Issues in the management of invasive pulmonary aspergillosis in non-neutropenic patients in the intensive care unit: A role for isavuconazole

Background: Almost half of all cases of invasive aspergillosis (IA) occur in the intensive care unit (ICU), with mortality rates of 70\u201380% for probable or proven cases. IA has become a major concern among non-neutropenic patients in the ICU with chronic obstructive pulmonary disease (COPD) but although prompt, appropriate antifungal therapy is crucial, diagnosis in this situation is challenging. Criteria for a probable diagnosis in critically ill patients have been proposed to help to expedite therapy. Methods: A case of probable invasive pulmonary aspergillosis (IPA) in a non-neutropenic patient admitted to the ICU was used to illustrate potential issues in the diagnostic work-up and management of patients in this setting. Results: A non-neutropenic 69-year-old man with COPD receiving clomipramine was diagnosed in the ICU with probable invasive aspergillosis based on the presence of severe chronic obstructive pulmonary disease, suspected X-linked granulomatous disease, nodular infiltrates and galactogamman positivity on bronchoalveolar lavage (BAL) fluid. Voriconazole was unsuitable due to the patient's prolonged QT interval and risk of a drug\u2013drug interaction with clomipramine. Isavuconazole was initiated and the patient's condition improved. The three-month course of isavuconazole treatment was well-tolerated and resulted in compete recovery of the patient. Conclusions: Voriconazole is a standard first-line treatment for IA but intravenous therapy is associated with toxicity and the potential for drug\u2013drug interactions. Isavuconazole is another first-line therapy which was effective and safe in the management of this critically ill non-neutropenic patient with baseline QT prolongation and potential drug\u2013drug interactions with voriconazole

Emerging treatment options for acute bacterial skin and skin structure infections: Focus on intravenous delafloxacin

The increase in hospitalization due to acute bacterial skin and skin structure infections (ABSSSI) caused by resistant pathogens supports the need for new treatment options. Antimicrobial options for ABSSSI that provide broad-spectrum coverage, including gram-negative pathogens and multidrug-resistant gram-positive bacteria, such as methicillinresistant Staphylococcus aureus (MRSA), are limited. Delafloxacin is a novel fluoroquinolone available as intravenous and oral formulations and is characterized by an increased efficacy in acidic environments and activity on bacterial biofilm. Delafloxacin displays enhanced in vitro activity against MRSA, and enterococci, while maintaining efficacy against gram-negative pathogens and anaerobes. Delafloxacin has been studied for the treatment of ABSSSI and respiratory infections. Phase III studies have demonstrated noninferiority of delafloxacin compared to vancomycin, linezolid, tigecycline, and the combination of vancomycin plus aztreonam in the treatment of ABSSSI. Due to its favorable pharmacokinetic characteristics, the wide spectrum of action, and the potential for sequential therapy, delafloxacin represents a promising option in the empirical and targeted treatment of ABSSSI, both in hospital- and in community-based care

Impact of new treatment options for hepatitis c virus infection in liver transplantation

Liver transplant candidates and recipients with hepatitis C virus (HCV)-related liver disease greatly benefit from an effective antiviral therapy. The achievement of a sustained virological response before transplantation can prevent the recurrence of post-transplant HCV disease that occurs universally and correlates with enhanced progression to graft cirrhosis. Previous standard-of-care regimens (e.g., pegylated-interferon plus ribavirin with or without first generation protease inhibitors, boceprevir and telaprevir) displayed suboptimal results and poor tolerance in liver transplant recipients. A new class of potent direct-acting antiviral agents (DAA) characterized by all-oral regimens with minimal side effects has been approved and included in the recent guidelines for the treatment of liver transplant recipients with recurrent HCV disease. Association of sofosbuvir with ribavirin and/or ledipasvir is recommended in liver transplant recipients and patients with decompensated cirrhosis. Other regimens include simeprevir, daclatasvir, and combination of other DAA. Possible interactions should be monitored, especially in coinfected human immunodeficiency virus/HCV patients receiving antiretrovirals

Is first-line antimicrobial therapy still adequate to treat MRSA in the ICU? A report from a highly endemic country

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Incidence and outcome of invasive candidiasis in intensive care units (ICUs) in Europe: results of the EUCANDICU project

BACKGROUND: The objective of this study was to assess the cumulative incidence of invasive candidiasis (IC) in intensive care units (ICUs) in Europe. METHODS: A multinational, multicenter, retrospective study was conducted in 23 ICUs in 9 European countries, representing the first phase of the candidemia/intra-abdominal candidiasis in European ICU project (EUCANDICU). RESULTS: During the study period, 570 episodes of ICU-acquired IC were observed, with a cumulative incidence of 7.07 episodes per 1000 ICU admissions, with important between-center variability. Separated, non-mutually exclusive cumulative incidences of candidemia and IAC were 5.52 and 1.84 episodes per 1000 ICU admissions, respectively. Crude 30-day mortality was 42%. Age (odds ratio [OR] 1.04 per year, 95% CI 1.02-1.06, p < 0.001), severe hepatic failure (OR 3.25, 95% 1.31-8.08, p 0.011), SOFA score at the onset of IC (OR 1.11 per point, 95% CI 1.04-1.17, p 0.001), and septic shock (OR 2.12, 95% CI 1.24-3.63, p 0.006) were associated with increased 30-day mortality in a secondary, exploratory analysis. CONCLUSIONS: The cumulative incidence of IC in 23 European ICUs was 7.07 episodes per 1000 ICU admissions. Future in-depth analyses will allow explaining part of the observed between-center variability, with the ultimate aim of helping to improve local infection control and antifungal stewardship projects and interventions

Infezioni delle vie urinarie: appropriatezza in antibioticoterapia

2Adequacy of antimicrobial therapy in urinary tract infections (UTI)Urinary tract infections are one of the most common reasons for antimicrobial prescriptions, however urine cultures are often unavailable and the choice of antibiotics is therefore empiric. The ideal antimicrobial agent must have specific pharmacokinetic and pharmacodynamic characteristics and an adequate spectrum of activity in order to obtain the potential eradication of the pathogen from the site of infection, minimizing the risk of recurrences and ensuring the best safety profile. There are several factors to be considered in the therapy choice: the type of infection, the increasing presence of extended-spectrum beta-lactamase (ESBL) producing bacteria showing resistance to most antibiotics and the problem of the bacterial internalization, that is a frequent cause of treatment failure and early recurrences. Prulifloxacin is a recent oral fluoroquinolone antibiotic approved in several European countries for the treatment of lower urinary tract infections and shows some interesting advantages in comparison with other antibiotics.nonenoneBassetti, Matteo; Carnelutti, AlessiaBassetti, Matteo; Carnelutti, Alessi

New therapeutic options for respiratory tract infections

Purpose of review: The progressive increase of respiratory tract infections caused by multidrug-resistant organisms (MDROs) has been associated with delays in the prescription of an adequate antibiotic treatment and increased mortality, representing a major concern in both community and hospital settings. When infections because of methicillin-resistant Staphylococcus aureus (MRSA) are suspected, vancomycin still represents the first choice, although its efficacy has been recently questioned in favor of new drugs, reported to provide better clinical outcomes. Moreover, few therapeutic options are currently available for the treatment of severe infections caused by Multidrug-resistant (MDR) Gram-negative pathogens, which are frequently resistant to all the available \u3b2-lactams, including carbapenems. We have reviewed the therapeutic options for the treatment of respiratory tract infections that have recently become available with promising implications for clinical practice, including ceftaroline, ceftrobiprole, tedizolid, telavancin, delafloxacin, eravacycline, and new \u3b2-lactams/\u3b2-lactamase inhibitors. Recent findings: A number of new antimicrobials with activity against MDROs have been recently approved for the treatment of respiratory tract infections, and other agents are under investigation. Recent developments, with a specific focus on the possible advantages of new drugs for the management of respiratory tract infections caused by MDROs in everyday clinical practice are discussed. Summary: Newly approved and investigational drugs for the treatment of respiratory tract infections are expected to offer many advantages for the management of patients with suspected or confirmed infections caused by MDROs. Most promising features among new compounds include the broad spectrum of activity against both MRSA and MDR Gram-negative bacteria, a limited risk of antimicrobial resistance, the availability of oral formulations, and a promising safety profil

New therapeutic options for skin and soft tissue infections

Purpose of reviewThe occurrence of methicillin-resistance in Staphylococcus aureus, that represents the most frequent cause of complicated skin and soft tissue infections (cSSTIs) worldwide, is a major concern and has been associated with increased length of stay, health care costs, and overall mortality. Although vancomycin is still considered the standard therapy in this setting, limitations of its use in clinical practice are represented by a progressive increase in methicillin-resistant S. aureus (MRSA) minimum inhibitory concentrations, drug-related toxicity, and the lack of an oral formulation. New therapeutic options for MRSA cSSTIs have recently become available, with promising implications for the management of cSSTIs in clinical practice.Recent findingsA number of new antimicrobials with activity against MRSA have been recently approved for the treatment of cSSTIs, and other agents are under investigation. We have reviewed the recent developments, with a specific focus on the possible advantages of new drugs for the management of cSSTIs into the everyday clinical practice.SummaryThe new approved drugs for the treatment of cSSTIs are expected to offer many advantages for the management of patients with suspected or confirmed MRSA cSSTIs. The most promising features of the new compounds include the availability of oral formulations, once-weekly intravenous regimens, and broad spectra of activity

Patient specific risk stratification for antimicrobial resistance and possible treatment strategies in gram-negative bacterial infections

Introduction: The isolation of multi-drug-resistant gram-negative (MDRGN) pathogens has progressively increased worldwide and has been associated with important delays in the prescription of an adequate antibiotic treatment, resulting in increased mortality rates. Patient\u2019s stratification for MDRGN infections to optimize the prescription of an adequate empiric antimicrobial regimen is crucial. Areas covered: This article covers MDRGN epidemiology, with a specific focus on risk factors for harbouring infections sustained by extended-spectrum-Beta-lactamase (ESBL), carbapenem resistant Enterobacteriacae (CRE), MDR Pseudomonas aeruginosa and MDR Acinetobacter baumanii. Moreover, we will propose an algorithm for the choice of empiric treatment when a MDRGN infection is suspected. Expert commentary: Although in clinical practice, a patient\u2019s stratification represents a challenge, whenever a MDRGN pathogen is suspected broad-spectrum, combination empiric treatment should be promptly started, looking for a balance between the prescription of an adequate empiric treatment and the risk of resistance selection