Epidemiology of Invasive Pulmonary Aspergillosis Among Intubated Patients With COVID-19: A Prospective Study.

BACKGROUND: We evaluated the incidence of invasive pulmonary aspergillosis among intubated patients with critical COVID-19 and evaluated different case definitions of invasive aspergillosis. METHODS: Prospective, multicenter study in adult patients with microbiologically confirmed COVID-19 receiving mechanical ventilation. All included participants underwent a screening protocol for invasive pulmonary aspergillosis with bronchoalveolar lavage galactomannan and cultures performed on admission at 7 days and in case of clinical deterioration. Cases were classified as coronavirus-associated pulmonary aspergillosis (CAPA) according to previous consensus definitions. The new definition was compared with putative invasive pulmonary aspergillosis (PIPA). RESULTS: 108 patients were enrolled. Probable CAPA was diagnosed in 30 (27.7%) patients after a median of 4 (2-8) days from intensive care unit (ICU) admission. Kaplan-Meier curves showed a significantly higher 30-day mortality rate from ICU admission among patients with either CAPA (44% vs 19%, P = .002) or PIPA (74% vs 26%, P < .001) when compared with patients not fulfilling criteria for aspergillosis. The association between CAPA (OR, 3.53; 95% CI, 1.29-9.67; P = .014) or PIPA (OR, 11.60; 95% CI, 3.24-41.29; P < .001) with 30-day mortality from ICU admission was confirmed, even after adjustment for confounders with a logistic regression model. Among patients with CAPA receiving voriconazole treatment (13 patients; 43%) a trend toward lower mortality (46% vs 59%; P = .30) and reduction in galactomannan index in consecutive samples were observed. CONCLUSIONS: We found a high incidence of CAPA among critically ill COVID-19 patients and its occurrence seems to change the natural course of disease.

Potential role of T2Candida in the management of empirical antifungal treatment in patients at high risk of candidaemia: a pilot single-centre study.

Objectives: We estimated the diagnostic accuracy of T2Candida, with blood culture (BC) as the gold standard, and compared turnaround time between these two techniques in order to investigate the potential role of T2Candida in the management of empirical antifungal treatment (EAT). Methods: We performed a single-centre prospective observational study in patients with severe sepsis or septic shock and multiple risk factors for candidaemia. Results: We analysed 46 out of 50 screened patients. All patients received an echinocandin as EAT; the median EAT duration was 7 days (IQR 4-13 days). BCs were negative in 31 (67.4%) patients, positive for bacteria in 14 (30.4%) patients and positive for Candida albicans in 1 (2.2%) patient. T2Candida was negative, invalid and positive in 37, 5 and 4 patients, respectively. T2Candida and BC results were concordant in all but three patients, where T2Candida was positive and BCs were negative. Two of them were on antifungal prophylaxis at the time of enrolment. T2Candida reduced time to a negative result by 5 days. T2Candida performance was: sensitivity = 100% (95% CI 2.5%-100%), specificity = 91.8% (95% CI 78%-98%), positive predictive value = 25% (95% CI 0.63%-80.6%) and negative predictive value = 100% (95% CI 89.7%-100%). Conclusions: In patients with multiple risk factors for candidaemia and severe sepsis or septic shock, T2Candida may be helpful to reduce the length of EAT.

Infectious Diseases Team for the Early Management of Severe Sepsis and Septic Shock in the Emergency Department.

Background: The impact on patient survival of an infectious disease (ID) team dedicated to the early management of severe sepsis/septic shock (SS/SS) in Emergency Department (ED) has yet to be assessed. Methods: A quasiexperimental pre-post study was performed at the general ED of our hospital. During the pre phase (June 2013-July 2014), all consecutive adult patients with SS/SS were managed according to the standard of care, data were prospectively collected. During the post phase (August 2014-October 2015), patients were managed in collaboration with a dedicated ID team performing a bedside patient evaluation within 1 hour of ED arrival. Results: Overall, 382 patients were included, 195 in the pre phase and 187 in the post phase. Median age was 82 years (interquartile range, 70-88). The most common infection sources were lung (43%) and urinary tract (17%); in 22% of cases, infection source remained unknown. During the post phase, overall compliance with the Surviving Sepsis Campaign (SSC) bundle and appropriateness of initial antibiotic therapy improved from 4.6% to 32% (P < .001) and from 30% to 79% (P < .001), respectively. Multivariate analysis showed that predictors of all-cause 14-day mortality were quick sepsis-related organ failure assessment ≥2 (hazard ratio [HR], 1.68; 95% confidence interval [CI], 1.15-2.45; P = .007), serum lactate ≥2 mmol/L (HR, 2.13; 95% CI, 1.39-3.25; P < .001), and unknown infection source (HR, 2.07; 95% CI, 1.42-3.02; P < .001); being attended during the post phase was a protective factor (HR, 0.64; 95% CI, 0.43-0.94; P = .026). Conclusion: Implementation of an ID team for the early management of SS/SS in the ED improved the adherence to SSC recommendations and patient survival.

¹8F-FDG PET/CT diagnosis of unexpected extracardiac septic embolisms in patients with suspected cardiac endocarditis.

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.

Incidence of renal toxicity in HIV-infected, antiretroviral-naïve patients starting tenofovir/emtricitabine associated with efavirenz, atazanavir/ritonavir, or lopinavir/ritonavir.

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.

Healthcare-associated infections and antimicrobial resistance in severe acquired brain injury: a retrospective multicenter study.

Background: Recent studies underscore that healthcare-associated infections (HAIs) and multidrug-resistant (MDR) HAIs affect rehabilitation outcomes and hospital length of stay (LOS) for severe acquired brain injury (sABI). Objective: This study aimed to estimate HAI incidence in different sABI rehabilitation settings and determine risk factors and HAI impact on neuromotor and cognitive recovery. Methods: We conducted a retrospective multicenter study in two semi-intensive units (SICUs), two high-specialty post-acute units (PAUs), and one long-term care (LTC) rehabilitation facility. Data extraction was performed by experienced clinicians, using a structured Excel file and they agreed upon criteria for case definitions of healthcare. The main outcome measures were the HAI and MDR HAI incidence and the LOS, the functional recovery was measured using the Level of Cognitive Functioning and Disability Rating Scale. Results: There were 134 sABI participants. The calculation of the probability level was adjusted for three pairwise comparisons among settings (0.05/3 = 0.017). The HAI and MDR HAI incidences were significantly higher in SICU (3.7 and 1.3 per 100 person-days) than in other settings (LTC: 1.9, p = 0.034 and 0.5, p = 0.026; PAU: 1.2, p < 0.001 and 0.3, p < 0.001). HAI and MDR HAI risk variables included older age, an increased number of devices, and carbapenemase-producing Enterobacteriaceae (CPE) colonization, while a high prealbumin plasma value seemed to have a protective effect. Conclusion: HAIs are related to longer LOS, and colonization is associated with poor prognosis and poor functional outcomes with reduced ability to achieve the cognitive capacity of self-care, employability, and independent living. The need to ensure the protection of non-colonized patients, especially those with severe disabilities on admission, is highlighted.

Statin therapy decreases serum levels of high-sensitivity C-reactive protein and tumor necrosis factor-α in HIV-infected patients treated with ritonavir-boosted protease inhibitors.

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.

Lopinavir/ritonavir trough concentrations with the tablet formulation in HIV-1-infected women during the third trimester of pregnancy.

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.

A Proof of Concept of the Usefulness of a TDM-Guided Strategy for Optimizing Pharmacokinetic/Pharmacodynamic Target of Continuous Infusion Ampicillin-Based Regimens in a Case Series of Patients with Enterococcal Bloodstream Infections and/or Endocarditis.

(1) Objective: To describe the usefulness of a real-time therapeutic drug monitoring (TDM)-based strategy for optimizing pharmacokinetic/pharmacodynamic (PK/PD) target attainment of continuous infusion (CI) ampicillin-based regimens in a case series of patients affected by suspected or documented enterococcal bloodstream infections (BSIs) and/or infective endocarditis (IE). (2) Methods: Patients treated with CI ampicillin-based regimens for documented or suspected enterococcal BSI/IE who underwent real-time therapeutic drug monitoring (TDM)-based expert clinical pharmacological advice (ECPA) between June 2021 and May 2022 were retrospectively assessed. Ampicillin concentrations were determined at steady state, and the free fraction (fCss) was calculated according to a plasma protein binding of 20%. The fCss/MIC ratio was selected as the PD parameter for ampicillin efficacy and was defined as optimal for values between 4 and 8. The requirement for TDM-guided ampicillin dosing adjustments was assessed. (3) Results: Data for 12 patients with documented (n = 10) or suspected (n = 2) enterococcal infections (7 with BSIs and 5 with IE) were retrieved. The ampicillin PK/PD target was optimal over time in all of the 10 documented infections. None of the enterococcal BSIs persisted. Following the first real-time TDM-based ECPA, ampicillin dosage was decreased by >50% in 11 out of 12 patients (91.7%). (4) Conclusions: CI may be helpful in attaining aggressive ampicillin PK/PD targets in patients affected by enterococcal BSIs and/or IE. Administration of CI ampicillin after loading coupled with real-time TDM-based ECPA could be a valuable strategy for managing enterococcal infections.

Relationship between Pharmacokinetic/Pharmacodynamic Target Attainment and Microbiological Outcome in Critically Ill COVID-19 Patients with Documented Gram-Negative Superinfections Treated with TDM-Guided Continuous-Infusion Meropenem.

Objectives: The objective of this study was to explore the relationship between pharmacokinetic/pharmacodynamic (PK/PD) target attainment of continuous-infusion (CI) meropenem and microbiological outcome in critical COVID-19 patients with documented Gram-negative superinfections. Methods: Patients receiving CI meropenem for documented Gram-negative infections at the COVID ICU of the IRCCS Azienda Ospedaliero-Universitaria di Bologna and undergoing therapeutic drug monitoring from January 2021 to February 2022 were retrospectively assessed. Average steady-state meropenem concentrations (Css) were calculated and the Css/MIC ratio was selected as a pharmacodynamic parameter of meropenem efficacy. The Css/MIC ratio was defined as optimal if ≥4, quasi-optimal if between 1 and 4, and suboptimal if <1. The relationship between Css/MIC and microbiological outcome was assessed. Results: Overall, 43 critical COVID-19 patients with documented Gram-negative infections were retrieved. Combination therapy was implemented in 26 cases. Css/MIC ratios were optimal in 27 (62.8%), quasi-optimal in 7 (16.3%), and suboptimal in 9 cases (20.9%). Microbiological failure occurred in 21 patients (48.8%), with no difference between monotherapy and combination therapy (43.8% vs. 53.8%; p = 0.53). The microbiological failure rate was significantly lower in patients with an optimal Css/MIC ratio compared to those with a quasi-optimal or suboptimal Css/MIC ratio (33.3% vs. 75.0%; p = 0.01). Conclusion: Suboptimal attainment of meropenem PK/PD targets may be a major determinant impacting on microbiological failure in critical COVID-19 patients with Gram-negative superinfections.

Neutralizing monoclonal antibodies for early treatment of hospital-acquired SARS-CoV-2 infection in hematologic patients.

Efficacy of early treatment with anti-SARS-CoV-2 spike protein monoclonal antibodies (mAbs) for nosocomial SARS-CoV-2 infection in hematologic patients is unknown. Retrospective, cohort study conducted in four Italian teaching hospitals. We included adult patients with hematologic malignancies and hospital-acquired SARS-CoV-2 infection diagnosed between November 2020 and December 2021. The principal exposure variable was administration of mAbs. The primary endpoint was clinical failure dea composite outcome of mortality and/or invasive and noninvasive ventilation within 90 days from infection onset. We included 52 patients with hospital-acquired SARS-CoV-2 infection. Males were 29 (60%), median age was 62 (interquartile range [IQR] 48-70). Forty-five (86%) patients were on chemotherapy or had received chemotherapy within 30 days. MAbs were administered in 19/52 (36%) patients. Clinical failure occurred in 22 (42%) patients; 21% (4/19) in mAbs group versus 54% (18/33) in non-mAbs group (p = 0.03). Other predictors of clinical failure were older age (median [IQR] 69 [61-72] versus 58 [46-66], p = 0.001), and higher Charlson comorbidity index (median [IQR], 5 [3.25-5] versus 3 [2-5], p = 0.002). At multivariable Cox regression model, mAbs were independently associated with a significantly lower rate of clinical failure (HR 0.11, 95% CI 0.01-0.85, p = 0.01), after adjusting for confounders. In conclusion, mAbs are promising for early treatment of hematologic patients with healthcare-related SARS-CoV-2 infection.

Oral Versus Standard Antimicrobial Treatment for Pyogenic Native Vertebral Osteomyelitis: A Single-Center, Retrospective, Propensity Score-Balanced Analysis.

Background: Interest in shorter antimicrobial regimens and oral treatment for osteoarticular infections is growing. The aim of this study is to assess whether there is an association between the administration of an entirely oral antibiotic therapy (OT) and the clinical outcome of native vertebral osteomyelitis (NVOs). Methods: We conducted a single-center, retrospective, observational study on consecutive patients with pyogenic NVOs over a 10-year period (2008-2018). We performed multivariate logistic regression analysis to identify risk factors for clinical failure, both in the whole population and in subgroups. The impact of OT versus standard treatment (intravenous induction followed by oral treatment whenever possible) was assessed in patients with a non-multidrug-resistant microorganism (MDRO) etiology, and the impact of a rifampin-containing regimen was assessed in patients affected by NVOs caused by staphylococci or of unknown etiology. Results: The study population included 249 patients, and 33 (13.3%) experienced clinical failure; the OT group consisted of 54 patients (21.7%). Multivariate regression analysis of the whole population selected Charlson comorbidity index (adjusted odds ratio [aOR], 1.291; 95% confidence interval [CI], 1.114-1.497; P = .001) and MDRO etiology (aOR, 3.301; 95% CI, 1.368-7.964; P = .008) as independent factors for clinical failure. Among patients affected by a non-MDRO NVO, OT was not associated with an increased risk of clinical failure (aOR, 0.487; 95% CI, .133-1.782; P = .271), even after adjustment for the propensity score of receiving OT. In the subgroup of patients with staphylococcal or unknown etiology, NVO rifampin was independently associated with favorable outcome (aOR, 0.315; 95% CI, .105-.949; P = .040). Conclusions: An entirely oral, highly bioavailable treatment, including rifampin, may be as effective as parenteral treatment in selected patients with NVOs.

Tenofovir-induced renal toxicity in 324 HIV-infected, antiretroviral-naïve patients.

To better evaluate the renal safety profile of tenofovir, we performed a retrospective study of HIV-infected antiretroviral-naïve 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.

Cefiderocol treatment for carbapenem-resistant Acinetobacter baumannii infection in the ICU during the COVID-19 pandemic: a multicentre cohort study.

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 < 0.001). Cefiderocol was associated with a non-significant lower mortality risk (HR 0.64, 95% CI 0.38-1.08, P = 0.10). CONCLUSIONS: Our study confirms the potential role of cefiderocol in the treatment of CR-Ab infection, but larger clinical studies are needed.

Prospective Study on Incidence, Risk Factors and Outcome of Recurrent Clostridioides difficile Infections.

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.

The Burden of Clostridioides Difficile Infection during the COVID-19 Pandemic: A Retrospective Case-Control Study in Italian Hospitals (CloVid).

Data on the burden of Clostridioides difficile infection (CDI) in Coronavirus Disease 2019 (COVID-19) patients are scant. We conducted an observational, retrospective, multicenter, 1:3 case (COVID-19 patients with CDI)-control (COVID-19 patients without CDI) study in Italy to assess incidence and outcomes, and to identify risk factors for CDI in COVID-19 patients. From February through July 2020, 8402 COVID-19 patients were admitted to eight Italian hospitals; 38 CDI cases were identified, including 32 hospital-onset-CDI (HO-CDI) and 6 community-onset, healthcare-associated-CDI (CO-HCA-CDI). HO-CDI incidence was 4.4 × 10,000 patient-days. The percentage of cases recovering without complications at discharge (i.e., pressure ulcers, chronic heart decompensation) was lower than among controls (p = 0.01); in-hospital stays was longer among cases, 35.0 versus 19.4 days (p = 0.0007). The presence of a previous hospitalisation (p = 0.001), previous steroid administration (p = 0.008) and the administration of antibiotics during the stay (p = 0.004) were risk factors associated with CDI. In conclusions, CDI complicates COVID-19, mainly in patients with co-morbidities and previous healthcare exposures. Its association with antibiotic usage and hospital acquired bacterial infections should lead to strengthen antimicrobial stewardship programmes and infection prevention and control activities.

Development and validation of a prediction model for severe respiratory failure in hospitalized patients with SARS-CoV-2 infection: a multicentre cohort study (PREDI-CO study).

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 <93% with 100% Fio2, respiratory rate >30 breaths/min or respiratory distress. Multivariable logistic regression models were built to identify predictors of SRF, ß-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.

The burden of colonization and infection by carbapenemase-producing Enterobacteriaceae in the neuro-rehabilitation setting: a prospective six-year experience.

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.