CAZ-AVI appears to be a promising drug for treatment of severe KPC-Kp infections, especially those involving bacteremia.

Improved understanding of risk factors associated with carbapenem-resistant-Klebsiella pneumoniae (CR-KP) infection after liver transplantation (LT) can aid development of effective preventive strategies. We performed a prospective cohort study of all adult patients undergoing LT at our hospital during 30-month period to define risk factors associated with CR-KP infection. All patients were screened for CR-KP carriage by rectal swabs before and after LT. No therapy was administered to decolonize or treat asymptomatic CR-KP carriers. All patients were monitored up to 180 days after LT. Of 237 transplant patients screened, 41 were identified as CR-KP carriers (11 at LT, 30 after LT), and 20 developed CR-KP infection (18 bloodstream-infection, 2 pneumonia) a median of 41.5 days after LT. CR-KP infection rates among patients non-colonized, colonized at LT, and colonized after LT were 2%, 18.2% and 46.7% (p < 0.001). Independent risk factors for CR-KP infection identified by multivariate analysis, included: renal-replacement-therapy; mechanical ventilation > 48 h; HCV recurrence, and colonization at any time with CR-KP. Based on these four variables, we developed a risk score that effectively discriminated patients at low versus higher risk for CR-KP infection (AUC 0.93, 95% CI 0.86-1.00, p < 0.001). Our results may help to design preventive strategies for LT recipients in CR-KP endemic areas.

Our analysis indicates that mixed subpopulations of ceftazidime/avibactam-resistant KPC-Kp emerge after ceftazidime/avibactam treatment. The evolution of different subpopulations that are highly resistant to ceftazidime/avibactam likely contributes to treatment failure, thereby highlighting the need for combination treatment strategies to limit selection of ceftazidime/avibactam-resistant KPC-Kp subpopulations.

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: Sp o 2 <93% with 100% Fi o 2 , respiratory rate >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/mm 3 (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.

MDRO account for nearly one-third of BSI in cirrhotic patients, often resulting in delayed or inadequate empirical antimicrobial therapy and increased mortality rates. Our data suggest that improved prevention and treatment strategies for MDRO are urgently needed in the liver cirrhosis patients.

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To the Editor, Many authors recently reported the effect of the severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) pandemic on patients affected by Inborn Errors of Immunity (IEI). 1,2 Although mostly experiencing a mild disease and the course of the infection is comparable or even less symptomatic than the general population, young male IEIs patients were more severely affected and more frequently admitted to intensive care unit compared with the age-matched healthy peers. 3 Most viral variants were actually first described in immunocompromised patients. 4,5 Indeed, impaired B and/or T cell function can be responsible for persisting viral shedding often observed in IEI patients with subsequent higher risk of persistent viral replication and mutation within the host. 6 Noteworthily, in the last 2 years Inborn Errors of type I IFN immunity and autoantibodymediated phenocopies of IEIs were identified as responsible for life-threatening COVID-19. These conditions were not considered in the studies about IEIs and SARS-CoV-2 infection. 7,8 Predisposition to increased risk and most severe infection in IEI, despite a lack of clear data in favor of a high risk for progression to severe COVID-19, led the scientific community to recommend the use of early SARS-CoV2-directed treatments to potentially reduce the incidence of long-lasting infection, as well as morbidity and mortality risk. 9Casirivimab-imdevimab, also known as REGEN-COV, is an antispike mAb that has been authorized for the treatment of high-risk patients (>12 years of age, >40 kg) with mild-to-moderate COVID-19. 10 Bamlanivimab, named LY-CoV555, then combined with etesevimab, showed a beneficial effect for accelerating the natural decline of the viral load over time. In December 2021, it was approved by FDA for patients<12 years. 10 Sotrovimab, formerly known as VIR-7831, is an engineered human mAb that neutralizes SARS-CoV-2. 10 There are several data confirming the safety and efficacy in both adults and pediatric population. 11 We describe a cohort of 63 SARS-CoV-2-infected IEI patients, providing the first case series report on the early employment of anti-SARS-CoV-2 treatments with antiviral drugs and MAbs in these patients (Table S1). Thirty-nine patients were younger than 18 years (median age 9.5 years), whereas 24 were adults (median age 33 years). Male-to-female ratio was 1:1. Seven individuals have been

Aim of this study was to evaluate the incidence of ceftazidime/avibactam resistance among KPCproducing Klebsiella pneumoniae (KPC-Kp) strnins isolated from patients with bloodstream infection. MethodsWe collected 120 carbapenemase producing Enterobacteriaceae (CPE) strnins from unique patients hospitalized in two Italian hospitals between Januaiy 2018 to Febmaiy 2019. Strains were phenotypically characterized for the type of carbapenemase production and susceptibility to ceftazidime/avibactam. Ceftazidime/avibactam-resistant strains were chai• acterized by wholegenome sequencmg. ResultsDm-ing the study period, we characterized 105 (87,5%) KPC producers among a total of 120 CPE strains. Ceftazidime-avibactam resistance was found in three KPC-Kp strnins isolated from patients with no histo1y of previous ceftazidime/avibactam-based treatment. Of note, two out of three ceftazidime-avibactam-resistant KPC-Kp were also resistant to meropenem/vaborbactam. Genomic chai•acterization showed that a ceftazidime/avibactam-resistant KPC-Kp hai•bored a mixed population with D179Y mutated KPC-2, while the other two ceftazidime-avibactam-resistant KPC-Kp possessed non-functional ompK35-ompK37 and mutated ompK36 porins associated with higher copy number of blaKPC gene. Conclusion 48Om results showed that incidence of ceftazidime/avibactam resistance emerged in KCP-Kp strains independently from previous antimicrobial exposme. Resistance to ceftazidime/avibactam was associated to mutations within blaKPc gene or porins deficiency associated to higher blaKPc copy number that is also related to the meropenem/vaborbactam resistance.