The controversial drive for intervention with ophthalmologic screening for Candida bloodstream infections

International Journal of Infectious Diseases, vol. 96, pp. 363–364

Abstract

We read the study by Shin et al., 2020Shin S.U. Yu Y. Kim S.S. et al.Clinical characteristics and risk factors for complications of candidaemia in adults: focus on endophthalmitis, endocarditis, and osteoarticular infections.Int J Infect Dis. 2020; 93: 126-132Abstract Full Text Full Text PDF PubMed Scopus (3) Google Scholar with concern regarding endogenous Candida endophthalmitis (ECE). They report high ECE incidence (12.9%) among ophthalmologically examined patients with candidaemia, of which nearly half (41.4%) were subjected to intravitreal injection ± vitreous aspiration, and/or vitrectomy, despite symptoms being absent in most (65%). They conclude: ‘Early active screening and treatment’ of ophthalmic candidaemia complications is needed (Shin et al., 2020Shin S.U. Yu Y. Kim S.S. et al.Clinical characteristics and risk factors for complications of candidaemia in adults: focus on endophthalmitis, endocarditis, and osteoarticular infections.Int J Infect Dis. 2020; 93: 126-132Abstract Full Text Full Text PDF PubMed Scopus (3) Google Scholar). We believe that their data do not support this recommendation. The authors do not define ECE, treatment indications or treatment failure criteria. They include cases without vitreous extension as ECE, falsely doubling the true incidence, as previously seen (Breazzano et al., 2019Breazzano M.P. Day Jr., H.R. Bloch K.C. et al.Systematic review without meta-analysis of utility in ophthalmologic screening for Candida blood stream infections.JAMA Ophthalmol. 2019; 137: 698-710Crossref PubMed Scopus (27) Google Scholar). This discrepancy is critical, since distinguishing between true endophthalmitis (always involving vitreous) and less serious disease has management implications (Breazzano et al., 2019Breazzano M.P. Day Jr., H.R. Bloch K.C. et al.Systematic review without meta-analysis of utility in ophthalmologic screening for Candida blood stream infections.JAMA Ophthalmol. 2019; 137: 698-710Crossref PubMed Scopus (27) Google Scholar, Day et al., 2019Day Jr., H.R. Breazzano M.P. Bloch K.C. et al.Response to Kato et al.: prevalence of, and risk factors for, hematogenous fungal endophthalmitis in patients with Candida bloodstream infection.Infection. 2019; 47: 501-502Crossref PubMed Scopus (3) Google Scholar, Donahue et al., 1994Donahue S.P. Greven C.M. Zuravleff J.J. et al.Intraocular candidiasis in patients with candidemia: clinical implications derived from a prospective multicenter study.Ophthalmology. 1994; 101: 1302-1309Abstract Full Text PDF PubMed Scopus (202) Google Scholar, Pappas et al., 2016Pappas P.G. Kauffman C.A. Andes D.R. et al.Executive summary: clinical practice guideline for the management of candidiasis: 2016 update by the Infectious Diseases Society of America.Clin Infect Dis. 2016; 62: 409-417Crossref PubMed Scopus (360) Google Scholar). Since 19% of ICU patients without candidaemia can exhibit indistinguishable ocular findings, it is essential to include control groups in these studies (Donahue et al., 1994Donahue S.P. Greven C.M. Zuravleff J.J. et al.Intraocular candidiasis in patients with candidemia: clinical implications derived from a prospective multicenter study.Ophthalmology. 1994; 101: 1302-1309Abstract Full Text PDF PubMed Scopus (202) Google Scholar, Rodríguez-Adrián et al., 2003Rodríguez-Adrián L.J. King R.T. Tamayo-Derat L.G. Miller J.W. Garcia C.A. Rex J.H. Retinal lesions as clues to disseminated bacterial and candidal infections: frequency, natural history, and etiology.Medicine (Baltimore). 2003; 82: 187-202Crossref PubMed Scopus (93) Google Scholar). The proportion of vitreous involvement among patients receiving invasive intervention is not provided. As six (20.7%) did not improve, it is unclear if these patients were subjected to unnecessary intervention, given an inaccurate diagnosis in half and no Candida growth from vitreous. At best, these patients had true endophthalmitis with severe disease, which was refractory to invasive intervention regardless of screening. At worst, these cases were not true endophthalmitis and subject to iatrogenic complications from an intervention that may not have been necessary. Iatrogenic complications are not infrequent and occasionally have devastating consequences (McCannel et al., 2003McCannel C.A. Nordlund J.R. Bacon D. Robertson D.M. Perioperative morbidity and mortality associated with vitreoretinal and ocular oncologic surgery performed under general anesthesia.Trans Am Ophthalmol Soc. 2003; 101: 209-213PubMed Google Scholar). Information is not provided regarding central catheter removal or timing of systemic antifungal therapy following candidaemia diagnosis; both are known to influence endophthalmitis outcomes and mortality (Breazzano et al., 2019Breazzano M.P. Day Jr., H.R. Bloch K.C. et al.Systematic review without meta-analysis of utility in ophthalmologic screening for Candida blood stream infections.JAMA Ophthalmol. 2019; 137: 698-710Crossref PubMed Scopus (27) Google Scholar, Pappas et al., 2016Pappas P.G. Kauffman C.A. Andes D.R. et al.Executive summary: clinical practice guideline for the management of candidiasis: 2016 update by the Infectious Diseases Society of America.Clin Infect Dis. 2016; 62: 409-417Crossref PubMed Scopus (360) Google Scholar, Cornely et al., 2012Cornely O.A. Bassetti M. Calandra T. et al.ESCMID guideline for the diagnosis and management of Candida diseases 2012: non-neutropenic adult patients.Clin Microbiol Infect. 2012; 18 Suppl 7: 19-37Abstract Full Text Full Text PDF PubMed Scopus (799) Google Scholar, Martínez-Vázquez et al., 1998Martínez-Vázquez C. Fernández-Ulloa J. Bordón J. et al.Candida albicans endophthalmitis in brown heroin addicts: response to early vitrectomy preceded and followed by antifungal therapy.Clin Infect Dis. 1998; 27: 1130-1133Crossref PubMed Scopus (84) Google Scholar). Early screening and invasive ophthalmologic interventions have not been demonstrated to improve outcomes (Breazzano et al., 2019Breazzano M.P. Day Jr., H.R. Bloch K.C. et al.Systematic review without meta-analysis of utility in ophthalmologic screening for Candida blood stream infections.JAMA Ophthalmol. 2019; 137: 698-710Crossref PubMed Scopus (27) Google Scholar, Vena et al., 2017Vena A. Muñoz P. Padilla B. et al.Is routine ophthalmoscopy really necessary in candidemic patients?.PLoS One. 2017; 12e0183485Crossref PubMed Scopus (19) Google Scholar). These recommendations are established by the Infectious Diseases Society of America (IDSA) (Pappas et al., 2016Pappas P.G. Kauffman C.A. Andes D.R. et al.Executive summary: clinical practice guideline for the management of candidiasis: 2016 update by the Infectious Diseases Society of America.Clin Infect Dis. 2016; 62: 409-417Crossref PubMed Scopus (360) Google Scholar), based upon evidence from a small case series (Martínez-Vázquez et al., 1998Martínez-Vázquez C. Fernández-Ulloa J. Bordón J. et al.Candida albicans endophthalmitis in brown heroin addicts: response to early vitrectomy preceded and followed by antifungal therapy.Clin Infect Dis. 1998; 27: 1130-1133Crossref PubMed Scopus (84) Google Scholar), although many cases may be effectively managed without invasive approaches (Breazzano et al., 2019Breazzano M.P. Day Jr., H.R. Bloch K.C. et al.Systematic review without meta-analysis of utility in ophthalmologic screening for Candida blood stream infections.JAMA Ophthalmol. 2019; 137: 698-710Crossref PubMed Scopus (27) Google Scholar, Cornely et al., 2012Cornely O.A. Bassetti M. Calandra T. et al.ESCMID guideline for the diagnosis and management of Candida diseases 2012: non-neutropenic adult patients.Clin Microbiol Infect. 2012; 18 Suppl 7: 19-37Abstract Full Text Full Text PDF PubMed Scopus (799) Google Scholar). A comparison of strategies is not provided, possibly because 31% of outcome data for ECE patients are missing (Shin et al., 2020Shin S.U. Yu Y. Kim S.S. et al.Clinical characteristics and risk factors for complications of candidaemia in adults: focus on endophthalmitis, endocarditis, and osteoarticular infections.Int J Infect Dis. 2020; 93: 126-132Abstract Full Text Full Text PDF PubMed Scopus (3) Google Scholar). Conclusions regarding outcomes are also limited by the large proportion of unscreened patients (70.6%), identified by these authors as an important source of selection bias (Shin et al., 2020Shin S.U. Yu Y. Kim S.S. et al.Clinical characteristics and risk factors for complications of candidaemia in adults: focus on endophthalmitis, endocarditis, and osteoarticular infections.Int J Infect Dis. 2020; 93: 126-132Abstract Full Text Full Text PDF PubMed Scopus (3) Google Scholar). Although the authors suggest that their findings support the IDSA guidelines (Pappas et al., 2016Pappas P.G. Kauffman C.A. Andes D.R. et al.Executive summary: clinical practice guideline for the management of candidiasis: 2016 update by the Infectious Diseases Society of America.Clin Infect Dis. 2016; 62: 409-417Crossref PubMed Scopus (360) Google Scholar), the study does not provide data that asymptomatic patients benefitted from screening or that invasive ophthalmologic procedures resulting from screening improved outcomes. In conclusion, the recommendation by Shin et al., 2020Shin S.U. Yu Y. Kim S.S. et al.Clinical characteristics and risk factors for complications of candidaemia in adults: focus on endophthalmitis, endocarditis, and osteoarticular infections.Int J Infect Dis. 2020; 93: 126-132Abstract Full Text Full Text PDF PubMed Scopus (3) Google Scholar to continue universal ophthalmologic screening for candidaemia should be tempered, as it is not supported by the data and may further drive invasive procedures leading to harm. This research was supported [in part] by the Intramural Research Program of the National Institutes of Health , National Institute of Allergy and Infectious Diseases (L.T.G.). This research was largely supported by an unrestricted grant from Research to Prevent Blindness for the Vanderbilt Eye Institute (J.B.B.). There are no other funding sources to report.

Authors 7

1. Mark P. Breazzano

   Northwell Health · NewYork–Presbyterian Hospital · Columbia University Irving Medical Center · Manhattan Eye, Ear and Throat Hospital · NYU Langone Health · New York University

   Affiliation as printed

   Department of Ophthalmology, Edward S. Harkness Eye Institute, Columbia University Irving Medical Center, New York-Presbyterian Hospital, New York, NY, USA; Department of Ophthalmology, New York University School of Medicine, New York University Langone Health, New York, NY, USA; Manhattan Eye, Ear, and Throat Hospital, Northwell Health, New York, NY, USA

   Department of Ophthalmology, Edward S. Harkness Eye Institute, Columbia University Irving Medical Center, New York–Presbyterian Hospital, New York, NY, USA

   Department of Ophthalmology, New York University School of Medicine, New York University Langone Health, New York, NY, USA

   Manhattan Eye, Ear, and Throat Hospital, Northwell Health, New York, NY, USA

2. Luca Tudor Giurgea

   National Institutes of Health

   Affiliation as printed

   Clinical Studies Unit, Laboratory of Infectious Diseases, National Institute of Infectious Diseases, National Institutes of Health, Bethesda, MD, USA

3. H. Russell Day

   Vanderbilt University

   Affiliation as printed

   Vanderbilt University School of Medicine, Nashville, TN, USA

4. Serena Fragiotta

   Sapienza University of Rome

   Affiliation as printed

   Department of Medico-Surgical Sciences and Biotechnologies, U.O.S.D. Ophthalmology, Sapienza University of Rome, Rome, Italy

   Department of Medico–Surgical Sciences and Biotechnologies, U.O.S.D. Ophthalmology, Sapienza University of Rome, Rome, Italy

5. Pedro Fernández-Avellaneda

   Hospital de Basurto

   Affiliation as printed

   Department of Ophthalmology, Basurto University Hospital, Bilbao, Spain

6. Elon H. C. van Dijk Aachen Department of Ophthalmology, Leiden University Medical Center

   Leiden University Medical Center

   Affiliation as printed

   Department of Ophthalmology, Leiden University Medical Center, Leiden, The Netherlands

7. Srilaxmi Bearelly

   NewYork–Presbyterian Hospital · Columbia University Irving Medical Center

   Affiliation as printed

   Department of Ophthalmology, Edward S. Harkness Eye Institute, Columbia University Irving Medical Center, New York-Presbyterian Hospital, New York, NY, USA

   Department of Ophthalmology, Edward S. Harkness Eye Institute, Columbia University Irving Medical Center, New York–Presbyterian Hospital, New York, NY, USA