Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
. 2020 Oct 7:27:100563.
doi: 10.1016/j.eclinm.2020.100563. eCollection 2020 Oct.

Potential missed opportunities for diagnosis of cryptococcosis and the association with mortality: A cohort study

Ana S Salazar  1   2 , Matthew R Keller  1 , Margaret A Olsen  1   2 , Katelin B Nickel  1 , Ige A George  1 , Lindsey Larson  1 , William G Powderly  1 , Andrej Spec  1
Affiliations

Potential missed opportunities for diagnosis of cryptococcosis and the association with mortality: A cohort study

Ana S Salazar et al. EClinicalMedicine. .

Abstract

Background: Cryptococcosis is one of the most common life-threatening opportunistic mycoses worldwide. Insidious presentation and slow onset of symptoms make it difficult to recognize, complicating the diagnostic process. Delays in diagnosis may lead to increased mortality. We aim to determine the frequency of missed opportunities for diagnosis of cryptococcosis and its effects on mortality.

Methods: To estimate the proportion of individuals with a potentially missed diagnosis for cryptococcosis in hospitalized patients, we conducted a retrospective cohort study using the Healthcare Cost and Utilization Project State Inpatient Databases from 2005 to 2015 from eight states. All hospitalized adult patients diagnosed with cryptococcal infection or cryptococcal meningitis were included. Potentially missed diagnoses were defined as admissions coded for a procedure or diagnosis suggestive of cryptococcosis in the 90-days prior to the initial cryptococcosis admission. Generalized estimating equations models were used to evaluate the association between underlying comorbidities and potential missed diagnosis of cryptococcosis and 90-day all-cause in-hospital mortality.

Findings: Of 5,354 patients with cryptococcosis, 2,445 (45·7%) were people living with HIV (PLWH). Among PLWH, 493/2,445 (20·2%) had a potentially missed diagnosis, of which 83/493 (16·8%) died while hospitalized compared with 265/1,952 (13·6%) of those without a potentially missed diagnosis (relative risk [RR] 1·04, 95% CI 0·99-1·09). Among HIV-negative patients, 977/2,909 (33·6%) had a potentially missed diagnosis, of which 236/977 (24·2%) died while hospitalized compared with 298/1,932 (15·4%) of those not missed (RR 1·12, 95% CI 1·07-1·16).

Interpretation: Missed opportunities to diagnose cryptococcosis are common despite highly efficacious diagnostic tests and are associated with increased risk of 90-day mortality in HIV-negative patients. A high index of clinical suspicion is paramount to promptly diagnose, treat, and improve cryptococcosis-related mortality.

Funding: National Center for Advancing Translational Sciences, Washington University Institute of Clinical and Translational Sciences, and the Agency for Healthcare Research and Quality.

Keywords: Administrative data; Cryptococcus; Delayed diagnosis; Misdiagnosis.

PubMed Disclaimer

Conflict of interest statement

AS reports grants and personal fees from Astellas Global Development Pharma and Mayne Pharma; grants from Scynexis, Cidara, MiraVista, and IMMY; and personal fees from Viamet, outside the submitted work. WGP reports grants and personal fees from Merck and Co, and Gilead Sciences. MK and KBN report grants from NIH; and grants from AHRQ. MAO reports grants from NIH/NCATS; grants from AHRQ, Pfizer; and grants and personal fees from Merck and Sanofi Pasteur, outside the submitted work. All other authors declare no competing interests.

Figures

Fig 1
Fig. 1
Flowchart for characterization of patients with cryptococcal disease stratified by HIV status. Potentially missed diagnoses for cryptococcal disease (CD) are common in both Persons Living with HIV (PLWH) and in HIV-negative populations. In the HIV-negative population, a potentially missed CD diagnosis is associated with higher mortality.
Fig 2
Fig. 2
Cox proportional hazards curves comparing time from index admission to death by potential missed diagnosis of cryptococcal disease for (a) persons living with HIV and (b) HIV-negative patients. Patients with a potential missed opportunity for diagnosis of Cryptococcus have a higher mortality amongst those that are HIV-negative, but not those that are HIV positive.
See this image and copyright information in PMC

References

    1. Park B.J., Wannemuehler K.A., Marston B.J., Govender N., Pappas P.G., Chiller T.M. Estimation of the current global burden of cryptococcal meningitis among persons living with HIV/AIDS. AIDS. 2009;23(4):525–530. - PubMed
    1. Rajasingham R., Smith R.M., Park B.J. Global burden of disease of HIV-associated cryptococcal meningitis: an updated analysis. Lancet Infect Dis. 2017;17(8):873–881. - PMC - PubMed
    1. Brizendine K.D., Baddley J.W., Pappas P.G. Predictors of mortality and differences in clinical features among patients with Cryptococcosis according to immune status. PLoS ONE. 2013;8(3):e60431. - PMC - PubMed
    1. Jongwutiwes U., Sungkanuparph S., Kiertiburanakul S. Comparison of clinical features and survival between cryptococcosis in human immunodeficiency virus (HIV)-positive and HIV-negative patients. Jpn J Infect Dis. 2008;61(2):111–115. - PubMed
    1. Liao C.H., Chi C.Y., Wang Y.J. Different presentations and outcomes between HIV-infected and HIV-uninfected patients with Cryptococcal meningitis. J Microbiol Immunol Infect. 2012;45(4):296–304. - PubMed

LinkOut - more resources