scholarly journals Insight into Acinetobacter baumannii: pathogenesis, global resistance, mechanisms of resistance, treatment options, and alternative modalities

2018 ◽  
Vol Volume 11 ◽  
pp. 1249-1260 ◽  
Author(s):  
Muhammad Asif ◽  
Iqbal Ahmad Alvi ◽  
Shafiq Ur Rehman
Keyword(s):  
Acinetobacter Baumannii ◽  
Treatment Options ◽  
Resistance Mechanisms ◽  
Mechanisms Of Resistance ◽  
Insight Into

scholarly journals Molecular Epidemiology of Carbapenem-Resistant Acinetobacter baumannii From Khartoum State, Sudan

2021 ◽  
Vol 12 ◽  
Author(s):  
Leena Al-Hassan ◽  
Hana Elbadawi ◽  
Einas Osman ◽  
Sara Ali ◽  
Kamal Elhag ◽  
...  
Keyword(s):  
Antibiotic Resistance ◽  
Molecular Epidemiology ◽  
Acinetobacter Baumannii ◽  
Core Genome ◽  
Treatment Options ◽  
Resistance Mechanisms ◽  
Multiple Antibiotic Resistance ◽  
Resistance Determinants ◽  
Carbapenem Resistant ◽  
Allelic Differences

Carbapenem resistant Acinetobacter baumannii (CRAb) is an important global pathogen contributing to increased morbidity and mortality in hospitalized patients, due to limited alternative treatment options. Nine international clonal (IC) lineages have been identified in many countries worldwide, however, data still lacks from some parts of the world, particularly in Africa. We hereby present the molecular epidemiology of MDR A. baumannii from four hospitals in Khartoum, Sudan, collected from 2017 to 2018. Forty-two isolates were whole-genome sequenced, and subsequent molecular epidemiology was determined by core genome MLST (cgMLST), and their resistomes identified. All isolates had an array of diverse antibiotic resistance mechanisms conferring resistance to multiple classes of antibiotics. We found a predominance (88%) of IC2 (with the intrinsic OXA-66 and acquired OXA-23), and some with NDM-1. IC2 isolates were sub-divided into 4 STs separated by 5 to 431 allelic differences, and with evidence of seven transmission clusters. Isolates belonging to IC1, IC5, and IC9 were also identified. These data illustrate that MDR IC2 A. baumannii are widely distributed in Khartoum hospitals and are in possession of multiple antibiotic resistance determinants.

scholarly journals Cancer Vaccines for Genitourinary Tumors: Recent Progresses and Future Possibilities

Vaccines ◽  
2021 ◽  
Vol 9 (6) ◽  
pp. 623
Author(s):  
Brigida Anna Maiorano ◽  
Giovanni Schinzari ◽  
Davide Ciardiello ◽  
Maria Grazia Rodriquenz ◽  
Antonio Cisternino ◽  
...  
Keyword(s):  
Cancer Vaccines ◽  
Viral Vectors ◽  
Checkpoint Inhibitors ◽  
Treatment Options ◽  
Tumor Development ◽  
Resistance Mechanisms ◽  
High Morbidity ◽  
Therapeutic Vaccines ◽  
Combination Strategies ◽  
New Treatment

Background: In the last years, many new treatment options have widened the therapeutic scenario of genitourinary malignancies. Immunotherapy has shown efficacy, especially in the urothelial and renal cell carcinomas, with no particular relevance in prostate cancer. However, despite the use of immune checkpoint inhibitors, there is still high morbidity and mortality among these neoplasms. Cancer vaccines represent another way to activate the immune system. We sought to summarize the most recent advances in vaccine therapy for genitourinary malignancies with this review. Methods: We searched PubMed, Embase and Cochrane Database for clinical trials conducted in the last ten years, focusing on cancer vaccines in the prostate, urothelial and renal cancer. Results: Various therapeutic vaccines, including DNA-based, RNA-based, peptide-based, dendritic cells, viral vectors and modified tumor cells, have been demonstrated to induce specific immune responses in a variable percentage of patients. However, these responses rarely corresponded to significant survival improvements. Conclusions: Further preclinical and clinical studies will improve the knowledge about cancer vaccines in genitourinary malignancies to optimize dosage, select targets with a driver role for tumor development and growth, and finally overcome resistance mechanisms. Combination strategies represent possibly more effective and long-lasting treatments.

scholarly journals Radiation-Inactivated Acinetobacter baumannii Vaccine Candidates

Vaccines ◽  
2021 ◽  
Vol 9 (2) ◽  
pp. 96
Author(s):  
Stephen J. Dollery ◽  
Daniel V. Zurawski ◽  
Elena K. Gaidamakova ◽  
Vera Y. Matrosova ◽  
John K. Tobin ◽  
...  
Keyword(s):  
Acinetobacter Baumannii ◽  
Treatment Options ◽  
Bacterial Pathogen ◽  
Multidrug Resistant ◽  
Bacterial Cells ◽  
Wound Infections ◽  
Protein Profiles ◽  
Vaccine Candidates ◽  
Rich Media ◽  
Life Threatening

Acinetobacter baumannii is a bacterial pathogen that is often multidrug-resistant (MDR) and causes a range of life-threatening illnesses, including pneumonia, septicemia, and wound infections. Some antibiotic treatments can reduce mortality if dosed early enough before an infection progresses, but there are few other treatment options when it comes to MDR-infection. Although several prophylactic strategies have been assessed, no vaccine candidates have advanced to clinical trials or have been approved. Herein, we rapidly produced protective whole-cell immunogens from planktonic and biofilm-like cultures of A. baumannii, strain AB5075 grown using a variety of methods. After selecting a panel of five cultures based on distinct protein profiles, replicative activity was extinguished by exposure to 10 kGy gamma radiation in the presence of a Deinococcus antioxidant complex composed of manganous (Mn2+) ions, a decapeptide, and orthophosphate. Mn2+ antioxidants prevent hydroxylation and carbonylation of irradiated proteins, but do not protect nucleic acids, yielding replication-deficient immunogenic A. baumannii vaccine candidates. Mice were immunized and boosted twice with 1.0 × 107 irradiated bacterial cells and then challenged intranasally with AB5075 using two mouse models. Planktonic cultures grown for 16 h in rich media and biofilm cultures grown in static cultures underneath minimal (M9) media stimulated immunity that led to 80–100% protection.

scholarly journals Characteristics Associated with Death in Patients with Carbapenem-Resistant Acinetobacter baumannii, United States, 2012–2017

2020 ◽  
Vol 41 (S1) ◽  
pp. s59-s60
Author(s):  
Hannah E. Reses ◽  
Kelly Hatfield ◽  
Jesse Jacob ◽  
Chris Bower ◽  
Elisabeth Vaeth ◽  
...  
Keyword(s):  
Septic Shock ◽  
Acinetobacter Baumannii ◽  
Treatment Options ◽  
Care Facility ◽  
Severe Illness ◽  
Emerging Infections ◽  
Term Care ◽  
Icu Stay ◽  
Carbapenem Resistant ◽  
Sterile Site

Background: Carbapenem-resistant Acinetobacter baumannii (CRAB) is an important cause of healthcare-associated infections with limited treatment options and high mortality. To describe risk factors for mortality, we evaluated characteristics associated with 30-day mortality in patients with CRAB identified through the Emerging Infections Program (EIP). Methods: From January 2012 through December 2017, 8 EIP sites (CO, GA, MD, MN, NM, NY, OR, TN) participated in active, laboratory-, and population-based surveillance for CRAB. An incident case was defined as patient’s first isolation in a 30-day period of A. baumannii complex from sterile sites or urine with resistance to ≥1 carbapenem (excluding ertapenem). Medical records were abstracted. Patients were matched to state vital records to assess mortality within 30 days of incident culture collection. We developed 2 multivariable logistic regression models (1 for sterile site cases and 1 for urine cases) to evaluate characteristics associated with 30-day mortality. Results: We identified 744 patients contributing 863 cases, of which 185 of 863 cases (21.4%) died within 30 days of culture, including 113 of 257 cases (44.0%) isolated from a sterile site and 72 of 606 cases (11.9%) isolated from urine. Among 628 hospitalized cases, death occurred in 159 cases (25.3%). Among hospitalized fatal cases, death occurred after hospital discharge in 27 of 57 urine cases (47.4%) and 21 of 102 cases from sterile sites (20.6%). Among sterile site cases, female sex, intensive care unit (ICU) stay after culture, location in a healthcare facility, including a long-term care facility (LTCF), 3 days before culture, and diagnosis of septic shock were associated with increased odds of death in the model (Fig. 1). In urine cases, age 40–54 or ≥75 years, ICU stay after culture, presence of an indwelling device other than a urinary catheter or central line (eg, endotracheal tube), location in a LTCF 3 days before culture, diagnosis of septic shock, and Charlson comorbidity score ≥3 were associated with increased odds of mortality (Fig. 2). Conclusion: Overall 30-day mortality was high among patients with CRAB, including patients with CRAB isolated from urine. A substantial fraction of mortality occurred after discharge, especially among patients with urine cases. Although there were some differences in characteristics associated with mortality in patients with CRAB isolated from sterile sites versus urine, LTCF exposure and severe illness were associated with mortality in both patient groups. CRAB was associated with major mortality in these patients with evidence of healthcare experience and complex illness. More work is needed to determine whether prevention of CRAB infections would improve outcomes.Funding: NoneDisclosures: None

scholarly journals Immunotherapy in Adrenocortical Carcinoma: Predictors of Response, Efficacy, Safety, and Mechanisms of Resistance

Biomedicines ◽  
2021 ◽  
Vol 9 (3) ◽  
pp. 304
Author(s):  
Marta Araujo-Castro ◽  
Eider Pascual-Corrales ◽  
Javier Molina-Cerrillo ◽  
Teresa Alonso-Gordoa
Keyword(s):  
Adrenocortical Carcinoma ◽  
Checkpoint Inhibitors ◽  
Treatment Options ◽  
Progression Free Survival ◽  
Mechanisms Of Resistance ◽  
Response Efficacy ◽  
Predictors Of Response ◽  
Primary Endpoints ◽  
Tumor Mutational Burden

Adrenocortical carcinoma (ACC) is a rare endocrine malignancy with limited treatment options in the advanced stages. Immunotherapy offers hope for altering the orthodox management of cancer, and its role in advanced ACC has been investigated in different studies. With the aim clarifying the role of immunotherapy in ACC we performed a comprehensive review about this topic focusing on the predictors of response, efficacy, safety, and the mechanisms of resistance. Five clinical trials with four immune checkpoint inhibitors (pembrolizumab, avelumab, nivolumab, and ipilimumab) have investigated the role of immunotherapy in advanced ACC. Despite, the different primary endpoints used in these studies, the reported rates of overall response rate and progression free survival were generally poor. Three main potential markers of response to immunotherapy in ACC have been described: Expression of PD-1 and PD-L1, microsatellite instability and tumor mutational burden. However, none of them has been validated in prospective studies. Several mechanisms of ACC immunoevasion may be responsible of immunotherapy failure, and a greater knowledge of these mechanisms might lead to the development of new strategies to overcome the immunotherapy resistance. In conclusion, although currently the role of immunotherapy is limited, the identification of immunological markers of response and the implementation of strategies to avoid immunotherapy resistance could improve the efficacy of this therapy.

scholarly journals Resistance Mechanisms of Multiresistant Pseudomonas aeruginosa Strains from Germany and Correlation with Hypermutation

2007 ◽  
Vol 51 (11) ◽  
pp. 4062-4070 ◽  
Author(s):  
B. Henrichfreise ◽  
I. Wiegand ◽  
W. Pfister ◽  
B. Wiedemann
Keyword(s):  
Pseudomonas Aeruginosa ◽  
Efflux Pump ◽  
Acquired Resistance ◽  
Resistance Mechanisms ◽  
Type Ii ◽  
Mechanisms Of Resistance ◽  
Resistance Determinants ◽  
Class 1 ◽  
Mutator Strains ◽  
Multiresistant Strains

ABSTRACT In this study, we analyzed the mechanisms of multiresistance for 22 clinical multiresistant and clonally different Pseudomonas aeruginosa strains from Germany. Twelve and 10 strains originated from cystic fibrosis (CF) and non-CF patients, respectively. Overproduction of the efflux systems MexAB-OprM, MexCD-OprJ, MexEF-OprN, and MexXY-OprM was studied. Furthermore, loss of OprD, alterations in type II topoisomerases, AmpC overproduction, and the presence of 25 acquired resistance determinants were investigated. The presence of a hypermutation phenotype was also taken into account. Besides modifications in GyrA (91%), the most frequent mechanisms of resistance were MexXY-OprM overproduction (82%), OprD loss (82%), and AmpC overproduction (73%). Clear differences between strains from CF and non-CF patients were found: numerous genes coding for aminoglycoside-modifying enzymes and located, partially in combination with β-lactamase genes, in class 1 integrons were found only in strains from non-CF patients. Furthermore, multiple modifications in type II topoisomerases conferring high quinolone resistance levels and overexpression of MexAB-OprM were exclusively detected in multiresistant strains from non-CF patients. Correlations of the detected phenotypes and resistance mechanisms revealed a great impact of efflux pump overproduction on multiresistance in P. aeruginosa. Confirming previous studies, we found that additional, unknown chromosomally mediated resistance mechanisms remain to be determined. In our study, 11 out of 12 strains and 3 out of 10 strains from CF patients and non-CF patients, respectively, were hypermutable. This extremely high proportion of mutator strains should be taken into consideration for the treatment of multiresistant P. aeruginosa.

Resistance to nitrofurantoin is an indicator of extensive drug-resistant (XDR) Enterobacteriaceae

2021 ◽  
Vol 70 (4) ◽  
Author(s):  
Balaram Khamari ◽  
Prakash Kumar ◽  
Bulagonda Eswarappa Pradeep
Keyword(s):  
Antimicrobial Agents ◽  
Efflux Pump ◽  
Treatment Options ◽  
Strong Association ◽  
Multidrug Resistant ◽  
Resistance Mechanisms ◽  
Resistant Bacteria ◽  
Drug Resistant ◽  
Content Type ◽  
Link Type

Introduction. Nitrofurantoin is one of the preferred antibiotics in the treatment of uropathogenic multidrug-resistant (MDR) infections. However, resistance to nitrofurantoin in extensively drug-resistant (XDR) bacteria has severely limited the treatment options. Gap statement. Information related to co-resistance or collateral sensitivity (CS) with reference to nitrofurantoin resistant bacteria is limited. Aim. To study the potential of nitrofurantoin resistance as an indicator of the XDR phenotype in Enterobacteriaceae . Methods. One hundred (45 nitrofurantoin-resistant, 21 intermediately resistant and 34 nitrofurantoin-susceptible) Enterobacteriaceae were analysed in this study. Antibiotic susceptibility testing (AST) against nitrofurantoin and 17 other antimicrobial agents across eight different classes was performed by using the Vitek 2.0 system. The isolates were screened for the prevalence of acquired antimicrobial resistance (AMR) and efflux pump genes by PCR. Results. In total, 51 % of nitrofurantoin-resistant and 28 % of intermediately nitrofurantoin resistant isolates exhibited XDR characteristics, while only 3 % of nitrofurantoin-sensitive isolates were XDR (P=0.0001). Significant co-resistance was observed between nitrofurantoin and other tested antibiotics (β-lactam, cephalosporin, carbapenem, aminoglycoside and tetracycline). Further, the prevalence of AMR and efflux pump genes was higher in the nitrofurantoin-resistant strains compared to the susceptible isolates. A strong association was observed between nitrofurantoin resistance and the presence of bla PER-1, bla NDM-1, bla OXA-48, ant(2) and oqxA-oqxB genes. Tigecycline (84 %) and colistin (95 %) were the only antibiotics to which the majority of the isolates were susceptible. Conclusion. Nitrofurantoin resistance could be an indicator of the XDR phenotype among Enterobacteriaceae , harbouring multiple AMR and efflux pump genes. Tigecycline and colistin are the only antibiotics that could be used in the treatment of such XDR infections. A deeper understanding of the co-resistance mechanisms in XDR pathogens and prescription of AST-based appropriate combination therapy may help mitigate this problem.

Diversity of polymyxin resistance mechanisms among Acinetobacter baumannii clinical isolates

2017 ◽  
Vol 87 (1) ◽  
pp. 37-44 ◽  
Author(s):  
Raquel Girardello ◽  
Marina Visconde ◽  
Rodrigo Cayô ◽  
Regina Célia Bressan Queiroz de Figueiredo ◽  
Marcelo Alves da Silva Mori ◽  
...  
Keyword(s):  
Acinetobacter Baumannii ◽  
Resistance Mechanisms ◽  
Clinical Isolates

scholarly journals Combining radiomics and mathematical modeling to elucidate mechanisms of resistance to immune checkpoint blockade in non-small cell lung cancer

2017 ◽  
Author(s):  
Daryoush Saeed-Vafa ◽  
Rafael Bravo ◽  
Jamie A. Dean ◽  
Asmaa El-Kenawi ◽  
Nathaniel Mon Père ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Checkpoint Inhibitor ◽  
Cancer Recurrence ◽  
Initial Response ◽  
Resistance Mechanisms ◽  
Ct Images ◽  
Immune Checkpoint Blockade ◽  
Imaging Features ◽  
Mechanisms Of Resistance ◽  
Number Of Patients

AbstractImmune therapies have shown promise in a number of cancers, and clinical trials using the anti-PD-L1/PD-1 checkpoint inhibitor in lung cancer have been successful for a number of patients. However, some patients either do not respond to the treatment or have cancer recurrence after an initial response. It is not clear which patients might fall into these categories or what mechanisms are responsible for treatment failure. To explore the different underlying biological mechanisms of resistance, we created a spatially explicit mathematical model with a modular framework. This construction enables different potential mechanisms to be turned on and off in order to adjust specific tumor and tissue interactions to match a specific patient's disease. In parallel, we developed a software suite to identify significant computed tomography (CT) imaging features correlated with outcome using data from an anti-PDL-1 checkpoint inhibitor clinical trial for lung cancer and a tool that extracts these features from both patient CT images and “virtual CT” images created from the cellular density profile of the model. The combination of our two toolkits provides a framework that feeds patient data through an iterative pipeline to identify predictive imaging features associated with outcome, whilst at the same time proposing hypotheses about the underlying resistance mechanisms.

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