Emergence of Fluconazole Resistance in a Candida parapsilosis Strain That Caused Infections in a Neonatal Intensive Care Unit

Abstract

Candida parapsilosis is an increasing cause of bloodstream infections (BSIs) in neonatal intensive care units (NICUs).During the last decades the incidence of candidemia in neonatal intensive care units (NICUs) has increased, and the most prevalent Candida species that cause candidemias have shifted over time from Candida albicans to Candida parapsilosis (12,16,23). The known risk factors for candidemia are prematurity; the use of central venous lines, intubation, parenteral nutrition, and broad-spectrum antibiotics; and prolonged hospitalization (16,18,20,26,35). In addition, in some reports colonization with Candida spp. was associated with an increased risk for candidemia, especially in very low birth weight (VLBW; Ͻ1,500 g) infants (4,25,26).In VLBW infants, prevention of fungal colonization by fluconazole prophylaxis has been shown to be effective (10, 11). The efficacy of this drug in preventing infections is, however, controversial (1, 3). In addition, selection of Candida species with primary resistance to fluconazole and development of resistance to azoles are potential threats (14,19). Two studies on fluconazole prophylaxis previously conducted in NICUs (10, 11) found no difference in the rates of fluconazole susceptibility among Candida isolates before and after a relatively short study period. Global surveillance studies also indicate that reduced susceptibility to fluconazole is extremely uncommon among bloodstream infection (BSI) isolates of C. parapsilosis (21).The NICU of the Hospital for Children and Adolescents (HCA), Helsinki University Central Hospital, Helsinki, Finland, has had problems with nosocomial C. parapsilosis infections for years. Fluconazole prophylaxis seemed to control the problem (27), but later, the number of infected or colonized patients in the NICU started to increase again.We describe a clonal outbreak caused by C. parapsilosis in the NICU during a 12-year period and the development of fluconazole resistance of the causative clone during the longterm use of fluconazole prophylaxis. MATERIALS AND METHODSSetting and surveillance. The 18-bed NICU of HCA serves a population of 1.4 million people with 470 annual admissions, including 150 VLBW infants. The NICU consists of five rooms. Sinks are available in each room, and handdisinfectant dispensers are available at each bed. Alcohol-based hand rub is used before and after any patient contact, and gloves are routinely used during aseptic procedures. Blood samples for culture are drawn from a peripheral vessel by venipuncture. Endotracheal aspirates are taken weekly from every patient in the NICU for surveillance culture, and other samples of other specimens are taken for culture whenever an infection is suspected. The empirical antimicrobial treatment for a suspected case of septicemia is a combination of ampicillin and netilmicin. All patients with either suspected or verified candidemia are treated with amphotericin B; since June 1999, liposomal amphotericin B has been used routinely.An in-house system of surveillance for noso...

Prevalence and antifungal susceptibility of Candida parapsilosis complex isolates collected from oral cavities of HIV-infected individuals

“…Candida parapsilosis is a well-known cause of nosocomial bloodstream infections, particularly among neonates and immunocompromised patients, and it is associated with candidaemia caused by intravascular and parenteral nutrition devices (Sarvikivi et al, 2005;Almirante et al, 2006;Pfaller & Diekema, 2002;Trofa et al, 2008). C. parapsilosis groups I, II and III were recently established as distinct species, which were classified by genotyping and designated C. parapsilosis sensu stricto, C. orthopsilosis and C. metapsilosis, respectively (Tavanti et al, 2005).…”

“…Members of the C. parapsilosis complex are normally susceptible to most antifungal compounds but previous studies reported decreased responsiveness to fluconazole (FLC) and caspofungin (CASPO) (Sarvikivi et al, 2005;Legout et al, 2006;Lockhart et al, 2008;van Asbeck et al, 2008;Gonçalves et al, 2010;Silva et al, 2009). It was also suggested that C. orthopsilosis and C. metapsilosis might be more susceptible to amphotericin B (AMB) and echinocandins than C. parapsilosis sensu stricto (Gomez-Lopez et al, 2008;van Asbeck et al, 2008;Garcia-Effron et al, 2008) and that these differences in antifungal susceptibility could affect choice of therapy.…”

Impact of ‘targeted’ fluconazole prophylaxis for preterm neonates: efficacy of a highly selective approach?

“…3 Several studies have demonstrated that prophylactic fluconazole decreases fungal colonization and subsequent invasive fungal infection in PT infants. [4][5][6][7][8] The duration of prophylaxis in most of these studies is from 4 to 6 weeks, starting at birth to 3 days of age. 4,5,8 The risk of invasive candidiasis persists from birth to 3 months, with the highest risk reported to be between 11 and 20 days of life.…”

“…[4][5][6][7][8] The duration of prophylaxis in most of these studies is from 4 to 6 weeks, starting at birth to 3 days of age. 4,5,8 The risk of invasive candidiasis persists from birth to 3 months, with the highest risk reported to be between 11 and 20 days of life. 1 The approach of prophylaxis, from 4 to 6 weeks, to all extremely low birth weight infants treats a large number of infants for a prolonged duration, some of whom may be at low risk for infection.…”

“…Over a 10-year period, a 1.1% incidence of native fluconazole-resistant systemic fungal infections was reported in one study and in two Candida parapsilosis isolates in another Finnish NICU. 4,9 Nevertheless, fluconazole prophylaxis (FP) for all extremely low birth weight infants in the NICU is not yet standard of care, particularly in centers with low rates of invasive candidiasis. 10,11 In an attempt to optimize benefits, we implemented an intermittent FP regimen for high-risk infants with multiple risk factors for invasive candidiasis.…”