to ampicillin, many reports discuss the more resistant E. faecium species, which can be successfully treated with IV linezolid. Other less commonly used drugs, particularly for treating VRE infections, are daptomycin, chloramphenicol, and quinupristin/dalfopristin. Daptomycin should preferably be delivered by both IV and IT/IVT routes to achieve sufficient levels in the CSF compartment. Regarding the prognosis of EVM, mortality varies between reports; however, there is uncertainty about the outcome because of the very low quality of evidence (Table 2).

5. Conclusions

The present case highlights the treatment of enterococcal ventriculitis/meningitis, an uncommon infection, with a combination of ampicillin and ceftriaxone. Despite the infection eradication, the patient died two months later; however, she did not present any evidence of infection at the time of her death. Further studies are needed to better define the generalizability and practical aspects of this antimicrobial scheme for the management of central nervous system infections.

Supplementary Materials

The following supporting information can be downloaded at: https://www.mdpi.com/article/10.3390/pathogens14010003/s1, Table S1: Enterococcal ventriculitis/meningitis reports in the literature.

Author Contributions

Conceptualization, M.K. and E.G.; software, K.P.; investigation, M.K., Z.A., E.G. and S.N.P.; writing—original draft preparation, M.K. and Z.A.; writing—review and editing, M.K., E.G., K.P. and E.A.; supervision, E.A. All authors have read and agreed to the published version of the manuscript.

Funding

This research received no external funding.

Institutional Review Board Statement

Ethical review and approval were waived for this study due to the retrospective and non-interventional nature of this report.

Informed Consent Statement

Written informed consent was obtained from the patient to publish this paper.

Data Availability Statement

The original contributions presented in this study are included in the article/Supplementary Materials. Further inquiries can be directed to the corresponding author.

Conflicts of Interest

The authors declare no conflicts of interest.

References

  1. Karvouniaris, M.; Brotis, A.; Tsiakos, K.; Palli, E.; Koulenti, D. Current Perspectives on the Diagnosis and Management of Healthcare-Associated Ventriculitis and Meningitis. Infect. Drug Resist. 2022, 15, 697–721. [Google Scholar] [CrossRef] [PubMed]
  2. Hasbun, R. Central Nervous System Device Infections. Curr. Infect. Dis. Rep. 2016, 18, 34. [Google Scholar] [CrossRef]
  3. Rogers, T.; Sok, K.; Erickson, T.; Aguilera, E.; Wootton, S.H.; O Murray, K.; Hasbun, R. The comparison of Gram-positive associated ventriculitis and meningitis in adults and children. Intensive Care Med. 2020, 46, 128–131. [Google Scholar] [CrossRef]
  4. García-Solache, M.; Rice, L.B. The Enterococcus: A Model of Adaptability to Its Environment. Clin. Microbiol. Rev. 2019, 32, e00058-18. [Google Scholar] [CrossRef] [PubMed]
  5. Pfaller, M.A.; Cormican, M.; Flamm, R.K.; Mendes, R.E.; Jones, R.N. Temporal and Geographic Variation in Antimicrobial Susceptibility and Resistance Patterns of Enterococci: Results from the SENTRY Antimicrobial Surveillance Program, 1997–2016. Open Forum. Infect. Dis. 2019, 6 (Suppl. S1), S54–S62. [Google Scholar] [CrossRef]
  6. Diekema, D.J.; Hsueh, P.-R.; Mendes, R.E.; Pfaller, M.A.; Rolston, K.V.; Sader, H.S.; Jones, R.N. The Microbiology of Bloodstream Infection: 20-Year Trends from the SENTRY Antimicrobial Surveillance Program. Antimicrob. Agents Chemother. 2019, 63, e00355-19. [Google Scholar] [CrossRef]
  7. Pintado, V.; Cabellos, C.; Moreno, S.; Meseguer, M.A.; Ayats, J.; Viladrich, P.F. Enterococcal Meningitis. A Clinical Study of 39 Cases and Review of the Literature. Medicine 2003, 82, 346–364. [Google Scholar] [CrossRef] [PubMed]
  8. Rodríguez-Guardado, A.; Asensi, V.; Torres, J.M.; Perez, F.; Blanco, A.; Maradona, J.A.; Carton, J.A. Post-surgical enterococcal meningitis: Clinical and epidemiological study of 20 cases. Scand. J. Infect. Dis. 2006, 38, 584–588. [Google Scholar] [CrossRef]
  9. Yousef Khan, F. Enterococcal meningitis/ventriculitis in Qatar-Experience with eight patients. Qatar Med. J. 2021, 2020, 46. [Google Scholar] [CrossRef] [PubMed]
  10. Rosselli Del Turco, E.; Bartoletti, M.; Dahl, A.; Cervera, C.; Pericas, J.M. How do I manage a patient with enterococcal bacteraemia? Clin. Microbiol. Infect. 2021, 27, 364–371. [Google Scholar] [CrossRef]
  11. Mercuro, N.J.; Davis, S.L.; Zervos, M.J.; Herc, E.S. Combatting resistant enterococcal infections: A pharmacotherapy review. Expert. Opin. Pharmacother. 2018, 19, 979–992. [Google Scholar] [CrossRef] [PubMed]
  12. Guan, L.; Beig, M.; Wang, L.; Navidifar, T.; Moradi, S.; Motallebi Tabaei, F.; Teymouri, Z.; Abedi Moghadam, M.; Sedighi, M. Global status antimicrobial resistance in clinical Enterococcus faecalis isolates: Systematic review and meta-analysis. Ann. Clin. Microbiol. Antimicrob. 2024, 23, 80. [Google Scholar] [CrossRef]
  13. Boucher, H.W.; Talbot, G.H.; Bradley, J.S.; Edwards, J.E.; Gilbert, D.; Rice, L.B.; Scheld, M.; Spellberg, B.; Bartlett, J. Bad Bugs, No Drugs: No ESKAPE! An Update from the Infectious Diseases Society of America. Clin. Infect. Dis. 2009, 48, 1–12. [Google Scholar] [CrossRef]
  14. Nau, R.; Sorgel, F.; Eiffert, H. Central nervous system infections and antimicrobial resistance: An evolving challenge. Curr. Opin. Neurol. 2021, 34, 456–467. [Google Scholar] [CrossRef]
  15. Tunkel, A.R.; Hasbun, R.; Bhimrah, A.; Byers, K.; Kaplan, S.L.; Scheld, W.M.; van de Beek, D.; Bleck, T.P.; Garton, H.J.L.; Zunt, J.R. Infectious Disease Society of America’s clinical practice guidelines for healthcare-associated ventriculitis and meningitis. Clin. Infect. Dis. 2017, 64, e34–e65. [Google Scholar] [CrossRef] [PubMed]
  16. Fernández-Hidalgo, N.; Almirante, B.; Gavaldà, J.; Gurgui, M.; Peña, C.; de Alarcón, A.; Ruiz, J.; Vilacosta, I.; Montejo, M.; Vallejo, N.; et al. Ampicillin plus ceftriaxone is as effective as ampicillin plus gentamicin for treating Enterococcus faecalis infective endocarditis. Clin. Infect. Dis. 2013, 56, 1261–1268. [Google Scholar] [CrossRef]
  17. Delgado, V.; Ajmone Marsan, N.; de Waha, S.; Bonaros, N.; Brida, M.; Burri, H.; Caselli, S.; Doenst, T.; Ederhy, S.; Erba, P.A.; et al. 2023 ESC Guidelines for the management of endocarditis Developed by the task force on the management of endocarditis of the European Society of Cardiology (ESC) Endorsed by the European Association for Cardio-Thoracic Surgery (EACTS) and the European Association of Nuclear Medicine (EANM). Eur. Heart J. 2023, 44, 3948–4042. [Google Scholar]
  18. Nau, R.; Sorgel, F.; Eiffert, H. Penetration of Drugs through the Blood-Cerebrospinal Fluid/Blood-Brain Barrier for Treatment of Central Nervous System Infections. Clin. Mirobiol Rev. 2010, 23, 858–883. [Google Scholar]
  19. Sime, F.B.; Roberts, M.S.; Roberts, J.A. Optimization of dosing regimens and dosing in special populations. Clin. Microbiol. Infect. 2015, 21, 886–893. [Google Scholar] [CrossRef]
  20. Danneels, P.; Hamel, J.-F.; Picard, L.; Rezig, S.; Martinet, P.; Lorleac’h, A.; Talarmin, J.P.; Buzelé, R.; Guimard, T.; Le Moal, G.; et al. Impact of Enterococcus faecalis endocarditis treatment on risk of relapse. Clin. Infect. Dis. 2023, 76, 281–290. [Google Scholar] [CrossRef] [PubMed]
  21. Losonsky, G.A.; Wolf, A.; Schwalbe, R.S.; Nataro, J.; Gibson, C.B.; Lewis, E.W. Successful treatment of meningitis due to multiply resistant Enterococcus faecium with a combination of intrathecal teicoplanin and intravenous antimicrobial agents. Clin. Infect. Dis. 1994, 19, 163–165. [Google Scholar] [CrossRef]
  22. Stevenson, K.B.; Murray, E.W.; Sarubbi, F.A. Enterococcal meningitis: Report of four cases and review. Clin. Infect. Dis. 1994, 18, 233–239. [Google Scholar] [CrossRef]
  23. Nachman, S.A.; Verma, R.; Egnor, M. Vancomycin-resistant Enterococcus faecium shunt infection in an infant: An antibiotic cure. Microb. Drug Resist. 1995, 1, 95–96. [Google Scholar] [CrossRef]
  24. Tan, T.Y.; Pitman, I.; Penrose-Stevens, A.; Simpson, B.A.; Flanagan, P.G. Treatment of a vancomycin-resistant Enterococcus faecium ventricular drain infection with quinupristin/dalfopristin and review of the literature. J. Infect. 2000, 41, 95–97. [Google Scholar] [CrossRef]
  25. Tush, G.M.; Huneycutt, S.; Phillips, A.; Ward, J.D. Intraventricular quinupristin/dalfopristin for the treatment of vancomycin-resistant Enterococcus faecium shunt infection. Clin. Infect. Dis. 1998, 26, 1460–1461. [Google Scholar] [CrossRef] [PubMed]
  26. Pérez Mato, S.; Robinson, S.; Bégué, R.E. Vancomycin-resistant Enterococcus faecium meningitis successfully treated with chloramphenicol. Pediatr. Infect. Dis. J. 1999, 18, 483–484. [Google Scholar] [CrossRef]
  27. Shaikh, Z.H.; Peloquin, C.A.; Ericson, C.D. Successful treatment of vancomycin-resistant Enterococcus faecium meningitis with linezolid: Case report and literature review. Scand. J. Infect. Dis. 2001, 33, 375–379. [Google Scholar] [PubMed]
  28. Steinmetz, M.P.; Vogelbaum, M.A.; De Georgia, M.A.; Andrefsky, J.C.; Isada, C. Successful treatment of vancomycin-resistant enterococcus meningitis with linezolid: Case report and review of the literature. Crit. Care Med. 2001, 29, 2383–2385. [Google Scholar] [CrossRef]
  29. Graham, P.L.; Ampofo, K.; Saiman, L. Linezolid treatment of vancomycin-resistant Enterococcus faecium ventriculitis. Pediatr. Infect. Dis. J. 2002, 21, 798–800. [Google Scholar] [CrossRef] [PubMed]
  30. Schnapp, A.; Elber-Dorozko, S.; Temper, V.; Gordon, O.; Averbuch, D. Enterococcal Central Nervous System Infections in Children: A 22 Years’ Experience in a Tertiary Center and Review of the Literature. Pediatr. Infect. Dis. J. 2024, 43, 731–735. [Google Scholar] [CrossRef]
  31. Kanchanapoom, T.; Koirala, J.; Goodrich, J.; Agamah, E.; Khardori, N. Treatment of central nervous system infection by vancomycin-resistant Enterococcus faecium. Diagn. Microbiol. Infect. Dis. 2003, 45, 213–215. [Google Scholar] [CrossRef]
  32. Scapellato, P.G.; Ormazabal, C.; Scapellato, J.L.; Bottaro, E.G. Meningitis due to vancomycin-resistant Enterococcus faecium successfully treated with combined intravenous and intraventricular chloramphenicol. J. Clin. Microbiol. 2005, 43, 3578–3579. [Google Scholar] [CrossRef]
  33. da Silva, P.S.; Monteiro Neto, H.; Sejas, L.M. Successful treatment of vancomycin-resistant Enterococcus ventriculitis in a child. Braz. J. Infect. Dis. 2007, 11, 297–299. [Google Scholar] [CrossRef] [PubMed]
  34. Elvy, J.; Porter, D.; Brown, E. Treatment of external ventricular drain-associated ventriculitis caused by Enterococcus faecalis with intraventricular daptomycin. J. Antimicrob. Chemother. 2008, 61, 461–462. [Google Scholar] [CrossRef]
  35. Maranich, A.M.; Rajnik, M. Successful treatment of vancomycin-resistant enterococcal ventriculitis in a pediatric patient with linezolid. Mil. Med. 2008, 173, 927–929. [Google Scholar] [CrossRef] [PubMed]
  36. Hartmann, C.; Peter, C.; Hermann, E.; Ure, B.; Sedlacek, L.; Hansen, G.; Bohnhorst, B. Successful treatment of vancomycin-resistant Enterococcus faecium ventriculitis with combined intravenous and intraventricular chloramphenicol in a newborn. J. Med. Microbiol. 2010, 59, 1371–1374. [Google Scholar] [CrossRef]
  37. Le, J.; Bookstaver, P.B.; Rudisill, C.N.; Hashem, M.G.; Iqbal, R.; James, C.L.; Sakoulas, G. Treatment of meningitis caused by vancomycin-resistant Enterococcus faecium: High-dose and combination daptomycin therapy. Ann. Pharmacother. 2010, 44, 2001–2006. [Google Scholar] [CrossRef]
  38. Çay, Ü.; Alabaz, D.; Özgür Gündeşlioğlu, Ö.; Kibar, F.; Çetin, C.; Oktay, K. Experience with enterococcal meningitis/ventriculitis in children. Pediatr. Int. 2023, 65, e15398. [Google Scholar] [CrossRef] [PubMed]
  39. Mueller, S.W.; Kiser, T.H.; Anderson, T.A.; Neumann, R.T. Intraventricular daptomycin and intravenous linezolid for the treatment of external ventricular-drain-associated ventriculitis due to vancomycin-resistant Enterococcus faecium. Ann. Pharmacother. 2012, 46, e35. [Google Scholar] [CrossRef]
  40. Knoll, B.M.; Hellmann, M.; Kotton, C.N. Vancomycin-resistant Enterococcus faecium meningitis in adults: Case series and review of the literature. Scand. J. Infect. Dis. 2013, 45, 131–139. [Google Scholar] [CrossRef] [PubMed]
  41. Khanum, I.; Anwar, S.; Farooque, A. Enterococcal Meningitis/Ventriculitis: A Tertiary Care Experience. Asian J. Neurosurg. 2019, 14, 102–105. [Google Scholar] [CrossRef]
  42. Qiu, J.J.; Tang, J.; Li, D.L. Success of linezolid therapy for post neurosurgical ventriculitis due to vancomycin-resistant Enterococcus faecium: Case report and literature review. Chin. Neurosurg. J. 2015, 1, 18. [Google Scholar] [CrossRef]
  43. Cearns, M.D.; McLintock, B.T.; Suttner, N.; Khalsa, K. Successful treatment of vancomycin-resistant Enterococcal infection of an external ventricular drain with 2 weeks of intravenous linezolid. Access Microbiol. 2022, 4, 000335. [Google Scholar] [CrossRef]
  44. Dhariwal, A.; Leff, R.; Allen, M.; Cherian, B. Intrathecal daptomycin use in a challenging case of Enterococcus faecium ventriculitis. Access Microbiol. 2022, 4, 000230. [Google Scholar] [CrossRef] [PubMed]
  45. Rei, K.M.; Reddy, V.; Andraos, C.; Brazdzionis, J.; Siddiqi, J. Catheter-Associated Vancomycin-Resistant Enterococcus faecium Ventriculitis and Multidrug-Resistant Acinetobacter baumannii Pneumonia with Subsequent Acinetobacter Ventriculitis: A Case Report. Cureus 2023, 15, e49058. [Google Scholar] [CrossRef] [PubMed]
  46. Inada, S.; Omori, K.; Kitagawa, H.; Koba, Y.; Nomura, T.; Shigemoto, N.; Taguchi, A.; Kinoshita, Y.; Hattori, N.; Ohge, H. Blood culture bottles for culturing cerebrospinal fluid in cases of bacterial meningitis caused by Enterococcus faecalis: A case report. J. Infect. Chemother. 2024, in press. [CrossRef] [PubMed]
  47. Gatti, M.; Viaggi, B.; Rossolini, G.M.; Pea, F.; Viale, P. Targeted Therapy of Severe Infections Caused by Staphylococcus aureus in Critically Ill Adult Patients: A Multidisciplinary Proposal of Therapeutic Algorithms Based on Real-World Evidence. Microorganisms 2023, 11, 394. [Google Scholar] [CrossRef] [PubMed]
  48. Lee, B.J.; Vu, B.N.; Seddon, A.N.; Hodgson, H.A.; Wang, S.K. Treatment Considerations for CNS Infections Caused by Vancomycin-Resistant Enterococcus faecium: A Focused Review of Linezolid and Daptomycin. Ann. Pharmacother. 2020, 54, 1243–1251. [Google Scholar] [CrossRef]
  49. Villani, P.; Regazzi, M.B.; Marubbi, F.; Viale, P.; Pagani, L.; Cristini, F.; Cadeo, B.; Carosi, G.; Bergomi, R. Cerebrospinal Fluid Linezolid Concentrations in Postneurosurgical Central Nervous System Infections. Antimicrob. Agents Chemother. 2002, 46, 936–937. [Google Scholar] [CrossRef] [PubMed]
  50. Beer, R.; Engelhardt, K.W.; Pfausler, B.; Broessner, G.; Helbok, R.; Lackner, P.; Brenneis, C.; Kaehler, S.T.; Georgopoulos, A.; Schmutzhard, E. Pharmacokinetics of intravenous linezolid in cerebrospinal fluid and plasma in neurointensive care patients with staphylococcal ventriculitis associated with external ventricular drains. Antimicrob. Agents Chemother. 2007, 51, 379–382. [Google Scholar] [CrossRef]
  51. Beach, J.E.; Perrott, J.; Turgeon, R.D.; Ensom, M.H.H. Penetration of Vancomycin into the Cerebrospinal Fluid: A Systematic Review. Clin. Pharmacokinet. 2017, 56, 1479–1490. [Google Scholar] [CrossRef] [PubMed]
  52. Arda, B.; Yamazhan, T.; Sipahi, O.R.; Islekel, S.; Buke, C.; Ulusoy, S. Meningitis due to methicillin-resistant Staphylococcus aureus (MRSA): Review of 10 cases. Int. J. Antimicrob. Agents 2005, 25, 414–418. [Google Scholar] [CrossRef]
  53. Turnidge, J.; Kahlmeter, G.; Canton, R.; MacGowan, A.; Giske, C.G.; European Committee on Antimicrobial Susceptibility Testing. Daptomycin in the treatment of enterococcal bloodstream infections and endocarditis: A EUCAST position paper. Clin. Microb. Infect. 2020, 26, 1039–1043. [Google Scholar] [CrossRef]
  54. Britt, N.S.; Potter, E.M.; Patel, N.; Steed, M.E. Comparative Effectiveness and Safety of Standard-, Medium-, and High-Dose Daptomycin Strategies for the Treatment of Vancomycin-Resistant Enterococcal Bacteremia Among Veterans Affairs Patients. Clin. Infect. Dis. 2017, 64, 605–613. [Google Scholar] [CrossRef] [PubMed]
  55. Shi, C.; Jin, W.; Xie, Y.; Zhou, D.; Xu, S.; Li, Q.; Lin, N. Efficacy and safety of daptomycin versus linezolid treatment in patients with vancomycin-resistant enterococcal bacteraemia: An updated systematic review and meta-analysis. J. Glob. Antimicrob. Resist. 2020, 21, 235–245. [Google Scholar] [CrossRef] [PubMed]
  56. Jaber, R.H.; Beahm, N.P. Daptomycin for the treatment of acute bacterial meningitis: A narrative review. Int. J. Antimicrob. Agents. 2023, 61, 106770. [Google Scholar] [CrossRef]
  57. Yahav, D.; Lador, A.; Paul, M.; Leibovici, L. Efficacy and safety of tigecycline: A systematic review and meta-analysis. J. Antimicrob. Chemother. 2011, 66, 1963–1971. [Google Scholar] [CrossRef]
  58. Pallotto, C.; Fiorio, M.; D’Avolio, A.; Sgrelli, A.; Baldelli, F.; Di Perri, G.; De Socio, G.V. Cerebrospinal fluid penetration of tigecycline. Scand. J. Infect. Dis. 2014, 46, 69–72. [Google Scholar] [CrossRef]
  59. Nau, R.; Blei, C.; Eiffert, H. Intrathecal Antibacterial and Antifungal Therapies. Clin. Microbiol. Rev. 2020, 33, e00190-19. [Google Scholar] [CrossRef]
  60. Tsolaki, V.; Karvouniaris, M.; Manoulakas, E.; Kotlia, P.; Karadontas, V.; Fotakopoulos, G.; Zakynthinos, E.; Makris, D. Intraventricular CNS treatment with Colistin-Tigecycline combination: A case series. J. Crit. Care 2018, 47, 338–341. [Google Scholar] [CrossRef]
  61. Civljak, R.; Giannella, M.; Di Bella, S.; Petrosillo, N. Could chloramphenicol be used against ESKAPE pathogens? A review of in vitro data in the literature from the 21st century. Expert. Rev. Anti Infect. Ther. 2014, 12, 249–264. [Google Scholar] [CrossRef] [PubMed]
  62. Eliakim-Raz, N.; Lador, A.; Leibovici-Weissman, Y.; Elbaz, M.; Paul, M.; Leibovici, L. Efficacy and safety of chloramphenicol: Joining the revival of old antibiotics? Systematic review and meta-analysis of randomized controlled trials. J. Antimicrob. Chemother. 2015, 70, 979–996. [Google Scholar] [CrossRef] [PubMed]
  63. Pfausler, B.; Spiss, H.; Dittrich, P.; Zeitlinger, M.; Schmutzhard, E.; Christian Joukhadar, C. Concentrations of fosfomycin in the cerebrospinal fluid of neurointensive care patients with ventriculostomy—Associated ventriculitis. J. Antimicrob. Chemother. 2004, 53, 848–852. [Google Scholar] [CrossRef]
  64. Tsegka, K.G.; Voulgaris, G.L.; Kyriakidou, M.; Falagas, M.E. Intravenous fosfomycin for the treatment of patients with central nervous system infections: Evaluation of the published evidence. Expert. Rev. Anti Infect. Ther. 2020, 18, 657–668. [Google Scholar] [CrossRef] [PubMed]
  65. Reissier, S.; Cattoir, V. Streptogramins for the treatment of infections caused by Gram-positive pathogens. Expert. Rev. Anti Infect. Ther. 2021, 19, 587–599. [Google Scholar] [CrossRef] [PubMed]
  66. Nau, R.; Seele, J.; Eiffert, H. New Antibiotics for the Treatment of Nosocomial Central Nervous System Infections. Antibiotics 2024, 13, 58. [Google Scholar] [CrossRef]
Table 1. CSF analysis and culture.
Table 1. CSF analysis and culture.
Before Treatment13th Treatment Day
WBC, n/μL200017
Glucose, mg/dL3108
Protein, mg/dL252264
CultureE. faecalisno isolate
Abbreviations: WBC, white blood cells.
Table 2. Treatment options for nosocomial enterococcal ventriculitis/meningitis according to previous reports.
Table 2. Treatment options for nosocomial enterococcal ventriculitis/meningitis according to previous reports.
Primary Antimicrobial AgentMost Common Companion Antimicrobial Target Species/Susceptibility to the AgentCSF PenetrationFrequency of Use *DoseDurationMortality #
Most commonly used primary agents
AmpicillinAGEnterococcus faecalis/yesRelatively low; the daily dose can be increased to improve delivery37%Adult, 15 g (or more); child, 200 mg/kg/dayMedian (IQR) 21 (15–24) days7.7%
LinezolidOccasionally rifampicin, IT/IVT daptomycin Enterococcus faecium/yes, including VREExcellent12.3%Adult, 600 mg ×2 14–28 days0%
VancomycinVariable: carbapenem, AG, cefalosporinE. faecalis/yes
E. faecium/yes, except VRE		Unpredictable26.1%Loading dose, adult, 15–30 mg/kg;
followed by adult, 30–60 mg/kg/day; child, 60 mg/kg/day §		NS10%
Less common primary agents
DaptomycinGentamycin, linezolid, IT/IVT daptomycinE. faecium/VRE includedPoor2.9%6–12 mg/kg20–30 days0%
Quinupristin/dalfopristinIT/IVT quinupristin/dalfopristin, linezolidE. faecium/VRE includedPoor2.9%7.5 mg/kg thrice dailyVariable50%
ChloramphenicolIT/IVT chloramphenicolE. faecium/VRE often includedExcellent2.2%Adult, 3 g daily; child, 100 mg/kg/day12–27 days0%
* The denominator is 138, the total number of reported cases. # Outcome evaluation is limited as the number of cases is small. § The post loading dose can be given by a continuous infusion; when it is administered by intermittent infusion, adjust dosing to maintain vancomycin’s trough concentrations of 15–20 μg/mL. Abbreviations: AG, aminoglycoside; IT, intrathecal; IVT, intraventricular; NS, not specified; VRE, vancomycin-resistant Enterococcus.
Disclaimer/Publisher’s Note: The statements, opinions and data contained in all publications are solely those of the individual author(s) and contributor(s) and not of MDPI and/or the editor(s). MDPI and/or the editor(s) disclaim responsibility for any injury to people or property resulting from any ideas, methods, instructions or products referred to in the content.

Share and Cite

MDPI and ACS Style

Karvouniaris, M.; Aidoni, Z.; Gkeka, E.; Primikyri, S.N.; Pagioulas, K.; Argiriadou, E. Treatment Options for Nosocomial Ventriculitis/Meningitis: A Case Report and Review of the Literature. Pathogens 2025, 14, 3. https://doi.org/10.3390/pathogens14010003

AMA Style

Karvouniaris M, Aidoni Z, Gkeka E, Primikyri SN, Pagioulas K, Argiriadou E. Treatment Options for Nosocomial Ventriculitis/Meningitis: A Case Report and Review of the Literature. Pathogens. 2025; 14(1):3. https://doi.org/10.3390/pathogens14010003

Chicago/Turabian Style

Karvouniaris, Marios, Zoi Aidoni, Eleni Gkeka, Stella Niki Primikyri, Konstantinos Pagioulas, and Elena Argiriadou. 2025. "Treatment Options for Nosocomial Ventriculitis/Meningitis: A Case Report and Review of the Literature" Pathogens 14, no. 1: 3. https://doi.org/10.3390/pathogens14010003

APA Style

Karvouniaris, M., Aidoni, Z., Gkeka, E., Primikyri, S. N., Pagioulas, K., & Argiriadou, E. (2025). Treatment Options for Nosocomial Ventriculitis/Meningitis: A Case Report and Review of the Literature. Pathogens, 14(1), 3. https://doi.org/10.3390/pathogens14010003

Note that from the first issue of 2016, this journal uses article numbers instead of page numbers. See further details here.

Article Metrics

Back to TopTop