Key-words:
Enterococcus species - nosocomial meningitis - vancomycin-resistant Enterococcus
Introduction
Enterococcus, a normal commensal of human gastrointestinal and genitourinary tract,
is now increasingly being recognized as one of the causative agents of healthcare-associated
infections such as surgical site infections and urinary tract infections over the
past few decades.[[1]],[[2]] The management of infections secondary to Enterococcus species (Enterococcus.spp)
is difficult because Enterococcus not only possesses intrinsic resistance to many
antimicrobial agents but also has the ability to acquire resistance against antibiotics
through genetic mutation.[[3]]
Enterococcal meningitis is very rare among bacterial meningitis and mostly nosocomial
in origin.[[4]],[[5]] Risk factors for enterococcal meningitis are neurosurgical procedures, underlying
immunosuppression, enterococcal infection, or colonization at other sites of the body
and central nervous system (CNS) devices.[[4]],[[5]],[[6]] CNS infections secondary to Enterococcus spp. are associated with high mortality.[[5]],[[6]],[[7]]
In this study, we have looked at the clinical features, therapeutic options with antimicrobial
susceptibility, and outcomes of enterococcal meningitis in a tertiary care hospital.
Subjects and Methods
We retrospectively reviewed medical records of all patients with acute bacterial meningitis
admitted to our hospital over the periods of 4 years, i.e., from 2013 to 2016.
Patient's clinical records, microbiology and other laboratory data were reviewed.
In the present study, the criteria of acute bacterial meningitis were as follows:
-
Patients with clinical presentation of acute bacterial meningitis including fever,
seizure, altered mental status, and headache
-
Positive cerebrospinal fluid (CSF) culture in patients with clinical presentation
of acute bacterial meningitis.
CSF parameters:
Nosocomial or healthcare-associated meningitis or ventriculitis was defined as clinical
features and CSF findings not present at the time of admission and developed 48 hrs
after admission. Mixed infection was defined as at least two or more than two organisms
isolated from CSF culture (exclusion criteria of study). The antibiotics susceptibility
was based on Clinical Laboratory Standard Institute document M-100.
Results
Demographic data
During the study period from years 2013 to 2016, a total of six patients were diagnosed
with identified as enterococcal meningitis/ventriculitis including three children
(age from 2–12 months) and 3 adults (age range from 40 to 71 years). All patients
had single pathogen isolated from CSF that is Enterococcus.spp.
Clinical features of the subjects
All of the patients developed meningitis after neurosurgical procedures such as craniotomy,
repair of myelomeningocele, and ventriculoperitoneal (VP) shunt. Majority of patients
(4 out of 6) had CNS devices in situ at the time of development of meningitis. Clinical
features and management are given in [[Table 1]].
Table 1: Clinical data of patients with enterococcal meningitis
Organism isolated and antibiotic sensitivity and resistance
Blood cultures and other body site cultures were negative for Enterococcus as well
as other organisms. The causative organism isolated from CSF culture of all patients
was Enterococcus spp. only and none of the patients had mixed bacterial infection.
The organism was present in Gram stain of CSF and isolated on blood agar culture medium.
It was identified by conventional biochemical reactions, API 20 STREP (BIOMERIEUX),
and its intrinsic resistance to ceftriaxone and clindamycin. The antibiotic susceptibility
was checked on Muller-Hinton agar by disk diffusion method and vancomycin minimum
inhibitory concentration was checked with E-strip (gradient diffusion method).
In all patients, Enterococcus spp. was resistant to ampicillin, Amoxicillin-clavulanate,
and oxytetracycline. Vancomycin-resistant Enterococcus (VRE) was also isolated in
CSF of two of our patients; however, VRE strains showed sensitivity to linezolid and
chloramphenicol.
Outcome
All patients treated with antibiotics according to culture and sensitivities and cured
as repeat CSF cultures were negative. Only two patients became neurologically dependent
because of their associated neurological condition and no mortality reported in the
current case series.
Discussion
Postoperative CNS infection after neurosurgical procedures is a serious problem with
a reported incidence of 0.8%–8%.[[8]],[[9]],[[10]],[[11]] The common bacterial pathogens associated with nosocomial meningitis after neurosurgical
interventions are Staphylococcus aureus, coagulase-negative Staphylococcus, Gram-negative
bacilli such as Pseudomonas aeruginosa, Acinetobacter, and Propionibacterium acnes.
Intracranial device can predispose to infections that could be due to contamination
and/or colonization of implanted devices.[[4]],[[5]],[[6]] Additional risk factors include the presence of infection with Enterococcus spp.
in other sites of the body, underlying chronic illnesses, and immunosuppressive states
such as diabetes and steroids therapy.[[5]],[[6]],[[12]],[[13]]
The emergence of resistant Enterococcus strains has complicated the management of
enterococcal infection. The invasive enterococcal infections such as endocarditis
require a combination of cell wall-active agents with other susceptible antimicrobials
such as aminoglycoside to achieve synergistic bactericidal activity. The simultaneous
use of a cell wall-active agent raises the permeability of the cell so that an intracellular
bactericidal concentration of accompanying antibiotic can be achieved.[[14]] Even though previously published cases of enterococcal meningitis were treated
with beta-lactam, glycopeptides, or other susceptible antibiotics either alone or
in combination,[[5]],[[13]] vancomycin can be used as a single agent with good clinical response.
Vancomycin-resistant enterococcal meningitis/ventriculitis (VRE meningitis/ventriculitis)
is very rare and only reported in the form of case report and case series in literature.
Limited therapeutic options are available for vancomycin-resistant CNS infections
and best possible therapy has not been established.[[15]],[[16]] VRE infections are successfully treated with antibiotics such as linezolid, daptomycin,
quinupristin-dalfopristin, rifampicin, and gentamicin.[[17]],[[18]],[[19]] The first case of treatment of VRE meningitis with linezolid was reported in 2001.
Linezolid has good meningeal penetration and is used alone or in combination with
other susceptible antibiotics for VRE meningitis/ventriculitis with favorable clinical
outcome.[[20]],[[21]],[[22]],[[23]]
Intrathecal or intraventricular antibiotics have been increasingly utilized in cases
of nosocomial meningitis/ventriculitis when systemic therapy is unable to sterilize
CSF. Antibiotics used for intrathecal or intraventricular route for cases of VRE meningitis/ventriculitis
are linezolid, gentamicin, daptomycin, chloramphenicol, and quinupristin/dalfopristin.[[15]],[[24]],[[25]],[[26]],[[27]] Removal of infected hardware like VP shunt is also recommended for better treatment
outcome.[[28]] Although reported mortality is high with enterococcal CNS infection,[[5]],[[13]] timely initiation of appropriate therapy improves outcomes.
Conclusions
Enterococcal meningitis should be suspected in patients who developed CNS infection
during hospital stay, especially after neurosurgical procedures. As enterococcal meningitis
is associated with significant mortality, early recognition and appropriate therapeutic
intervention have prime importance for good clinical outcome.
