Current Challenges in the Management of Infective Endocarditis

Infective endocarditis is a relatively rare, but deadly cause of sepsis, with an overall mortality ranging from 20 to 25% in most series. Although the classic clinical classification into syndromes of acute or subacute endocarditis have not completely lost their usefulness, current clinical forms have changed according to the profound epidemiological changes observed in developed countries. In this review, we aim to address the changing epidemiology of endocarditis, several recent advances in the understanding of the pathophysiology of endocarditis and endocarditis-triggered sepsis, new useful diagnostic tools as well as current concepts in the medical and surgical management of this disease. Given its complexity, the management of infective endocarditis requires the close collaboration of multidisciplinary endocarditis teams that must decide on the diagnostic approach; the appropriate initial treatment in the critical phase; the detection of patients needing surgery and the timing of this intervention; and finally the accurate selection of patients for out-of-hospital treatment, either at home hospitalization or with oral antibiotic treatment

Understanding and Managing Sepsis in Patients With Cancer in the Era of Antimicrobial Resistance

Sepsis is a frequent complication in immunosuppressed cancer patients and hematopoietic stem cell transplant recipients that is associated with high morbidity and mortality rates. The worldwide emergence of antimicrobial resistance is of special concern in this population because any delay in starting adequate empirical antibiotic therapy can lead to poor outcomes. In this review, we aim to address: (1) the mechanisms involved in the development of sepsis and septic shock in these patients; (2) the risk factors associated with a worse prognosis; (3) the impact of adequate initial empirical antibiotic therapy given the current era of widespread antimicrobial resistance; and (4) the optimal management of sepsis, including adequate and early source control of infection, optimized antibiotic use based on the pharmacokinetic and pharmacodynamics changes in these patients, and the role of the new available antibiotics

Infections simulating immune checkpoint inhibitor toxicities: uncommon and deceptive

Use of immune checkpoint inhibitors (ICIs), a revolutionary treatment in modern oncology, is frequently complicated by immune-related adverse events (irAEs), which can be confused with infections, and vice versa, thus complicating management decisions. In this study, we review the published cases of infections as simulators of irAEs in cancer patients

A fresh look at polymicrobial bloodstream infection in cancer patients

Objectives: To assess the current incidence, clinical features, risk factors, aetiology, antimicrobial resistance and outcomes of polymicrobial bloodstream infection (PBSI) in patients with cancer. Methods: All prospectively collected episodes of PBSI in hospitalised patients were compared with episodes of monomicrobial bloodstream infection (MBSI) between 2006 and 2015. Results: We identified 194 (10.2%) episodes of PBSI and 1702 MBSI (89.8%). The presence of cholangitis, biliary stenting, neutropenia, corticosteroids, neutropenic enterocolitis and other abdominal infections were identified as risk factors for PBSI. Overall, Gram-negative organisms were the most frequent aetiology, but Enterococcus spp. were especially frequent causes of Gram-positive PBSI (30.8%). Multidrug-resistant (MDR) organisms were more commonly found in PBSI than in MBSI (20.6% vs 12.9%; p = 0.003). Compared to patients with MBSI, those with PBSI presented with higher early (15% vs 1.4%; p = 0.04) and overall (32% vs 20.9%; p<0.001) case-fatality rates. Risk factors for overall case-fatality were a high-risk MASCC (Multinational Association of Supportive Care in Cancer) index score, corticosteroid use, persistent bacteraemia and septic shock. Conclusions PBSI is a frequent complication in patients with cancer and is responsible for high mortality rates. Physicians should identify patients at risk for PBSI and provide empiric antibiotic therapy that covers the most frequent pathogens involved in these infections, including MDR strains

Prolonged vs short-term infusion of β-lactam antibiotics for the treatment of febrile neutropenia: A systematic review and meta-analysis

Background: The optimisation of the use of beta-lactam antibiotics (BLA) via prolonged infusions in life-threatening complications such as febrile neutropenia (FN) is still controversial. This systematic review and meta-analysis aim to evaluate the efficacy of this strategy in onco-haematological patients with FN. Methods: A systematic search was performed of PubMed, Web of Science, Cochrane, EMBASE, World Health Organization, and ClinicalTrials.gov, from database inception until December 2022. The search included randomised controlled trials (RCTs) and observational studies that compared prolonged vs short-term infusions of the same BLA. The primary outcome was all-cause mortality. Secondary outcomes were defervescence, requirement of vasoactive drugs, length of hospital stay and adverse events. Pooled risk ratios were calculated using random effects models. Results: Five studies were included, comprising 691 episodes of FN, mainly in haematological patients. Prolonged infusion was not associated with a reduction in all-cause mortality (pRR 0.83; 95% confidence interval 0.47-1.48). Nor differences were found in secondary outcomes. Conclusions: The limited data available did not show significant differences in terms of all-cause mortality or significant secondary outcomes in patients with FN receiving BLA in prolonged vs. short-term infusion. High-quality RCTs are needed to determine whether there are subgroups of FN patients who would benefit from prolonged BLA infusion. (c) 2023 The Author(s). Published by Elsevier Ltd on behalf of The British Infection Association. This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/)

Isavuconazole prophylaxis against invasive fungal infections in allogeneic stem cell transplantation: a single-center experience

Patients undergoing allogeneic stem cell transplantation (alloHCT) require profound immunosuppression is required to preserve graft function and prevent graft-versus host disease (GVHD), resulting in a high risk of infectious complications such as invasive fungal diseases (IFIs). Posaconazole is approved for primary antifungal prophylaxis alloHCT. However, posaconazole is associated with drug-drug interactions which may lead to relevant toxicities limiting it uses in hematological patients. Other triazoles, amphotericine B, and echinocandins can be used in patients at high risk of IFIs. However, there is less evidence supporting the efficacy of these drugs for the prevention of IFIs

Influenza and Bacterial Coinfection in Adults With Community-Acquired Pneumonia Admitted to Conventional Wards: Risk Factors, Clinical Features, and Outcomes

Background. Relevance of viral and bacterial coinfection (VBC) in non-intensive care unit (ICU) hospitalized adults with community-acquired pneumonia (CAP) is poorly characterized. We aim to determine risk factors, features, and outcomes of VBCCAP in this setting. Methods. This is a prospective cohort of adults admitted to conventional wards with CAP. Patients were divided into VBC-CAP, viral CAP (V-CAP), and bacterial CAP (B-CAP) groups. Independent risk and prognostic factors for VBC-CAP were identified. Results. We documented 1123 episodes: 57 (5.1%) VBC-CAP, 98 (8.7%) V-CAP, and 968 (86.1%) B-CAP. Patients with VBCCAP were younger than those with B-CAP (54 vs 71 years; P < .001). Chronic respiratory disease was more frequent in patients with VBC-CAP than in those with V-CAP (26.3% vs 14.3%%; P = .001). Among those with influenza (n = 153), the VBC-CAP group received empirical oseltamivir less often (56.1% vs 73.5%; P < .001). Patients with VBC-CAP also had more respiratory distress (21.1% VBC-CAP; 19.4% V-CAP, and 9.8% B-CAP; P < .001) and required ICU admission more often (31.6% VBC-CAP, 31.6% V-CAP, and 12.8% B-CAP; P < .001). Me 30-day case-fatality rate was 3.5% in the VBC-CAP group, 3.1% in the V-CAP group, and 6.3% in the B-CAP group (P = .232). Furthermore, VBC-CAP was associated with severity criteria (odds ratio [OR], 5.219; P < .001) and lack of empirical oseltamivir therapy in influenza cases (OR, 0.401; P < .043). Conclusions. Viral and bacterial coinfection-CAP involved younger patients with comorbidities and with poor influenza vaccination rate. Patients with VBC-CAP presented more respiratory complications and more often required ICU admission. Nevertheless, 30-day mortality rate was low and related either to severity criteria or to delayed initiation of oseltamivir therapy

Host- and Pathogen-Related Factors for Acute Cardiac Events in Pneumococcal Pneumonia

Background: Acute cardiac events (ACEs) are increasingly being recognized as a major complication in pneumococcal community-acquired pneumonia (CAP). Information regarding host- and pathogen-related factors for ACEs, including pneumococcal serotypes and clonal complexes, is scarce. Methods: A retrospective study was conducted of a prospective cohort of patients hospitalized for CAP between 1996 and 2019. Logistic regression and funnel plot analyses were performed to determine host- and pathogen-related factors for ACEs. Results: Of 1739 episodes of pneumococcal CAP, 1 or more ACEs occurred in 304 (17.5%) patients, the most frequent being arrhythmia (n = 207), heart failure (n = 135), and myocardial infarction (n = 23). The majority of ACEs (73.4%) occurred within 48 hours of admission. Factors independently associated with ACEs were older age, preexisting heart conditions, pneumococcal bacteremia, septic shock at admission, and high-risk pneumonia. Among 983 pneumococcal isolates, 872 (88.7%) were serotyped and 742 (75.5%) genotyped. The funnel plot analyses did not find any statistically significant association between serotypes or clonal complexes with ACEs. Nevertheless, there was a trend toward an association between CC230 and these complications. ACEs were independently associated with 30-day mortality (adjusted odds ratio, 1.88; 95% CI, 1.11-3.13). Conclusions: ACEs are frequent in pneumococcal pneumonia and are associated with increased mortality. The risk factors defined in this study may help identify patients who must undergo close follow-up, including heart rhythm monitoring, and special care to avoid fluid overload, particularly during the first 48 hours of admission. These high-risk patients should be the target for preventive intervention strategies

Effect of statin use on outcomes of adults with candidemia

Background: Statins have immunomodulatory properties and hinder Candida growth. However, it is unknown whether they may improve prognosis in patients with candidemia. We sought to determine the effect of prior statin use on the clinical outcomes of patients suffering candidemia. Methods and Findings: Multicenter cohort study of hospitalized adults with candidemia between 2005 and 2011 in six hospitals in Spain, Brazil and Argentina. Of 326 candidemias, 44 (13.5%) occurred in statin users and 282 (86.5%) in statin non-users. The median value of APACHE II at candidemia diagnosis was similar between groups (18 vs. 16; p=.36). Candida albicans was the most commonly isolated species, followed by C. parapsilosis, C. tropicalis, C. glabrata, and C. krusei. There were no differences regarding appropriate empirical antifungal treatment. Statin users had a lower early (5 d) case-fatality rate than non-users (4.5 vs. 17%; p=.031). This effect was not observed with other cardiovascular drugs (aspirin, beta blockers and ACE inhibitors). Independent factor related to early case-fatality rate was APACHE II score (AOR, 1.08; 95% CI, 1.03-1.14; p=.002). An appropriate empirical antifungal therapy (AOR, 0.11; 95% CI, 0.04-0.26; p=<.001) and prior statin use were independently associated with lower early case-fatality (AOR, 0.17; 95% CI, 0.03-0.93; p=.041). Fourteen days (14d) and overall (30d) case-fatality rates were similar between groups (27% vs. 29%; p=0.77 and 40% vs. 44%; p=.66). Conclusions: The use of statins might have a beneficial effect on outcomes of patients with candidemia. This hypothesis deserves further evaluation in randomized trials

Effect of albumin administration on outcomes in hypoalbuminemic patients hospitalized with community-acquired pneumonia (ALBUCAP): a prospective, randomized, phase III clinical controlled trial - a trial protocol

Background: Community-acquired pneumonia (CAP) remains a leading cause of death worldwide, and hypoalbuminemia is associated with worse outcomes. However, it remains uncertain whether albumin administration could have any beneficial effects. We aim to assess whether the administration of albumin in hypoalbuminemic patients with CAP increases the proportion of clinically stable patients at day 5 compared with the standard of care alone. Methods: This is a trial protocol for a superiority, non-blinded, multicenter, randomized, phase 3, interventional controlled clinical trial. The primary endpoint will be the proportion of clinical stable patients at day 5 (intention to treat), defined as those with stable vital signs for at least 24 h. The secondary endpoints will be time to clinical stability, duration of intravenous and total antibiotic treatment, length of hospital stay, intensive care unit admission, duration of mechanical ventilation and vasopressor treatment, adverse events, readmission within 30 days, and all-cause mortality. The trial has been approved by the Spanish Medicines and Healthcare Products Regulatory Agency. The investigators commit to publish the data in peer-reviewed journals within a year of the study completion date. Subjects will be recruited from three Spanish hospitals over a planned enrolment period of 2 years. A follow-up visit will be performed 1 month after discharge. We have estimated the need for a sample size of 360 patients at a two-sided 5% alpha-level with a power of 80% based on intention to treat. Eligible participants must be hospitalized, hypoalbuminemic (≤ 30 g/L), non-immunosuppressed, adults, and diagnosed with CAP. They will be randomly assigned (1:1) to receive standard care plus albumin (20 g in 100 mL) every 12 h for 4 days or standard care alone. Discussion: If this randomized trial confirms the hypothesis, it should lead to a change in current clinical practice for the management of hypoalbuminemic patients with CAP