Abstract
Aims
Due to the increase of severely immunocompromised patients, of invasive procedures including central intravascular catheters, and of the use of broad-spectrum antibiotics, the incidence of Candida bloodstream infections has risen intensely in the last decades. Candida bloodstream infection is a serious disease with high mortality. Optimized diagnostic and therapeutic management can improve outcome. Thus, the aim of our mini-review is to highlight important and often missed opportunities in the management of Candida bloodstream infection.
Methods
We searched the published literature and describe the essentials in the management of Candida bloodstream infection.
Results
Four essentials were identified: (1) isolation of Candida spp. from a blood culture should always be considered relevant and requires treatment. Daily blood cultures should be drawn to determine cessation of candidemia. (2) Central venous catheter (CVC) and/or other indwelling devices should be removed. (3) Echinocandins are the first choice. Antifungal treatment should be continued for at least 14 days after cessation of fungemia. Susceptibility testing should be performed to identify resistance and to facilitate transition to oral treatment. (4) In persistent candidemia, echocardiography is an important investigation; ophthalmoscopy should be considered.
Conclusion
Further efforts should be undertaken to increase the adherence to the essentials in the management of Candia bloodstream infection.
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Introduction
The incidence of Candida bloodstream infections has risen intensely in the last decades. Candida bloodstream infection is a serious disease with high mortality . Optimized diagnostic and therapeutic management can improve outcome as recently shown in a cohort of 213 patients with candidemia [1]. Thus, the aim of our mini-review is to highlight important and often missed opportunities in the management of Candida bloodstream infection.
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1.
Isolation of Candida spp. from a blood culture should always be considered relevant and requires treatment. Daily blood cultures should be drawn to determine cessation of candidemia.
Candida bloodstream infection increases overall mortality (20–49%), and attributable mortality has been reported to be about 15% [2,3,4,5]. Candida spp. isolated from a single peripheral or central-line blood culture defines Candida bloodstream infection and requires prompt targeted treatment. Blood cultures are triggered by clinical signs. Daily follow-up blood cultures should be drawn until sterile. This is essential for the determination of treatment duration (see 3), and not to miss the detection of further organ involvement (see 4).
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2.
Central venous catheter (CVC) and/or other indwelling devices should be removed.
Central venous catheters (CVC) and other indwelling devices should be removed as early as possible when they are presumed to be the source of candidemia [6, 7]. An analysis of seven prospective randomized controlled trials for treatment of candidemia [8] and further observational studies [9,10,11,12] showed an association of CVC removal and better overall outcome.
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3.
Echinocandins are the first choice. Antifungal treatment should be continued for at least 14 days after cessation of fungemia. Susceptibility testing should be performed to identify resistance and to facilitate transition to oral treatment.
In treatment of candidemia, a large well-designed randomized clinical trial found superior efficacy of anidulafungin over fluconazole [13]. The results were extrapolated to superiority of the echinocandin class over the azole class [14]. Caspofungin and micafungin had previously proven better tolerability than deoxycholate and liposomal amphotericin B formulations [15, 16]. Both echinocandins had similar efficacy and tolerability in another large trial [17]. Higher than standard doses of caspofungin and micafungin have been evaluated, but had no significant effect on efficacy [17, 18]. In conclusion, all three echinocandins are valid choices for Candida blood stream infection [14, 19]. Treatment duration in uncomplicated candidemia should last until 14 days after cessation of blood stream infection [14]. Thus repeat blood cultures are essential to avoid under—as well as overtreatment. The duration is based on consensus rather than experimental evidence [14, 20]. Susceptibility testing is an essential investigation for two main reasons. It adequately addresses increasing reports of echinocandin resistance [21, 22], and is a prerequisite for any transition to oral azole treatment [14].
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4.
In persistent candidemia, echocardiography is an important investigation; ophthalmoscopy should be considered.
If candidemia persists, further clinical diagnostic work-up is important. It should always include echocardiography, while ophthalmoscopy may be considered on an individual basis.
It is highly recommended to perform echocardiography to detect clinically occult Candida endocarditis [23]. Transthoracic echocardiography is sufficient to diagnose endocarditis, but transoesophageal echocardiography is needed to reliably exclude Candida endocarditis. Signs of endocarditis include persistent positive follow-up blood cultures, persistent fever despite appropriate treatment, or new cardiac symptoms such as a new heart murmur, signs of heart failure, or embolism [24, 25]. A prospective cohort of 187 patients showed that at least 4.2% of candidemia patients have Candida endocarditis. The authors recommend echocardiography due to the initially and mostly hidden nature of Candida endocarditis [23].
Ocular involvement is a rare complication of candidemia [26]. It is mostly asymptomatic and of favorable outcome [27]. Ophthalmoscopy is currently recommended for all patients with candidemia, but has been questioned recently: a post hoc analysis of a prospective, multicenter, population-based candidemia surveillance in Spain did not yield evidence of increased ocular involvement in candidemic patients initially treated with echinocandins [28].
Conclusion
Candida bloodstream increases mortality. Optimized diagnostic and therapeutic management can improve outcome. We herein give an overview of the essentials in management of Candida bloodstream infection.
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SCM has nothing to declare. OAC has received research grants from Actelion, Amplyx, Arsanis, Astellas, AstraZeneca, Basilea, Bayer, Cidara, F2G, Gilead, GSK, Leeds University, Matinas, Medicines Company, MedPace, Melinta, Merck/MSD, Miltenyi, Pfizer, Rempex, Roche, Sanofi Pasteur, Scynexis, and Seres is a consultant to Allecra Therapeutics, Amplyx, Actelion, Astellas, Basilea, Cidara, Da Volterra, F2G, Gilead, IQVIA, Janssen, Matinas, Menarini, Merck/MSD, Paratek, PSI, Scynexis, Seres, Summit, Tetraphase, Vical, and received lecture honoraria from Astellas, Basilea, Gilead, Merck/MSD, and Pfizer. NJ has received lecture fees and travel expenses from Novartis and Gilead, as well as lecture fees from Labor Stein GmbH and travel expenses from Basilea. She received fees for carrying out a clinical study commissioned by InfectoPharm Arzneimittel.
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Mellinghoff, S.C., Cornely, O.A. & Jung, N. Essentials in Candida bloodstream infection. Infection 46, 897–899 (2018). https://doi.org/10.1007/s15010-018-1218-1
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DOI: https://doi.org/10.1007/s15010-018-1218-1