1,721,115 research outputs found
Bloodstream infections in patients with liver cirrhosis
No full textABSTRACT: Bloodstream infections are a serious complication in patients with liver cirrhosis. Dysregulated intestinal bacterial translocation is the predominant pathophysiological mechanism of infections in this setting. For this reason enteric Gram-negative bacteria are commonly encountered as the first etiological cause of infection. However, through the years, the improvement in the management of cirrhosis, the recourse to invasive procedures and the global spread of multidrug resistant pathogens have importantly changed the current epidemiology. Bloodstream infections in cirrhotic patients are characterized by high mortality rate and complications including metastatic infections, infective endocarditis, and endotipsitis (or transjugular intrahepatic portosystemic shunt-related infection). For this reason early identification of patients at risk for mortality and appropriated therapeutic management is mandatory. Liver cirrhosis can significantly change the pharmacokinetic behavior of antimicrobials. In fact hypoproteinaemia, ascitis and third space expansion and impairment of renal function can be translated in an unpredictable drug exposure
Use of meropenem in treating carbapenem-resistant Enterobacteriaceae infections
No full textIntroduction: The epidemiology of carbapenem resistant Enterobacterales (CRE) is increasingly worldwide. Production of carbapenemases is the most common and efficient mechanism of carbapenem resistance, and could theoretically be overcome by optimizing the pharmacokinetic/pharmacodynamic (PK/PD) behavior of meropenem. Areas covered: This article overviews the available literature concerning the potential role that meropenem may still have in the treatment carbapenem-resistant Enterobacteriaceae infections. Clinical studies published in English language until June 2019 were searched on PubMed database. Expert commentary: High-dose continuous infusion meropenem-based combination regimens could still represent a valuable option for treating CRE infections in specific circumstances. Knowledge of the local prevalent mechanisms of carbapenem resistance, of patient clinical severity, of the site of infection, of an accurate minimum inhibitory concentration (MIC) value, coupled with the possibility of carrying-out a real-time therapeutic drug monitoring (TDM)-based PK/PD optimization of drug exposure must all be considered as fundamental for properly pursuing this goal
Prevention of infections in nursing homes: Antibiotic prophylaxis versus infection control and antimicrobial stewardship measures
No full textBecause of the lack of structural and human resources for implementing more effective and safe preventive procedures, antimicrobial prophylaxis is often used to prevent infections in nursing homes. However, if data on the efficacy of antibiotic prophylaxis in nursing homes are null, there is a plenty of evidence that the inappropriate use of antimicrobials in this setting is associated with a high rate of colonization and infection with multi-drug-resistant organisms (MDROs), and of Clostridium difficile infection (CDI). Here, we have reviewed the infection epidemiology, the burden of MDROs and CDI, the antibiotic use and some potential infection preventive measures in nursing homes, pointing up the peculiarities of this setting and the absolute need of a more prudential use of antimicrobials
Management of bacterial and fungal infections in cirrhosis: The MDRO challenge
No full textBacterial infections are frequent in cirrhotic patients with acute decompensation or acute-on-chronic liver failure and can complicate the clinical course. Delayed diagnosis and inappropriate empirical treatments are associated with poor prognosis and increased mortality. Fungal infections are much less frequent, usually nosocomial and associated with extremely high short-term mortality. Early diagnosis and adequate empirical treatment of infections is therefore key in the management of these patients. In recent decades, antibiotic resistance has become a major worldwide problem in patients with cirrhosis, warranting a more complex approach to antibiotic treatment that includes the use of broad-spectrum antibiotics, new administration strategies, novel drugs and de-escalation policies. Herein, we review epidemiological changes, the main types of multidrug-resistant organisms, mechanisms of resistance, new rapid diagnostic tools and currently available therapeutic options for bacterial and fungal infections in cirrhosis
Carbapenemase-producing Enterobacteriaceae in transplant patients
No full textCarbapenemase-producing Enterobacteriaceae (CPE) are a serious public health concern and represent a major threat to immunocompromised hosts, including solid organ (SOT) and stem cell transplant (HSCT) recipients. Transplant patients are at particular risk of developing CPE colonization and/or infection due to their frequent exposure to prolonged courses of broad-spectrum antibiotics, altered immunocompetence and exposure to invasive procedures and immunosuppressive drugs. Gut colonization with CPE, in particular carbapenem-resistant Klebsiella pneumoniae, may occur before or after SOT in 2%-27% of patients and among 2%-9% of HSCT and has been associated with increased risk of developing CPE infections. In endemic areas, CPE infections occur in up to 18% of SOT, and HSCT patients can account for 5%-18% of all patients with CPE bacteraemia. Mortality rates up to 70% have been associated with CPE infections in both patient populations. The rapid initiation of an active therapy against CPE is advocated in these infections. Therapeutic options, however, are limited by the paucity of novel compounds that are currently available and by potential antibiotic-associated toxicities. Therefore, a multidisciplinary approach involving infection control and antimicrobial stewardship programmes still represents the mainstay for the management of CPE infections among transplant patients. The evidence for the use of prevention strategies such as CPE-targeted perioperative prophylaxis or gut decolonization is still scarce. Large, multicentre trials are required to better define prevention strategies and to guide the management of CPE infections in the transplant setting
3D dynamic cultures of HGSOC organoids to model innovative and standard therapies
Full text linkHigh-grade serous ovarian cancer (HGSOC) needs new technologies for improving cancer diagnosis and therapy. It is a fatal disease with few options for the patients. In this context, dynamic culture systems coupling with patient-derived cancer 3D microstructures could offer a new opportunity for exploring novel therapeutic approaches. In this study, we optimized a passive microfluidic platform with 3D cancer organoids, which allows a standardized approach among different patients, a minimum requirement of samples, multiple interrogations of biological events, and a rapid response. The passive flow was optimized to improve the growth of cancer organoids, avoiding the disruption of the extracellular matrix (ECM). Under optimized conditions of the OrganoFlow (tilting angle of 15° and an interval of rocking every 8 min), the cancer organoids grow faster than when they are in static conditions and the number of dead cells is reduced over time. To calculate the IC 50 values of standard chemotherapeutic drugs (carboplatin, paclitaxel, and doxorubicin) and targeted drugs (ATRA), different approaches were utilized. Resazurin staining, ATP-based assay, and DAPI/PI colocalization assays were compared, and the IC 50 values were calculated. The results showed that in the passive flow, the IC 50 values are lower than in static conditions. FITC-labeled paclitaxel shows a better penetration of ECM under passive flow than in static conditions, and cancer organoids start to die after 48 h instead of 96 h, respectively. Cancer organoids are the last frontiers for ex vivo testing of drugs that replicate the response of patients in the clinic. For this study, organoids derived from ascites or tissues of patients with Ovarian Cancer have been used. In conclusion, it was possible to develop a protocol for organoid cultures in a passive microfluidic platform with a higher growth rate, faster drug response, and better penetration of drugs into ECM, maintaining the samples' vitals and collecting the data on the same plate for up to 16 drugs
Multidrug-Resistant Bacterial Infections in Solid Organ Transplant Candidates and Recipients
No full textThe current era is ruled by an alarming evolution of antimicrobial resistance. Solid organ transplant recipients are prone to develop infections caused by multidrug-resistant pathogens. The current challenges in this setting include screening of donors and recipients, and prevention/treatment of donor-derived and posttransplant infections. The epidemiology of these infections varies between centers, type of transplanted organ, and pathogen. Treatment options are limited. Efforts to reduce carbapenem antibiotic pressure and infection control measures are necessary to reverse the spread of multidrug-resistant pathogens. Novel drugs for gram-negative multidrug-resistant bacilli may contribute to reduce carbapenemase diffusion and reduce the rate of treatment failure
Reply: Implementation of a Meningitis Care Bundle in the Emergency Room Reduces Mortality Associated With Acute Bacterial Meningitis
No full textThe role of extended infusion β-lactams in the treatment of bloodstream infections in patients with liver cirrhosis
No full textINTRODUCTION: Bloodstream infections (BSIs) in patients with liver cirrhosis are associated with significant morbidity and mortality. Early appropriated antibiotic treatment is essential for the correct management of these patients. Areas covered: This review covers several aspects of how the pharmacokinetic/pharmacodynamic behavior of antimicrobials may change in patients with liver cirrhosis. Common features of cirrhosis, including hypoproteinemia, third space expansion and impairment of renal function may alter drug distribution in patients receiving hydrophilic drugs like β-lactams, which are often frontline agents. β-lactams exhibit time-dependent pharmacodynamics and achieve maximal bacterial killing when serum drug and tissue concentrations exceed a multiple of the minimal inhibitory concentration (MIC) during the dosing interval (%fT>MIC). Administration of β-lactams by extended infusion strategies improves the rate of this pharmacodynamic target attainment and has been associated with improved outcomes in several randomized trials in critically-ill patients. Expert commentary: Observational studies have suggested that cirrhotic patients have improved outcomes when beta-lactam therapy is administered by extended or continuum infusion. Given the multiple pathophysiological features of liver cirrhosis that impact antimicrobial behavior and the high incidence of multidrug resistance in this population, additional studies are needed to understand how cirrhosis affects the pharmacokinetics and pharmacodynamics of antibacterial therapy
Opportunistic infections in end stage liver disease
No full textLiver cirrhosis is the 10th most common cause of death in Western world and infection is associated with a high morbidity and mortality, and represents the leading cause of acute liver decompensation. Patients with end-stage liver disease exhibit an important impairment of immune system. This condition, called cirrhosis-associated immune dysfunction, summarizes both local and systemic immune system alterations in liver cirrhosis that play a pivotal role in determining both the high incidence of infections and the ominous infections related mortality in this population. Another concerning feature of infections in cirrhotic patients is the growing prevalence of multidrug-resistant or extensively drug-resistant pathogens, which are associated with higher mortality, increased length of in-hospital stay and higher healthcare related costs if compared with infection caused by susceptible strains. Finally, patient with liver cirrhosis have several unique pathophysio-logical characteristics including hypoalbuminemia and reduction binding to proteins; altered distribution; altered clearance of the antimicrobials that can affect the pharmaco-kinetic/pharmacodynamic of antimicrobials
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