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Hospital-acquired infections (HAI) are common in cirrhosis with antibiotics frequently used to prevent infections, but their efficacy for this role is unknown. To investigate this, we used Albumin to Prevent Infection in Chronic Liver Failure (ATTIRE) data to evaluate whether antibiotic use in patients without infection prevented HAI. In ATTIRE patients without infection at baseline grouped by antibiotic prescription or not, we studied HAI during trial treatment period and mortality, with propensity score matching to account for differences in disease severity. Two hundred three of 408 patients prescribed antibiotics at enrollment did not have infection and they were more unwell than noninfected patients not given antibiotics. There were no differences in subsequent HAI comparing antibiotic treated (39/203, 19.2%) to nonantibiotic treated (73/360, 20.3%; P = 0.83). Twenty-eight-day mortality was higher in antibiotic-treated patients ( P = 0.004) likely reflecting increased disease severity. Matching groups using propensity scoring revealed no differences in HAI or mortality. In noninfected patients at enrollment treated with/without rifaximin, there were no differences in HAI ( P = 0.16) or mortality, confirmed with propensity matching. Patients given long-term antibiotic prophylaxis at discharge had no differences in 6-month mortality compared with nonantibiotic patients, although antibiotic-treated patients had more infections at trial entry, with numbers too small for matching. Half of antibiotics at study entry were given to patients without an infection diagnosis which did not reduce the overall risk of HAI or improve mortality. This supports prompt de-escalation or discontinuation of antibiotics guided by culture sensitivities at 24-48 hours after commencement if no infection and the patient is improving.

Background: The clinical response of patients with severe acute respiratory syndrome (SARS) to a combination of lopinavir/ritonavir and ribavirin was examined after establishing the in vitro antiviral susceptibility of the SARS associated coronavirus to a panel of antiviral agents. Methods: The in vitro susceptibility of the prototype of SARS associated coronavirus to a panel of nucleoside analogues and protease inhibitors currently licensed for clinical use was studied. Forty one patients with SARS followed for 3 weeks were treated with a combination of lopinavir/ritonavir and ribavirin. The clinical progress and virological outcomes were monitored and compared with 111 patients treated with ribavirin only who served as historical controls. Results: In vitro antiviral activity against SARS associated coronavirus was demonstrated for lopinavir and ribavirin at concentrations of 4 µg/ml and 50 µg/ml, respectively, only at 48 hours. The adverse clinical outcome (ARDS or death) was significantly lower in the treatment group than in the historical controls (2.4% v 28.8%, p<0.001) at day 21 after the onset of symptoms. The adverse outcome remained significantly lower in the treatment group than in the controls—both those diagnosed early (p<0.001) and those diagnosed later in the course of the epidemic (p = 0.002)—but there was no significant difference in adverse outcome rates between the two time periods (p = 0.548). No time related difference in outcome was observed in the control groups. A reduction in steroid usage and nosocomial infections was seen in patients initially treated with lopinavir/ritonavir, and these patients had a decreasing viral load and rising peripheral lymphocyte count. Multivariate analysis showed that age, hepatitis B carrier status, and lack of treatment with this antiviral combination were independent predictors of an adverse outcome. Lopinavir/ritonavir treatment was associated with a better outcome even when adjusted for baseline lactate dehydrogenase level. Conclusions: The apparent favourable clinical response with lopinavir/ritonavir and ribavirin supports further randomised placebo controlled trials in patients with SARS.

Background and objectives: At present, Romania and parts of the European Union are facing an increasingly challenging public health problem consisting of nosocomial Clostridioides difficile infection (CDI), mostly in the elderly. Relapse cases have become more frequent, which present higher morbidity and mortality rates than the initial CDI infection. The aim of this study is to determine the predictive factors for recurrence, with the purpose of reducing the exposure of patients diagnosed with CDI, as well as aiming to initiate early treatment. Materials and Methods: In this retrospective descriptive study, we analyze a database from the First Department of Infectious Diseases at the Dr. Victor Babes Clinical Hospital for Infectious Diseases and Pulmonology in Timisoara, looking for patient history of CDI recurrences. We analyzed CDI recurrence in patients aged ≥65 years from 1 January 2016 to 31 December 2019, identifying 77 cases of CDI recurrence. The determination of predictive factors for recurrence involved the formation of a randomized control group, consisting of 74 patients aged ≥65 years who were diagnosed with C. difficile enterocolitis, but did not suffer a recurrence and survived ≥2 weeks after symptom onset. Results: Immunocompromised status, pre-existing gastrointestinal disease, and fever on initial hospitalization for CDI were all found to be significant independent positive predictive factors for the condition recurring in elderly Romanian patients. Conclusions: As the geriatric population in Romania grows, the national health system becomes increasingly overburdened, both from a financial standpoint and a human resources perspective. The analysis of factors predictive for CDI recurrence is, thus, of the utmost importance, particularly for the early identification of patients most at risk of CDI recurrence. Our findings could help physicians to identify recurrence early, consequently benefitting patients by a rapid intervention with a potential decrease in the associated complications and mortality.

FUO despite a high-quality workup after a reasonable amount of time has elapsed to rule out self-limited fevers remains a challenge. The clinician must pay close attention to the patient history, aided by the development of molecular diagnostic tests, to distinguish infections from other causes.

Supplemental oxygen is often administered liberally to acutely ill adults, but the credibility of the evidence for this practice is unclear. We systematically reviewed the efficacy and safety of liberal versus conservative oxygen therapy in acutely ill adults. In the Improving Oxygen Therapy in Acute-illness (IOTA) systematic review and meta-analysis, we searched the Cochrane Central Register of Controlled Trials, MEDLINE, Embase, HealthSTAR, LILACS, PapersFirst, and the WHO International Clinical Trials Registry from inception to Oct 25, 2017, for randomised controlled trials comparing liberal and conservative oxygen therapy in acutely ill adults (aged ≥18 years). Studies limited to patients with chronic respiratory diseases or psychiatric disease, patients on extracorporeal life support, or patients treated with hyperbaric oxygen therapy or elective surgery were excluded. We screened studies and extracted summary estimates independently and in duplicate. We also extracted individual patient-level data from survival curves. The main outcomes were mortality (in-hospital, at 30 days, and at longest follow-up) and morbidity (disability at longest follow-up, risk of hospital-acquired pneumonia, any hospital-acquired infection, and length of hospital stay) assessed by random-effects meta-analyses. We assessed quality of evidence using the grading of recommendations assessment, development, and evaluation approach. This study is registered with PROSPERO, number CRD42017065697. 25 randomised controlled trials enrolled 16 037 patients with sepsis, critical illness, stroke, trauma, myocardial infarction, or cardiac arrest, and patients who had emergency surgery. Compared with a conservative oxygen strategy, a liberal oxygen strategy (median baseline saturation of peripheral oxygen [SpO2] across trials, 96% [range 94–99%, IQR 96–98]) increased mortality in-hospital (relative risk [RR] 1·21, 95% CI 1·03–1·43, I2=0%, high quality), at 30 days (RR 1·14, 95% CI 1·01–1·29, I2=0%, high quality), and at longest follow-up (RR 1·10, 95% CI 1·00–1·20, I2=0%, high quality). Morbidity outcomes were similar between groups. Findings were robust to trial sequential, subgroup, and sensitivity analyses. In acutely ill adults, high-quality evidence shows that liberal oxygen therapy increases mortality without improving other patient-important outcomes. Supplemental oxygen might become unfavourable above an SpO2 range of 94–96%. These results support the conservative administration of oxygen therapy. None.

Mucormycosis is an emerging angioinvasive infection caused by the ubiquitous filamentous fungi of the Mucorales order of the class of Zygomycetes. Mucormycosis has emerged as the third most common invasive mycosis in order of importance after candidiasis and aspergillosis in patients with hematological and allogeneic stem cell transplantation. Mucormycosis also remains a threat in patients with diabetes mellitus in the Western world. Furthermore, this disease is increasingly recognized in recently developed countries, such as India, mainly in patients with uncontrolled diabetes or trauma. Epidemiological data on this type of mycosis are scant. Therefore, our ability to determine the burden of disease is limited. Based on anatomic localization, mucormycosis can be classified as one of 6 forms: (1) rhinocerebral, (2) pulmonary, (3) cutaneous, (4) gastrointestinal, (5) disseminated, and (6) uncommon presentations. The underlying conditions can influence clinical presentation and outcome. This review describes the emerging epidemiology and the clinical manifestations of mucormycosis.

Neonatal sepsis is the cause of substantial morbidity and mortality. Precise estimates of neonatal sepsis burden vary by setting. Differing estimates of disease burden have been reported from high-income countries compared with reports from low-income and middle-income countries. The clinical manifestations range from subclinical infection to severe manifestations of focal or systemic disease. The source of the pathogen might be attributed to an in-utero infection, acquisition from maternal flora, or postnatal acquisition from the hospital or community. The timing of exposure, inoculum size, immune status of the infant, and virulence of the causative agent influence the clinical expression of neonatal sepsis. Immunological immaturity of the neonate might result in an impaired response to infectious agents. This is especially evident in premature infants whose prolonged stays in hospital and need for invasive procedures place them at increased risk for hospital-acquired infections. Clinically, there is often little difference between sepsis that is caused by an identified pathogen and sepsis that is caused by an unknown pathogen. Culture-independent diagnostics, the use of sepsis prediction scores, judicious antimicrobial use, and the development of preventive measures including maternal vaccines are ongoing efforts designed to reduce the burden of neonatal sepsis.

A case-control study was undertaken in an acute district general hospital to identify risk factors for hospital-acquired bacteraemia caused by methicillin-resistant Staphylococcus aureus (MRSA). Cases of hospital-acquired MRSA bacteraemia were defined as consecutive patients from whom MRSA was isolated from a blood sample taken on the third or subsequent day after admission. Controls were randomly selected from patients admitted to the hospital over the same time period with a length of stay of more than 2 days who did not have bacteraemia. Data on 42 of the 46 cases of hospital-acquired bacteraemia and 90 of the 92 controls were available for analysis. There were no significant differences in the age or sex of cases and controls. After adjusting for confounding factors, insertion of a central line [adjusted odds ratio (aOR) 35·3, 95% confidence interval (CI) 3·8–325·5] or urinary catheter (aOR 37·1, 95% CI 7·1–193·2) during the admission, and surgical site infection (aOR 4·3, 95% CI 1·2–14·6) all remained independent risk factors for MRSA bacteraemia. The adjusted population attributable fraction, showed that 51% of hospital-acquired MRSA bacteraemia cases were attributable to a urinary catheter, 39% to a central line, and 16% to a surgical site infection. In the United Kingdom, measures to reduce the incidence of hospital-acquired MRSA bacteraemia in acute general hospitals should focus on improving infection control procedures for the insertion and, most importantly, care of central lines and urinary catheters.

Abstract Rationale Sepsis can be complicated by secondary infections. We explored the possibility that patients with sepsis developing a secondary infection while in the intensive care unit (ICU) display sustained inflammatory, vascular, and procoagulant responses. Objectives To compare systemic proinflammatory host responses in patients with sepsis who acquire a new infection with those who do not. Methods Consecutive patients with sepsis with a length of ICU stay greater than 48 hours were prospectively analyzed for the development of ICU-acquired infections. Twenty host response biomarkers reflective of key pathways implicated in sepsis pathogenesis were measured during the first 4 days after ICU admission and at the day of an ICU-acquired infection or noninfectious complication. Measurements and Main Results Of 1,237 admissions for sepsis (1,089 patients), 178 (14.4%) admissions were complicated by ICU-acquired infections (at Day 10 [6–13], median with interquartile range). Patients who developed a secondary infection showed higher disease severity scores and higher mortality up to 1 year than those who did not. Analyses of biomarkers in patients who later went on to develop secondary infections revealed a more dysregulated host response during the first 4 days after admission, as reflected by enhanced inflammation, stronger endothelial cell activation, a more disturbed vascular integrity, and evidence for enhanced coagulation activation. Host response reactions were similar at the time of ICU-acquired infectious or noninfectious complications. Conclusions Patients with sepsis who developed an ICU-acquired infection showed a more dysregulated proinflammatory and vascular host response during the first 4 days of ICU admission than those who did not develop a secondary infection.

Rotavirus is a common cause of infectious gastroenteritis in infants and children. The role of rotavirus infections in adults has potentially been underappreciated and there is a paucity of data on incidence and outcome of acute kidney injury in adult patients. We conducted a retrospective cohort study of adult hospitalized patients with microbiologically confirmed rotavirus infection. The primary outcome was occurrence of acute kidney injury related to rotavirus infection. Secondary outcomes were in-hospital mortality, duration of hospitalization and occurrence of sodium disorders. 314 hospitalized adult patients with rotavirus infection (mean age 73.2 (± 15.6) years, 39.5% with diabetes mellitus and 33.4% with chronic kidney disease (CKD)) were evaluated. 200 patients (63.7%) had community-acquired and 114 patients (36.3%) had nosocomial rotavirus infection. Acute kidney injury (AKI) occurred in 127 (40.4%) patients. AKI occurred more often in patients with community-acquired than nosocomial infection (110 (55.0%) vs 17 (14.9%), p < 0.001). In the multivariate logistic regression analysis, preexisting CKD (OR 3.29, CI 1.92-5.77, p < 0.001) and community-acquired route of rotavirus infection (OR 8.00 (CI 4.43-15.3, p < 0.001) were significantly associated with the development of AKI. 26 (8.3%) patients died in hospital. Patients with AKI had worse survival (HR 2.63 (CI 1.20-5.74) p = 0.01). In the multivariate Cox regression analysis only age, but not AKI, was still significantly associated with mortality (HR 1.06, CI 1.01-1.11, p = 0.01). Hyponatremia was detected in 60 (30.6%) of 196 patients with community-acquired infection. Dehydration occurred in only 5 (2.6%) patients. Adult outpatients with rotavirus infection and certain risk factors (e.g., CKD) have a high risk of developing AKI. Patients should seek medical attention with a low threshold and, if necessary, undergo hospitalization to counteract volume depletion and the development of acute renal injury. Hyponatremia frequently occurs while dehydration is rare. Recommendations in outpatients at risk for AKI should focus on increasing salt intake rather than water intake.