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Objectives To analyse the impact of cefiderocol use on outcome in patients admitted to the ICU for severe COVID-19 and further diagnosed with carbapenem-resistant Acinetobacter baumannii (CR-Ab) infection. Methods Retrospective multicentre observational study was performed at four Italian hospitals, from January 2020 to April 2021. Adult patients admitted to ICU for severe COVID-19 and further diagnosed with CR-Ab infections were enrolled. Patients treated with cefiderocol, as compassionate use, for at least 72 h were compared with those receiving alternative regimens. Primary endpoint was all-cause 28 day mortality. The impact of cefiderocol on mortality was evaluated by multivariable Cox regression model. Results In total, 107 patients were enrolled (76% male, median age 65 years). The median time from ICU admission to CR-Ab infection diagnosis was 14 (IQR 8–20) days, and the main types of CR-Ab infections were bloodstream infection (58%) and lower respiratory tract infection (41%). Cefiderocol was administered to 42 patients within a median of 2 (IQR 1–4) days after CR-Ab infection diagnosis and as monotherapy in all cases. The remaining patients received colistin, mostly (82%) administered as combination therapy. All-cause 28 day mortality rate was 57%, without differences between groups (cefiderocol 55% versus colistin 58% P = 0.70). In multivariable analysis, the independent risk factor for mortality was SOFA score (HR 1.24, 95% CI 1.15–1.38, P Conclusions Our study confirms the potential role of cefiderocol in the treatment of CR-Ab infection, but larger clinical studies are needed.

Background: Limited and wide-ranging data are available on the recurrent Clostridioides difficile infection (rCDI) incidence rate. Methods: We performed a cohort study with the aim to assess the incidence of and risk factors for rCDI. Adult patients with a first CDI, hospitalized in 15 Italian hospitals, were prospectively included and followed-up for 30 d after the end of antimicrobial treatment for their first CDI. A case–control study was performed to identify risk factors associated with 30-day onset rCDI. Results: Three hundred nine patients with a first CDI were included in the study, 32% of the CDI episodes (99/309) were severe/complicated, complete follow-up was available for 288 patients (19 died during the first CDI episode, and 2 were lost during follow-up). At the end of the study, the crude all-cause mortality rate was 10.7% (33 deaths/309 patients). Two hundred seventy-one patients completed the follow-up, rCDI occurred in 21% of patients (56/271) with an incidence rate of 72/10,000 patient-days. Logistic regression analysis identified exposure to cephalosporin as an independent risk factor associated with rCDI (RR: 1.7, 95% CI: 1.1–2.7, p = 0.03). Conclusion: Our study confirms the relevance of rCDI in terms of morbidity and mortality and provides a reliable estimation of its incidence.

Objectives: We aimed to develop and validate a risk score to predict severe respiratory failure (SRF) among patients hospitalized with coronavirus disease-2019 (COVID-19). Methods: We performed a multicentre cohort study among hospitalized (>24 hours) patients diagnosed with COVID-19 from 22 February to 3 April 2020, at 11 Italian hospitals. Patients were divided into derivation and validation cohorts according to random sorting of hospitals. SRF was assessed from admission to hospital discharge and was defined as: SpO2 30 breaths/min or respiratory distress. Multivariable logistic regression models were built to identify predictors of SRF, β-coefficients were used to develop a risk score. Trial Registration NCT04316949. Results: We analysed 1113 patients (644 derivation, 469 validation cohort). Mean (±SD) age was 65.7 (±15) years, 704 (63.3%) were male. SRF occurred in 189/644 (29%) and 187/469 (40%) patients in the derivation and validation cohorts, respectively. At multivariate analysis, risk factors for SRF in the derivation cohort assessed at hospitalization were age ≥70 years (OR 2.74; 95% CI 1.66–4.50), obesity (OR 4.62; 95% CI 2.78–7.70), body temperature ≥38°C (OR 1.73; 95% CI 1.30–2.29), respiratory rate ≥22 breaths/min (OR 3.75; 95% CI 2.01–7.01), lymphocytes ≤900 cells/mm3 (OR 2.69; 95% CI 1.60–4.51), creatinine ≥1 mg/dL (OR 2.38; 95% CI 1.59–3.56), C-reactive protein ≥10 mg/dL (OR 5.91; 95% CI 4.88–7.17) and lactate dehydrogenase ≥350 IU/L (OR 2.39; 95% CI 1.11–5.11). Assigning points to each variable, an individual risk score (PREDI-CO score) was obtained. Area under the receiver-operator curve was 0.89 (0.86–0.92). At a score of >3, sensitivity, specificity, and positive and negative predictive values were 71.6% (65%–79%), 89.1% (86%–92%), 74% (67%–80%) and 89% (85%–91%), respectively. PREDI-CO score showed similar prognostic ability in the validation cohort: area under the receiver-operator curve 0.85 (0.81–0.88). At a score of >3, sensitivity, specificity, and positive and negative predictive values were 80% (73%–85%), 76% (70%–81%), 69% (60%–74%) and 85% (80%–89%), respectively. Conclusion: PREDI-CO score can be useful to allocate resources and prioritize treatments during the COVID-19 pandemic.

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Marjolin’s ulcer is a squamous cell carcinoma (SCC) arising from any site of established chronic inflammation, especially with presence of scar tissue.An emblematic case report of locally disseminated SCC arising from a chronic osteomyelitis of the left leg complicated by recurring soft tissue infections lasting since 46 years is presented and discussed according to the available international literature evidence. Concurrent diseases, supporting factors, clinical and histopathological presentation, differential diagnosis, and time and mode of management of this potentially functional- and life-threatening pathological condition are reviewed and discussed to offer a theme to daily clinical care.

Objective: To assess the predictive value of superficial ulcer swab culture to make a microbiological diagnosis of deep wound infections in spinal cord injury (SCI) patients with advanced-stage pressure ulcers.Methods: From July 2011 to February 2014, we performed a prospective, single-centre study on adult SCI patients undergoing scheduled surgical debridement and reconstruction for advanced-stage pressure ulcers, at Montecatone Rehabilitation Institute, a 150-bed hospital dedicated to SCI care. Three superficial ulcer swabs were preoperatively collected using the Levine technique, then sent for culture. In surgery, multiple bone and soft-tissue specimens were taken and sent for culture and histological examination. No antibiotics were administered before surgery. The results of swabs and intraoperative specimens were compared.Results: In all, 116 patients were included, median age 49 years; a majority were males with post-traumatic paraplegia. According to intraoperative specimen cultures, the most common microorganisms were Staphylococcus aureus, Proteus mirabilis, and Pseudomonas aeruginosa, found in 31, 27, and 16 cases, respectively. Concordance between superficial swabs and intraoperative specimen culture was found in only in 25 out of 116 cases (22%). The main reason for non-concordance was the yielding of different micro-organisms (41 out of 116); false negatives (swab negative/intraoperative positive) accounted for 31 out of 116 and false positives (swab positive/intraoperative negative) for 19 out of 116. When compared with intraoperative specimens, sensitivity and specificity of the swab culture were 80% and 54%, respectively.Conclusions: Our results confirm that in patients with advanced-stage pressure ulcers, the cultures of a superficial ulcer swab are not useful in either the diagnosis of a superinfection or the prediction of the role of involved micro-organisms. (C) 2017 European Society of Clinical Microbiology and Infectious Diseases. Published by Elsevier Ltd. All rights reserved.

Background: Severe acute respiratory syndrome-coronavirus-2 (SARS-CoV-2)-associated coronavirus disease-2019 (COVID-19) is spreading worldwide challenging healthcare resources. To provide the best possible care for patients, efficient prognosis is needed. Methods: We performed a multicentre cohort study to develop and validate a risk score for severe respiratory failure (SRF) among hospitalized patients diagnosed with COVID-19. Study population included all adult patients with RT-PCR on nasopharyngeal swab positive for SARS-CoV-2, hospitalized from February 22 to April 3 2020, at 11 hospitals from four Italian Regions. Exclusion criteria were early ( 30bpm, or respiratory distress. Findings: Of the 1265 included patients, 1044 patients were analyzed, (581 derivation, 463 validation cohort). Mean age was 65.7±15 years, 661 (63·3%) were male. SRF rates were 29% and 38% in derivation and validation cohort, respectively. At multivariate analysis, risk factors for SRF in the derivation cohort were age ≥70 years, obesity, body temperature ≥38°C, RR ≥22bpm, lymphocytes ≤900/mm3, creatinine ≥ 1 mg/dl, C-reactive protein ≥10mg/dl, and lactate dehydrogenase ≥350IU/L at hospitalization. Area under receiver-operator curve (AUROC) was 0·90 (95%CI 0.86-0.93). Assigning points to each variable an individual risk score (PREDICO score) was obtained. At risk score of >3, sensitivity, specificity, positive and negative predictive values were 71·6% (64-78), 89·1% (85-92), 72·9% (65-79), and 88·4% (85-91), respectively; positive and negative likelihood ratios were 6·56 (95% CI 4·9-8·77) and 0·31 (95%CI 0·25-0·40), respectively. PREDICO score showed similar prognostic ability in the validation cohort: AUROC 0·80 (0·74-0·88). Interpretation: Using eight variables, easy to obtain at hospitalization, patients with COVID-19 could be classified according to their probability of developing SRF during hospitalization. PREDICO score can be useful to allocate resources and prioritize treatments during COVID-19 pandemic. Trial Registration: NCT04316949. Funding Statement: None. Declaration of Interests: Authors state no conflict of interest related to the content of the present study. Ethics Approval Statement: The study was approved by the Ethic Committee of the promoting center (Comitato Etico Indipendente di Area Vasta Emilia Centro, n. 283/2020/Oss/AOUBo).

We describe the high burden of carbapenemase-producing Enterobacteriaceae (CPE) colonization and infection in a neuro-rehabilitation hospital in Italy over a 6-year period. Overall, 9.3% of patients were found to be CPE carriers on admission; the rates of CPE in-hospital acquisition and CPE-BSI were 9.2 and 2.9 cases per 10,000 patient days, respectively.

PURPOSE: Acute infective endocarditis is a potentially life-threatening disease. Its outcome strongly depends on systemic embolization and extracardiac infections. When present, these conditions usually lead to a more aggressive therapeutic approach. However, the diagnosis of peripheral septic embolism is very challenging. (18)F-Fluorodeoxyglucose (FDG) positron emission tomography (PET)/CT has proven to be accurate for the detection of inflammatory diseases and occult infections. The aim of this study was to assess the added value of (18)F-FDG PET/CT in the detection of extracardiac embolisms in the evaluation of patients with suspected valvular endocarditis (VE). METHODS: Seventy-one patients with suspected infective endocarditis, enrolled between June 2010 and December 2012, underwent (18)F-FDG PET/CT with the standard procedure on a dedicated PET/CT scanner. Extracardiac findings were subsequently evaluated with other imaging procedures. RESULTS: Of the 71 patients with suspicion of infective endocarditis, we found unexpected extracardiac findings in 17 patients (24 \%) without any clinical suspicion. Extracardiac findings were subsequently evaluated with other imaging procedures. CONCLUSION: PET/CT detected unexpected extra sites of infection in 24 \% of cases, leading to changes in therapeutic management in a very relevant percentage of patients. These findings may have important therapeutic implications.

OBJECTIVETo assess the impact of an antimicrobial stewardship program (ASP) on antibiotic consumption, Clostridium difficile infections (CDI), and antimicrobial resistance patterns in a rehabilitation hospital.DESIGNQuasi-experimental study of the periods before (from January 2011 to June 2012) and after (from July 2012 to December 2014) ASP implementation.SETTING150-bed rehabilitation hospital dedicated to patients with spinal-cord injuries.INTERVENTIONBeginning in July 2012, an ASP was implemented based on systematic bedside infectious disease (ID) consultation and structural interventions (ie, revision of protocols for antibiotic prophylaxis and education focused on the appropriateness of antibiotic prescriptions). Antibiotic consumption, occurrence of CDI, and antimicrobial resistance patterns of selected microorganisms were compared between periods before and after the ASP implementation.RESULTSAntibiotic consumption decreased from 42 to 22 defined daily dose (DDD) per 100 patient days (PP=.01) and fluoroquinolones (from 11.8 to 0.99 DDD per 100 patient days; P=.006), with no increases in mortality or length of stay. The incidence of CDI decreased from 3.6 to 1.2 cases per 10,000 patient days (P=.001). Between 2011 and 2014, the prevalence of extensively drug-resistant (XDR) strains decreased from 55% to 12% in P. aeruginosa (PA. baumannii (P=.03). The prevalence of ESBL-producing strains decreased from 42% to 17% in E. coli (P=.0007) and from 62% to 15% in P. mirabilis (P=.0001). In K. pneumoniae, the prevalence of carbapenem-resistant strains decreased from 42% to 17% (P=.005), and the prevalence of in methicillin-resistant S. aureus strains decreased from 77% to 40% (PCONCLUSIONSAn ASP based on ID consultation was effective in reducing antibiotic consumption without affecting patient outcomes and in improving antimicrobial resistance patterns in a rehabilitation hospital.Infect Control Hosp Epidemiol. 2016;1–7

A probable case report of an abdominal botryomycosis has been hypothesized in a patient with a stable HIV infection under an effective antiretroviral therapy. Hyperpyrexia, abdominal pain and tenderness, and a thickening of small intestinal walls associated with multiple mesenteric adenopathies and a peritoneal involvement, prompted an ultrasonography-guided fine needle biopsy, and later a laparoscopy-laparotomy which excluded a neoplastic or lymphoproliferative disorders, showing only abundant fibrotic and necrotic-steatonecrotic tissue, with sparse multinuclear giant cells type Langhans. The prompt response to surgical intervention and a treatment with i.v. meropenem alone might be referred to a concurrent gram-negative infection of abdominal origin, until a late culture of an atypical Mycobacterium came to our attention over one month after the end of hospitalization. An updated literature search is presented and discussed, in relationship with the observed, extremely infrequent case reports of botryomycosis in different clinical settings.

OBJECTIVES: We performed a retrospective cohort study of HIV-infected antiretroviral-naïve patients starting a first antiretroviral therapy with tenofovir/emtricitabine plus efavirenz (EFV), atazanavir/ritonavir (ATV/r), or lopinavir/ritonavir (LPV/r). METHODS: The incidence of renal impairment or proximal tubular dysfunction was evaluated during a 12-month follow-up. Renal impairment was diagnosed by a reduced estimated glomerular filtration rate (eGFR) calculated using the Modification of Diet in Renal Disease (MDRD) formula, and tubular dysfunction was diagnosed when ≥ 2 among proteinuria, glucosuria, hypouricaemia, hypophosphataemia, and hypokalaemia, were identified. RESULTS: A total of 235 patients were enrolled: 82 taking EFV, 78 ATV/r, and 75 LPV/r. The mean decline in eGFR after the 12-month follow-up was significantly greater in subjects treated with ATV/r (-10.4 ml/min/1.73 m(2)) than in those receiving EFV (- 5.1; p = 0.002) or LPV/r (-4.8; p = 0.003). Similarly, a significantly higher incidence of proximal tubulopathy was observed among ATV/r-treated patients (14.1%) compared with patients receiving EFV (4.9%) or LPV/r (5.3%). CONCLUSIONS: In our retrospective study, naïve patients receiving tenofovir/emtricitabine and ATV/r for 12 months showed a significantly higher decline in eGFR and a significantly higher incidence of proximal tubulopathy than those receiving tenofovir/emtricitabine plus EFV or LPV/r, even though clinically evident renal toxicity associated with tenofovir-based treatment is a very uncommon event.

none 11 no Multidrug resistance associated with extended-spectrum beta-lactamase (ESBL) and Klebsiella pneumoniae carbapenemase (KPC) among K. pneumoniae is endemic in southern Europe. We retrospectively analyzed the impact of resistance on the appropriateness of empirical therapy and treatment outcomes of K. pneumoniae bloodstream infections (BSIs) during a 2-year period at a 1420-bed tertiary-care teaching hospital in northern Italy. We identified 217 unique patient BSIs, including 92 (42%) KPCpositive, 49 (23%) ESBL-positive, and 1 (0.5%) metallo-betalactamase-positive isolates. Adequate empirical therapy was administered in 74% of infections caused by non-ESBL non-KPC strains, versus 33% of ESBL and 23% of KPC cases (p

Recent studies have shown that rosuvastatin significantly decreases serum levels of inflammatory biomarkers and slows progression of carotid atherosclerosis in the general population. However, there are no data about its effect on progression of atherosclerosis in HIV-infected patients. Adult patients with HIV infection, on stable antiretroviral therapy, with asymptomatic carotid atherosclerosis and hypercholesterolemia, who started a rosuvastatin treatment at 10 mg daily during the period 2007-2009 were enrolled and followed-up for 24 months. Thirty-six patients (30 males) were enrolled, with a mean age of 49 years, a mean duration of current antiretroviral therapy of 38 months, and a mean 10-year risk of myocardial infarction of 18.5%. Rosuvastatin led to a significant decrease in mean values of intima-media thickness in all extracranial carotid arteries, with the greatest magnitude observed in carotid bifurcations (a mean decrease of 18.7% in the right artery and of 21.4% in the left artery) and in internal carotid arteries (a mean decrease of 23.7% in the right artery and of 25.6% in the left artery). Moreover, there was a significant reduction in mean levels of total cholesterol, low-density lipoprotein (LDL) cholesterol, and triglycerides versus respective baseline values associated with a significantly decreased mean cardiovascular risk. The treatment with rosuvastatin was well tolerated, and serious adverse events were not reported. A 24-month treatment with rosuvastatin in HIV-infected patients on highly active antiretroviral therapy (HAART) with subclinical atherosclerosis and a moderate cardiovascular risk seems to promote significantly favorable changes in carotid atherosclerosis, associated with a favorable effect on serum lipid levels and a good tolerability profile.

BACKGROUND: Statins are lipid-lowering drugs that exhibit anti-inflammatory and immune-modulatory properties, leading to a reduction of serum levels of C-reactive protein (CRP) in the general population. OBJECTIVE: Because very limited data are available today, our objective was to assess the lipid-lowering effects of statins and their capacity to decrease selected soluble markers of inflammation in HIV-infected patients. METHODS: Retrospective cohort study of HIV-infected adult patients with hypercholesterolemia who were receiving a stable antiretroviral regimen including a ritonavir-boosted protease inhibitor and who started a lipid-lowering therapy with rosuvastatin (10 mg daily), atorvastatin (10 mg daily), or pravastatin (40 mg daily) and were followed-up for at least 12 months. One hundred and fifty-one patients were enrolled in the study: 51 in the rosuvastatin group, 47 in the atorvastatin group, and 53 in the pravastatin group. The primary observation was change in plasma lipid levels and serum markers of inflammation (high-sensitivity C-reactive protein [hsCRP], interleukin-6 [IL-6], and tumor necrosis factor-α [TNF- α]), while secondary observations include immunovirological parameters and safety profile of statins. RESULTS: One year after starting the statin therapy, patients treated with rosuvastatin had significantly greater decreases in total cholesterol and LDL cholesterol than subjects on atorvastatin or pravastatin. All statins led to a similar, significant reduction in serum levels of hsCRP and TNF-α, without correlation between biomarkers and lipid values, and toxicity rates were similar for all 3 statins. CONCLUSION: Our findings suggest that rosuvastatin has a significantly greater lipid-lowering effect than atorvastatin or pravastatin, but all 3 statins exert a similar effect in lowering markers of inflammation as hsCRP and TNF-α.

OBJECTIVES: An observational, open-label study was performed to assess changes of lopinavir/ritonavir plasma concentrations during pregnancy. METHODS: Adult HIV-1-infected women during the third trimester of pregnancy and on stable antiretroviral treatment including zidovudine/lamivudine plus lopinavir/ritonavir tablets (400/100 mg twice daily) were asked to participate. This group was compared with a group of non-pregnant HIV-1-infected women receiving the same antiretroviral regimen. The trough plasma concentration (C(trough)) of lopinavir and ritonavir was assessed at steady-state by a validated high-performance liquid chromatography (HPLC)-tandem mass spectrometry method. RESULTS: A total of 41 HIV-positive female patients were enrolled in the study, with a median age of 28 y (range 20-37 y). These patients were stratified into 2 groups: 21 women in the third trimester of pregnancy (group A) and 20 non-pregnant women (group B). The geometric mean (95% confidence interval (CI)) plasma C(trough) of lopinavir was 4205 (2418-6896) ng/ml in group A and 5098 (3187-8084) ng/ml in group B. The reduction in lopinavir plasma levels observed in group A was not significant (geometric mean ratio 0.87, 95% CI 0.62-1.32; p = 0.411). No correlation was found between lopinavir plasma levels and adverse events (such as diarrhoea and hyperlipidaemia) or immunological parameters of HIV disease, and no changes in plasma HIV viral load were reported. CONCLUSION: In this study, a slight but not significant decrease in the plasma lopinavir C(trough) was found during the third trimester of pregnancy, suggesting that standard dosing of the tablet formulation is also appropriate during the later stages of pregnancy.

To better evaluate the renal safety profile of tenofovir, we performed a retrospective study of HIV-infected antiretroviral-naive patients starting a first antiretroviral therapy between July 2004 and July 2008, and followed-up for 24 months. The glomerular filtration rate (GFR) was calculated using the MDRD formula, and tubular dysfunction was diagnosed with 2 or more of the following: proteinuria, glucosuria, hypouricemia, hypophosphatemia and hypokalemia. Overall, 324 patients were enrolled: 201 were tenofovir-exposed and were compared with 123 tenofovir-unexposed subjects. In both the unadjusted and adjusted analyses, tenofovir-exposed subjects had a significantly greater decline in GFR and a significantly higher incidence of proximal tubular dysfunction through 24 months. Reduced glomerular and tubular functions were significantly associated with older age, diabetes, hypertension and concomitant therapy with a protease inhibitor.

Amiodarone, which has been used since 1967 as an antiarrhythmic drug, gives rise to a variety of cardiac and extracardiac adverse side-effects. Among these, pulmonary toxicity is considered the most frequent and serious extracardiac side-effect, since it may occur in various atypical forms and often limits the drug's clinical use. We encountered a 67-year-old white male patient with suspected amiodarone pneumonitis characterized by multiple lung nodules associated with pleural and pericardial effusion and peripheral neuropathy. Because differential diagnosis with pulmonary infectious diseases may be extremely difficult, the attending physician should therefore bear in mind the possibility of amiodarone pneumonitis whenever the drug is given.

Metabolic complications of antiretroviral therapy in HIV-infected patients include insulin resistance, diabetes mellitus, dyslipidaemia and lipodystrophy syndrome. Metabolic syndrome is an aggregation of central obesity with glucose and lipid metabolism alterations that confers an increased risk of cardiovascular disease, which reproduces the antiretroviral-associated metabolic and morphological abnormalities. In this study, we report the prevalence of diabetes mellitus, hyperinsulinaemia and metabolic syndrome among 755 adult patients with HIV-1 infection referred to our outpatients unit. The prevalence of diabetes mellitus and metabolic syndrome was 4.5% and 9.1%, respectively. A longer exposure to antiretroviral therapy and a diagnosis of lipodystrophy syndrome were significantly associated with both metabolic disturbances.