Change in Colony Morphology of Candida lusitaniae in Association with Development of Amphotericin B Resistance

Abstract

It is not uncommon to see amphotericin B treatment failure in patients with systemic infection caused by Candida lusitaniae. We report a patient with stage IV ovarian carcinoma and C. lusitaniae sepsis whose treatment with amphotericin B failed. The initial blood isolate was susceptible to amphotericin B in vitro; however, the MIC for a blood isolate recovered 7 weeks after treatment began showed a fourfold increase. Direct subculture of two positive blood samples obtained within a week of the patient's death showed the coexistence of two distinct colony color variants on CHROMagar Candida (CAC). One variant was susceptible to amphotericin B, and one was resistant. These results emphasize the importance of repeat amphotericin B susceptibility testing for patients with persistent C. lusitaniae infection. The presence of colony variants on CAC may signal the emergence of amphotericin B resistance in C. lusitaniae and should be investigated.Candida lusitaniae is considered an opportunistic pathogen, causing infection primarily in immunocompromised patients (1)(2)(3)(4)(5)17). Recent studies have shown that the incidence of serious infection caused by C. lusitaniae is increasing. Clinical management of systemic infection by this organism is challenging because of innate amphotericin B resistance in some isolates (3, 10, 16). Moreover, some isolates of C. lusitaniae may develop amphotericin B resistance in vivo, a finding which is supported by in vitro studies (14). Recently, Yoon et al. reported high-frequency, reversible, in vitro switching of isolates from being amphotericin B susceptible to amphotericin B resistant after exposure to the drug (18). Here we report a case of fatal systemic infection caused by C. lusitaniae with amphotericin B treatment failure. Blood cultures obtained during therapy yielded colonies with distinct differences in color on CHROMagar Candida (CAC) between amphotericin B-susceptible and amphotericin B-resistant strains. CASE REPORTA 69-year-old woman with stage IV metastatic ovarian carcinoma had fever for 5 days, respiratory distress, and metabolic acidosis despite metronidazole and imipenem therapy for 2 weeks. The culture of a central venous pressure catheter tip and three Isolator (Wampole Laboratories, Cranbury, N.J.) blood cultures drawn 2 days later were positive for C. lusitaniae. The catheter line was removed, and empiric treatment with fluconazole was started on day 1 (Table 1). The treatment was switched to amphotericin B at 35 mg (0.7 mg/kg of body weight) four times a day on day 6 and then to lipid complex amphotericin B (Abelcet) at 350 mg (7 mg/kg) four times a day on day 10 because of persistent fungemia, which was confirmed by another positive blood culture. The patient's symptoms improved, and after approximately 5 weeks of hospitalization, she was discharged on continuing treatment with lipid complex amphotericin B. Seven days after discharge, she experienced shortness of breath and was readmitted. She denied having fever, chills, or nausea. A pleural effusion prompted...

In Vitro Activity of Seven Systemically Active Antifungal Agents against a Large Global Collection of RareCandidaSpecies as Determined by CLSI Broth Microdilution Methods

“…lusitaniae (teleomorph, Clavispora lusitaniae) most often causes fungemia in patients with malignancies and other comorbid conditions (6,30). C. lusitaniae is often mentioned in the literature as being capable of developing resistance to amphotericin B during the course of therapy, and infection may present as breakthrough fungemia in immunocompromised patients (10,34,50,53,55,56,60,65,66,112). Although this species clearly can develop secondary resistance to amphotericin B (6,28,71), the frequency with which this resistance may be seen clinically is not known.…”

“…Whereas C. guilliermondii and C. lusitaniae have been described to be amphotericin B-resistant Candida species (6,24,79), both of these species appear to be susceptible to amphotericin B upon initial isolation from blood (Table 2). Thus, resistance to amphotericin B may develop secondarily during treatment, and repeat amphotericin B susceptibility testing is recommended for patients with persistent infection with these (and other) species while on amphotericin B therapy (6,50,79).…”

The First Isolation of Ustilaginomycetous Anamorphic Yeasts, Pseudozyma Species, from Patients' Blood and a Description of Two New Species: P. parantarctica and P. thailandica

“…While the susceptibility of unusual yeasts to antifungal agents varies, drug-resistant yeasts have been identified. Candida haemulonii, C. lusitaniae, Pichia farinosa, and Trichosporon asahii are resistant to amphotericin B (5,10,13,18). C. inconspicua, C. norvegensis, and some species of Rhodotorula are resistant to fluconazole (1,5).…”

Candida pseudohaemulonii Sp. Nov., an Amphotericin B‐ and Azole‐Resistant Yeast Species, Isolated from the Blood of a Patient from Thailand

“…Despite more than 40 years of clinical use, resistance to amphotericin B is very rare. Only C. lusitaniae, C. haemulonii, and Trichosporon asahii have reduced sensitivity to this drug (2,9,11,16). Although C. pseudohaemulonii and the two types of C. haemulonii are resistant to both amphotericin B and azole agents, they are very susceptible to 5-FC and micafungin.…”