|Ahead of print publication
Nosocomial recurrent bacterial meningitis/ventriculitis postelective surgery in a case of total knee replacement
Vaidehi Rajwadkar1, Gurpreet Singh Bhalla2, Naveen Grover3, Manbeer Singh Sarao4
1 Graded Specialist Microbiology, MH, Jodhpur, India
2 Classified Specialist Microbiology, PD Fellow, CSIR-IMTech, Chandigarh, India
3 Prof Path & Microbiology, Army Hospital (R&R), New Delhi, India
4 Medical Officer, Medical Oncology, Fortis Hospital, Shalimar Bagh, New Delhi, India
|Date of Submission||10-Jun-2020|
|Date of Decision||10-Jul-2020|
|Date of Acceptance||18-Oct-2020|
|Date of Web Publication||01-Apr-2021|
Gurpreet Singh Bhalla,
PD Fellow,CSIR-IMTech, Chandigarh
Source of Support: None, Conflict of Interest: None
Multiple causes can result in nosocomial meningitis. Here, we report a case of recurrent healthcare-associated bacterial meningitis caused by different bacteria in a postoperative case, who has been successfully treated with appropriate antibiotic therapy. A 65-year-old woman underwent an elective bilateral total knee replacement. On the postoperative day 5, she exhibited features of meningitis. Acinetobacter baumannii was isolated from the cerebrospinal fluid (CSF) culture. Magnetic resonance imaging of the brain was suggestive of ventriculitis. Later, she had to be shifted to the intensive care unit. An external ventricular drain (EVD) was placed due to persisting ventriculitis. Subsequent CSF culture sent from EVD repeatedly showed growth of Burkholderia cepacia. After the CSF cultures became sterile, a thecoperitoneal shunt was placed. She showed significant clinical improvement and was discharged. She was readmitted after 11 days with altered sensorium. Computed tomography of the head showed an increase in the noncommunicating hydrocephalus. The CSF cytology was inconclusive. An EVD was immediately placed. Vancomycin-resistant Enterococcus faecium was isolated from a repeat CSF culture. A ventriculoperitoneal shunt was placed after the CSF cultures showed no growth. She showed dramatic improvement in sensorium and cognition and was discharged. This case highlights the diagnosis and successful management of recurrent central nervous system nosocomial infection caused by rare but emerging healthcare-associated infections. To the best of our knowledge, this is the only case of recurrent nosocomial meningitis caused by three different bacteria and is also one of the rare cases of nosocomial meningitis caused by B. cepacia and vancomycin-resistant E. faecium.
Keywords: Emerging pathogens, healthcare-associated infection, recurrent central nervous system infection
| Introduction|| |
Nosocomial meningitis may result from invasive procedures, complicated head trauma, or in rare cases, metastatic infection in patients with healthcare-associated bacteremia. A different spectrum of microorganisms (e.g., multidrug-resistant Gram-negative bacilli and Staphylococcus spp.) are the more likely etiologic agents of nosocomial meningitis. Ventriculitis and meningitis may develop after a prolonged time, after hospital discharge, or even many years later. The diagnosis of these infections remains challenging owing to subtle changes in the cerebrospinal fluid (CSF) parameters, creating confusion about the etiology whether it is related to infection, the placement of devices, or following neurosurgery.
Here, we report a case of recurrent healthcare-associated bacterial meningitis caused by different bacteria in a postelective total knee replacement (TKR) case and who has been successfully treated with appropriate antibiotic therapy.
| Case Report|| |
A 65-year-old woman, with a medical history of diabetes mellitus type 2, underwent elective bilateral TKR under spinal anesthesia. On the postoperative day 5, she complained of a headache and vomiting and had started to talk irrelevantly. On examination, she had moderate-grade fever, pupils were bilaterally symmetrical and responsive, neck rigidity was present, and Kernig's sign was positive. Fundoscopy revealed papilledema. Motor and sensory examinations were within normal limits. Systemic examination was unremarkable. Intravenous (IV) antibiotics meropenem (2 g/8 hourly) and vancomycin (1 g/12 hourly) were started empirically.
Laboratory investigations revealed a total leukocyte count of 7900/mm3. Computed tomography (CT) of the brain was normal, and CSF analysis revealed 1900 white cells/μL (80% neutrophils), glucose <20 mg/dL (blood glucose level: 156 mg/dL), and proteins 847 mg/dL, which was consistent with a bacterial infection. Acinetobacter baumannii was isolated on CSF culture, which was susceptible to tigecycline and colistin. Bacterial identification was performed using an automated identification system, VITEK®2 Compact (bioMérieux, France). Colistin 3 MU IV was started. CSF analysis repeated 5 days later revealed 500 white cells/μL (45% neutrophils), glucose 42 mg/dL, and proteins 340 mg/dL, while CSF culture was sterile.
A repeat CSF examination after 9 days of colistin was still showing high white cell count (565/μL) (40% neutrophils) and low glucose of 42 mg/dL and proteins of 340 mg/dL. Magnetic resonance imaging (MRI) of the brain [Figure 1] showed bilateral ventricular enlargement with diffusion restriction in the dependent areas of ventricles, suggestive of ventriculitis. No leptomeningeal enhancement was seen. She was then administered intrathecal colistin through a lumbar intrathecal catheter in addition to IV antibiotics (meropenem and colistin) for another 13 days. Daily CSF analysis showed a persistent hypoglycorrhachia and cultures were repeatedly sterile.
|Figure 1: Bilateral ventricular enlargement with diffusion restriction, suggestive of ventriculitis|
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She had now become more drowsy than usual and was shifted to the intensive care unit. MRI of the brain [Figure 2] revealed persisting ventriculitis with mild hydrocephalus and nonenhancing basal cisternal exudates, so the lumbar drain was replaced by an external ventricular drain (EVD). Meropenem and vancomycin were discontinued, and intraventricular colistin was administered for 28 days. Because of chronic hypoglycorrhachia, meningitis, and raised CSF white cell counts in a diabetic patient not responding to standard antibiotic therapy, a possibility of fungal meningitis was raised. The CSF received for galactomannan was marginally positive (3.19). However, Gram's stain and wet mount showed no fungal elements, and CSF cultures were sterile. Amphotericin B was added, and after 4–5 days of treatment, she started improving clinically with the CSF glucose returning to normal. A total cumulative dose of amphotericin B of 2 g over 3 weeks was given. The CSF culture sent from EVD after 6 days of amphotericin B repeatedly showed growth of Burkholderia cepacia on 2 consecutive days. Bacterial identification was performed using automated identification and AST system, VITEK®2 Compact (bioMérieux, France). The antibiotics were optimized to the culture sensitivity report, and she was switched to IV minocycline, oral trimethoprim/sulfamethoxazole, and IV ceftazidime for 21 days. After the CSF cultures became sterile, a thecoperitoneal shunt was placed. She showed significant clinical improvement and was discharged from the hospital.
She remained asymptomatic for 7 days, after which her sensorium started deteriorating again and she stopped oral intake. She was readmitted on day 11 postdischarge. However, there was no history of fever, vomiting, seizures, or loss of consciousness. A CT head showed an increase in hydrocephalus which was noncommunicating. The CSF cytology showed white cell count of 10/μL (80% lymphocytes), a glucose of 56 mg/dL, and proteins of 370 mg/dL, with a total leukocyte count of 9350/mm3 (neutrophils 79%). The CSF culture was sterile. An EVD was immediately placed. She was administered IV ceftazidime 2 g/8 hourly and vancomycin 1 g/12 hourly empirically. However, her sensorium remained altered despite treatment. Owing to the previous culture of B. cepacia, vancomycin was stopped, and IV minocycline 100 mg/12 hourly and oral trimethoprim/sulfamethoxazole/6 hourly were added. Vancomycin-resistant Enterococcus faecium (vancomycin-resistant Enterococcus – VRE) was isolated from a repeat CSF culture that was susceptible to linezolid and tigecycline. Linezolid 600 mg/12 hourly IV was added after which the cultures became sterile.
A ventriculoperitoneal shunt was placed after the CSF cultures showed no growth, and CSF cytology was normal. She showed dramatic improvement in sensorium and cognition and was discharged on a 1-week course of oral linezolid. The course has been uneventful since then.
| Discussion|| |
Nosocomial bacterial meningitis may result from invasive procedures (e.g., craniotomy, placement of internal or external ventricular catheters, lumbar puncture, intrathecal infusions of medications, or spinal anesthesia), complicated head trauma, or in rare cases, metastatic infection in patients with hospital-acquired bacteremia. Nosocomial bacterial meningitis is caused by a different spectrum of microorganisms compared to the community-acquired ones.
In our case, we suspect this to be lumbar puncture meningitis caused after spinal anesthesia given for TKR by A. baumannii, which led to a cascade of events causing recurrent device-associated meningitis caused by B. cepacia and later by VRE on two separate occasions. A majority of lumbar puncture meningitis cases occur after spinal anesthesia or myelography. The risk of meningitis after lumbar puncture may be substantially decreased if aseptic conditions are met (i.e., hand disinfection and site preparation) and if operators wear face masks and operating caps when performing such procedures.
Meningitis caused by A. baumannii is well recognized and has been described by many physicians worldwide. Most of the case reports about meningitis were associated with EVD, leaking CSF, or head trauma.,,
Numerous reports about postoperative infections with A. baumannii in neurosurgery successfully managed by intraventricular or intrathecal colistin have been published in various journals around the world. Colistin was introduced for clinical use from the 1950s and abrogated in the 1980s, due to severe renal toxicity and neurovirulence. Despite emerging resistance, colistin was found to be useful for multidrug resistance and extensive drug resistance in Gram-negative bacteria, including Acinetobacter spp., Gounden et al. compared colistin with tobramycin and found that colistin was still effective for A. baumannii despite resistance to other antibiotics, and no difference in renal toxicity was revealed among these antibiotics.
This case also illustrates B. cepacia complex as a rare but emerging cause of nosocomial bacterial meningitis and the complexity of its management due to the inherent resistance to multiple antibiotics.
B. cepacia is an opportunistic Gram-negative bacterium, inherently resistant to multiple antibiotics and a highly transmissible bacterium found in the soil and moist environments. The bacterium causes severe lung infections in cystic fibrosis and immunocompromised patients and is an emerging Gram-negative bacterium causing nosocomial infections. Outbreaks can occur through exposure to contaminated solutions such as antiseptics, disinfectants, nebulizer solutions, and dextrose solutions in hospitalized patients. The management of B. cepacia infection is challenging as it evades the action of multiple antimicrobials through intrinsic and acquired resistance mechanisms., These mechanisms include the production of β-lactamases, carbapenemases, and antibacterial drug efflux pumps, as well as the ability to modify bacterial lipopolysaccharide structure, decrease the number of membrane porins, and mutate antimicrobial binding targets. Although these resistance mechanisms have limited our antimicrobial armamentarium against B. cepacia infections, certain isolates show susceptibility to beta-lactams, including ceftazidime, meropenem, and piperacillin. These medications are considered alternatives to trimethoprim/sulfamethoxazole, the primary regimen for therapy and prophylaxis of B. cepacia infections. Moreover, beta-lactams can be used as a treatment option when patients have an intolerance, allergy, or resistance to trimethoprim/sulfamethoxazole., In our case, only trimethoprim/sulfamethoxazole, minocycline, and ceftazidime showed activity against the isolate, which supports trimethoprim/sulfamethoxazole as a valid option to treat B. cepacia infections, including meningitis.,,
The prevalence of nosocomial infections caused by Enterococcus species has increased during the past few years, and there is a significant increase in resistance to antibiotics in the clinical isolates of E. faecium. The emergence of resistance to multiple antibiotics, including vancomycin, has made the management of enterococcal infections a challenge. Linezolid is an oxazolidinone antibiotic with bacteriostatic activity against VRE and has good CSF penetration. In our case, the VRE meningitis was successfully managed with linezolid, and it appears to be a useful drug for the treatment of patients with VRE central nervous system (CNS) infections., The mortality rate of patients with enterococcal meningitis is high, ranging from 13% to 33%., Enterococcus faecalis causes most cases of enterococcal meningitis. E. faecium is responsible for only 10% of the cases of enterococcal meningitis, but it poses a treatment challenge because of its high rates of resistance to ampicillin and vancomycin. The presumed pathogenesis is enterococcal bacteremia originating from the gastrointestinal tract with secondary seeding of the meninges. A thecoperitoneal shunt facilitates this transfer. Although formal clinical studies are necessary, linezolid appears to be a promising antimicrobial agent for the treatment of patients with vancomycin-resistant enterococcal CNS infections. Enterococcal resistance to linezolid, however, has already been reported clinically.
Our case highlights the diagnosis and successful management of recurrent CNS nosocomial infection caused by rare, but emerging bacteria such as B. cepacia and VRE. To the best of our knowledge, this is the only case of recurrent nosocomial meningitis caused by three different bacteria and is also one of the rare cases of nosocomial meningitis caused by B. cepacia.
Infections of the CNS have been previously described,,, but there are only a few reports of B. cepacia causing meningitis. B. cepacia is a rare and emerging cause of meningitis, as demonstrated in our case. The combination of its complex antimicrobial susceptibility profile and the ability to evade multiple antimicrobials make its management quite complicated. Trimethoprim/sulfamethoxazole remains useful in the management of meningitis since it provides excellent penetration into the CSF. Hence, CSF culture is strongly recommended. Rapid identification of the causative organism with strict infection control measures must be applied to avoid the spread of these organisms. Furthermore, the awareness of infections caused by B. cepacia should be spread among healthcare workers because of its high transmissibility, intrinsic resistance to multiple antibiotics, high mortality, and most importantly, the knowledge that this organism can be sensitive to simple antibiotics such as trimethoprim/sulfamethoxazole.
Declaration of patient consent
The authors certify that they have obtained all appropriate patient consent forms. In the form the patient(s) has/have given his/her/their consent for his/her/their images and other clinical information to be reported in the journal. The patients understand that their names and initials will not be published and due efforts will be made to conceal their identity, but anonymity cannot be guaranteed.
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Conflicts of interest
There are no conflicts of interest.
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