Bezlotoxumab in the treatment of Clostridioides difficile infections: a real-life experience.

OBJECTIVE: Following the approval of bezlotoxumab in 2017, studies evaluating its effectiveness in prevention of Clostridioides difficile infection under "real-life" conditions are scarce. METHODS: We conducted a retrospective study developed in a large tertiary care hospital describing the use and outcomes of patients with Clostridioides difficile infection (CDI) treated with bezlotoxumab. RESULTS: A total of 16 patients were include, all of whom had an episode of CDI with high probability of recurrence and 14 of them had some kind of immunosuppression. Bezlotoxumab was effective in the prevention of CDI recurrence in 11 of the 14 cases in which follow up was possible, without significant side effects. CONCLUSIONS: Bezlotoxumab was well tolerated and the incidence of recurrent CDI in a high-risk population for recurrence was only 21.4%.

Impact of the Inclusion of an Aminoglycoside to the Initial Empirical Antibiotic Therapy for Gram-Negative Bloodstream Infections in Hematological Neutropenic Patients: a Propensity-Matched Cohort Study (AMINOLACTAM Study).

To test the hypothesis that the addition of an aminoglycoside to a ß-lactam antibiotic could provide better outcomes than ß-lactam monotherapy for the initial empirical treatment of hematological neutropenic patients with subsequently documented Gram-negative bacillus (GNB) bloodstream infection (BSI), a multinational, retrospective, cohort study of GNB BSI episodes in hematological neutropenic patients in six centers (2010 to 2017) was conducted. Combination therapy (ß-lactam plus aminoglycoside) was compared to ß-lactam monotherapy. The primary endpoint was the case fatality rate, assessed at 7 and 30 days from BSI onset. Secondary endpoints were nephrotoxicity and persistent BSI. Propensity score (PS) matching was performed. Among 542 GNB BSI episodes, 304 (56%) were initially treated with combination therapy, with cefepime plus amikacin being most common (158/304 [52%]). Overall, Escherichia coli (273/304 [50.4%]) was the main etiological agent, followed by Pseudomonas aeruginosa, which predominated in the combination group (76/304 [25%] versus 28/238 [11.8%]; P < 0.001). Multidrug resistance rates were similar between groups (83/294 [28.2%] versus 63/233 [27%]; P = 0.95). In the multivariate analysis, combination therapy was associated with a lower 7-day case fatality rate (odds ratio [OR], 0.37; 95% CI, 0.14 to 0.91; P = 0.035) with a tendency toward lower mortality at 30 days (OR, 0.56; 95% CI, 0.29 to 1.08; P = 0.084). After PS matching, these differences remained for the 7-day case fatality rate (OR, 0.33; 95% CI, 0.13 to 0.82; P = 0.017). In addition, aminoglycoside use was not significantly associated with renal function impairment (OR, 1.12; 95% CI, 0.26 to 4.87; P = 0.9). The addition of an aminoglycoside to the initial empirical therapy regimen for febrile neutropenic hematological patients should be considered.

Is biofilm production a prognostic marker in adults with candidaemia?

OBJECTIVES: The role of biofilm production in the outcome of candidaemia remains under discussion. Current evidence relies on variable biofilm detection methods while evaluating distinct clinical end points. We aimed to determine the impact of biofilm production measured by metabolic activity (MA) and biomass (BM) on the prognosis of adults with candidaemia. METHODS: Retrospective cohort including 280 adults with candidaemia admitted from 2010 to 2016. BM was assessed using crystal violet binding stain and the XTT reduction assay was used to detect MA. Strains were classified as high and moderate-low biofilm producers according to published cut-offs. The primary outcome was overall mortality within 7 and 30 days. The secondary outcome was unfavourable prognosis defined as metastatic infection, admission to an intensive care unit due to the severity of candidaemia, or death within 30 days. RESULTS: High BM and high MA were detected in 90 (32.1%) and 114 (40.7%) of the 280 isolates, respectively. Comparison of high and moderate-low biofilm forming isolates revealed no correlation between biofilm production and 7-day mortality (BM high 15/90 (16.7%) versus moderate-low 24/190 (12.6%); MA high 12/114 (10.5%) versus moderate-low 27/166 (16.3%)), 30-day mortality (BM high 34/90 (37.8%) versus moderate-low 61/190 (32.1%); MA high 33/114 (28.9%) versus moderate-low 62/166 (37.3%)), or unfavourable prognosis (BM high 45/90 (50.0%) versus moderate-low 73/190 (38.4%); MA high 41/114 (36.0%) versus moderate-low 77/166 (46.4%)). CONCLUSIONS: Biofilm production was not a predictor of mortality or of unfavourable prognosis in adults with candidaemia.

The misleading effect of serum galactomannan testing in high-risk haematology patients receiving prophylaxis with micafungin.

OBJECTIVES: To investigate the performance of the routine serum galactomannan (sGM) assay in the diagnosis of invasive aspergillosis (IA) in high-risk haematology patients receiving prophylaxis with micafungin. METHODS: Retrospective study including all haematological patients who received prophylaxis with micafungin during high-risk IA episodes (neutropenic patients after chemotherapy for acute myeloid leukaemia/myelodysplastic syndrome; allogeneic haematopoietic stem-cell transplantation during early neutropenic phase or graft-versus-host disease requiring high prednisone doses) and for whom at least one sGM result was available. Episodes were classified as follows: true-positive (positive GM in the context of IA), false-positive (positive GM result in patients who had no evidence of IA), true-negative (negative GM test results and no IA), or false-negative (negative GM test in the context of IA). Non-evaluable patients were excluded. RESULTS: Among 146 evaluable episodes, four were true-positive in the context of probable breakthrough IA (incidence of breakthrough IA, 2.7%); 111/146 high-risk episodes (76%) were considered true-negative and 31/146 (21.2%) were considered false-positive. No false-negative episodes were detected. All but one of the false-positive episodes were detected in surveillance GM tests, leading to high-resolution CT scans in eight cases (8/31; 25.8%), all of which were negative. The positive predictive and negative predictive values of sGM for surveillance and diagnostic approaches were 3.2% (1/31) and 100% (110/110) and 75% (3/4) and 100% (1/1), respectively. CONCLUSIONS: Surveillance of asymptomatic patients receiving prophylaxis with micafungin using sGM is unnecessary, because the results are either negative or false-positive. However, sGM remains useful in the diagnosis of breakthrough IA in symptomatic patients during prophylaxis.

Risk factors for late recurrent candidaemia. A retrospective matched case-control study.

Incidence, risk factors and clinical significance of late recurrent (LR) candidaemia (>1 month between episodes) remains unclear. The 1219 episodes of candidaemia detected from January 1985 to December 2014 were reviewed. We selected all cases with more than one episode separated by at least 30 days after clinical resolution in the interim (cases) and compared each of them with two controls (patients with single episodes of candidaemia). Clinical strains were genotyped to differentiate relapses from re-infection. Eighteen patients (1.48%) had 36 episodes of LR candidaemia (median 4 months). Independent risk factors for recurrence in the multivariate analysis were: underlying gastrointestinal disease (OR 67.16; 95% CI 5.23-861.71; p 0.001) and fungaemia due to Candida parapsilosis (OR 9.10; 95% 1.33-62.00; p 0.02). All episodes of LR candidaemia diagnosed during the first 3 months were due to an intravascular source of infection, whereas in those occurring after 3 months the main source of the disease was the abdomen, followed by endocarditis, and urinary tract. Molecular typing showed that 42.9% of LR candidaemias were relapses and 57.1% were re-infections. Neither time of recurrence nor clinical origin could predict type of recurrence. LR candidaemia is a relatively rare event that is more frequent in patients who have an initial episode of candidaemia due to C. parapsilosis or an underlying gastrointestinal disease. Episodes of LR candidaemia that occur within the first 3 months should prompt an attempt to exclude an intravascular source of infection, whereas those occurring later point to an intra-abdominal origin.

Catastrophic antiphospholipid syndrome triggered by fulminant disseminated herpes simplex infection in a patient with systemic lupus erythematosus.

Infections are considered one of the most common causes of morbidity and mortality in patients with systemic lupus erythematosus (SLE), and occasionally can trigger a catastrophic antiphospholipid syndrome (APS). We describe a 22-year-old SLE patient with lupus nephritis under immunosuppressant therapy and asymptomatic carrier of antiphospholipid antibodies, who was admitted with tonsillitis and acute hepatitis, developing multiorgan failure in a few hours. Postmortem examination revealed hepatic necrosis, tonsillitis, pharyngitis and uterine cervicitis caused by herpes simplex virus (HSV) together with microthrombosis in lungs and glomerular arterioles, suggesting the diagnosis of fulminant HSV disseminated infection and catastrophic APS.

[Inappropriate drug prescription and adverse drug effects in elderly patients]. / Prescripción inadecuada y efectos adversos a medicamentos en pacientes de edad avanzada.

AIMS: Inappropriate drug prescription (IP) has been related to higher hospitalization rates and development of adverse drug effects (ADE). We have studied the inappropriate drug prescriptions given to elderly patients admitted to the hospital and the frequency and severity of the adverse events related with them. PATIENTS AND METHODS: A prospective study was conducted in a sample of 100 patients over 65 years admitted in an Internal Medicine Department in whom at least one inappropriate drug prescription (Beers and STOPP (B-S) criteria [Screening Tool of Older Person's Prescriptions]) as outpatients or during the first 48 hours after the admission. The relationship of the adverse events with the inappropriate drug prescription was established using the Naranjo algorithm. RESULTS: A total of 97 patients, mean age 81 years (range 66-101) were included. The total amount of medicines prescribed during the hospital stay was 865, average of 9 (range 3-16). Thirty two percent was being treated with more than 10 drugs. A total of 153 (17.7%) were B-S drugs. There were 26 ADEs, 18 related with B-S drugs. Digoxin and lorazepam were the IP drugs most frequently prescribed and those related with a larger number of ADE. Fifty six percent of the ADEs were considered severe. Institutionalized elderly patients were treated with more drugs, but not more B-S medicaments. CONCLUSIONS: The frequency of ADEs related to IP is very high in the elderly. It is necessary to implement strategies to identify, and use properly these drugs in elderly population.