Antibiotic Resistance to Molecules Commonly Prescribed for the Treatment of Antibiotic-Resistant Gram-Positive Pathogens: What Is Relevant for the Clinician?

Antibiotic resistance in Gram-positive pathogens is a relevant concern, particularly in the hospital setting. Several antibiotics are now available to treat these drug-resistant pathogens, such as daptomycin, dalbavancin, linezolid, tedizolid, ceftaroline, ceftobiprole, and fosfomycin. However, antibiotic resistance can also affect these newer molecules. Overall, this is not a frequent phenomenon, but it is a growing concern in some settings and can compromise the effectiveness of these molecules, leaving few therapeutic options. We reviewed the available evidence about the epidemiology of antibiotic resistance to these antibiotics and the main molecular mechanisms of resistance, particularly methicillin-resistant Sthaphylococcus aureus, methicillin-resistant coagulase-negative staphylococci, vancomycin-resistant Enterococcus faecium, and penicillin-resistant Streptococcus pneumoniae. We discussed the interpretation of susceptibility tests when minimum inhibitory concentrations are not available. We focused on the risk of the emergence of resistance during treatment, particularly for daptomycin and fosfomycin, and we discussed the strategies that can be implemented to reduce this phenomenon, which can lead to clinical failure despite appropriate antibiotic treatment. The judicious use of antibiotics, epidemiological surveillance, and infection control measures is essential to preserving the efficacy of these drugs.

Which Are the Best Regimens of Broad-Spectrum Beta-Lactam Antibiotics in Burn Patients? A Systematic Review of Evidence from Pharmacology Studies.

BACKGROUND: Burn injury causes profound pathophysiological changes in the pharmacokinetic/pharmacodynamic (PK/PD) properties of antibiotics. Infections are among the principal complications after burn injuries, and broad-spectrum beta-lactams are the cornerstone of treatment. The aim of this study was to review the evidence for the best regimens of these antibiotics in the burn patient population. METHODS: We performed a systematic review of evidence available on MEDLINE (from its inception to 2023) of pharmacology studies that focused on the use of 13 broad-spectrum beta-lactams in burn patients. We extracted and synthetized data on drug regimens and their ability to attain adequate PK/PD targets. RESULTS: We selected 35 studies for analysis. Overall, studies showed that both high doses and the continuous infusion (CI) of broad-spectrum beta-lactams were needed to achieve internationally-recognized PK/PD targets, ideally with therapeutic drug monitoring guidance. The most extensive evidence concerned meropenem, but similar conclusions could be drawn about piperacillin-tazobactam, ceftazidime, cefepime, imipenem-clinastatin and aztreonam. Insufficient data were available about new beta-lactam-beta-lactamase inhibitor combinations, ceftaroline, ceftobiprole and cefiderocol. CONCLUSIONS: Both high doses and CI of broad-spectrum beta-lactams are needed when treating burn patients due to the peculiar changes in the PK/PD of antibiotics in this population. Further studies are needed, particularly about newer antibiotics.

Scientific literature on neglected tropical diseases: a bibliometric analysis.

Neglected tropical diseases (NTDs) are a group of diseases mainly affecting people in low- and middle-income Countries. The aim of this study was to perform a bibliometric analysis of the scientific literature on NTDs. Using the MeSH database, we quantified the number of publications on MEDLINE targeting each NTD, which were published from 1 January 1999 to 31 January 2019. In order to weight the number of publications targeting a given NTD according to the total number of publications/year, we calculated a Yearly Publication Index (YPI) for each NTD/year. Linear regression was used to determine if there was a significant increase or decrease of YPI over time. In order to weight the number of publications according to disease burden (expressed in Disability-adjusted life years - DALYs) we calculated a DALYs-weighted Publication Index (DWPI) for each NTD. The highest absolute number of publications focused on leishmaniasis, dengue and Chagas disease; the lowest on tungiasis, dracunculiasis, chromoblastomycosis and yaws. The number of publications significantly increased for chikungunya, chromoblastomycosis, dengue, leishmaniasis, snakebite envenoming, and yaws. It significantly decreased for ascariasis, cysticercosis, echinococcosis, leprosy, lymphatic filariasis, mycetoma, onchocerciasis. Leprosy had the highest DWPI (i.e. the highest number of publication considering the burden of disease), followed by Chagas disease; lymphatic filariasis had the lowest, followed by onchocerciasis. Overall, lymphatic filariasis, onchocerciasis and ascariasis presented the worst scenario, with both very few publications compared with their disease burden and a decreasing number of publications.

Alarming correlation between multidrug-resistant bacteriobilia and morbidity after pancreatic surgery.

BACKGROUND: Pancreatic surgery is characterized by high morbidity and mortality. Biliary colonization may affect clinical outcomes in these patients. AIMS: This study aimed to verify whether bacteriobilia and multidrug resistance (MDR) detected during and after pancreatic surgery may have an impact on post-operative outcomes. METHODS: Data from patients undergoing pancreatic surgery involving bile duct transection (2016-2022) in two high-volume centers were analyzed in relationship to overall morbidity, major morbidity and mortality after pancreato-duodenectomy (PD) or total pancreatectomy (TP). Simple and multivariable regressions were used. RESULTS: 227 patients submitted to PD (n=129) or TP (n=98) were included. Of them, 133 had preoperative biliary drainage (BD; 56.6%), mostly with the employment of endoscopic stents (91.7%). Bacteriobilia was detected in 111 patients (48.9%), and remarkably, observed in patients with BD (p=0.001). In addition, 25 MDR pathogens were identified (22.5%), with a significant prevalence in patients with BD. Multivariable regression analysis showed BD was strongly related to MDR isolation (odds ratio [OR]: 5.61; p=0.010). MDR isolation was the main factor linked to a higher number of major complications (OR: 2.75; p=0.041), including major infection complications (OR: 2.94; p=0.031). CONCLUSIONS: Isolation of MDR from biliary swab during PD or TP significantly increases the risk of a worse post-operative outcome. Pre-operative precautions could improve patient safety.

Infection-Related Ventilator-Associated Complications in Critically Ill Patients with Trauma: A Retrospective Analysis.

BACKGROUND: Trauma is a leading cause of death and disability. Patients with trauma undergoing invasive mechanical ventilation (IMV) are at risk for ventilator-associated events (VAEs) potentially associated with a longer duration of IMV and increased stay in the intensive care unit (ICU). METHODS: We conducted a retrospective cohort study aimed to evaluate the incidence of infection-related ventilator-associated complications (IVACs), possible ventilator-associated pneumonia (PVAP), and their characteristics among patients experiencing severe trauma that required ICU admission and IMV for at least four days. We also determined pathogens implicated in PVAP episodes and characterized the use of antimicrobial therapy. RESULTS: In total, 88 adult patients were included in the main analysis. In this study, we observed that 29.5% of patients developed a respiratory infection during ICU stay. Among them, five patients (19.2%) suffered from respiratory infections due to multi-drug resistant bacteria. Patients who developed IVAC/PVAP presented lower total GCS (median value, 7; (IQR, 9) vs. 12.5, (IQR, 8); p = 0.068) than those who did not develop IVAC/PVAP. CONCLUSIONS: We observed that less than one-third of trauma patients fulfilling criteria for ventilator associated events developed a respiratory infection during the ICU stay.

A Proposal for a Classification Guiding the Selection of Appropriate Antibiotic Therapy for Intra-Abdominal Infections.

Adequately controlling the source of infection and prescribing appropriately antibiotic therapy are the cornerstones of the management of patients with intra-abdominal infections (IAIs). Correctly classifying patients with IAIs is crucial to assessing the severity of their clinical condition and deciding the strategy of the treatment, including a correct empiric antibiotic therapy. Best practices in prescribing antibiotics may impact patient outcomes and the cost of treatment, as well as the risk of "opportunistic" infections such as Clostridioides difficile infection and the development and spread of antimicrobial resistance. This review aims to identify a correct classification of IAIs, guiding clinicians in the selection of the best antibiotic therapy in patients with IAIs.

Model of Care for Microelimination of Hepatitis C Virus Infection among People Who Inject Drugs.

BACKGROUND: People who inject drugs (PWID) are the largest group at risk for HCV infection. Despite the direct acting antivirals (DAA) advancements, HCV elimination has been hindered by real-life difficulties in PWID. AIMS: This study aimed to assess the impact of a multidisciplinary intervention strategy where HCV screening, treatment and follow-up were performed at the same location on efficacy and safety of DAA-therapy in real-life PWID population. METHODS: All HCV-infected PWID referred to five specialized outpatient centers for drug addicts (SerDs) in Northern Italy were prospectively enrolled from May 2015 to December 2019. Hepatologists and SerDs healthcare workers collaborated together in the management of PWID inside the SerDs. Sustained virologic response (SVR), safety of treatment, proportion of patients lost to follow-up and reinfection rate were evaluated. RESULTS: A total of 358 PWID started antiviral treatment. About 50% of patients had advanced fibrosis/cirrhosis, 69% received opioid substitution treatment, and 20.7% self-reported recent injecting use. SVR was achieved in 338 (94.4%) patients. Two patients died during treatment; one prematurely discontinued, resulting in a non-responder; twelve were lost during treatment/follow-up; and five relapsed. No serious adverse events were reported. SVR was lower in recent PWID than in former ones (89.2% vs. 95.8%; p = 0.028). Seven reinfections were detected, equating to an incidence of 1.25/100 person-years. Reinfection was associated with recent drug use (OR 11.07, 95%CI 2.10-58.38; p = 0.005). CONCLUSION: Our embedded treatment model could be appropriate to increase the linkage to care of HCV-infected PWID. In this setting, DAA regimens are well tolerated and highly effective, achieving a lower rate of reinfection.

Patients with HIV and cirrhosis: the risk for hepatocellular carcinoma after direct-acting antivirals for hepatitis C virus.

OBJECTIVES: Hepatocellular carcinoma (HCC) has become a major issue in coinfected HIV/HCV patients with liver cirrhosis. We aimed to determine the rate of HCC occurrence after a direct-acting antiviral (DAA) treatment and to evaluate the factors associated with the risk of HCC in this population. DESIGN: We conducted a retrospective multicenter observational study including cirrhotic HIV/HCV-coinfected patients treated with DAAs, between October 2014 and January 2017. METHODS: We collected demographics characteristics, data regarding HIV and HCV infections and treatment with DAAs. We investigated the rate and the time of occurrence of HCC. Statistical analysis explored the factors associated to development of liver cancer. RESULTS: During a median follow-up of 55 months, 24 out of 232 patients developed HCC, after a median of 22.5 months from starting DAAs. Factors associated with HCC were a higher Child--Pugh Turcotte (CPT) score (P = 0.002), HCV genotype 3 (P = 0.04), previous HCC (P < 0.001) and CD4+ cell count nadir greater than 350 cells/µl (P = 0.001), whereas antiretroviral therapy (ART) was associated to a lower rate of cancer (P = 0.02). At multivariable analysis CPT score and a history of HCC remained independently associated with HCC after DAAs (P = 0.003 and P < 0.001, respectively), and ART administration maintained its protective role (P = 0.047), regardless of HIV RNA at baseline. CONCLUSION: Our study highlights the importance of a long-lasting follow-up for HCC after HCV eradication, mostly in those patients with advanced cirrhosis and history of HCC. Furthermore, our data showed a potential role of ART itself (and not of undetectable HIV RNA) in reducing the risk for HCC development.

Breakthrough invasive fungal infection after liver transplantation in patients on targeted antifungal prophylaxis: A prospective multicentre study.

OBJECTIVE: To investigate the rate of and the risk factors for breakthrough-IFI (b-IFI) after orthotopic liver transplantation (OLT) according to the new definition proposed by Mycoses-Study-Group-Education-and-Research-Consortium (MSG-ERC) and the European-Confederation-of-Medical-Mycology (ECMM). METHODS: Multicenter prospective study of adult patients who underwent OLT at three Italian hospitals, from January 2015 to December 2018. Targeted antifungal prophylaxis (TAP) protocol was developed and shared among participating centers. Follow-up was 1-year after OLT. B-IFI was defined as infection occurring during exposure to antifungal prophylaxis. Risk factors for b-IFI were analyzed among patients exposed to prophylaxis by univariable analysis. RESULTS: We enrolled 485 OLT patients. Overall compliance to TAP protocol was 64.3%, 220 patients received antifungal prophylaxis, 172 according to TAP protocol. Twenty-nine patients were diagnosed of IFI within 1 year after OLT. Of them, 11 presented with b-IFI within 17 (IQR 11-33) and 16 (IQR 4-30) days from OLT and from antifungal onset, respectively. Then out of 11 patients with b-IFI were classified as having high risk of IFI and were receiving anti-mould prophylaxis, nine with echinocandins and one with polyenes. Comparison of patients with and without b-IFI showed significant differences for prior Candida colonization, need of renal replacement therapy after OLT, re-operation, and CMV infection (whole blood CMV-DNA >100 000 copies/mL). Although non-significant, a higher rate of b-IFI in patients on echinocandins was observed (8.2% vs 1.8%, P = .06). CONCLUSIONS: We observed 5% of b-IFI among OLT patients exposed to antifungal prophylaxis. The impact of echinocandins on b-IFI risk in this setting should be further explored.

COVID-19 in solid organ transplant recipients: No difference in survival compared to general population.

Coronavirus disease 2019 (COVID-19) may be associated with worse outcome in solid organ transplant (SOT) recipients. We performed a prospective cohort study of hospitalized patients with confirmed diagnosis of COVID-19, from March 15 to April 30, 2020, at two tertiary hospitals in Emilia-Romagna Region. SOT recipients were compared with non-SOT patients. Primary endpoint was all-cause 30-day mortality. Relationship between SOT status and mortality was investigated by univariable and multivariable Cox regression analysis. Patients were assessed from COVID-19 diagnosis to death or 30-day whichever occurred first. Study cohort consisted of 885 patients, of them 24 SOT recipients (n = 22, kidney, n = 2 liver). SOT recipients were younger, had lower BMI, but higher Charlson Index. At admission they presented less frequently with fever and respiratory failure. No difference in 30-day mortality between the two groups (19% vs 22.1%) was found; however, there was a trend toward higher rate of respiratory failure (50% vs 33.1%, P = .07) in SOT recipients. Superinfections were more represented in SOT recipients, (50% vs 15.5%, P < .001). At multivariate analysis adjusted for main covariates, there was no association between SOT and 30-day mortality HR 1.15 (95% CI 0.39-3.35) P = .79. Our data suggest that mortality among COVID-19 SOT recipients is similar to general population.

Efficacy of corticosteroid treatment for hospitalized patients with severe COVID-19: a multicentre study.

OBJECTIVE: To assess the efficacy of corticosteroids in patients with coronavirus disease 2019 (COVID-19). METHODS: A multicentre observational study was performed from 22 February through 30 June 2020. We included consecutive adult patients with severe COVID-19, defined as respiratory rate ≥30 breath per minute, oxygen saturation ≤93% on ambient air or arterial partial pressure of oxygen to fraction of inspired oxygen ≤300 mm Hg. We excluded patients being treated with other immunomodulant drugs, receiving low-dose corticosteroids and receiving corticosteroids 72 hours after admission. The primary endpoint was 30-day mortality from hospital admission. The main exposure variable was corticosteroid therapy at a dose of ≥0.5 mg/kg of prednisone equivalents. It was introduced as binomial covariate in a logistic regression model for the primary endpoint and inverse probability of treatment weighting using the propensity score. RESULTS: Of 1717 patients with COVID-19 evaluated, 513 were included in the study, and of these, 170 (33%) were treated with corticosteroids. During hospitalization, 166 patients (34%) met the criteria of the primary outcome (60/170, 35% in the corticosteroid group and 106/343, 31% in the noncorticosteroid group). At multivariable analysis corticosteroid treatment was not associated with lower 30-day mortality rate (adjusted odds ratio, 0.59; 95% confidence interval (CI), 0.20-1.74; p 0.33). After inverse probability of treatment weighting, corticosteroids were not associated with lower 30-day mortality (average treatment effect, 0.05; 95% CI, -0.02 to 0.09; p 0.12). However, subgroup analysis revealed that in patients with PO2/FiO2 < 200 mm Hg at admission (135 patients, 52 (38%) treated with corticosteroids), corticosteroid treatment was associated with a lower risk of 30-day mortality (23/52, 44% vs. 45/83, 54%; adjusted odds ratio, 0.20; 95% CI, 0.04-0.90; p 0.036). CONCLUSIONS: The effect of corticosteroid treatment on mortality might be limited to critically ill COVID-19 patients.

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.

A proposal for a comprehensive approach to infections across the surgical pathway.

Despite evidence supporting the effectiveness of best practices in infection prevention and management, many healthcare workers fail to implement them and evidence-based practices tend to be underused in routine practice. Prevention and management of infections across the surgical pathway should always focus on collaboration among all healthcare workers sharing knowledge of best practices. To clarify key issues in the prevention and management of infections across the surgical pathway, a multidisciplinary task force of experts convened in Ancona, Italy, on May 31, 2019, for a national meeting. This document represents the executive summary of the final statements approved by the expert panel.

Sixty-Day Mortality Among 520 Italian Hospitalized COVID-19 Patients According to the Adopted Ventilatory Strategy in the Context of an Integrated Multidisciplinary Clinical Organization: A Population-Based Cohort Study.

PURPOSE: Although the decision of which ventilation strategy to adopt in COVID-19 patients is crucial, yet the most appropriate means of carrying out this undertaking is not supported by strong evidence. We therefore described the organization of a province-level healthcare system during the occurrence of the COVID-19 epidemic and the 60-day outcomes of the hospitalized COVID-19 patients according to the respiratory strategy adopted given the limited available resources. PATIENTS AND METHODS: All COVID-19 patients (26/02/2020-18/04/2020) in the Rimini Province of Italy were included in this population-based cohort study. The hospitalized patients were classified according to the maximum level of respiratory support: oxygen supplementation (Oxygen group), non-invasive ventilation (NIV-only group), invasive mechanical ventilation (IMV-only group), and IMV after an NIV trial (IMV-after-NIV group). Sixty-day mortality risk was estimated with a Cox proportional hazard analysis adjusted by age, sex, and administration of steroids, canakinumab, and tocilizumab. RESULTS: We identified a total of 1,424 symptomatic patients: 520 (36.5%) were hospitalized, while 904 (63.5%) were treated at home with no 60-day deaths. Based on the respiratory support, 408 (78.5%) were assigned to the Oxygen group, 46 (8.8%) to the NIV-only group, 25 (4.8%) to the IMV-after-NIV group, and 41 (7.9%) to the IMV-only group. There was no significant difference in the PaO2/FiO2 at IMV inception in the IMV-after-NIV and IMV-only groups (p=0.9). Overall 60-day mortality was 24.2% (Oxygen: 23.0%; NIV-only: 19.6%; IMV-after-NIV: 32.0%; IMV-only: 36.6%; p=0.165). Compared with the Oxygen group, the adjusted 60-day mortality risk significantly increased in the IMV-after-NIV (HR 2.776; p=0.024) and IMV-only groups (HR 2.966; p=0.001). CONCLUSION: This study provided a population-based estimate of the impact of the COVID-19 outbreak in a severely affected Italian province. A similar 60-day mortality risk was found for patients undergoing immediate IMV and those intubated after an NIV trial with favorable outcomes after prolonged IMV.

Italian recommendations for influenza and pneumococcal vaccination in adult patients with autoimmune rheumatic diseases.

OBJECTIVES: To provide evidence-based recommendations for vaccination against influenza virus and S. pneumoniae in patients with autoimmune rheumatic diseases (ARDs). METHODS: A Consensus Committee including physicians with expertise in rheumatic and infectious diseases was established by two Italian scientific societies, Società Italiana di Reumatologia (SIR) and Società Italiana di Malattie Infettive e Tropicali (SIMIT). The experts were invited to develop evidence-based recommendations concerning vaccinations in ARDs patients, based on their clinical status before and after undergoing immunosuppressive treatments. Key clinical questions were formulated for the systematic literature reviews, based on the clinical pathway. A search was made in Medline (via PubMed) according to the original MeSH strategy from October 2009 and a keyword strategy from January 2016 up to December 2017, updating existing EULAR recommendations. Specific recommendations were separately voted and scored from 0 (no agreement with) to 100 (maximal agreement) and supporting evidence graded. The mean and standard deviation of the scores were calculated to determine the level of agreement among the experts' panel for each recommendation. Total cumulative agreement ≥70 defined consensus for each statement. RESULTS: Nine recommendations, based on 6 key clinical questions addressed by the expert committee, were proposed. The aim of this work is to integrate the 2011 EULAR recommendations on vaccination against influenza and S. pneumoniae in ARDs patients. An implementation plan was proposed to improve the vaccination status of these patients and their safety during immunosuppressive treatments. CONCLUSIONS: Influenza and pneumococcus vaccinations are effective and safe in patients with ARDs. More efforts should be made to translate the accumulated evidence into practice.

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.

Impact on Mortality of a Bundle for the Management of Enterococcal Bloodstream Infection.

OBJECTIVE: In this study, we evaluated the effectiveness of a management bundle for Enterococcus spp bloodstream infection (E-BSI). METHOD: This was a single-center, quasi-experimental (pre/post) study. In the prephase (January 2014 to December 2015), patients with monomicrobial E-BSI were retrospectively enrolled. During the post- or intervention phase (January 2016 to December 2017), all patients with incident E-BSI were prospectively enrolled in a nonmandatory intervention arm comprising infectious disease consultation, echocardiography, follow-up blood cultures, and early targeted antibiotic treatment. Patients were followed up to 1 year after E-BSI. The primary outcome was 30-day mortality. RESULTS: Overall, 368 patients were enrolled, with 173 in the prephase and 195 in the postphase. The entire bundle was applied in 15% and 61% patients during the pre- and postphase, respectively (P < .001). Patients enrolled in the postphase had a significant lower 30-day mortality rate (20% vs 32%, P = .0042). At multivariate analysis, factors independently associated to mortality were age (hazard ratio [HR], 1.03; 95% confidence interval [CI], 1.00-1.05), intensive care unit admission (HR, 2.51; 95% CI, 1.18-3.89), and healthcare-associated (HR, 2.32; 95% CI, 1.05-5.16) and hospital-acquired infection (HR, 2.85; 95% CI, 1.34-4.76), whereas being enrolled in the postphase period (HR, 0.49; 95% CI, 0.32-0.75) was associated with improved survival. Results were consistent also in the subgroups with severe sepsis (HR, 0.37; 95% CI, 0.16-0.90) or healthcare-associated infections (HR, 0.53; 95% CI, 0.31-0.93). A significantly lower 1-year mortality was observed in patients enrolled in the postphase period (50% vs 68%, P < .001). CONCLUSIONS: The introduction of a bundle for the management of E-BSI was associated with improved 30-day and 1-year survival.