Kodamaea ohmeri infections in humans: A systematic review.

BACKGROUND: Kodamaea ohmeri, previously known as Pichia ohmeri or Yamadazyma ohmeri, belongs to the Saccharomycetaceae family and the Ascomycetae class, is the telomorphic form of C guilliermondii var. membranaefaciens and is frequently mistaken for Candida, as they belong to the same family. It has been isolated from environmental sources, such as sand, pools, seawater and fruits, while the last decades it is recognised as a rare pathogen that causes life-threatening infections in humans. The purpose of this study was to systemically review all published cases of K ohmeri infections in the literature and describe the epidemiology, microbiology, antimicrobial susceptibility, treatment and outcomes of these infections in humans. METHODS: Systematic review of PubMed (through 27th December 2019) for studies providing epidemiological, clinical, microbiological as well as treatment data and outcomes of K ohmeri infections. RESULTS: A total of 35 studies, containing data of 44 patients, were included in the analysis. The most common K ohmeri infections were those of the bloodstream, infective endocarditis and onychomycosis. Previous antibiotic use, presence of a central venous catheter, parenteral nutrition and cancer were very common among patients. Mortality was high in the case of fungemias but low for other types of infections. Amphotericin B and fluconazole are the most common agents used for treatment, even though alarming MICs for fluconazole were noted. CONCLUSIONS: This systematic review thoroughly describes infections by K ohmeri and provides information on their epidemiology, clinical presentation, microbiology, antibiotic resistance patterns, treatment and outcomes.

Molecular identification and antifungal susceptibility of yeast isolates causing fungemia collected in a population-based study in Spain in 2010 and 2011.

We report the molecular identifications and antifungal susceptibilities of the isolates causing fungemia collected in the CANDIPOP population-based study conducted in 29 Spanish hospitals. A total of 781 isolates (from 767 patients, 14 of them having mixed fungemia) were collected. The species found most frequently were Candida albicans (44.6%), Candida parapsilosis (24.5%), Candida glabrata (13.2%), Candida tropicalis (7.6%), Candida krusei (1.9%), Candida guilliermondii (1.7%), and Candida lusitaniae (1.3%). Other Candida and non-Candida species accounted for approximately 5% of the isolates. The presence of cryptic species was low. Compared to findings of previous studies conducted in Spain, the frequency of C. glabrata has increased. Antifungal susceptibility testing was performed by using EUCAST and CLSI M27-A3 reference procedures; the two methods were comparable. The rate of fluconazole-susceptible isolates was 80%, which appears to be a decrease compared to findings of previous studies, explained mainly by the higher frequency of C. glabrata. Using the species-specific breakpoints and epidemiological cutoff values, the rate of voriconazole and posaconazole in vitro resistance was low (<2%). In the case of C. tropicalis, using the EUCAST procedure, the rate of azole resistance was around 20%. There was a correlation between the previous use of azoles and the presence of fluconazole-resistant isolates. Resistance to echinocandins was very rare (2%), and resistance to amphotericin B also was very uncommon. The sequencing of the hot spot (HS) regions from FKS1 or FKS2 genes in echinocandin-resistant isolates revealed previously described point mutations. The decrease in the susceptibility to fluconazole in Spanish isolates should be closely monitored in future studies.

Ethanol lock therapy to reduce the incidence of catheter-related bloodstream infections in home parenteral nutrition patients with intestinal failure: preliminary experience.

BACKGROUND: Catheter-related bloodstream infections (CRBSI) cause morbidity and mortality in patients with intestinal failure dependent on parenteral nutrition. Ethanol lock of central venous catheters may decrease CRBSI, but limited pediatric data are available. METHODS: Home parenteral nutrition patients with at least one previous CRBSI were initiated on a 70% ethanol lock protocol for a minimum of 4 hours. Infection rates (per 1000 catheter days) before and after initiation of ethanol locks were compared using a paired t test. RESULTS: Ten patients (4 girls; median age, 44 months [range, 31-129 months]) began ethanol lock therapy after a total of 91 CRBSIs (37 gram-positive, 30 gram-negative, and 24 fungal) with a mean of 10.2 ± 6.2 per 1000 catheter days. Patients received ethanol lock for an average of 227 ± 64 days with only 3 CRBSI occurring (CRBSI rate of 0.9 ± 1.8 per 1000 catheter days [P = .005]). Central venous catheter replacements decreased from 5.6 per 1000 days to 0.3 per 1000 days posttherapy (P = .038). Ethanol lock was discontinued in 2 of 10 patients because of catheter thrombosis. CONCLUSION: Preliminary results demonstrate a significant decrease in CRBSI with a 70% ethanol lock protocol. Catheter thrombosis may be a limitation that needs to be addressed. With such a dramatic therapeutic effect, a randomized trial is feasible and should be performed.

[Changes in the epidemiology of fungaemia and fluconazole susceptibility of blood isolates during the last 10 years in Spain: results from the FUNGEMYCA study]. / Variación de la epidemiología de las fungemias y de la sensibilidad al fluconazol de los aislamientos de hemocultivos en los últimos 10 años en España: resultados del estudio FUNGEMYCA.

BACKGROUND: Recent epidemiological surveillance studies have reported an increase in fungaemia caused by non-Candida albicans species, as well as a decrease in fluconazole susceptibility. OBJECTIVES: To evaluate changes in the epidemiology of fungaemia in Spain comparing data from a new surveillance epidemiological study conducted in 2009 with a previous study carried out from 1997 to 1999 (Pemán J, et al. Eur J Clin Microbiol Infect Dis. 2005). METHODS: From January 2009 to February 2010, 44 Spanish hospitals participated in a prospective multicentre fungaemia surveillance study to ascertain whether there have been changes in the epidemiology and fluconazole susceptibility. Susceptibility was determined by the colorimetric method Sensititre Yeast One. Demographic and clinical data and the first isolate of each episode were gathered. RESULTS: A total of 1,377 isolates from 1,357 fungaemia episodes were collected, 46.7% from patients older than 64years and 8.6% from children less than 1 year old. C. albicans (44.7%), Candida parapsilosis (29.1%), Candida glabrata (11.5%), Candida tropicalis (8.2%), and Candida krusei (1.9%) were the most frequent species isolated. Distribution varied with the geographical area. C. albicans incidence has increased significantly in the last 10years in Cataluña (39.1 vs. 54.7%, P=0.03) and decreased in the Valencian Community (49.1 vs. 34.6%, P=0.002) and Extremadura (58.3 vs. 20%, P=0.01). Susceptibility to fluconazole was similar for all geographical areas, although resistance in C. albicans was ten times greater for patients aged more than 64years. The overall rate of fluconazole resistance (MIC > 32 mg/L) has decreased with respect to that obtained 10years ago (3.7 vs. 2.5%) mainly in C. albicans (3 vs. 1.6%). CONCLUSIONS: In the last ten years, species distribution and fluconazole susceptibility have not significantly changed, although a lower rate of fluconazole resistance has been observed. Species distribution varies with hospital, hospitalization Unit and geographical area.

Invasive candidiasis in the intensive care unit.

Invasive fungal disease by Candida spp. is on the rise in the modem era of prolonged patient survival by virtue of improved critical care measures, novel chemotherapy regimens, and increasing immunosuppression following organ transplants. Invasive candidiasis (IC) in the setting of an intensive care unit results in prolonged hospital stay and increased morbidity. Clinical suspicion plays a major role in the diagnosis of IC, as current laboratory methods are not very sensitive. Various serum markers and molecular techniques are under development to improve diagnostic strategies. Treatment options involve an expanding spectrum of antifungals. Knowledge of local epidemiology and the risk factors that predispose patients to this disease are essential for effective patient care in an intensive care setting.

Antibiotic use and impact on outcome from bacteraemic critical illness: the BActeraemia Study in Intensive Care (BASIC).

BACKGROUND: The lack of prospective, randomized, controlled trial data to guide optimal antibiotic use in bacteraemic critically ill patients has led to a wide variety of strategies and major issues with drug resistance. We therefore prospectively investigated the epidemiology of bacteraemia and fungaemia in intensive care units (ICUs); and the impact of timing, type and appropriateness of antibiotic intervention. METHODS: We conducted a multinational, multicentre, prospective observational study in 132 ICUs from 26 countries with no interventions. RESULTS: 1702 patients [European (69.6%), Australasian (12.2%), South American (8.3%) and Asian (9.9%)] developed 1942 bacteraemic episodes over the study period. Mortality rates were similar for those receiving empirical (40.5%), semi-targeted (37.6%) or fully targeted (33.3%) antibiotic therapy (P=0.40), and in those initially receiving broad- (39.3%) or restricted-spectrum (39.1%) therapy (P=0.94). First-line therapy was effective in terms of the antibiogram (where available) in 70.4% of cases. This in vitro susceptibility ranged from 76.3% for broad-spectrum antibiotics to 46.3% for restricted-spectrum antibiotics (P<0.0001). However, no antibiotic policy-associated variable, including in vitro susceptibility (odds ratio 0.89, 95% confidence interval 0.61-1.30), was a statistically significant predictor of mortality. CONCLUSIONS: We could not show an impact of antibiotics on mortality in critically ill patients, despite in vitro activity and early commencement. Randomized, multicentre trials are urgently needed to establish the appropriate duration, timing and combinations of antibiotics that will both optimally treat infection and minimize development of resistance and other complications.

[Risk factors associated with colonization by Candida spp in neonates hospitalized in a Neonatal Intensive Care Unit in Brazil]. / Fatores de risco associados à colonização por Candida spp em neonatos internados em uma Unidade de Terapia Intensiva Neonatal brasileira.

The objectives of this study were to investigate the participation of Candida albicans and non-albicans as colonization and sepsis agents, along with the risk factors associated with the neonates in the neonatal intensive care unit of the clinical hospital of the Federal University of Uberlândia. Epidemiological surveillance was implemented through the National Healthcare Safety Network between August 2007 and April 2008. The incidence rate for sepsis with microbiological criteria was 6.7/1,000 patients/day, which was shown as only one case of candidemia. Approximately 19% of the neonates were colonized by Candida, which was identified as Candida albicans (50%) and Candida not-albicans (50%). The significant risk factors for Candida spp colonization were gestational age of between 26 and 30 weeks, previous antibiotic use and umbilical central vascular catheter. The overall mortality among the neonates hospitalized with sepsis over the study period was 11.8%. However, the neonate with candidemia did not die.

Fatores de risco associados à colonização por Candida spp em neonatos internados em uma Unidade de Terapia Intensiva Neonatal brasileira / Risk factors associated with colonization by Candida spp in neonates hospitalized in a Neonatal Intensive Care Unit in Brazil

Os objetivos desse estudo foram investigar a participação de Candida albicans e não-albicans como agente de colonização e sepse, bem como os fatores de risco associados aos neonatos internados na Unidade de Terapia Intensiva Neonatal do Hospital de Clínicas da Universidade Federal de Uberlândia. Foi realizada vigilância epidemiológica pelo sistema National Healthcare Safety Network no período entre agosto de 2007 e abril de 2008. A taxa de incidência de sepse com critério microbiológico foi de 6,7/1.000 paciente/dia, constatando-se apenas um caso de candidemia. Aproximadamente, 19 por cento dos neonatos estavam colonizados por Candida, identificadas como Candida albicans (50 por cento) e Candida não-albicans (50 por cento). Os fatores de risco significantes para colonização por Candida spp foram a idade gestacional entre 26 e 30 semanas, o uso prévio de antibiótico e o cateter vascular central umbilical. A mortalidade total foi de 11,8 por cento nos neonatos internados durante o período de estudo com sepse, porém o recém-nascido com candidemia não evoluiu para óbito.

The objectives of this study were to investigate the participation of Candida albicans and non-albicans as colonization and sepsis agents, along with the risk factors associated with the neonates in the neonatal intensive care unit of the clinical hospital of the Federal University of Uberlândia. Epidemiological surveillance was implemented through the National Healthcare Safety Network between August 2007 and April 2008. The incidence rate for sepsis with microbiological criteria was 6.7/1,000 patients/day, which was shown as only one case of candidemia. Approximately 19 percent of the neonates were colonized by Candida, which was identified as Candida albicans (50 percent) and Candida not-albicans (50 percent). The significant risk factors for Candida spp colonization were gestational age of between 26 and 30 weeks, previous antibiotic use and umbilical central vascular catheter. The overall mortality among the neonates hospitalized with sepsis over the study period was 11.8 percent. However, the neonate with candidemia did not die.

Epidemiology of candidemia at a Children's hospital, 2002 to 2006.

BACKGROUND: There are few recent studies evaluating trends in the epidemiology of candidemia including changes in species or utilization of antifungal agents in children. METHODS: We performed a retrospective case series of candidemia at our children's hospital from 2002 to 2006. Our objectives were to study trends in the rates of candidemia, demographic characteristics, Candida species, antifungal susceptibility, and antifungal utilization. These data were obtained from the electronic medical records. RESULTS: There were 203 episodes of candidemia in 154 subjects. During the study period, the average rate of candidemia was 5.52 per 1000 patient-discharges and did not change throughout the study. The mean and median ages of subjects were 3 years versus 9 months, respectively, and 38% were less than 3 months of age. Gastrointestinal disorders were a common comorbid condition (33%), especially for subjects with multiple episodes of candidemia. Overall, Candida parapsilosis and Candida albicans caused 43% and 26% of episodes, respectively, and candidemia caused by Candida glabrata (5.3%-23%) and Candida krusei (0%-8.5%) increased during the study. Ninety-eight percent of C. albicans and C. parapsilosis isolates remained susceptible to all antifungal drugs. From 2003-2006, the use of antifungal agents increased from 79 days to 150 days per 1000 hospital-days. CONCLUSIONS: While antifungal use at our hospital increased, candidemia rates remained stable. C. parapsilosis was the most common species but other non-C. albicans species increased during the study period. Local epidemiology should be monitored in pediatric populations for potential impact on management strategies.

Fungaemia caused by Candida glabrata with reduced susceptibility to fluconazole due to altered gene expression: risk factors, antifungal treatment and outcome.

BACKGROUND: The role of Candida glabrata in fungaemia is attributed in part to its reduced susceptibility to azoles, usually due to altered expression of genes encoding drug efflux pumps. The aims of this study were to identify risk factors for fungaemia due to C. glabrata isolates with decreased susceptibility to fluconazole and to analyse the response to antifungal treatment and the clinical outcome of C. glabrata infections in hospitalized patients. METHODS: A retrospective case-case-control study was conducted at a university hospital from 2000 to 2006. Three patient groups were studied: 14 patients infected by a fluconazole-less-susceptible isolate [susceptible-dose-dependent (SDD) or resistant]; 21 patients infected by a fluconazole-susceptible (FS) isolate; and 70 uninfected controls. We measured expression of the drug efflux pump-encoding CgCDR1 and CgCDR2 genes in isolates of the two infected groups using quantitative real-time PCR. RESULTS: Multivariable analysis found that patients with prior fluconazole use [odds ratio (OR) 12.24, 95% confidence intervals (CIs) 1.77-84.39, P = 0.01], diabetes (OR 10.47, 95% CI 1.96-55.96, P = 0.006) and a central venous catheter (CVC) (OR 8.48, 95% CI 1.82-39.36, P = 0.006) were more likely to develop fungaemia due to a less-susceptible isolate. Previous surgery (OR 7.73, 95% CI 2.18-27.41, P = 0.002) was an independent risk factor for fungaemia due to a susceptible isolate, in addition to the presence of a CVC (OR 5.48, 95% CI 1.69-17.72, P = 0.004). The crude 30 day mortality rate was high for both case groups. Seven patients received inadequate antifungal treatment, including five infected by a fluconazole-resistant isolate but empirically treated with fluconazole; six of these seven patients died. Expression of the CgCDR genes was up-regulated in all fluconazole-resistant and, to a lesser extent, SDD isolates, but not in the FS isolates. CONCLUSIONS: Our data suggest that when candidaemia is suspected or detected, a more broad-spectrum antifungal drug (i.e. echinocandins or amphotericin B) should be considered as initial treatment for patients with prior azole exposure.

Increasing incidence of Candida parapsilosis candidemia with caspofungin usage.

OBJECTIVES: To determine the impact on the change in epidemiology of Candida species at our institution since the introduction of caspofungin. METHODS: A 5-year retrospective review of all candidemia at a major tertiary care center. Only one episode of candidemia per patient per admission was counted. All antifungal defined daily doses were also collected in this same time period. Regression analysis was performed on the data and correlation statistics among antifungal use and Candida species were assessed using a Pearson correlation analysis. RESULTS: There were 469 individual episodes of candidemia between fiscal year 2002 and 2006 with the rate increasing every year. On regression analysis there was a significant increase in Candida parapsilosis candidemia (R(2)=0.90, p=0.02) and significant increase in caspofungin usage (R(2)=0.80, p<0.01), with a correspondingly significant decline in conventional (R(2)=-0.77, p<0.01) and lipid amphotericin B (R(2)=-0.95, p<0.05) usage. We found correlations between increased caspofungin usage (R(2)=0.94, p=0.017) and increased C. parapsilosis candidemia and decreased Candida tropicalis candidemia (R(2)=0.92, p<0.05) and a trend towards decreased Candida glabrata (R(2)=0.64, p=0.1). CONCLUSIONS: We showed significant correlations between increased caspofungin usage and an increased incidence of C. parapsilosis candidemia and reduction in C. tropicalis candidemia, with a trend towards less C. glabrata candidemia.

[Potential of anidulafungin in hematological patients]. / Potencial de anidulafungina en el paciente hematológico.

Until relatively recently, the treatment available for invasive fungal infections in hematological patients consisted of amphotericin B and azoles. Each of these groups had limitations and secondary effects. The echinocandins are a new class of antifungal agent that has shown promising results in the treatment of numerous invasive fungal infections. Anidulafungin is a new echinocandin that, in addition to showing potent in vitro activity against Aspergillus spp. and Candida spp. (including fluconazole- and amphotericin B-resistant microorganisms), also provides some advantages over other candins. In humans, these drugs are degraded through biotransformation rather than a metabolic process. No drug interactions have been found. In hematological patients, anidulafungin would play a "potential" role as empirical therapy in febrile neutropenia, as is the case of caspofungin. Given the epidemiology of Candida infection in these patients, anidulafungin could be used as initial therapy in candidemia before starting treatment with oral flucozanole, if indicated by the fungigram. This drug would also be indicated in the treatment of invasive Aspergillus spp. infections in patients with hepatic or renal insufficiency or in those taking concomitant medications. The available in vitro studies also suggest an important role for this drug in combinations of antifungal agents. Given the excellent safety profile and absence of interactions of anidulafungin, this drug will undoubtedly be of great utility in the management of difficult-to-treat mycotic infections in hematological patients.

Fungemia at a tertiary care hospital: incidence, therapy, and distribution and antifungal susceptibility of causative species.

The aim of this study was to review fungal bloodstream infections at a large tertiary care hospital to evaluate the incidence of fungemia and the distribution of causative species during the period 2001-2005. Another aim was to assess the extent of antifungal resistance. A review of all episodes of fungemia at the University Hospitals of Leuven (Belgium) was conducted between January 2001 and December 2005. For the first yeast isolate collected from each non-mould fungemic episode during a 1-year period (June 2004-June 2005), susceptibility to seven antifungal agents was determined using Sensititre YeastOne plates (Trek Diagnostic Systems, East Grinstead, UK), and the antifungal therapy was reviewed. The annual incidence of fungemia ranged between 1.30 and 1.68 episodes per 10,000 patient-days (on a total of 2,680,932 patient-days), with a decreasing trend observed over the 5-year study period. The most common species were Candida albicans (59%), Candida glabrata (22%), Candida parapsilosis (10%), and Candida tropicalis (4%). Overall, fluconazole resistance was rare (1.6%) and was detected only in C. glabrata and C. krusei. Voriconazole and caspofungin inhibited 100% of the isolates at a concentration of

Biofilm production by Candida species and inadequate antifungal therapy as predictors of mortality for patients with candidemia.

Nosocomial Candida bloodstream infections rank among infections with highest mortality rates. A retrospective cohort analysis was conducted at Catholic University Hospital to estimate the risk factors for mortality of patients with candidemia. We reviewed records for patients with a Candida bloodstream infection over a 5-year period (January 2000 through December 2004). Two hundred ninety-four patients (42.1% male; mean age +/- standard deviation, 65 +/- 12 years) were studied. Patients most commonly were admitted with a surgical diagnosis (162 patients [55.1%]), had a central venous catheter (213 [72.4%]), cancer (118 [40.1%]), or diabetes (58 [19.7%]). One hundred fifty-four (52.3%) patients died within 30 days. Of 294 patients, 168 (57.1%) were infected by Candida albicans, 64 (21.7%) by Candida parapsilosis, 28 (9.5%) by Candida tropicalis, and 26 (8.8%) by Candida glabrata. When fungal isolates were tested for biofilm formation capacity, biofilm production was most commonly observed for isolates of C. tropicalis (20 of 28 patients [71.4%]), followed by C. glabrata (6 of 26 [23.1%]), C. albicans (38 of 168 [22.6%]), and C. parapsilosis (14 of 64 [21.8%]). Multivariable analysis identified inadequate antifungal therapy (odds ratio [OR], 2.35; 95% confidence interval [95% CI], 1.09 to 5.10; P = 0.03), infection with overall biofilm-forming Candida species (OR, 2.33; 95% CI, 1.26 to 4.30; P = 0.007), and Acute Physiology and Chronic Health Evaluation III scores (OR, 1.03; 95% CI, 1.01 to 1.15; P < 0.001) as independent predictors of mortality. Notably, if mortality was analyzed according to the different biofilm-forming Candida species studied, only infections caused by C. albicans (P < 0.001) and C. parapsilosis (P = 0.003) correlated with increased mortality. Together with well-established factors, Candida biofilm production was therefore shown to be associated with greater mortality of patients with candidemia, probably by preventing complete organism eradication from the blood.

Microorganisms Isolated from Blood Cultures and Their Antimicrobial Susceptibility Patterns At a University Hospital During 1994-2003 / 대한진단검사의학회지

BACKGROUND: Blood culture is important for the determination of the etiologic agent of bacteremia. Analysis of blood culture results and antimicrobial susceptibility trend can provide clinicians with relevant information for the empirical treatment of patients. METHODS: The species and antimicrobial susceptibility of the isolates from blood cultures at the Severance Hospital during 1994-2003 were analysed. Blood specimens were cultured for 7 days using tryptic soy broth and thioglycollate medium. Identification of organism was based on conventional methods or commercial kit systems. Antimicrobial susceptibility was tested by a disk diffusion method. RESULTS: Of 536,916 blood specimens cultured, 24,877 (4.6%) from 13,102 patients were positive. Among the isolates, 93.1% were aerobic or facultative anaerobic bacteria, 3.3% anaerobes, and 3.6% fungi. Escherichia coli was isolated most frequently, followed by Staphylococcus aureus, -hemolytic Streptococcus, Enterococcus spp., and Klebsiella pneumoniae. The proportion of patients with Enterococcus faecium and K. pneumoniae gradually increased during this study. Enterococcus, S. aureus and alpha-hemolytic Streptococcus were frequently isolated from the age group of less than 2 yr. E. coli, Enterococcus spp., K. pneumoniae and S. aureus from the age group of over 50 yr. Oxacillin-resistant S. aureus decreased, whereas vancomycin-resistant E. faecium and imipenemresistant Pseudomonas aeruginosa and Acinetobacter baumannii increased. CONCLUSIONS: E. coli was the most common cause of bacteremia and S. aureus, -hemolytic Streptococcus, and K. pneumoniae were frequently isolated pathogens. The bacteremia due to Enterococcus, K. pneumoniae, fungi, vancomycin-resistant E. faecium, and imipenem-resistant P. aeruginosa and A. baumannii gradually increased during this period.

Trends in fungaemia and antifungal susceptibility in the Netherlands.

We retrospectively evaluated fungaemia over the period 1996 to 2001 in five university hospitals. Over 350,000 blood cultures were collected during more than 7 million days of hospitalisation. The average rate of fungaemia over the six-year period was 0.82 per 10,000 patient days (range 0.65 to 1.21 per 10,000 patient days). The proportion of bloodstream infections caused by Candida albicans remained stable throughout the study period with a mean of 53% (range 48 to 62%). This is a change from trends described in previous studies, including a survey performed in the Netherlands. This study shows a new, stable rate of fungaemia and no further signs of increasing rate of infections due to non-albicans Candida species. Susceptibility to all tested antifungal agents remained stable throughout the study period.

Neonatal candidiasis: analysis of epidemiology, drug susceptibility, and molecular typing of causative isolates.

A prospective observational study of invasive candidiasis was conducted in the neonatal intensive care unit of Aristotle University in Hippokration Hospital between 1994 and 2000. During this period, 59 neonates developed invasive candidiasis (58 cases of candidemia and 1 case of peritonitis), resulting in an overall incidence of 1.28% that showed a decreasing trend over the study period. Eleven (18.6%) cases developed within the first week of life and the others within a mean (+/-SEM) of 13.4+/-1.7 days after birth. The three most frequent causative species were Candida albicans (65.5%), Candida parapsilosis (15.5%), and Candida tropicalis (7%). C. albicans was the predominant species between 1994 and 1998, whereas, non-albicans Candida spp., particularly C. parapsilosis, were the most frequent species during the period 1999-2000 (P<0.001). While the overall mortality due to candidemia was 29% (17 of 59 cases), mortality associated with C. albicans and C. parapsilosis was 39.5% and 11.1%, respectively (P=0.032), and that observed in the 1999-2000 period was 0% (P=0.011). Virtually all isolates were susceptible to amphotericin B, flucytosine, fluconazole, and itraconazole, and no increases in minimal inhibitory concentrations were observed during these years. With the exception of a limited cluster of cases due to genotypically identical isolates, no clonal relation of C. albicans isolates was found. Moreover, no clonal persistence of C. albicans and no decrease in antifungal drug susceptibility occurred over the 6-year study period. Non-albicans Candida spp., mostly C. parapsilosis, have emerged as important pathogens in neonatal intensive care units, with infected patients having better outcomes as compared to patients infected with C. albicans.

Outbreak of Candida rugosa candidemia: an emerging pathogen that may be refractory to amphotericin B therapy.

Candida rugosa has been rarely reported as a human pathogen. We retrospectively evaluated a cluster of Candida rugosa candidemia cases occurring in six hospitalized patients from a tertiary care teaching hospital in São Paulo, Brazil. Genetic relatedness among the six C. rugosa outbreak isolates was characterized by RAPD assay using 3 different 10-mer primers and by pulsed field gel electrophoresis. The source of the outbreak was not identified. All patients had been subjected to invasive medical procedures, including central venous catheterization, surgery or dialysis. Two patients were undergoing amphotericin B therapy prior to the onset of candidemia. The crude mortality rate was very high, despite antifungal therapy. C. rugosa may represent an emerging pathogen associated with invasive medical procedures, able to infect immunocompetent hosts causing serious systemic infection refractory to amphotericin B therapy.

Hematogenous infections due to Candida parapsilosis: changing trends in fungemic patients at a comprehensive cancer center during the last four decades.

This study was performed to evaluate trends in species distribution in patients' with hematogenous candidiasis at a comprehensive cancer center. The results of a retrospective analysis from January 1, 1993 to December 31, 1998 were compared with prior reports from Memorial Sloan-Kettering Cancer Center in the last forty years. In 570 total episodes since 1974, 43.9% were due to Candida albicans. During 1990's, C. parapsilosis emerged as the most frequent yeast species in the non-C. albicans group (36.1% during 1993-1998 from 20.9% 1974-1982; p < 0.01). An increase in C. krusei from 5.9% (1974-1982) to 10.5% during the recent six years (1993-1998) was also noticed. The proportion of C. tropicalis among non-albicans fungemia during 1974-1982 was 42.8%, whereas in 1993 to 1998 a marked decline in C. tropicalis hematogenous infection was observed (27.8%; p < 0.01). During 1998, the incidence of candidemia declined from 7.1% (1972-1973) and 6.5% (1982) to 3.4% (p < 0.01), and improved survival among fungemic patients (33% mortality in 1998; 77.3% during 1974-1982; p < 0.001) was encouraging. The increase in C. parapsilosis bloodstream invasion during 1990's was associated with a significant reduction in the endogenous non-albicans Candida tropicalis infection that probably resulted in part due to the common prophylaxis, and/or preemptive fluconazole given routinely in high-risk patients undergoing treatment for cancer. The widespread use of extraneous implantable and/or semi-implantable indwelling intra-vascular devices may also have played an important role in promoting (exogenous) C. parapsilosis infection. This study emphasizes the importance of periodic evaluation of candidemia, especially at centers caring for patients at risk.