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Size Matters: Measurement of Capsule Diameter in Cryptococcus neoformans
Published on: February 27, 2018
Microsatellite typing and susceptibilities of serial Cryptococcus neoformans isolates from Cuban patients with
María T Illnait-Zaragozí1, Gerardo F Martínez-Machín, Carlos M Fernández-Andreu
1Department of Bacteriology and Mycology, Instituto Pedro Kourí, Havana, Cuba.
Background:
Cryptococcus neoformans is commonly associated with meningoencephalitis in immunocompromised patients and occasionally in apparently healthy individuals. Recurrence of infection after initial treatment is not uncommon. We studied C. neoformans isolates from 7 Cuban patients with recurrent cryptococcal meningitis. Antifungal susceptibility and genotyping with microsatellite molecular typing were carried out.
Methods:
Isolates (n = 19) were recovered from cerebrospinal fluid, blood, urine and semen. Antifungal susceptibilities for amphotericin B, fluconazole, flucytosine, itraconazole, voriconazole, posaconazole and isavuconazole were tested by CLSI M27A3 broth microdilution method. Genotyping was done using a panel of 9 microsatellite (STR) markers: (CT)n, (TG)n, (TA)n, (CTA)n, (TCT)n, (CCA)n, (TTAT)n, (ATCC)n and (TATT)n.
Results:
The average number of isolates/patient was 2.71. The mean time interval between the collection of any two isolates was 52.5 days. All strains were identified as C. neoformans var. grubii (serotype Aα). Although none of the strains were resistant to the studied drugs, in serial isolates from two patients, MICs values of triazoles increased 4-5 log2 dilutions over time. STR patterns showed 14 distinctive profiles. In three patients the recurrent infection was associated with genotypically identical isolates. The four other patients had relapse isolates which were genotypically different from the initial infecting strain.
Conclusion:
Recurrences of cryptococcal meningitis in our series of patients was not associated with development of drug resistance of the original strain but by an initial infection with different strains or a reinfection with a new strain.
Insights
Recurrent cryptococcal meningitis is often due to infection with different strains, not drug resistance. Genotyping revealed new or distinct strains caused relapses in most patients studied.
Area of Science:
- Mycology
- Infectious Diseases
- Genetics
Background:
- Cryptococcus neoformans causes meningoencephalitis, particularly in immunocompromised individuals.
- Recurrent cryptococcal meningitis is a clinical challenge.
- This study investigated recurrent cases in Cuban patients.
Purpose of the Study:
- To analyze antifungal susceptibility and genetic profiles of C. neoformans isolates from patients with recurrent meningitis.
- To understand the mechanisms behind cryptococcal meningitis recurrence.
Main Methods:
- Collected 19 C. neoformans isolates from cerebrospinal fluid, blood, urine, and semen.
- Performed antifungal susceptibility testing using broth microdilution.
- Genotyped isolates using 9 distinct microsatellite (STR) markers.
Main Results:
- All C. neoformans strains were identified as var. grubii (serotype Aα).
- No strains exhibited drug resistance, but triazole MICs increased in serial isolates from two patients.
- Genotyping revealed 14 distinct profiles; three patients had identical isolates, while four had genotypically different relapse strains.
Conclusions:
- Recurrent cryptococcal meningitis in this cohort was not linked to acquired drug resistance.
- Recurrence was attributed to initial infection with multiple strains or reinfection with a new strain.
