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Table of Contents
CASE REPORT
Year : 2020  |  Volume : 14  |  Issue : 1  |  Page : 68-70

Polymicrobial meningitis in a renal transplant recipient – “cryptococcus neoformans and acinetobacter baumannii coinfection with elizabethkingia meningoseptica superinfection“


1 Department of Nephrology, Postgraduate Institute of Medical Education and Research, Chandigarh, India
2 Department of Microbiology, Postgraduate Institute of Medical Education and Research, Chandigarh, India

Date of Submission26-Sep-2019
Date of Acceptance22-Jan-2020
Date of Web Publication31-Mar-2020

Correspondence Address:
Dr. Krishan Lal Gupta
Former Head of Department of Nephrology, Postgraduate Institute of Medical Education and Research, Chandigarh - 160 012
India
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Source of Support: None, Conflict of Interest: None


DOI: 10.4103/ijot.ijot_52_19

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  Abstract 


Although rare, polymicrobial meningitis has been infrequently reported in renal transplant recipients (RTRs). In this context, we describe a RTR on triple immunosuppression therapy, with stable graft function, who had presented with fever and altered sensorium of 2 days' duration. Evaluation revealed polymicrobial meningitis, which was initially attributed to concurrent infection by Cryptococcus neoformans and Acinetobacter baumannii and was later superinfected with Elizabethkingia meningoseptica. The overall prognosis in polymicrobial meningitis remains dismal, re-emphasizing the importance of early suspicion and prompt microbiological diagnosis for targeted antimicrobial therapy.

Keywords: Acinetobacter baumannii, Cryptococcus neoformans, Elizabethkingia meningoseptica, polymicrobial meningitis, superinfection


How to cite this article:
Sood V, Gupta S, Ramachandran R, Gupta KL. Polymicrobial meningitis in a renal transplant recipient – “cryptococcus neoformans and acinetobacter baumannii coinfection with elizabethkingia meningoseptica superinfection“. Indian J Transplant 2020;14:68-70

How to cite this URL:
Sood V, Gupta S, Ramachandran R, Gupta KL. Polymicrobial meningitis in a renal transplant recipient – “cryptococcus neoformans and acinetobacter baumannii coinfection with elizabethkingia meningoseptica superinfection“. Indian J Transplant [serial online] 2020 [cited 2020 Jul 6];14:68-70. Available from: http://www.ijtonline.in/text.asp?2020/14/1/68/281769




  Introduction Top


Opportunistic infections are well known in renal transplant recipients (RTRs). Around 30% of RTRs develop neurological complications,[1] with one of the most common being meningitis. Unlike brain abscess, meningitis in an adult is usually presumed to be of monomicrobial etiology,[2] however polymicrobial meningitis, although uncommon, has been infrequently reported,[3] particularly consequent to an immunocompromised state. Hereby, we report polymicrobial meningitis in a RTR, initially ascribed to Cryptococcus neoformans and Acinetobacter baumannii coinfection and subsequently superinfected by Elizabethkingia meningoseptica.


  Case Report Top


A 57-year-old male had undergone a live emotionally related renal transplant in 2007, due to diabetic kidney disease, with his wife as a blood group-compatible donor and had stable graft function (serum creatinine − 1.4 mg/dL) on triple immunosuppression therapy (tacrolimus, mycophenolate mofetil, and prednisolone). The patient was on insulin, oral antidiabetic drug, and long-term antibiotic prophylaxis in view of recurrent urinary tract infections, although the genitourinary tract was never thoroughly evaluated. The patient presented to the emergency department with fever and altered sensorium of 2 days. The attendants denied history of preceding headache, vomiting, seizures, syncope, ear discharge, head injury, loin pain, dysuria, pyuria, hematuria, or oliguria. On evaluation, the patient was drowsy (Glasgow Coma Score − 13/15) and had a pulse rate of 76/min and blood pressure of 120/76 mmHg. Besides altered mentation, clinical examination was remarkable for terminal neck stiffness without any other localizing focal neurological deficit. His initial hemogram was normal (hemoglobin – 12.6 g/dL and leukocyte count – 7800 cells/mm3), and viral markers including HIV1 and 2 by enzyme-linked immunosorbent assay were negative. The patient had poor glycemic control (HbA1c – 9.5%) and acute allograft dysfunction (creatinine – 2.3 mg/dL). Urine microscopy revealed few pus cells with no protein or erythrocytes, and the whole-blood trough tacrolimus level was 5.7 ng/mL. Cerebrospinal fluid (CSF) analysis suggested meningitis with raised protein (125.5 mg/dL), cell count (84 cells/mm3; polymorphs – 60%), and low sugar (58 mg/dL; corresponding blood sugar of 230 mg/dL). Gram stain and mycobacterial workup (acid-fast bacilli stain, adenosine deaminase, and polymerase chain reaction [PCR]) was negative. India ink showed rounded encapsulated yeast, and cryptococcal antigen was positive (1:8). Herpes simplex and Toxoplasma PCR along with cytology for malignant cells was negative. Immunosuppression was curtailed (mycophenolate mofetil and tacrolimus were withheld), and amphotericin was initiated along with flucytosine. Sabouraud agar confirmed C. neoformans. Concurrent Automated blood culture grew Gram-negative bacilli (nonfermentative, oxidase negative) on primary blood agar plate and brain–heart infusion broth, suggesting A. baumannii coinfection, which was also isolated from the blood (>106 colony-forming units [cfu]/mL), urine (105 cfu/mL), as well as bronchoalveolar lavage (BAL) aspirate (104 cfu/mL) and was sensitive only to colistin which was added subsequently in renal modified dosages. Contrast imaging of the brain revealed only meningeal enhancement, and imaging of kidneys did not reveal any abscess, calculus, or pyelonephritis. He deteriorated with new-onset status epilepticus and nosocomial pneumonia, requiring antiepileptic drugs and ventilatory support. Repeat CSF analysis after 2 weeks of antimicrobial therapy revealed superinfection with E. meningoseptica, which was later demonstrated in blood culture as well. Further course was complicated by refractory septic shock and acute kidney injury, requiring inotropes and renal replacement therapy, despite which he succumbed to his illness, and his family did not give consent for autopsy.


  Discussion Top


“Polymicrobial meningitis“ includes “mixed“ (two or more organisms isolated concomitantly from initial CSF cultures[4]) and “superinfection“ (new pathogen[s] from new culture during the therapeutic course of acute meningitis[5]). The reported incidence of mixed infection in adult meningitis varies from 7% to 11%,[6] mostly (over 70%) following neurosurgical intervention, especially following the insertion of an external ventricular drainage device, and carries higher mortality (over 30%).

To the best of our knowledge, this is the first incidence of polymicrobial meningitis in a RTR involving three distinct culprit microorganisms, with initial “mixed“ infection ascribed to C. neoformans and A. baumannii coinfection, followed by “superinfection“ with E. meningoseptica subsequently and hence reported for its novelty.

Independently, Cryptococcus remains one of the most common cause of chronic meningitis among RTRs because of its propensity to invade the central nervous system after dissemination from lungs, which are the initial site of infection by these microorganisms.[7]

Demonstration of A. baumannii, a prolific nosocomial pathogen, may just represent colonization[8] in up to half of the cases, making it imperative to clinically differentiate between infection and pseudo-infection.[9] However, presence of overt risk factors in the index patient (poor glycemic control, immunosuppression therapy, recurrent urinary tract infections,[10] and prolonged empirical antibiotic prophylaxis) along with simultaneous isolation from CSF as well as blood, BAL, and urine suggested fulminant[11]A. baumannii-related sepsis, consequent to hematogenous dissemination of the pathogen from the urinary tract. Although well established for meningitis in neurosurgical setting, A. baumannii has also been infrequently described as a cause of primary de novo meningitis.[12] Negative Gram stain of CSF possibly could be attributed to marked pleocytosis and heavily proteinaceous nature, which may have obscured the bacilli.

Intravenous (IV) colistin has limited blood–brain barrier permeability, possibly due to high molecular weight and polycationic structure.[13] Guidelines, therefore, recommend either intraventricular (IVT) or intrathecal (IT) colistin[14] for multidrug-resistant and extensively drug-resistant A. baumannii ventriculitis and meningitis. The index patient was managed initially with IV colistin in view of fulminant A. baumannii sepsis, however additional IVT/IT colistin for multidrug-resistant A. baumannii meningitis although contemplated could not be administered due to status epilepticus.[15]

Repeat lumbar puncture in view of worsening sensorium with new-onset status epilepticus in the index patient revealed superinfection with E. meningoseptica, a Gram-negative pathogen, notorious for infections among low-birth-weight infants[16] or immunocompromised patients.[17] Repeat CSF culture, therefore, becomes mandatory in the absence of anticipated clinical response or for the exclusion of a possible superinfection.


  Conclusion Top


Clinical and laboratory features of acute polymicrobial meningitis are not unique; nevertheless, high suspicion in an immunocompromised patient, backed up by expedited microbiological evaluation, prevents delay in the correct identification of the causative agents.

Learning objectives

  1. “Polymicrobial meningitis“ includes “mixed“ and “superinfection“
  2. As both the clinical and laboratory features of polymicrobial meningitis are nonspecific, absence of anticipated clinical response, therefore, mandates repeat CSF culture to exclude possible superinfection
  3. Demonstration of A. baumannii may just represent colonization in up to half of the cases, making it imperative to clinically differentiate between infection and pseudo-infection so as to avoid diagnostic errors and unnecessary antibiotic therapy.


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.

Acknowledgment

The authors would like to thank the Department of Microbiology for their support.

Financial support and sponsorship

Nil.

Conflicts of interest

There are no conflicts of interest.



 
  References Top

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Chang WN, Lu CH, Huang CR, Tsai NW, Chuang YC, Chang CC, et al. Changing epidemiology of adult bacterial meningitis in southern Taiwan: A hospital-based study. Infection 2008;36:15-22.  Back to cited text no. 4
    
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Huang CR, Chen SF, Lu CH, Chuang YC, Tsai NW, Chang CC, et al. Clinical characteristics and therapeutics outcomes of nosocomial superinfection in adult bacterial meningitis. BMC Infect Dis 2011;11:133.  Back to cited text no. 5
    
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Cisneros JM, Rodríguez-Baño J. Nosocomial bacteremia due to Acinetobacter baumannii: Epidemiology, clinical features and treatment. Clin Microbiol Infect 2002;8:687-93.  Back to cited text no. 9
    
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Falagas ME, Karveli EA, Kelesidis I, Kelesidis T. Community-acquired Acinetobacter infections. Eur J Clin Microbiol Infect Dis 2007;26:857-68.  Back to cited text no. 12
    
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Markantonis SL, Markou N, Fousteri M, Sakellaridis N, Karatzas S, Alamanos I, et al. Penetration of colistin into cerebrospinal fluid. Antimicrob Agents Chemother 2009;53:4907-10.  Back to cited text no. 13
    
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Tunkel AR, Hartman BJ, Kaplan SL, Kaufman BA, Roos KL, Scheld WM, et al. Practice guidelines for the management of bacterial meningitis. Clin Infect Dis 2004;39:1267-84.  Back to cited text no. 14
    
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Karaiskos I, Galani L, Baziaka F, Giamarellou H. Intraventricular and intrathecal colistin as the last therapeutic resort for the treatment of multidrug-resistant and extensively drug-resistant Acinetobacter baumannii ventriculitis and meningitis: A literature review. Int J Antimicrob Agents 2013;41:499-508.  Back to cited text no. 15
    
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Hsu MS, Liao CH, Huang YT, Liu CY, Yang CJ, Kao KL, et al. Clinical features, antimicrobial susceptibilities, and outcomes of Elizabethkingia meningoseptica (Chryseobacterium meningosepticum) bacteraemia at a medical centre in Taiwan, 1999-2006. Eur J Clin Microbiol Infect Dis 2011;30:1271-8.  Back to cited text no. 16
    
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Jean SS, Lee WS, Chen FL, Ou TY, Hsueh PR. Elizabethkingia meningoseptica: An important emerging pathogen causing healthcare-associated infections. J Hosp Infect 2014;86:244-9.  Back to cited text no. 17
    



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