Low utilization of vancomycin in febrile neutropenia: real-world evidence from 4 Brazilian centers.

PURPOSE: The prompt initiation of a betalactam antibiotic in febrile neutropenic patients is considered standard of care, while the empiric use of vancomycin is recommended by guidelines in specific situations, with a low level of evidence. The objective of this study was to assess the utilization of vancomycin in the management of febrile neutropenia within four Brazilian medical centers that implemented more stringent criteria for its administration. METHODS: A comprehensive retrospective analysis was performed encompassing all instances of febrile neutropenia observed during the period from 2013 to 2019. The primary focus was to identify the reasons for initiating vancomycin therapy. RESULTS: A total of 536 consecutive episodes of febrile neutropenia were documented, involving 384 patients with a median age of 52 years (range 18-86). Chemotherapy preceded febrile neutropenia in 59.7% of cases, while 40.3% occurred after hematopoietic stem cell transplantation. The most prevalent underlying diseases were acute myeloid leukemia (26.5%) and non-Hodgkin's lymphoma (22%). According to international guidelines, vancomycin should have been initiated at the onset of fever in 145 episodes (27%); however, it was administered in only 27 cases (5.0%). Three episodes were associated with Staphylococcus aureus bacteremia, two of which were methicillin resistant. The 15-day and 30-day mortality rates were 5.0% and 9.9%, respectively. CONCLUSIONS: The results of this study underscore the notably low utilization rate of vancomycin in cases of febrile neutropenia, despite clear indications outlined in established guidelines. These findings emphasize the importance of carefully implementing guideline recommendations, considering local epidemiological factors, especially when the strength of recommendation is weak.

Invasive Aspergillosis in Patients with Acute Leukemia: Comparison Between Acute Myeloid and Acute Lymphoid Leukemia.

BACKGROUND: The epidemiology of invasive aspergillosis (IA) in patients with acute lymphoid leukemia (ALL) has not been well characterized. OBJECTIVES: To identify potential peculiarities in the natural history, treatment response and outcome of IA diagnosed in patients with ALL and AML. METHODS: This is a retrospective cohort study conducted in seven tertiary-care hospitals between 2009 and 2017 of all consecutive episodes of IA occurring in adult patients with acute leukemia. Demographic characteristics, underlying disease and recent treatment, antifungal prophylaxis, neutropenia, receipt of corticosteroids, clinical and radiological findings, mycological results, antifungal therapy, and 6-week and 12-week survival were recorded. RESULTS: We identified 77 cases of IA in 54 patients with AML and 23 patients with ALL. The majority of patients developed IA in the context of induction chemotherapy for newly diagnosed (48.0%) or relapsed (41.6%) leukemia, with no differences between ALL and AML. Lung involvement was more frequent in AML (96.3% vs. 82.6%, p = 0.06) and rhinosinusitis was more common in ALL (43.5% vs. 24.1%, p = 0.09). Galactomannan was the microbiologic documentation of IA in 76.6%, with similar patterns of positivity in AML and ALL. The 6-week survival of IA in patients with AML and ALL was 63.0% and 56.5%, respectively (p = 0.60). CONCLUSIONS: The epidemiology, clinical presentation, diagnosis and outcome of IA in ALL patients are similar to patients with AML.

EQUAL Fusariosis score 2021: An European Confederation of Medical Mycology score derived from current guidelines to measure QUALity of the clinical management of invasive fusariosis.

BACKGROUND: Invasive fusariosis is a serious infection affecting mostly patients with haematologic malignancies and hematopoietic cell transplant recipients. OBJECTIVES: To develop a scoring tool that evaluates guideline adherence in the management of invasive fusariosis. METHODS: We reviewed two guidelines, provided by the European Society for Clinical Microbiology and Infectious Diseases (ESCMID) and the European Confederation of Medical Mycology (ECMM), and selected the strongest recommendations for management quality as the bases for the scoring tool. RESULTS: We reviewed the recommendations regarding primary and secondary prophylaxis, diagnostics procedures (images, blood cultures, biopsy of skin lesions with direct examination, culture and histopathology, species identification, antifungal susceptibility tests and antigen detection), treatment choices and follow-up procedures. The tool comprises 18 items, with a maximum of 24 points. CONCLUSIONS: The EQUAL score Fusariosis is a tool that may help clinicians to measure guidelines adherence.

Epidemiology of invasive fungal disease in haematologic patients.

Invasive fungal disease (IFD) is frequent in patients with haematologic malignancies and in recipients of haematopoietic cell transplantation (HCT). An epidemiologic study conducted in Brazil reported a high incidence of IFD in haematologic patients, and invasive fusariosis was the leading IFD. A limitation of that study was that galactomannan was not available for at least half of the study period. In order to characterise the epidemiology and burden of IFD in three cohorts, HCT, acute myeloid leukaemia (AML) or myelodysplasia (MDS), and acute lymphoid leukaemia (ALL), we conducted a prospective multicentre cohort study in four haematologic Brazilian centres. From August 2015 to July 2016, all patients receiving induction chemotherapy for newly diagnosed or relapsed AML, MDS or ALL, and all HCT recipients receiving conditioning regimen were followed during the period of neutropenia following chemotherapy or the conditioning regimen. During a 1-year period, 192 patients were enrolled: 122 HCT recipients (71 allogeneic, 51 autologous), 46 with AML, and 24 with ALL. The global incidence of IFD was 13.0% (25 cases, 11 proven and 14 probable). Invasive aspergillosis (14 cases) was the leading IFD, followed by candidemia (6 cases) and fusariosis (3 cases). The incidence of IFD was 26.1% in AML/MDS, 16.7% in ALL, 11.3% in allogeneic HCT, and 2.0% in autologous HCT. The burden of IFD in haematologic patients in Brazil is high, with a higher frequency in AML and ALL. Invasive aspergillosis is the leading IFD, followed by invasive candidiasis and fusariosis.

Increased incidence of candidemia in a tertiary care hospital with the COVID-19 pandemic.

BACKGROUND: The incidence of candidemia in our hospital has been stable over an 18-year period (1.3 episodes per 1000 admissions). Since March 2020, we have observed an increase in cases of candidemia. METHODS: In March 2020, the hospital was prepared to receive patients with COVID-19, with cancellation of elective procedures, discharge of less sick patients and the activation of beds for COVID-19. We compared the incidence of candidemia in 2 periods: from January 2019 to February 2020 (period 1) and from March to September 2020 (period 2). RESULTS: We diagnosed 41 episodes of candidemia, 16 in period 1 and 25 in period 2 (9 COVID-19 patients). Compared with non-COVID-19 patients, COVID-19 patients with candidemia were more likely to be under mechanical ventilation (100% vs. 34.4%, P < .001). The median number of monthly admissions in period 1 and 2 was 723 (interquartile range 655-836) and 523 (interquartile range 389-574), respectively. The incidence of candidemia (per 1000 admissions) was 1.54 in period 1 and 7.44 in period 2 (P < .001). In period 2, the incidence of candidemia (per 1000 admissions) was 4.76 if we consider only cases of candidemia in non-COVID-19 patients, 2.68 if we consider only cases of candidemia in COVID-19 patients and 14.80 considering only admissions of patients with COVID-19. CONCLUSIONS: The increase in the incidence of candidemia in our hospital may be attributed to 2 factors: a reduction in the number of admissions (denominator) and the occurrence of candidemia in COVID-19 patients.

Shock and Early Death in Hematologic Patients with Febrile Neutropenia.

Empirical antibiotic therapy with a beta-lactam is the standard of care in febrile neutropenia (FN) and is given to prevent early death. The addition of vancomycin is recommended in certain circumstances, but the quality of evidence is low, reflecting the lack of clinical data. In order to characterize the epidemiology of early death and shock in FN, we reviewed all episodes of FN from 2003 to 2017 at University Hospital, Federal University of Rio de Janeiro, and looked at factors associated with shock at first fever and early death (within 3 days from first fever) by univariate and multivariate analyses. Among 1,305 episodes of FN, shock occurred in 42 episodes (3.2%) and early death in 15 (1.1%). Predictors of shock were bacteremia due to Escherichia coli (odds ratio [OR], 8.47; 95% confidence interval [95% CI], 4.08 to 17.55; P < 0.001), Enterobacter sp. (OR, 7.53; 95% CI, 1.60 to 35.33; P = 0.01), and Acinetobacter sp. (OR, 6.95; 95% CI, 1.49 to 32.36; P = 0.01). Factors associated with early death were non-Hodgkin's lymphoma (OR, 3.57; 95% CI, 1.18 to 10.73; P = 0.02), pneumonia (OR, 21.36; 95% CI, 5.72 to 79.72; P < 0.001), shock (OR, 11.64: 95% CI, 2.77 to 48.86; P = 0.01), and bacteremia due to Klebsiella pneumoniae (OR, 5.91; 95% CI, 1.11 to 31.47; P = 0.03). Adequate empirical antibiotic therapy was protective (OR, 0.23; 95% CI, 0.07 to 0.81; P = 0.02). Shock or early death was not associated with Gram-positive bacteremia; catheter-related, skin, or soft tissue infection; or inadequate Gram-positive coverage. These data challenge guideline recommendations for the empirical use of vancomycin at first fever in neutropenic patients.

Ceftazidime-Avibactam as Salvage Therapy for Infections Caused by Enterobacteriales Coresistant to Carbapenems and Polymyxins.

In this article, we report a case series of patients with infections caused by Enterobacteriales coresistant to carbapenems and polymyxins who were treated with ceftazidime/avibactam (CAZ-AVI) salvage therapy on a compassionate-use protocol. We enrolled 29 adult patients in 3 centers that had an infection due to a resistant microorganism and for whom the treatments available were considered ineffective, treated them with CAZ-AVI, and assessed clinical and microbiological cure at the end of treatment and all-cause mortality at 14 days and 30 days. The antimicrobial susceptibility profile was determined using broth microdilution, and total genomic DNA was sequenced. Twelve (41.4%) patients had bacteremia, and 48.3% (14/29) of the infections were treated with combination therapy. All strains were producers of KPC-2 and were susceptible to CAZ-AVI (MIC90, 1 µg/ml). Clinical success was high (24/29 [82.7%; 95% confidence interval, 64.2 to 94.2%]), even for the bacteremic cases (75%). The 14-day and 30-day mortality rates were 9/29 (31%) and 15/29 (51.7%), respectively. The 14-day mortality rate for pneumonia was the same as that for bloodstream infections (33.3%) and although not significant, we found that patients with renal impairment that received adjusted doses of CAZ-AVI had high mortality (4/9 [44%]; P = 0.22). We concluded that CAZ-AVI is an option for the treatment of severe infections due to difficult-to-treat drug-resistant Enterobacteriales.

Performance of 1,3-beta-D-glucan in the diagnosis and monitoring of invasive fusariosis.

Invasive fusariosis (IF) usually presents with high fungal burden at diagnosis, and this may contribute to its high mortality rate. The use 1,3-beta-D-glucan (BDG) may help to establish the diagnosis at an earlier disease stage and to monitor treatment. To evaluate the performance of BDG in the diagnosis of IF and its kinetics in relation to the outcome, we retrospectively tested serum samples of 13 cases of IF, analysed the temporal relationship between the first positive BDG test and the date of the diagnosis of IF, and the kinetics of BDG in relation to patients' outcome. We selected 13 controls with similar underlying diseases as cases, at least two serum samples stored, and no invasive fungal disease. Twelve patients with IF had at least one positive BDG (median 4, range 1-16). The test was positive before the diagnosis of IF in 11 of the 12 patients (91.6%), at a median of 10 days (range 1-32). The median BDG value increased (from 109 to 316 pg/mL, P = 0.04) in patients who died by day 30, and did not change significantly (99-101 pg/mL, P = 0.60) in survivors. Using two consecutive BDG tests, sensitivity, specificity, and positive and negative predictive values were 85%, 69%, 7% and 99%, respectively. BDG is positive in the majority of patients with IF, usually before the diagnosis, but the low positive predictive value limits its use to diagnose IF earlier. Once therapy is started, decreasing BDG values suggests treatment response.

Outcomes of patients with invasive fusariosis who undergo further immunosuppressive treatments, is there a role for secondary prophylaxis?

BACKGROUND: Patients treated for invasive aspergillosis may relapse during subsequent periods of immunosuppression and should receive secondary prophylaxis. Little is known about the frequency of relapse and practices of secondary prophylaxis for invasive fusariosis (IF). OBJECTIVES: Evaluate practices of secondary prophylaxis and the frequency of relapse in patients who survived IF and were exposed to subsequent periods of immunosuppression. METHODS: Multicentre retrospective study of patients with haematological malignancies who developed IF, survived the initial fungal disease period, and were exposed to subsequent periods of immunosuppression. RESULTS: Among 40 patients, 35 received additional chemotherapy and developed neutropenia (median, 24 days; range, 4-104), and five received glucocorticoids for the treatment of graft-vs-host disease. Overall, 32 patients received secondary prophylaxis (voriconazole in 24) for a median of 112 days (range, 12-468). IF relapsed in five patients (12.5%): 2/8 (25%) not on prophylaxis and 3/32 (9.4%) receiving prophylaxis. Among 28 patients with disseminated IF, relapse occurred in 2/2 (100%) not on prophylaxis and in 3/26 (11.5%) on prophylaxis (P = 0.03). All patients who relapsed IF died. CONCLUSIONS: Patients with IF who survive the initial disease may relapse if exposed to subsequent episodes of immunosuppressive therapies. Secondary prophylaxis should be considered, especially if IF was disseminated.

Antimold Prophylaxis May Reduce the Risk of Invasive Fusariosis in Hematologic Patients with Superficial Skin Lesions with Positive Culture for Fusarium.

Hematologic patients with superficial skin lesions on admission growing Fusarium spp. are at a high risk for developing invasive fusariosis during neutropenia. We evaluated the impact of primary prophylaxis with a mold-active azole in preventing invasive fusariosis in these patients. Between August 2008 and December 2014, patients with acute leukemia or aplastic anemia and recipients of hematopoietic cell transplants were screened on admission with dermatologic and direct exams and fungal cultures of superficial skin lesions. Until November 2009, no interventions were made. Beginning in December 2009, patients with baseline skin lesions and a direct exam and/or culture suggestive of the presence of Fusarium spp. received prophylaxis with voriconazole or posaconazole. Skin lesions in the extremities (mostly onychomycosis and interdigital intertrigo) were present on admission in 88 of 239 episodes (36.8%); 44 lesions had hyaline septate hyphae identified by direct exam, and cultures from 11 lesions grew Fusarium spp. Antimold prophylaxis was given for 20 episodes (voriconazole for 17 and posaconazole for 3). Invasive fusariosis was diagnosed in 14 episodes (5.8%). Among patients with baseline skin lesions with positive cultures for Fusarium spp., 4 of 5 without antimold prophylaxis developed invasive fusariosis versus 0 of 6 with antimold prophylaxis (P = 0.01; 95% confidence interval for the difference between proportions, 22% to 96%). Primary antifungal prophylaxis with an antimold azole may prevent the occurrence of invasive fusariosis in high-risk hematologic patients with superficial skin lesions on admission growing Fusarium spp.

Discontinuation of empirical antifungal therapy in ICU patients using 1,3-ß-d-glucan.

BACKGROUND: Empirical antifungal therapy in high-risk ICU patients is an attractive strategy, but overuse of antifungal agents is a potential problem. OBJECTIVES: We evaluated if ICU patients at high risk to develop candidaemia identified by a prediction rule could discontinue empirical antifungal therapy on the basis of repeatedly negative 1-3-ß-d-glucan (BDG) tests. METHODS: We conducted a multicentre cohort study in 85 ICU patients receiving antibiotics or with central venous catheter plus two additional factors (dialysis, parenteral nutrition, surgery, pancreatitis or receipt of corticosteroids or other immunosuppressive agents) plus either fever, hypothermia, hypotension, acidosis, elevated C-reactive protein or leucocytosis. Blood cultures (days 1 and 2) and BDG (days 1-3, baseline period) were performed and anidulafungin was given. On day 4, patients with negative blood cultures and BDG discontinued antifungal therapy. Registered in ClinicalTrials.gov (NCT01734525). RESULTS: The incidence of candidaemia was 8.2% in patients selected versus 0.5% in patients without entry criteria (16.9 times higher). Sixty-four patients (75.3%) had baseline positive BDG, including 7 with candidaemia. All 21 patients with baseline negative BDG discontinued anidulafungin on day 4. None developed candidaemia until day 30. CONCLUSIONS: Early discontinuation of empirical echinocandin therapy in high-risk ICU patients based on consecutive negative BDG tests may be a reasonable strategy, with great potential to reduce the overuse of echinocandins in ICU patients. Prospective studies with a higher number of patients are needed.

Fusariosis.

Fusarium species are frequent agents of onychomycosis and fungal keratitis, and occasional agents of invasive disease. The clinical spectrum of fusariosis in the lungs includes allergic disease (allergic bronchopulmonary fusariosis), hypersensitivity pneumonitis, colonization of a preexisting cavity, and pneumonia. Fusarial pneumonia occurs almost exclusively in severely immunocompromised patients, especially acute leukemia patients and recipients of allogeneic cell transplantation. In such patients, invasive fusariosis is usually disseminated, and pneumonia occurs in almost 50% of cases. The radiologic picture is similar to invasive aspergillosis, with alveolar infiltrates, nodules with or without halo sign, ground-glass infiltrates, and pleural effusions. Different from aspergillosis is the frequent occurrence of disseminated nodular and papular skin lesions and positive blood cultures. The drug of choice for the treatment of invasive fusariosis is either voriconazole or liposomal amphotericin B. The outcome is usually poor, and largely dependent on the recovery of the immune status of the host, particularly neutropenia.

Effect of the implosion and demolition of a hospital building on the concentration of fungi in the air.

Building renovations increase the concentration of Aspergillus conidia in the air. In 2010, one wing of the hospital building was imploded due to structural problems. To evaluate the impact of building implosion on the concentration of fungi in the air, the demolition was performed in two phases: mechanical demolition of 30 m of the building, followed by implosion of the wing. Patients at high risk for aspergillosis were placed in protected wards. Air sampling was performed during mechanical demolition, on the day of implosion and after implosion. Total and specific fungal concentrations were compared in the different areas and periods of sampling, using the anova test. The incidence of IA in the year before and after implosion was calculated. The mean concentration of Aspergillus increased during mechanical demolition and on the day of implosion. However, in the most protected areas, there was no significant difference in the concentration of fungi. The incidence of invasive aspergillosis (cases per 1000 admissions) was 0.9 in the 12 months before, 0.4 during, and 0.5 in the 12 months after mechanical demolition (P > 0.05). Continuous monitoring of the quality of air and effective infection control measures are important to minimize the impact of building demolition.

Increased incidence of invasive fusariosis with cutaneous portal of entry, Brazil.

Invasive fusariosis (IF) is an infection with Fusarium spp. fungi that primarily affects patients with hematologic malignancies and hematopoietic cell transplant recipients. A cutaneous portal of entry is occasionally reported. We reviewed all cases of IF in Brazil during 2000-2010, divided into 2 periods: 2000-2005 (period 1) and 2006-2010 (period 2). We calculated incidence rates of IF and of superficial infections with Fusarium spp. fungi identified in patients at a dermatology outpatient unit. IF incidence for periods 1 and 2 was 0.86 cases versus 10.23 cases per 1,000 admissions (p<0.001), respectively; superficial fusarial infection incidence was 7.23 versus 16.26 positive cultures per 1,000 superficial cultures (p<0.001), respectively. Of 21 cases of IF, 14 showed a primary cutaneous portal of entry. Further studies are needed to identify reservoirs of these fungi in the community and to implement preventive measures for patients at risk.

Ciprofloxacin prophylaxis in high risk neutropenic patients: effects on outcomes, antimicrobial therapy and resistance.

BACKGROUND: The use of quinolone prophylaxis in high-risk neutropenic patients is considered standard of care but the development of resistance is a concern. Previous studies have focused mainly on quinolone resistance among patients receiving prophylaxis, with very few data reporting its impact on the hospital microbial epidemiology. METHODS: We analyzed a cohort of 329 episodes of chemotherapy-induced neutropenia in adults, and compared two periods: 2005 (period 1, no prophylaxis, n=110) and 2006-2008 (period 2, ciprofloxacin prophylaxis, n=219). Outcomes analyzed were the frequency of febrile neutropenia, bacteremia, duration of antibiotic therapy and hospitalization, and antimicrobial resistance to ciprofloxacin and extended-spectrum beta-lactamase [ESBL] production. We analyzed resistance rates (by patients-day) in the cohort, as well as in other patients (neutropenic and non-neutropenic, 11,975 patients-day) admitted to the hematology unit in the same period, taking into consideration the general resistance patterns in the hospital. RESULTS: Quinolone prophylaxis (period 2) resulted in fewer episodes of febrile neutropenia (159/219 [73%] vs. 102/110 [93%], Chi-square 18.09, p = 0.00002), and bacteremia (49/219 [22] vs. 36/110 [33%], Chi-square 4.10, p = 0.04), shorter duration of antibiotic therapy (p = 0.0002) and hospitalization (p = 0.002), but more frequent use of carbapenems (79/219 [36%] vs. 15/110 [14%], Chi-square 18.06, p = 0.0002). In addition, period 2 was associated with higher rates of quinolone resistance (6.77 vs. 3.02 per 1,000 patients-day, p = 0.03). The rate of ESBL-producing enterobacteria in the two periods was slightly higher in patients receiving quinolone prophylaxis (1.27 vs. 0.38 per 1,000 patients-day, p = 0.26) as well as in the hematology unit overall (1.59 vs. 0.53 per 1,000 patients-day, p = 0.08), but remained stable in the whole hospital (0.53 vs. 0.56 per 1,000 patients-day, p = 0.74). CONCLUSIONS: Ciprofloxacin prophylaxis was beneficial in high risk neutropenic patients, but important modifications in the prescription of carbapenems and on antimicrobial resistance patterns of isolates were observed. The importance of hospital or ward ecology must be taken into account when deciding for quinolone prophylaxis in high-risk neutropenic patients.

Practical issues related to non-Aspergillus invasive mold infections.

Infection by non-Aspergillus molds has been increasingly reported. The management of such infections is challenging both for diagnosis and treatment, including the need of well-trained mycologists to properly identify rare fungi, difficulties in distinguishing between contamination, colonization and infection, the lack of randomized studies comparing different drugs or regimens, poor activity of available antifungal agents, lack of correlation between in vitro antifungal susceptibility tests and clinical outcome, and poor prognosis. Mucormycosis and fusariosis are the most frequent non-Aspergillus mold infections. Mucormycosis occurs more frequently in four major groups of patients: solid organ transplant recipients, patients with hematologic malignancies receiving chemotherapy or hematopoietic cell transplantation, diabetic patients, and immunocompetent individuals who suffer various types of skin and soft tissue trauma. Invasive fusariosis occurs almost exclusively in patients with hematologic malignancies. In this review we discuss practical issues related to the management of these and other non-Aspergillus mold infections.

Invasive Fungal Infections Associated with COVID-19.

The COVID-19 pandemic caused >6 million deaths worldwide, often from respiratory failure. Complications frequently occurred in hospitalized patients, particularly in the intensive care unit. Among these, fungal infections were a cause of high morbidity and mortality. Invasive aspergillosis, candidiasis and mucormycosis were the most serious of these infections. Risk factors included alterations in immune defense mechanisms by COVID-19 itself, as well as immunosuppression due to various therapies utilized in severely ill patients. Diagnosis was often challenging due to lack of sensitivity of current testing. Outcomes were generally poor, due to significant co-morbidities and delayed diagnosis, with mortality rates >50% in some studies. High index of clinical suspicion is needed to facilitate early diagnosis and initiation of appropriate antifungal therapy.

Evaluation of a stewardship program of antifungal use at a Brazilian tertiary care hospital.

INTRODUCTION: Stewardship programs have been developed to optimize the use of antibiotics, but programs focusing on antifungal agents are less frequent. OBJECTIVE: To evaluate the quality of antifungal prescriptions in a tertiary care hospital, and to test if a simple educational activity could improve the quality of prescriptions. METHODS: The study comprised three phases: 1) Retrospective audit of all antifungal prescriptions in a 6-month period, applying a score based on six parameters: indication, drug, dosage, route of administration, microbiologic adequacy after results of cultures, switching to an oral agent, and duration of treatment; 2) Creation of text boxes in the electronic medical records with information about antifungal agents, shown during prescription; 3) Retrospective audit of all antifungal prescriptions in a 6-month period, applying the same 6-parameters score, and comparison between the two periods. RESULTS: Among 333 prescriptions, fluconazole was the most frequently (80.5%) prescribed agent. Hematology (26.7%), Infectious Diseases Department (22.8%), Internal Medicine (15.9%) and Intensive Care Unit (14.4%) were the units with most antifungal prescriptions. The median score for the 333 prescriptions was 8.0 (range 0 - 10), and 72.7% of prescriptions were considered inappropriate. The median and mean scores in the first and second audit were 8.0 and 6.9, and 8.0 and 7.9, respectively (p<0.001). All items that comprised the score improved from the first to the second audit. Likewise, there was a reduction of inappropriate prescriptions (80.2% in the first audit vs. 64.6% in the second audit, p=0.001). CONCLUSIONS: A large proportion of inappropriate prescriptions was observed, which improved with the implementation of simple educational activities.

Earlier response assessment in invasive aspergillosis based on the kinetics of serum Aspergillus galactomannan: proposal for a new definition.

BACKGROUND: Current criteria for assessing treatment response of invasive aspergillosis (IA) rely on nonspecific subjective parameters. We hypothesized that an Aspergillus-specific response definition based on the kinetics of serum Aspergillus galactomannan index (GMI) would provide earlier and more objective response assessment. METHODS: We compared the 6-week European Organization for Research and Treatment of Cancer/Mycoses Study Group (EORTC/MSG) response criteria with GMI-based response among 115 cancer patients with IA. Success according to GMI required survival with repeatedly negative GMI for ≥2 weeks. Time to response and agreement between the 2 definitions were the study endpoints. RESULTS: Success according to EORTC/MSG and GMI criteria was observed in 73 patients (63%) and 83 patients (72%), respectively. The GMI-based response was determined at a median of 21 days after treatment initiation (range, 15-41 days), 3 weeks before the EORTC/MSG time point, in 72 (87%) of 83 responders. Agreement between definitions was shown in all 32 nonresponders and in 73 of the 83 responders (91% overall), with an excellent κ correlation coefficient of 0.819. Among 10 patients with discordant response (EORTC/MSG failure, GMI success), 1 is alive without IA 3 years after diagnosis; for the other, aspergillosis could not be detected at autopsy. The presence of other life-threatening complications in the remaining 8 patients indicates that IA had resolved. CONCLUSIONS: The Aspergillus-specific GMI-based criteria compare favorably to current response definitions for IA and significantly shorten time to response assessment. These criteria rely on a simple, reproducible, objective, and Aspergillus-specific test and should serve as the primary endpoint in trials of IA.

Detection of cross-infection associated to a Brazilian PCR-ribotype of Clostridium difficile in a university hospital in Rio de Janeiro, Brazil.

Clostridium difficile is an important nosocomial enteric pathogen and is the etiological agent of pseudomembranous colites. Recently, the rates of C. difficile infection (CDI) have increased worldwide, but in Brazil few data about this situation and the incidence of clonal types of C. difficile exist. This study aimed to isolate and characterize C. difficile strains from samples obtained of a university hospital (HUCFF) in Rio de Janeiro city, Brazil. CDI was identified by ELISA in 27.1% of HUCFF-in-patients enrolled in the study, and the bacterium was recovered from eight of these fecal samples. All strains, except one, presented tcdA and tcdB genes and presented neither the cdtA and cdtB genes nor any significant deletions in the tcdC gene. All strains were sensitive to metronidazole, vancomycin and moxifloxacin, and resistant to clindamycin, ciprofloxacin and levofloxacin. PCR-ribotyping and PFGE revealed four different clonal types among the isolates. The Brazilian PCR-ribotype 133 accounted for 50% of strains isolated, and PCR-ribotype 233 strains were obtained from 25% of the in-patients. The prevalence and resurgence of the Brazilian PCR-ribotype 133 among the hospitalized patients of HUCFF was established, and cross-infection of different patients associated to the same PCR-ribotypes was detected. Our results emphasize the importance of the diagnosis and control of CDI in order to prevent the emergence of specific clones that can lead to C. difficile-associated outbreaks in Brazilian hospitals.