Candida infections in the intensive care unit: epidemiology, risk factors and therapeutic strategies

This article reviews the epidemiology, predisposing risk factors and outcome of systemic Candida spp. infections in the intensive care unit setting. Incidence of systemic Candida infections in patients requiring intensive care has increased substantially in recent years; while diagnosis of serious Candida infection may be difficult, the clinical conditions which predispose patients to these infections are now better understood and effective antifungal therapies are becoming increasingly available. Severe fungal infections are generally associated with poor outcomes in these patients. Patients at highest risk for Candida infection may be potential candidates for early, presumptive therapy. In this article we review antifungal treatment, including the use of polyenes, azoles and echinocandines, and the role of prophylaxis.     

Candida infections in the intensive care unit: epidemiology,risk factors and therapeutic strategies

This article reviews the epidemiology, predisposing risk factors and outcome of systemic Candida spp. infections in the intensive care unit setting. Incidence of systemic Candida infections in patients requiring intensive care has increased substantially in recent years; while diagnosis of serious Candida infection may be difficult, the clinical conditions which predispose patients to these infections are now better understood and effective antifungal therapies are becoming increasingly available. Severe fungal infections are generally associated with poor outcomes in these patients. Patients at highest risk for Candida infection may be potential candidates for early, presumptive therapy. In this article we review antifungal treatment, including the use of polyenes, azoles and echinocandines, and the role of prophylaxis.     

Impact of fluconazole prophylaxis on fungal colonization and infection rates in neutropenic patients. The Canadian Fluconazole Study

Fungal colonization profiles from four different anatomical sites were evaluated in 266 neutropenic cancer patients receiving intensive cytotoxic therapy for acute leukaemia or for autologous marrow transplantation. At the beginning of chemotherapy patients were allocated randomly to receive oral fluconazole 400 mg daily or an identical placebo until prophylaxis failure or marrow recovery. Candida albicans colonization was reduced from 30 to 10% in the fluconazole recipients while it increased from 32 to 57% in the placebo patients (P<0.001). By the end of prophylaxis, colonization with non-albicans Candida species increased from 7 to 21% and 8 to 18% in the fluconazole and placebo patients, respectively (P = 0.396). Although Candida glabrata was isolated more frequently at the end of the prophylactic period in the fluconazole patients than in the placebo patients (16 versus 7%), only one definite invasive C. glabrata infection was noted. Overall, definite invasive fungal infections were documented in 26 patients [four fluconazole versus 22 placebo patients (P< or =0.001)]. In 23 (92%) patients the infections were caused by persistently colonizing or newly acquired organisms. While probable invasive fungal infections were noted in five fluconazole patients, 10 placebo patients were also affected (P = 0.19). An end-of-prophylaxis colonization index >0.25 was 76% sensitive but only 69% specific for invasive fungal infection. However, a colonization index < or =0.25 at baseline had a negative predictive value of 88% for development of invasive fungal infection. Fluconazole prophylaxis decreased colonization by fungi and subsequent invasive fungal infections in neutropenic cancer patients.     

Prevention and management of oral infections in cancer patients

 The successful prevention and management of oral infections and infections from the oral cavity in cancer patients are based on identification of risk patients, selection of patients for prophylactic measures, diagnosis of infection and implementation of directed or empiric antimicrobial therapy. Identification of patients at risk for infection is based on each patient's type of oral microbial colonization and the presence of latent viral infections. Systemic and local resistance to infection will be decisive, and in many patients the risk can be estimated from the expected myelosuppressive effect of anticancer treatment. Diagnosis of infection is often based on clinical findings together with the results of microbiological investigations. Biopsies could be useful, but can seldom be obtained. Blood samples are mandatory for isolation of microorganisms involved in systemic infections in myelosuppressed patients. Prevention of infection requires both local and systemic measures. Elimination of the risk of a breach in the first line of defence is urgent, and the maintenance of mucosal integrity is important. Monitoring microbial colonization is common, as is the institution of antiviral prophylaxis in patients with increased anti-HSV IgG (ELISA >10 000). Antifungal prophylaxis, to avoid colonization and superinfection, should be instituted in patients with low neutrophil counts. Gastrointestinal prophylaxis with quinolones is also commonly used in these patient groups. Treatment of oral infections in cancer patients should include systemic antimicrobial agents in most cases. Special attention should be directed to oral infections in neutropenic (<0.5×l0⁹/l) patients in whom oral microorganisms are the leading cause of bacteraemia. Invasive fungal infections of the oral cavity can be associated with systemic fungal infection and are indications for the use of liposomal amphotericin B. Published online: 21 May 1999     

Bench-to-bedside review: Therapeutic management of invasive candidiasis in the intensive care unit

Candida is one of the most frequent pathogens in bloodstream infections, and is associated with significant morbidity and mortality. The epidemiology of species responsible for invasive candidiasis, both at local and worldwide levels, has been changing - shifting from Candida albicans to non-albicans species, which can be resistant to fluconazole (Candida krusei and Candida glabrata) or difficult to eradicate because of biofilm production (Candida parapsilosis). Numerous intensive care unit patients have multiple risk factors for developing this infection, which include prolonged hospitalisation, use of broad-spectrum antibiotics, presence of intravascular catheters, parenteral nutrition, high Acute Physiology and Chronic Health Evaluation score, and so forth. Moreover, delaying the specific therapy was shown to further increase morbidity and mortality. To minimise the impact of this infection, several management strategies have been developed - prophylaxis, empirical therapy, pre-emptive therapy and culture-based treatment. Compared with prophylaxis, empirical and pre-emptive approaches allow one to reduce the exposure to antifungals by targeting only the patients at high risk of candidemia, without delaying therapy until the moment blood Candida is identified in blood cultures. The agents recommended for initial treatment of candidemia in critically ill patients include echinocandins and lipid formulation of amphotericin B.     

Strategies for managing systemic fungal infection and the place of itraconazole

Systemic fungal infections are an increasing cause of mortality and morbidity in patients with haematological malignancies and certain other conditions associated with profound immunosuppression. The majority of such infections are caused by Aspergillus and Candida species. In recent years, the number of available drugs effective in the therapy of these difficult infections has expanded. Large clinical trials have been performed in different settings such as prophylaxis, empirical and first-line therapy. For prophylaxis, the azoles fluconazole and itraconazole have been most widely studied. These azoles are available in both oral and intravenous formulations. Itraconazole has a wide spectrum of activity including Aspergillus, Candida albicans and non-albicans species. Two large studies comparing the use of itraconazole with fluconazole for primary prophylaxis in high-risk patients who were recipients of allogeneic stem cell transplants have recently been reported. These have confirmed that itraconazole is effective in this setting in reducing the rate of systemic fungal infections. However, there are concerns with regard to increased toxicity and the potential for drug interactions with itraconazole compared with fluconazole. In the empirical setting, large randomized studies support the use of caspofungin and liposomal amphotericin B. Voriconazole and lipid-associated amphotericin B have been shown to be effective in first-line therapy and caspofungin for salvage. New approaches to management include efforts at improving diagnosis, combination antifungal therapy and treatment strategies for emerging moulds.     

New perspectives in the diagnosis of systemic fungal infections

Profound and prolonged neutropenia following chemotherapy is a major risk factor for systemic fungal infections. Mortality associated with disseminated fungal infection is high, and treatment with conventional amphotericin B is complicated by renal toxicity. Candida and Aspergillus are among the major pathogens in these patients. Many patients remaining neutropenic over a prolonged period of time will receive empirical antifungal therapy. The clinical and laboratory diagnoses of these infections are neither sensitive nor specific and are generally limited in the early detection of invasive fungal infection. However, several new approaches to diagnosis are being developed, which should be translated into routine practice, based on a greater understanding of the pathogenesis of systemic fungal infection and virulence determinants of fungal pathogens. These include antigen detection and polymerase chain reaction. Patients with presumed fungal infection require more intense and accurate monitoring for signs of disseminated infection. Early diagnosis may guide appropriate treatment and prevent mortality. Continued development of commercial tests should help achieve the objective of definitive diagnostic tests for systemic fungal infections.     

How to select an antifungal agent in critically ill patients

Fungal infections are common in critically ill patients and are associated with increased morbidity and mortality. Candida spp are the most commonly isolated fungal pathogens. The last 2 decades have seen an increased incidence of fungal infections in critical illness and the emergence of new pathogenic fungal species and also the development of more effective (better bioavailability) and safer (less toxicity, fewer drug interactions) drugs. The distinction between colonization and infection can be difficult, and problems diagnosing infection may delay initiation of antifungal treatment. A number of factors have been identified that can help to distinguish patients at high risk for fungal infection. The antifungal agents that are most frequently used in the intensive care unit are the first- and second-generation azoles and the echinocandins; amphotericin B derivatives (mainly the liposomal agents) are less widely used because of adverse effects. The choice of antifungal agent in critically ill patients will depend on the aim of therapy (prophylaxis, pre-emptive, empiric, definitive), as well as on local epidemiology and specific properties of the drug (antifungal spectrum, efficacy, toxicity, pharmacokinetic/pharmacodynamic properties, cost). In this article we will review all these aspects and propose an algorithm to guide selection of antifungal agents in critically ill patients.     

侵袭性真菌病111例临床特点及体外药敏分析

目的了解侵袭性真菌病111例的病原菌分布及临床特点,为临床及实验室侵袭性真菌病的诊治提供参考资料。方法回顾性分析复旦大学附属华山医院2004年1月2（）（）6年12月血液、正常无菌体液（包括脑脊液、胸水、腹水、胆汁、关节腔积液等）、深部脏器组织（包括肺、肝、脑等）中真菌培养或镜检阳性的病例,以及自痰、支气管肺泡灌洗液曲霉或隐球菌培养阳性的病例,根据诊断标准对其中确诊及拟诊的侵袭性真菌病进行分析。结果本研究共人选侵袭性真菌病病例111例。其中确诊（proven）1（）4例,拟诊（probable）7例。属社区获得性感染61例,医院感染50例。感染部位以血流最常见,51例（45．9％）,其次为中枢神经系统44例（39．6％）、肺部感染14例（12．6％）。病原真菌以念珠菌属最常见,50株（45．0％）,其次为隐球菌47株（42．3％）、曲霉12株（10．8％）。社区获得性真菌病61例,主要为中枢神经系统44例（72．1％）和肺部12例（19．7％）。社区获得性感染中占优势的真菌为隐球菌47例（77．0％）、曲霉10株（16．4％）。医院感染真菌病50例,最常见为血流感染48例（96．0％）,病原真菌以念珠菌属最为常见,47株（94．0％）,其中又以白念珠菌占多数。多数医院感染患者都存在基础疾病和多种诱发因素。其中深静脉置管与医院血流感染的关系密切,64．7％念珠菌性血流感染患者深静脉置管超过1周,且11例患者静脉留置管与血培养呈相同的菌种。而社区获得性真菌病中超过一半患者无明确的基础疾病和诱发因素。本组病例病死率为14．4％（16例）。其中医院感染侵袭性真菌病病死率18．0％（9／50）,高于社区获得性侵袭性真菌病病死率11．5％（7／61）。不同真菌病的病死率以曲霉为最高（33．3％）。结论侵袭性真菌病中以血流感染、中枢神经系统感染及肺部感染为常见。病原真菌依次为念珠菌、隐球菌和曲霉。社区获得性真菌病以隐球菌脑膜炎最多见。医院感染则以念珠菌血流感染最多见。侵袭性曲霉病病死率相对较高。     

Adequacy of empirical antifungal therapy and effect on outcome among patients with invasive Candida species infections

OBJECTIVES: Although inadequate antimicrobial therapy has been demonstrated in multiple studies to increase the risk for death in bacterial infections, few data investigating the effect of antifungal therapy on outcome of serious fungal disease are available. We sought to assess the adequacy of empirical therapy and its effect on mortality in invasive Candida species infections. METHODS: Population-based surveillance of all patients with Candida spp. cultured from blood and/or cerebrospinal fluid was conducted. Adequacy of empirical therapy was assessed according to published guidelines. RESULTS: During a 5 year period, 207 patients had an invasive Candida spp. infection identified; in 199 cases (96%) adequate data were available for assessment of treatment and outcome at hospital discharge. One hundred and three (52%) cases were due to Candida albicans, 44 (22%) were due to Candida glabrata and the remainder were due to other species. Between the time of culture draw and reporting of a positive culture, only 64 (32%) patients were treated with empirical therapy; this was deemed adequate in 51 (26%). Patients who received adequate empirical therapy had a significant decrease in crude mortality [14/51 (27%) versus 68/148 (46%); risk ratio 0.60 (95% confidence interval 0.37-0.96); P = 0.02]. After adjusting for age and the need for intensive care unit admission in logistic regression analysis, the use of adequate empirical therapy was independently associated with a reduced risk for death [odds ratio 0.46 (95% confidence interval 0.22-1.00); P = 0.05]. CONCLUSIONS: Adequate empirical therapy is used in a minority of patients with invasive Candida spp. infections but is associated with improved survival.     

Necrotizing colitis caused by systemic aspergillosis in a burn patient.

The incidence of invasive fungal infections has continued to rise over the past three decades, especially in the immunocompromised and intensive care unit population. Candida species are the most common pathogen to cause such invasive infections. However, Aspergillus species are currently on the rise and constitute a much more aggressive and serious infection. All Aspergillus species cause a wide spectrum of diseases from colonization to hypersensitivity reactions. It can also cause chronic necrotizing infections leading to rapidly progressive angioinvasion, often resulting in death. Invasive Aspergillus infection almost always occurs in patients who are immunosuppressed. We report here a case of aspergillosis causing invasive systemic infection and mycotic colitis in a burn patient. The clinical presentation was one of septic shock with rapidly progressing dissemination leading to necrotizing colitis and eventual demise. Pathologic findings involved necrotizing enterocolitis with invasive Aspergillus hyphae. Given the rarity of this entity and usual progression to death in humans, proper diagnosis and treatment of such fungal infections are being investigated. Reports are reviewed, and possible mechanisms resulting in Aspergillus infection in this individual are discussed.     

Early diagnosis of fungal infection in immunocompromised patients

Techniques for the diagnosis of invasive fungal infection, including antigen testing, nucleic acid detection and radiological imaging, have improved greatly in recent years. They have the potential to impact on patient management through replacing empirical antifungal strategies with targeted and pre-emptive therapy. Factors that influence performance of these diagnostic tests include underlying disease, the prevalence of fungal infection in particular populations and prophylactic antifungal drug strategies. Understanding these factors is necessary for rational use of antifungal agents and optimal management and prevention of fungal infection in immunosuppressed patients.     

Antifungal agents for preventing fungal infections in non-neutropenic critically ill and surgical patients: systematic review and meta-analysis of randomized clinical trials

OBJECTIVES: This study aims to systematically identify and summarize the effects of antifungal prophylaxis in non-neutropenic critically ill adult patients on all-cause mortality and the incidence of invasive fungal infections. METHODS: Systematic review and meta-analysis of randomized controlled trials in all languages comparing the prophylactic use of any antifungal agent or regimen with placebo, no antifungal or another antifungal agent or regimen in non-neutropenic critically ill adult patients. We searched the Cochrane Central Register of Controlled Trials (CENTRAL, The Cochrane Library, Issue 3, 2005), MEDLINE (1966 to 2 September 2005) and EMBASE (1980 to week 36, 2005). We also hand-searched reference lists, abstracts of conference proceedings and scientific meetings (1998-2004) and contacted authors of included studies and pharmaceutical manufacturers. The primary outcomes assessed were all-cause mortality and proven invasive fungal infections. Two reviewers independently applied selection criteria, performed quality assessment and extracted data using an intention-to-treat approach. Data were synthesized using the random effects model and expressed as relative risk with 95% confidence intervals. RESULTS: Twelve unique trials (eight comparing fluconazole and four ketoconazole with no antifungal or a non-absorbable agent) involving 1606 randomized patients were included. For both outcomes of total mortality and invasive fungal infections, almost all trials of fluconazole and ketoconazole separately showed a non-significant risk reduction with prophylaxis. When combined, fluconazole/ketoconazole reduced total mortality by one-quarter (relative risk 0.76, 95% confidence interval 0.59-0.97) and invasive fungal infections by about one-half (relative risk 0.46, 95% confidence interval 0.31-0.68). No significant increase in the incidence of infection or colonization with the azole-resistant fungal pathogens Candida glabrata or Candida krusei was demonstrated, although the confidence intervals of the summary effect measures were wide. Adverse effects requiring treatment discontinuation were not more common amongst patients receiving prophylaxis. Results across all trials were homogeneous despite considerable heterogeneity in clinical and methodological characteristics. CONCLUSIONS: Prophylaxis with fluconazole or ketoconazole in critically ill patients reduces invasive fungal infections by one-half and total mortality by one-quarter. Although no significant increase in azole-resistant Candida species associated with prophylaxis was demonstrated, trials were not powered to exclude such an effect. In patients at increased risk of invasive fungal infections, antifungal prophylaxis with fluconazole should be considered.     

Prospective Study of Candida Species in Patients at a Comprehensive Cancer Center

Since most nosocomial systemic yeast infections arise from the endogenous flora of the patient, we prospectively evaluated the species stratification and antifungal susceptibility profile of Candida spp. associated with heavy colonization and systemic infection in patients at Memorial Sloan-Kettering Cancer Center in New York. A total of 349 Candida isolates were obtained from 223 patients during the later half of 1998. Cancer was the most common underlying disease, occurring in 91% of the patients, including 61.8% with organ and 23.7% with hematological malignancies; 4.4% of the patients had AIDS. Candida albicans was the predominant species (67.3%); among 114 non-albicans Candida spp., C. glabrata (45.6%) was the most frequent, followed by C. tropicalis (18.4%), C. parapsilosis (16.6%), and C. krusei (9.6%). The overall resistance to triazole-based agents among all yeast isolates was 9.4 and 10.8% for fluconazole and itraconazole, respectively. A total of 5% of C. albicans strains were resistant to triazole antifungals, whereas 30.8 and 46.2% of C. glabrata strains were resistant to fluconazole (MIC > or = 64 microg/ml) and itraconazole (MIC > or = 1 microg/ml), respectively. A significant association was observed between prior treatment with triazole and isolation of fluconazole-resistant C. albicans (P = 0.005, OR 36), although this relationship was not seen in C. glabrata isolates (P = 0.4). This study reinforces the importance of periodic, prospective surveillance of clinical fungal isolates to determine appropriate prophylactic, empiric, and preemptive antifungal therapy for the highly susceptible patient population.     

Caspofungin acetate for treatment of invasive fungal infections

OBJECTIVE: To briefly discuss the changing epidemiology of fungal infections and review currently available agents; provide a review of caspofungin; and discuss its pharmacology, pharmacokinetics, dosing guidelines, safety and efficacy, and role in the treatment of invasive fungal infections as it relates to current antifungal therapy. DATA SOURCES: A MEDLINE (1966 to August 2002) database search using key words caspofungin, echino candins, fungal infections, and invasive aspergillosis, was completed to identify relevant articles including reviews, recent studies, treatment guidelines, and data from Merck and Company. STUDY SELECTION: In vitro studies and all clinical trials were evaluated to summarize the clinical efficacy and safety of caspofungin. DATA SYNTHESIS: The incidence of fungal infections is increasing as the population at risk expands. Cost, resistance, and morbidity and mortality are key issues. Adding to the antifungal armamentarium is necessary to address these therapeutic dilemmas. Caspofungin is the first member of a new class of antifungal agents, the echinocandins, to be approved for clinical use. Caspofungin is classified as a glucan synthase inhibitor and represents a class of agents with a novel mechanism of action. Unlike currently available agents (polyenes, pyrimidines, azoles) that exert their effect on the fungal cell membrane, the echinocandins are the first agents to inhibit fungal cell wall synthesis. Caspofungin exhibits activity against Aspergillus spp. and Candida spp., including non-albicans species. Data from clinical trials demonstrate that caspofungin is effective in patients with invasive aspergillosis as well as candida esophagitis. Its Food and Drug Administration-approved indication is limited to invasive aspergillosis refractory to or intolerant of current therapy. CONCLUSIONS: Caspofungin has activity against Aspergillus spp. as well as a variety of Candida spp. Clinical data support its usefulness in the treatment of invasive aspergillosis and select candida infections. As additional clinical data become available, it seems likely that the therapeutic role of caspofungin will expand.     

Host defense mechanisms in invasive candidiasis originating in the GI tract

Candida spp. rank among the leading causative agents of nosocomial infections. The increasing number of patients at risk of invasive candidiasis makes a rise in the incidence of this fungal infection expected. Disruption of GI tract integrity and ablation of immune cell populations, such as those resulting from cancer chemotherapy, are recognized as key factors leading to fungal dissemination. However, the individual role of these immune barriers in preventing Candida host colonization and invasion are yet to be fully understood. This article evaluates recently published results on a new murine model of systemic candidiasis originating in the GI tract that might prove a valuable setting for the accurate study of host immune mechanisms, fungal virulence factors and novel therapeutic approaches.     

普外科真菌感染84例临床调查

目的：探讨普外科真菌感染的现状及临床特性．为外科手术后真菌感染的防治提供参考依据。方法：回顾性调查2002年1月-2003年12月本院普外科疑似真菌感染患者的临床概况，对其中经真菌涂片、培养阳性，并伴有临床症状、体征诊断为真菌感染患者的感染类型、危险因素和病原菌分布作进一步分析。结果：①我科2年中共有242株真菌培养阳性的临床标本。其中确诊或疑诊为真菌感染者84例。感染部位以消化道最常见。病原菌以白念念珠菌最常见，占58．2％。其次为光滑念珠菌、热带念珠菌和克柔念珠菌。②外科手术、长时间用抗菌药、恶性肿瘤、胃肠外营养是最常见的危险因素，50％以上的患者存在上述情况。③与感染有关的手术类型最多见的是胰十二指肠切除术．各病种中亦以胰腺肿瘤及炎症最多。④除抗厌氧菌药物外，第三代头孢菌素、亚胺培南、去甲万古霉素是曾有真菌感染的患者最常使用的抗生素。结论：①白念念珠菌仍为外科真菌感染的主要致病菌，而非白念念珠菌感染呈上升趋势。②我院普外科真菌感染以消化道感染为主。③尽量减少手术创伤、合理使用抗生素、尽早使用肠内营养、规范各类导管操作和护理等均是真菌感染的重要预防措施。     

Fluconazole for the management of invasive candidiasis: where do we stand after 15 years?

Candida spp. are responsible for most of the fungal infections in humans. Available since 1990, fluconazole is well established as a leading drug in the setting of prevention and treatment of mucosal and invasive candidiasis. Fluconazole displays predictable pharmacokinetics and an excellent tolerance profile in all groups, including the elderly and children. Fluconazole is a fungistatic drug against yeasts and lacks activity against moulds. Candida krusei is intrinsically resistant to fluconazole, and other species, notably Candida glabrata, often manifest reduced susceptibility. Emergence of azole-resistant strains as well as discovery of new antifungal drugs (new triazoles and echinocandins) have raised important questions about its use as a first line drug. The aim of this review is to summarize the main available data on the position of fluconazole in the prophylaxis or curative treatment of invasive Candida spp. infections. Fluconazole is still a major drug for antifungal prophylaxis in the setting of transplantation (solid organ and bone marrow), intensive care unit, and in neutropenic patients. Prophylactic fluconazole still has a place in HIV-positive patients in viro-immunological failure with recurrent mucosal candidiasis. Fluconazole can be used in adult neutropenic patients with systemic candidiasis, as long as the species identified is a priori susceptible. Among non-neutropenic patients with candidaemia fluconazole is one of the first line drugs for susceptible species. Cases reports and uncontrolled studies have also reported its efficacy in the setting of osteoarthritis, endophthalmitis, meningitis, endocarditis and peritonitis caused by Candida spp. among immunocompetent adults. In paediatrics, fluconazole is a well tolerated and major prophylactic drug for high-risk neonates, as well as an alternative treatment for neonatal candidiasis. Importantly 15 years after its introduction in the antifungal armamentarium, fluconazole is still a first line treatment option in several cases of invasive candidiasis. Its prophylactic use should however be limited to selected high-risk patients to limit the risk of emergence of azole-resistant strains.     

Trichosporon species infection in bone marrow transplanted patients

Trichosporon species are emerging as opportunistic agents that cause systemic diseases in immunocompromised patients. Patients undergoing bone marrow transplant are submitted to intense and prolonged periods of neutropenia and consequently to several risk factors to fungal infections as the use of broad spectrum antibiotics and invasive devices. Two cases of fungal infections caused by Trichosporon asahii var. asahii and T. inkin in patients with bone marrow transplant are described T. asahii var. asahii was responsible for fungemia and the identification of this microorganism was later performed. T. inkin caused vascular accesses infection and was recovered from an implanted Hickman-Broviac catheter. Both patients were under oral fluconazole prophylaxis. The patient with systemic infection died despite the therapy with amphotericin B and the patient with catheter-related infection recovered from the fungal infection after catheter removal. Difficulties in the identification of this microorganism lead to delays in treatment and post-mortem diagnosis.     

Candida spp. colonization significance in critically ill medical patients: a prospective study

Objective Multiple-site colonization with Candida species is commonly recognized as a major risk factor for invasive fungal infection in critically ill patients. The fungal colonization density could be of predictive value for the diagnosis of systemic candidiasis in high-risk surgical patients. Little is known about it in the medical ICU setting.Design and setting Prospective observational study in the eight-bed medical intensive care unit of a teaching hospital.Subjects 92 consecutive nonneutropenic patients hospitalized for more than 7 days.Measurements and results The colonization index (ratio of the number of culture-positive surveillance sites for Candida spp. to the number of sites cultured) was calculated weekly upon ICU admission until death or discharge. The 0.50 threshold was reached in 36 (39.1%) patients, almost exclusively in those with detectable fungal colonization upon ICU admission. The duration of broad-spectrum antibiotic therapy was found to be the main factor that independently promoted fungal growth as measured through the colonization index.Conclusions Candida spp. multiple-site colonization is frequently met among the critically ill medical patients. Broad-spectrum antibiotic therapy was found to promote fungal growth in patients with prior colonization. Since most of the invasive candidiasis in the ICU setting are thought to be subsequent to colonization in high-risk patients, reducing antibiotic use could be useful in preventing fungal infections.