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Purpose of Review: Infections caused by multidrug-resistant Acinetobacter baumannii present a significant global health challenge. Available treatment options are limited and frequently constrained by unfavourable safety and pharmacokinetic profiles. Sulbactam-durlobactam is a novel β-lactamase inhibitors combination specifically developed to target A. baumannii, including carbapenem-resistant strains. The purpose of this review is to assess the current evidence supporting the role of sulbactam-durlobactam in the management of A. baumannii infections., Recent Findings: We summarize the available evidence regarding the pharmacokinetic and pharmacodynamic profiles of sulbactam-durlobactam from key in-vitro and in-vivo studies. Additionally, efficacy results from the Phase III randomized controlled trial and real-world data on sulbactam-durlobactam's use against severe A. baumannii infections are also discussed., Summary: Sulbactam-durlobactam is a promising addition to the treatment options for carbapenem-resistant A. baumannii infections. Ongoing research and vigilance are essential to monitor the development of in-vivo resistance, assess effectiveness across diverse patient populations, and explore potential synergistic combinations with other antimicrobials. Careful stewardship and comprehensive clinician education will be crucial to optimizing the clinical use of sulbactam-durlobactam., (Copyright © 2024 Wolters Kluwer Health, Inc. All rights reserved.)

Purpose of Review: To discuss novel antibiotics under clinical development, focusing on agents showing in-vitro activity against metallo-β-lactamases (MBL)-producing carbapenem-resistant Gram-negative bacteria (CR-GNB)., Recent Findings: Currently, only a few approved agents show activity, alone or in synergistic combinations, against MBL-producing CR-GNB. If approved by regulatory agencies in case of favorable results from ongoing (and, for some agents, already completed) phase-3 studies, some novel β-lactam/β-lactamase inhibitor (BL/BLI) combinations could become available in the next few years as additional important options for treating MBL-producing CR-GNB infections. Additional interesting agents that belong both to BL/BLI combinations and to antibiotic classes other than BL and BL/BLI combinations have also shown activity against MBL-producing CR-GNB, with most of them being in early phases of clinical development., Summary: Improving the use of these novel agents through virtuous antimicrobial stewardship frameworks able to guarantee both the efficacious treatment of infections requiring their use and the avoidance of their use whenever not necessary remains a challenge of utmost importance that should not be overlooked., (Copyright © 2024 The Author(s). Published by Wolters Kluwer Health, Inc.)

Purpose of Review: To review the rationale for and the potential clinical benefits of an early approach to viral acute respiratory infections with NSAIDs to switch off the inflammatory cascade before the inflammatory process becomes complicated., Recent Findings: It has been shown that in COVID-19 as in other viral respiratory infections proinflammatory cytokines are produced, which are responsible of respiratory and systemic symptoms. There have been concerns that NSAIDs could increase susceptibility to SARS-CoV-2 infection or aggravate COVID-19. However, recent articles reviewing experimental research, observational clinical studies, randomized clinical trials, and meta-analyses conclude that there is no basis to limit the use of NSAIDs, which may instead represent effective self-care measures to control symptoms., Summary: The inflammatory response plays a pivotal role in the early phase of acute respiratory tract infections (ARTIs); a correct diagnosis of the cause and a prompt therapeutic approach with NSAIDs may have the potential to control the pathophysiological mechanisms that can complicate the condition, while reducing symptoms to the benefit of the patient. A timely treatment with NSAIDs may limit the inappropriate use of other categories of drugs, such as antibiotics, which are useless when viral cause is confirmed and whose inappropriate use is responsible for the development of resistance., (Copyright © 2024 The Author(s). Published by Wolters Kluwer Health, Inc.)

Purpose of Review: To provide a brief overview of drugs in Phase II and III of development for the treatment of acute bacterial skin and skin structure infections (ABSSSI), offering insights into potential customized treatment options., Recent Findings: Several drugs are currently in advanced stages of evaluation for the treatment of ABSSSI, and numerous molecules are entering in the early development phases. Notably, many of these drugs exhibit unique mechanisms of action and interesting antimicrobial spectrum., Summary: Tailoring antibiotic therapy based on patient characteristics, likely pathogens, type, site and severity of ABSSSI is crucial. Given the inherent limitations of available treatments, the development of novel agents is a pivotal avenue. Such advancements hold promise for enhancing treatment efficacy and simplifying drug selection for ABSSSI in everyday clinical practice., (Copyright © 2024 Wolters Kluwer Health, Inc. All rights reserved.)

Purpose of Review: Serious infections caused by nonfermenting Gram-negative bacteria (NF-GNB) pose a significant challenge for clinicians due to the limited treatment options available, which are frequently associated with issues of toxicity and unfavourable pharmacokinetic profiles. The aim of this review is to provide a brief overview of the existing data concerning the ongoing development of antiinfective agents targeting NF-GNB., Recent Findings: Several agents exhibiting efficacy against NF-GNB are under clinical investigation. Durlobactam-sulbactam and cefepime-taniborbactam emerge as promising therapeutic avenues against carbapenem-resistant Acinetobacter baumanii . Cefepime-zidebactam may serve as a suitable treatment option for urinary tract infections caused by a wide range of NF-GNB. Cefepime-enmetazobactam demonstrates potent in vitro activity against various NF-GNB strains; however, its role as an anti- Pseudomonal agent is inadequately substantiated by available data. Xeruborbactam is a wide β-lactamase inhibitor that can be associated with a range of agents, enhancing in-vitro activity of these against many NF-GNB, including those resistant to newer, broader spectrum options. Lastly, murepavadin appears to be a potential pathogen-specific solution for severe Pseudomonas infections; however, additional investigation is necessary to establish the safety profile of this compound., Summary: Each of the novel molecules reviewed possesses an interesting range of in-vitro activity against NF-GNB. In addition, some of them have already been proved effective in vivo, underscoring their potential as future treatment options., (Copyright © 2023 Wolters Kluwer Health, Inc. All rights reserved.)

Purpose of Review: In the present narrative review, we discuss the characteristics and differences between the Infectious Diseases Society of America (IDSA) and European Society of Clinical Microbiology and Infectious Diseases (ESCMID) guidelines in terms on their recommendations/suggestions for the treatment of Pseudomonas aeruginosa and Acinetobacter baumannii infections., Recent Findings: Treatment of severe infections caused by nonfermenting gram-negative bacteria (NF-GNB) is posing both novel hopes and novel challenges to physicians worldwide, and both the IDSA and the ESCMID have recently updated/released their guidelines or guidance documents, based on different philosophies and providing recommendations for the treatment of NF-GNB infections. In order to correctly exploit recent advances in the treatment of such infections, IDSA and ESCMID approaches should be viewed as complementary and evolving, and should not preclude further revision based on accumulating evidence on the use of novel β-lactams and β-lactam/β-lactamase inhibitor combinations., Summary: A joint consideration of both philosophies should leave the door opened for the wise use of novel agents, ultimately building precious experience on their use that could favorably influence future guidelines revisions., (Copyright © 2023 Wolters Kluwer Health, Inc. All rights reserved.)

Purpose of Review: The aim of this article is to review skin and soft tissue infections due to rapidly growing mycobacteria (RGM), with a particular focus on recently published literature (2021-2022)., Recent Findings: RGM are increasingly reported as a cause of skin and soft tissue infections, both in the community setting and as a cause of nosocomial outbreaks. Recent advances in molecular methods have expanded the number of species of RGM and resulted in increased diagnosis. New treatment options are under evaluation particularly for Mycobacterium abscessus , the most difficult-to-treat among RGM., Summary: RGM are an uncommon cause of skin and soft tissue infections and a high clinical suspicion together with advanced laboratory facilities are required for diagnosis. Species identification and antimicrobial susceptibility testing are essential to drive appropriate treatment, which combines surgical debridement with prolonged antimycobacterial combination therapy., (Copyright © 2023 Wolters Kluwer Health, Inc. All rights reserved.)

Purpose of Review: Nosocomial infections caused by Acinetobacter baumannii currently represent a serious challenge for clinicians because treatment options are limited and frequently associated with significant toxicity. Cefiderocol is a first-in-class siderophore cephalosporin that has a proven efficacy for the treatment of multidrug-resistant Gram-negative infections, including carbapenem-resistant A. baumannii. The aim of this review is to evaluate the current evidence for the role of cefiderocol in the management of A. baumannii infections., Recent Findings: In this review, we briefly summarize the available data on the efficacy (from randomized controlled trials) and on effectiveness and cure rates (from observational studies), pertaining to the use of cefiderocol for treatment of serious A. baumannii infections., Summary: Cefiderocol represents a promising and safe antibiotic option for treating patients with carbapenem-resistant A. baumannii infections. Due to conflicting mortality data from available experience, well-designed future randomized controlled trials and real-life studies are needed., (Copyright © 2022 Wolters Kluwer Health, Inc. All rights reserved.)

Purpose of Review: To discuss empirical therapy for severe infections due to Gram-negative bacteria with difficult-to-treat resistance (GNB-DTR) in current clinical practice, focusing in particular on the positioning of novel therapeutic agents and rapid diagnostic tests., Recent Findings: The current era of novel agents active against GNB-DTR and showing differential activity against specific determinants of resistance is an unprecedented scenario, in which the clinical reasoning leading to the choice of the empirical therapy for treating severe GNB-DTR infections is becoming more complex, but it also allows for enhanced treatment precision., Summary: Novel agents should be used in line with antimicrobial stewardship principles, aimed at reducing selective pressure for antimicrobial resistance. However, this does not mean that they should not be used. Indeed, excesses in restrictive uses may be unethical by precluding access to the most effective and less toxic treatments for patients with severe GNB-DTR infections. Given these premises (the 'how'), empirical treatment with novel agents should be considered in all patients with risk factors for GNB-DTR and severe clinical presentation of acute infection (the 'when'). Furthermore, empirical novel agents should preferably be continued only for a few hours, until de-escalation, modification, or confirmation (as targeted therapy) is made possible by the results of rapid diagnostic tests (the 'how long')., (Copyright © 2022 Wolters Kluwer Health, Inc. All rights reserved.)

Purpose of Review: Acute bacterial skin and skin structure infections (ABSSSI) are a leading cause of morbidity, with a considerable variety of clinical presentation and a wide range of etiological pathogens. Of importance, the spread of multidrug-resistant (MDR) strains (i.e. methicillin-resistant Staphylococcus aureus or Gram-negative bacteria) is increasingly reported in some regions. in this review, we summarize the current clinical approach to patients with ABSSSI., Recent Findings: Accurate diagnosis and identification of risk factors for MDR pathogens are key determinants for administering appropriate therapy in patients with ABSSSI. In daily clinical practice, this can be critical as there are many features defining the 'high risk patient' including both disease and host-associated risk factors., Summary: Antibiotic therapy should be based according to the different clinical spectrum of disease belonging to the ABSSSI, on the pathogens most likely to be involved and local resistance. Careful evaluation of antibiotic therapy after 48-72 h of initial therapy could help clinicians to early identify patients with treatment failure and to consider an alternative approach. Close monitoring of patients with multiple comorbidities, drug-drug interaction or adverse host factors are also necessary., (Copyright © 2022 Wolters Kluwer Health, Inc. All rights reserved.)

Purpose of Review: Coronavirus disease 2019 (COVID-19) is a well established respiratory tract illness. Recent studies in adults and children have shown an increasing number of patients reporting polymorphic cutaneous manifestations during COVID-19, including different types of rashes, from maculopapular, vascular, vesicular to atypical forms., Recent Findings: Although pathogenesis of skin manifestations is still not fully understood, it has been proposed that cutaneous involvement during COVID-19 may be the results of the activation of the immune response against severe acute respiratory syndrome coronavirus-2, the reactivation or co-infection of herpesviruses or drug hypersensitivity., Summary: According to available literature, skin manifestations in patients with COVID-19 may be categorized on the basis of their clinical presentations as follows: erythematous rashes, lesions of vascular origin, vesicular rash, urticarial rash and acute generalized exanthematous pustulosis (AGEP), erythema multiforme and other polymorphic erythema/atypical reactions. Prompt recognition of these cutaneous manifestations represents a crucial point to facilitate diagnosis and management of COVID-19 patients., (Copyright © 2022 Wolters Kluwer Health, Inc. All rights reserved.)

Purpose of Review: Some patients with coronavirus disease 2019 (COVID-19) may develop pulmonary bacterial coinfection or superinfection, that could unfavorably impact their prognosis., Recent Findings: The exact burden of methicillin-resistant Staphylococcus aureus (MRSA) lung infection in peculiar populations such as patients with COVID-19 remains somewhat elusive, possibly because of wide heterogeneity in methods and endpoints across studies., Summary: There was important heterogeneity in the retrieved literature on the epidemiology of MRSA lung infection in patients with COVID-19, both when considering all other bacteria as the denominator (relative prevalence ranging from 2% to 29%) and when considering only S. aureus as the denominator (relative prevalence ranging from 11% to 65%). Overall, MRSA is among the most frequent causative agents of pulmonary infection in patients with COVID-19. Improving our ability to rapidly reach etiological diagnosis of bacterial lung infection in COVID-19 patients remains fundamental if we are to improve the rates of appropriate antibiotic therapy in patients with COVID-19 and concomitant/superimposed MRSA infection, at the same time avoiding antibiotic overuse in line with antimicrobial stewardship principles., (Copyright © 2022 Wolters Kluwer Health, Inc. All rights reserved.)

Purpose of Review: To discuss the current literature on novel agents for the treatment of carbapenem-resistant nonfermenting Gram-negative bacteria (NF-GNB) infections., Recent Findings: Some novel agents have recently become available that are expected to replace classical polymyxins as the first-line options for the treatment of carbapenem-resistant NF-GNB infections., Summary: In this narrative review, we provide a brief overview of the differential activity of various recently approved agents against NF-GNB most encountered in the daily clinical practice, as well as the results from phase-3 randomized clinical trials and large postapproval observational studies, with special focus on NF-GNB. Since resistance to novel agents has already been reported, the use of novel agents needs to be optimized, based on their differential activity (not only in terms of targeted bacteria, but also of resistance determinants), the local microbiological epidemiology, and the most updated pharmacokinetic/pharmacodynamic data. Large real-life experiences remain of crucial importance for further refining the optimal treatment of NF-GNB infections in the daily clinical practice., (Copyright © 2021 Wolters Kluwer Health, Inc. All rights reserved.)

Purpose of Review: Extended-spectrum β-lactamases (ESBL)- and ampicillinase class C (AmpC)-producing Enterobacterales represent one of the major public threats of the current era. As a consequence, during the last decades there have been great efforts to develop new therapeutic agents against these microorganisms. The aim of this review is to summarize the clinical features associated with novel antibiotics with activity against ESBL- and AmpC-producing isolates., Recent Findings: There a number of therapeutic agents with activity against ESBL and AmpC than have been introduced and approved over the past few years. Ceftazidime-avibactam and ceftolozane-tazobactam are both carbapenem sparing agents that appear interesting alternatives for treatment of serious Gram-negative infections. Other new β-lactams/ β-lactamase inhibitors (e.g. cefepime-enmetazobactam; ceftaroline fosamil-avibactam; aztreonam-avibactam and cefepime-zidebactam) as well as eravacycline, omadacycline, and plazomicin are also promising agents for treatment of ESBL- and AmpC- infections, but further clinical data are needed to establish their efficacy in comparison to carbapenems. The role of carbapenems/ β-lactamase inhibitors remains to be clarified., Summary: New therapeutic agents against ESBL- and AmpC-producing Enterobacterales have distinctive specificities and limitations that require further investigations. Future randomized clinical trials are required to define the best strategy for their use in patients with serious infections due to ESBL- and/or AmpC- infections., (Copyright © 2021 Wolters Kluwer Health, Inc. All rights reserved.)

Purpose of Review: To discuss the currently available evidence about the use oritavancin and dalbavancin for the treatment of acute bacterial skin and skin structure infections (ABSSSI) and for other potential indications., Recent Findings: In this review, we briefly summarize the available data on efficacy (from randomized controlled trials) and on effectiveness and cure rates (from observational studies) pertaining to the use of oritavancin and dalbavancin either for ABSSSI or for other indications., Summary: Oritavancin and dalbavancin are valid options for outpatient therapy and early discharge in patients with ABSSSI, especially when adherence to oral therapy cannot be guaranteed or no oral choices are available. Furthermore, it is worth noting that a non-negligible portion (sometimes the majority) of oritavancin and dalbavancin use in available real-life experiences is for indications other than ABSSSI, especially for Gram-positive osteomyelitis and endocarditis. The number of studies on the use of long-acting lipoglycopeptides for these currently off-label indications is rapidly increasing and will help to further optimize the use of these peculiar antibiotics in the forthcoming future., (Copyright © 2021 Wolters Kluwer Health, Inc. All rights reserved.)

Purpose of Review: To summarize the available results of primary analyses from high-quality randomized studies of either recently approved or possible future agents for the treatment of acute bacterial skin and skin structure infections (ABSSSI)., Recent Findings: In the last 2 decades, several novel agents have been approved for the treatment of ABSSSI, that are also active against methicillin-resistant Staphylococcus aureus (MRSA). In addition to already available agents, further molecules are in clinical development that could become available for treating ABSSSI in the forthcoming future., Summary: The current and future availability of several new-generation antibiotics will allow to modulate therapeutic choices not only on efficacy but also on other relevant factors such as the combination of the drug safety profile and the comorbidities of any given patient, the expected adherence to outpatient therapy, and the possibilities of early discharge or avoiding hospitalization by means of oral formulations, early switch from intravenous to oral therapy, or single-dose administration of long-acting intravenous agents. With the advent of new-generation antibiotics, all these factors are becoming increasingly essential for tailoring treatment to individual patients in line with the principles of personalized medicine, and for optimizing the use of healthcare resources., (Copyright © 2020 Wolters Kluwer Health, Inc. All rights reserved.)

Purpose of Review: The widespread diffusion of extended-spectrum β-lactamases (ESBLs)-producing Enterobacteriales currently represents a major threat for public health worldwide. Carbapenems are currently considered the first-line choice for serious ESBL infections. However, the dramatic global increase in ESBL prevalence has led to a significant overuse of carbapenems that has promoted the selection and spread of carbapenemases, which might further prejudicated our ability to treat infections due to multidrug-resistant pathogens. Therefore, strategies to limit the use of carbapenems should be implemented., Recent Findings: Although piperacillin-tazobactam should no longer be considered an alternative to carbapenems for definitive treatment of bloodstream infections due to ESBL-producing strains, it might still represent an alternative for step-down therapy or for low-to-moderate severity infection originating from urinary or biliary sources and when piperacillin-tazobactam minimum inhibitory concentration of 4 mg/l or less. Ceftazidime-avibactam and ceftolozane-tazobactam are both carbapenem sparing agents that appear interesting alternatives for treatment of serious ESBL infections. New β-lactams/β-lactamase inhibitors (BL/BLI), including cefepime-enmetazobactam, ceftaroline fosamil-avibactam, aztreonam-avibactam and cefepime-zidebactam, are also promising agents for treatment of ESBL infections, but further clinical data are needed to establish their efficacy relative to carbapenems. The role of carbapenems/β-lactamase inhibitors remain to be clarified., Summary: New BL/BLI have distinctive specificities and limitations that require further investigations. Future randomized clinical trials are required to define the best strategy for their administering for ESBL infections.

Purpose of Review: To discuss a possible clinical reasoning for treating resistant Gram-negative bacteria (GNB) infections in daily clinical practice, as well as developing a research agenda for the field., Recent Findings: Novel agents, both belonging to β-lactams and to other classes of antimicrobials, have recently become available, likely replacing polymyxins or polymyxin-based combination regimens as the preferred choices for the first-line treatment of severe resistant GNB infections in the near future., Summary: The peculiar characteristics of novel agents for severe resistant GNB infections have abruptly made the structure of previous therapeutic algorithms somewhat obsolete, in view of the differential activity of most of them against different classes of carbapenemases. Furthermore, other agents showing activity against resistant GNB are in late phase of clinical development. Optimizing the use of novel agents in order both to guarantee the best available treatment to patients and to delay the emergence and spread of resistance is an important task that cannot be postponed, especially considering the unavailability of well tolerated and fully efficacious options for treating resistant GNB infections that we faced in the last 15 years.

Purpose of Review: Previous studies suggest an association between depression and increased risk of various type of infections, including acute bacterial skin and skin structure infections (ABSSSI). Here, we review the latest advancement in our understanding of immunity in patients with depression and its relevance to disease management and diagnosis, with a special focus on patients suffering from ABSSSI., Recent Findings: Recent studies have highlighted the role of hypothalamic-pituitary-adrenal axis, neuro-endocrine stress signaling pathways and behavioral attitudes (substance abuse and homelessness) in the pathogenesis of infections in depressed patients. Furthermore, acute bacterial infections, in turn, have emerged as a possible risk for depression development because of different mechanisms including antibiotic-driven changes in the microbiota., Summary: Recent evidences have emphasized the threat that comanagement of depression and infection pose to infectious disease physician and psychiatrist. Depressed patients with ABSSSI must be closely monitored for drug side-effects, drug-drug interactions, toxicity, and adequate compliance. New management strategies including new long-acting antibiotics (e.g., dalbavancin) are welcome.

Purpose of Review: To summarize the available efficacy and safety data of novel agents for treating acute bacterial skin and skin-structure infections (ABSSSI), focusing on those active against methicillin-resistant Staphylococcus aureus (MRSA)., Recent Findings: There are now several agents active against MRSA that are approved for the treatment of ABSSSI, including tedizolid, ceftaroline, dalbavancin, telavancin, oritavancin, delafloxacin, and omadacycline. In addition, iclaprim has completed phase-3 randomized clinical trials (RCTs)., Summary: Considering the similar efficacy that arose from direct comparisons in phase-3 RCTs, in order to adopt the best approach for treating ABSSSI on patient-tailored basis, the different safety profiles and formulations of the different available agents should be balanced by taking into account the specific features of each treated patient in terms of baseline comorbidities, related risk of toxicity, need for hospitalization, possibility of early discharge, and expected adherence to outpatient oral therapy.

Purpose of Review: In recent years, traditional β-lactams have dramatically reduced their effectiveness against gram-negative bacteria mainly because of their ability to express multiple β-lactamase or carabapenemases that are not hydrolyzed by the old β-lactam inhibitors (BLIs) such as clavulanic acid, tazobactam, and sulbactam. New BLIs molecules have been developed to face the need of compounds that are active against multidrug or pandrug resistant gram-negative pathogens. The aim of this review is to summarize the new generation of BLIs and β-lactams combinations., Recent Findings: A number of new molecules with activity against Ambler class A (e.g., extended-spectrum β-lactamases, serine carbapenemases), class C (e.g., AmpC), or class D (e.g., oxacillinase-48) have been recently approved in combination with old β-lactams for the treatment of multidrug-resistant bacteria, and other agents are under investigation. These new compounds include diazabicyclooctanones non-β-lactam inhibitors (e.g., avibactam, relebactam, nacubactam) and boronic acid inhibitors (e.g., vaborbactam)., Summary: Newly approved and investigational new BLIs are expected to offer many advantages for the management of patients with multidrug-resistant gram-negative pathogens. Promising characteristics of new compounds include high activity against multi drug resistance gram-negative bacteria and a favorable safety profile.

Purpose of Review: In the last decade, an increasing interest in using fosfomycin for the treatment of multidrug-resistant gram-negative (MDR-GNB) infections have been registered, especially when none or only a few other active alternatives remained available., Recent Findings: Fosfomycin may remain active against a considerable proportion of MDR-GNB. In observational studies, a possible curative effect of oral fosfomycin monotherapy has been described for uncomplicated urinary tract infections (UTI) and bacterial prostatitis caused by MDR-GNB, whereas intravenous fosfomycin has been mostly used in combination with other agents for various type of severe MDR-GNB infections. The ZEUS randomized controlled trial (RCT) has started to provide high-level evidence about the possible use of fosfomycin for complicated UTI caused by extended-spectrum β-lactamase-producing GNB, but no results of large RCT are currently available to firmly guide the use of fosfomycin for carbapenem-resistant GNB., Summary: Fosfomycin is an important therapeutic option for MDR-GNB infections. Further pharmacokinetic/pharmacodynamic and clinical research is needed to optimize its use.

Purpose of Review: An increase of skin and soft tissue infections involving Staphylococcus aureus has been reported in community and hospital settings. Methicillin resistance in S. aureus is associated with treatment failure and increased mortality. Recently, new antimicrobials with enhanced activity against methicillin-resistant Staph. aureus have been approved for the treatment of skin and soft tissue infections. Among these, novel oxazolidinones and lipoglycopeptides represent options with favorable pharmacokinetic characteristics and safety profiles., Recent Findings: Newly approved compounds include tedizolid, characterized by the availability of both oral and intravenous formulation and once daily administration and dalbavancin, a long-acting antimicrobial allowing for weekly administration. These new molecules present advantages, such as enhanced activity against multidrug-resistant Gram-positive bacteria and favorable safety profiles., Summary: We have reviewed the pharmacokinetic characteristics and the implications for use in skin and soft tissue infections of tedizolid and dalbavancin. Advantages associated with the use of these compounds include the possibility for early patient discharge, reduced hospital length of stay, and outpatient treatment, with potential impact on morbidity, mortality, and overall health-care costs.

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. Therapeutical approach should be based on a multidisciplinary team. In our center, a two-stage approach is preferred. As regards the choice of the empirical antibiotic backbone, individual risk factors for multiple-drug resistant (MDR) pathogens should be considered. Several studies enhance the possibility to shorten the length of antibiotic couses., Recent Findings: Some interesting improvements have been made in the setting of PJIs management. As regards diagnosis, novel biomarkers and nuclear imaging are acquiring more importance. Molecular biology techniques also offer the possibility to formulate rapid microbiological identification. The pattern of PJIs is evolving towards higher rates of MDR causes. During the last decade, a number of new antibiotic molecules with activity against MDRs have been approved. Some of them are also available either in oral formulation or as long-acting compounds, offering the opportunity for early patient's discharge, with expected healthcare costs saving., Summary: Management of PJIs still represents a major threat for clinicians. Improvements in surgical techniques and antibiotic pipeline promise to revolutionize the approach in next years. Despite data from our experience confirm the efficacy of shorter antibiotic courses and the value of new molecules, randomized clinical trials are lacking. More data are needed in order to modify the routine clinical practice.

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., Recent Findings: Ceftolozane/tazobactam and ceftazidime/avibactam are the first drugs constituting the use of new beta-lactamase inhibitors. Ceftolozane/tazobactam is the drug of choice for treating MDR/XDR P. aeruginosa infections. Ceftazidime/avibactam is the best drug available for treating KPC and OXA-48 carbapenemase-producing Enterobacteriaceae. Ceftolozane/tazobactam and ceftazidime/avibactam are both carbapenem-sparing agents for treating ESBL-producing Enterobacteriaceae. The role of carbapenem/inhibitors remains to be clarified., Summary: Each BLBLI combination has distinctive specificities and limitations that need to be investigated cautiously. Randomized trials will play a key role in defining the best strategies. Infection control measures and prompt diagnosis remain fundamental to prevent dissemination of MDR pathogens in healthcare settings and to optimize early antimicrobial treatment.

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., Summary: New molecules such as ceftolozane-tazobactam, ceftazidime-avibactam, and imipenem-relebactam have shown an adequate activity against P. aeruginosa, especially against multidrug resistance strains. Other nonantibiotic alternative treatments, such as antibodies, bacteriocins or phage therapy, have shown promising results, but future clinical studies are needed.

Purpose of Review: The increase of skin and soft tissue infections (SSTIs) represents a major concern both in community and in the hospital setting. Staphylococcus aureus is the most frequently isolated pathogen, and the rise in infections due to methicillin-resistant Staphylococcus aureus (MRSA) has been associated with inadequate antibiotic treatment and increased morbidity., Recent Findings: A number of new antimicrobials with activity against drug-resistant Gram-positive pathogens, including MRSA, have been recently approved for the treatment of SSTIs. New lipoglycopeptides, in particular dalbavancin, are long-acting antibiotics with potential for infrequent administration, offering the possibility for outpatient treatment and early hospital discharge., Summary: Dalbavancin is a new lipoglycopeptide showing high activity against Gram-positive bacteria, including drug-resistant strains. Dalbavancin presents a distinctive pharmacokinetic profile with a terminal prolonged half-life of approximately 14 days. This characteristic allows once-weekly dosing interval, avoiding the need for daily dosing and offering an advantage over other compounds for potential use in the outpatient setting or to promote early hospital discharge. Dalbavancin has a favorable adverse effect profile and appears to be a promising new alternative for treatment of SSTIs. We have reviewed the pharmacokinetic properties of dalbavancin and the clinical evidence for its use in complicated SSTIs and other potential applications.

Purpose of Review: Ventilator-associated pneumonia (VAP) caused by multidrug-resistant (MDR) bacteria represents a global emerging problem. Delayed prescription of an adequate treatment for VAP has been associated with higher morbidity and mortality. New molecules have been developed to face the need of compounds that are active against resistant Gram-positive and Gram-negative pathogens. The aim of this review is to summarize the current scenario of new therapeutic options for the treatment of VAP., Recent Findings: A number of new antibiotics with activity against MDR have been recently approved for the treatment of VAP, and other agents are under investigation. In this review, the authors summarize the current therapeutic options for the treatment of VAP that showed promising implications for clinical practice, including new compounds belonging to old antibiotic classes (e.g., ceftolozane/tazobactam, ceftazidime/avibactam meropenem/vaborbactam, imipenem/relebactam, tedizolid, cefiderocol, eravacycline, and plazomicin) and novel chemical classes, such as murepavadin. Nebulized antibiotics that are currently in development for the treatment of pneumonia in mechanically ventilated patients are also presented., Summary: Newly approved and investigational drugs for the treatment of VAP are expected to offer many advantages for the management of patients with respiratory infections caused by MDR. Promising characteristics of new compounds include high activity against both methicillin-resistant Staphylococcus aureus and MDR Gram-negative bacteria and a favorable safety profile.

Purpose of Review: Skin and soft tissue infections prevalence is increasing and represent a frequent cause of hospital admission. New guidelines have become available in order to better define these infections and their response to antimicrobial treatment. Gram-positive bacteria, in particular Staphylococcus aureus, remain the most frequently isolated pathogens in skin and soft tissue infections. To treat complicated forms and infections caused by drug-resistant bacteria, hospital admission and administration of intravenous antibiotics are often required, impacting on healthcare costs and patients' morbidity., Recent Findings: New therapeutic options offer efficacy against drug-resistant Gram-positive bacteria as well as potential to favor early patients' discharge, including the possibility for intravenous to oral switch and infrequent drug administration because of prolonged drug half-life. Although data from real-world studies on new antimicrobials is awaited, clinicians need clear direction on how to optimize the treatment of skin and soft tissue infections in order to avoid prolonged hospitalizations and extra costs. Early assessment of patient's clinical conditions and response to treatment appear useful in order to facilitate patients' discharge., Summary: We have reported the evidence for early intravenous to oral switch and early hospital discharge for patients with skin and soft tissue infections. New therapeutic options that represent promising tools in promoting an optimized management of these infections have also been reviewed.

Purpose of Review: Methicillin-resistant Staphylococcus aureus (MRSA) has become a major public health issue worldwide over the last years. MRSA is frequently implicated in the development of skin and soft tissue infections, leading to significant increases in morbidity, mortality and overall healthcare costs., Recent Findings: In order to face the threat of MRSA, major changes in clinical management of skin and soft tissue infections are required. The identification of populations at risk for the acquisition of infections due to MRSA, together with the improvement of the diagnostic techniques, is paramount. Moreover, a number of new antimicrobials with activity against MRSA have been recently developed and approved for the treatment of skin and soft tissue infections, however, the use of the new drugs in the wide clinical practice remains limited., Summary: We reviewed the current epidemiology of MRSA in skin and soft tissue infections, with particular focus on implications for clinical management. The potential role of new antibiotic options against MRSA infections is also discussed.

Purpose of Review: 18F-Fluorodeoxyglucose positron emission tomography/computed tomography is a well-established technique for diagnosis and management of a number of neoplastic conditions. However, in recent years the body of literature regarding its potential role in infectious diseases has progressively increased, with promising results., Recent Findings: So far 18F-fluorodeoxyglucose positron emission tomography/computed tomography has a well-established role and is recommended by guidelines only in a few settings, such as prosthetic valve endocarditis, vascular device infections, and chronic osteomyelitis. However, even the lack of large, prospective randomized trials, an increasing number of small series and case reports suggest a potential role in the diagnosis, disease staging, and monitoring of treatment response of several other infective conditions., Summary: In this article, we summarize the available evidence and potential future applications of 18F-fluorodeoxyglucose positron emission tomography/computed tomography in the diagnosis and management of infectious diseases.

Purpose of Review: Multidrug-resistant (MDR) Enterobacteriaceae are often related to the production of extended-spectrum b-lactamases (ESBLs) and carbapenemase-producing Enterobacteriaceae (CRE), and represent an increasing global threat. Recommendations for the therapeutic management of MDR-related infections, however, are mainly derived from retrospective and nonrandomized prospective studies. The aim of this review is to discuss the challenges in the treatment of patients with infections because of MDR Enterobacteriaceae and provide an expert opinion while awaiting for more definitive data., Recent Findings: To avoid the selection of carbapenemase-producing Enterobacteriaceae, carbapenem-sparing strategies should be considered. B-lactams/b-lactamase inhibitors, mainly piperacillin-tazobactam, minimum inhibitory concentration (MIC) 16/4mg/ml or less represents the best alternative to carbapenems for the treatment of ESBL-producing strains. Overall, combination therapy may be preferred over monotherapy for CRE. The combination of a carbapenem-containing regimen with colistin or high-dose tigecycline or aminoglycoside can be administered at high-dose prolonged infusion with therapeutic drug monitoring for the treatment of CRE with MIC for meropenem 8-16 mg/l or less. For MIC higher than 8-16 mg/l, the use of meropenem should be avoided and various combination therapies based on the in-vitro susceptibility of antimicrobials (e.g., colistin, high-dose tigecycline, fosfomycin, and aminoglycosides) should be selected., Summary: Carbapenem-sparing strategies should be used, when feasible, for ESBL infections. The majority of available nonrandomized studies highlight that combination for CRE seem to offer some therapeutic advantage over monotherapy. Strict infection control measures toward MDR Gram-negative pathogens remain necessary while awaiting for new treatment options.

Purpose of Review: The 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 Findings: A 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., Summary: The 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.

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 β-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 β-lactams/β-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 profile.