Ceftobiprole quantification in human serum by HPLC-UV to implement routine TDM in clinical practice.

BACKGROUND AND AIMS: Ceftobiprole is a recent 5th generation parenteral cephalosporin with antibacterial activity against a large range Gram+ and Gram- bacteria. Therapeutic drug monitoring (TDM) is an essential tool for maintaining plasma concentrations of antibiotics above the MIC by the end of the dosing interval, thus preventing the resistant strain diffusion. TDM is already recommended for other cephalosporins, and it is a reasonable tool contributing to the safety and efficacy of these drugs. During the treatment of patients in real-life, a number of pharmacokinetic (PK) changes not normally seen in healthy volunteers can occur which can impair the pharmacokinetic/pharmacodynamic target attainment. We aimed to develop simple and rapid HPLC-UV method for determination of ceftobiprole in human serum to implement TDM in clinical practice and support PKs and pharmacokinetic/pharmacodynamic (PK/PD) studies. MATERIALS AND METHODS: Samples preparation of calibration standards, QC, and anonymous patients serum samples was performed by protein precipitation by adding 0.01 ml of sulphosalicylic acid at 30 % to 0.1 ml of each sample. Then samples were vortexed and the centrifuged at 12,000 rpm for 10 min at 4 °C. Fifty microlitres of clear supernatant were diluted 1:1 with mobile phase and transferred into HPLC autosampler held at 8 °C. Chromatographic separation was carried out in a gradient mode at 35 °C on an ultra-Biphenyl column using a Thermo Scientific chromatographic system with a Diode array. Data management was performed with Chromeleon 7.4 software. RESULTS: The HPLC-UV method proved to be linear over wide concentration ranges (0.5-50.0 mg/L) and was accurate and reproducible in the absence of matrix effects, allowing for robust, specific, and rapid quantification of ceftobiprole from a low amount of serum (0.1 mL). The mean steady state Ctrough and Cend values measured in the anonymous patients' samples were 6.26 ± 3.81 mg/L and 22.56 ± 15.69 mg/L, respectively. CONCLUSIONS: We report a broadened simple and fast HPLC with UV detection method for quantification of ceftobiprole in human serum to implement ceftobiprole TDM as clinical routine, and support future (PK/PD) studies in special patients' population.

Stenotrophomonas maltophilia Outbreak in an ICU: Investigation of Possible Routes of Transmission and Implementation of Infection Control Measures.

Stenotrophomonas maltophilia, a non-fermentative, ubiquitous, gram-negative aerobic bacterium, is associated with high mortality rates, particularly in immunocompromised or debilitated patients. The prevalence rate of ICU-acquired pneumonia episodes caused by this microorganism has been found to be 2%. S. maltophilia has been identified as one of the top 10 microorganisms responsible for such infections in EU/EEA countries. This study describes an outbreak of S. maltophilia in an intensive care unit of a hospital in northern Italy. This includes an epidemiological investigation of the cases, the environmental microbiological controls carried out, a comparison of the strains by multilocus sequence typing (MLST), and the measures taken to prevent and control the outbreak. Among the seven clinical isolates of S. maltophilia analyzed herein, six demonstrated susceptibilities to trimethoprim-sulfamethoxazole. Conversely, one isolate of S. maltophilia exhibited resistance to first-line antibiotics. ST was found to be identical for six patients (ST 4), as well as in the environmental feedback on the trolley of Box 2. The analysis of the temporal and spatial progression of the outbreak has suggested that the transmission of S. maltophilia may have occurred through cross-transmission during care practices.

Preventive Vitamin D Supplementation and Risk for COVID-19 Infection: A Systematic Review and Meta-Analysis.

Over the past few decades, vitamin D has been found to play a crucial role in bone homeostasis, muscle function, oncogenesis, immune response and metabolism. In the context of the COVID-19 pandemic, numerous researchers have tried to determine the role vitamin D might play in the immune response to the virus. The aim of this systematic review and meta-analysis is to demonstrate that preventive vitamin D supplementation can play a protective role in the incidence of COVID-19, mortality and admission to intensive care units (ICUs). A comprehensive search on the PubMed/MEDLINE, Scopus, Cochrane and Google Scholar databases was performed on 15 May 2023, and two of the authors independently screened the literature. As effect measures, we calculated the Odds Ratios with their corresponding 95% confidence intervals (ICs). The assessment of potential bias and the evaluation of study quality will be conducted independently by two researchers. Sixteen publications were selected for inclusion in the meta-analysis. Our findings indicate that vitamin D supplementation has a protective effect against the incidence of COVID-19 in RCT studies (OR 0.403, 95% IC 0.218, 0.747), in the incidence of COVID-19 in analytical studies (OR = 0.592, 95% IC 0.476-0.736) and in ICU admission (OR 0.317, 95% IC 0.147-0.680). Subsequent analyses were conducted by type of subject treated (patient/healthcare workers) and type of supplementation (vitamin D vs. placebo/no treatment or high dose vs. low dose). Our meta-analysis suggests a definitive and significant association between the protective role of vitamin D and COVID-19 incidence and ICU admission.

Innovative Approaches to Monitor Central Line Associated Bloodstream Infections (CLABSIs) Bundle Efficacy in Intensive Care Unit (ICU): Role of Device Standardized Infection Rate (dSIR) and Standardized Utilization Ratio (SUR)-An Italian Experience.

In several settings, the COVID-19 pandemic determined a negative impact on the occurrence of healthcare-associated infection, particularly for on central lines associated bloodstream infections (CLABSI). In our setting, we observed a significant increase in CLABSI in our intensive care unit (ICU) during 2020 and 2021 vs. 2018 to 2019. A refresher training activity on central venous catheter (CVC) management bundles was carried out in September-October 2021 for the ICU health staff. We assessed the impact of bundle implementation by means of standardized indicators, such as the Device Utilization Ratio (DUR), in this case, the Central Line Utilization Ratio, the Standardized Utilization Ratio (SUR), and the device Standardized Infection Ratio (dSIR). Standardized ratios for device use and infection ratio were computed using data from 2018 and 2019 as expectation data. After bundle implementation, we observed a significant reduction of dSIR (p < 0.001), which dropped from 3.23 and 2.99 in the 2020-2021 biennium to 1.11 in 2022 (CLABSI in the first quarter only); no more CLABSI were observed afterwards. Standardized ratios proved helpful in identify increasing trends of CLABSI in the ICU and monitoring the impact of a simple effective tool, i.e., training on and implementation of a bundle for CVC management.

Mortality in KPC-producing Klebsiella pneumoniae bloodstream infections: a changing landscape.

OBJECTIVES: To assess the impact of carbapenem resistance on mortality in Klebsiella pneumoniae bloodstream infection (BSI) in the era of novel ß-lactam/ß-lactamase inhibitor combinations. MATERIAL AND METHODS: Retrospective study of patients with K. pneumoniae BSI between January and August 2020 in 16 centres (CARBANEW study within the MULTI-SITA project). RESULTS: Overall, 426 patients were included: 107/426 (25%) had carbapenem-resistant K. pneumoniae (CR-Kp) BSI and 319/426 (75%) had carbapenem-susceptible K. pneumoniae (CS-Kp) BSI. Crude cumulative 30 day mortality was 33.8% and 20.7% in patients with, respectively, CR-Kp BSI and CS-Kp BSI (P = 0.027). Carbapenemase production or carbapenemase-encoding genes were detected in 84/98 tested CR-Kp isolates (85.7%), mainly KPC (78/84; 92.9%). Ceftazidime/avibactam was the most frequently used appropriate therapy for CR-Kp BSI (80/107; 74.7%). In multivariable analyses, variables showing an unfavourable association with mortality after correction for multiple testing were age-adjusted Charlson comorbidity index (HR 1.20; 95% CI 1.10-1.31, P < 0.001) and Pitt score (HR 1.33; 95% CI 1.15-1.55, P < 0.001), but not carbapenem resistance (HR 1.28, 95% CI 0.74-2.22, P = 0.410). In a propensity score-matched analysis, there was no difference in mortality between patients appropriately treated with ceftazidime/avibactam for CR-Kp BSI and patients appropriately treated with other agents (mainly meropenem monotherapy or piperacillin/tazobactam monotherapy) for CS-Kp BSI (HR 1.07; 95% CI 0.50-2.29, P = 0.866). CONCLUSIONS: Our results suggest that the increased mortality in CR-Kp BSI compared with CS-Kp BSI is not (or no longer) dependent on the type of therapy in areas where ceftazidime/avibactam-susceptible KPC-producing isolates are the most prevalent type of CR-Kp.

Reversibility of Central Nervous System Adverse Events in Course of Art.

The purpose of this study is to evaluate the frequency of central nervous system adverse events (CNS-AE) on dolutegravir (DTG) and non-DTG containing ART, and their reversibility, in the observational prospective SCOLTA cohort. Factors associated with CNS-AE were estimated using a Cox proportional-hazards model. 4939 people living with HIV (PLWH) were enrolled in DTG (n = 1179) and non-DTG (n = 3760) cohorts. Sixty-six SNC-AE leading to ART discontinuation were reported, 39/1179 (3.3%) in DTG and 27/3760 (0.7%) in non-DTG cohort. PLWH naïve to ART, with higher CD4 + T count and with psychiatric disorders were more likely to develop a CNS-AE. The risk was lower in non-DTG than DTG-cohort (aHR 0.33, 95% CI 0.19−0.55, p < 0.0001). One-year follow-up was available for 63/66 PLWH with CNS-AE. AE resolution was reported in 35/39 and 23/24 cases in DTG and non-DTG cohorts, respectively. The probability of AE reversibility was not different based on ART class, sex, ethnicity, CDC stage, or baseline psychiatric disorder. At the same time, a lower rate of event resolution was found in PLWH older than 50 years (p = 0.017). In conclusion, CNS-AE leading to ART discontinuation was more frequent in DTG than non-DTG treated PLWH. Most CNS-AE resolved after ART switch, similarly in both DTG and non-DTG cohorts.

Factors Associated with Inadequate Intravenous Colistin Dosages: Post Hoc Analysis of a Multicenter, Cross-Sectional Study.

Colistin is a last-resort agent for the treatment of infections due to Gram-negative bacteria with difficult-to-treat resistance. The primary objective of this post hoc analysis of a cross-sectional study conducted in 22 Italian hospitals was to assess factors associated with inadequate intravenous colistin dosage. Overall, 187 patients receiving intravenous colistin were included in the analyses. Inadequate colistin dosages were administered in 27% of cases (50/187). In multivariable analysis, AKI (dummy variable with KDIGO stage 0 as a reference, odds ratio (OR) 3.98 with 95% confidence interval (CI) 1.48-10.74 for stage 1, OR 4.44 with 95% CI 1.17-16.93 for stage 2, OR 9.41 with 95% CI 1.59-55.70 for stage 3; overall p = 0.001) retained an independent association with inadequate colistin dosage, whereas the presence of a central venous catheter was associated with adequate colistin dosage (OR: 0.34 for inadequate dosage, 95% CI: 0.16-0.72, p = 0.004). These results were confirmed in an additional multivariable model with the center as a random effect. The association between AKI and inadequate dosage may reflect the perception of an increased risk of nephrotoxicity in patients with impaired renal function, which nonetheless should not be accompanied by dosage reductions beyond those recommended and could represent the target of dedicated antimicrobial stewardship efforts.

Riding the COVID Waves: Clinical Trends, Outcomes, and Remaining Pitfalls of the SARS-CoV-2 Pandemic: An Analysis of Two High-Incidence Periods at a Hospital in Northern Italy.

BACKGROUND: Italy was the first western country to face an uncontrolled outbreak of SARS-CoV-2 infection. The epidemic began in March 2020 within a context characterised by a general lack of knowledge about the disease. The first scientific evidence emerged months later, leading to treatment changes. The aim of our study was to evaluate the effects of these changes. METHODS: Data from a hospital in Genoa, Italy, were analysed. Patients deceased from SARS-CoV-2 infection were selected. Data were compared by dividing patients into two cohorts: "phase A" (March-May 2020) and "phase B" (October-December 2020). RESULTS: A total of 5142 patients were admitted. There were 274 SARS-CoV-2-related deaths (162 phase A and 112 phase B). No differences were observed in terms of demographics, presentation, or comorbidities. A significant increase was recorded in corticosteroid use. Mortality was 33.36% during phase A, falling to 21.71% during phase B. When subdividing the trend during the two phases by age, we found a difference in people aged 65-74 years. CONCLUSIONS: There is scarce evidence regarding treatment for SARS-CoV-2 (especially for severe infection). However, treatment changes improved the prognosis for people under the age of 75. The prognosis for older people remains poor, despite the improvements achieved.

Early Detection of Sepsis With Machine Learning Techniques: A Brief Clinical Perspective.

Sepsis is a major cause of death worldwide. Over the past years, prediction of clinically relevant events through machine learning models has gained particular attention. In the present perspective, we provide a brief, clinician-oriented vision on the following relevant aspects concerning the use of machine learning predictive models for the early detection of sepsis in the daily practice: (i) the controversy of sepsis definition and its influence on the development of prediction models; (ii) the choice and availability of input features; (iii) the measure of the model performance, the output, and their usefulness in the clinical practice. The increasing involvement of artificial intelligence and machine learning in health care cannot be disregarded, despite important pitfalls that should be always carefully taken into consideration. In the long run, a rigorous multidisciplinary approach to enrich our understanding in the application of machine learning techniques for the early recognition of sepsis may show potential to augment medical decision-making when facing this heterogeneous and complex syndrome.

Trends in the Incidence and Antibiotic Resistance of Enterococcal Bloodstream Isolates: A 7-Year Retrospective Multicenter Epidemiological Study in Italy.

The spread of resistance to vancomycin and other last-resort drugs in Enterococcus spp. remains of concern. In Italy, surveillance data for enterococcal bloodstream isolates in humans are scant. The aim of our study was to assess the incidence trends of bacteremias due to Enterococcus species and their prevalence trends of antimicrobial resistance. We retrospectively included all consecutive not-duplicate Enterococcus species isolated from blood cultures, in patients from 11 Italian hospitals (2011-2017). Incidence was defined as the number of isolates per 10,000 patient-days, while resistance prevalence was defined as the number of resistant strains divided by the number of tested strains. We included 4,858 isolates (59%, 36%, and 5% due to Enterococcus faecalis, E. faecium, and other Enterococcus spp., respectively). Over the study period, the incidence of bacteremias due to E. faecalis (incidence rate ratio [IRR]: 1.02, 95% confidence interval [CI]: 1.00-1.04, p = 0.008) and E. faecium increased (IRR: 1.03, 95% CI: 1.01-1.05, p < 0.001) alongside with the whole enterococcal bacteremias trend (IRR: 1.02, 95% CIs: 1.01-1.04, p = 0.002). A progressive increase in vancomycin-resistant E. faecium (VREfm) bacteremias was observed. Resistance to tigecycline and linezolid was rarely reported. The incidence of enterococcal bloodstream isolates is increasing in Italy, together with the prevalence of VREfm. Resistance to linezolid, a cornerstone drug used in the treatment of VRE bloodstream infection, remains negligible.

Culture-negative infective endocarditis (CNIE): impact on postoperative mortality.

INTRODUCTION: Poor postoperative outcomes have been reported after surgery for infective endocarditis (IE). Whether the absence of positive cultures impacts the prognosis remains a matter of discussion. The aim of this study was to evaluate the impact of negative cultures on the prognosis of surgically treated IE. METHODS: This was a single-center, retrospective study. From January 2000 to June 2019, all patients who underwent valvular surgery for IE were included in the study. The primary endpoint was early postoperative mortality. A covariate balancing propensity score was developed to minimize the differences between the culture-positive IE (CPIE) and culture-negative IE (CNIE) cohorts. Using the estimated propensity scores as weights, an inverse probability treatment weighting (IPTW) model was built to generate a weighted cohort. Then, to adjust for confounding related to CPIE and CNIE, a doubly robust method that combines regression model with IPTW by propensity score was adopted to estimate the causal effect of the exposure on the outcome. RESULTS: During the study period, 327 consecutive patients underwent valvular repair/replacement with the use of cardiopulmonary bypass and cardioplegic cardiac arrest for IE. Their mean age was 61.4 ± 15.4 years, and 246 were males (75.2%). Native valve IE and prosthetic valve IE accounted for 87.5% and 12.5% of cases, respectively. Aortic (182/327, 55.7%) and mitral valves (166/327, 50.8%) were mostly involved; 20.5% of isolated mitral valve diseases were repaired (22/107 patients). The tricuspid valve was involved in 10 patients (3.3%), and the pulmonary valve in 1 patient (<1%). Fifty-nine patients had multiple-valve disease (18.0%). Blood cultures were negative in 136/327 (41.6 %). A higher postoperative mortality was registered in CNIE than in CPIE patients (19% vs 9%, respectively, p = 0.01). The doubly robust analysis after IPTW by propensity score showed CNIE to be associated with early postoperative mortality (odds ratio 2.10; 95% CI, 1.04-4.26, p = 0.04). CONCLUSIONS: In our cohort, CNIE was associated with a higher early postoperative mortality in surgically treated IE patients after dedicated adjustment for confounding. In this perspective, any effort to improve preoperative microbiological diagnosis, thus allowing targeted therapeutic initiatives, might lead to overall better postoperative outcomes in surgically treated IE.

Clinical Features and Mortality of Nosocomial Candidemia in Very Old Patients: A Multicentre Italian Study.

INTRODUCTION: Being elderly is a well-known risk factor for candidemia, but few data are available on the prognostic impact of candidemia in the very old (VO) subjects, as defined as people aged ≥75 years. OBJECTIVE: The aim of this study was to assess risk factors for nosocomial candidemia in two groups of candidemia patients, consisting of VO patients (≥75 years) and adult and old (AO) patients (18-74 years). In addition, risk factors for death (30-day mortality) were analysed separately in the two groups. METHODS: We included all consecutive candidemia episodes from January 2011 to December 2013 occurring in six referral hospitals in north-eastern Italy. RESULTS: A total of 683 nosocomial candidemia episodes occurred. Of those, 293 (42.9%) episodes were in VO and 390 (57.1%) in AO patients. Hospitalization in medical wards, chronic renal failure, urinary catheter, and peripheral parenteral nutrition (PPN) were more common in VO than in AO patients. In the former patient group, adequate antifungal therapy (73.2%) and central venous catheter (CVC) removal (67.6%) occurred less frequently than in AO patients (82.5 and 80%, p < 0.002 and p < 0.004, respectively). Thirty-day mortality was higher in VO compared to AO patients (47.8 vs. 23.6%, p < 0.0001). In AO patients, independent risk factors for death were age (OR 1.04, 95% CI 1.00-1.09, p = 0.038), recent history of chemotherapy (OR 22.01, 95% CI 3.12-155.20, p = 0.002), and severity of sepsis (OR 40.68, 95% CI 7.42-223.10, p < 0.001); CVC removal was associated with higher probability of survival (OR 0.10, 95% CI 0.03-0.33, p < 0.001). In VO patients, independent risk factors for death were PPN (OR 3.5, 95% CI 1.17-10.47, p = 0.025) and hospitalization in medical wards (OR 2.58, 95% CI 1.02-6.53, p = 0.046), while CVC removal was associated with improved survival (OR 0.40, 95% CI 0.16-1.00, p = 0.050). CONCLUSION: Thirty-day mortality was high among VO patients and was associated with inadequate management of candidemia, especially in medical wards.

Risk Factors for Candidemia After Open Heart Surgery: Results From a Multicenter Case-Control Study.

BACKGROUND: Candida species are among the most frequent causative agents of health care-associated bloodstream infections, with mortality >40% in critically ill patients. Specific populations of critically ill patients may present peculiar risk factors related to their reason for intensive care unit admission. The primary objective of the present study was to assess the predictors of candidemia after open heart surgery. METHODS: This retrospective, matched case-control study was conducted in 8 Italian hospitals from 2009 to 2016. The primary study objective was to assess factors associated with the development of candidemia after open heart surgery. RESULTS: Overall, 222 patients (74 cases and 148 controls) were included in the study. Candidemia developed at a median time (interquartile range) of 23 (14-36) days after surgery. In multivariable analysis, independent predictors of candidemia were New York Heart Association class III or IV (odds ratio [OR], 23.81; 95% CI, 5.73-98.95; P < .001), previous therapy with carbapenems (OR, 8.87; 95% CI, 2.57-30.67; P = .001), and previous therapy with fluoroquinolones (OR, 5.73; 95% CI, 1.61-20.41; P = .007). Crude 30-day mortality of candidemia was 53% (39/74). Septic shock was independently associated with mortality in the multivariable model (OR, 5.64; 95% CI, 1.91-16.63; P = .002). No association between prolonged cardiopulmonary bypass time and candidemia was observed in this study. CONCLUSIONS: Previous broad-spectrum antibiotic therapy and high NYHA class were independent predictors of candidemia in cardiac surgery patients with prolonged postoperative intensive care unit stay.

Adequate duration of therapy in severe fungal infections.

PURPOSE OF REVIEW: To highlight recent findings on the adequate duration of antifungal therapy in patients with invasive fungal disease (IFD). RECENT FINDINGS: Plenty of published data available suggest that there is no additional clinical benefit at a certain point after initiation of antifungal treatment in patients with confirmed IFD. Moreover, the prolonged antifungal exposure can be associated with an increased risk of side effects and toxicity as well as striking risk for developing antifungal resistance or rising unnecessary healthcare costs. Recent data suggest that, in the presence of an adequate initial antifungal therapy and adequate source control of the infection, new stratified approaches integrating clinical judgment, biomarkers and microbiological eradication, should be considered as an alternative to the 'one-size-fits-all' treatment duration currently used worldwide. SUMMARY: The optimal duration of antifungal therapy is still an unresolved issue that depends by many key elements including the host; the pathogen and its microbiological eradication, the adequateness of initial antifungal therapy and the promptness of source control of the infection. In general, many patients with invasive candidiasis can be treated with a 2 weeks course of antifungal therapy. Longer antifungal course (6 weeks or more) is generally required for patients with invasive aspergilosis.

Migrants and imported disease: Trends of admission in an Italian infectious disease ward during the migration crisis of 2015-2017.

BACKGROUND: Since 2014, the migrant population residing in Europe has dramatically increased. Migrants' unmet health needs represent a barrier to integration and should be promptly addressed, without stigma, in order to favour resettlement. METHODS: All-cause of admissions in the migrant population at the Infectious Disease Clinic of Policlinico San Martino Hospital in Genoa between 2015 and 2017 were analysed. Patients were classified by duration of residence in Italy according to the Recommendation on Statistics of International Migration, cause of hospitalization, and region of origin. All data were evaluated with SPSS Statistics. RESULTS: Two hundred thirty-five people were admitted, 86 (36.5%) of them residing in Italy for less than 1 year. Except for a significant increase in migrants from Africa, there was no change considering the area of origin, hospitalization reason or by comparing residency in Italy for more or less than 1 year. A considerable number of hospitalizations were related to non-communicable pathologies and latent tuberculosis infection. Residents in Italy for less than 1 year or with active tuberculosis had prolonged hospitalizations, while HIV-infected had shorter hospital stays. CONCLUSIONS: No difference in terms of diagnosis were found between migrants with longer or shorter period of residence in Italy. Adequate outpatient services for the management of communicable diseases could significantly reduce the length of hospitalizations in the migrant population.

Innovative therapies for acute bacterial skin and skin-structure infections (ABSSSI) caused by methicillin-resistant Staphylococcus aureus: advances in phase I and II trials.

INTRODUCTION: Methicillin-resistant Staphylococcus aureus (MRSA) is among the most frequent causative agents of acute bacterial skin and skin-structure infections (ABSSSI) and has been associated with increased risks of invasive disease and of treatment failure. AREAS COVERED: In this review, we focus on those novel anti-MRSA agents currently in phase I or II of clinical development that may enrich the armamentarium against ABSSSI caused by MRSA in the future. EXPERT OPINION: Promising agents belonging to either old or novel antibiotic classes are currently in early phases of clinical development and may become available in the future for the effective treatment of ABSSSI caused by MRSA. In particular, the future availability of agents belonging to novel classes will be important for guaranteeing an effective treatment and for allowing outpatient treatment/early discharge, with a consequent reduced impact on healthcare resources. However, this does not mean that we can relax our efforts directed toward improving the responsible use of already available agents. Indeed, preserving their activity in the long term is crucial for optimizing the use of healthcare resources.

Role of new antibiotics in the treatment of acute bacterial skin and skin-structure infections.

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.

Clinical Experience with Ceftazidime-Avibactam for the Treatment of Infections due to Multidrug-Resistant Gram-Negative Bacteria Other than Carbapenem-Resistant Enterobacterales.

BACKGROUND: Experience in real clinical practice with ceftazidime-avibactam for the treatment of serious infections due to gram-negative bacteria (GNB) other than carbapenem-resistant Enterobacterales (CRE) is very limited. METHODS: We carried out a retrospective multicenter study of patients hospitalized in 13 Italian hospitals who received ≤72 h of ceftazidime-avibactam for GNB other than CRE to assess the rates of clinical success, resistance development, and occurrence of adverse events. RESULTS: Ceftazidime-avibactam was used to treat 41 patients with GNB infections other than CRE. Median age was 62 years and 68% of them were male. The main causative agents were P.aeruginosa (33/41; 80.5%) and extended spectrum beta lactamase (ESBL)-producing Enterobacterales (4/41, 9.8%). Four patients had polymicrobial infections. All strains were susceptible to ceftazidime-avibactam. The most common primary infection was nosocomial pneumonia (n = 20; 48.8%), primary bacteremia (n = 7; 17.1%), intra-abdominal infection (n = 4; 9.8%), and bone infection (n = 4; 9.8%). Ceftazidime-avibactam was mainly administered as a combination treatment (n = 33; 80.5%) and the median length of therapy was 13 days. Clinical success at the end of the follow-up period was 90.5%, and the only risk factor for treatment failure at multivariate analysis was receiving continuous renal replacement therapy during ceftazidime-avibactam. There was no association between clinical failures and type of primary infection, microbiological isolates, and monotherapy with ceftazidime-avibactam. Only one patient experienced recurrent infection 5 days after the end of treatment. Development of resistance to ceftazidime-avibactam was not detected in any case during the whole follow-up period. No adverse events related to ceftazidime-avibactam were observed in the study population. CONCLUSIONS: Ceftazidime-avibactam may be a valuable therapeutic option for serious infections due to GNB other than CRE.

Changing epidemiology of candidaemia: Increase in fluconazole-resistant Candida parapsilosis.

AIM: During the last decade a continuous increase in non-albicans species isolation has been observed with Candida parapsilosis being one of the leading species. Aim of this study was to describe the epidemiology of candidemia, particularly of C parapsilosis, its predictors and clinical outcome. MATERIALS AND METHODS: Incidences of candidemia was evaluated analyzing data from both a prospective collection (2012-2016) and a retrospective one (2008-2011). Predictors and outcome were based only on the prospective phase. C parapsilosis potential clusters were analysed by randomly amplified polymorphic DNA (RAPD) technique. RESULTS: 1240 episodes were identified. Incidences of candidemia increased from 1.97 episodes/10 000 patient-days in 2008 to 4.59/10 000 patient-days in 2016 (P < .001), mainly due to an increase of C parapsilosis (incidence rate ratio, IRR: 1.04, P < .001). 33.0% of C parapsilosis strains were resistant to fluconazole; no resistance to echinocandins was found. Independent predictors of C parapsilosis candidemia were time of infection (P = .007), previous use of echinocandins (P < .0001) and year in which the episode was registered (P < .0001). 30 days mortality was 32.4% for C parapsilosis, with a significant difference compared to C non-parapsilosis. Potential clonal C parapsilosis strains were detected by genetic analyses, showing RAPD profile A as the most represented (72.6% of isolates). DISCUSSION: C parapsilosis candidemia is an emerging issue in our center, possibly attributed to some extent to horizontal transmission of the pathogen, as confirmed by the analysis of isolates similarities. Further microbiological and epidemiological investigations are needed in order to identify the most effective measures to reduce the rate of this infection.