Worldwide, there has been a notable shift away from C. albicans among patients with Candida BSI (13). Our study showed a high frequency in non-C. albicans candidaemia (Figure 1). These strains had a higher cost and length of hospital stay than C. albicans (14). C. glabrata was the predominantly isolated Candida species among our candidaemia patients, representing thirty percent of cases, followed by C. albicans and C. parapsilosis. These findings differ from those of previous local studies. Two studies conducted in Saudi Arabia in a university hospital and armed force hospital between 1998 to 1999 and 1996 to 2002 concluded that C. albicans was the most commonly isolated Candida species among patients with candidaemia, followed by C. tropicalis and C. parapsilosis (8, 11). Moreover, C. albicans remained the dominant isolated species among candidaemia cases in many studies (1, 2, 15, 16). Geographic variation significantly affects the species distribution of Candida (2). A systematic review summarizing the distribution of Candida species found a high concentration of C. albicans isolates in Northern and Central Europe in addition to the USA; however, non-C. albicans species were more common in South America, Asia and Southern Europe (17).
Antifungal resistance is a growing primary concern for most healthcare providers. We analysed one hundred and twenty-two Candida BSI cases for resistance. Twenty-one percent of all isolates were resistant to one or more antifungal agents. The patient’s risk of developing antifungal resistance was a primary concern in our study. We looked for many possible predisposing factors for drug insensitivity 90 days prior to a candidaemia episode. Patient’s previous exposures to broad-spectrum antibiotics, antifungals and corticosteroids were reported; none of the aforementioned risk factors showed a significant association with antifungal resistance in our study despite a positive association of previous antimicrobial exposure to fluconazole resistance among candidaemia in a previous study (18). However, previous exposure to echinocandins was significantly associated with antifungal resistance among our patients. Many researchers have confirmed that decreased susceptibility to Candida is significantly associated with previous antifungal exposure and an inappropriate prior course of antifungal therapy (6, 19, 20). In fact, fluconazole exposure was found to be a risk factor for gene mutation and overexposure that leads to future fluconazole-resistant C. parapsilosis (21). Furthermore, we investigated patient comorbidities and history of invasive procedures or surgery. Many studies addressed drug-resistant candidaemia among cancer patients and considered them a high-risk group (22). However, our cohort found that antifungal resistance was low among candidaemia patients with non-haematological malignancy. On the other hand, invasive ventilation was significantly associated with drug resistance; this result has been concluded by many researchers, who found that Candida resistance is dramatically higher among critical-care patients (17).
C. parapsilosis is known to have a high affinity for fluconazole, and resistance was absent in an earlier prospective trial (23). In our study, up to thirty-three percent of C. parapsilosis strains were insensitive to fluconazole. Clinical resistance to echinocandins is rare; however, some cases of caspofungin resistance in patients with prolonged exposure to echinocandins have been reported (13). Our study found few cases of echinocandin resistance. A 2012 US study investigated changes in the incidence of antifungal drug resistance, showing a 7% resistance to fluconazole and only 1% to echinocandin (15). In a US multicentre candidaemia surveillance programme, an increase in the rate of echinocandin resistance was mainly found in C. glabrata, despite it being the preferred treatment (7). Indeed, patients with fluconazole resistance were at higher risk for C. glabrata-associated echinocandin resistance (16). The variation in antifungal resistance patterns across geographic regions was addressed in a report on SENTRY antimicrobial surveillance, which observed a detectable resistance to anidulafungin, micafungin, and azoles among isolates of C. glabrata from North America (24).
Candida BSI contributed to a prolonged hospital stay and an increase in the overall healthcare cost (2). Furthermore, drug resistance was associated with overall mortality (10, 22). Despite the increase in length of hospital stay and mortality among our patients with antifungal resistance, the results were not significant.
The retrospective nature of our study could prevent us from identifying all risk factors related to our candidaemia cases. Data on source control and appropriateness of antifungal treatment in terms of timing and dosing of antifungals were not included in our study. Patients who transferred from an outside hospital had no previous records in our system, and risk factors were identified only by physician evaluation notes and nurse documentation. Another limitation is the unavailability of susceptibility data between 2006 and 2011 for all Candida species isolated during our study period, as the request for data was sent out and performed only upon physician request. Although KFSHRC-J is a bone marrow transplantation centre, the number of patients with haematological malignancies involved in our study was small, which prevents us from investigating fluconazole pre-exposure as a risk factor for drug-resistant candidaemia.