Clinical effectiveness of cefiderocol for the treatment of bloodstream infections due to carbapenem-resistant Acinetobacter baumannii during the COVID-19 era: a single center, observational study.

BACKGROUND: We assessed the clinical effectiveness of cefiderocol (CFDC) in comparison with colistin (COL) for the treatment of carbapenem-resistant Acinetobacter baumannii (CRAB) bloodstream infections (BSI). MATERIALS/METHODS: Retrospective cohort study including adults with CRAB-BSI. Outcomes were mortality, clinical cure and adverse events during therapy. The average treatment effect of CFDC compared to COL was weighted with the inverse-probability treatment weight (IPTW). RESULTS: Overall, 104 patients were included (50 CFDC, 54 COL), median age 66.5 years, median Charlson Comorbidity Index 5, septic shock in 33.6% of patients. Primary BSI accounted for 43.3% of cases, followed by ventilator-associated pneumonia (VAP) (26%), catheter-related BSI (20.2%) and hospital-acquired pneumonia (HAP) (9.6%). Although not significantly, mortality at all time points was lower for CFDC than COL, while clinical cure was higher in CFDC than COL (66% vs. 44.4%, p = 0.027). Adverse events were more frequent in COL than CFDC-group (38.8% vs. 10%, p < 0.0001), primarily attributed to acute kidney injury (AKI) in the COL group. Patients with bacteremic HAP/VAP treated with CFDC had a significant lower 30-d mortality and higher clinical cure than COL (p = 0.008 and p = 0.0008, respectively). Increment of CCI (p = 0.005), ICU (p = 0.025), SARS-CoV2 (p = 0.006) and ECMO (p < 0.0001) were independently associated with 30-d mortality, while receiving CFDC was not associated with survival. CONCLUSIONS: CFDC could represent an effective and safe treatment option for CRAB BSI, especially in patients with bacteremic HAP/VAP and frail patients where the risk of acute renal failure during therapy should be avoided.

Ceftazidime/avibactam-resistant meropenem-susceptible KPC-producing Klebsiella pneumoniae: Analysis of cases and evaluation of in vitro activity of fosfomycin-containing combinations.

OBJECTIVES: Little is known regarding outcomes and optimal therapeutic regimens of infections caused by Klebsiella pneumoniae carbapenemase-producing Klebsiella pneumoniae (KPC-Kp) resistant to ceftazidime/avibactam (CZA) and susceptible to meropenem (MEM). Although susceptible to MEM in vitro, the possibility of developing MEM resistance overtime is a concern. We describe the clinical characteristics of patients with colonization/infection due to KPC variants with a focus on the in vitro activity of fosfomycin (FOS)-containing combinations. METHODS: Patients with colonization/infection due to a KPC variant were included. Fosfomycin susceptibility was performed by agar dilution method. Synergistic activity of FOS-based combinations was evaluated by gradient strip-agar diffusion method. The emergence of in vitro MEM resistance was also tested. RESULTS: Eleven patients were included: eight with infection [four with ventilator-associated pneumonia and four with bloodstream infections] and three with colonization. Previous therapy with CZA was administered to all patients (with a mean cumulative duration of 23 days). All subjects with infection received meropenem, in monotherapy (n = 4) or with amikacin (n = 2) or fosfomycin (n = 2), and achieved clinical cure. A new CZA-susceptible and MEM-resistant KPC-Kp strain was subsequently isolated in three patients (27.3%). Meropenem/vaborbactam (MVB) showed high in vitro activity, while FOS+MEM combination was synergistic in 40% of cases. In vitro resistance to MEM was observed with maintenance of CZA resistance. CONCLUSIONS: Detection of KPC variants may occur within the same patient, especially if CZA has been previously administered. Although clinical success has been obtained with carbapenems, the emergence of MEM resistance is a concern. Fosfomycin plus meropenem is synergistic and may be a valuable combination option for KPC variants, while MVB may be considered in monotherapy. The detection of KPC variants in an endemic setting for KPC-Kp represents a worryingly emerging condition. The optimal therapeutic approach is still unknown and the development of meropenem resistance is of concern, which may lead to therapeutic failure in clinical practice. In these cases, the addition of fosfomycin to meropenem, or a more potent antibiotic, such as meropenem/vaborbactam, may be valuable therapeutic options.

Effect of ceftazidime/avibactam plus fosfomycin combination on 30†day mortality in patients with bloodstream infections caused by KPC-producing Klebsiella pneumoniae: results from a multicentre retrospective study.

Introduction: The primary outcome of the study was to evaluate the effect on 30 day mortality of the combination ceftazidime/avibactam + fosfomycin in the treatment of bloodstream infections (BSIs) caused by KPC-producing Klebsiella pneumoniae (KPC-Kp). Materials and methods: From October 2018 to March 2021, a retrospective, two-centre study was performed on patients with KPC-Kp BSI hospitalized at Sapienza University (Rome) and ISMETT-IRCCS (Palermo) and treated with ceftazidime/avibactam-containing regimens. A matched cohort (1:1) analysis was performed. Cases were patients receiving ceftazidime/avibactam + fosfomycin and controls were patients receiving ceftazidime/avibactam alone or in combination with in vitro non-active drugs different from fosfomycin (ceftazidime/avibactam ±â€Šother). Patients were matched for age, Charlson comorbidity index, ward of isolation (ICU or non-ICU), source of infection and severity of BSI, expressed as INCREMENT carbapenemase-producing Enterobacteriaceae (CPE) score. Results: Overall, 221 patients were included in the study. Following the 1:1 match, 122 subjects were retrieved: 61 cases (ceftazidime/avibactam + fosfomycin) and 61 controls (ceftazidime/avibactam ±â€Šother). No difference in overall mortality emerged between cases and controls, whereas controls had more non-BSI KPC-Kp infections and a higher number of deaths attributable to secondary infections. Almost half of ceftazidime/avibactam + fosfomycin patients were prescribed fosfomycin without MIC fosfomycin availability. No difference in the outcome emerged after stratification for fosfomycin susceptibility availability and dosage. SARS-CoV-2 infection and ICS ≥ 8 independently predicted 30 day mortality, whereas an appropriate definitive therapy was protective. Conclusions: Our data show that fosfomycin was used in the treatment of KPC-Kp BSI independently from having its susceptibility testing available. Although no difference was found in 30 day overall mortality, ceftazidime/avibactam + fosfomycin was associated with a lower rate of subsequent KPC-Kp infections and secondary infections than other ceftazidime/avibactam-based regimens.

Clinical course of Coronavirus Disease-19 in patients with haematological malignancies is characterized by a longer time to respiratory deterioration compared to non-haematological ones: results from a case-control study.

BACKGROUND: We evaluated clinical features and risk factors for mortality in patients with haematological malignancies and COVID-19. METHODS: Retrospective, case-control (1:3) study in hospitalized patients with COVID-19. Cases were patients with haematological malignancies and COVID-19, controls had COVID-19 without haematological malignancies. Patients were matched for sex, age and time of hospitalization. RESULTS: Overall, 66 cases and 198 controls were included in the study. Cases had higher prior corticosteroid use, infection rates, thrombocytopenia and neutropenia and more likely received corticosteroids and antibiotics than controls. Cases had higher respiratory deterioration than controls (78.7% vs 65.5%, p = 0.04). Notably, 29% of cases developed respiratory worsening > 10 days after hospital admission, compared to only 5% in controls. Intensive Care Unit admission and mortality were higher in cases than in controls (27% vs 8%, p = 0.002, and 35% vs 10%, p < 0.001). At multivariable analysis, having haematological malignancy [OR4.76, p < 0.001], chronic corticosteroid therapy [OR3.65, p = 0.004], prior infections [OR57.7, p = 0.006], thrombocytopenia [OR3.03, p < 0.001] and neutropenia [OR31.1, p = 0.001], low albumin levels [OR3.1, p = 0.001] and ≥ 10 days from hospital admission to respiratory worsening [OR3.3, p = 0.002] were independently associated with mortality. In cases, neutropenia [OR3.1, p < 0.001], prior infections [OR7.7, p < 0.001], ≥ 10 days to respiratory worsening [OR4.1, p < 0.001], multiple myeloma [OR1.5, p = 0.044], the variation of the CT lung score during hospitalization [OR2.6, p = 0.006] and active treatment [OR 4.4, p < 0.001] all were associated with a worse outcome. CONCLUSION: An underlying haematological malignancy was associated with a worse clinical outcome in COVID-19 patients. A prolonged clinical monitoring is needed, since respiratory worsening may occur later during hospitalization.

Comparison of clinical features and outcomes in COVID-19 and influenza pneumonia patients requiring intensive care unit admission.

BACKGROUND: Little is known in distinguishing clinical features and outcomes between coronavirus disease-19 (COVID-19) and influenza (FLU). MATERIALS/METHODS: Retrospective, single-centre study including patients with COVID-19 or FLU pneumonia admitted to the Intensive care Unit (ICU) of Policlinico Umberto I (Rome). Aims were: (1) to assess clinical features and differences of patients with COVID-19 and FLU, (2) to identify clinical and/or laboratory factors associated with FLU or COVID-19 and (3) to evaluate 30-day mortality, bacterial superinfections, thrombotic events and invasive pulmonary aspergillosis (IPA) in patients with FLU versus COVID-19. RESULTS: Overall, 74 patients were included (19, 25.7%, FLU and 55, 74.3%, COVID-19), median age 67 years (58-76). COVID-19 patients were more male (p = 0.013), with a lower percentage of COPD (Chronic Obstructive Pulmonary Disease) and chronic kidney disease (CKD) (p = 0.001 and p = 0.037, respectively) than FLU. SOFA score was higher (p = 0.020) and lymphocytes were significantly lower in FLU than in COVID-19 [395.5 vs 770.0 cells/mmc, p = 0.005]. At multivariable analysis, male sex (OR 6.1, p < 0.002), age > 65 years (OR 2.4, p = 0.024) and lymphocyte count > 725 cells/mmc at ICU admission (OR 5.1, p = 0.024) were significantly associated with COVID-19, whereas CKD and COPD were associated with FLU (OR 0.1 and OR 0.16, p = 0.020 and p < 0.001, respectively). No differences in mortality, bacterial superinfections and thrombotic events were observed, whereas IPA was mostly associated with FLU (31.5% vs 3.6%, p = 0.0029). CONCLUSIONS: In critically ill patients, male sex, age > 65 years and lymphocytes > 725 cells/mmc are related to COVID-19. FLU is associated with a significantly higher risk of IPA than COVID-19.

Determinants of prolonged viral RNA shedding in hospitalized patients with SARS-CoV-2 infection.

OBJECTIVE: To evaluate determinants of prolonged viral RNA shedding in hospitalized patients with SARS-CoV-2 infection. MATERIALS AND METHODS: Hospitalized patients with SARS-CoV-2 positive nasopharyngeal RT-PCR were included in a single-center, retrospective study. Patients were divided in 2 groups according to the timing of viral clearance [≤14 days, "early clearance (EC)" and >14 days, "late clearance (LC)"]. RESULTS: 179 patients were included in the study (101 EC, 78 LC), with median age 62 years. Median time of viral shedding was 14 days (EC/LC 10 and 19 days, respectively, P < 0.0001). Univariate analyses showed that age, male gender, receiving corticosteroids, receiving tocilizumab, ICU admission, low albumin and NLR ratio were associated with late viral clearance. In the multivariable analysis, older age (P = 0.016), albumin level (P = 0.048), corticosteroids (P = 0.021), and tocilizumab (P = 0.015) were significantly associated with late viral clearance. CONCLUSIONS: Age, albumin, tocilizumab and corticosteroid treatment were independently associated with a prolonged SARS-CoV-2 RNA shedding.

Co-infection of SARS-CoV-2 with Chlamydia or Mycoplasma pneumoniae: a case series and review of the literature.

INTRODUCTION: The novel coronavirus SARS-CoV-2 has spread all over the world causing a global pandemic and representing a great medical challenge. Nowadays, there is limited knowledge on the rate of co-infections with other respiratory pathogens, with viral co-infection being the most representative agents. Co-infection with Mycoplasma pneumoniae has been described both in adults and pediatrics whereas only two cases of Chlamydia pneumoniae have been reported in a large US study so far. METHODS: In the present report, we describe a series of seven patients where co-infection with C. pneumoniae (n = 5) or M. pneumoniae (n = 2) and SARS-CoV-2 was detected in a large teaching hospital in Rome. RESULTS AND CONCLUSION: An extensive review of the updated literature regarding the co-infection between SARS-CoV-2 and these atypical pathogens is also performed.

Multimodal surveillance of healthcare associated infections in an intensive care unit of a large teaching hospital

BACKGROUND: Healthcare-associated infections (HAIs), or nosocomial infections, represent a significant burden in terms of mortality, morbidity, length of stay and costs for patients hospitalized in intensive care units (ICUs). Surveillance systems are recommended by national and international institutions to gather data on HAIs in order to develop and evaluate interventions that reduce the risk of HAIs. STUDY DESIGN: Here we describe the methodology and the results of the surveillance system implemented in the ICU of the Policlinico Umberto I, a large teaching hospital in Rome, from April 2016 to October 2018. METHODS: The multimodal infection surveillance system integrates four different approaches: i) active surveillance of inpatients; ii) environmental microbiological surveillance; iii) surveillance of isolated microorganisms; and iv) behavioral surveillance of healthcare personnel. Data were collected on catheter-related bloodstream infections, ventilation-associated pneumonia, catheter-associated urinary tract infections and primary bloodstream infections that developed in patients after 48 h in the ICU. For environmental surveillance 14 points were selected for sampling (i.e. bed edges, medication carts, PC keyboards, sink faucets). The system of active surveillance of HAIs also included surveillance of microorganisms, consisting of the molecular genotyping of bacterial isolates by pulsed-field gel electrophoresis (PFGE). From 1 November 2016, monitoring of compliance with guidelines for hand hygiene (HH) and proper glove or gown use by healthcare personnel was included in the surveillance system. After the first six months (baseline phase), a multimodal intervention to improve adherence to guidelines by healthcare personnel was conducted with the ICU staff. RESULTS: Overall, 773 patients were included in the active surveillance. The overall incidence rate of device-related HAIs was 14.1 (95% CI: 12.2-16.3) per 1000 patient-days. The monthly device-related HAI incident rate showed a decreasing trend over time, with peaks of incidence becoming progressively lower. The most common bacterial isolates were Klebsiella pneumoniae (20.7%), Acinetobacter baumannii (17.2%), Pseudomonas aeruginosa (13.4%) and Staphylococcus aureus (5.4%). Acinetobacter baumannii and Klebsiella pneumoniae showed the highest proportion of isolates with a multidrug-resistant profile. A total of 819 environmental samples were collected, from which 305 bacterial isolates were retrieved. The most frequent bacterial isolates were Acinetobacter baumannii (27.2%), Staphylococcus aureus (12.1%), Enterococcus faecalis (11.1%), Klebsiella pneumoniae (5.2%) and Pseudomonas aeruginosa (4.7%). All Acinetobacter baumannii, Pseudomonas aeruginosa and Klebsiella pneumoniae environmental isolates were at least multidrug-resistant. Genotyping showed a limited number of major PFGE patterns for both clinical and environmental isolates of Klebsiella pneumoniae and Acinetobacter baumannii. Behavioral compliance rates significantly improved from baseline to post-intervention phase. CONCLUSIONS: By integrating information gathered from active surveillance, environmental microbiological surveillance, surveillance of bacterial isolates and behavioral surveillance of healthcare personnel, the multimodal infection surveillance system returned a precise and detailed view of the infectious risk and microbial ecology of the ICU.

Prevention of surgical site infections in orthopaedic surgery: a synthesis of current recommendations.

Despite adopted precautions, surgical site infection (SSI) rate in orthopaedic surgery and its consequences still remain a major problem. Worldwide, infection prevention and control in perioperative settings are considered of primary importance for every healthcare system. The management of perioperative infections carries a heavy psychological and financial burden, since patients who experience SSI have increased hospital length of stay, morbidity and mortality rates, and higher hospital costs. As the treatment of such infections is particularly difficult in the presence of an implanted biomaterial, the prevention of SSI in orthopaedic surgery represents a challenging key issue, requiring the integration of a range of measures before, during and after surgery. In fact, over the years several aspects of SSI prevention have been studied in order to identify the best SSI prevention strategies and set out appropriate clinical practices. This article will review and summarize the recent international guidelines released on this subject together with other published relevant evidence.

Risk factors for recurrence in patients with Clostridium difficile infection due to 027 and non-027 ribotypes.

OBJECTIVES: Our objective was to evaluate factors associated with recurrence in patients with 027+ and 027- Clostridium difficile infection (CDI). METHODS: Patients with CDI observed between January and December 2014 in six hospitals were consecutively included in the study. The 027 ribotype was deduced by the presence of tcdB, tcdB, cdt genes and the deletion Δ117 in tcdC (Xpert® C. difficile/Epi). Recurrence was defined as a positive laboratory test result for C. difficile more than 14 days but within 8 weeks after the initial diagnosis date with reappearance of symptoms. To identify factors associated with recurrence in 027+ and 027- CDI, a multivariate analysis was performed in each patient group. Subdistributional hazard ratios (sHRs) and 95% confidence intervals (95%CIs) were calculated. RESULTS: Overall, 238 patients with 027+ CDI and 267 with 027- CDI were analysed. On multivariate analysis metronidazole monotherapy (sHR 2.380, 95%CI 1.549-3.60, p <0.001) and immunosuppressive treatment (sHR 3.116, 95%CI 1.906-5.090, p <0.001) were factors associated with recurrence in patients with 027+ CDI. In this patient group, metronidazole monotherapy was independently associated with recurrence in both mild/moderate (sHR 1.894, 95%CI 1.051-3.410, p 0.033) and severe CDI (sHR 2.476, 95%CI 1.281-4.790, p 0.007). Conversely, non-severe disease (sHR 3.704, 95%CI 1.437-9.524, p 0.007) and absence of chronic renal failure (sHR 16.129, 95%CI 2.155-125.000, p 0.007) were associated with recurrence in 027- CDI. CONCLUSIONS: Compared to vancomycin, metronidazole monotherapy appears less effective in curing CDI without relapse in the 027+ patient group, independently of disease severity.

Morphological and molecular responses in ovaries of Mytilus galloprovincialis collected in two different sites of the Naples Bay.

Mytilus galloprovincialis female specimens were collected from two mussel farms located in two sites next to Castel dell'Ovo, a historical complex located in the Naples Bay. Such sites were named, respectively, A-area and B-area for the different microbiological parameters so that mussels from A-area can be sold without purification, whereas mussels from B-area must be purified before sale. The mussels were collected during the nonreproductive (summer 2009) and reproductive periods (autumn 2009). Gonadosomatic index, structural organization of the ovary, presence of apoptosis, estrogen receptors expression, as well as the bisphenol A (BPA) content in the ovaries, were evaluated. Ovaries from specimens collected in area B showed a different and significant distribution of the investigated biomarkers as well as of BPA content in respect to those measured in the A-area specimens, confirming that mussels are valid sentinel organisms to biomonitor in the Naples bay too.

Predictors of outcome in patients with severe sepsis or septic shock due to extended-spectrum ß-lactamase-producing Enterobacteriaceae.

PURPOSE: There are few data in the literature regarding sepsis or septic shock due to extended-spectrum ß-lactamases (ESBL)-producing Enterobacteriaceae (E). The aim of this study was to assess predictors of outcome in septic patients with bloodstream infection (BSI) caused by ESBL-E. METHODS: Patients with severe sepsis or septic shock and BSI due to ESBL-E were selected from the INCREMENT database. The primary endpoint of the study was the evaluation of predictors of outcome after 30 days from development of severe sepsis or septic shock due to ESBL-E infection. Three cohorts were created for analysis: global, empirical-therapy and targeted-therapy cohorts. RESULTS: 367 septic patients were analysed. Overall mortality was 43.9% at 30 days. Escherichia coli (62.4%) and Klebsiella pneumoniae (27.2%) were the most frequent isolates. ß-lactam/ß-lactamase inhibitor (BLBLI) combinations were the most empirically used drug (43.6%), followed by carbapenems (29.4%). Empirical therapy was active in vitro in 249 (67.8%) patients, and escalation of antibiotic therapy was reported in 287 (78.2%) patients. Cox regression analysis showed that age, Charlson Comorbidity Index, McCabe classification, Pitt bacteremia score, abdominal source of infection and escalation of antibiotic therapy were independently associated with 30-day mortality. No differences in survival were reported in patients treated with BLBLI combinations or carbapenems in empirical or definitive therapy. CONCLUSIONS: BSI due to ESBL-E in patients who developed severe sepsis or septic shock was associated with high 30-day mortality. Comorbidities, severity scores, source of infection and antibiotic therapy escalation were important determinants of unfavorable outcome.

Predictors of mortality in nursing-home residents with pneumonia: a multicentre study.

OBJECTIVES: To evaluate predictors of mortality in patients residing in nursing-homes (NHs) or long-term care facilities (LTCFs) with diagnosis of NH-acquired pneumonia (NHAP). METHODS: We conducted an observational, prospective study (December 2013-December 2015) of patients residing in nine NHs/LTCFs of Central and Northern Italy with diagnosis of NHAP. Data on demographics, comorbidities, microbiology, and therapies were entered into an electronic database. To identify risk factors associated with 30-day mortality, we performed univariable and multivariable analyses, and predictors were internally validated using a bootstrap resampling procedure. We derived a prediction rule using the coefficients obtained from the multivariable logistic regression. The model obtained was assessed using the area under the receiver operating characteristic curve (AUROC). RESULTS: Overall, 446 patients with NHAP were included in the final cohort. The median age was 80 (IQR 75-87) years. A definite aetiology was obtained in 120 (26.9%) patients; of these, 66 (55%) had a culture positive for a multidrug-resistant pathogen. The 30-day mortality was 28.7%. On multivariate analysis, malnutrition (OR 7.8; 95% CI 3-20.2, 2 points), bilateral pneumonia (OR 3.7; 95% CI 1.4-9.8, 1 point), acute mental status deterioration (OR 6.2; 95% CI 2.2-17.6, 2 points), hypotension (OR 7.7; 95% CI 2.3-24.9, 2 points), and PaO2/FiO2 ratio ≤250 (OR 7.4; 95% CI 2.2-24.2, 2 points) were independently associated with 30-day mortality. The derived prediction rule showed an AUROC of 0.83 (95% CI 0.78-0.87, p <0.001). CONCLUSIONS: NH residents with pneumonia have specific risk factors associated with 30-day mortality. Malnutrition and acute mental change appear as major determinants of death in this population.

Role of biomarkers in adult sepsis and their application for a good laboratory practice: a pilot study.

This study measured Procalcitonin (PCT), Presepsin (PRE-S) and pro-Adrenomedullin (pro-ADM) in intensive care unit (ICU) patient’s blood to assess their contribution to accurate diagnosis of sepsis and potential predictive impact on prognosis. The final aim was to improve the use of infection biomarkers for optimizing the impact of laboratory medicine on clinical outcomes, focusing on the good management of resources designed to produce maximum effectiveness and efficiency. Sixty-four adult patients were studied during their hospitalization in ICU; blood samples were collected and categorized according to their clinical diagnosis and illness severity, and sepsis marker levels were measured on automated immunoassay platforms. PCT, PRE-S and pro-ADM infection markers were significantly lower in controls than in sepsis or septic shock groups. The area under the curve, by ROC curve analysis, was 0.945 for PCT, 0.756 for PRE-S and 0.741 for pro-ADM. Sepsis diagnostic accuracy was not improved by combining PCT, PRE-S and pro-ADM measures. Preliminary data demonstrated that, despite PRE-S and pro-ADM being able to differentiate between septic and non-septic patients with accuracy, PCT remains the most reliable marker available. The results obtained still do not allow us to consider a combination of markers, because it would merely increase laboratory costs without improving diagnostic performance. Furthermore, the results confirm a possible prognostic role of pro-ADM in septic states, but no correlation between biomarker levels and survival at 48 h was detected. Hence PCT, PRE-S, nor pro-ADM can be used to predict short-term prognosis.

Assessment of risk factors for candidemia in non-neutropenic patients hospitalized in Internal Medicine wards: A multicenter study.

BACKGROUND: An increasing prevalence of candidemia has been reported in Internal Medicine wards (IMWs). The aim of our study was to identify risk factors for candidemia among non-neutropenic patients hospitalized in IMWs. METHODS: A multicenter case-control study was performed in three hospitals in Italy. Patients developing candidemia (cases) were compared to patients without candidemia (controls) matched by age, time of admission and duration of hospitalization. A logistic regression analysis identified risk factors for candidemia, and a new risk score was developed. Validation was performed on an external cohort of patients. RESULTS: Overall, 951 patients (317 cases of candidemia and 634 controls) were included in the derivation cohort, while 270 patients (90 patients with candidemia and 180 controls) constituted the validation cohort. Severe sepsis or septic shock, recent Clostridium difficile infection, diabetes mellitus, total parenteral nutrition, chronic obstructive pulmonary disease, concomitant intravenous glycopeptide therapy, presence of peripherally inserted central catheter, previous antibiotic therapy and immunosuppressive therapy were factors independently associated with candidemia. The new risk score showed good area under the curve (AUC) values in both derivation (AUC 0.973 95% CI 0.809-0.997, p<0.001) and validation cohort (0.867 95% CI 0.710-0.931, p<0.001). A threshold of 3 leads to a sensitivity of 87% and a specificity of 83%. CONCLUSION: Non-neutropenic patients admitted in IMWs have peculiar risk factors for candidemia. A new risk score with a good performance could facilitate the identification of candidates to early antifungal therapy.

Current and future trends in antibiotic therapy of acute bacterial skin and skin-structure infections.

In 2013 the US Food and Drug Administration (FDA) issued recommendations and guidance on developing drugs for treatment of skin infection using a new definition of acute bacterial skin and skin-structure infection (ABSSSI). The new classification includes cellulitis, erysipelas, major skin abscesses and wound infection with a considerable extension of skin involvement, clearly referring to a severe subset of skin infections. The main goal of the FDA was to better identify specific infections where the advantages of a new antibiotic could be precisely estimated through quantifiable parameters, such as improvement of the lesion size and of systemic signs of infection. Before the spread and diffusion of methicillin-resistant Staphylococcus aureus (MRSA) in skin infections, antibiotic therapy was relatively straightforward. Using an empiric approach, a ß-lactam was the preferred therapy and cultures from patients were rarely obtained. With the emergence of MRSA in the community setting, initial ABSSSI management has been changed and readdressed. Dalbavancin, oritavancin and tedizolid are new drugs, approved or in development for ABSSSI treatment, that also proved to be efficient against MRSA. Dalbavancin and oritavancin have a long half-life and can be dosed less frequently. This in turn makes it possible to treat patients with ABSSSI in an outpatient setting, avoiding hospitalization or potentially allowing earlier discharge, without compromising efficacy. In conclusion, characteristics of long-acting antibiotics could represent an opportunity for the management of ABSSSI and could profoundly modify the management of these infections by reducing or in some cases eliminating both costs and risks of hospitalization.

Predictors of outcome in ICU patients with septic shock caused by Klebsiella pneumoniae carbapenemase-producing K. pneumoniae.

The aim of this study was to identify factors associated with mortality in intensive care unit patients with Klebsiella pneumoniae carbapenemase-producing K. pneumoniae (KPC-Kp) septic shock. A retrospective analysis of intensive care unit patients with KPC-Kp infection and septic shock observed in a large teaching hospital from November 2010 to December 2014 was performed. A total of 111 patients were included in the study. The most frequent source of infection was unknown-focus bacteraemia in 53 patients (47.7%). The rate of resistance to colistin was 51.3%; 30-day mortality was reported for 44 patients (39.6%). Surviving patients were more frequently treated with an initial therapy (within 24 hours) including two or more antibiotics displaying in vitro activity against the isolated KPC-Kp strain (41.8 vs. 18.1%, p 0.01) and were also more likely to receive a definitive therapy including two or more in vitro active antibiotics (85.1 vs. 15.9%, p <0.001). Cox regression analysis revealed that a colistin-containing antibiotic regimen (hazard ratio (HR) 0.21, confidence interval (CI) 95% 0.05-0.72, p <0.001), use of two or more in vitro active antibiotics as definite therapy (HR 0.08, CI 95% 0.02-0.21, p <0.001) and control of removable source of infection (HR 0.14, CI 95% 0.04-0.25, p <0.001) were associated with favourable outcome; colistin resistance (HR 8.09, CI 95% 3.14-11.23, p 0.001) and intra-abdominal source of infection (HR 2.92, CI 95% 2.11-4.12, p 0.002) were associated with death. In conclusion, use of a definitive therapy with at least two antibiotics displaying in vitro activity against the KPC-Kp isolates was the most important determinant of favourable outcome, whilst isolation of colistin-resistant strains was associated with death in septic patients with KPC-Kp infection.