Management of vertebral osteomyelitis over an eight-year period: The UDIPROVE (UDIne PROtocol on VErtebral osteomyelitis)

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 \u2013 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)

Population pharmacokinetics and pharmacodynamic target attainment of isavuconazole against aspergillus fumigatus and aspergillus flavus in adult patients with invasive fungal diseases: Should therapeutic drug monitoring for isavuconazole be considered as mandatory as for the other mold-active azoles?

Isavuconazole is a newer broad-spectrum triazole approved for the treatment of invasive fungal disease. The objective of this study was to conduct a population pharmacokinetic and pharma-codynamic analysis of isavuconazole in a retrospective cohort of hospitalized patients. A nonlinear mixed-effect approach with Monte Carlo simulations was conducted to assess the probability of target attainment (PTA) of an area under the concentration–time curve (AUC24 h )/minimum inhibitory concentration (MIC) ratio of 33.4 (defined as efficacy threshold against A. fumigatus and A. flavus) associated with a maintenance dose (MD) of 100, 200 and 300 mg daily after loading. The cumulative fraction of response (CFR) against the EUCAST MIC distributions of A. fumigatus and A. flavus was calculated as well. The proportion of trough concentrations (Ctrough ) exceeding a defined threshold of toxicity (>5.13 mg/L) was estimated. A total of 50 patients, with a median age of 61.5 years, pro-vided 199 plasma isavuconazole concentrations. Invasive pulmonary aspergillosis was the prevalent type of infection and accounted for 80% (40/50) of cases. No clinical covariates were retained by the model. With the standard MD of 200 mg daily, CFRs were always ≥90% during the first two months of treatment. The risk of Ctrough < 1.0 mg/L was around 1%, and that of Ctrough > 5.13 mg/L was 27.7 and 39.2% at 28 and 60 days, respectively, due to isavuconazole accumulation over time. Our findings suggest that TDM for isavuconazole should not be considered as mandatory as for the other mold-active azoles voriconazole and posaconazole

Risk Factors for Intra-Abdominal Candidiasis in Intensive Care Units: Results from EUCANDICU Study

Introduction: Intra-abdominal infections represent the second most frequently acquired infection in the intensive care unit (ICU), with mortality rates ranging from 20% to 50%. Candida spp. may be responsible for up to 10–30% of cases. This study assesses risk factors for development of intra-abdominal candidiasis (IAC) among patients admitted to ICU. Methods: We performed a case–control study in 26 European ICUs during the period January 2015–December 2016. Patients at least 18 years old who developed an episode of microbiologically documented IAC during their stay in the ICU (at least 48 h after admission) served as the case cohort. The control group consisted of adult patients who did not develop episodes of IAC during ICU admission. Matching was performed at a ratio of 1:1 according to time at risk (i.e. controls had to have at least the same length of ICU stay as their matched cases prior to IAC onset), ICU ward and period of study. Results: During the study period, 101 case patients with a diagnosis of IAC were included in the study. On univariate analysis, severe hepatic failure, prior receipt of antibiotics, prior receipt of parenteral nutrition, abdominal drain, prior bacterial infection, anastomotic leakage, recurrent gastrointestinal perforation, prior receipt of antifungal drugs and higher median number of abdominal surgical interventions were associated with IAC development. On multivariate analysis, recurrent gastrointestinal perforation (OR 13.90; 95% CI 2.65–72.82, p = 0.002), anastomotic leakage (OR 6.61; 95% CI 1.98–21.99, p = 0.002), abdominal drain (OR 6.58; 95% CI 1.73–25.06, p = 0.006), prior receipt of antifungal drugs (OR 4.26; 95% CI 1.04–17.46, p = 0.04) or antibiotics (OR 3.78; 95% CI 1.32–10.52, p = 0.01) were independently associated with IAC. Conclusions: Gastrointestinal perforation, anastomotic leakage, abdominal drain and prior receipt of antifungals or antibiotics may help to identify critically ill patients with higher probability of developing IAC. Prospective studies are needed to identify which patients will benefit from early antifungal treatment

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

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

New therapeutic options for skin and soft tissue infections

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

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

Introduction: The isolation of multi-drug-resistant gram-negative (MDRGN) pathogens has progressively increased worldwide and has been associated with important delays in the prescription of an adequate antibiotic treatment, resulting in increased mortality rates. Patient'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

Neuraminidase inhibitors as a strategy for influenza treatment: pros, cons and future perspectives

reserved3noIntroduction: 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.mixedBassetti M.; Castaldo N.; Carnelutti A.Bassetti, M.; Castaldo, N.; Carnelutti, A

Bloodstream infections in the intensive care unit

ABSTRACT: Bloodstream infections (BSIs) represent a common complication among critically ill patients and a leading cause of morbidity and mortality. The prompt initiation of an effective antibiotic therapy is necessary in order to reduce mortality and to improve clinical outcomes. However, the choice of the empiric antibiotic regimen is often challenging, due to the worldwide spread of multi-drug resistant (MDR) organisms with reduced susceptibility to the available broad-spectrum antimicrobials. New therapeutic strategies are 5 to improve the effectiveness of antibiotic treatment while minimizing the risk of resistance selection

Emerging drugs for treating methicillin-resistant Staphylococcus aureus

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