Epidemiology and Risk Factors for Nosocomial Infections in Left Ventricular Assist Device Recipients.

Left ventricular assist devices (LVADs) have been increasingly used as a valid option to improve the prognosis and reduce the symptoms of end-stage heart failure. However, long-term complications, mostly infections and coagulation disorders, are frequent. We described the epidemiology and risk factors for nosocomial infections (NIs) in a cohort of adult patients who underwent continuous-flow LVAD implant between January 2010 and December 2017 in Turin, Italy. Secondary outcomes were the prevalence of multidrug-resistant (MDR) bacteria and mortality. Results: Overall, 64 LVADs were implanted. A total of 32 (50%) patients experienced at least one episode of NI, with a total of 46 infectious events. VAD-related infections occurred in 22 patients (68.8%). Non VAD-related NIs occurred in 12 patients (37.5%), mainly low respiratory tract infections. Length of intensive care unit admission was a risk factor for NI (OR 1.224, 95%CI; 1.049, 1.429). Gram-negative bacilli were responsible for 58.8% of VAD-related infections and 79.5% of non-VAD related infections. In sixteen patients (50%), at least one episode of infection was related to an MDR strain. INTERMACS class and length of MV were independent risk factors for NIs by MDR strains (respectively, OR 2.12, 95%CI: 1.08, 6.80; p = 0.02 and OR 1.46, 95%CI: 1.07, 5.52, p = 0.047). In-hospital mortality was 6.3%. No differences in mortality were observed between infected and non-infected patients (p = 0.61) even when caused by MDR strains (p = 0.143). Conclusion: the rate of nosocomial infections in LVAD patients is associated with the length of ICU admission, and the etiology of nosocomial infection after LVAD implant is mainly due to GNB, including a high rate of MDR strains, especially KPC-KP and MDR PA.

Nosocomial Infections in Adult Patients Supported by Extracorporeal Membrane Oxygenation in a Cardiac Intensive Care Unit.

The use of venoarterial (VA) extracorporeal membrane oxygenation therapy (ECMO) in patients admitted to cardiac intensive care units (CICU) has increased. Data regarding infections in this population are scarce. In this retrospective study, we analyzed the risk factors, outcome, and predictors of in-hospital mortality due to nosocomial infections in patients with ECMO admitted to a single coronary intensive care unit between July 2013 and March 2019 treated with VA-ECMO for >48 h. From 69 patients treated with VA-ECMO >48 h, (median age 58 years), 29 (42.0%) patients developed 34 episodes of infections with an infection rate of 0.92/1000 ECMO days. The most frequent were ventilator-associated pneumonia (57.6%), tracheobronchitis (9.1%), bloodstream infections (9.1%), skin and soft tissue infections (9.1%), and cytomegalovirus reactivation (9.1%). In-hospital mortality was 47.8%, but no association with nosocomial infections was found (p = 0.75). The number of days on ECMO (OR 1.14, 95% CI 1.01-1.30, p = 0.029) and noninfectious complications were higher in the infected patients (OR: 3.8 95% CI = 1.05-14.1). A higher baseline creatinine value (OR: 8.2 95% CI = 1.12-60.2) and higher blood lactate level at 4 h after ECMO initiation (OR: 2.0 95% CI = 1.23-3.29) were significant and independent risk factors for mortality. Conclusions: Nosocomial infections in medical patients treated with VA-ECMO are very frequent, mostly Gram-negative respiratory infections. Preventive measures could play an important role for these patients.

Efficacy of bezlotoxumab in preventing the recurrence of Clostridioides difficile infection: an Italian multicenter cohort study.

OBJECTIVES: Bezlotoxumab (BEZ) is a promising tool for preventing the recurrence of Clostridioides difficile infection (rCDI). The aim of the study was to emulate, in a real-world setting, the MODIFY trials in a cohort of participants with multiple risk factors for rCDI treated with BEZ in addition to the standard of care (SoC) versus SoC alone. METHODS: A multicenter cohort study was conducted including 442 patients with Clostridioides difficile infection from 2018 to 2022, collected from 18 Italian centers. The main outcome was the 30-day occurrence of rCDI. The secondary outcomes were (i) all-cause mortality at 30 days (ii) and the composite outcome (30-day recurrence and/or all-cause death). RESULTS: rCDI at day 30 occurred in 54 (12%): 11 in the BEZ + SoC group and 43 treated with SoC alone (8% vs 14%, odds ratio [OR] = 0.58, 95% confidence interval [CI]: 0.31-1.09, P = 0.09). The difference between BEZ + SoC versus SoC was statistically significant after controlling for confounding factors (adjusted OR = 0.40, 95% CI: 018-0.88, P = 0.02) and even more using the composite outcome (adjusted OR = 0.35, 95% CI: 0.17-0.73, P = 0.005). CONCLUSION: Our study confirms the efficacy of BEZ + SoC for the prevention of rCDI and death in a real-world setting. BEZ should be routinely considered among participants at high risk of rCDI regardless of age, type of Clostridioides difficile infection therapy (vancomycin vs fidaxomicin), and number of risk factors.

REDS study: Retrospective effectiveness study of dalbavancin and other standard of care of the same IV antibiotic class in patients with ABSSSI.

OBJECTIVES: Acute bacterial skin and skin-structure infections (ABSSSIs) are a common source of morbidity in both the community and hospital settings. The current standard of care (SoC) requires multiple-dose intravenous (IV) regimens, which are associated with high hospitalisation rates, concomitant event risks and costs. Dalbavancin is a lipoglycopeptide, long-acting antibiotic that is effective against Gram-positive microorganisms, including methicillin-resistant Staphylococcus aureus (MRSA). Dalbavancin allows treatment of ABSSSIs with a single-shot IV administration or once weekly for 2 weeks, enabling clinicians to treat patients in an outpatient setting or to shorten the length of hospital stay. METHODS: This multicentre, observational, retrospective study compared hospitalised patients who received dalbavancin and patients treated with the three most used IV antibiotics of the same or similar class: vancomycin, teicoplanin and daptomycin. The primary outcome was the time to discharge after starting the study antibiotics. RESULTS: The primary endpoint, time to discharge from the study therapy start, was measured for both groups: the median number of days was 6.5 in the dalbavancin group vs. 11.0 days in the SoC group. Moreover, in subpopulations of patients receiving one or more concomitant antibiotics active for Gram-positives, MRSA and patients with the most prevalent comorbidity (i.e., diabetes), the advantage of dalbavancin in terms of length of stay was confirmed, with a halved time to discharge or more. Safety data on dalbavancin were consistent with data collected in clinical trials. No serious adverse drug reactions related to dalbavancin were reported and most of them were classified as skin and subcutaneous tissue disorders. One serious ADR was reported for daptomycin. CONCLUSIONS: Although the analysis was only descriptive, it can be concluded that dalbavancin may enable a remarkable reduction in length of hospital stay, also confirming the clinical effectiveness and good safety profile demonstrated in clinical trials in a real-world setting.

Predictors of mortality in patients with COVID-19 infection in different health-care settings: A retrospective analysis from a CORACLE study group.

BACKGROUND: Despite the large number of hospitalized patients affected by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection, few data are available about risk factors and mortality in subjects with nosocomially acquired respiratory infection of Coronavirus Disease 2019 (COVID-19). METHODS: We retrospectively evaluated in a multicentric study -during the pre-vaccination era-all patients admitted with confirmed diagnosis of nosocomial COVID-19 (NC). Patients were classified according to provenance: hospital-acquired NC or long-term care (LTC) facilities. RESULTS: Among overall 1047 patients evaluated with COVID-19, 137 had a confirmed diagnosis of NC (13%). 78 (56.9%) patients had hospital-acquired NC and 59 (43%) had LTC NC. Overall mortality was 35.8%, in hospital-acquired NC 24.4%, in LTC NC 50.8% (p < 0.001) (Log Rank test: p = 0.001). Timing of diagnosis was significantly different between hospital acquired and LTC NC (3.5 vs 10 days, p < 0.001). In multivariate analysis age, intensive-care unit admission, LTC provenance and sepsis were significant predictors of mortality in patients with NC infection. CONCLUSION: Patients with NC are at higher risk of mortality (especially for LTC NC) and required preventive strategies, early diagnosis, and treatment to avoid COVID-19 cluster.

Pharmacokinetic of Cefiderocol in Critically Ill Patients Receiving Renal Replacement Therapy: A Case Series.

Background: Cefiderocol is a novel parenteral siderophore cephalosporin, demonstrating enhanced activity against multidrug-resistant (MDR) Gram-negative bacteria and difficult-to-treat Acinetobacter baumannii (DTR-AB). Plasma-free trough concentration (fCtrough) over the minimum inhibitory concentration (MIC) was reported as the best pharmacokinetic parameter to describe the microbiological efficacy of cefiderocol. Materials and methods: We retrospectively described the pharmacokinetic and pharmacodynamic profile of three critically ill patients admitted to the intensive care unit, receiving cefiderocol under compassionate use to treat severe DTR-AB infections while undergoing continuous venovenous haemofiltration. Cefiderocol was administrated at a dosage of 2 g every 8 h infused over 3 h. Therapeutic drug monitoring (TDM) was assessed at the steady state. Cthrough was evaluated by assuming a plasma protein binding of 58.0%. The fCmin/MIC was calculated assuming a cefiderocol MIC equal to the PK-PD breakpoint of susceptibility ≤ 2. The association between the PK/PD parameters and microbiological outcome was assessed. Results: fCtrough/MIC were >12 in 2 patients and 2.9 in the 1 who rapidly recovered from renal failure. Microbiological cure occurred in 3/3 of patients. None of the 3 patients died within 30 days. Conclusions: A cefiderocol dosage of 2 g q8 h in critically ill patients with AKI undergoing CVVH may bring about a very high plasma concentration, corresponding to essentially 100% free time over the MIC for DTR-AB.

Ten Years of KPC-Kp Bloodstream Infections Experience: Impact of Early Appropriate Empirical Therapy on Mortality.

Background. In K. pneumoniae KPC (KPC-Kp) bloodstream infections (BSI), INCREMENT CPE score >7, Charlson Comorbidity Index (CCI) ≥3 and septic shock are recognized predictors of mortality, with a possible beneficial effect of combination therapy in seriously ill patients. Materials and Methods. We conducted a ten-year retrospective study including all KPC-Kp BSI in patients ≥18 years of age with the aim to evaluate the characteristics and impact of appropriate empirical therapy, either monotherapy or combination therapy, and targeted therapy on mortality. Appropriate therapy was defined as at least one active antimicrobial agent with in vitro activity against KPC-kp demonstrated by susceptibility testing, administered within 48 h from blood culture collection. Results. The median age of the 435 analyzed patients was 66.09 years (IQR 54.87−73.98). The median CCI was 4. KPC-Kp colonization was present in 324 patients (74.48%). The probable origin of the KPC-Kp BSI was not identified in 136 patients (31.26%), whereas in 120 (27.59%) patients, it was CVC-related, and in 118 (27.13%), it was respiratory. Source control was achieved in 87 patients (72.5%) with CVC-related KPC-Kp BSI. The twenty-eight-day survival was 70.45% for empirical monotherapy, 63.88% for empirical combination therapy and 57.05% for targeted therapy (p = 0.0399). A probable source of KPC-Kp BSI other than urinary, CVC or abdominal [aHR 1.64 (IC 1.15−2.34) p = 0.006] and deferred targeted therapy [HR 1.67 (IC 1.12−2.51), p= 0.013] emerged as predictors of mortality, whereas source control [HR 0.62 (IC 0.44−0.86), p = 0.005] and ceftazidime/avibactam administration in empirical therapy [aHR 0.37 (IC 0.20−0.68) p = 0.002] appeared as protective factors. Discussion. These data underline the importance of source control together with timing appropriateness in the early start of empirical therapy over the choice of monotherapy or combination therapy and the use of ceftazidime/avibactam against KPC-Kp BSI.

Real-Life Experience of Molnupiravir in Hospitalized Patients Who Developed SARS-CoV2-Infection: Preliminary Results from CORACLE Registry.

Real-life experience of molnupiravir treatment is lacking, especially in people hospitalized for underlying diseases not related to COVID-19. We conducted a retrospective analysis regarding molnupiravir therapy in patients with SARS-CoV-2 infection admitted for underlying diseases not associated with COVID-19. Forty-four patients were included. The median age was 79 years (interquartile range [IQR]: 51-93 years), and most males were 57,4%. The median Charlson Comorbidity Index and 4C score were, respectively, 5 (IQR: 3-10) and 9.9 (IQR: 4-12). Moreover, 77.5% of the patients had at least two doses of the anti-SARS-CoV-2 vaccine, although 10.6% had not received any SARS-CoV-2 vaccine. Frequent comorbidities were cardiovascular diseases (68.1%), and diabetes (31.9%), and most admissions were for the acute chronic heart (20.4%) or liver (8.5%) failure. After molnupiravir started, 8 (18.1%) patients developed acute respiratory failure, and five (11.4%) patients died during hospitalisation. Moreover, molnupiravir treatment does not result in a statistically significant change in laboratory markers except for an increase in the monocyte count (p = 0.048, Z = 1.978). Molnupiravir treatment in our analysis was safe and well tolerated. In addition, no patients' characteristics were found significantly related to hospital mortality or an increase in oxygen support. The efficacy of the molecule remains controversial in large clinical studies, and further studies, including larger populations, are required to fill the gap in this issue.

Meropenem/Vaborbactam and Cefiderocol as Combination or Monotherapy to Treat Multi-Drug Resistant Gram-Negative Infections: A Regional Cross-Sectional Survey from Piedmont Infectious Disease Unit Network (PIDUN).

Meropenem/vaborbactam (MV) and cefiderocol were recently approved by the Food and Drug Administration and European Medicines Agency and are among the most promising antibacterial in treatment regimens against multi-drug resistant (MDR) gram-negative bacilli. A survey with close-ended questions was proposed to infectious disease (ID) and intensive care unit (ICU) physicians of Piedmont and Valle d'Aosta Region's hospitals. The aim was to collect data about habits and prescriptions of cefiderocol and MV. Twenty-three physicians (11 ID specialists and 12 anesthesiologists) in 13 Italian hospitals took part in the survey. Both cefiderocol and MV were mostly used as target therapy after a previous treatment failure and after ID specialist consult. The most frequent MDR pathogen in hospitals was Klebsiella pneumoniae carbapenemase-producing bacteria (KPC), followed by P. aeruginosa and A. baumannii. MDRs were more frequently isolated in ICU. In conclusion, cefiderocol was used in empiric regimens when A.baumannii was suspected, while MV was more used in suspect of KPC. MV and cefiderocol can be the first option in empiric treatment for critically ill patients in settings with high risk of MDR. The treatment should then be followed by rapid de-escalation when microbiological results are available.

The Diagnostic Relevance of ß-D-Glucan for Candidemia within Internal Medicine Wards.

Candidemia diagnosis is based on the combination of clinical, microbiological and laboratory data. We aimed to evaluate performances and accuracy of (1,3)-ß-D-glucan (BDG) at various cut-offs in internal medicine patients. An observational retrospective−prospective study was performed. Patients with at least two determinations of BDG and paired, associated blood cultures within ±48 h were considered. A total of 140 patients were included: 26 with Candida spp. blood-stream infections (BSI) and 114 without candidemia. Patients with candidemia were older and had higher BDG values, need of parenteral nutrition, higher colonization by Candida in more than one site, presence of percutaneous gastrostomy and higher Candida or Charlson scores. BDG maintained the best compromise between sensitivity, specificity and optimal negative predictive value was 150 pg/mL. BDG values at cut-off of 150 pg/mL increase the strength of association between BDG and development of candidemia (Odds Ratio­OR 5.58; CI 2.48−12.53 vs. OR 1.06; CI 1.003−1.008). Analyzing BDG > 150 pg/mL along with Candida score > 2 and Charlson score > 4, the strength of the association amongst BDG, clinical scores and development of candidemia is increased. The overall clinical evaluation with the help of scores that consider BDG values > 150 pg/mL, Candida score > 2 and Charlson score > 4 in combination seems to predict better the need of antifungal empiric treatment.

Cefiderocol use in Gram negative infections with limited therapeutic options: Is combination therapy the key?

OBJECTIVES: To date limited information about cefiderocol use is provided by real life studies. Our aim is to evaluate characteristics and outcome of patients with Gram-negative infections with limited therapeutic options treated with cefiderocol in combination or monotherapy. METHODS: We retrospectively collected data on demographical, clinical characteristics and clinical cure, in-hospital and 30-days mortality, microbiological failure and Clostridioides difficile infections of all patients ≥ 18 years old treated with cefiderocol for ≥ 48 h. RESULTS: There were 18 patients of which 14 (77.8%) treated with cefiderocol in combination and 4 (22.2%) with monotherapy. Median age was 54.5 (IQR 35.25-65.75) vs 70.5 (IQR 57.5-78.25) years old, respectively and ward of admission was the ICU in the 78.57% vs 100% of cases. In the 50% vs 100% of cases infections were VAP with concomitant bloodstream infections. Median SOFA score was 10 (IQR 4.5-12.5) vs 5 (IQR 4-6) and APACHE II score was 13.5 (IQR 7.5-18) vs 16 (IQR 8.5-23.5), respectively. Isolated pathogen was carbapenems-resistant Acinetobacter baumannii in 78.57% vs 100% of cases. Median duration of cefiderocol treatment was 9.5 (IQR 7-13.25) vs 9 days (IQR 5.5-12.5) and in 77.8% patients it was used in combination therapy, of which 57.1% were colistin-spairing regimens. Clinical cure was achieved in 64.29% for combination therapy vs 75% of monotherapy treated patients, 30-days mortality rate was 28.57% vs 25% and 30-day ICU admission rate was 14.29% vs 50%, respectively. No statistically significant differences were observed between combination therapy and monotherapy treated patients. CONCLUSIONS: To date, no differences have been demonstrated between cefiderocol monotherapy or combination. Further studies are required to understand whether cefiderocol combination therapy could provide an advantage in outcome in seriously-ill patients.

Impact of an empiric antimicrobial therapy manual on antimicrobial usage and multidrug resistant organism trends in a large Italian teaching hospital.

Aim: To evaluate the changes in antimicrobial consumption and multidrug-resistant microorganism trends after introducing an empiric antimicrobial therapy manual to support antimicrobial stewardship. Methods: A 4-year prospective interventional study assessed the effect of introducing an empiric antimicrobial therapy manual in medical and surgical wards during two periods: pre-intervention period (January 2015-May 2017) and post-intervention period (June 2017-December 2019). Outcomes included microorganism trends of bloodstream infections (BSI) for Klebsiella pneumoniae carbapenemase-producing bacteria (KPC), extended spectrum beta-lactamase ESBL-E. coli, meticillin-resistant Staphylococcus aureus (MRSA) and Candida albicans. Also, Clostridioides difficile infection (CDI) episodes were included. Rates were normalised per 1000 patient-days (PD). Antimicrobial consumption was assessed as defined daily dose (DDD)/1000 PD in interrupted time series analysis. Results: In medical wards, we observed a significant decrease in the consumption of piperacillin-tazobactam and a decrease in the trends of tigecycline and vancomycin consumption. In surgical wards, there was a significant decrease in consumption of fluoroquinolones and piperacillin-tazobactam. This decrease was maintained in trend for all the antimicrobials but was significant for tigecycline only. In medical wards, there was a significant reduction of MRSA and C. albicans. In surgical wards, we observed a decrease in MRSA, ESBL-E. coli, C. albicans and CDI. KPC cases decreased by 22.5% in medical wards and 74.3% in surgical wards. Conclusion: The results suggest that a persuasive educational approach to antimicrobial stewardship, with the introduction of an empiric antimicrobial manual and continuous education, resulted in reductions in both antimicrobial use and healthcare-associated BSI caused by multidrug-resistant organisms. More studies with longer follow up are needed to investigate the effect of antimicrobial stewardship on clinical outcomes.

Temocillin: Applications in Antimicrobial Stewardship as a Potential Carbapenem-Sparing Antibiotic.

Temocillin is an old antibiotic, but given its particular characteristics, it may be a suitable alternative to carbapenems for treating infections due to ESBL-producing Enterobacterales and uncomplicated UTI due to KPC-producers. In this narrative review, the main research question was to summarize current evidence on temocillin and its uses in infectious diseases. A search was run on PubMed using the terms ('Temocillin' [Mesh]) AND ('Infection' [Mesh]). Current knowledge regarding temocillin in urinary tract infection, blood-stream infections, pneumonia, intra-abdominal infections, central nervous system infections, skin and soft tissues infections, surgical sites infections and osteoarticular Infections were summarized. Temocillin retain a favourable profile on microbiota and risk of Clostridioides difficile infections and could be an option for treating outpatients. Temocillin may be a valuable tool to treat susceptible pathogens and for which a carbapenem could be spared. Other advantages in temocillin use are that it is well-tolerated; it is associated with a low rate of C. difficile infections; it is active against ESBL, AmpC, and KPC-producing Enterobacterales; and it can be used in the OPAT clinical setting.

Testosterone as a Biomarker of Adverse Clinical Outcomes in SARS-CoV-2 Pneumonia.

Background: The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) may affect testicles. Lower testosterone levels have been associated with worse clinical outcomes and higher mortality. Our objective was to evaluate the hypothalamic−pituitary−gonadal axis of men admitted with SARS-CoV-2 pneumonia and its link with the pneumonia-treatment intensification. Short-term changes in hormonal parameters were also assessed. Methods: Men admitted with SARS-CoV-2 pneumonia were recruited in two different hospitals in Piedmont, Italy. In all patients, the assessment of total testosterone (TT), calculated free testosterone (cFT), gonadotropins, inhibin B (InhB), and other biochemical evaluations were performed at admission (T0) and before discharge (T1). Through a review of medical records, clinical history was recorded, including data on pneumonia severity. Results: Thirty-five men (median age 64 [58−74] years) were recruited. Lower TT and cFT levels at T0 were associated with CPAP therapy (p = 0.045 and 0.028, respectively), even after adjusting for age and PaO2/FIO2 ratio in a multivariable analysis. In those discharged alive, lower TT and cFT levels were associated with longer hospital stay (p < 0.01). TT, cFT, and InhB were below the normal range at T0 and significantly increased at T1 (TT 1.98 [1.30−2.72] vs. 2.53 [1.28−3.37] ng/mL, p = 0.038; cFT (0.0441 [0.0256−0.0742] vs. 0.0702 [0.0314−0.0778] ng/mL, p = 0.046; InhB 60.75 [25.35−88.02] vs. 77.05 [51.15−134.50], p < 0.01). Conclusions: Both TT and cFT levels are associated with adverse clinical outcomes in men admitted with SARS-CoV-2 pneumonia. As TT, cFT and InhB levels increase before discharge, short-term functional recovery of steroidogenesis and an indirect improvement of spermatozoa functional status could be hypothesized.

Factors Influencing the Intracellular Concentrations of the Sofosbuvir Metabolite GS-331007 (in PBMCs) at 30 Days of Therapy.

Sofosbuvir (SOF) is an HCV NS5B polymerase inhibitor, and GS-331007 is its major metabolite. The aim of this study was to investigate whether clinical and pharmacological factors could influence GS-331007 intracellular (IC) concentrations in peripheral blood mononuclear cells (PBMCs) associated with a sustained virological response in patients treated with SOF and ribavirin (RBV). Drug levels were analyzed using liquid chromatography at different days of therapy, whereas variants in genes encoding transporters and nuclear factors were investigated using real-time PCR. This study enrolled 245 patients treated with SOF; 245 samples were analyzed for pharmacogenetics and 50 were analyzed for IC pharmacokinetics. The GS-331007 IC concentration at 30 days was associated with its plasma concentration determinate at 30, 60 and 90 days of SOF-therapy and with daclatasvir concentrations at 7 days of therapy. No genetic polymorphism affected IC exposure. In linear multivariate analysis, ledipasvir treatment, baseline albumin and estimated glomerular filtration rate were significant predictors of IC exposure. This study presents data on an IC evaluation in a cohort of patients treated with SOF, also considering pharmacogenetics. These results could be useful for regions where SOF-RBV treatment is considered the standard of care; moreover, they could further deepen the knowledge of IC exposure for similar drugs in the future.

Liver involvement and mortality in COVID-19: A retrospective analysis from the CORACLE study group.

Introduction: liver abnormalities are common in COVID-19 patients and associated with higher morbidity and mortality. We aimed to investigate clinical significance and effect on the mortality of abnormal liver function tests (ALFTs) in COVID-19 patients. Methods: we retrospectively evaluated in a multicentre study all patients admitted with confirmed diagnosis of COVID-19. Results: 434 patients were included in this analysis. Among overall patients, 311 (71.6%) had normal baseline ALT levels. 123 patients showed overall abnormal liver function tests (ALFTs) at baseline [101 ALFTs <2x UNL and 22 ≥2 UNL]. Overall in-hospital mortality was 14% and mean duration of hospitalization was 10.5 days. Hypertension (50.5%), cardiovascular diseases (39.6%), diabetes (23%) were frequent comorbidities and 53.7% of patients had ARDS. At multivariate analysis, the presence of ARDS at baseline (OR=6.11; 95% CI: 3.03-12.32; p<0.000); cardiovascular diseases (OR=4; 95% CI: 2.05-7.81; p<0.000); dementia (OR=3.93; 95%CI:1.87-8.26; p<0.000) and no smoking (OR=4.6; 95% CI: 1.45-14.61; p=0.010) resulted significantly predictive of in-hospital mortality. The presence of ALFTs at baseline was not significantly associated with mortality (OR=3.44; 95% CI=0.81-14.58; p=0.094). Conclusion: ALFTs was frequently observed in COVID-19 patients, but the overall in-hospital mortality was mainly determined by the severity of illness, comorbidities and presence of ARDS.

Beta Lactams Plus Daptomycin Combination Therapy for Infective Endocarditis: An Italian National Survey (BADAS).

BACKGROUND: infective endocarditis (IE) remains a severe disease frequently encountered in clinical practice and often requiring interdisciplinary medical and surgical management. This national survey aims to describe the clinical prescribing habits of the use of daptomycin in the setting of IE and the possible role for combination therapy with beta-lactams. METHODS: The study was a cross-sectional internet-based questionnaire survey on therapy with daptomycin. The questionnaire was designed with closed-ended questions and distributed using the SurveyMonkey® platform between October 2019 to December 2020. RESULTS: 55 clinicians from twelve Italians regions joined the questionnaire. The survey reported use of daptomycin as first-line choice in 31.48% of cases and as the first-line anti-MRSA agent in 44.44%. The empiric use of daptomycin was stated in the high suspicion of MRSA rather than MSSA, enterococcal or streptococcal IE. The rationale of daptomycin for the empirical treatment of native and prosthetic valve IE was mostly the possibility of administering an aminoglycoside-sparing combination regimen, high bacterial killing rate and high clinical efficacy. CONCLUSIONS: In conclusion, in selected patients, daptomycin could be a feasible option for the treatment of infective endocarditis in line with data from the European registry of daptomycin.

Clinical and microbiological characteristics of bloodstream infections caused by Enterococcus spp. within internal medicine wards: a two-year single-centre experience.

Enterococcal bloodstream infections (E-BSI) constitute the second cause of Gram-positive bacterial BSI in Europe with a high rate of in-hospital mortality. Furthermore, E-BSI treatment is still challenging because of intrinsic and acquired antibiotic resistances. We conducted a retrospective, 2-year, observational, single-centre study to evaluate clinical outcome and risk factors for E-BSI mortality in internal medicine wards. 201patients with E-BSI were included in the analysis. Infection rate was 2.4/1000 days of hospital admission. Most E-BSI were hospital acquired (78.1%). The median age was 68 years. Charlson Comorbidity Index, adjusted for age, was 5 (range 4-6). Patients with E-BSI frequently had at least one invasive device, predominantly a central venous (73%) or a bladder catheter (61.7%). Enterococcus faecium accounted for 47.94% of E-BSI (resistance rate to ampicillin or vancomycin was 22.2 and 23.3%, respectively) and Enterococcus faecalis for 52.08% (resistance rate to ampicillin or vancomycin was 3.1 and 2.2%, respectively). Among all E-BSI, 25% of patients received appropriate therapy. In total, 59% of E-BSI underwent echocardiography. At the multivariate analysis, resistance to vancomycin (OR 2.09, p = 0.025), sepsis (OR 2.57, p = 0.003) and septic shock (OR 3.82, p = 0.004) was a predictor of mortality. No difference in 28-day survival was observed between appropriate or inappropriate treatment, except for endocarditis. However, E-BSI sources in clinical practices are not always properly investigated, including the rule-out of intracardiac vegetations. We did not demonstrate a difference in mortality for inappropriate therapy in the absence of endocarditis in comorbid patients with a long history of medicalization.

Nodular Cutaneous Lesions in Immune-Compromised Hosts as a Clue for the Diagnosis of Disseminated Nocardiosis: From Bedside to Microbiological Identification.

BACKGROUND: Nocardia is a group of ubiquitous bacteria known to cause opportunistic infections in immunocompromised hosts, including those affected by malignancies and solid-organ or hematopoietic stem cell transplants. Pulmonary involvement, occurring in two-thirds of cases, is the most frequent presentation. Diagnosis might be challenging both because of microbiological technical issues, but also because of the variability of organ involvement and mimicry. METHODS: We describe four cases of disseminated nocardiosis caused by N. farcinica observed between September 2021 and November 2021 in immune-compromised hosts presenting with nodular cutaneous lesions that had raised a high degree of clinical suspect and led to microbiological identification through MALDI-TOF MS. RESULTS: Cutaneous involvement is typically reported in immunocompetent hosts with primary cutaneous nocardiosis with multiple forms of manifestation; nonetheless, disseminated nocardiosis rarely involves the skin and subcutaneous tissues, and this occurs as a result of metastatic spread. Our cases were disseminated nocardiosis in which the metastatic cutaneous involvement, even if rare, provided a clue for the diagnosis. CONCLUSIONS: The pathomorphosis of disseminated nocardiosis may have changed in the current years with more rapid spread due to advanced immunosuppression. For this reason, after clinical suspicion, the prompt start of an active targeted therapy based on rapid microbiological identification might potentially open the way to hopeful results, even in the most immune-compromised patients.