Risk Factors For Fungal Infection Research Articles

Bacterial and fungal organisms in otitis externa patients without fungal infection risk factors in Erzurum, Turkey

SummaryAim: To describe the bacterial and fungal organisms in otitis externa patients without other risk factors for fungal infections.Study designCross sectional cohort descriptive study.Materials and MethodsEar swabs were obtained from 362 patients aged 1 to 55 years old with clinically diagnosed otitis externa in Erzurum, Turkey, between January 2006 and April 2007, and cultured for aerobic and anaerobic bacteria and fungi, using EMB, 5% sheep's blood, chocolate agar, anaerobic blood agar plate, thioglycollate broth and sabaroud agar using standard microbiological technique to diagnose isolates.Results219 cultures were positive and a total of 267 isolates were obtained. Of the isolates, 68.16% (n: 182) were aerobic or facultative bacteria, 1.12 % (3) were anaerobic bacteria, 30.71 % (82) were fungi and 17.5 % (38) were polymicrobial infections.ConclusionFungal organisms especially Candida species may be isolated from ears of otitis externa patients without fungal infection risk factors such as ear self-cleaning, local antimicrobial, antifungal or corticosteroid drops or systemic antimicrobial or antifungal agents within the preceding week. Bacterial and fungal cultures may be recommended, and anti-fungal agents may be added, to treatment regimens in patients with otitis externa.

Perforación gástrica asociada a infección por Candida

Notable causes of gastroduodenal ulcer are Helicobacter pylori infection, intake of non-steroidal anti-inflammatory agents, neoplastic disease, acid hypersecretory states and secondary peptic ulcer disease. There are case reports of healthy patients or those with risk factors for fungal infection who develop gastroduodenal ulcer perforation associated with the presence of fungi in ascitic fluid or gastroduodenal ulcer tissue but without the above-mentioned etiological factors. Thus, other factors and pathogens may be involved in the pathogenesis of perforation. The use of antifungal agents in patients following surgery for a perforated gastroduodenal ulcer is controversial. We report two cases of healthy patients who underwent surgery for perforated gastroduodenal ulcer, in whom the most frequent causes of perforation were excluded. Only the presence of Candida in the ulcer was found.

Pulmonary Fungal Infections in Kidney Transplant Recipients: An 8-Year Study

Invasive fungal infections are among the most important causes of mortality among transplant patients. One of the most common manifestations of these infections is pulmonary fungal infection (PFI). The present study sought to evaluate the rate of PFI in kidney transplant patients. Materials and Methods We retrospectively analyzed the data of 595 patients who underwent kidney transplantation from February 1999 to February 2007. Bronchoalveolar lavage (BAL) culture and tissue biopsy were used to confirm PFI. Results Thirteen of 595 patients (2.2%) experienced PFI. The most common pathogen (8/13, 41.5%) was Aspergillus, with 5 (38.5%) infected with Aspergillus only, 2 (15.4%) with both Aspergillus and Candida, and 1 (7.7%) with Aspergillus and mucormycosis. Seven of 13 (53.8%) died and 4 (30.7%) lost the transplanted kidney. Immunosuppressive therapy following rejection and prescription of broad spectrum antibiotics were the most important risk factors for fungal infections in these patients. Conclusions Fungal infections are among the most important causes of mortality among transplant patients, of which the most common manifestation is pulmonary. Immunosuppressive therapy and broad spectrum antibiotics are important risk factors, and Aspergillus is the most common pathogen responsible for fungal infections.

Prevalence and outcome of fungal infection in patients with severe acute pancreatitis

To study the prevalence of risk factors and outcome of fungal infections in patients with severe acute pancreatitis. Fifty consecutive patients with severe acute pancreatitis were investigated for evidence of fungal infection by weekly culture of body fluids and aspirate from pancreatic/peripancreatic tissue and samples collected at necrosectomy. All patients were managed as per a standard protocol. Patients with documented fungal infection were treated with intravenous amphotericin or fluconazole. Data were analyzed using SPSS software (version 13), and risk factors for fungal infection and mortality were determined. Fungal infection was documented in 18 (36%) of 50 patients with Candida albicans (the commonest species). The incidence of fungal infection steadily increased with increasing duration of hospital stay. Those with fungal infection more often had evidence of respiratory failure (P = 0.031) and hypotension (P = 0.031) at admission, prolonged hospital stay > 4 weeks (P = 0.034), longer duration of antibiotics (P = 0.003), received total parenteral nutrition (P = 0.005), and required mechanical ventilation (P = 0.001) in contrast to those without fungal infection. The logistic regression analysis found the independent risk factors for fungal infection to be antibiotic therapy for > 4 weeks and hypotension at hospitalization. Of the 18 patients with fungal infection, 13 were administered intravenous antifungals; eight of these patients survived, while the five who did not receive antifungals died. Fungal infection was detected in 36% of our patients. The independent risk factors associated with it were hypotension at hospitalization and prolonged antibiotic therapy. Antifungal therapy improved their chances of survival.

270: Preceeding Respiratory Viral Infection Is a Strong Risk Factor for Fungal Infection in Lung Transplant Recipients

270: Preceeding Respiratory Viral Infection Is a Strong Risk Factor for Fungal Infection in Lung Transplant Recipients

Quantification by Superconducting Quantum Interference Device (SQUID) of Iron Overload after Allogeneic Hematopoietic Stem Cell Transplantation (HSCT).

Introduction. Iron overload (IO) is an adverse prognostic factor in patients who undergo allogeneic HSCT for thalassemia and appears to play a similar role in patients with other hematological disorders. Estimation of IO is primarily based on serum ferritin, however many confounding factors particularly in HSCT recipients may result in frequent ferritin overestimation. Aim of the study was to quantify IO by SQUID after HSCT and evaluate the impact on hepatic function and infections. Additionally, the feasibility of iron-depletion has been investigated.Methods. Between December 2005 and December 2007, 102 consecutive pts who were admitted at our outpatient department have been analyzed. Patients received HSCT from a matched sibling (n=66), a partially matched relative (n=4) or a matched unrelated donor (n=32). Primary diagnosis included acute leukemia/MDS in 61% of cases. Assessment of IO after HSCT included serum ferritin and in those with hyperferritinemia (> 1000 ng/ml), liver iron concentration (LIC) was evaluated by SQUID magnetic susceptometry. Iron removal therapy was offered to patients with moderate (LIC 1000–2000 microg/gww) or severe (LIC >2000 microg/gww) IO.Results. Patients who were in complete remission underwent ferritin assessment at a median time of 578 days from transplantation. Fifty-seven had a ferritin level below the threshold of 1000 ng/ml; in this cohort the median time from HSCT to ferritin assessment was 1006 days, significantly different from the median time of 183 days of the 45 patients who had a ferritin level > 1000 ng/ml. LIC evaluated by SQUID was available for 42/45 patients with elevated ferritin values. Overall, 29 patients had moderate to severe IO: median LIC values were 1493 microg/gww (range 1030–3253 microg/gww). Thirteen patients had normal LIC values (LIC<400 microg/gww) despite high serum ferritin levels. Multivariate analysis showed a significant correlation between ferritin levels > 1000 ng/ml and the occurrence of liver dysfunction defined by the presence of at least one abnormal liver function test (LFT) on two or more occasions (OR 6.8; 95%CI 2.2–20.6); the correlation hold the statistical significance even including into the multivariate model the different time of ferritin assessment. In addition, the rate of proven/probable invasive fungal disease was significantly higher among patients with hyperferritinemia as compared to patients with normal ferritin levels (13% vs 0%; p=.006). Nineteen of the 23 patients considered eligible to iron depletion, underwent regular phlebotomy: 9 patients completed the program after a median time of 10 months (range 3–13 months), reaching the target of ferritin < 500 ng/ml; for 6 patients the program is still ongoing, while 4 patients discontinued the phlebotomy protocol (relapse n=2; hypotension, n=1; progressive anemia, n=1). In 8/9 patients who were revaluated by SQUID at the end of iron depletion program there was a significant decrease of LIC (median 1368 microg/gww to 606 microg/gww; p=.005) that parallels changes of serum ferritin; one patient did not show e remarkable reduction of LIC despite serum ferritin normalization.. Three of the 4 patients ineligible to phlebotomy were successfully treated with deferasirox and 1 patient was treated with deferoxamine.Conclusion. The measurement of LIC obtained by SQUID documented the presence of moderate/severe IO in 69% of the patients with high ferritin levels. Our preliminary data showed that in HSCT recipients, high ferritin level is an independent risk factor for the occurrence of abnormal LFTs and IO may be considered a potential risk factor for fungal infections. A phlebotomy program resulted feasible in 65% of the patients who might benefit from a procedure of iron depletion

Surgical Wound Mucormycosis Necessitating Hand Amputation: A Case Report

We report an unusual case of cutaneous mucormycosis in a 17-year-old man who had no risk factors for fungal infection. The aggressive nature of cutaneous mucormycosis is illustrated. A high index of suspicion is crucial for identifying and preventing progression of this disease, which can lead to limb amputation, even death. Extra vigilance should be given to those who are immunocompromised, including those receiving short courses of steroids. Early recognition, prompt surgical intervention and initiation of an appropriate antifungal treatment are crucial in the management of this rare but potentially limb- and life-threatening infection.

Fungal prophylaxis in very low birth weight neonates: nystatin, fluconazole or nothing?

To examine recent evidence on the efficacy of antifungal prophylaxis to prevent neonatal systemic fungal infection. The review also aims to examine other relevant data, including the incidence of fungal infection, adverse effects of antifungal therapy and avoidable risk factors. There is strong evidence that systemic fluconazole prophylaxis reduces the incidence of systemic fungal infections, with a trend towards reduction in mortality. However, the preprophylaxis incidence of fungal infection has been very high in the published studies. Fluconazole use is sometimes associated with cholestasis and there are theoretical concerns as well that prophylactic fluconazole will select for fluconazole-resistant organisms and nonalbicans Candida infections. There is reasonable evidence that oral nystatin is effective in preventing fungal infections and at the same time it is inexpensive and well tolerated. The reported incidence of systemic fungal infections is much lower in the UK than in the USA and Italy. Oral nystatin prophylaxis is inexpensive, effective and nontoxic and should be used routinely for babies of birth weight less than 1500 g. Systemic fluconazole, which is more toxic and may select for resistant fungi, is probably only indicated when the rate of fungal infection remains high despite introducing measures targeting known risk factors for fungal infection. These measures include introducing enteral feeds early, reducing the duration of parenteral feeding, and reducing the use of broad spectrum antibiotics, particularly cephalosporins. Future studies of prophylactic fluconazole should use oral nystatin, not placebo, as the comparator.

DIAGNOSTIC BRONCHOALVEOLAR LAVAGE FOR PULMONARY FUNGAL INFECTIONS IN CRITICALLY ILL CHILDREN

INTRODUCTION: The incidence of pulmonary fungal infection is increasing worldwide, particularly in critically ill patients. OBJECTIVE: The objective of this study was to assess bronchoalveolar lavage (BAL) as a diagnostic specimen for clinically and radiologically suspected fungal pneumonia in critically ill children. METHODS: Thirty-five children who were admitted to the PICU of Ain Shams University because of their critical illness were included. All children underwent full medical history; thorough clinical examination, including general and local chest examination and basic laboratory investigations (from that, the Pediatric Risk of Mortality [PRISM] score was calculated to evaluate the critical illness severity); chest imaging; and bronchoscopic collection of BAL and microbiological assessment of BAL and blood using direct microscopic examination, cultured on Sabouraud dextrose agar, and fungal antigen detection using the enzyme-linked immunosorbent test for both Aspergillus galactomannan antigen and Candida mannan antigen. RESULTS: Pulmonary fungal infection was documented in 77% of the studied children. BAL investigations proved to have a higher diagnostic yield in comparison with blood. Positive fungal antigens in BAL fluid were significantly higher than positive BAL fungal cultures in studied children. Analysis of the risk factors for fungal infection among the studied patients revealed that prolonged PICU stay (≥1 week) and high PRISM score (mean: 35.9 ± 6.46) were significant risk factors for fungal infection. CONCLUSIONS: BAL fluid investigation has a significantly higher diagnostic value for pulmonary fungal infections than that of the blood. The results may be further improved especially if both culture and antigen fungal detections are combined.

Positive Fungal Cultures in Burn Patients: A Multicenter Review

Fungal infections are increasingly common in burn patients. We performed this study to determine the incidence and outcomes of fungal cultures in acutely burned patients. Members of the American Burn Association's Multicenter Trials Group were asked to review patients admitted during 2002-2003 who developed one or more cultures positive for fungal organisms. Data on demographics, site(s), species and number of cultures, and presence of risk factors for fungal infections were collected. Patients were categorized as untreated (including prophylactic topical antifungals therapy), nonsystemic treatment (nonprophylactic topical antifungal therapy, surgery, removal of foreign bodies), or systemic treatment (enteral or parenteral therapy). Fifteen institutions reviewed 6918 patients, of whom 435 (6.3%) had positive fungal cultures. These patients had mean age of 33.2 +/- 23.6 years, burn size of 34.8 +/- 22.7%TBSA, and 38% had inhalation injuries. Organisms included Candida species (371 patients; 85%), yeast non-Candida (93 patients, 21%), Aspergillus (60 patients, 14%), other mold (39 patients, 9.0%), and others (6 patients, 1.4%). Systemically treated patients were older, had larger burns, more inhalation injuries, more risk factors, a higher incidence of multiple positive cultures, and significantly increased mortality (21.2%), compared with nonsystemic (mortality 5.0%) or untreated patients (mortality 7.8%). In multivariate analysis, increasing age and burn size, number of culture sites, and cultures positive for Aspergillus or other mold correlated with mortality. Positive fungal cultures occur frequently in patients with large burns. The low mortality for untreated patients suggests that appropriate clinical judgment was used in most treatment decisions. Nonetheless, indications for treatment of fungal isolates in burn patients remain unclear, and should be developed.

The Effect Of Candida Infections On Mortality Of ICU Patients: Results Of Sixty-Three Patients

Backgrounds: The aim of this study was to compare the fungal infections' mortality rates with other our ICU patients having fungal infections' risk factors and prolonged stay. Methods: We performed this retrospective, observational, comparative study on 63 ICU patients with Candida infection and 62 controls. The patients with Candida infection compared with controls for risk factors for fungal infections and mortality. Candida infections were composed of patients with candidemia and candiduria. We also compared candidemia/candiduria cases exclusively to the control group in respect to mortality and morbidity. Results: No statistically significant difference was established for mortality between candida group and controls (50.79 % and 48.38 % respectively, p=0.859). The mortality rates of candiduria and candidemia groups were also similar (46.66% versus 54.55%, p=0.617). When we compared with candidemia and controls for mortality rate, there was no statistically differences between them (54.55% versus 48.38, p=0.668). The mortality rate of the candiduria group was also similar to the controls (46.66% versus 48.38%, p=1). Conclusion: The severity of blood infections developed by Candida is well-known; however candiduria should not dismissed but managed more aggressively. We observed that candiduria had similar mortality rate to candidemia. This study was presented with preliminary data in 26 th International Symposium on Intensive Care and Emergency Medicine, Brussels, 2006.

Risk Factors for Fungal Infections Identified in Burn-Injured Patients

Risk Factors for Fungal Infections Identified in Burn-Injured Patients

Invasive fungal infection in systemic lupus erythematosus: an analysis of 15 cases and a literature review

To analyse 15 cases of invasive fungal infection and mortality parameters in the largest series in the last 35 yrs of patients with systemic lupus erythematosus (SLE) at a single medical centre. Fifteen patients with SLE and invasive fungal infections were retrospectively enrolled. Clinical and laboratory data, fungal species and infected sites, corticosteroid and immunosuppressant doses and SLE disease activity index were assessed retrospectively. Comparison and correlation analyses utilized Fisher's exact test, the chi-square test, Mann-Whitney U-test or the Wilcoxon signed-rank test where appropriate. In contrast to other review reports, Cryptococcus neoformans was the most commonly identified fungus in this Taiwanese series. Notably, the prevalence of autoimmune haemolytic anaemia and positive results for the anti-cardiolipin antibody in this study were significantly higher than those in SLE patients in general (P < 0.0001 and P < 0.0001, respectively). Fungal infection contributed to cause of death in 7 of 15 (46.7%) patients, of which Cryptococcus neoformans accounted for six of these infections. Low-dose prednisolone (<1 or <0.5 mg/kg/day based on arbitrary division) prior to fungal infection tended to correlate with 1 yr mortality after diagnosis of SLE (P = 0.077 or P = 0.080). However, following fungal infection, patients who died from infection itself had been prescribed with higher prednisolone dose or equivalent than surviving patients (P = 0.016). All SLE patients with fungal infections had active SLE (SLEDAI >7). Cryptococcus neoformans infection accounted for most fatalities in SLE patients with fungal infections in this series. Active lupus disease is probably a risk factor for fungal infection in SLE patients. Notably, low prednisolone doses prior to fungal infection or high prednisolone doses following fungal infection tended to associate with or correlated to fatality, respectively. Therefore, we suggest that different prednisolone doses prescribed at various times impact the incidence of fungal infection and its associated mortality.

Higher fungal infection rate in elderly patients (more than 80 years old) suffering from diffuse large B cell lymphoma and treated with rituximab plus CHOP

Although adding rituximab to standard cyclophosphamide, doxorubicin, vincristine, and prednisone (CHOP) chemotherapy is an efficacious and well-tolerated regimen in elderly patients with diffuse large B cell lymphoma (DLBCL), it may increase susceptibility to opportunistic infections, and such cases have been reported. Our study was to identify the risk factors for fungal infection in a retrospective case-control matched study of 34 elderly DLBCL patients treated with rituximab plus CHOP (R-CHOP) and 35 control patients treated with the standard CHOP regimen at the Taipei Veterans General Hospital, Taiwan. The rate of overall infection was similar in both groups. However, subgroup analysis found that the fungal infection rate was significantly different, 41.7 and 17.1%, in the R-CHOP and CHOP groups, respectively, (P = 0.03). Univariate analysis identified the rituximab plus CHOP chemotherapy regimen (P = 0.03), age older than 80 years (P = 0.04), and bone marrow involvement (P = 0.04) as risk factors for development of fungal infection, whereas, multivariate regression analysis identified only rituximab plus CHOP and old age. Adding rituximab to the standard CHOP regimen in elderly DLBCL patients might increase the incidence of fungal infection especially in those older than 80 years old.

Empiric guidelines for treatment of Candida infection in high-risk neonates

The incidence of neonatal Candida infection is steadily increasing and has been reported to be 1.6% in infants admitted to neonatal intensive care units (NICUs) [3].The use of therapeutic guidelines based on risk factors for fungal infection is important for achieving an early diagnosis of invasive Candida infection and for obtaining a decrease of its morbidity and mortality [1]. We performed this study in order to evaluate the efficacy of empiric guidelines in reducing proven mortality resulting from Candida infection.

Positive Fungal Cultures in Burn Patients - A Multicenter Review

Fungal infections are increasingly common in burn patients. We performed this study to determine the incidence and outcomes of fungal cultures in acutely burned patients. Members of the American Burn Association's Multicenter Trials Group were asked to review patients admitted during 2002-2003 who developed one or more cultures positive for fungal organisms. Data on demographics, site(s), species and number of cultures, and presence of risk factors for fungal infections were collected. Patients were categorized as untreated (including prophylactic topical antifungals therapy), nonsystemic treatment (nonprophylactic topical antifungal therapy, surgery, removal of foreign bodies), or systemic treatment (enteral or parenteral therapy). Fifteen institutions reviewed 6918 patients, of whom 435 (6.3%) had positive fungal cultures. These patients had mean age of 33.2 ± 23.6 years, burn size of 34.8 ± 22.7%TBSA, and 38% had inhalation injuries. Organisms included Candida species (371 patients; 85%), yeast non-Candida (93 patients, 21%), Aspergillus (60 patients, 14%), other mold (39 patients, 9.0%), and others (6 patients, 1.4%). Systemically treated patients were older, had larger burns, more inhalation injuries, more risk factors, a higher incidence of multiple positive cultures, and significantly increased mortality (21.2%), compared with nonsystemic (mortality 5.0%) or untreated patients (mortality 7.8%). In multivariate analysis, increasing age and burn size, number of culture sites, and cultures positive for Aspergillus or other mold correlated with mortality. Positive fungal cultures occur frequently in patients with large burns. The low mortality for untreated patients suggests that appropriate clinical judgment was used in most treatment decisions. Nonetheless, indications for treatment of fungal isolates in burn patients remain unclear, and should be developed.

Antibiotics Administration and Risk of Fungal Infection in Burns

Exposure to antibiotics is a major risk factor for fungal infections (1). Alterations of the gut and skin flora allows progressive colonization by Candida sp, which may result in an invasive candidiasis (2). The impact varies among different classes of antibiotics, and cephalosporins have the more pronounced effect in non burned patients. We explore the impact of exposure to different classes of antibiotics on candida colonization in burned patients. Using our prospective research clinical database, we included all burned patients consecutively admitted from July 1st 2002 to September 20th 2005, until discharge or first candida identified. Antibiotics were classified according to the WHO criteria. Systematic screening cultures were routinely performed in all patients. The incidence of colonization was compared according to the type of antibiotics used and expressed as odd ratios and we calculated the number of patients to be exposed to antibiotics to become colonized. Over 3 years, we included 404 burned patients. 280 (69%) received antibiotics and 75 (27% of them) become colonized by Candida, as compared to no colonization in those not exposed to antibiotics (OR 45.1). The risk was correlated with the antibiotic selection pressure ((Figure). All classes were associated with significant risk of candida colonization, except cephalosorins (Table)

Multifocal Candida species colonization as a trigger for early antifungal therapy in critically ill patients: What about other risk factors for fungal infection?*

Service de Réanimation Médicale, Dijon University Hospital, Dijon, France This author has nothing to disclose.

Invasive Fungal Infections in Reduced Intensity Cord Blood Transplantation (RICBT).

<Background> Invasive fungal infection is one of the most fatal complications after stem cell transplantation (SCT). EBMT group reported the risk factors of invasive fungal infections were delayed neutrophile engraftment and steroid use for acute graft versus host disease (GVHD) in cord blood transplantation with myeloablative regimens. However it has not been clear about invasive fungal infections after RICBT.<Objective> The 1st purpose of this report was to investigate the incidence and pathogens of invasive fungal infections and the 2nd was to identify the risk factors for fungal infections after RICBT.<Patients and Methods> We reviewed medical records of 103 patients with hematological diseases who had received RICBT between March 2002 and May 2005 at Toranomon Hospital, Tokyo, Japan. Median age was 57 years (17–79). Primary diseases were advanced (n=81) or standard (n=22). Median follow-up was 14 months (0.5–27). Conditioning regimen was fludarabine 125 mg/m2, melphalan 80 mg/m2 and TBI 4 Gy. GVHD prophylaxis was cyclosporine (n=67) or tacrolimus (n=43). Median total nucleated cells (TNC): 2.8 x 10^7 cells (1.7–5.2); Median CD34+: 0.78 x 10^5 cells (0.01–3.28); HLA match: 6/6 (n=2), 5/6 (n=16), 4/6 (n=88), 3/6 (n=1). Fluconazole 200mg/day was used as prophylaxis of fungal infections. Diagnosis of invasive fungal infection was made with the following EORTC/MSG criteria. The following factors were considered potential predictors of outcomes about 2nd purpose: patient's age, infused TNC dose, disease status at transplantation, speed of netrophile engraftment, pre-engraftment reactions (PER) which we reported (Clin Cancer Res. 10:3586–92, 2004), and acute GVHD.<Results> Neutrophile (>500/μL) and platelet recovery (>20,000/μL) were observed in 83% at day 60 (median; 22 day), 55% at day 100 (43day), respectively. Cumulative incidence of acute GVHD (II-IV) was 33%. OS were 39% (95% CI: 29–50) in all cases, 67% (95% CI: 47–87) in standard, and 32% (95% CI: 20–43) in advanced (p<0.05), respectively. Incidence of invasive fungal infections was 12% (95% CI: 6–20) and median onset day was 23 days (1–84) after RICBT. Pathogens of invasive fungal infections comprised 9 cases of probable invasive pulmonary aspergillosis, and one case each of Candida pneumonia and Trichosporon sepsis. Incidence of invasive fungal infections in patients with PER+/steroids + (n=22) was 28% (95% CI: 9–43), in patients without PER (n=80) was 7% (95% CI: 1–14). In multivariate analysis, the most important risk factor of invasive fungal infections was steroid use for PER (p<0.05), while other factors did not influence.<Discussion/Conclusion> In our experience with reduced intensity cord blood transplantation, the only risk factor for invasive fungal infections was steroid use for PER within 30 days. Invasive fungal infections, especially invasive aspergillosis, remain an important complication after allogeneic stem cell transplantation, regardless of the type of conditioning regimens and the sources of stem cells. [Display omitted]

Prophylaxis of Candida infections in adult trauma and surgical intensive care patients: a systematic review and meta-analysis

To determine whether systemic antifungal prophylaxis decreases infectious morbidity and mortality in nonneutropenic, critically ill, trauma and surgical intensive care unit (ICU) adult patients. Systematic review and meta-analysis of randomized clinical trials. We used a fixed effect model, with risk ratio (RR) and 95% confidence intervals (CI). Patients admitted to ICU after surgery or trauma, with multiple risk factors for fungal infections. Nine studies (seven double blind) with a total of 1,226 patients compared ketoconazole (three) or fluconazole (six) to placebo (eight) or no treatment (one). Prophylaxis with azole was associated with reduced rates of candidemia (RR 0.30, 95% CI 0.10-0.82), mortality attributable to Candida infection (RR 0.25, 95% CI 0.08-0.80), and overall mortality (RR 0.60, 95% CI 0.45-0.81). Time to event analysis showed a significantly lower probability of fungal infections in treated patients. There was no evidence of statistical heterogeneity between studies, and publication bias assessment gave a negative results. There was, however, wide variability in the definition and reporting of some relevant clinical outcomes (e.g., confirmed or suspected infections, colonization) and pooling of these outcome measures was not feasible. Prophylaxis of candidal infection among critically ill ICU patients has beneficial effect on certain outcome measures, but additional data from well designed clinical trials and long-term epidemiological observations are needed to provide firm recommendations for the selection of subgroups of patients who would most benefit from prophylaxis and to determine the effect of prophylaxis on fungal resistance patterns.