An outbreak of candidemia due to Candida tropicalis in a neonatal intensive care unit

An outbreak of candidemia due to Candida tropicalis involving 16 neonates (gestational age 28-36 weeks) is reported. All infants had received hyperalimentation and at least one course of antibiotics. The commonest clinical manifestations included episodes of acute respiratory distress and lack of response to antibacterial antibiotic therapy. Candida tropicalis was recovered from blood in all the 16 infants and urine cultures were positive in 14 infants. Environmental sampling yielded C. tropicalis from one each of the blankets and mattresses used for neonates. Four of five urinary tract isolates and both environmental isolates genotyped by arbitrarily primed-PCR with several random primers were shown to belong to the same genotype.     

Design and use of Candida scores at the intensive care unit

Invasive Candida infections are recognised as a cause of increased morbidity and mortality in intensive care patients, particularly those with recent extensive gastroabdominal surgery. Due to the difficulties of diagnosis, several authors have analysed risk factors suggestive of invasive candidiasis to identify patients at highest risk. Such patients may be potential candidates for preemptive antifungal therapy before becoming seriously ill. The extent of body site colonisation due to Candida species was recognised to be related with consequent invasive disease. The quantification of the colonisation was expressed as the Candida colonisation index. Based on the evaluation of independent risk factors predictive of invasive Candida infections, clinically relevant scores were evaluated in the last decade. Particularly, the Candida score that combines the clinical risk factors preceding surgery, total parenteral nutrition and severe sepsis with Candida multi-site colonisation can be considered a useful bedside scoring system to discern patients with mere Candida colonisation from patients with the risk of invasive candidiasis in non-neutropaenic critically ill patient population.     

Improvement of a clinical prediction rule for clinical trials on prophylaxis for invasive candidiasis in the intensive care unit

We created a clinical prediction rule to identify patients at risk of invasive candidiasis (IC) in the intensive care unit (ICU) (Eur J Clin Microbiol Infect Dis 2007; 26 :271). The rule applies to <10% of patients in ICUs. We sought to create a more inclusive rule for clinical trials. Retrospective review of patients admitted to ICU ≥ 4 days, collecting risk factors and outcomes. Variations of the rule based on introduction of mechanical ventilation and risk factors were assessed. We reviewed 597 patients with a mean APACHE II score of 14.4, mean ICU stay of 12.5 days and mean ventilation time of 10.7 days. A variation of the rule requiring mechanical ventilation AND central venous catheter AND broad spectrum antibiotics on days 1–3 AND an additional risk factor applied to 18% of patients, maintaining the incidence of IC at 10%. Modification of our original rule resulted in a more inclusive rule for studies.     

Invasive candidosis in intensive care unit patients

The incidence of invasive candidosis is increasing worldwide and the mortality is high. In the intensive care unit diagnostic measurements, correct evaluation of the findings and the right indication for antifungal treatment remain problematic. So determination of potential risk factors is very important. The therapeutic use of antifungal drugs is often limited by important disadvantages like inadequate spectrum, application form or side effects. New antifungals give hope for the near future.     

Diagnosis of systemic Candida infections in patients of the intensive care unit. Significance of serum antigens and antibodies

The combined detection of Candida antigen and antibody for the determination of systemic Candida infections (SCI) was investigated. One hundred and four patients from the intensive care unit (ICU) were analysed. Seventeen of the patients were suspected of having SCI, based on clinical and laboratory criteria. In these patients, Candida antigens and antibodies were analysed extensively. Ten patients had a positive Candida antigen (titre >1:16) determined by the latex agglutination assay Cand-Tec(R) and their median antibody titre was 1:160 in the indirect haemagglutination test (HAT). Seven antigen-negative patients had a median titre of 1:1280 (HAT). Forty-one of 42 colonized control patients had negative antigen titres and a median antibody titre of 1:160. The sensitivities and specificities were 58.8% and 97.6% for antigenemia, and 52.9% and 85.7% for antibody detection. These values reached 100.0% and 83.3%, respectively, when the results of both tests were combined. This indicates a high degree of concordance between serological results (Candida antigen and/or antibodies) and clinical presentation. We conclude, that the combined investigation of antigen and antibody titres might be a helpful tool in the characterization of SCI in ICU patients, if antigen titres are >or=1:16 or antibody titres (HAT) are >or=1:640.     

Molecular epidemiology of Candida species isolated from clinical specimens of intensive care unit patients

Epidemiological analysis of nosocomial Candida infections has gained importance due to an increase in these infections during the recent years. This study investigated the prevalence of clinical infections of Candida in anesthesiology intensive care unit patients, and ascertains the level of genetic diversity in the Candida species. A total of 70 Candida isolates, consisting of 42 Candida albicans, 16 Candida glabrata and 12 Candida tropicalis strains isolated from various clinical sites of infection of anesthesiology intensive care unit patients, were analysed. The susceptibility of the isolates against amphotericin B and fluconazole was determined by microdilution method according to Clinical and Laboratory Standards Institute M27-A2 standards. The strains were typed by random amplified polymorphic DNA (RAPD)-PCR using OPE-03, OPE-18, RP4-2 and AP50-1 primers. In the patients with Candida infections, most isolates exhibited different RAPD patterns. Only three C. albicans pairs isolated within a short time period had the same RAPD pattern. Most of the Candida infections in the anesthesiology intensive care unit of our hospital seem to be caused by endogenous strains. Exogenous spread of C. albicans infections occurred less frequently.     

Molecular epidemiology of Candida species isolated from urine at an intensive care unit

Candida spp. has been the leading microorganism isolated from the urine specimens of patients hospitalized at the Anesthesiology and Reanimation intensive care unit (ICU) of Dokuz Eylul University Hospital, Izmir, since 1998. This study was undertaken to investigate the clonal relationship of Candida urine isolates in order to find the mode of spread among the patients. Epidemiological surveillance of 38 Candida albicans, 15 Candida tropicalis and 12 Candida glabrata recovered from the urine specimens of patients who were hospitalized in the ICU between June 11, 2000 and October 15, 2001 was carried out by antifungal susceptibility testing and randomly amplified polymorphic DNA (RAPD) analysis. Two short primers [Cnd3 (5'-CCAGATGCAC-3') and Cnd4 (5'-ACGGTACACT-3')] were used for RAPD. None of the isolates had high minimal inhibitory concentration (MIC) values (>1 microg ml(-1)) against amphotericin B with MIC50 values of 0.5 microg ml(-1), 0.5 microg ml(-1) and 0.125 microg ml(-1) for C. albicans, C. tropicalis and C. glabrata isolates, respectively. However, three C. glabrata isolates were resistant and one C. albicans and five C. glabrata isolates were dose-dependent susceptible (D-DS) to fluconazole. Among C. albicans isolates 19 and 20 patterns were detected with primers Cnd3 and Cnd4, respectively. When primers Cnd3 and Cnd4 were evaluated together, three and four genotypes were identified for C. tropicalis and C. glabrata isolates, respectively. Our results suggest that the source of C. albicans isolates was mostly endogenous. It is difficult to interpret the mode of spread of C. tropicalis and C. glabrata urine isolates as we obtained insufficient banding patterns for these species.     

Evaluation of antifungals in the surgical intensive care unit: a multi-institutional study

In the USA, >50% of candidemia episodes occur in medical or surgical intensive care units (SICU). However, studies focused on patterns and rationale for antifungal use are lacking. The objective of this study was to evaluate systemic antifungal usage in SICU patients. Retrospective audit of SICU patients receiving antifungal therapy from four American hospitals. Medical records were reviewed for demographics, hospital variables, microbiology results, antifungal regimens and indications for therapy. A total of 2411 patient-days of antifungal use were evaluated in 225 patients. Fluconazole was the most frequently prescribed antifungal (1846 patient-days) followed by amphotericin B deoxycholate (251 patient-days), lipid formulations of amphotericin B (201 patient-days), itraconazole (71 patient-days), and caspofungin (42 patient-days). Antifungals were prescribed empirically (44%), for preemptive therapy in critically ill patients colonised with Candida (43%), or for candidiasis (12%). Candida species were recovered from 98% of patients with positive fungal cultures most commonly from pulmonary (53%) or urinary sources (17%). Fluconazole is the most frequently prescribed antifungal agent in SICUs and is most often prescribed for empiric or preemptive indications. Research efforts to identify patients who warrant preemptive antifungal therapy for invasive candidiasis could dramatically change antifungal prescribing patterns in the SICU.     

Survival and predictors of outcome in patients with acute leukemia admitted to the intensive care unit

BACKGROUND: Predictors of outcome and rates of successful discharge have not been defined for patients with acute leukemia admitted to intensive care units (ICUs) in the US. METHODS: This is a retrospective analysis of 90 patients with acute leukemia (no history of bone marrow transplant) admitted to an ICU from 2001-2004. The primary endpoints were improvement and subsequent discharge from the ICU, discharge from the hospital, and 2-month survival after hospital discharge. Secondary endpoints were 6- and 12-month survival. Univariate and multivariate logistic regression analyses were performed to identify factors predicting outcome. RESULTS: The median age of patients was 54 years and 48 (53%) were male. The most common reason for ICU transfer for all patients was respiratory compromise. The majority of all patients (68%) were eventually placed on ventilator support and approximately half required pressors. During the ICU course, 29 patients (32%) improved and subsequently resumed aggressive leukemia management, and 24 patients (27%) survived to be discharged from the hospital. The 2-, 6-, and 12-month overall survival was 24 (27%), 16 (18%), and 14 (16%), respectively. Higher APACHE II score, use of pressors, undergoing bone marrow transplantation preparative regimen, and adverse cytogenetics predicted worse outcome. Newly diagnosed leukemia, type of leukemia, or age did not. CONCLUSIONS: One of 4 patients with acute leukemia survived an ICU admission to be discharged from the hospital and were alive 2 months later. A diagnosis of acute leukemia should not disqualify patients from an ICU admission.     

Epidemiology,risk factors for and outcome of candidaemia among non‐neutropenic patients in a Greek intensive care unit

To determine the epidemiology, risk factors for and outcome of candidaemia in critically ill patients, a matched case–control study was performed in a 25‐bed intensive care unit (ICU) from August 2004 to January 2006. Candidaemia occurred in 33 patients; each patient was matched to four controls according to admission illness severity, diagnostic category and length of ICU stay. Candida non‐albicans species predominated (67.7%). The presence of acute respiratory distress syndrome (ARDS) was the only independent risk factor for candidaemia development (OR, 2.93; 95% CI 1.09–7.81, P = 0.032). Mortality was 60.6% among patients with candidaemia and 22% among controls (P < 0.001). The presence of candidaemia (OR, 9.37; 95% CI 3.48–25.26, P < 0.001) and the illness severity on admission (acute physiologic and chronic health evaluation II score, OR, 1.17; 95% CI 1.12–1.24, P < 0.001) were independently associated with mortality. Among candidaemic patients, risk factors for mortality were the severity of organ dysfunction (sequential organ failure assessment score, OR, 1.57; 95% CI 1.00–2.46, P = 0.05) and a low serum albumin level (OR, 0.74; 95% CI 0.59–0.94, P = 0.012) both of them occurred on candidaemia onset. We conclude that in critically ill patients matched for illness severity and length of ICU stay, the only independent risk factor for candidaemia was the presence of ARDS. Mortality was independently associated with acquisition of candidaemia and with the illness severity at candidaemia onset.     

Invasive fungal infections in the intensive care unit: a multicentre, prospective, observational study in Italy (2006-2008)

Critically ill patients admitted to intensive care units (ICU) are highly susceptible to healthcare-associated infections caused by fungi. A prospective sequential survey of invasive fungal infections was conducted from May 2006 to April 2008 in 38 ICUs of 27 Italian hospitals. A total of 384 fungal infections (318 invasive Candida infections, three cryptococcosis and 63 mould infections) were notified. The median rate of candidaemia was 10.08 per 1000 admissions. In 15% of cases, the infection was already present at the time of admission to ICU. Seventy-seven percent of Candida infections were diagnosed in surgical patients. Candida albicans was isolated in 60% of cases, Candida glabrata and Candida parapsilosis in 13%, each. Candida glabrata had the highest crude mortality rate (60%). Aspergillus infection was diagnosed in 32 medical and 25 surgical patients. The median rate was 6.31 per 1000 admissions. Corticosteroid treatment was the major host factor. Aspergillosis was demonstrated to be more severe than candidiasis as the crude mortality rate was significantly higher (63% vs. 46%), given an equal index of severity, Simplified Acute Physiology Score (SAPS-II). The present large nationwide survey points out the considerable morbidity and mortality of invasive fungal infections in surgical as well as medical patients in ICU.     

Candida bloodstream infections in Serbia: First multicentre report of a national prospective observational survey in intensive care units

Candida bloodstream infections (BSI) are a significant cause of mortality in intensive care units (ICU), hereof the prospective 12‐months (2014‐2015) hospital‐ and laboratory‐based survey was performed at the Serbian National Reference Medical Mycology Laboratory (NRMML). Candida identification was done by a matrix‐assisted laser desorption/ionisation time‐of‐flight mass spectrometry and a susceptibility test, according to the Clinical and Laboratory Standards Institute methodology. Among nine centres (265 beds; 10 820 patient admissions), four neonatal/paediatric (NICU/PICUs) and five adult centres (ICUs) participated, representing 89 beds and 3446 patient admissions, 166 beds and 7347 patient admissions respectively. The NRMML received 43 isolates, 17 from NICU/PICUs and 26 from adult ICUs. C. albicans dominated highly in NICU/PICUs (~71%), whereas C. albicans and C. parapsilosis were equally distributed within adults (46%, each), both accounting for ~90% of received isolates. The resistance to itraconazole and flucytosine were 25% and 2.4% respectively. In addition, the 2 C. albicans were azole cross‐resistant (4.6%). The overall incidence of CandidaBSI was ~3.97 cases/1000 patient admissions (4.93 in NICU/PICU and 3.53 in adult ICU). The 30‐day mortality was ~37%, most associated with C. tropicalis and C. glabrataBSI. Data from this national survey may contribute to improving the Balkan and Mediterranean region epidemiology of CandidaBSI within ICUs.     

Short‐ and long‐term survival of patients with metastatic solid cancer admitted to the intensive care unit: prognostic factors

CARUSO P., FERREIRA A.C., LAURIENZO C.E., TITTON L.N., DA SILVA MAIA TERABE D., CARNIELI D.S. & DEHEINZELIN D. (2010) European Journal of Cancer Care 19 , 260–266
Short‐ and long‐term survival of patients with metastatic solid cancer admitted to the intensive care unit: prognostic factors Decisions for intensive care unit (ICU) admissions in patients with advanced cancer are complex, and the knowledge of survival rates and prognostic factors are essential to these decisions. Ours objectives were to describe the short‐ and long‐term survival of patients with metastatic solid cancer admitted to an ICU due to emergencies and to study the prognostic factors presented at ICU admission that could be associated with hospital mortality. We retrospectively analysed the charts of all patients with metastatic solid cancer admitted over a 1‐year period. This gave a study sample of 83 patients. The ICU, hospital, 1‐year and 2‐year survival rates were 55.4%, 28.9%, 12.0% and 2.4% respectively. Thrombocytopenia (odds ratio 26.2; P = 0.006) and simplified acute physiology score (SAPS II) (odds ratio 1.09; P = 0.026) were independent factors associated with higher hospital mortality. In conclusion, the survival rates of patients with metastatic solid cancer admitted to the ICU due to emergencies were low, but of the same magnitude as other groups of cancer patients admitted to the ICU. The SAPS II score and thrombocytopenia on admission were associated with higher hospital mortality. The characteristics of the metastatic disease, such as number of organs with metastasis and central nervous system metastasis were not associated with the hospital mortality.     

Candida glabrata prosthetic joint infection,successfully treated with anidulafungin: A case report and review of the literature

Non‐albicans Candida prosthetic joint infection (PJI) is extremely rare. A case of a Candida glabrata knee PJI is a 68‐year‐old splenectomised female smoker, suffering from chronic obstructive pulmonary disease (COPD) and alcoholism is reported. The patient presented with a peri‐prosthetic fracture, 15 years after total knee replacement surgery. Cultures of the intraoperative peri‐prosthetic tissue and materials yielded C. glabrata, as well as a methicillin‐resistant S. epidermitis. The patient was treated with anidulafungin and vancomycin. The knee prosthetic joint was removed and cement‐spacer with vancomycin and gentamycin was placed. Additionally, an external fixation was performed. A second stage revision surgery was planned, after completion of the antimicrobial and antifungal treatment. The patient is followed up for 4 months without signs, symptoms or findings of infection. PJI Candida infections require a high clinical suspicion index. It is of utmost importance to report these cases, since there is no consensus yet of the proper antifungal treatment. Furthermore, a literature review regarding treatment of those cases is provided. First‐line treatment with an echinocandin seems most proper, due to their fungicidal properties, their effectiveness against biofilm, as well as their minimal toxicity, making them ideal for long‐term use. Further experience is needed, for better understanding the disease's pathogenesis and optimal treatment.