Efficacy and Safety of Meropenem-Vaborbactam Versus Best Available Therapy for the Treatment of Carbapenem-Resistant Enterobacteriaceae Infections in Patients Without Prior Antimicrobial Failure: A Post Hoc Analysis.

Introduction: Infections due to Klebsiella pneumoniae carbapenemase (KPC)-producing Enterobacteriaceae are associated with increased morbidity and high mortality. Meropenem-vaborbactam (MV) is a novel β-lactam/β-lactamase inhibitor combination active against KPC-producing Enterobacteriaceae. The aim of this post hoc analysis of the TANGO-II randomized controlled trial was to assess the efficacy of MV versus best available therapy (BAT) in the subgroup of patients without prior antimicrobial failure.

Valuing antibiotics: The role of the hospital clinician.

The global public health threat of antibiotic-resistant infections as well as the lack of new treatments in clinical development is a critical issue. Reasons for this include diminished commercial incentives for pharmaceutical companies to develop new antibiotics, which part-reflects a shift in antibiotic marketing paradigm from broad deployment to targeted therapy in relatively small patient populations. Such changes are encouraged by antimicrobial stewardship (AMS).

Diagnostic and therapeutic approach to infectious diseases in solid organ transplant recipients.

Purpose: Prognosis of solid organ transplant (SOT) recipients has improved, mainly because of better prevention of rejection by immunosuppressive therapies. However, SOT recipients are highly susceptible to conventional and opportunistic infections, which represent a major cause of morbidity, graft dysfunction and mortality.

Methods: Narrative review.

ESICM/ESCMID task force on practical management of invasive candidiasis in critically ill patients.

Introduction: The term invasive candidiasis (IC) refers to both bloodstream and deep-seated invasive infections, such as peritonitis, caused by Candida species. Several guidelines on the management of candidemia and invasive infection due to Candida species have recently been published, but none of them focuses specifically on critically ill patients admitted to intensive care units (ICUs).

Material And Methods: In the absence of available scientific evidence, the resulting recommendations are based solely on epidemiological and clinical evidence in conjunction with expert opinion.

Prosthetic joint infections: clinical management, diagnosis, and treatment.

Purpose Of Review: Prosthetic joint infections (PJIs) represent one of the most disastrous complications in prosthetic surgery, requiring long hospitalization, prolonged antimicrobial treatment and repeated surgical interventions. No gold standard test to formulate diagnosis exist. A combination of high index of suspicion, physical examination, microbiological and biohumoral investigations is required.

Rationalizing antimicrobial therapy in the ICU: a narrative review.

The massive consumption of antibiotics in the ICU is responsible for substantial ecological side effects that promote the dissemination of multidrug-resistant bacteria (MDRB) in this environment. Strikingly, up to half of ICU patients receiving empirical antibiotic therapy have no definitively confirmed infection, while de-escalation and shortened treatment duration are insufficiently considered in those with documented sepsis, highlighting the potential benefit of implementing antibiotic stewardship programs (ASP) and other quality improvement initiatives. The objective of this narrative review is to summarize the available evidence, emerging options, and unsolved controversies for the optimization of antibiotic therapy in the ICU.

Role of procalcitonin in bacteremic patients and its potential use in predicting infection etiology.

Bloodstream infections (BSI) and their evolution to sepsis or septic shock are one of the most important causes of morbidity and mortality; for this reason, arapid recognition and diagnosis of these infections are crucial to improve patients' outcome. Area covered: Procalcitonin (PCT) is considered an important biomarker for diagnosis of infection, routinely used to identify patients developing severe bacterial infections. In this scenario, management of BSI is complicated by the increasing rate of multidrug-resistantstrains, and an early recognition of severe infections is mandatory.

Ceftolozane/tazobactam for the treatment of serious Pseudomonas aeruginosa infections: a multicentre nationwide clinical experience.

This study describes the largest clinical experience using ceftolozane/tazobactam (C/T) for different Pseudomonas aeruginosa infections. A retrospective study was performed at 22 hospitals in Italy (June 2016-March 2018). All adult patients treated with ≥4 days of C/T were enrolled.

Rational approach in the management of Pseudomonas aeruginosa infections.

Purpose Of Review: This review details the management of Pseudomonas aeruginosa infections covering both current and future treatment options that are and may be available for the clinicians.

Recent Findings: Pseudomonas aeruginosa infections are a great concern in hospital-acquired infections with very limited therapeutic options. The increasing antibiotic resistance has led to a need for different treatment choices that range from the use of new antibiotics to new nonantibiotic alternative agents to kill or disarm the pathogen.

The ideal patient profile for new beta-lactam/beta-lactamase inhibitors.

Purpose Of Review: The worldwide spread of extended-spectrum beta-lactamase (ESBL)-producing bacteria, the overuse of carbapenems, the emergence of carbapenemase-producing organisms and the growing importance of multidrug-resistant and/or extended drug-resistant strains have totally changed prescribers' habits, leading to very few treatment options in many cases. Beta-lactam/beta-lactamase inhibitor (BLBLI) combinations should be considered as an alternative to carbapenems for treating ESBL-producing bacteria and Pseudomonas aeruginosa infections. The purpose of this study was to provide insight concerning the patients who would constitute ideal candidates to receive these new BLBLI combinations.

Effect and Safety of Meropenem-Vaborbactam versus Best-Available Therapy in Patients with Carbapenem-Resistant Enterobacteriaceae Infections: The TANGO II Randomized Clinical Trial.

Introduction: Treatment options for carbapenem-resistant Enterobacteriaceae (CRE) infections are limited and CRE infections remain associated with high clinical failure and mortality rates, particularly in vulnerable patient populations. A Phase 3, multinational, open-label, randomized controlled trial (TANGO II) was conducted from 2014 to 2017 to evaluate the efficacy/safety of meropenem-vaborbactam monotherapy versus best available therapy (BAT) for CRE.

Methods: A total of 77 patients with confirmed/suspected CRE infection (bacteremia, hospital-acquired/ventilator-associated bacterial pneumonia, complicated intra-abdominal infection, complicated urinary tract infection/acute pyelonephritis) were randomized, and 47 with confirmed CRE infection formed the primary analysis population (microbiologic-CRE-modified intent-to-treat, mCRE-MITT).

Multidrug-resistant Klebsiella pneumoniae: challenges for treatment, prevention and infection control.

Management of antimicrobial resistance in multi-drug-resistant-Klebsiella pneumoniae (MDR-KP) is a major challenge for clinicians. The optimal treatment option for MDR-KP infections is still not well established. Combination therapies including high-dose meropenem, colistin, fosfomycin, tigecycline, and aminoglycosides are widely used, with suboptimal results.

Fluconazole resistance is not a predictor of poor outcome in patients with cryptococcosis.

Background: Cryptococcus isolates with high MICs to fluconazole are increasingly reported, and a potential clinical impact has been advocated. However, there are different methods to evaluate fluconazole MICs and comparative analysis among such techniques and their comprehensive correlation with clinical outcome are not available.

Methods: Over a 13-year period (2000-2013), fluconazole MICs were determined for 62 cryptococcal isolates recovered from 22 patients with cryptococcosis using CLSI M27-A3, EUCAST, E test and Sensititre YeastOne, simultaneously.

Risk stratification and treatment of ICU-acquired pneumonia caused by multidrug- resistant/extensively drug-resistant/pandrug-resistant bacteria.

Purpose Of Review: Describe the risk factors and discuss the management of multidrug-resistant (MDR) bacteria responsible for pneumonia among critically ill patients, including methicillin-resistant Staphylococcus aureus, extended spectrum beta-lactamase-producing Enterobactericeae, carbapenem-resistant Enterobactericeae, multidrug resistant Pseudomonas aeruginosa, and Acinetobacter baumannii.

Recent Findings: Multiple factors have been associated with infections because of MDR bacteria, including prolonged hospital stay, presence of invasive devices, mechanical ventilation, colonization with resistant pathogens, and use of broad-spectrum antibiotics. Management of these infections includes the prompt use of appropriate antimicrobial therapy, implementation of antimicrobial stewardship protocols, and targeted active microbiology surveillance.

A prognostic score for the resolution of bacteremia by Gram-negative bacteria resistant to carbapenems.

The management of bacteremia by carbapenem-resistant Gram-negative bacteria (CRGNB) necessitates a surrogate marker for response to treatment. We developed a prognostic score of bacteremia resolution using a test and a validation cohort. In the test cohort, five protein biomarkers were measured in serial daily serum samples from 39 patients with ventilator-associated pneumonia (VAP) and CRGNB bacteremia.

Repeated antifungal use audits are essential for selecting the targets for intervention in antifungal stewardship.

A previous audit to assess the quality of antifungal use was performed in our hospital in 2011. After 5 years of antifungal stewardship program (AFS), we performed a follow-up audit in order to describe the long-term effect of such program. Using a predefined score, we evaluated the antifungal use in 100 consecutive adult inpatients receiving systemic antifungals.

How to manage infections.

Infections with have become a real concern in hospital-acquired infections, especially in critically ill and immunocompromised patients. The major problem leading to high mortality lies in the appearance of drug-resistant strains. Therefore, a vast number of approaches to develop novel anti-infectives is currently pursued.

T2MR contributes to the very early diagnosis of complicated candidaemia. A prospective study.

Objectives: Diagnosis of complicated candidaemia represents a challenge for clinicians since early clinical manifestations may be non-specific and difficult to identify, thus precluding an appropriate treatment.

Patients And Methods: This was a multicentre prospective study for predicting complicated episodes in patients with bloodstream infection caused by Candida species, while assessing the value of follow-up blood cultures (BCs) and the persistence of positive results for T2Candida MR (T2MR) and blood β-d-glucan (BDG) tests. Immediately after the first positive BC yielding Candida species, samples were obtained on days 0, +2, +4, +7 and +14, to simultaneously perform follow-up BC, T2MR and BDG.

T2Candida MR as a predictor of outcome in patients with suspected invasive candidiasis starting empirical antifungal treatment: a prospective pilot study.

Objectives: We assessed the potential role of T2Candida MR (T2MR) and serological biomarkers [β-d-glucan (BDG) or Candida albicans germ tube antibodies (CAGTA)], alone or in combination with standard cultures, for identifying patients with suspected invasive candidiasis (IC), who may benefit from maintaining antifungal therapy.

Methods: Prospective observational multicentre study including all adult patients receiving empirical antifungal therapy for suspected IC, from January to June 2017. CAGTA, BDG and T2MR were determined at baseline and at +2 and +4 days after enrolment.