Cryptococcus gattii Meningitis Complicated by Listeria monocytogenes Infection

LETTERS recommended breakpoint, we designed MHC1 with a colis- tin concentration of only 1 µg/mL to minimize false-nega- tive results. However, some colistin-susceptible organisms might grow on MHC1 (<5% in our study), resulting in the low PCR-positive rate for mcr-1 among isolates. Exact epidemiology of the mcr-1 gene is unknown, indicating a need to conduct accurate surveillance of the gene’s prevalence in humans. Additional mechanisms unique to the mcr-1 gene may contribute to colistin resis- tance, suggested by the wide variation in colistin MICs among mcr-1–carrying Enterobacteriaceae. This study was partially supported by the Health and Medical Research Fund, Food and Health Bureau, Hong Kong Special Administrative Region Government (reference nos. HKM-15-M10 and HKM-15-M12). References 1. Liu YY, Wang Y, Walsh TR, Yi LX, Zhang R, Spencer J, et al. Emergence of plasmid-mediated colistin resistance mechanism MCR-1 in animals and human beings in China: a microbiological and molecular biological study. Lancet Infect Dis. 2016;16:161–8. http://dx.doi.org/10.1016/S1473-3099(15)00424-7 2. Jorgensen JH, Pfaller MA, Carroll KC, Funke G, Landry ML, Richter SS, et al., editors. Manual of clinical microbiology, 11th ed. Washington: ASM Press; 2015. 3. Clinical and Laboratory Standards Institute. Performance standards for antimicrobial susceptibility testing. 25th edition. M100–S25. Wayne (PA): The Institute; 2015. 4. Cheng VC, Chan JF, Wong SC, Chen JH, Tai JW, Yan MK, et al. Proactive infection control measures to prevent nosocomial transmission of carbapenem-resistant Enterobacteriaceae in a non-endemic area. Chin Med J (Engl). 2013;126:4504–9. 5. Agriculture, Fisheries & Conservation Department. Hong Kong Special Administrative Region. Hong Kong: the facts. 2015 Feb [cited 2016 Jan 15]. http://www.gov.hk/en/about/abouthk/factsheets/ docs/agriculture.pdf 6. Census and Statistics Department. Hong Kong Special Administrative Region. Hong Kong merchandise trade statistics imports. 2015 Apr [cited 2016 Jan 15]. http://www.statistics.gov.hk/ pub/B10200012015MM04B0100.pdf 7. Falgenhauer L, Waezsada S-E, Yao Y, Imirzalioglu C, Kasbohrer A, Roesler U, et al.; RESET consortium. Colistin resistance gene mcr-1 in extended-spectrum β-lactamase-producing and carbapenemase- producing Gram-negative bacteria in Germany. Lancet Infect Dis. 2016;16:282–3. http://dx.doi.org/10.1016/S1473-3099(16)00009-8 8. Malhotra-Kumar S, Xavier BB, Das AJ, Lammens C, Butaye P, Goossens H. Colistin resistance gene mcr-1 harboured on a multidrug resistant plasmid. Lancet Infect Dis. 2016;16:283–4. http://dx.doi.org/10.1016/S1473-3099(16)00012-8 9. Tse H, Yuen KY. Dissemination of the mcr-1 colistin resistance gene. Lancet Infect Dis. 2016;16:145–6. http://dx.doi.org/10.1016/ S1473-3099(15)00532-0 10. European Committee on Antimicrobial Susceptibility Testing. Breakpoint tables for interpretation of MICs and zone diameters: version 6.0. 2016 Jan 1 [cited 2016 Mar 15]. http://www.eucast. org/fileadmin/src/media/PDFs/EUCAST_files/Breakpoint_ tables/v_6.0_Breakpoint_table.pdf Address for correspondence: Kwok-Yung Yuen, Carol Yu Centre for Infection, The University of Hong Kong, Queen Mary Hospital, Pokfulam Rd, Pokfulam, Hong Kong, China; email: kyyuen@hku.hk Cryptococcus gattii Meningitis Complicated by Listeria monocytogenes Infection Robert G. Deiss, Michael Bolaris, Angel Wang, Scott G. Filler Author affiliations: Uniformed Services University of the Health Sciences, Bethesda, Maryland, USA (R.G. Deiss); Henry M. Jackson Foundation for the Advancement of Military Medicine, Bethesda (R.G. Deiss): Naval Medical Center of San Diego, San Diego, California, USA (R.G. Deiss); Harbor-UCLA Medical Center, Los Angeles, California, USA (M. Bolaris, A. Wang, S.G. Filler); David Geffen School of Medicine at UCLA, Los Angeles (S.G. Filler) DOI: http://dx.doi.org/10.3201/eid2209.160142 To the Editor: Among immunocompetent persons with cryptococcal disease, infection with a second organ- ism is rare; all reported cases have involved concomitant mycobacterial infections (1). Immunosuppression is not a necessary precondition for infection with Cryptococcus gattii (2), and among immunocompetent persons, C. gattii infection confers high mortality rates: up to 24% according to a large case series (3). In addition, cryptococcomas are frequently observed in patients with C. gattii, as opposed to C. neoformans, infection, commonly necessitating longer courses of treatment. We report a fatal case of C. gattii and Listeria monocytogenes co-infection in an immunocompe- tent woman with cryptococcomas. The patient was a previously healthy 23-year-old His- panic woman who was hospitalized in 2009 after weeks of headache and recent-onset diplopia. Lumbar puncture re- vealed elevated opening pressure of 52 cm H 2 O; elevated leukocytes (1,030 cells/μL: 31% neutrophils, 55% lym- phocytes, 14% monocytes); elevated protein concentra- tion (117 g/L); and decreased glucose concentration (30 mg/dL). Cerebrospinal fluid (CSF) cryptococcal antigen (CrAg) titer was 1:64, and culture grew C. gattii. HIV an- tibody test result was negative. Magnetic resonance imag- ing of the brain demonstrated scattered enhancing round lesions within the cerebrum and cerebellum, consistent with cryptococcomas. The patient was prescribed intrave- nous amphotericin B (1 mg/kg/d) and intravenous flucyto- sine (2 g/6 h) (Table); after 5 days of therapy, culture of a repeat lumbar puncture sample was negative. The patient was then given intravenous liposomal amphotericin at 7 mg/kg, and after a 14-day induction period she was dis- charged with instructions to take fluconazole orally (400 mg 2×/d) and to continue amphotericin B infusions (3×/ wk) (Table). Emerging Infectious Diseases • www.cdc.gov/eid • Vol. 22, No. 9, September 2016

To the Editor: Among immunocompetent persons with cryptococcal disease, infection with a second organism is rare; all reported cases have involved concomitant mycobacterial infections (1). Immunosuppression is not a necessary precondition for infection with Cryptococcus gattii (2), and among immunocompetent persons, C. gattii infection confers high mortality rates: up to 24% according to a large case series (3). In addition, cryptococcomas are frequently observed in patients with C. gattii, as opposed to C. neoformans, infection, commonly necessitating longer courses of treatment. We report a fatal case of C. gattii and Listeria monocytogenes co-infection in an immunocompetent woman with cryptococcomas.
The patient was a previously healthy 23-year-old Hispanic woman who was hospitalized in 2009 after weeks of headache and recent-onset diplopia. Lumbar puncture revealed elevated opening pressure of 52 cm H 2 O; elevated leukocytes (1,030 cells/μL: 31% neutrophils, 55% lymphocytes, 14% monocytes); elevated protein concentration (117 g/L); and decreased glucose concentration (30 mg/dL). Cerebrospinal fluid (CSF) cryptococcal antigen (CrAg) titer was 1:64, and culture grew C. gattii. HIV antibody test result was negative. Magnetic resonance imaging of the brain demonstrated scattered enhancing round lesions within the cerebrum and cerebellum, consistent with cryptococcomas. The patient was prescribed intravenous amphotericin B (1 mg/kg/d) and intravenous flucytosine (2 g/6 h) (Table); after 5 days of therapy, culture of a repeat lumbar puncture sample was negative. The patient was then given intravenous liposomal amphotericin at 7 mg/kg, and after a 14-day induction period she was discharged with instructions to take fluconazole orally (400 mg 2×/d) and to continue amphotericin B infusions (3×/ wk) (Table).
One week after hospital discharge, the patient experienced recurrent headache and low-grade fever and was readmitted. Repeat lumbar puncture indicated an opening pressure of 46 cm H 2 O but improvement of all other clinical parameters (Table). CSF CrAg titer was 1:8 and culture was negative. Repeat brain magnetic resonance images revealed no hydrocephalus, minimal edema, and decreased size and number of cryptococcomas. She was again given amphotericin B (5 mg/kg/d) and intravenous flucytosine (3 g/6 h) and fluconazole (600 mg/12 h). Placement of a ventricular-peritoneal shunt was deferred, and the patient required frequent lumbar punctures to relieve elevated intracranial pressure. After 3 weeks of therapy, she began taking oral dexamethasone (2 mg 4×/d) to reduce intracranial pressure and control symptoms consistent with immune reconstitution inflammatory syndrome. After 30 days of antifungal therapy during this second hospitalization, she experienced symptomatic improvement and was discharged with amphotericin B (5 mg/kg to be infused 3×/wk), fluconazole (600 mg 2×/d), and dexamethasone (tapering dosage).
Two weeks later (11 weeks after initial admission), she returned to the hospital with worsening headache and fever. Lumbar puncture demonstrated a leukocyte count of 1,010 cells/μL (74% neutrophils, 12% lymphocytes, 14% monocytes), glucose 17 mg/dL, protein 258 g/L, and an opening pressure of >55 cm H 2 O. CSF culture grew L. monocytogenes. The patient was prescribed ceftriaxone, ampicil-lin, and trimethoprim/sulfamethoxazole. Shortly after the lumbar puncture, she experienced status epilepticus and became comatose. Despite emergent craniotomy for relief of intracranial pressure, she remained comatose for several days; subsequently, supportive care was withdrawn and the patient died shortly thereafter.
This case highlights the difficulties of managing severe cryptococcal disease. This patient experienced headache over 3 months and symptom relapse during 10 weeks of anticryptococcal therapy. As was done in this case, practice guidelines recommend a longer duration of polyene antimycotic induction for patients with cryptococcomas than for those without (4), and longer courses of therapy are commonly described for infections caused by C. gattii than for those caused by C. neoformans (5). Corticosteroids are commonly used to treat immune reconstitution inflammatory syndrome associated with cryptococcal meningitis (6), although recently, they have been associated with adverse outcomes (7). As indicated by this case, corticosteroids remain a risk factor for secondary infection with several pathogens, including Listeria. No epidemiologic exposure to Listeria was identified for this patient.
C. gattii infection has been reported in 8 states, including California (3); we have found the pathogen in the soil south of Los Angeles, California, particularly in association with Canary Island pines and sweet gum trees (8)  granulocyte-macrophage (GM) colony-stimulating factor (9). Although these autoantibodies have not been reported in patients with Listeria infections, susceptibility to infection caused by this bacterium is increased in GM-colonystimulating factor -/-mice (10). Autoantibodies against GM-colony-stimulating factor or perhaps other cytokines might have impaired the patient's host defense against these organisms; unfortunately, our report is limited by lack of serum for further testing. This case demonstrates the difficulties of managing patients with C. gattii infection and an unusual co-infection with L. monocytogenes. Initiation of corticosteroids for the management of severe cryptococcal disease should be undertaken with caution. The differential diagnosis for worsening cryptococcal disease should include acute or subacute bacterial meningitis, particularly when the patient is receiving corticosteroids for the management of immune reconstitution inflammatory syndrome or associated complications.