Fungal Foe and Mechanical Hearts: A Retrospective Case Series on Candida auris Bloodstream Infection With Left Ventricular Assist Devices

Abstract No guidelines currently exist for the management of Candida auris bloodstream infection in patients with left ventricular assist devices (LVADs). We aim to share our management experience through this retrospective case series outlining 15 episodes of C auris candidemia identified in 7 patients over 18 months. The initial source of candidemia was central venous catheter in 5 patients, driveline exit site infection in 1 patient, and possible pump infection in 1 patient. All patients were initially treated with micafungin. Despite susceptibility to micafungin, 4 patients experienced recurrent C auris candidemia. All patients died within 1 year of their first episode of C auris candidemia. Source control is challenging in patients with LVADs, and strict infection prevention measures should be practiced. More studies are needed to evaluate the role of newer antifungal agents, use of combination antifungal regimens, and impact on morbidity in patients with LVADs.

There is no specific literature on Candida auris BSI management in patients with LVADs.C auris is a multidrug-resistant (MDR) yeast causing infections in patients with healthcare exposure with associated mortality up to 70% [7,8].C auris incidence is increasing at an alarming rate, with 3851 clinical cases reported in the USA from 2021 to 2022 [9,10].The World Health Organization has categorized C auris into the critical priority group [11].
Patients with LVADs have frequent healthcare exposure and may also have central venous catheters (CVCs), further increasing C auris infection risk [12].The Infectious Diseases Society of America candidiasis guidelines recommend treating candida-related LVAD infections similarly to native valve endocarditis, followed by fluconazole chronic suppression if possible [13].However, 90% of C auris isolates in the USA are fluconazole-resistant [14].The Centers for Disease Control and Prevention (CDC) offer treatment guidelines for C auris infections, but no guidance exists for LVAD-related infections [15].
Through this retrospective case series of 7 patients with LVAD-associated C auris BSIs, we aim to share our experience of infection management and patient outcomes.

METHODS
MedStar Health Research Institute institutional review board approval was obtained.We included nonpregnant patients ≥18 years old with LVAD who had ≥1 blood culture(s) growing C auris and admitted at a tertiary care hospital from 1 January 2021 through 30 June 2022.Through chart review, we extracted data including demographics, comorbidities, healthcare or nursing facility exposure 90 days before candidemia, antifungal treatment, antifungal minimal inhibitory concentrations, concomitant infections, and candidemia source.Initial candidemia episode was defined as the first blood culture that grew C auris.Subsequent candidemia episodes, or recurrences, were defined as a blood culture growing C auris after a negative blood culture in a patient with a prior C auris candidemia episode.Candidemia episodes were categorized according to 2011 ISHLT VAD infection definitions [3].We reviewed outcomes such as time to clear candidemia, number of recurrences, and death, adjudicated by S. D. and A. M.
Our local health department recommended targeted C auris screening starting in April 2021 [16].Patients admitted from high-risk facilities were screened for C auris colonization via axillary and groin swab culture.All patients with a positive C auris screen or culture were placed on contact isolation for index and future hospitalizations.

RESULTS
Baseline characteristics are outlined in Table 1.Seven patients with 15 episodes of C auris BSI were identified.Four patients had at least 1 candidemia recurrence.All patients had prolonged (>15 days) exposure to a healthcare or nursing facility within 90 days of initial candidemia.Initial candidemia sources were identified as: CVC (5 patients), possible pump infection (1 patient), and driveline exit site infection (DLES) (1 patient).All patients received micafungin as initial treatment.Time from LVAD implant to first candidemia episode ranged from 112 to 2374 days and time from initial C auris BSI to death ranged from 12 to 358 days.Patient 1 was admitted before C aris screening initiation in April 2021, patient 2 had a positive screen 2 months before admission, and the remaining patients did not meet screening criteria.

BRIEF CASE SUMMARIES
Cases are summarized in Table 2.
Case 1: A 73-year-old male with end-stage renal disease on hemodialysis via CVC on intravenous antibiotics for presumed LVAD pump infection was admitted from nursing home with septic shock from C auris and C albicans candidemia and MDR P aeruginosa pneumonia.The CVC was removed, micafungin was started, and blood cultures cleared after 2 days.He was discharged on micafungin for 6 weeks and antibacterials but readmitted 25 days later with MDR P aeruginosa pneumonia.He was transitioned to comfort care and died.
Case 2: A 62-year-old male with end-stage renal disease on hemodialysis via tunneled CVC, LVAD-related vancomycinresistant Enterococcus faecium mediastinitis, presented from nursing home with septic shock from C auris candidemia and bacterial pneumonia.Micafungin was started, CVC was removed, blood cultures cleared after 3 days, and he was discharged on 6 weeks of micafungin and antibacterials.He was readmitted 17 days later with septic shock; blood cultures grew methicillin-resistant S aureus (MRSA), Enterococcus faecium, and C auris.Micafungin was continued with BSI clearance after 7 days.Transesophageal echocardiogram (TEE) was not done because of hemodynamic instability, and the patient died after transition to comfort care.Case 3: A 52-year-old male on antibacterial suppression for prior LVAD infection presented with DLES discharge and C auris BSI.Micafungin was started and BSI cleared in 4 days.He underwent DLES debridement; tissue cultures grew MDR P aeruginosa.He was discharged on micafungin for 2 weeks and antibacterials.He was readmitted 80 days later with DLES discharge and recurrence of C auris BSI.DLES debridement tissue cultures grew P aeruginosa and C auris.He was started on micafungin and liposomal amphotericin B (AMB).TEE revealed automatic implantable cardioverterdefibrillator (AICD) lead vegetation resulting in AICD extraction.AICD culture grew C auris and 70 days later candidemia cleared.He was discharged on caspofungin, oral posaconazole, and antibacterials.He was readmitted 9 days later with C auris candidemia and MDR P aeruginosa bacteremia.He was started on micafungin, flucytosine, and antibiotics.The patient had persistent candidemia, was transitioned to comfort care, and died.
Case 4: A 39-year-old female underwent LVAD implantation complicated by cardiac arrest requiring percutaneous gastrostomy tube placement complicated by peritonitis requiring exploratory laparotomy.She developed C auris candidemia 125 days into hospitalization, was started on micafungin, and BSI cleared in 6 days.Candidemia recurred after 8 days and persisted; AMB was added.Transthoracic echocardiogram did not reveal vegetations and TEE was not pursued as the source was attributed  Case 5: A 35-year-old male with LVAD, history of C glabrata peritonitis, vancomycin-resistant Enterococcus AICD endocarditis on antibacterial suppression, presented with sepsis.DLES discharge culture grew P aeruginosa.DLES was not debrided because of hemodynamic instability.TEE revealed lead vegetation and AICD was explanted.On hospitalization day 60, he developed C auris BSI and MDR P aeruginosa pneumonia.He was started on micafungin and antibiotics.Candidemia cleared in 8 days; however, he developed worsening lung abscess and eventually died.
Case 6: A 65-year-old female with history of methicillinsensitive Staphylococcus aureus pump infection on chronic antibiotic suppression presented with DLES discharge.Her longterm peripherally inserted central catheter was removed and she underwent DLES debridement.Admission blood cultures grew MRSA and C auris, whereas DLES debridement culture grew MRSA, C auris, MDR P aeruginosa, and MDR Acinetobacter baumannii.Candidemia cleared after 7 days of micafungin and she was discharged on micafungin and antibacterials.She was readmitted 38 days later with AICD shocks; blood cultures grew C auris.She was started on micafungin and AMB with tunneled CVC removal.TEE revealed AICD lead vegetation, but she was deemed high risk for explant.Candidemia cleared within 11 days and she was discharged on antibacterials, micafungin, and posaconazole.She was readmitted 34 days later with sepsis, respiratory failure, and no laboratory evidence of candidemia.The patient desired comfort care and died.
Case 7: A 61-year-old male with prior DLES infection presented with DLES discharge.Hospitalization was complicated by cardiac arrest from septic shock and bowel ischemia requiring resection.One month of empiric antibiotics and micafungin were completed.Total parenteral nutrition was started via tunneled CVC.He developed C auris candidemia, which prompted CVC removal.Micafungin was started, candidemia cleared in 5 days, and the patient was discharged.He died 51 days later from gastrointestinal bleeding.No culture data were available from the time of discharge to readmission.

ANTIFUNGAL SUSCEPTIBILITY DATA
All isolates were susceptible to micafungin per CDC breakpoints and 13/15 were resistant to fluconazole (Table 3).Despite susceptibility to micafungin, 4 patients had candidemia recurrences.

DISCUSSION
Currently, no specific guidelines exist on the management of C auris BSI in patients with LVADs.We report a novel case series of 7 cases with 15 episodes of C auris BSI in LVAD patients, including management and outcomes.C auris BSIs were difficult to eradicate in the setting of LVADs.Six patients had concomitant MDR infections and all died within 1 year of initial C auris BSI.This suggests that C auris BSI is a poor prognostic indicator in patients with LVADs and may require aggressive upfront therapy.Source control was challenging in non-CVC-related infections.Though pump exchange or heart transplantation can be pursued for refractory pump infections, cases 3 and 4 were deemed high-risk candidates [17,18,19].Infectious Diseases Society of America guidelines also recommend AICD removal with candidal cardiac infections along with chronic antifungal treatment for LVADs that cannot be removed; case 6 was deemed high risk for AICD explantation [13].
Despite susceptibility to micafungin, 4 patients had recurrent BSI.This reflects the ability of C auris to make biofilms and the associated challenges of achieving adequate source control [12].Four episodes were treated with combination antifungal therapy; there is minimal guidance regarding this clinical practice [20].Newer antifungal agents such as fosmanogepix, ibrexafungerp, and opelconazole have demonstrated activity against C auris biofilm formation and may become future options to treat C auris infections in LVAD patients [21].
Although no formal investigation was conducted, the cases were unlikely to be secondary to a single center-associated outbreak.All patients had exposure to different healthcare facilities before candidemia, 6 candidemia episodes were present on admission, 1 episode occurred in a patient with prior positive C auris screen, and initial episodes were spread over time (13 months).Once identified, all patients were placed on contact isolation and routine and terminal cleaning was performed per CDC recommendations.
The descriptive nature of a case series and small sample size limits assessment of C auris attributable mortality.All patients died within 1 year of their first episode of C auris candidemia.One patient was candidemic, whereas 6 patients had MDR bacterial infections at time of death, making it difficult to establish a causal relationship between C auris BSI and mortality.Most LVADs were placed as destination therapy; thus, we cannot assess the impact of C auris infection on transplant status.Although all patients died within 1 year of initial candidemia episode, 6 patients had prior LVAD-related infections along with other comorbidities, signaling an overall high-risk baseline.
In conclusion, C auris candidemia is a challenging infection to treat in patients with LVADs.To address this, strategies need to be developed surrounding early detection of candidemia, LVAD-specific infection prevention protocols, and source control.Early combination treatment or newer antifungal agents may be an option to clear candidemia quickly and should be evaluated with further studies.

Notes
Patient consent statement.This study does not include factors necessitating patient consent and the retrospective study design was approved by MedStar Health institutional review board.
Potential conflicts of interest.All authors: No reported conflicts.NOVEL ID CASES • OFID • 5

Table 2 . Summary of Cases
as possible pump infection.She was discharged on micafungin and AMB for presumed pump infection.She was readmitted 69 days later with C auris and Candida krusei BSI with Stenotrophomonas pneumonia.Blood cultures cleared after 8 days and she was discharged on lifelong micafungin and AMB.Nine days later, she was readmitted with a C auris BSI and again discharged on micafungin and AMB.No culture data were available to document clearance until readmission 141 days later for shock and right ventricular failure.She subsequently passed away.

Table 2 . Continued
Patient was discharged after episode 4.5 on lifelong antifungal therapy and readmitted 141 d later.No culture data were available to document candidemia clearance between admissions.
Abbreviationsb Episode 4.3 did not undergo susceptibility testing.