Present and Future Perspectives on Therapeutic Options for Carbapenemase-Producing Enterobacterales Infections.
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SUBMITTER: Vrancianu CO
PROVIDER: S-EPMC8065494 | biostudies-literature |
REPOSITORIES: biostudies-literature
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Project description:BackgroundCarbapenemase-producing Enterobacterales (CPE) infections have been occasionally described in patients with coronavirus disease-19 (COVID-19). We assess the clinical features and outcome of these infections.MethodsIn this retrospective single-centre, case-control study, we included 54 patients with CPE infection: 30 case-patients (COVID-19) and 24 controls (non-COVID-19), collected between March and May 2020. We compared the epidemiological, clinical features, and outcome between cases and controls.ResultsCPE infection was more frequent in COVID-19 patients than in controls (1.1 vs. 0.5%, p = .005). COVID-19 patients were younger, had a lower frequency of underlying diseases (p = .01), and a lower median Charlson score (p = .002). Predisposing factors such as antimicrobial use, mechanical ventilation, or ICU admission, were more frequent in COVID-19 patients (p < .05). There were 73 episodes of infection (42 cases and 31 controls) that were more frequently hospital-acquired and diagnosed at the ICU in COVID-19 patients (p < .001). Urinary tract was the most common source of infection (47.9%), followed by pneumonia (23.3%). The frequency of severe sepsis or shock (p = .01) as well as the median SOFA score (p = .04) was higher in cases than in controls. Klebsiella pneumoniae (80.8%), Serratia marcescens (11%) and Enterobacter cloacae (4.1%) were the most common bacteria in both groups (KPC 56.2%, OXA-48 26% and VIM 17.8%). Overall 30-d mortality rate of COVID-19 patients and controls was 30 and 16.7%, respectively (p = .25).ConclusionsCOVID-19 patients have an increased risk of CPE infections, which usually present as severe, nosocomial infections, appearing in critically-ill patients and associated with a high mortality.
| S-EPMC8425444 | biostudies-literature
Project description:BackgroundData on household transmission of carbapenemase-producing Enterobacterales (CPE) remain limited. We studied risk of CPE household co-colonization and transmission in Ontario, Canada.MethodsWe enrolled CPE index cases (identified via population-based surveillance from January 2015 to October 2018) and their household contacts. At months 0, 3, 6, 9, and 12, participants provided rectal and groin swabs. Swabs were cultured for CPE until September 2017, when direct polymerase chain reaction (PCR; with culture of specimens if a carbapenemase gene was detected) replaced culture. CPE risk factor data were collected by interview and combined with isolate whole-genome sequencing to determine likelihood of household transmission. Risk factors for household contact colonization were explored using a multivariable logistic regression model with generalized estimating equations.ResultsNinety-five households with 177 household contacts participated. Sixteen (9%) household contacts in 16 (17%) households were CPE-colonized. Household transmission was confirmed in 3/177 (2%) cases, probable in 2/177 (1%), possible in 9/177 (5%), and unlikely in 2/177 (1%). Household contacts were more likely to be colonized if they were the index case's spouse (odds ratio [OR], 6.17; 95% confidence interval [CI], 1.05-36.35), if their index case remained CPE-colonized at household enrollment (OR, 7.00; 95% CI, 1.92-25.49), or if they had at least 1 set of specimens processed after direct PCR was introduced (OR, 6.46; 95% CI, 1.52-27.40).ConclusionsNine percent of household contacts were CPE-colonized; 3% were a result of household transmission. Hospitals may consider admission screening for patients known to have CPE-colonized household contacts.
| S-EPMC8662791 | biostudies-literature
Project description:Background: Patients with COVID-19 may be at increased risk for secondary bacterial infections with MDR pathogens, including carbapenemase-producing Enterobacterales (CPE).Objectives: We sought to rapidly investigate the clinical characteristics, population structure and mechanisms of resistance of CPE causing secondary infections in patients with COVID-19.Methods: We retrospectively identified CPE clinical isolates collected from patients testing positive for SARS-CoV-2 between March and April 2020 at our medical centre in New York City. Available isolates underwent nanopore sequencing for rapid genotyping, antibiotic resistance gene detection and phylogenetic analysis.Results: We identified 31 CPE isolates from 13 patients, including 27 Klebsiella pneumoniae and 4 Enterobacter cloacae complex isolates. Most patients (11/13) had a positive respiratory culture and 7/13 developed bacteraemia; treatment failure was common. Twenty isolates were available for WGS. Most K. pneumoniae (16/17) belonged to ST258 and encoded KPC (15 KPC-2; 1 KPC-3); one ST70 isolate encoded KPC-2. E. cloacae isolates belonged to ST270 and encoded NDM-1. Nanopore sequencing enabled identification of at least four distinct ST258 lineages in COVID-19 patients, which were validated by Illumina sequencing data.Conclusions: While CPE prevalence has declined substantially in New York City in recent years, increased detection in patients with COVID-19 may signal a re-emergence of these highly resistant pathogens in the wake of the global pandemic. Increased surveillance and antimicrobial stewardship efforts, as well as identification of optimal treatment approaches for CPE, will be needed to mitigate their future impact.
| S-EPMC7717307 | biostudies-literature
Project description:Over the past 2 decades, there has been an extraordinary progress in the regimens developed for the treatment of human epidermal growth factor receptor 2 (HER2)-positive breast cancer. Trastuzumab, pertuzumab, lapatinib, and ado-trastuzumab emtansine (T-DM1) are commonly recommended anti-HER2 target agents by the U.S. Food and Drug Administration. This review summarizes the most significant and updated research on clinical scenarios related to HER2-positive breast cancer management in order to revise the guidelines of everyday clinical practices. In this article, we present the data on anti-HER2 clinical research of neoadjuvant, adjuvant, and metastatic studies from the past 2 decades. We also highlight some of the promising strategies that should be critically considered. Lastly, this review lists some of the ongoing clinical trials, findings of which may soon be available.
| S-EPMC6799843 | biostudies-literature
Project description:Carbapenemase-producing Enterobacterales (CPE) pose an increasing threat to patient safety and healthcare systems globally. We present molecular epidemiology of CPE in Finland during 2012-2018 with detailed characteristics of CPE strains causing clusters during the same time period. All Finnish clinical microbiology laboratories send Enterobacterales isolates with reduced susceptibility to carbapenems or isolates producing carbapenemase to the reference laboratory for further characterization by whole genome sequencing (WGS). In total, 231 CPE strains from 202 patients were identified during 2012-2018. Of the strains, 59% were found by screening and 32% from clinical specimens, the latter were most commonly urine. Travel and/or hospitalization history abroad was reported for 108/171 strains (63%). The most common species were Klebsiella pneumoniae (45%), Escherichia coli (40%), and Citrobacter freundii (6%), and the most common carbapenemase genes blaNDM-like (35%), blaOXA-48-like (33%), and blaKPC-like (31%). During 2012-2018, the annual number of CPE strains increased from 9 to 70 and different sequence types from 7 to 33, and blaOXA-48-like genes became the most prevalent. Of the clusters, 3/8 were linked to traveling or hospitalization abroad and 5/8 were caused by K. pneumoniae clone clonal complex 258. Most of the clusters were caused by K. pneumoniae producing KPC. High variety among different sequence types indicates that majority of CPE cases detected in Finland are likely imported from foreign countries. Nearly one-third of the cases are not found by screening suggesting that there is hidden transmission occurring in the healthcare settings.
| S-EPMC7427707 | biostudies-literature
Project description:In the hospital department dedicated to COVID-19-patient, infection prevention and control measures were upgraded. Therefore, the cross-transmission of other micro-organisms was thought unlikely to occur. However, we report an outbreak of NDM-5-producing E. coli in a 12-beds ICU dedicated to COVID-19 patients. This outbreak involved 6 patients of which 5 were asymptomatic carriers and 1 was infected. Several findings might have contributed to cross-transmission including the multiple-bedroom configuration of the department, uncomplete compliance for standard and contact precautions, overwork due to the burden of the disease, lack of training of staff for the care of ICU-patients, and misuse of gloves. Furthermore, as infection prevention and control measures were thought to be the applied, contact patients were not screened for eXDR carriage. Applying rigorously standard and contact precautions and performing screening in contact patients when indicated must be the rules in COVID-19 wards.
| S-EPMC7529666 | biostudies-literature
Project description:During the last 15 years we have witnessed an unprecedented expansion in the drugs developed to target human epidermal growth factor receptor-2 (HER-2) positive breast cancer. Trastuzumab, pertuzumab, ado-trastuzumab emtansine and lapatinib are currently food and drug administration (FDA)-approved for the treatment of breast cancer patients with HER-2 over-expressed. However, given the amount of information gathered from years of uninterrupted clinical research, it is essential to have periodic updates that succinctly recapitulate what we have learnt over these last years and help us to apply that information in our daily practice. This review will pursue that objective. We will summarize the most relevant and updated information related to the state of the art management of HER-2 positive breast cancer in all the clinical scenarios including the adjuvant, neoadjuvant and metastatic settings. But we will also critically appraise that literature in order to highlight some key clinical concepts that should not be overlooked. Lastly, this review will also point out some of the most promising strategies that are currently being tested and may soon become available.
| S-EPMC4127614 | biostudies-literature
Project description:The COVID-19 pandemic represents an unprecedented challenge for the researchers to offer safe, tolerable, and effective treatment strategies for its causative agent known as SARS-CoV-2. With the rapid evolution of the pandemic, even the off-label use of existing drugs has been restricted by limited availability. Several old antivirals, antimalarial, and biological drugs are being reconsidered as possible therapies. The effectiveness of the controversial treatment options for COVID-19 such as nonsteroidal antiinflammatory drugs, angiotensin 2 conversion enzyme inhibitors and selective angiotensin receptor blockers was also discussed. A systemic search in the PubMed, Science Direct, LitCovid, Chinese Clinical Trial Registry, and ClinicalTrials.gov data bases was conducted using the keywords "coronavirus drug therapy," passive immunotherapy for COVID-19', "convalescent plasma therapy," (CPT) "drugs for COVID-19 treatment," "SARS-CoV-2," "COVID-19," "2019-nCoV," "coronavirus immunology," "microbiology," "virology," and individual drug names. Systematic reviews, case presentations and very recent clinical guidelines were included. This narrative review summarizes the available information on possible therapies for COVID-19, providing recent data to health professionals.
| S-EPMC7522523 | biostudies-literature
Project description:Background: Non-alcoholic steatohepatitis (NASH) is a chronic liver disease with severe complications and without approved therapies. Currently, there is limited data on the overall burden of the disease for patients or on patient needs and preferences. This study investigates patient preferences in relation to potential future therapies for NASH. In addition, the factors that are relevant to patients and their importance in relation to future treatment options are explored. Method: Telephone in-depth interviews (TDIs) preceded an online 30-min quantitative survey. The online survey included (1) multiple choice questions (MCQs) on NASH diagnosis and disease background. (2) An exercise to determine patients' satisfaction levels with information provided at diagnosis, and to explore symptomatology in detail. (3) Exercises to evaluate potential new products and product attributes, including a "drag and drop" ranking exercise, and an adaptive choice-based conjoint exercise (ACBC). (4) The EQ-5D-5L questionnaire and the Visual Analog Scale (VAS), which measures patients' health status. (5) Collection of socio-demographic data, and (6) Questions to measure patient satisfaction with the survey. Results: There were 166 patients included in this study from Canada [n = 36], Germany [n = 50], the UK [n = 30], and USA [n = 50]. Fifty seven percent of patients [n = 94] had had a liver biopsy for confirmation of NASH. Patients were often unable to link their symptoms to NASH or other conditions. ACBC results showed that efficacy, defined as "impact on liver status" was the single most important attribute of a potential future NASH therapy. Other attributes considered to have secondary importance included impact on weight, symptom control and the presence of side effects. The EQ-5D utility score was 0.81 and VAS = 67.2. Conclusion: "Impact on liver status" is the primary outcome sought. Patients demonstrate a general lack of understanding of their disease and appeared to be unfamiliar with longer-term consequences of NASH. It is necessary to improve patient understanding of NASH and its progressive nature, and there is a need for improving confirmatory diagnosis and monitoring.
| S-EPMC6457207 | biostudies-literature
Project description:Carbapenems are considered last-line beta-lactams for the treatment of infections caused by multidrug-resistant Gram-negative bacteria. However, their activity is compromised by the rising prevalence of carbapenemase-producing Enterobacterales (CPE), which are especially marked in the Indian subcontinent. In Pakistan, previous reports have warned about the possible spread of CPE in the community, but data are still partial. This study was carried out to analyse the prevalence of CPE, the genetic characterisation, and phylogenetic links among the spreading CPE in the community. In this cohort study, we collected 306 rectal swabs from patients visiting Benazir Bhutto hospital, Rawalpindi. CPEs were screened by using ertapenem-supplemented MacConkey agar. Identification was performed by using conventional biochemical tests, and genomes were sequenced using Illumina chemistry. Antibiotic resistance genes, plasmid incompatibility groups, and Escherichia coli phylogroups were determined in silico. Sequence types were determined by using MLST tool. The prevalence of CPE carriage observed was 14.4% (44/306 samples). The most common carbapenemase-encoding gene was bla-NDM-5 (n = 58) followed by blaNDM-1 (n = 7), blaNDM (non-assigned variant, n = 4), blaOXA-181 (n = 3), blaOXA-232 (n = 3) and blaNDM-7 (n = 1). Most of the CPE were E. coli (55/64, 86%), and the genomic analysis revealed a pauciclonal diffusion of E. coli with ST167 (n = 14), 405 (n = 10), 940 (n = 8), 648 (n = 6) and 617 (n = 5). We obtained a second sample from 94 patients during their hospital stay in whom carriage was negative at admission and found that 7 (7.4%) acquired a CPE. Our results indicate that the prevalence of CPE carriage in the Pakistani urban community was high and driven by the dissemination of some E. coli clones, with ST167 being the most frequent. The high CPE carriage in the community poses a serious public health threat and calls for implementation of adequate preventive measures.
| S-EPMC9269877 | biostudies-literature