Occurrence Of Invasive Fungal Infections Research Articles

Assessment of microbiological air quality in hemato-oncology units and its relationship with the occurrence of invasive fungal infections: an integrative review

Worldwide aging of the human population has promoted an increase in the incidence of neoplasia, including hematological cancers, which render patients particularly vulnerable to invasive fungal infections. For this reason, air filtration in hematooncology units has been recommended. However, scarce literature has assessed the impact of microbiological air quality on the occurrence of fungal infections in this population. We performed an integrative review of studies in the MEDLINE database that were published between January 1980 and October 2012, using the following combinations of keywords: air × quality × HEPA, air × quality × hematology, and airborne fungal infections. The search yielded only 13 articles, suggesting that high-efficiency filtering of the ambient air in hemato-oncology units can prevent the incidence of invasive fungal infections. However, no randomized clinical trial was found to confirm this suggestion. Currently, there is no consensus about the maximum allowable count of fungi in the air, which complicates filtration monitoring, including filter maintenance and replacement, and needs to be addressed in future studies.

Clinical study of invasive fungal infection secondary to systemic lupus erythematosus

To study the clinical characteristics of invasive fungal infection secondary to systemic lupus erythematosus (SLE). We observed the clinical features and experimental examination in 91 patients treated in Xiangya Hospital in recent years, of which 48 patients with invasive fungal infection and 41 patients without invasive fungal infection. The invasive fungal infection secondary to SLE mainly occurred in the lungs, nervous system, and urinary system. The fungi were mainly Candida albins and Aspergillus. The rate of invasive fungal infection in SLE patients and the level of CRP and TNF-α in these patients were significantly increased. The occurrence of invasive fungal infection was positively correlated with the prolonged course of disease, long-term use of immunosuppressants and antibiotics, and occurrence of complications, such as hypoproteinemia, leukocytopenia, and so on. The levels of C-reactive protein (CRP) and tumor necrosis factor-α(TNF-α) were increased in SLE patients with invasive fungal infection. The clinical features of SLE patients with invasive fungal infections are long course of disease, long-time use of immunosuppressants or antibiotics, and occurrence of complications, such as hypoproteinemia or leukopenia. The level of CRP and TNF-α can be used as an important reference index for diagnosing invasive fungal infections.

Colony-stimulating factors for prevention and treatment of infectious complications in patients with acute myelogenous leukemia

Acute myelogenous leukemia (AML) is a fatal bone marrow cancer. Colony-stimulating factors (CSFs) are frequently administered during and after chemotherapy to reduce complications. However, their safety with regard to disease-related outcomes and survival in AML is unclear.Therefore, we performed a systematic review and meta-analysis to evaluate the impact of CSFs on patient outcomes, including survival. To assess the safety/efficacy of CSFs with regard to disease-related outcomes and survival in patients with AML. We conducted a comprehensive search strategy. We identified relevant randomized clinical trials by searching the Cochrane Central Register of Controlled Trials (The Cochrane Library 2010, Issue 7), MEDLINE (January 1966 to July 2010), LILACS (up to December 2009), databases of ongoing trials and relevant conference proceedings. Randomized controlled trials that compared the addition of CSFs during and following chemotherapy to chemotherapy alone in patients with AML. We excluded trials evaluating the role of CSFs administered for the purpose of stem cell collection and/or priming (e.g. before and/or only for the duration of chemotherapy). Two review authors appraised the quality of trials and extracted data. For each trial, we expressed results as relative risk (RR) with 95% confidence intervals (CI) for dichotomous data. We analyzed time-to-event outcomes as hazard ratios (HRs). The search yielded 19 trials including 5256 patients. The addition of CSFs to chemotherapy yielded no difference in all-cause mortality at 30 days and at the end of follow up (RR 0.97; 95% CI 0.80 to 1.18 andRR 1.01; 95% CI 0.98 to 1.05, respectively) or in overall survival (HR 1.00; 95% 0.93 to 1.08). There was no difference in complete remission rates (RR 1.03; 95% CI 0.99 to 1.07), relapse rates (RR 0.97; 95% CI 0.89 to 1.05) and disease-free survival (HR 1.00; 95% CI 0.90 to 1.13). CSFs did not decrease the occurrence of bacteremias (RR 0.96; 95% CI 0.82 to 1.12), nor the occurrence of invasive fungal infections (RR 1.40; 95% CI 0.90 to 2.19). CSFs marginally increased adverse events requiring discontinuation of CSFs as compared to the control arm (RR 1.33; 95% CI 1.00 to 1.56). In summary, colony-stimulating factors should not be given routinely to acute myelogenous leukemia patients post-chemotherapy since they do not affect overall survival or infectious parameters including the rate of bacteremias and invasive fungal infections.

Clinical characteristics and risk factors of 27 liver failure patients complicated by invasive fungal infections

To investigate the clinical feature, risk factors and outcome of treatment in patients with liver failure complicated by invasive fungal infections. Retro-spective analysis of the clinical data and related factors of 27 patients with liver failure com-plicated by invasive fungal infections was per-formed. These patients were admitted from January 2007 to August 2009 in our department. Among them, Candida albicans accounted for 17cases (54.84%), albicans tropicals for 4 cases (12.90%). Fungal infection in respiratory tract and alimentary tract accounted for 58.06% and 11% respectively. 81.25% of them had fever fluctuating from 37.4oC to 40oC. 81.25% had elevated white blood cell counts .All had the usage of broad-spectrum of antibiotics, whereas some of them used corticosteroids and had invasive medical manipulation for the treatment. Most patients deteriorated after invasive fungal infections. 21 cases accepted with the treatment of antifungal drugs and mortality rate was 63.00%. It was found that the invasive fungal infection possibility of patients with liver failure significantly increased. To prevent the occurrence of invasive fungal infection, promptly early treatment of liver failure, proper use of antibiotics, cautious use or disuse of corticosteroids, reduction of invasive medical manipulation should be well done. Early detection and treatment of fungal infection are vital to decrease in mortality rate.

Epidemiology, risk factors, and outcomes of invasive fungal infection in adults with acute myelogenous leukemia undergoing intensive induction chemotherapy.

6579 Background: The epidemiology and outcomes of invasive fungal infections (IFI) in patients with acute myelogenous leukemia (AML) have been poorly described. Methods: We performed a single center, retrospective analysis of the epidemiology, risk factors and clinical outcomes of IFIs in newly-diagnosed AML patients undergoing intensive, multi-agent induction timed sequential therapy (TST). Patients did not receive antifungal prophylaxis. IFIs were defined using EORTC/MSG criteria. Results: Of 97 consecutive patients (58% male; median age 53, range 22-72) admitted in 2007 and 2008, 27 (28%) had IFI, of which 7 (26%) were proven, 1 (4%) probable, and 17 (68%) possible with lung CT findings characteristic of fungal (mold) pneumonia. Of 8 proven/probable cases, 4 were due to molds and 4 were due to yeasts. Of 91 (94%) receiving antifungal therapy beginning median day 7 (range day -14 through day 25) of AML treatment; 41 (42%) received monotherapy (66% liposomal amphotericin B, 34% voriconazole) and the rest received multiple antifungals. Using univariate analysis, we identified risk factors for IFIs (Table 1). Occurrence of IFI was associated with lower complete remission rate (52% vs. 70% -IFI, p=0.06) and a decrease in 6 month survival (58% vs. 85% -IFI, p=0.01). Conclusions: AML patients with IFIs are more likely to die within 6 months of beginning intensive induction TST. Through this analysis, we are able to identify risk factors that may be associated with development of IFIs. Such identification may help to develop effective preventive antifungal strategies for high risk AML patients. Risk factors for + IFI cohort (overall), and for IFIs due to yeasts and molds No IFI (N=70) IFI (N=27) P- value IFI- yeasts (N=4) P-value IFI-moulds (N=23) P-value Age > 50 years (%) 49 70 0.07 75 NS 70 0.09 Presenting blast count > 10,000 (%) 26 44 0.09 50 NS 43 0.12 Time to ANC < 100 cells/mm3* 7 5 0.08 4 0.16 5 0.16 Time to recovery of ANC >100 cells/mm3* 22.5 26 0.07 25 NS 27 0.12 Onset of mucositis** 14 11.5 0.03 8.5 0.14 12 0.06 Duration of parenteral nutrition* 10 15 0.04 15 NS 14.5 0.07 NS: Non significant, ANC: Absolute neutrophil count. * Median Days of AML therapy (begins on Day 1) No significant financial relationships to disclose.

Antifungal prophylaxis with micafungin in neutropenic patients with hematological malignancies

The aim of the study was to assess the antifungal prophylactic efficacy, safety, and tolerability of micafungin, 150 mg daily, and to evaluate the usefulness of monitoring 1,3-β-d-glucan (BG) in neutropenic patients undergoing chemotherapy for hematological malignancies. This investigation was a retrospective, non-randomized study. A group of patients who did not receive systemic antifungal prophylaxis was compared to another group of patients who received micafungin 150 mg daily. All patients admitted with hematological malignancy and undergoing chemotherapy or stem cell transplant were included. The plasma BG level was measured once weekly. The clinical endpoint was the diagnosis of invasive fungal infection (IFI). Antifungal prophylaxis led to a significant decrease in the occurrence of IFI (from 12.3% to 1.5%, p = 0.001). Few severe adverse effects clearly attributable to micafungin were seen. Sensitivity, specificity, positive predictive value, negative predictive value, and efficiency of BG values >8.9 pg/mL for diagnosis of IFI were 0.90, 0.99, 0.82, 0.99, and 0.99, respectively. Micafungin, 150 mg daily, is an effective and safe drug for antifungal prophylaxis, and monitoring of BG antigenemia is a useful tool for diagnosis of IFI in neutropenic patients with hematological malignancies.

Population pharmacokinetics of posaconazole in neutropenic patients receiving chemotherapy for acute myelogenous leukemia or myelodysplastic syndrome

Objective:The relationship between patient characteristics and posaconazole exposures was evaluated in a population pharmacokinetic (PK) model using trial data from neutropenic patients administered oral posaconazole suspension as antifungal prophylaxis.Methods:Data were analyzed using nonlinear mixed-effects modeling. Covariates were tested using the forward addition, Objective Function (OF) cut-off of 3.84, followed by the backward elimination (OF cut-off 10.88) steps in NONMEM. These covariates included demographics, mucositis, neutropenia, vomiting, diarrhea, proton pump inhibitor (PPI) or H2-receptor antagonist usage and baseline bilirubin or baseline gamma-glutamyl transferase (GGT) levels ≥2 × upper limit of normal (ULN). A correlation between posaconazole PK and the occurrence of invasive fungal infection (IFI) was also examined.Results:Statistically significant associations were demonstrated between posaconazole PK and diarrhea, PPI intake, race, and baseline GGT and bilirubin levels. These covariates did not predominate in patients who developed IFI.Conclusion:This analysis provides information regarding the correlation of patient covariates with posaconazole exposures estimated in a clinical setting. The results of this analysis agree with previously reported analyses. However, because of the successful prophylaxis and the low number of posaconazole-treated patients with IFI proven or probable (IFIPP), the absence of a statistically significant relationship between IFIPP and exposure may not mean this relationship does not exist. A meta-analysis of several efficacy trials or exploring alternate composite endpoints for efficacy may be needed to answer this question.

Does the Occurrence of Invasive Fungal Infection in Acute Leukemia Patients, Impact on the Chemotherapy Schedule and Event-Free Survival? a Case-Control Study

Background: In acute leukemia (AL) patients, mortality rates of the most common IFI (i.e., aspergillosis and candidiasis) are well illustrated in the literature from the IFI diagnosis, as well as the rate of fungal relapse during subsequent periods at risk, such as neutropenic phases, or transplant. However, few data are available about the impact of IFI on the subsequent chemotherapy schedule and the indirect impact of IFI on the relapse-free and overall survival. Clinicians are usually reluctant to give the full chemotherapy doses on time, due to the risk of life-threatening fungal relapse during the subsequent courses. Even with secondary prophylaxis, they often delay or decrease the doses of chemotherapy. This may impact on the leukemia outcome. The aim of this case-control study was to assess the potential impact of proven or probable IFI onset on the application of the chemotherapy schedule in AL patients, and its consequences on the leukemia outcome, by comparing patients with and without IFI in a single institution. Delays and changes in chemotherapy doses and drug choices were evaluated and compared to the planned schedule in the protocol.Methods: All consecutive AL patients with a first episode of proven or probable IFI according to the EORTC-MSG criteria between 2000–2006 were reviewed. All patients have been treated in, or according to, clinical research protocols where timing and doses of chemotherapy were predefined. Patients who were planned for allogeneic transplant were excluded as those who were at their last consolidation course when they got IFI or in a palliative phase of the leukemia. Any delay, dose decrease, or dose change were defined as any difference compared to the planned schedule. We planned to include 3 control patients for each case, selected among AL patients without IFI, and matched for age, sex, type of AL, chemotherapy protocol, and year of treatment. 27 case and 76 control patients were finally included. The event-free survival (EFS) was defined as survival without evidence of relapse or progression, or death of any cause.Results: The mean age of the 27 case patients (26 myeloid and 1 lymphoblastic AL) was 52 y (± 13), the M/F ratio was 14/13 IFI (7 candidiasis, 19 aspergillosis, 1 zygomycosis) was proven for 10 patients (37%), and probable for 17 (63%). Twenty (71%) of these IFI occurred during the first induction phase. All patients were treated for their IFI with ≥ 1 antifungal, and 4 of them had a surgical resection of the main fungal lesion(s). These 27 patients were compared to 76 controls (73 myeloid and 3 lymphoblastic AL) without IFI. A delay of the next course of chemotherapy according to the planned protocol was significantly more frequent in the IFI group (16/27, 59%) than in the control group (16/76, 21%) (p=.001). Similarly, the dose or choice of the drugs was modified more frequently in the IFI group (7/27, 26%) than in the control group (6/76, 8%) (p=.037). Only 9 (33%) patients got their next chemotherapy course without any modification in time, dose, or choice of drug, vs. 19/76 (75%) in the control group (p<.0001). The EFS of the IFI group was lower than that of the control group, although this difference was not significant.Conclusion: In this single-institution case-control study, the occurrence of IFI significantly modified the application of chemotherapy courses, both on timing of the courses, and dose and choice of the drugs when compared to patients without IFI. Although the difference was not significant, there was a tendency for a lower EFS in the IFI group when compared to the control group.−

Treatment Options for Invasive Fungal Infections

Clinicians face an increasing occurrence of invasive fungal infections. These are due not only to traditional yeast and mould species but also to rare pathogens that can be difficult to treat. The introduction of new agents has expanded the options for treating common and rare mycotic infections with antifungal efficacy at least equal, and safety far superior, to that of a once-limited choice of therapies. Patients with invasive mycoses frequently have concomitant disorders and require multidrug regimens. Clinicians must be aware of the potential for interactions among agents available for treating invasive mycoses in patients with serious underlying conditions.

Prevention and monitoring of invasive fungal infections in pediatric patients with cancer and hematologic disorders

The occurrence of invasive fungal infection (IFIs) in a pediatric hematology/oncology unit after renovation of the ventilation system, and initiating routine azole antifungal prophylaxis was monitored. In addition, the value of serial screening for Aspergillus galactomannan (GM) for diagnosing invasive aspergillosis was assessed. A total of 98 consecutive high-risk pediatric patients were prospectively surveyed for signs of IFI and weekly monitored for serum GM. The data was not made available to treating physicians. Only 2 patients had proven and 27 possible IFI based on the European Organization for Research and Treatment of Cancer/Mycoses Study Group definitions. The incidence of proven IFI was 1/31 (3.2%) in the allogeneic stem cell transplant (SCT) (Aspergillus spp), 0/26 in the autologous SCT, and 1/60 (1.6%) in the induction therapy group (C. krusei). GM was detected at least in one tested sample in 12/98 patients (12.2%), in five patients in two or more sequential samples. In the latter group, IFI was proven in one patient and could not be excluded in the others. Four of the five patients belonged to the 31 allogeneic and one to the 26 autologous SCT patients. In patients with only one positive GM test none developed signs of IFI and only one received empirical amphotericin B. With the currently used preventative and prophylactic measures, IFI is uncommon in children with high-risk for infection. Regular screening for GM could be useful among allogeneic SCT patients and two positive samples should prompt further investigative procedures and pre-emptive antifungal therapy.

Invasive fungal infections after allogeneic peripheral blood stem cell transplantation: incidence and risk factors in 395 patients.

We have analysed the incidence and risk factors for the occurrence of invasive fungal infections (IFI) among 395 recipients of an allogeneic peripheral blood stem cell transplantation (PBSCT) from a human leucocyte antigen (HLA)-identical sibling. IFI (n = 50) occurred in 46 patients, giving an overall probability of 14%. There were 12 cases of invasive candidiasis (3%), with only one death. Non-Candida IFI occurred in 37 patients (12% probability), mostly invasive aspergillosis (n = 32). In multivariate analysis the only two significant variables associated with a higher risk of developing a non-Candida IFI were the development of moderate-to-severe graft-versus-host disease (GvHD, P < 0.0001; OR 4.6) and having received steroid prophylaxis for GvHD (P = 0.04; OR 2.1). In multivariate analysis the variables associated with a lower overall survival after PBSCT were development of a non-Candida IFI (P < 0.0001; OR 5.6), non-early disease phase (P = 0.0001; OR 1.9), steroid prophylaxis (P = 0.02; OR 1.4), moderate-to-severe GvHD (P = 0.01; OR 1.6) and cytomegalovirus infection post transplant (P = 0.001; OR 1.8). Our results show that non-Candida IFI (in particular aspergillosis) was an important cause of infectious morbidity and mortality after an HLA-identical sibling PBSCT, while invasive candidiasis was rare. Use of steroid prophylaxis and, in particular, the development of moderate-to-severe GvHD post transplant were risk factors for non-Candida IFI. Prophylactic strategies for these infections should thus take into account these risk factors.