Rhodotorula, Saccharomyces, Geotrichum and Rare Yeasts

A group of yeasts that are mostly environmental, dietary, or commensal organisms cause invasive infection in a small number of patients, nearly always those with central venous catheters, parenteral nutrition, neutropenia, prematurity, or long stays in intensive care.

Their clinical importance lies in three features: they are easily dismissed as contaminants, they are often misidentified by routine systems, and many are intrinsically resistant to the drugs used empirically for candidaemia (echinocandins and fluconazole).

A delayed identification therefore means delayed effective therapy.

Species level identification by mass spectrometry or sequencing is required for any yeast from blood or a sterile site that is not Candida albicans, and a yeast like organism that fails to behave as expected on routine media prompts repeat identification.

Rhodotorula are basidiomycete yeasts found in soil, water, air, plants, and dairy products, and on skin and in the gut. They form coral red, pink, salmon, or orange mucoid colonies because of carotenoid pigments, and are urease positive, non fermentative, and germ tube negative. The medically important species are Rhodotorula mucilaginosa (the commonest), Rhodotorula glutinis (now Rhodotorula toruloides), and Rhodotorula minuta (now Rhodosporidiobolus).

• Hosts and settings: central venous catheters (the dominant risk, present in over 70 percent of cases), haematological malignancy and neutropenia, corticosteroids, HIV, diabetes, parenteral nutrition, peritoneal dialysis, and prior echinocandin or azole exposure, which selects for resistant yeasts.
• Syndromes: catheter related fungaemia (the commonest), endocarditis, meningitis, peritonitis in dialysis, endophthalmitis and keratitis, and, rarely, skin and soft tissue infection.
• Outcome: crude mortality of fungaemia is about 10 to 20 percent and lower than for Candida, and removal of the catheter strongly affects the outcome.
• Susceptibility: amphotericin B is the most active agent. Echinocandins have no useful activity, and fluconazole MICs are high. Voriconazole, posaconazole, and itraconazole are variable, and flucytosine is variable.
• Treatment: remove the central venous catheter, and give amphotericin B deoxycholate 0.5 to 1 mg per kg daily or liposomal amphotericin B 3 to 5 mg per kg daily, usually for at least 2 weeks after the first negative blood culture. Susceptibility testing guides step down to voriconazole or other azole if the isolate is susceptible. Endocarditis and meningitis need prolonged therapy, with valve surgery in endocarditis.

Saccharomyces cerevisiae (baker's and brewer's yeast) and Saccharomyces cerevisiae variety boulardii (the probiotic Saccharomyces boulardii) are ascomycete yeasts present in food and the human gut and vagina. They are non pathogenic in healthy people and cause fungaemia and other invasive disease mainly in patients who receive probiotics.

• Source: the probiotic strain used orally or by enteral tube. Colonisation of the gut can lead to bloodstream infection through gut translocation, or through contamination of central venous catheter hubs and the hospital environment when capsules or sachets are opened near patients (aerosolised powder).
• Settings: intensive care patients on probiotics, with central venous catheters, enteral feeding, broad spectrum antibacterials, and severe illness; immunosuppressed patients; neonates and preterm infants in some reports. Vaginal infection with Saccharomyces cerevisiae resembles vulvovaginal candidiasis, often in women exposed to baker's yeast or probiotics.
• Identification: it grows quickly on Sabouraud agar and forms cream colonies, is germ tube negative, and forms ascospores on sporulation medium. On chromogenic media it can resemble Candida glabrata, and automated systems and some mass spectrometry databases misidentify it as Candida glabrata, so the laboratory is told that the patient receives a probiotic.
• Susceptibility: amphotericin B is active. Echinocandins are active, and fluconazole MICs are variable and often raised.
• Treatment: stop the probiotic, remove the catheter, and give an echinocandin (caspofungin 70 mg then 50 mg daily, micafungin 100 mg daily, or anidulafungin 200 mg then 100 mg daily), amphotericin B 0.5 to 1 mg per kg daily (or liposomal 3 to 5 mg per kg daily), or fluconazole 400 mg daily (6 mg per kg) for susceptible isolates, for 14 days after the first negative blood culture. Vaginal infection responds to topical azoles.
• Prevention: probiotics are avoided in patients with central venous catheters, severe illness, immunosuppression, and neonates, and probiotic capsules are opened away from the patient and catheter sites.

Saprochaete species are intrinsically resistant to echinocandins and often to fluconazole and flucytosine, so breakthrough infection occurs during prophylaxis and empirical therapy with echinocandins.

Amphotericin B and voriconazole are active in many isolates, and the usual approach is liposomal amphotericin B 3 to 5 mg per kg daily, or voriconazole 6 mg per kg every 12 hours for 2 doses then 4 mg per kg every 12 hours (oral 200 mg every 12 hours), or both together in severe disease, with removal of catheters, recovery of the neutrophil count, and granulocyte colony stimulating factor. Treatment continues for several weeks, and until neutropenia resolves. Outbreak investigation seeks a contaminated source.

• Treat every yeast in blood as significant, and request identification beyond "yeast".
• Use mass spectrometry with an updated database, and sequence the D1/D2 region or the internal transcribed spacer region when identification fails or is unexpected.
• Review the patient's exposure: catheter, parenteral lipid, probiotic, dairy, pet contact, and recent echinocandin or azole.
• Test susceptibility by broth microdilution, with the caveat that breakpoints are not defined for most of these organisms, and use epidemiological cutoff values and MIC distributions.
• Remove the catheter, search for metastatic infection (echocardiography and fundoscopy), and begin amphotericin B based therapy until identification and susceptibility are known when the patient is critically ill and an echinocandin would be ineffective.
• Consider an outbreak when two or more cases occur in a unit within a short time.