ORCID Profile
0000-0001-8097-366X
Current Organisations
IRCCS Ospedale San Raffaele
,
Bernhard-Nocht-Institut für Tropenmedizin
,
Università degli Studi di Milano
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Publisher: Oxford University Press (OUP)
Date: 30-10-2019
DOI: 10.1093/CID/CIZ450
Abstract: Antimicrobial resistance (AMR) is a major global health concern, yet, there are noticeable gaps in AMR surveillance data in regions such as sub-Saharan Africa. We aimed to measure the prevalence of extended-spectrum β-lactamase (ESBL) producing Gram-negative bacteria in bloodstream infections from 12 sentinel sites in sub-Saharan Africa. Data were generated during the Typhoid Fever Surveillance in Africa Program (TSAP), in which standardized blood cultures were performed on febrile patients attending 12 health facilities in 9 sub-Saharan African countries between 2010 and 2014. Pathogenic bloodstream isolates were identified at the sites and then subsequently confirmed at a central reference laboratory. Antimicrobial susceptibility testing, detection of ESBL production, and conventional multiplex polymerase chain reaction (PCR) testing for genes encoding for β-lactamase were performed on all pathogens. Five hundred and five pathogenic Gram-negative bloodstream isolates were isolated during the study period and available for further characterization. This included 423 Enterobacteriaceae. Phenotypically, 61 (12.1%) isolates exhibited ESBL activity, and genotypically, 47 (9.3%) yielded a PCR licon for at least one of the screened ESBL genes. Among specific Gram-negative isolates, 40 (45.5%) of 88 Klebsiella spp., 7 (5.7%) of 122 Escherichia coli, 6 (16.2%) of 37 Acinetobacter spp., and 2 (1.3%) of 159 of nontyphoidal Salmonella (NTS) showed phenotypic ESBL activity. Our findings confirm the presence of ESBL production among pathogens causing bloodstream infections in sub-Saharan Africa. With few alternatives for managing ESBL-producing pathogens in the African setting, measures to control the development and proliferation of AMR organisms are urgently needed.
Publisher: Informa UK Limited
Date: 02-09-2015
Publisher: Cold Spring Harbor Laboratory
Date: 13-05-2022
DOI: 10.1101/2022.05.13.491767
Abstract: Reduced susceptibility to ART, the first-line treatment against malaria, is common in South East Asia (SEA). It is caused by point mutations, mostly in kelch13 ( k13 ) but also in other genes, like upb1 . K13 and its compartment neighbors (KICs), including UBP1, are involved in endocytosis of host cell cytosol. We tested 135 mutations in KICs but none conferred ART resistance. Double mutations of k13 C580Y with k13 R539T or k13 C580Y with ubp1 R3138H, did also not increase resistance. In contrast, k13 C580Y parasites subjected to consecutive RSAs did, but the k13 sequence was not altered. Using isogenic parasites with different k13 mutations, we found correlations between K13 protein amount, resistance and fitness cost. Titration of K13 and KIC7 indicated that the cellular levels of these proteins determined resistance through the rate of endocytosis. While fitness cost of k13 mutations correlated with ART resistance, ubp1 R3138H caused a disproportionately higher fitness cost. ART resistance is only a partial resistance with a proportion of ring stages surviving physiological ART levels. The correlation of resistance with fitness cost in isogenic lines indicates that fitness cost likely prevents resistance levels permitting survival of all ring stages under physiological ART concentrations. We also found no indication that double mutations in k13 , including the two most common resistance mutations in SEA, or with non- k13 genes, are a threat to lead to higher resistance. However, repeated ART exposure increased resistance by mechanisms not altering k13 gene sequence, indicating changes in the background of these parasites. The disproportionally high fitness cost of ubp1 R3138H may explain why kic mutations affecting resistance are rare and highlights the unique property of K13 to influence endocytosis only in ring stages.
Publisher: Wiley
Date: 09-03-2021
DOI: 10.1111/ANAE.15458
Abstract: Peri‐operative SARS‐CoV‐2 infection increases postoperative mortality. The aim of this study was to determine the optimal duration of planned delay before surgery in patients who have had SARS‐CoV‐2 infection. This international, multicentre, prospective cohort study included patients undergoing elective or emergency surgery during October 2020. Surgical patients with pre‐operative SARS‐CoV‐2 infection were compared with those without previous SARS‐CoV‐2 infection. The primary outcome measure was 30‐day postoperative mortality. Logistic regression models were used to calculate adjusted 30‐day mortality rates stratified by time from diagnosis of SARS‐CoV‐2 infection to surgery. Among 140,231 patients (116 countries), 3127 patients (2.2%) had a pre‐operative SARS‐CoV‐2 diagnosis. Adjusted 30‐day mortality in patients without SARS‐CoV‐2 infection was 1.5% (95%CI 1.4–1.5). In patients with a pre‐operative SARS‐CoV‐2 diagnosis, mortality was increased in patients having surgery within 0–2 weeks, 3–4 weeks and 5–6 weeks of the diagnosis (odds ratio (95%CI) 4.1 (3.3–4.8), 3.9 (2.6–5.1) and 3.6 (2.0–5.2), respectively). Surgery performed ≥ 7 weeks after SARS‐CoV‐2 diagnosis was associated with a similar mortality risk to baseline (odds ratio (95%CI) 1.5 (0.9–2.1)). After a ≥ 7 week delay in undertaking surgery following SARS‐CoV‐2 infection, patients with ongoing symptoms had a higher mortality than patients whose symptoms had resolved or who had been asymptomatic (6.0% (95%CI 3.2–8.7) vs. 2.4% (95%CI 1.4–3.4) vs. 1.3% (95%CI 0.6–2.0), respectively). Where possible, surgery should be delayed for at least 7 weeks following SARS‐CoV‐2 infection. Patients with ongoing symptoms ≥ 7 weeks from diagnosis may benefit from further delay.
Publisher: Wiley
Date: 24-08-2021
DOI: 10.1111/ANAE.15563
Abstract: SARS‐CoV‐2 has been associated with an increased rate of venous thromboembolism in critically ill patients. Since surgical patients are already at higher risk of venous thromboembolism than general populations, this study aimed to determine if patients with peri‐operative or prior SARS‐CoV‐2 were at further increased risk of venous thromboembolism. We conducted a planned sub‐study and analysis from an international, multicentre, prospective cohort study of elective and emergency patients undergoing surgery during October 2020. Patients from all surgical specialties were included. The primary outcome measure was venous thromboembolism (pulmonary embolism or deep vein thrombosis) within 30 days of surgery. SARS‐CoV‐2 diagnosis was defined as peri‐operative (7 days before to 30 days after surgery) recent (1–6 weeks before surgery) previous (≥7 weeks before surgery) or none. Information on prophylaxis regimens or pre‐operative anti‐coagulation for baseline comorbidities was not available. Postoperative venous thromboembolism rate was 0.5% (666/123,591) in patients without SARS‐CoV‐2 2.2% (50/2317) in patients with peri‐operative SARS‐CoV‐2 1.6% (15/953) in patients with recent SARS‐CoV‐2 and 1.0% (11/1148) in patients with previous SARS‐CoV‐2. After adjustment for confounding factors, patients with peri‐operative (adjusted odds ratio 1.5 (95%CI 1.1–2.0)) and recent SARS‐CoV‐2 (1.9 (95%CI 1.2–3.3)) remained at higher risk of venous thromboembolism, with a borderline finding in previous SARS‐CoV‐2 (1.7 (95%CI 0.9–3.0)). Overall, venous thromboembolism was independently associated with 30‐day mortality (5.4 (95%CI 4.3–6.7)). In patients with SARS‐CoV‐2, mortality without venous thromboembolism was 7.4% (319/4342) and with venous thromboembolism was 40.8% (31/76). Patients undergoing surgery with peri‐operative or recent SARS‐CoV‐2 appear to be at increased risk of postoperative venous thromboembolism compared with patients with no history of SARS‐CoV‐2 infection. Optimal venous thromboembolism prophylaxis and treatment are unknown in this cohort of patients, and these data should be interpreted accordingly.
Publisher: Springer Science and Business Media LLC
Date: 30-11-2018
DOI: 10.1038/S41467-018-07370-Z
Abstract: There is paucity of data regarding the geographical distribution, incidence, and phylogenetics of multi-drug resistant (MDR) Salmonella Typhi in sub-Saharan Africa. Here we present a phylogenetic reconstruction of whole genome sequenced 249 contemporaneous S . Typhi isolated between 2008-2015 in 11 sub-Saharan African countries, in context of the 2,057 global S . Typhi genomic framework. Despite the broad genetic ersity, the majority of organisms (225/249 90%) belong to only three genotypes, 4.3.1 (H58) (99/249 40%), 3.1.1 (97/249 39%), and 2.3.2 (29/249 12%). Genotypes 4.3.1 and 3.1.1 are confined within East and West Africa, respectively. MDR phenotype is found in over 50% of organisms restricted within these dominant genotypes. High incidences of MDR S . Typhi are calculated in locations with a high burden of typhoid, specifically in children aged years. Antimicrobial stewardship, MDR surveillance, and the introduction of typhoid conjugate vaccines will be critical for the control of MDR typhoid in Africa.
Publisher: Elsevier BV
Date: 03-2017
Publisher: Oxford University Press (OUP)
Date: 24-03-2021
DOI: 10.1093/BJS/ZNAB101
Abstract: Preoperative SARS-CoV-2 vaccination could support safer elective surgery. Vaccine numbers are limited so this study aimed to inform their prioritization by modelling. The primary outcome was the number needed to vaccinate (NNV) to prevent one COVID-19-related death in 1 year. NNVs were based on postoperative SARS-CoV-2 rates and mortality in an international cohort study (surgical patients), and community SARS-CoV-2 incidence and case fatality data (general population). NNV estimates were stratified by age (18–49, 50–69, 70 or more years) and type of surgery. Best- and worst-case scenarios were used to describe uncertainty. NNVs were more favourable in surgical patients than the general population. The most favourable NNVs were in patients aged 70 years or more needing cancer surgery (351 best case 196, worst case 816) or non-cancer surgery (733 best case 407, worst case 1664). Both exceeded the NNV in the general population (1840 best case 1196, worst case 3066). NNVs for surgical patients remained favourable at a range of SARS-CoV-2 incidence rates in sensitivity analysis modelling. Globally, prioritizing preoperative vaccination of patients needing elective surgery ahead of the general population could prevent an additional 58 687 (best case 115 007, worst case 20 177) COVID-19-related deaths in 1 year. As global roll out of SARS-CoV-2 vaccination proceeds, patients needing elective surgery should be prioritized ahead of the general population.
Publisher: Wiley
Date: 09-08-2021
DOI: 10.1111/ANAE.15560
Abstract: We aimed to determine the impact of pre‐operative isolation on postoperative pulmonary complications after elective surgery during the global SARS‐CoV‐2 pandemic. We performed an international prospective cohort study including patients undergoing elective surgery in October 2020. Isolation was defined as the period before surgery during which patients did not leave their house or receive visitors from outside their household. The primary outcome was postoperative pulmonary complications, adjusted in multivariable models for measured confounders. Pre‐defined sub‐group analyses were performed for the primary outcome. A total of 96,454 patients from 114 countries were included and overall, 26,948 (27.9%) patients isolated before surgery. Postoperative pulmonary complications were recorded in 1947 (2.0%) patients of which 227 (11.7%) were associated with SARS‐CoV‐2 infection. Patients who isolated pre‐operatively were older, had more respiratory comorbidities and were more commonly from areas of high SARS‐CoV‐2 incidence and high‐income countries. Although the overall rates of postoperative pulmonary complications were similar in those that isolated and those that did not (2.1% vs 2.0%, respectively), isolation was associated with higher rates of postoperative pulmonary complications after adjustment (adjusted OR 1.20, 95%CI 1.05–1.36, p = 0.005). Sensitivity analyses revealed no further differences when patients were categorised by: pre‐operative testing use of COVID‐19‐free pathways or community SARS‐CoV‐2 prevalence. The rate of postoperative pulmonary complications increased with periods of isolation longer than 3 days, with an OR (95%CI) at 4–7 days or ≥ 8 days of 1.25 (1.04–1.48), p = 0.015 and 1.31 (1.11–1.55), p = 0.001, respectively. Isolation before elective surgery might be associated with a small but clinically important increased risk of postoperative pulmonary complications. Longer periods of isolation showed no reduction in the risk of postoperative pulmonary complications. These findings have significant implications for global provision of elective surgical care.
Location: United Kingdom of Great Britain and Northern Ireland
No related grants have been discovered for Paolo Ivo Cavoretto.