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Summary Vertebral osteomyelitis (VO), also known as spondylodiscitis, describes infections of the vertebrae and intervertebral discs. Discitis describes infection limited to the intervertebral discs; in clinical practice both discitis and VO can be regarded as different stages of a single entity. VO can be caused by bacteria, fungi and parasites The incidence of VO is increasing globally representing 3-5% of all osteomyelitis with an estimated incidence ranging from 4 to 24 per million per year. Increasing incidence has been attributed to a combination of improved diagnostics, increased healthcare associated infections, haemodialysis, indwelling catheters, intravenous drug use, spinal instrumentation, immunocompromised hosts and an ageing population [1] . If left untreated, VO can lead to irreversible spinal cord injury, deformity, neurologic deficits, septicaemia, and mortality (mortality rates ranges 4%–29%). VO is typically treated with antibiotics, but up to 40% to 50% of VO patients may eventually require surgical intervention [1] , [2] , [3] Despite advances in diagnostic modalities, medical and surgical care, there are still many controversial areas with regards to both diagnostic and therapeutic strategies in VO. In this review a number of ‘hot topics’ on VO were selected and reviewed by members of the Skin, Soft Tissue and Bone Infections Working Group of the International Society of Antimicrobial Chemotherapy (ISAC). This group includes international scientists, microbiology and infectious diseases clinicians and academics, whose aim is to advance the education and the science of infection management. This paper is an in-depth review of the current literature, providing a summary of the various aspects of VO and expert opinions and insights from the authors’ own experience, highlighting areas for future study and research.

Introduction Tedizolid phosphate is an oxazolidinone approved for the treatment of acute bacterial skin and skin-structure infections (ABSSSIs) and active against methicillin-resistant Staphylococcus aureus. Aims The objective of this article was to review the evidence for the efficacy and safety of tedizolid phosphate for the treatment of ABSSSI. Evidence review Approval of tedizolid phosphate for the treatment of ABSSSI was based on the results of two phase III randomized controlled trials, ESTABLISH-1 (NCT01170221) and ESTABLISH-2 (NCT01421511), comparing 6-day once-daily tedizolid vs 10-day twice-daily linezolid. In ESTABLISH-1, noninferiority was met with early clinical response rates of 79.5% and 79.4% in tedizolid and linezolid groups, respectively (difference 0.1%, 95% CI –6.1% to 6.2%, with a 10% noninferiority margin). In ESTABLISH-2, noninferiority was met with 85% and 83% rates of early clinical response in tedizolid and linezolid groups, respectively (difference 2.6%, 95% CI –3.0% to 8.2%). Pooled data from ESTABLISH-1 and ESTABLISH-2 indicated a lower frequency of thrombocytopenia in tedizolid-treated than in linezolid-treated patients. Conclusion Tedizolid offers the option of an intravenous to oral switch, allows once-daily administration, and presents lower risk of myelotoxicity when a 6-day course is used for the treatment of ABSSSI. Greater economic cost associated with this antibiotic could be offset by its shorter treatment duration and possibility of oral administration in routine clinical practice, although either sponsored or nonsponsored postmarketing observational experience remains essential for ultimately confirming the effectiveness and tolerability of tedizolid outside clinical trials.

Limited data on varicella zoster virus (VZV) vaccine responses are available in HIV-positive adults, especially among those with end-stage renal disease on dialysis or undergoing kidney transplantation (KT). Serological and T cell responses were analyzed using anti-VZV IgG titers, enzyme-linked immunosorbent assay and flow cytometric intracellular cytokine staining (ICS) in two HIV-positive kidney transplant candidates undergoing dialysis and receiving VZV immunization. The results were compared with two HIV-positive and two HIV-negative VZV-seropositive patients (two kidney transplant candidates and two kidney transplant recipients), and with one HIV-negative vaccinee. HIV-positive VZV-susceptible patients received two doses of VZV vaccine 12 weeks apart. No adverse events were reported. Serological data were indicative of immunological response in one patient and corresponded to T cell responses. The second patient showed only a transient increase in anti-VZV IgG titers, but reported positive CD4+ T cell responses that were maintained after KT. Positive T cell and serological responses were detected in both HIV-positive and HIV-negative controls. VZV vaccination appeared safe and effective in HIV-positive KT candidates. VZV-specific T cell immunity was detected among transplant candidates and after KT. The assessment of VZV-specific T cell immunity using flow cytometric ICS may be more reliable compared to serology in assessing responses to VZV vaccine in this group.

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.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.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.

Introduction: Influenza represents a major public health threat worldwide. Implementation of good personal health and hygiene habits, together with vaccination, is the most effective tools to reduce influenza burden both in community and in healthcare setting. However, achieving adequate vaccination rates is challenging, and vaccination does not always guarantee complete protection. Neuraminidase inhibitors represent an important measure to reduce the risk of influenza-related complications among high-risk patients developing influenza infection. Areas covered: Neuraminidase inhibitors have been proven to be safe and effective in reducing influenza severity, duration of symptoms, hospitalizations, and influenza-related-mortality. Here the authors review the available data on neuraminidase inhibitors, including the mechanism of action, pharmacokinetics, efficacy, safety and current indications for their use in clinical practice. Expert opinion: Although vaccination is the most effective tool to reduce influenza-associated morbidity and mortality, neuraminidase inhibitors represent an important option for the treatment of patients with influenza infection, particularly in high-risk categories. Moreover, antivirals play an important role in influenza prevention and prophylaxis in selected settings.

The progressive increase in antimicrobial resistance represents a major concern among critically ill patients, leading to prolonged length of hospital stay and increased mortality [1]. In this setting, prescription of adequate antibiotic treatment, which is of outstanding importance to reduce mortality rates and improve clinical outcomes, is frequently delayed, and the most commonly employed empiric antibiotic regimens are often inappropriate [2]. To confront the problem of antimicrobial resistance, many new antibiotics with activity against multidrug resistant (MDR) pathogens have recently been approved, and other agents are currently under investigation. Here we review the characteristics of the new therapeutic options for the treatment of serious infections caused by MDR pathogens, with a specific focus on the potential advantages of these drugs for the management of critically ill patients in everyday clinical practice.

Background Scarce data are available about immune cell frequencies in HIV-positive recipients of liver transplant. Alterations in immune subsets can lead to persistent immune activation and disease progression or reduced HIV-specific responses. In liver transplantation, impaired immune tolerance can lead to organ rejection. Methods HIV-positive subjects with undetectable HIVRNA and CD4 > 100/mm3 were included. Control groups were non-transplanted HIV-positive patients with similar immunovirological parameters and healthy subjects. B cells (memory, transitional, and mature subsets), T cells (effector TH1, nonclassic TH1, TH17, TH1/17; T regulatory naive and effector subsets and CD8+ T regulatory cells), and NK cells (CD56dim and CD56bright subsets) were analyzed by flow cytometry. Results A total of 56 patients, including 14 HIV-positive transplant recipients (HIV-LT), 14 HIV-positive controls, and 28 healthy controls were included. Median age of HIV-LT patients was 54.9 years with median time from transplant of 7.6 years. Eleven (79%) were HIV/HCV coinfected. Compared to nontransplanted patients, HIV-LT displayed significantly increased frequency of T CD8+ cells, lower percentage of T CD4+ cell, and lower number of nonclassic TH1, TH1/17 cells and naive T CD4+ regulatory cells (Tregs). Healthy controls showed increased numbers of B cell subsets and decreased percentage of T effector subpopulations compared to HIV-LT. Compared to HIV-positive patients, healthy controls had higher B cells, NK cells, CD4+ T cells, naive CD4+ Tregs but lower CD8+ T cells, effector Tregs, CD8+ Tregs, and all T effector cell subsets. Conclusions Immune cell subpopulations potentially associated with HIV progression and organ rejection were detected in HIV-positive transplant recipients. We confirmed altered frequencies of B, T, and NK cell populations in HIV-positive liver transplant recipients compared to healthy controls. The imbalance among immune cell subsets deserves further studies to identify markers of transplant outcome and potential therapeutic targets.

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. © 2019 The Author(s).

Objectives: Vertebral osteomyelitis (VO) is a compelling clinical entity for clinicians because of its insidious and indolent course, which makes diagnosis difficult. Methods: All patients with a suspected diagnosis of VO were analyzed over an 8-year period (January 2009 to January 2017). The UDIPROVE protocol (UDIne PROtocol on VErtebral osteomyelitis) was applied in all cases. The primary endpoint was the performance of the UDIPROVE protocol to obtain the causal bacteria of infection. Results: During the study period, 133 episodes of confirmed VO were observed. The etiology of infection was obtained in 73.6% of cases: 70.5% were gram-positive, 16.3% were gram-negative, and 13.2% were mycobacteria. 18F-Fluorodeoxyglucose positron emission tomography/computed tomography (FDG-PET/CT) showed that for tubercular VO, the median standard uptake value (SUV) was higher when compared with VO caused by other bacteria. Clinical cure at the end of therapy was reported in 85.7% of patients. Previous antimicrobial therapy and a delay of more than 5 days in performing biopsy were associated with an undiagnosed etiology of VO. Targeted antibacterial therapy and follow-up with FDG-PET/CT were associated with clinical cure at the end of therapy, while the involvement of more than two vertebrae and inadequate drainage were associated with failure. Conclusions: Rigorous application of the UDIPROVE protocol allowed the causative pathogens of VO to be obtained – at about twice the rate reported in the literature. The use of FDG-PET/CT for the follow-up of infection was more reliable when compared to magnetic resonance imaging (MRI). Keywords: Vertebral osteomyelitis, Vertebral biopsy, C-reactive protein, FDG-PET/CT, MRI

Introduction: In clinical practice, methicillin-resistant Staphylococcus aureus (MRSA) represents a major threat and has been associated with high rates of inadequate antibiotic treatment and significant increases in morbidity, mortality, and overall healthcare costs. The association between the prescription of an inappropriate or delayed antibiotic and impaired clinical outcomes has been widely described. Areas covered: To address the threat of MRSA, many new therapeutic options with a peculiar activity against MRSA have been recently developed and approved. New agents are characterized by specific issues in terms of spectrum of activity, pharmacokinetics, risk of drug-drug interactions, and toxicity, with potential advantages that should be considered in everyday clinical practice. Expert opinion: The most attractive characteristic of new drugs is represented by the broad spectrum of activity against multidrug-resistant pathogens; moreover, new compounds in most cases are characterized by favorable toxicity profiles compared with old drugs currently used in clinical practice. Some of the new antimicrobials will be also available as oral formulations, with the potential for oral switch, even in infections due to resistant pathogens. In particular conditions/populations (e.g. liver failure, renal disease, pregnancy, diabetic, children, and elderly), novel antibiotics with reduced toxicity could be an important option, including after hospital discharge.

Introduction: Methicillin-resistant Staphylococcus aureus (MRSA) infections represent a leading cause of infection-related morbidity and mortality worldwide. There has been a welcome increase in the number of agents available for the treatment of MRSA infection over the last decade and several clinical trials are currently investigating the role of new experimental strategies.Areas covered: The purpose of this manuscript is to review the efficacy and safety of recently approved anti-MRSA molecules as well as some newer agents currently under investigation with a specific focus on the potential role of these drugs in everyday clinical practice.Expert opinion: Many new drugs with an activity against MRSA have been recently approved or are in an advanced stage of development. All these compounds represent promising options to enhance our antibiotic armamentarium. However, data regarding the use of these new compounds in real-life terms are limited and their best placement in therapy and in terms of optimization of medical resources and balance of cost-effectiveness requires further investigation.

Pneumocystis jiroveci pneumonia in non-HIV patients is infrequent and characterized by atypical presentations and increased severity. Although hematogenous dissemination from the lungs can lead to extrapulmonary infections, isolation of oocysts from blood in human subjects has not been documented. We report a case of P. jiroveci pneumonia with persistent isolation of oocysts from blood and positivity of P. jiroveci polymerase chain reaction. The patient presented with bilateral diffuse pulmonary nodules and received prolonged treatment with trimethoprim/sulfamethoxazole.

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. New antimicrobials targeting MDR-KP have been developed during the last decades and are now at various stages of clinical research. Areas covered: The PubMed database was searched to review the most significant literature on the topic, with a special consideration for articles coming from endemic countries. Expert commentary: We reviewed the currently available treatment options, discussing the characteristics of new antibiotics with activity against MDR Gram-negative bacteria and the strategies for preventing the spread of MDR-KP. While we wait for real-world data from novel compounds, coordinated strategies and common efforts in infection control and stewardship programs remain the cornerstone for limiting, or potentially reversing, conditions that favor the spread of MDR-KP.

Infections due to multidrug-resistant (MDR) bacteria are burdened by high mortality rates. The development of new compounds to face the global threat of resistance is urgently needed. Combination regimens including "old" high-dose antimicrobials are currently limited by the risk of toxicity, resistance selection, and reduced efficacy. Following the Infectious Diseases Society of America call to develop 10 new antibacterials by 2020, new molecules are currently under development or have become available for use in clinical practice.We have reviewed safety characteristics and tolerability of old antimicrobials that are currently employed in combination regimens as well as new antimicrobials, including beta-lactams/beta-lactamase inhibitors, new cephalosporins, quinolones, and aminoglycosides.The availability of new compounds that show in vitro efficacy against MDR represents a unique opportunity to face the threat of resistance and to optimize the current use of antimicrobials, potentially reducing toxicity. Agents that are potentially active against MDR Gram-negatives are ceftozolane/tazobactam, new carbapenems and cephalosporins, the combination of avibactam with ceftazidime, and plazomicin. Further data from clinical trials and post-marketing studies for drugs targeting MDR pathogens are crucial to confirm their efficacy and safety.

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.

Background: Almost half of all cases of invasive aspergillosis (IA) occur in the intensive care unit (ICU), with mortality rates of 70–80% 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–drug 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–drug 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–drug interactions with voriconazole. Keywords: Aspergillosis, Non-neutropenic, Isavuconazole, QT prolongation, Drug interactions

Elda Righi,Alessia Carnelutti,Antonio Vena,Matteo Bassetti Infectious Diseases Division, Santa Maria della Misericordia University Hospital, Udine, Italy Abstract: 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 methicillin-resistant 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. Keywords: bacterial skin and skin structure infections, multidrug-resistant bacteria, methicillin-resistant Staphylococcus aureus, delafloxacin

Delayed antimicrobial prescriptions and inappropriate treatment can lead to poor outcomes in pneumonia. In nosocomial infections, especially in countries reporting high rates of antimicrobial resistance, the presence of multidrug-resistant gram-negative and gam-positive bacteria can limit options for adequate antimicrobial treatment. New antibiotics, belonging to known classes of antimicrobials or characterized by novel mechanisms of actions, have recently been approved or are under development. Advantages of the new compounds include enhanced spectrum of activity against resistant bacteria, high lung penetration, good tolerability, and possibility for intravenous to oral sequential therapy. This article reviews characteristics of newly approved and investigational compounds.

PURPOSE: The aim of the study was to describe the characteristics of cirrhotic patients with candidemia and intra-abdominal candidiasis (IAC) and to evaluate the risk factors associated with 30-day mortality. METHODS: A multicenter multinational retrospective study including all consecutive episodes of candidemia and IAC in adult patients with liver cirrhosis in 14 European hospitals during the period 2011-2013 was performed. RESULTS: A total of 241 episodes (169 candidemia, 72 IAC) were included. Most Candida infections were acquired in hospital (208, 86.3%), mainly in the intensive care unit (ICU) (121, 50.2%). At clinical presentation, fever was seen in 60.6% of episodes (146/241) and septic shock in 34.9% (84/241). C. albicans was the most common species (found in 131 episodes, 54.4%), followed by C. glabrata (35, 14.5%) and C. parapsilosis (34, 14.1%). Overall, the 30-day mortality was 35.3%. Multivariable analysis identified candidemia (OR 2.2, 95% CI 1.2-4.5) and septic shock (OR 3.2, 95% CI 1.7-6) as independent factors associated with 30-day mortality. Adequate antifungal treatment (OR 0.4, 95% CI 0.3-0.9) was associated with survival benefit. CONCLUSIONS: A shift towards increasing prevalence of C. glabrata and C. parapsilosis species in patients with liver disease was documented. Candidemia and IAC were associated with significant mortality in cirrhotic patients. Thirty-day mortality was associated with candidemia and severe clinical presentation, whereas adequate antifungal treatment improved the prognosis.

The net state of immunosuppression, the occurrence of infections, drug-drug interactions, and toxicity can compromise the outcome of liver transplant recipients with multiple comorbidities. We present a 67-year-old man who developed early posttransplant severe chronic obstructive pulmonary disease exacerbation, pulmonary aspergillosis, and cytomegalovirus reactivation. Drug-drug interactions between azoles and cyclosporine, along with renal and liver toxicity, required adjustments in dosage. Interferon-gamma production from antigen-stimulated T cells was recorded. Early diagnosis and treatment, along with therapeutic drug monitoring and recovery of T-cell immunity, were key factors for a positive outcome.

Lors d’une interview donnée lors du Directors Guild of America’s Digital Day à Los Angeles, le 17 mai 2003, l’écrivain William Gibson considéré comme l’un des pères du mouvement cyberpunk a déclaré « Toute technologie émergente échappe spontanément à tout contrôle et ses répercussions sont imprévisibles. » La fin du XXe siècle a été le théâtre d’une révolution qui a permis l’essor d’une nouvelle source d’énergie, le nucléaire, mais également de l’électronique et donc de l’informatique. Cette ...

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.

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.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.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.

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's 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's 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.

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.

Background Anti-MRSA antibiotic under- and overprescribing for ABSSSI is common. To address this, we previously developed an MRSA risk assessment tool using prior literature and patient data from a single health system in Detroit, Michigan, USA. The objective of this study was to validate this risk assessment tool internationally. Methods Multicenter, international, prospective cohort study. Inclusion: age ≥ 18 y; purulent ABSSSI from July 2016 to March 2018. Exclusion: no culture; osteoarticular infection; bite wounds; odontogenic infections. Patient MRSA risk scores were computed using the following criteria (point value): previous MRSA infection/colonization (2); previous hospitalization (1); previous antibiotics (1); chronic kidney disease (1); intravenous drug use (1); HIV/AIDS (1); diabetes with obesity (1). The likelihood ratio of each patient’s score was used to convert local surveillance MRSA percentage (prior probability) into an individual patient estimated MRSA probability (posterior probability). The predictive performance of local surveillance MRSA percentage, MRSA risk score, and estimated MRSA probability were quantified using the area under the Receiver Operating Characteristic curve (aROC) and compared using the Hanley and McNeil method. Results 203 patients from 7 international sites included. The most common infection types were wound (28.6%), abscess (25.1%), and cellulitis with an abscess (20.7%). MRSA was observed in 33% of patients and ranged from 10% in Beijing, CN to 58.8% in Mexico City, MX. MRSA was significantly more prevalent among patients with higher MRSA risk scores (Figure 1). The MRSA risk score aROC (95% CI) [0.748 (0.678–0.819)] was significantly greater than local surveillance MRSA percentage [0.646 (0.569–0.722)] (P = 0.016). The estimated MRSA probability aROC [0.781 (0.716–0.845)] was significantly greater than local surveillance MRSA percentage (P < 0.001) but not the MRSA risk score (P = 0.192). Conclusion The MRSA risk score and estimated MRSA probability were significantly more predictive of MRSA ABSSSI compared with local MRSA surveillance percentage. Further study, including potential impact of this MRSA risk assessment tool on prescribing patterns are required before widespread application. Disclosures K. Claeys, Nabriva: Scientific Advisor, Consulting fee Melinta: Scientific Advisor, Consulting fee. M. Dryden, Motif BioSciences: Board Member, Consulting fee. M. J. Rybak, Allergan: Consultant, Grant Investigator and Speaker’s Bureau, Research grant and Research support. Achaogen: Consultant, Grant Investigator and Speaker’s Bureau, Consulting fee, Research grant and Research support. Bayer: Consultant, Grant Investigator and Speaker’s Bureau, Consulting fee, Research grant and Research support. Melinta: Consultant, Grant Investigator and Speaker’s Bureau, Consulting fee, Research grant and Research support. Merck: Consultant, Grant Investigator and Speaker’s Bureau, Consulting fee, Research grant and Research support. Theravance: Consultant, Grant Investigator and Speaker’s Bureau, Consulting fee, Research grant and Research support. Sunovian: Consultant, Grant Investigator and Speaker’s Bureau, Consulting fee, Research grant and Research support. Zavante: Consultant, Grant Investigator and Speaker’s Bureau, Consulting fee, Research grant and Research support. NIAID: Consultant, Grant Investigator and Speaker’s Bureau, Consulting fee, Research grant and Research support.