US Pharm. 2021;45(4):HS-12-HS-16.
ABSTRACT: Healthcare-associated ventriculitis and meningitis is a serious infection that most commonly has a bacterial etiology, including Gram-positive and Gram-negative microorganisms. According to guidelines released by the Infectious Diseases Society of America, the recommended empiric antimicrobial treatment for these types of infections is vancomycin in combination with an antipseudomonal beta-lactam—either cefepime, ceftazidime, or meropenem. Therapy should be modified and directed toward the identified pathogen, with a typical treatment duration of 10 to 14 days. Pharmacists are in a key position to understand the diagnostic challenges and recommend appropriate empiric and directed antimicrobial treatment for the management of these infections.
Healthcare-associated ventriculitis and meningitis refers to an infection that results from an invasive procedure related to the placement of a device (such as a cerebrospinal fluid [CSF] shunt, CSF drain, intrathecal infusion pump, or deep brain stimulation hardware) or as a complication related to neurosurgery or head trauma.1,2 In terms of devices, CSF shunts or drains are the most common causes of infection.3 Healthcare-associated ventriculitis and meningitis are considered to be diagnostic challenges.1,2,4,5 It is important for pharmacists to know the appropriate management of these serious infections, which are associated with significant neurologic morbidity and mortality, including moderate-to-severe disability, persistent vegetative state, or death.2-5 This article reviews the etiology, diagnostic considerations, and management of healthcare-associated bacterial ventriculitis and meningitis, including information from the Infectious Diseases Society of America (IDSA) guidelines.
The most common bacterial etiologies of healthcare-associated ventriculitis and meningitis are Staphylococcus aureus, coagulase-negative staphylococci (such as Staphylococcus epidermidis), Cutibacterium acnes (formerly named Propionibacterium acnes) and Gram-negative bacilli, including Escherichia coli, Enterobacter spp., Citrobacter spp., Serratia spp., and Pseudomonas aeruginosa.1,6 Fungal pathogens are much less common than bacteria.1 In terms of fungal etiology, Candida species most commonly cause infection in the post-operative setting, while Candida spp., Aspergillus spp., and Cryptococcus neoformans have been found to cause infection in patients with traumatic head injuries.1
Clinical Presentation and Diagnosis
The diagnosis of healthcare-associated ventriculitis and meningitis is challenging for many reasons.1,2,4,5 Although CSF Gram stain and culture are important for diagnosis, initiation of antimicrobial therapy prior to collection of CSF impacts the sensitivity of these tests and can result in false-negative results.2,5,7 Additionally, the clinical presentation of infection may vary based on the infecting pathogen (coagulase-negative staphylococci and C acnes are more indolent pathogens that may cause less meningeal inflammation and associated symptoms); source of infection (a device-related infection may present with a surgical wound infection with or without meningitis symptoms); and the patient’s age (altered mental status may be more common in those aged ≥65 years).1,2,4,5,8 It may also be difficult to distinguish symptoms of infection from the presence of an underlying neurologic disease or condition.1,2,4,5
Signs and symptoms of healthcare-associated ventriculitis and meningitis may vary and include new headache, fever, nausea, lethargy, new or worsening altered mental status, seizures, erythema, tenderness or drainage at a surgical site, and/or peritonitis/abdominal tenderness in those with ventriculoperitoneal shunts.1,2,5 CSF fluid should be collected if healthcare-associated ventriculitis and meningitis is suspected in order to establish the diagnosis of infection.1,2,5 CSF cultures should be held for at least 10 days (to allow for detection of slower-growing microorganisms such as C acnes) for suspected CSF shunt or drain infections in those with initial negative cultures.1 CSF may also be assessed for white blood cell count, glucose, protein, lactate, and biomarkers such as procalcitonin.1,2,5 Although CSF pleocytosis (generally defined as an elevated white blood cell count in CSF), hypoglycorrhachia (defined as a low glucose level in the CSF), or elevated protein, lactate, or procalcitonin levels in CSF are suggestive of infection, they are not as specific as CSF culture with respect to diagnosis.1,9,10 Nucleic acid amplification tests and testing for fungal pathogens of CSF may also be performed.1,5 The guidelines also recommend neuroimaging in patients with suspected infection to determine the source of infection and to identify any complications.1
CSF cultures are considered to be the most important test for diagnosing healthcare-associated ventriculitis and meningitis.1 The IDSA guidelines further state that single or multiple positive CSF cultures in patients with CSF pleocytosis and/or hypoglycorrhachia, or an increasing cell count, with clinical symptoms suspicious for ventriculitis or meningitis, is indicative of a CSF drain infection.1 For patients with neurosurgery or head trauma, CSF pleocytosis with a positive culture and symptoms of infection are indicative of healthcare-associated ventriculitis or meningitis, while low glucose and elevated protein concentrations in the CSF are suggestive of the diagnosis of infection.1 However, a main limitation of the IDSA definitions is that they are not applicable to those who have negative CSF cultures due to previous treatment with antimicrobial therapy.2,5
The CDC National Healthcare Safety Network (CDC/NHSN), a healthcare-associated infection tracking system used in the United States, publishes surveillance definitions for specific types of infections, including a case definition of healthcare-associated meningitis or ventriculitis (TABLE 1).11,12 Although the guidelines state that this definition is useful in defining the likelihood of a true infection, some authors have pointed out that this definition has limitations, including that it was created for surveillance purposes and not for clinical diagnosis.1,2,4,5
In terms of antimicrobial selection, the principles of treatment for healthcare-associated ventriculitis and meningitis stated in the IDSA guidelines include that the antimicrobial agent must penetrate the central nervous system (CNS), achieve adequate therapeutic concentrations in the CSF, and display bactericidal activity against the suspected or confirmed infecting pathogen(s).1 It is recommended to use an empiric antimicrobial treatment regimen of IV vancomycin to cover Gram-positive pathogens plus an antipseudomonal beta-lactam agent—either IV cefepime, ceftazidime, or meropenem—to cover Gram-negative pathogens.1 The selection of an agent for Gram-negative coverage should be based on local susceptibility patterns according to the institution’s antibiogram.1,2 For a patient who cannot receive any of the recommended agents to cover Gram-negative pathogens (such as a patient with a contraindication to meropenem and anaphylaxis to cephalosporins), the guidelines recommend using either aztreonam or ciprofloxacin, with the choice of agent based on local antimicrobial susceptibility patterns.1 Additionally, it is recommended to modify the empiric antimicrobial regimen if a patient is colonized with or has an infection at another body site with a resistant organism.1 In addition to antimicrobial therapy, it is recommended to remove the infected device in order to increase the likelihood of treatment success.1-3,5
Directed Treatment of Selected Pathogens
Once the causative microorganism has been identified and the results of susceptibility tests are known, antimicrobial therapy should be modified as indicated in TABLE 2.1,6,13,14 Rifampin is added as part of combination therapy for infections caused by staphylococci (if the microorganism is susceptible) and prosthetic material (such as a CSF drain or CSF shunt) is present.1 For treatment of infection caused by a Gram-negative pathogen, selection of the most appropriate agent should be guided by results of susceptibility testing and the agent’s ability to penetrate the CNS.1 Dosing of recommended empiric and directed antibiotic agents commonly used for healthcare-associated ventriculitis and meningitis is included in TABLE 3.1,15 For treatment of fungal meningitis, the definitive treatment depends upon the isolated pathogen.1
Role of Intraventricular Antibiotics
Although intraventricular administration of therapy allows a medication to bypass the blood-CSF barrier and be delivered directly into the intraventricular system at the site of infection, the IDSA guidelines state that since there are no clinical trials that have demonstrated the efficacy and safety of this route of administration, there is insufficient evidence to recommend their general use.1 However, the guidelines state that intraventricular antimicrobial agents may be considered in patients who have a poor response to systemic IV antimicrobial therapy alone.1 Additionally, this route of administration may be used in combination with systemic antimicrobial therapy for the treatment of multidrug-resistant pathogens.2,15 The reader is referred to the IDSA guidelines for additional information as related to dosing and considerations for use of antimicrobial agents given via this route.1
Duration of Therapy
The duration of therapy for healthcare-associated ventriculitis and meningitis is based upon the infecting microorganism, with CSF findings and the presence of clinical symptoms impacting duration of therapy for selected pathogens, as indicated in TABLE 4.1,6 For patients who are on appropriate antimicrobial therapy based on susceptibility testing who have repeatedly positive CSF cultures, therapy should be continued for 10 to 14 days after the last positive culture.1
Follow-Up and Monitoring
All patients should be monitored for hypersensitivity reactions to any antimicrobial agents included as part of their treatment regimen, as well as for the development of Clostridioides difficile infection, which can occur from antimicrobial exposure.16 Additionally, all patients with healthcare-associated ventriculitis and meningitis should be monitored for clinical response to treatment.1 Those with a device-related infection should be monitored and assessed for negative CSF cultures, as there are different recommendations for when device reimplantation can occur after documentation of negative cultures based on the type of device and the infecting pathogen.1,3 For all patients without definitive clinical improvement, additional CSF analysis (including for assessment of improvement in CSF parameters and conversion to negative CSF cultures) is recommended.1
Pharmacists can play an integral role in the management of healthcare-associated ventriculitis and meningitis by working collaboratively with clinicians for the treatment of patients with these serious infections. In addition to being aware of their diagnostic challenges and considerations, pharmacists can work with providers to select the most appropriate empiric and directed antimicrobial therapy regimen based on patient-specific factors. Pharmacists are in a key position to ensure appropriate treatment and monitoring for these types of infections.
The content contained in this article is for informational purposes only. The content is not intended to be a substitute for professional advice. Reliance on any information provided in this article is solely at your own risk.
1. 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(6):e34-e65.
2. Hasbun R. Healthcare-associated ventriculitis: current and emerging diagnostic and treatment strategies. Expert Rev Anti Infect Ther. 2020;1-7. E-pub ahead of print.
3. Hasbun R. Central nervous system device infections. Curr Infect Dis Rep. 2016;18(11):34.
4. Srihawan C, Castelblanco RL, Salazar L, et al. Clinical characteristics and predictors of adverse outcome in adult and pediatric patients with healthcare-associated ventriculitis and meningitis. Open Forum Infect Dis. 2016;3(2):ofw077.
5. Martin RM, Zimmermann LL, Huynh M, Polage CR. Diagnostic approach to health care- and device-associated central nervous system infections. J Clin Microbiol. 2018;56(11):e00861-18.
6. Dréno B, Pécastaings S, Corvec S, et al. Cutibacterium acnes (Propionibacterium acnes) and acne vulgaris: a brief look at the latest updates. J Eur Acad Dermatol Venereol. 2018;32(Suppl 2):5-14.
7. Rogers T, Sok K, Erickson T, et al. Impact of antibiotic therapy in the microbiological yield of healthcare-associated ventriculitis and meningitis. Open Forum Infect Dis. 2019;6(3):ofz050.
8. Srihawan C, Habib O, Salazar L, Hasbun R. Healthcare-associated meningitis or ventriculitis in older adults. J Am Geriatr Soc. 2017;65(12):2646-2650.
9. Brown BL, Fidell A, Ingolia G, et al. Infectious causes and outcomes in patients presenting with cerebral spinal fluid pleocytosis. J Neurovirol. 2019;25(4):448-456.
10. Chow E, Troy SB. The differential diagnosis of hypoglycorrhachia in adult patients. Am J Med Sci. 2014;348(3):186-190.
11. CDC. CDC National Healthcare Safety Network (NHSN). www.cdc.gov/nhsn/index.html. Accessed January 22, 2021.
12. CDC. CDC/NHSN surveillance definitions for specific types of infections. January 2021. www.cdc.gov/nhsn/pdfs/pscmanual/17pscnosinfdef_current.pdf. Accessed January 22, 2021.
13. Adeolu M, Alnajar S, Naushad S, Gupta RS. Genome-based phylogeny and taxonomy of the ‘Enterobacteriales’: proposal for Enterobacterales ord. nov. divided into the families Enterobacteriaceae, Erwiniaceae fam. nov., Pectobacteriaceae fam. nov., Yersiniaceae fam. nov., Hafniaceae fam. nov., Morganellaceae fam. nov., and Budviciaceae fam. nov. Int J Syst Evol Microbiol. 2016;66(12):5575-5599.
14. Tamma PD, Aitken SL, Bonomo RA, et al. Infectious Diseases Society of America guidance on the treatment of extended-spectrum-betalactamase producing Enterobacterales (ESBL-E), carbapenem-resistant Enterobacterales (CRE), and Pseudomonas aeruginosa with difficult-to-treat resistance (DTR-P. aeruginosa). Clin Infect Dis. 2020; Oct 27:ciaa1478. Epub ahead of print.
15. Nau R, Blei C, Eiffert H. Intrathecal antibacterial and antifungal therapies. Clin Microbiol Rev. 2020;33(3):e00190-19.
16. Lexi-Comp Online. Hudson, OH: UpToDate, Inc; 2021. www.lexi.com. Accessed March 12, 2021.
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