Current concepts in the prevention of pathogen transmission via blood/plasma-derived products for bleeding disorders.

The pathogen safety of blood/plasma-derived products has historically been a subject of significant concern to the medical community. Measures such as donor selection and blood screening have contributed to increase the safety of these products, but pathogen transmission does still occur. Reasons for this include lack of sensitivity/specificity of current screening methods, lack of reliable screening tests for some pathogens (e.g. prions) and the fact that many potentially harmful infectious agents are not routinely screened for. Methods for the purification/inactivation of blood/plasma-derived products have been developed in order to further reduce the residual risk, but low concentrations of pathogens do not necessarily imply a low level of risk for the patient and so the overall challenge of minimising risk remains. This review aims to discuss the variable level of pathogenic risk and describes the current screening methods used to prevent/detect the presence of pathogens in blood/plasma-derived products.

Validation of sterility testing of cord blood: challenges and results.

BACKGROUND: Sterility testing for cord blood (CB) products is mandatory to prevent transplantation-transmitted microbial infections. Here, the automated BacT/ALERT (bioMérieux) culture system was validated to detect microbial contamination in CB units processed at the Canadian National Public Cord Blood Bank. STUDY DESIGN AND METHODS: A three-phase validation was developed. CB units were prepared with pentastarch (Phases 1 and 2) or hetastarch (Phase 3). In Phase 1, CB was spiked with approximately 100 colony-forming units/mL of Pseudomonas aeruginosa, Klebsiella pneumoniae, Staphylococcus aureus, Staphylococcus epidermidis, Bacteroides fragilis, and Candida albicans. Plasma (8 mL) and buffy coat (BC; 0.5 and 8 mL) were inoculated into culture bottles. In Phases 2 and 3, a mix of red blood cells (RBCs) and plasma (4 mL each) was used as the inoculant. In Phase 3, Aspergillus brasiliensis was added as a test organism and microbial concentrations in the by-product RBCs and plasma were determined. The BC fractions were cryopreserved and tested 3 months later. RESULTS: In Phase 1, bacteria failed to grow in CB units containing antibiotics. Thus, antibiotic-free units were used for the other phases. C. albicans was not always captured in plasma, but using a mix of RBCs and plasma, all organisms were detected. The use of pentastarch or hetastarch did not affect microbial recovery. C. albicans and A. brasiliensis were preferentially recovered in RBCs and BC. Cryopreservation did not affect microbial survival during CB processing. CONCLUSIONS: A mix of plasma and RBCs is appropriate for CB sterility testing. Interestingly, fungi preferentially segregate to cellular fractions. The clinical significance of the bactericidal /or bacteriostatic effect of antibiotics in CB merits further investigation.

[Invasive fungal infection in solid organ transplant]. / Infección fúngica invasora en el trasplante de órgano sólido.

Invasive fungal infections (IFI) represent a serious threat for patients undergoing solid organ transplantation (SOT). IFI in SOT has a significant incidence and mortality not due to negligence. The management of IFI in SOT involves specific recommendations and has been individualized to the type of transplant and patient. The current review presents an overview of epidemiology, diagnosis, treatment and prevention of IFI in TOS. Depending on risk factors for different IFIs and transplant type, this paper includes the main recommendations based on previous publications and on the opinion of the authors on the prophylaxis and treatment of these patients. These recommendations highlight epidemiology changes and the emergence of new antifungals. The current document has focused mainly on Candidaspp. and Aspergillusspp., with a special mention to the rest of yeasts and moulds that are common in SOT.

Nosocomial transmission of Candida pelliculosa fungemia in a pediatric intensive care unit and review of the literature.

Horizontal transmission of Candida species in the hospital environment and the fungemia rates have increased in the past decade. We describe a nosocomial cluster of fungemia caused by Candida pelliculosa (teleomorph Pichia anomala) in four infants hospitalized in the pediatric intensive care unit. Candida isolates had strictly related fingerprints, as generated by randomly amplified polymorphic DNA analysis using five different primer sets. The four babies were all treated successfully and recovered. All of the isolates were susceptible to the antifungals tested including amphotericin B, flucytosine, fluconazole, miconazole, micafungin, itraconazole, and voriconazole. Infection control procedures were adapted in the unit and no relapse was detected. In addition, 30 publications presenting 450 pediatric and 28 adult cases are reviewed.

Candida parapsilosis fungemia in neonates: genotyping results suggest healthcare workers hands as source, and review of published studies.

An outbreak of Candida parapsilosis fungemia involving 17 neonatal intensive care unit (NICU) patients was studied. There were 14 blood culture and nine colonizing isolates from other sites available. The hands of NICU healthcare workers (HCW) yielded eight isolates. Screening of the isolates by random amplified polymorphic DNA (RAPD) method showed only three profiles. Typing by restriction fragment length polymorphism (RFLP) revealed all blood isolates were RFLP subtype VII-1. Among the nine infant colonizing isolates, there were four different RFLP subtypes; four of the isolates were subtype VII-1. Seven of the eight isolates from HCW were RFLP subtype VII-1. The majority of infant colonizers were not found in the blood, suggesting a possible direct spread of the epidemic subtype VII-1 strain from HCW hands to infant blood. The source of the infant colonizing strains is unclear, but non-VII-1 strains may be largely of maternal origin and VII-1 strains from HCW. These findings reinforce prior studies that have implicated HCW hands as the source of nosocomial, including neonatal, fungemia.

Kodamaea (Pichia) ohmeri fungaemia in a premature neonate.

Kodamaea ohmeri is a yeast that rarely causes human infections. The first case of K. ohmeri fungaemia in a premature neonate is reported; it was successfully treated with liposomal amphotericin B. Biochemical identification of the yeast was performed by Vitek II and API and was confirmed by rRNA gene sequencing. K. ohmeri as a human pathogenic yeast is uncommon to hospitalized neonates and immunocompromised individuals.

Secular trends of candidemia in a large tertiary-care hospital from 1988 to 2000: emergence of Candida parapsilosis.

OBJECTIVE: To analyze the secular trends of candidemia in a large tertiary-care hospital to determine the overall incidence, as well as the incidence by ward and by species, and to detect the occurrence of outbreaks. DESIGN: Retrospective descriptive analysis. Secular trends were calculated using the Mantel-Haenszel test. SETTING: A large tertiary-care referral center in Spain with a pediatric intensive care unit (ICU) to which more than 500 children with congenital cardiac disease are admitted annually. PATIENTS: All patients with candidemia occurring from 1988 to 2000 were included. Cases were identified from laboratory records of blood cultures. RESULTS: There were 331 episodes of candidemia. The overall incidence of nosocomial candidemia was 0.6 episode per 1,000 admissions and remained stable throughout the study period (P = .925). The species most frequently isolated was Candida albicans, but the incidence of C. parapsilosis candidemia increased (P = .035). In the pediatric ICU, the incidence of C. parapsilosis was 5.6 episodes per 1,000 admissions and it was the predominant species. Outbreaks occurred occasionally in the pediatric ICU, suggesting nosocomial transmission. CONCLUSIONS: During this 13-year period, the incidence of candidemia remained stable in this hospital, but C. parapsilosis increased in frequency. Occasional outbreaks of candidemia suggested nosocomial transmission of Candida species.

Differences in biofilm production by three genotypes of Candida parapsilosis from clinical sources.

Three distinct genotypes of Candida parapsilosis (group I, II, and III) have been identified among clinical isolates but their clinical significance remains unclear. We investigated the distribution of C. parapsilosis genotypes in isolates from blood, all other sites from patients, and the hands of health care workers (HCWs), and we examined the relationship between genotype and biofilm positivity. The 53 bloodstream isolates and 38 of 39 HCW isolates were categorized as group I, whereas the 67 non-blood isolates taken from patients were distributed in groups I (n=43), II (n=13), and III (n=11). Biofilm positivity was observed in 77% (103 of 134) of group I isolates versus 0% (0 of 25) of non-group I (groups II and III) isolates (P < 0.01). There was no difference in biofilm production among group I isolates from blood (81%), other clinical specimens (72%), and the hands of HCWs (73%). This study has shown that biofilm production differs among three genotypes of C. parapsilosis isolates and that a majority of C. parapsilosis isolates from the bloodstream (100%), the hands of HCWs (97%), and all other sites from patients (64%) belong to group I, which has the ability to produce biofilm.

[Infections by Candida sp. in intensive care. Survey of French practices]. / Infections à Candida sp en réanimation. Enquête sur les pratiques françaises.

OBJECTIVE: The isolation of Candida sp in nosocomial infections is on the increase and over the past 10 years many guidelines for "good" practices and recommendations have been published on the modalities for the management of systemic candidiasis. The aim of this paper was to assess the habits in the intensive care units in this domain in France. METHOD: A transversal survey on the habits was conducted from March to May 2001, using a questionnaire mailed to 200 intensive care units. RESULTS: One hundred eighty questionnaires (surgical reanimation: 12%, medical: 18%, medico-surgical: 70%) out of 200 (92.5%) were returned. The indirect diagnostic examinations: serology, search for antigenemia and PCR (Polymerase Chain Reaction) were never used in 21, 35 and 65% of cases. The systematic search for colonisation (a mean of 4 areas sampled) was conducted in all the patients by 19% of the investigators, in some patients by 53%, and never by 28%. An antifungal treatment was prescribed: in the presence of a positive haemoculture alone, once out of twice if the sample had been taken from a central catheter and in 2 cases out of 3 when the sample was peripheral. It was prescribed 6 times out of 10 after isolation of Candida sp following surgery or on needle aspiration of an intra-abdominal abscess, varyingly in the case of cadiduria, isolation of a Candida sp in a broncho-pulmonary sample or in abdominal draining and positive culture of a catheter, depending on the intensity of the colonisation, the severity of the clinical picture and the presence of factors of risk for Candida infection. It is still prescribed empirically depending on the same elements and the absence of explanation for worsening. When faced with candidemia in a non-neutropenic patient, a central catheter is not changed in 18% of cases. Depending on the microbiology, fluconazole is prescribed in: the identification of yeast without further precision (78% of cases), Candida sp without further precision (86% of cases), Candida non albicans without further precision (57% of cases), C. albicans (93% of cases), Candida non albicans other than C. krusei and C. glabrata (62% of cases), C. glabrata (36% of cases) with an increase in dose in 1 out of 2 cases. In the presence of C. glabrata or C. krusei, amphotericin B is the choice in respectively 51 and 75% of cases. To adapt the treatment.

Effects of nosocomial candidemia on outcomes of critically ill patients.

PURPOSE: To determine whether nosocomial candidemia is associated with increased mortality in intensive care unit (ICU) patients. SUBJECTS AND METHODS: We performed a retrospective (1992 to 2000) cohort study of 73 ICU patients with candidemia and 146 matched controls. Controls were matched based on disease severity as measured by the Acute Physiology and Chronic Health Evaluation (APACHE) II score (+/- 1 point), diagnostic category, and length of ICU stay before onset of candidemia. RESULTS: In comparison with the control group, patients with candidemia developed more acute respiratory failure (97% [n = 71] vs. 88% [n = 129], P = 0.03) during their ICU stay. They were mechanically ventilated for a longer period (29 +/- 26 days vs. 19 +/- 19 days, P<0.01) and had a longer stay in the ICU (36 +/- 33 days vs. 25 +/- 23 days, P = 0.02) as well as in the hospital (77 +/- 81 days vs. 64 +/- 69 days, P = 0.04). There was no difference in in-hospital mortality between the groups (48% [n = 35] vs. 43% [n = 62], P = 0.44), a difference of 5% (95% confidence interval [CI]: -8% to 19%). In a multivariate analysis, older age (hazard ratio [HR] = 1.13 per 10 years; 95% CI: 1.04 to 1.23; P = 0.004), acute renal failure (HR = 1.4; 95% CI: 1.1 to 2.0; P = 0.02), and unfavorable APACHE II scores (HR = 1.10 per 5 points; 95% CI: 1.00 to 1.20; P = 0.05) were independent predictors of mortality. Candidemia was not associated with mortality in a model that adjusted for these factors (HR = 0.9; 95% CI: 0.7 to 1.2; P = 0.53). CONCLUSION: Nosocomial candidemia does not adversely affect the outcome in ICU patients in whom mortality is attributable to age, the severity of underlying disease, and acute illness.

Horizontal transmission of Candida parapsilosis candidemia in a neonatal intensive care unit.

This report describes the nosocomial acquisition of Candida parapsilosis candidemia by one of the six premature newborns housed in the same room of a neonatal intensive care unit at the Ospedale Santa Chiara, Pisa, Italy. The infant had progeria, a disorder characterized by retarded physical development and progressive senile degeneration. The infant, who was not found to harbor C. parapsilosis at the time of his admission to the intensive care unit, had exhibited symptomatic conjunctivitis before the onset of a severe bloodstream infection. In order to evaluate the source of infection and the route of transmission, two independent molecular typing methods were used to determine the genetic relatedness among the isolates recovered from the newborn, the inanimate hospital environment, hospital personnel, topically and intravenously administered medicaments, and indwelling catheters. Among the isolates collected, only those recovered from the hands of two nurses attending the newborns and from both the conjunctiva and the blood of the infected infant were genetically indistinguishable. Since C. parapsilosis was never recovered from indwelling catheters or from any of the drugs administered to the newborn, we concluded that (i) horizontal transmission of C. parapsilosis occurred through direct interaction between nurses and the newborn and (ii) the conjunctiva was the site through which C. parapsilosis entered the bloodstream. This finding highlights the possibility that a previous C. parapsilosis colonization and/or infection of other body sites may be a predisposing condition for subsequent C. parapsilosis hematogenous dissemination in severely ill newborns.

Fungemia with Saccharomyces cerevisiae in two newborns, only one of whom had been treated with ultra-levura.

Ultra-Levura (Upsamedica, Spain) is a yeast (Saccharomyces boulardii) widely used as a biotherapeutic agent. To date, few adverse effects have been reported, although fungemia with Saccharomyces cerevisiae can occur in weak and immunosuppressed patients. Reported here are two cases of fungemia with Saccharomyces cerevisiae. One patient had been treated with Ultra-Levura and the other contracted the infection from the first. This is the first report of infection with Saccharomyces boulardii (Saccharomyces cerevisiae) in a patient who was not being treated with the agent.

National epidemiology of mycoses survey (NEMIS): variations in rates of bloodstream infections due to Candida species in seven surgical intensive care units and six neonatal intensive care units.

Candida species are the fourth most frequent cause of nosocomial bloodstream infections, and 25%-50% occur in critical care units. During an 18-month prospective study period, all patients admitted for > or = 72 hours to the surgical (SICUs) or neonatal intensive care units (NICUs) at each of the participant institutions were followed daily. Among 4,276 patients admitted to the seven SICUs in six centers, there were 42 nosocomial bloodstream infections due to Candida species (9.8/1,000 admissions; 0.99/1,000 patient-days). Of 2,847 babies admitted to the six NICUs, 35 acquired a nosocomial bloodstream infection due to Candida species (12.3/1,000 admissions; 0.64/1,000 patient-days). The following were the most commonly isolated Candida species causing bloodstream infections in the SICU: Candida albicans, 48%; Candida glabrata, 24%; Candida tropicalis, 19%; Candida parapsilosis, 7%; Candida species not otherwise specified, 2%. In the NICU the distribution was as follows: C. albicans, 63%; C. glabrata, 6%; C. parapsilosis, 29%; other, 3%. Of the patients, 30%-50% developed incidental stool colonization, 23% of SICU patients developed incidental urine colonization, and one-third of SICU health care workers' hands were positive for Candida species.

Outbreak of Candida parapsilosis fungemia in neonatal intensive care units: clinical implications and genotyping analysis.

During a 5-month period, 17 infants hospitalized in neonatal intensive care units of a medical center and a branch hospital developed 18 episodes of Candida parapsilosis fungemia. The mean age at onset was 35 days. Prior to fungemia, all the infants had received hyperalimentation and antibiotics, and 15 infants had had central venous catheters. The presenting symptoms were variable but only vague in 40% of the episodes. Despite administration of antifungal agents, subsequent eradication of fungemia was achieved in only two-thirds of the episodes. None of the environmental samples was positive for C. parapsilosis, while 20% of hand-washing samples of staff working in both units yielded this microorganism. Four genotypes with two main types were identified from 14 outbreak strains and eight genotypes from 14 hand-washing strains, with one type predominant. The results suggest that C. parapsilosis fungemia increases the morbidity and mortality of neonates but does not cause acute lethal events. The outbreak was caused by two main genotypes, possibly via cross-infection by the hands of health care workers.

Perinatal candidiasis and transient maternal candidemia: report of one case.

A premature infant who contracted candida pneumonia and candidemia early in the postnatal period was reported. Fungal hyphae was found in the pus-like gastric aspirate soon after birth, giving the first clue to the diagnosis and prompting an early institution of antifungal therapy. Maternal candidemia was documented in the immediate postpartum period, which resolved spontaneously without specific antifungal treatment.

Nosocomial candidemia: risk factors and attributable mortality.

Over the past decade, the incidence of hospital-acquired bloodstream infections caused by Candida species has risen and the species associated with such infections have changed. The incidence of candidemia is dramatically higher in high-risk, critical-care units than in other parts of the hospital. Certain underlying physical conditions including acute leukemia, leukopenia, burns, gastrointestinal disease, and premature birth predispose patients to nosocomial candidemia. Independent risk factors include prior treatment with multiple antibiotics, prior Hickman catheterization, isolation of Candida species from sites other than the blood, and prior hemodialysis. In this article some of the challenges posed by the management of nosocomial candidemia are presented in three case studies. In addition, the results of several investigations of nosocomial candidemia at the University of Iowa Hospitals and Clinics are reviewed.

Evidence of nosocomial spread of Candida albicans causing bloodstream infection in a neonatal intensive care unit.

Candida albicans is an increasingly important bloodstream pathogen. We investigated a cluster of bloodstream infections in the neonatal intensive care unit (NICU) to determine whether nosocomial transmission occurred. Subjects included any patient in the NICU who developed clinically significant bloodstream infection with C. albicans from January 1984 to December 1987 (N = 7). Isolates were typed by restriction fragment length polymorphism analysis using a C. albicans-specific DNA probe (27A). Four of the neonates were infected from June to August 1984 (1.4 infections per 100 admissions) (the epidemic period) versus none in the period from January to May 1984, and three in the period from September 1984 to December 1987 (0.12 infections per 100 admissions) (P = .002). Three of the four patients in the epidemic period were infected with identical strains, readily distinguished from epidemiologically unrelated strains from the NICU. We conclude that nosocomial transmission of C. albicans occurred and that neonates in intensive care units may represent one group at increased risk.

A study of a hospital cluster of systemic candidosis using DNA typing methods.

A cluster of disseminated Candida albicans infections, which occurred at the Intensive Care Unit of the Department of Heart Surgery, was investigated. Ten patients became infected and seven died. A wide microbiological surveillance was carried out. A total of 14 isolates of Candida albicans, four environmental and ten human, were examined using the Restriction Endonuclease Analysis (REA) of DNA. The isolates were classified into five different main groups. Five of the clinical isolates had the predominant pattern Ab and two more clinical strains were very closely related. Two more isolates from the emergency kit desk and the hands of a nurse gave the same REA profile. Such a relationship proved the epidemic nature of the cluster, with most of the patients cross-infected, and strongly suggested transmission on the hands of the staff as a determinant of the epidemic. Thus, REA has the potential to address many important questions in the study of nosocomial epidemiology of Candida albicans.