Multidrug-resistant ventriculitis: Diagnostic and therapeutic challenges

INTRODUCTION

Chronic meningitis is defined as inflammation of the meninges, with signs and symptoms persisting for at least 4 weeks without alleviation.^[1] Chronic meningitis is very uncommon and accounts for <10% of all neuro^[2] infections. Ventriculitis is the inflammation of the ependymal lining of the cerebral ventricles secondary to an infectious process. Ventriculitis can be secondary to meningitis, cerebral abscess, shunt infection, trauma, cerebrospinal fluid (CSF) leak and post-neurosurgery. Refinement of surgical technique and use of advanced devices in CSF shunt insertion have improved survival and the quality of life of children with hydrocephalus. The most frequent and disabling complication of these procedures is shunt infection, which is estimated to occur in from 2% to 27% of cases.^[3] Here, we are reporting one such case which presented with chronic multidrug-resistant (MDR) meningitis secondary to ventriculoperitoneal (VP) shunt infection.

CASE REPORT

A 7-year-old child with spastic quadriplegic cerebral palsy and hydrocephalus with VP shunt in situ presented following per rectal extrusion of shunt. Distal end was resected and the proximal end was ligated off. About 24 h later, the child developed dropping sensorium, persistent vomiting with deteriorating Glasgow Come Scale (GCS). In view of signs of shunt obstruction, the proximal end was externalised to facilitate CSF drainage. CSF culture showed growth of Klebsiella oxytoca sensitive to intravenous (IV) meropenem which was continued for 3 weeks through a peripherally inserted central catheter (PICC).

The child was readmitted 15 days later with fever and lethargy. Computed tomography (CT) brain [Figure 1] showed dilated lateral ventricle and third ventricle with irregular margins and internal septations, with no evidence of abscess. CSF culture on this occasion was positive for Enterococcus faecalis; hence, vancomycin was commenced. VP shunt was removed and an external ventricular drain (EVD) was inserted. IV levetiracetam was initiated in view of generalised tonic-clonic seizures. Repeat CSF culture done a week later showed Pseudomonas aeruginosa and K. oxytoca growth resistant to carbapenems. Antimicrobial resistance testing confirmed New Delhi metalloproteinase variant of carbapenem-resistant enterobacteriaceae (CRE). Hence, IV ceftazidime/avibactam, aztreonam along with intraventricular administration of amikacin and vancomycin, was commenced after a multidisciplinary meeting with neurosurgeon and infectious diseases team. CSF cartridge-based nucleic acid amplification test for mycobacterium tuberculosis was negative. IV and intraventricular antibiotics were continued for 3 further weeks. Three subsequent CSF cultures taken 1 week apart showed no further growth.

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Figure 1:

Computed tomography brain-dilated 3rd and lateral ventricles with internal septations.

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The child underwent the removal of EVD and programmable VP shunt insertion on the opposite side. The child was discharged following the procedure on IV antibiotics for further 1 week.

DISCUSSION

During 3 months of hospitalisation, CSF was infected with MDR bacteria on multiple occasions. A study by Mostafavi et al., showed that the frequency of Gram-negative bacterial shunt infections is on a rising trend.^[4] Factors attributing to MDR meningitis include partially treated meningitis, inadvertent use of antibiotics, shunt infections, tubercular meningitis and neoplasm. It has been reported that Gram-negative bacilli are responsible for 7–27.5% of all VP shunt infections.^[5,6] In a multicentre study conducted by Gundeslioglu et al. in Turkey, the most isolated pathogens from VP shunt infections were coagulase-negative staphylococci (42.5%), P. aeruginosa (14.9%), Klebsiella pneumoniae (10.1%) and Staphylococcus aureus (10.1%).^[7] However, in our case, the initial isolate of Klebsiella was sensitive to meropenem, followed by Enterococcus infection for which intraventricular vancomycin was initiated. Carbapenem-resistant P. aeruginosa and Klebsiella (CRE) growth was present in subsequent CSF samples, hence was treated with ceftazidime-avibactam and aztreonam.

In view of MDR ventriculitis, shunt was replaced with an EVD as a temporary measure until CSF cultures were sterile. A previous study by Mostafavi et al. showed that in addition to antibiotic treatment, removing the VP shunt temporarily is the most effective approach to eliminating shunt infection.^[4] In a recent multicentre retrospective cohort study, Lewin et al., showed that intraventricular antibiotic therapy using drugs such as vancomycin and aminoglycosides, CSF sterilisation was achieved in 88.4% and reduces mortality as well as hospital stay.^[8] In our case, both vancomycin and amikacin were administered through intraventricular route in addition to IV antibiotics.

During the course of the stay, our child underwent four lumbar punctures, two PICC line insertions, two EVD insertions and six CT scans which reflect complexity of the case. PICC lines were inserted to facilitate the administration of antibiotics over a prolonged period of time. A study by Pitiriga et al. showed that PICC lines have the least risk of central line associated bloodstream infection (CLABSI) as compared to central lines.^[9] There was an accidental displacement of EVD which resulted in ventricular dilatation and sudden drop in GCS. EVD was replaced with a programmable VP shunt on the opposite side.

Literature suggests that initial dosing of vancomycin for either ventriculitis or shunt infections should range from 5 to 10 mg/d in infants and 10–20 mg/d in children and adults. Empiric dosage does not predictably produce desired CNS concentrations; therefore, individualised dosing guided by CSF vancomycin concentrations is recommended.^[10]

CONCLUSION

1. Chronic meningitis remains a diagnostic and therapeutic challenge, especially in a child with chronic illness with VP shunt in situ.

2. A multidisciplinary team of paediatric intensivist, neurosurgeon and infectious disease specialist is imperative for the best outcomes.

3. Simultaneous administration of IV and intraventricular antibiotics improves survival and cure rates in MDR meningitis.

4. In cases of MDR meningitis with VP shunt infection, removal of VP shunt with temporary EVD insertion remains the mainstay of treatment. Revision of VP shunt is completed when the CSF is sterile.

5. Infection with carbapenem-resistant organisms is on the rise and poses a real threat to the available antibiotic armamentarium.

6. Measures such as strict adherence to local antibiotic policies, appropriate utilisation of novel agents and limiting unnecessary use of antibiotics help in strengthening hospital antibiotic stewardship programmes.