Evidence map›Paper›PMID 26324276›Full record

Trial reportAntimicrobial agents and chemotherapy2015

Increased Antifungal Drug Resistance in Clinical Isolates of Cryptococcus neoformans in Uganda.

Kyle D Smith, Beatrice Achan, Kathy Huppler Hullsiek, Tami R McDonald, Laura H Okagaki, Ali A Alhadab, Andrew Akampurira, Joshua R Rhein, David B Meya, David R Boulware and 2 more

Registry-linked trialOpen access · bronzeAbstract readClinical Trial
In one paragraph

Trial report in Antimicrobial agents and chemotherapy, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to trial NCT01802385 (Adjunctive Sertraline for the Treatment of HIV-Associated Cryptococcal Meningitis), which is not on this map. Cited by 109 papers, 3 of them syntheses that pooled it.

0numbers the graph read from it
0cells of the map it votes in
109citing papers in PubMed, 3 pooled it
10.5field-weighted citation impact, top 1% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

NCT01802385 phase3completednot on this map

Adjunctive Sertraline for the Treatment of HIV-Associated Cryptococcal Meningitis

TypeinterventionalSponsorUniversity of MinnesotaRan2015 to 2017Enrolled460ConditionsCryptococcal Meningitis, Fungal MeningitisArmsSertraline
3 · Its place in the literature

Who cites it

109 citing papers in PubMed, 3 syntheses or guidelines pooled it, 187 citations in OpenAlex.

  1. Guideline
  2. Pooled it
  3. Pooled it
  4. Trial
  5. Trial
  6. Trial
  7. Trial
  8. Article
  9. A review of the current anti-New microbes and new infections · 2026
    Review
  10. Review
  11. Towards understanding a potentialOne health (Amsterdam, Netherlands) · 2025
    Article
  12. Article
  13. Assessing the Anti-Cryptococcus Antifungal Potential of Artemisinin.International journal of molecular sciences · 2025
    Article
  14. Review
  15. InFuture microbiology · 2025
    Article
  16. Genomic Characterization ofVeterinary sciences · 2025
    Article
  17. Review
  18. Article
  19. Review
  20. Review

49 more citing papers are in PubMed but not listed here.

4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

12 authors at 5 institutions in 2 countries.

Kyle D SmithDepartment of Microbiology, University of Minnesota, Minneapolis, Minnesota, USA.
Beatrice AchanDepartment of Medical Microbiology, Makerere University, Kampala, Uganda.
Kathy Huppler HullsiekDivision of Biostatistics, School of Public Health, University of Minnesota, Minneapolis, Minnesota, USA.
Tami R McDonaldDepartment of Biology, St. Catherine University, St. Paul, Minnesota, USA.
Laura H OkagakiCenter for Integrated Fungal Research, North Carolina State University, Raleigh, North Carolina, USA.
Ali A AlhadabDepartment of Experimental and Clinical Pharmacology, University of Minnesota, Minneapolis, Minnesota, USA.
Andrew AkampuriraInfectious Diseases Institute, Makerere University, Kampala, Uganda.
Joshua R RheinDepartment of Medicine, University of Minnesota, Minneapolis, Minnesota, USA.
David B MeyaInfectious Diseases Institute, Makerere University, Kampala, Uganda Department of Medicine, University of Minnesota, Minneapolis, Minnesota, USA Department of Medicine, Makerere University, Kampala, Uganda.
David R BoulwareDepartment of Medicine, University of Minnesota, Minneapolis, Minnesota, USA.
Kirsten NielsenDepartment of Microbiology, University of Minnesota, Minneapolis, Minnesota, USA knielsen@umn.edu.
ASTRO-CM/COAT Team
University of Minnesota · USMakerere University · UGInfectious Diseases Institute · UGNorth Carolina State University · USSt. Catherine University · US

Funding

Medical Education for Services to All Ugandans (MESAU)R24TW008886 · FIC · MAKERERE UNIVERSITY COLLEGE OF HEALTH SCIENCES · PI SEWANKAMBO, NELSON K · 2010 to 2015
$9.2M
Improving Diagnostics and Neurocognitive Outcomes in HIV/AIDS-related MeningitisR01NS086312 · NINDS · UNIVERSITY OF MINNESOTA · PI David R Boulware, David Bisagaya Meya · 2013 to 2026
$8.3M
Trial for the Optimal Timing of HIV Therapy after Cryptococcal MeningitisU01AI089244 · NIAID · UNIVERSITY OF MINNESOTA · PI BOULWARE, DAVID R · 2010 to 2014
$7.6M
Infectious Disease Training in Clinical InvestigationT32AI055433 · NIAID · UNIVERSITY OF MINNESOTA TWIN CITIES · PI David R Boulware · 2003 to 2026
$6.1M
Northern/Pacific Universities Global Health Research Training ConsortiumR25TW009345 · FIC · UNIVERSITY OF WASHINGTON · PI KOLARS, JOSEPH C., NERURKAR, VIVEK RAMCHANDRA · 2012 to 2016
$5.9M
Outcomes of Cryptococcal Meningitis in UgandaK24AI096925 · NIAID · UNIVERSITY OF MINNESOTA · PI BOHJANEN, PAUL R · 2011 to 2015
$1.0M
FIC NIH HHS R24 TW008886FIC NIH HHS R24TW008886FIC NIH HHS R25 TW009345FIC NIH HHS R25TW009345NIAID NIH HHS K24 AI096925NIAID NIH HHS T32 AI055433NIAID NIH HHS T32AI055433NIAID NIH HHS U01 AI089244NIAID NIH HHS U01AI089244NINDS NIH HHS R01 NS086312NINDS NIH HHS R01NS086312
6 · The paper itself

Abstract

Cryptococcal antigen screening is recommended among people living with AIDS when entering HIV care with a CD4 count of <100 cells/μl, and preemptive fluconazole monotherapy treatment is recommended for those with subclinical cryptococcal antigenemia. Yet, knowledge is limited of current antimicrobial resistance in Africa. We examined antifungal drug susceptibility in 198 clinical isolates collected from Kampala, Uganda, between 2010 and 2014 using the CLSI broth microdilution assay. In comparison with two previous studies from 1998 to 1999 that reported an MIC50 of 4 μg/ml and an MIC90 of 8 μg/ml prior to widespread human fluconazole and agricultural azole fungicide usage, we report an upward shift in the fluconazole MIC50 to 8 μg/ml and an MIC90 value of 32 μg/ml, with 31% of isolates with a fluconazole MIC of ≥ 16 μg/ml. We observed an amphotericin B MIC50 of 0.5 μg/ml and an MIC90 of 1 μg/ml, of which 99.5% of isolates (197 of 198 isolates) were still susceptible. No correlation between MIC and clinical outcome was observed in the context of amphotericin B and fluconazole combination induction therapy. We also analyzed Cryptococcus susceptibility to sertraline, with an MIC50 of 4 μg/ml, suggesting that sertraline is a promising oral, low-cost, available, novel medication and a possible alternative to fluconazole. Although the CLSI broth microdilution assay is ideal to standardize results, limit human bias, and increase assay capacity, such assays are often inaccessible in low-income countries. Thus, we also developed and validated an assay that could easily be implemented in a resource-limited setting, with similar susceptibility results (P = 0.52).

Indexed as

Drug Resistance, FungalAmphotericin BAntifungal AgentsCD4 Lymphocyte CountCD4-Positive T-LymphocytesCoinfectionCryptococcus neoformansDrug Therapy, CombinationFemaleFluconazoleHIVHIV InfectionsHumansMaleMeningitis, CryptococcalMicrobial Sensitivity TestsAmphotericin BAntifungal AgentsFluconazole

Identifiers

PMID26324276
PMCPMC4649209
OpenAlexW2337544181

What OpenQuestion holds

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Registered trials

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.