The Etiology, Antibiotic Therapy and Outcomes of Bacteremic Skin and Soft-Tissue Infections in Onco-Hematological Patients.

OBJECTIVES: to assess the current epidemiology, antibiotic therapy and outcomes of onco- hematological patients with bacteremic skin and soft-tissue infections (SSTIs), and to identify the risk factors for Gram-negative bacilli (GNB) infection and for early and overall mortality. METHODS: episodes of bacteremic SSTIs occurring in cancer patients at two hospitals were prospectively recorded and retrospectively analyzed. RESULTS: Of 164 episodes of bacteremic SSTIs, 53% occurred in patients with solid tumors and 47% with hematological malignancies. GNB represented 45.5% of all episodes, led by Pseudomonas aeruginosa (37.8%). Multidrug resistance rate was 16%. Inadequate empirical antibiotic therapy (IEAT) occurred in 17.7% of episodes, rising to 34.6% in those due to resistant bacteria. Independent risk factors for GNB infection were corticosteroid therapy and skin necrosis. Early and overall case-fatality rates were 12% and 21%, respectively. Risk factors for early mortality were older age, septic shock, and IEAT, and for overall mortality were older age, septic shock and resistant bacteria. CONCLUSIONS: GNB bacteremic SSTI was common, particularly if corticosteroid therapy or skin necrosis. IEAT was frequent in resistant bacteria infections. Mortality occurred mainly in older patients with septic shock, resistant bacteria and IEAT. These results might guide empirical antibiotic therapy in this high-risk population.

Spinal cord compression of neoplastic origin: surgical experience using a common clinical language.

PURPOSE: To assess the value of a common clinical language in a multidisciplinary tumour board for spinal metastasis, using both the Rades score and the Spinal Instability Neoplastic Score (SINS) for multidisciplinary decision-making. METHODS: Retrospective study of 60 consecutive patients treated surgically for MSCC. The indication for surgery was done in a multidisciplinary board, basically according to SINS and RADES scores. Three prognostic groups were defined according to the Rades score: poor (Rades 1: 20-30 points), intermediate (Rades 2: 31-35), and good (Rades 3: 36-45). RESULTS: The 2-year overall survival (OS) rate was 50%, with median survival of 19 months. By Rades prognostic group (1, 2, 3), median OS was 6 months, 15 months, and not reached, respectively. OS rates at 6 months (Rades 1, 2, 3) were 51, 69, and 74.1%, respectively. Within the Rades 1 group, 6-month survival in patients with new-onset cancer was 68 vs. 40% in those with a known primary. The overall complication rate ≥ grade 3 was 23.3% (n = 14). In patients who underwent urgent surgery (< 48 h), the complication rate was 45.5% (5/11) versus 18.3% (9/49) in the planned surgeries. CONCLUSIONS: Our findings supports the utility of using a common language in multidisciplinary tumour board for spinal metastasis. The 2-year OS rate in this series was 50%, which is the highest OS reported to date in this population. In the poor prognosis subgroup (Rades 1), OS at 6 months was higher in patients with new-onset cancer versus those with a known primary (68 vs. 40%). These findings suggest that surgery should be the first treatment option in patients with MSCC as first symptom of cancer although a predicted poor prognosis.

COVID-19 in breast cancer patients: a subanalysis of the OnCovid registry.

BACKGROUND: Cancer patients are at higher risk of COVID-19 complications and mortality than the rest of the population. Breast cancer patients seem to have better prognosis when infected by SARS-CoV-2 than other cancer patients. METHODS: We report a subanalysis of the OnCovid study providing more detailed information in the breast cancer population. RESULTS: We included 495 breast cancer patients with a SARS-CoV-2 infection. Mean age was 62.6 years; 31.5% presented more than one comorbidity. The most frequent breast cancer subtype was luminal-like (n = 245, 49.5%) and 177 (35.8%) had metastatic disease. A total of 332 (67.1%) patients were receiving active treatment, with radical intent in 232 (47.6%) of them. Hospitalization rate was 58.2% and all-cause mortality rate was 20.3%. One hundred twenty-nine (26.1%) patients developed one COVID-19 complication, being acute respiratory failure the most common (n = 74, 15.0%). In the multivariable analysis, age older than 70 years, presence of COVID-19 complications, and metastatic disease were factors correlated with worse outcomes, while ongoing anticancer therapy at time of COVID-19 diagnosis appeared to be a protective factor. No particular oncological treatment was related to higher risk of complications. In the context of SARS-CoV-2 infection, 73 (18.3%) patients had some kind of modification on their oncologic treatment. At the first oncological reassessment (median time: 46.9 days ± 36.7), 255 (51.6%) patients reported to be fully recovered from the infection. There were 39 patients (7.9%) with long-term SARS-CoV-2-related complications. CONCLUSION: In the context of COVID-19, our data confirm that breast cancer patients appear to have lower complications and mortality rate than expected in other cancer populations. Most breast cancer patients can be safely treated for their neoplasm during SARS-CoV-2 pandemic. Oncological treatment has no impact on the risk of SARS-CoV-2 complications, and, especially in the curative setting, the treatment should be modified as little as possible.

The clinical evaluation of the wish to hasten death is not upsetting for advanced cancer patients: A cross-sectional study.

BACKGROUND: An important concern of healthcare professionals when exploring the wish to hasten death with patients is the risk of causing them some type of distress. AIM: To assess the opinion of hospitalized patients with advanced cancer about the proactive assessment of the wish to hasten death. DESIGN: Descriptive, cross-sectional study. SETTING/PARTICIPANTS: We assessed 193 advanced cancer patients admitted to an oncology ward for the wish to hasten death using a semi-structured clinical interview. After the assessment the participants were surveyed to determine whether they found the interview upsetting and, if so to what extent, and also their opinion regarding the assessment's importance. RESULTS: The wish to hasten death was reported by 46 (23.8%) patients. The majority of patients (94.8%) did not find talking about the wish to hasten death to be upsetting, regardless of whether they presented it or not. The majority of patients (79.3%) considered that it was either quite or extremely important for the clinician to proactively assess the wish to hasten death and discuss this topic, regardless of whether they experienced it. CONCLUSIONS: In this study, most of the advanced cancer patients did not find the assessment of wish to hasten death to be upsetting, and a substantial proportion of patients in this study believe that it is important to routinely evaluate it in this setting. These findings suggest that healthcare professionals can explore the wish to hasten death proactively in routine clinical practice without fear of upsetting patients.

Successful treatment with brigatinib in a patient with ALK-rearranged lung adenocarcinoma who developed crizotinib-induced interstitial lung disease.

We present a 45-year-old patient diagnosed with anaplastic lymphoma kinase (ALK)-rearranged metastatic lung cancer who developed grade 4 interstitial lung disease (ILD) while on crizotinib treatment and was lately treated with brigatinib with no reappearance of ILD. To our knowledge, this is the first case report of successful treatment with brigatinib after crizotinib-induced ILD. Even though ILD secondary to brigatinib has been reported in clinical trials, no pulmonary toxicity has been seen in our patient, suggesting no crosslink lung toxicity between crizotinib and brigatinib.

Bloodstream infections in neutropenic patients with cancer: differences between patients with haematological malignancies and solid tumours.

OBJECTIVES: We sought to identify the characteristics, aetiology, antibiotic resistance and outcomes of bloodstream infection (BSI) in neutropenic patients with haematological malignancies (HM) and in those with solid tumours (ST) and assess their impact on empirical therapy and outcomes. METHODS: All episodes of BSI in neutropenic patients with HM and ST were prospectively recorded and compared. RESULTS: Of 579 episodes of BSI, 493 occurred in patients with HM and 86 in patients with ST. An endogenous source and catheter-related infection were more frequent in patients with HM, whereas pneumonia and urinary tract were more common in the ST group. BSI was mainly due to Gram-negative bacilli. Coagulase-negative staphylococci were more frequent in patients with HM, while Pseudomonas aeruginosa was more common in patients with ST and was the leading cause of pneumonia. Multidrug-resistant Gram-negative bacilli (MDRGNB) were more frequently isolated in haematological patients who more often received inadequate empirical therapy than those with ST. Case-fatality rates were higher in patients with ST. CONCLUSIONS: We identified significant differences in BSI in neutropenic patients with HM and ST. MDRGNB were more often isolated in patients with HM. Pneumonia due to P. aeruginosa was particularly frequent among patients with ST. Case-fatality rates were higher in patients with ST.

Bloodstream infections in patients with solid tumors: epidemiology, antibiotic therapy, and outcomes in 528 episodes in a single cancer center.

Current information regarding bloodstream infection (BSI) in patients with solid tumors is scarce. We assessed the epidemiology, antibiotic therapy, and outcomes of BSI in these patients. We also compared patients who died with those who survived to identify risk factors associated with mortality. From January 2006 to July 2012 all episodes of BSI in patients with solid tumors at a cancer center were prospectively recorded and analyzed. A total of 528 episodes of BSI were documented in 489 patients. The most frequent neoplasms were hepatobiliary tumors (19%), followed by lung cancer (18%) and lower gastrointestinal malignancies (16%). Many patients had received corticosteroid therapy (41%), and 15% had neutropenia (<500 neutrophils/µL) at the time of BSI. The most common source of BSI was cholangitis (21%), followed by other abdominal (19.5%) and urinary tract infections (17%). Gram-negative BSI occurred in 55% of cases, mainly due to Escherichia coli (55%), Pseudomonas aeruginosa (18%), and Klebsiella pneumoniae (16%). Among gram-positive BSI (35%), viridans group streptococci were the most frequent causative organisms (22%), followed by Staphylococcus aureus (21%) and Enterococcus species (18%). We identified 61 multidrug-resistant (MDR) organisms (13%), mainly extended-spectrum ß-lactamase-producing Enterobacteriaceae (n = 20) and AmpC-producing Enterobacteriaceae (n = 13). The majority of patients with BSI caused by MDR organisms had received antibiotics (70%), and they had been previously hospitalized (61.4%) more frequently than patients with BSI caused by susceptible strains. Inadequate empirical antibiotic therapy was given to 23% of patients, with a higher proportion in those with BSI due to a MDR strain (69%). Early (<48 h) and overall (30 d) case-fatality rates were 7% and 32%, respectively. The overall case-fatality rate was higher among cases caused by MDR organisms (39.3%). The only independent risk factors for the early case-fatality rate were the endogenous source of BSI (odds ratio [OR], 3.57; 95% confidence interval [CI], 1.06-12.02), shock at presentation (OR, 3.63; 95% CI, 1.63-8.09), and corticosteroid therapy (OR, 3.245; 95% CI, 1.43-7.32). The independent risk factors for overall case-fatality rate were the presence of a chronic advanced cancer (OR, 35.39; 95% CI, 2.48-504.91), shock at presentation (OR, 25.84; 95% CI, 3.73-179.0), and corticosteroid therapy (OR, 6.98; 95% CI, 1.61-30.21).BSI in patients with solid tumors occurred mainly among those with hepatobiliary cancer, and cholangitis was the most frequent source; gram-negative bacilli were the most frequent causative agents. MDR organisms were relatively common, particularly in patients who had previously received antibiotics and had been hospitalized; these patients were frequently treated with inadequate empirical antibiotic therapy and had a poorer outcome. The case-fatality rate of patients with solid tumors and BSI was high and was associated with chronic advanced cancer, corticosteroid therapy, and shock at presentation.

Bacteraemia due to extended-spectrum beta-lactamase-producing Escherichia coli (ESBL-EC) in cancer patients: clinical features, risk factors, molecular epidemiology and outcome.

OBJECTIVES: To assess the clinical features, risk factors, molecular epidemiology and outcome of extended-spectrum beta-lactamase-producing Escherichia coli (ESBL-EC) bacteraemia in hospitalized cancer patients. METHODS: Episodes of ESBL-EC bacteraemia were compared with a susceptible control group in a 3 year prospective study. ESBL-EC strains were studied by PCR and isoelectric focusing, and molecular typing was performed by PFGE. RESULTS: Out of 531 episodes of bacteraemia, 135 were caused by E. coli. Seventeen of these cases involved ESBL-EC-producing strains (12.6%). In the multivariate analysis, female gender [odds ratio (OR) 3.43; 95% confidence interval (CI) 1.03-11.4] and previous antibiotic therapy (OR 3.22; 95% CI 1.00-10.3) were found to be independent risk factors for ESBL acquisition. An analysis of ESBL-EC isolates revealed a polyclonal distribution with CTX-M predominance (59%). Patients with ESBL-EC bacteraemia were more likely to have received an inadequate empirical antibiotic therapy (65% versus 6%; P = 0.000), and the time to adequate therapy was longer in this group (0 versus 1.50 days; P = 0.000). The overall mortality rate was 22%, ranging from 20% to 35% (P = 0.20). Risk factors for mortality were solid tumour (OR 19.41; 95% CI 4.66-80.83), corticosteroid therapy (OR 3.04 95% CI 1.05-8.81) and intensive care unit admission (OR 248.24, 95% CI 18.49-3332.14). In neutropenic patients, ESBL-EC bacteraemia was associated with poorer outcome and a higher overall mortality rate (37.5% versus 6.5%; P = 0.01). CONCLUSIONS: In our centre, ESBL-EC bacteraemia is frequent among cancer patients, especially in those exposed to antibiotic pressure. All ESBL-EC strains were unrelated and most of them carried a CTX-M group enzyme. Patients with ESBL-EC bacteraemia received inadequate empirical antibiotic therapy more frequently than patients carrying a susceptible strain, but significant differences in mortality could not be demonstrated.

[beta-Lactam antibiotics]. / Antibióticos betalactámicos.

Betalactams, which act by inhibiting the last phase of bacterial cell wall synthesis, constitute the largest family of antimicrobial agents and the most extensively used in current clinical practice. These drug have a slow bactericidal action that is relatively independent of plasma concentrations, little toxicity and a broad therapeutic margin. Their spectrum has increased over the years with the incorporation of new molecules having greater activity against gram-negative bacilli. Nevertheless, the progressive emergence of acquired resistance has limited the empirical use of betalactams and their efficacy in certain situations. Despite this problem, penicillin is still the treatment of choice for a large number of classic infections, cephalosporins are widely used in surgical prophylaxis and severe community-acquired infections, carbapenems are the choice for mixed nosocomial and multiresistant bacterial infections and betalactamase inhibitors permit the effective use of amino- and ureido-penicillins in highly significant infections.