Antimicrobial susceptibility testing determined by Alfred 60/AST (Alifax®) in a multi-sites lab: performance's evaluation and optimization of workflow.

PURPOSE: New techniques are needed to speed-up the identification and antimicrobial susceptibility testing (AST) of bacteria associated with bloodstream infections. Alfred 60/AST (Alifax®, Polverara, Italy) performs AST by light scattering directly from positive blood cultures. METHODS: We evaluated Alfred 60/AST performances for 4 months. Each new episode of bacteraemia was included and AST were compared to either our rapid automated AST (Vitek® 2) or disk diffusion method. The discrepancies were investigated using Etest®. The time-to-result (TTR) was evaluated by comparing the blood volume inserted into Alfred 60/AST, i.e. 2 versus 7 blood drops. Taking into account the TTR, the workflow of positive blood cultures and the availability of AST results was studied in order to optimize the implementation of Alfred 60/AST. RESULTS: A total of 249 samples and 1108 antibiotics for AST were tested. After exclusion of unavailable results, 1008 antibiotics were analysed. 94.9% (n = 957/1008) of the antibiotics showed categorical agreement. There were 14 very major errors (VME), 24 major errors (ME) and 13 minor errors (mE). The VME were mostly related to clindamycin (64.3%) whereas meropenem and piperacillin-tazobactam constituted the major part (37.5% and 61.5%) of ME and mE respectively. Results were highly reliable for Enterobacterales and enterococci. The mean TTR ranged between 4.3 and 6.3 h and was statistically 20 min faster when applying the 7 blood drops protocol. We showed that Alfred 60/AST could give relievable results within working hours for positive blood culture which are flagged the same day between 12:00 am and 12:00 pm. CONCLUSION: Our study confirmed that Alfred 60/AST gives reliable AST results in a short period of time, especially for Enterobacterales and enterococci. AST could thus be easily obtained the same day of a positive blood culture. Clinical impact studies are mandatory to validate a 24/24 working.

A general chemotherapy myelotoxicity score to predict febrile neutropenia in hematological malignancies.

BACKGROUND: Chemotherapy-induced neutropenia is the most common adverse effect of chemotherapy and is often complicated by febrile neutropenia (FN). The objective of this study is to validate a classification of aggressiveness of a chemotherapy regimen and to evaluate its usefulness in a risk prediction model of FN in patients with hematological cancer at the beginning of a chemotherapy cycle. PATIENTS AND METHODS: Two hundred and sixty-six patients were prospectively enrolled and followed during 1053 cycles. Relevant patient informations were collected at the beginning of the first cycle and the number of days of FN were counted in the follow-up [dichotomized (no FN versus >or= 1 day of FN)]. RESULTS: Aggressive chemotherapy regimen is the major predictor of FN [odds ratio 5.2 (3.2-8.4)]. The other independent predictors are the underlying disease, an involvement of bone marrow, body surface

Non-Hodgkin's lymphoma and tuberculosis coexistence in the same organs: a report of two cases.

Non-Hodgkin's lymphoma (NHL) may be preceded by chronic inflammatory diseases and furthermore has been related to immune deficiency. Tuberculosis (TB), on the other hand, is a chronic infectious disease whose presentation and reactivation is known to be promoted by cell mediated immunodeficiency. The coexistence of NHL and TB in the same organ is rare. We report two cases of NHL and TB coexistence in two different organs: cervical lymph nodes and kidney. The cases illustrate how misleading the concurrence of NHL and TB infection can be, delaying the diagnosis and treatment of either disease.

Low mannose-binding lectin concentration is associated with severe infection in patients with hematological cancer who are undergoing chemotherapy.

BACKGROUND: Mannose-binding lectin (MBL) is a serum lectin involved in innate immune response. Low serum MBL concentration may constitute a risk factor for infection in patients receiving myelosuppressive chemotherapy. METHODS: We conducted a prospective, observational study that assessed MBL concentration as a risk factor for infection in patients with hematological malignancy who were hospitalized to undergo at least 1 chemotherapy cycle. MBL deficiency was defined using an algorithm that considered the serum MBL concentration and the MBL genotype. The primary end point was the ratio of duration of febrile neutropenia to the duration of neutropenia. Secondary end points included the incidence of severe infection (e.g., sepsis, pneumonia, bacteremia, and invasive fungal infection). Logistic regression analysis was conducted, and Fisher's exact test was used to analyze binary outcomes, and Kaplan-Meier estimates and log rank tests were used for time-to-event variables. RESULTS: We analyzed 255 patients who received 569 cycles of chemotherapy. The median duration of neutropenia per cycle was 7 days (interquartile range, 0-13 days). Sixty-two patients (24%) were found to have MBL deficiency. Febrile neutropenia occurred at least once in 200 patients. No difference in the primary outcome was seen. The incidence of severe infection was higher among MBL-deficient patients than among non-MBL-deficient patients (1.96 vs. 1.34 cases per 100 days for analysis of all patients [P=.008] and 1.85 vs. 0.94 cases per 100 days excluding patients with acute leukemia [P<.001]). CONCLUSIONS: MBL deficiency does not predispose adults with hematological cancer to more-frequent or more-prolonged febrile episodes during myelosuppressive chemotherapy, but MBL-deficient patients have a greater number of severe infections and experience their first severe infection earlier, compared with nondeficient patients.

Bacteraemia in febrile neutropenic cancer patients.

A total of 2142 patients with febrile neutropenia resulting from cancer chemotherapy were registered in two observational studies and followed prospectively in different institutions. There were 499 (23%) patients with bacteraemia who are reviewed here. The relative frequencies of Gram-positive, Gram-negative and polymicrobial bacteraemias were 57%, 34% and 10% with respective mortality rates of 5%, 18% and 13%. Mortality rates were significantly higher in bacteraemic patients than in non-bacteraemic patients; a trend for higher mortality was observed (without reaching statistical significance) in those patients in whom bacteraemia was associated with a clinical site of infection compared to bacteraemic patients without any clinical documentation. Prophylactic antibiotics but not granulopoiesis stimulating factors were associated with a lower incidence of Gram-negative bacteraemia; however, neither prophylactic approach influenced the subsequent rate of complications in the patients who developed bacteraemia. The present study also confirms that the MASCC scoring system can identify a group of bacteraemic patients with a relatively low risk of complications and death (MASCC >/=21). On the other hand, in patients with very low levels of the MASCC score (<15), and then with predicted very unfavourable risk, the rate of complications and death was dramatically high, irrespective of the microbiological nature of the bacteraemia.

Bacteremia due to Stomatococcus mucilaginosus in neutropenic patients in the setting of a cancer institute.

This study reviews the clinical manifestations, causes and frequency of Stomatococcus mucilaginosus bacteremia in neutropenic cancer patients. We analyzed retrospectively all clinical and microbiological records of patients with S. mucilaginosus bacteremia. The incidence was compared with that of other pathogens causing bacteremia during neutropenia for the same period. S. mucilaginosus represented 5.9% of bacteremias in our neutropenic patients. Seven patients with hematologic malignancies and one with breast cancer are described. The common clinical presentation was one of sepsis. All patients presented with damaged mucosal barriers as the probable portal of entry, from either stomatitis or enterocolitis. All patients survived.

Autoimmune haemolytic anaemia in a patient treated with capecitabine.

A 61-year-old female, followed-up for a metastatic breast cancer, was admitted in our institution with conjunctival icterus, asthenia and abdominal crampoid pain. The patient was included in a clinical trial comparing the efficiency of capecitabine monotherapy versus capecitabine conjugated with a new biological agent in a randomised and double blind trial. The patient was in the capecitabine alone arm. Biological tests performed upon admission suggested the diagnosis of haemolytic anaemia. Moreover, the direct Coombs test result was twice positive indicating autoimmune haemolytic anaemia. Capecitabine has been reported to cause haemolysis either alone or combined with lapatinib, each time with a mechanism other than immunological. In this clinical case, capecitabine is the most likely factor causing an autoimmune haemolytic anaemia.

Impact of rapid microbial identification directly from positive blood cultures using matrix-assisted laser desorption/ionization time-of-flight mass spectrometry on patient management.

For septic patients, delaying the initiation of antimicrobial therapy or choosing an inappropriate antibiotic can considerably worsen their prognosis. This study evaluated the impact of rapid microbial identification (RMI) from positive blood cultures on the management of patients with suspected sepsis. During a 6-month period, RMI by matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF MS) was performed for all new episodes of bacteraemia. For each patient, the infectious disease specialist was contacted and questioned about his therapeutic decisions made based on the Gram staining and the RMI. This information was collected to evaluate the number of RMIs that led to a therapeutic change or to a modification of the patient's general management (e.g. fast removal of infected catheters). During the study period, 277 new episodes of bacteraemia were recorded. In 71.12% of the cases, MALDI-TOF MS resulted in a successful RMI (197/277). For adult and paediatric patients, 13.38% (21/157) and 2.50% (1/40) of the RMIs, respectively, resulted in modification of the treatment regimen, according to the survey. In many other cases, the MALDI-TOF MS was a helpful tool for infectious disease specialists because it confirmed suspected cases of contamination, especially in the paediatric population (15/40 RMIs, 37.50%), or suggested complementary diagnostic testing. This study emphasizes the benefits of RMI from positive blood cultures. Although the use of this technique represents an extra cost for the laboratory, RMI using MALDI-TOF MS has been implemented in our daily practice.

A late complication of percutaneous radial artery cannulation.

Radial artery pseudoaneurysms occurring as a late complication of percutaneous radial artery cannulation are rare, while those which are infected are exceptional. Known risk factors are age-related with patients being in their seventies and onwards, the duration of the radial artery catheter and staphylococcal catheter-related infections. We report the case of an 82-year-old patient who developed a mycotic radial artery pseudoaneurysm as a late complication of arterial catheterization.

Can we predict the duration of chemotherapy-induced neutropenia in febrile neutropenic patients, focusing on regimen-specific risk factors? A retrospective analysis.

BACKGROUND: The aim of the study was to elaborate a predictive model for the duration of chemotherapy-induced neutropenia (CIN) allowing the identification of patients with a higher risk of complications, especially complicated febrile neutropenia, who might benefit from preventive measures. PATIENTS AND METHODS: A score ranging from 0 to 4 on the basis of expected CIN was attributed to each cytotoxic agent given as part of chemotherapy treatment in solid tumours for patients with febrile neutropenia (FN). The individual scores were combined into several overall scores. RESULTS: A total of 203 patients with FN were eligible for this retrospective analysis. We were able to identify two groups of patients with statistically different neutropenia durations with median durations until hematological recovery of ANC > or =0.5 and > or =1.0 x 10(9)/l, being respectively 6 versus 4 days (P = 0.03) and 8 versus 6 days (P = 0.01). CONCLUSIONS: The duration of neutropenia is directly influenced by the aggressiveness of the chemotherapy regimen. In this retrospective study, we were able to identify a group of patients who needed two more additional days to recover from grade 3 and grade 4 neutropenia, based on the degree of aggressiveness of the cytotoxic agents used.

Causes of fever in cancer patients (prospective study over 477 episodes).

GOALS OF WORK: The aim of this study was to determine the causes of fever among cancer patients. METHODS: All febrile cancer patients were followed up prospectively. Clinical, microbiological and radiological documentations were performed. Aetiologies of fever, type of tumour, site of infection, type of microorganism and outcome were assessed and compared between neutropenics and non-neutropenics. RESULTS: Four hundred and seventy-seven episodes were evaluated. Infection, non-infectious causes and fever of unknown origin represented 67, 23 and 10%, respectively. The respiratory tract is the most frequently involved site in infection (29%), and in microbiologically documented infections, Gram-negative bacilli were predominant. The tumour itself (27%) or an invasive procedure (17%) were the main causes of non-infectious febrile episodes. Mortality from infection was higher among non-neutropenic (11.1%) than neutropenic patients (4.3%). CONCLUSION: Fever in cancer patients remains a challenge, and the differentiation between infectious and non-infectious causes at onset of fever is very difficult. Despite all the prophylactic measures, infection is still the principal cause. However, the infection-related mortality is low either in neutropenic or non-neutropenic patients.

Febrile neutropenia and Fusobacterium bacteremia: clinical experience with 13 cases.

OBJECTIVES: To assess the disease spectrum of Fusobacterium bacteremia in our neutropenic patients and review the literature. METHODS: This was a 6.5-year retrospective study in which all the records of neutropenic patients with Fusobacterium bacteremia were analyzed. RESULTS: Fusobacterium bacteremia was found in 13 neutropenic patients, 10 with hematological malignancies and 3 with solid tumors. The standard clinical presentation was that of primary bacteremia with benign evolution under antibiotics with anaerobic coverage. Most patients presented with oral mucositis as the probable portal of entry. Coinfection with other germs was documented in four patients. No patient had a localized infection documented. Most patients were receiving ciprofloxacin chemoprophylaxis. None of the patients had catheter-related infection. All tested strains were susceptible to all standard anaerobic agents. Fusobacterium spp. were responsible for 5% of bacteremias in neutropenic patients in our hospital during the last 6.5 years. CONCLUSION: Fusobacterium bacteremia is a possible cause of febrile neutropenia, especially in the setting of quinolone prophylaxis and oral mucositis after intense chemotherapeutic regimens. We think that its benign outcome if there is no localized infection detected does not justify the use of antianaerobic prophylaxis. Combination of beta-lactams and beta-lactamase inhibitors is a safe and reasonable treatment.

Disseminated infection due to Cylindrocarpon (Fusarium) lichenicola in a neutropenic patient with acute leukaemia: report of a case and review of the literature.

Described here is an unusual case of disseminated Cylindrocarpon lichenicola (Fusarium lichenicola) infection originating from a toenail lesion of a neutropenic woman with cellulitis of the foot and underlying acute leukaemia. A computed tomography scan of the chest showed multiple, ill-defined, nodular infiltrates with alveolar consolidation. The fungus was isolated from both the nail and the skin of the infected toe. Susceptibility testing revealed low minimum inhibitory concentrations for amphotericin B (0.78 micro g/ml) and voriconazole (1.56 micro g/ml) and high minimum inhibitory concentrations (>100 micro g/ml) for fluconazole, ketoconazole and itraconazole. The infection resolved after treatment with a total dose of 1 g of amphotericin B followed by oral itraconazole and bone marrow regeneration.