scholarly journals A Bayesian approach to modeling antimicrobial multidrug resistance

PLoS ONE ◽  
2021 ◽  
Vol 16 (12) ◽  
pp. e0261528
Min Zhang ◽  
Chong Wang ◽  
Annette O’Connor

Multidrug resistance (MDR) has been a significant threat to public health and effective treatment of bacterial infections. Current identification of MDR is primarily based upon the large proportions of isolates resistant to multiple antibiotics simultaneously, and therefore is a belated evaluation. For bacteria with MDR, we expect to see strong correlations in both the quantitative minimum inhibitory concentration (MIC) and the binary susceptibility as classified by the pre-determined breakpoints. Being able to detect correlations from these two perspectives allows us to find multidrug resistant bacteria proactively. In this paper, we provide a Bayesian framework that estimates the resistance level jointly for antibiotics belonging to different classes with a Gaussian mixture model, where the correlation in the latent MIC can be inferred from the Gaussian parameters and the correlation in binary susceptibility can be inferred from the mixing weights. By augmenting the laboratory measurement with the latent MIC variable to account for the censored data, and by adopting the latent class variable to represent the MIC components, our model was shown to be accurate and robust compared with the current assessment of correlations. Applying the model to Salmonella heidelberg samples isolated from human participants in National Antimicrobial Resistance Monitoring System (NARMS) provides us with signs of joint resistance to Amoxicillin-clavulanic acid & Cephalothin and joint resistance to Ampicillin & Cephalothin. Large correlations estimated from our model could serve as a timely tool for early detection of MDR, and hence a signal for clinical intervention.

Antibiotics ◽  
2021 ◽  
Vol 10 (5) ◽  
pp. 571
Nicole Zacharias ◽  
Iris Löckener ◽  
Sarah M. Essert ◽  
Esther Sib ◽  
Gabriele Bierbaum ◽  

Bacterial infections have been treated effectively by antibiotics since the discovery of penicillin in 1928. A worldwide increase in the use of antibiotics led to the emergence of antibiotic resistant strains in almost all bacterial pathogens, which complicates the treatment of infectious diseases. Antibiotic-resistant bacteria play an important role in increasing the risk associated with the usage of surface waters (e.g., irrigation, recreation) and the spread of the resistance genes. Many studies show that important pathogenic antibiotic-resistant bacteria can enter the environment by the discharge of sewage treatment plants and combined sewage overflow events. Mussels have successfully been used as bio-indicators of heavy metals, chemicals and parasites; they may also be efficient bio-indicators for viruses and bacteria. In this study an influence of the discharge of a sewage treatment plant could be shown in regard to the presence of E. coli in higher concentrations in the mussels downstream the treatment plant. Antibiotic-resistant bacteria, resistant against one or two classes of antibiotics and relevance for human health could be detected in the mussels at different sampling sites of the river Rhine. No multidrug-resistant bacteria could be isolated from the mussels, although they were found in samples of the surrounding water body.

Molecules ◽  
2021 ◽  
Vol 26 (7) ◽  
pp. 2047
Magda Ferreira ◽  
Maria Ogren ◽  
Joana N. R. Dias ◽  
Marta Silva ◽  
Solange Gil ◽  

Antimicrobial drugs are key tools to prevent and treat bacterial infections. Despite the early success of antibiotics, the current treatment of bacterial infections faces serious challenges due to the emergence and spread of resistant bacteria. Moreover, the decline of research and private investment in new antibiotics further aggravates this antibiotic crisis era. Overcoming the complexity of antimicrobial resistance must go beyond the search of new classes of antibiotics and include the development of alternative solutions. The evolution of nanomedicine has allowed the design of new drug delivery systems with improved therapeutic index for the incorporated compounds. One of the most promising strategies is their association to lipid-based delivery (nano)systems. A drug’s encapsulation in liposomes has been demonstrated to increase its accumulation at the infection site, minimizing drug toxicity and protecting the antibiotic from peripheral degradation. In addition, liposomes may be designed to fuse with bacterial cells, holding the potential to overcome antimicrobial resistance and biofilm formation and constituting a promising solution for the treatment of potential fatal multidrug-resistant bacterial infections, such as methicillin resistant Staphylococcus aureus. In this review, we aim to address the applicability of antibiotic encapsulated liposomes as an effective therapeutic strategy for bacterial infections.

Antibiotics ◽  
2020 ◽  
Vol 9 (2) ◽  
pp. 80 ◽  
Silpak Biswas ◽  
Mohammed Elbediwi ◽  
Guimin Gu ◽  
Min Yue

Colistin is considered to be a ‘last-resort’ antimicrobial for the treatment of multidrug-resistant Gram-negative bacterial infections. Identification of Enterobacteriaceae, carrying the transferable colistin resistance gene mcr-1, has recently provoked a global health concern. This report presents the first detection of a hydrogen sulfide (H2S)-producing Escherichia coli variant isolated from a human in China, with multidrug resistance (MDR) properties, including colistin resistance by the mcr-1 gene, which could have great implications for the treatment of human infections.

2018 ◽  
Vol 115 (51) ◽  
pp. 12887-12895 ◽  
Stephen J. Baker ◽  
David J. Payne ◽  
Rino Rappuoli ◽  
Ennio De Gregorio

Bacterial infections have been traditionally controlled by antibiotics and vaccines, and these approaches have greatly improved health and longevity. However, multiple stakeholders are declaring that the lack of new interventions is putting our ability to prevent and treat bacterial infections at risk. Vaccine and antibiotic approaches still have the potential to address this threat. Innovative vaccine technologies, such as reverse vaccinology, novel adjuvants, and rationally designed bacterial outer membrane vesicles, together with progress in polysaccharide conjugation and antigen design, have the potential to boost the development of vaccines targeting several classes of multidrug-resistant bacteria. Furthermore, new approaches to deliver small-molecule antibacterials into bacteria, such as hijacking active uptake pathways and potentiator approaches, along with a focus on alternative modalities, such as targeting host factors, blocking bacterial virulence factors, monoclonal antibodies, and microbiome interventions, all have potential. Both vaccines and antibacterial approaches are needed to tackle the global challenge of antimicrobial resistance (AMR), and both areas have the underpinning science to address this need. However, a concerted research agenda and rethinking of the value society puts on interventions that save lives, by preventing or treating life-threatening bacterial infections, are needed to bring these ideas to fruition.

2017 ◽  
Vol 63 (11) ◽  
pp. 865-879 ◽  
Ayman El-Shibiny ◽  
Salma El-Sahhar

Since their discovery in 1915, bacteriophages have been used to treat bacterial infections in animals and humans because of their unique ability to infect their specific bacterial hosts without affecting other bacterial populations. The research carried out in this field throughout the 20th century, largely in Georgia, part of USSR and Poland, led to the establishment of phage therapy protocols. However, the discovery of penicillin and sulfonamide antibiotics in the Western World during the 1930s was a setback in the advancement of phage therapy. The misuse of antibiotics has reduced their efficacy in controlling pathogens and has led to an increase in the number of antibiotic-resistant bacteria. As an alternative to antibiotics, bacteriophages have become a topic of interest with the emergence of multidrug-resistant bacteria, which are a threat to public health. Recent studies have indicated that bacteriophages can be used indirectly to detect pathogenic bacteria or directly as biocontrol agents. Moreover, they can be used to develop new molecules for clinical applications, vaccine production, drug design, and in the nanomedicine field via phage display.

2018 ◽  
Vol 14 ◽  
pp. 2881-2896 ◽  
Laura Carro

Antibiotics are potent pharmacological weapons against bacterial infections; however, the growing antibiotic resistance of microorganisms is compromising the efficacy of the currently available pharmacotherapies. Even though antimicrobial resistance is not a new problem, antibiotic development has failed to match the growth of resistant pathogens and hence, it is highly critical to discover new anti-infective drugs with novel mechanisms of action which will help reducing the burden of multidrug-resistant microorganisms. Protein–protein interactions (PPIs) are involved in a myriad of vital cellular processes and have become an attractive target to treat diseases. Therefore, targeting PPI networks in bacteria may offer a new and unconventional point of intervention to develop novel anti-infective drugs which can combat the ever-increasing rate of multidrug-resistant bacteria. This review describes the progress achieved towards the discovery of molecules that disrupt PPI systems in bacteria for which inhibitors have been identified and whose targets could represent an alternative lead discovery strategy to obtain new anti-infective molecules.

2020 ◽  
Ai-Min Jiang ◽  
Xin Shi ◽  
Na Liu ◽  
Huan Gao ◽  
Meng-Di Ren ◽  

Abstract Background: Bacterial infections are the most frequent complications in patients with malignancy, and the epidemiology of nosocomial infections among cancer patients has changed over time. This study aimed to evaluate characteristics, antibiotic-resistant patterns, and prognosis of nosocomial infections caused by multidrug-resistant (MDR) bacteria in cancer patients. Methods: This retrospective observational study analyzed cancer patients with MDR bacteria caused nosocomial infections from August 2013 to May 2019. The extracted clinical data were recorded in a standardized form and compared based on the patient’s survival status after infection during hospitalization. Data were analyzed by using independent samples t-test, Chi-square test, and binary logistic regression. P -values < 0.05 were considered statistically significant. Results: Overall, 257 cancer patients developed nosocomial infections caused by MDR bacteria. Extended-spectrum β-lactamase producing Enterobacteriaceae (ESBL-PE) was the most frequently isolated multidrug-resistant Gram-negative bacteria (MDRGNB), followed by Acinetobacter baumannii , and Stenotrophomonas maltophilia . Smoking history, cancer patients who received intrapleural/abdominal infusion within 30 days, presence of indwelling urinary catheter, and haemoglobin were independent factors for in-hospital mortality in the study population. The isolated MDR bacteria were mainly sensitive to amikacin, meropenem, imipenem, tigecycline, and piperacillin/tazobactam. Conclusions: This study confirms that MDR bacteria caused nosocomial infections were widely prevalent in cancer patients. ESBL-PE was the most commonly MDR bacteria, and the isolated MDR strains were mainly sensitive to amikacin, meropenem, imipenem, tigecycline, and piperacillin/tazobactam. Former smokers, cancer patients who received intrapleural/abdominal infusion within 30 days, presence of indwelling urinary catheter, and anemia were associated with increased in-hospital mortality. Our findings suggest that clinicians should think highly of nosocomial infections caused by MDR in cancer patients and advise policymakers to develop a guideline.

2021 ◽  
Vol 42 (6supl2) ◽  
pp. 3813-3824
Rodrigo Pacheco Ornellas ◽  
Hugo Peralva Lopes ◽  
Daniela de Queiroz Baptista ◽  
Thomas Salles Dias ◽  

Broiler chickens and derived products are a key source of Shiga toxin-producing Escherichia coli (STEC) in humans. This pathotype is responsible for causing severe episodes of diarrhea, which can progress to systemic complications. A rapid and accurate diagnosis of the disease, and early treatment of the infection with antimicrobials, can prevent it worsening. However, multidrug-resistant strains have potentially negative implications for treatment success. In this context, the aim of the present study was to isolate and identify multidrug-resistant STEC strains from broiler chickens and carcasses. Of 171 E. coli strains, isolated by conventional microbiological techniques and submitted to Polymerase Chain Reaction (PCR), for detection of stx1 and stx2 genes, 21.05% (36/171) were STEC pathotype, and most of them (66.67% - 24/36) carried both stx1 and eae genes. The multidrug resistance pattern was observed in 75% (27/36) of STEC strains. The presence of STEC in broiler chickens and carcasses reinforces that these sources may act as reservoirs for this pathotype. Multidrug-resistant bacteria contaminating animal products represent a public health issue because of the possibility of spread of multidrug-resistant determinants in the food chain and a higher risk of failure in human treatment when antimicrobials are needed.

2021 ◽  
Vol 11 (18) ◽  
pp. 8479
Sereen M. B. Bataineh ◽  
Yaser H. Tarazi ◽  
Wafá A. Ahmad

The aim of this study was to evaluate the in vitro antimicrobial activity of medicinal Methanolic plant extracts against multidrug-resistant bacteria to determine the cytotoxicity of these extracts on eukaryotic cells, and to confirm their efficacy against Methicillin-Resistant Staphylococcus aureus (MRSA) in experimental animals. The effects of the methanol extract of sixty folk plants were investigated on; MRSA, Extended Spectrum Beta-Lactamase E. coli and MDR Pseudomonas aeruginosa by disc diffusion and MIC assay. Cytotoxicity was determined using MTT and hemolysis of human erythrocytes. Three plant extracts with the highest antimicrobial activities were tested using a challenge experiment on mice. Systemic infection was performed by intraperitoneal inoculation of (5 × 106 CFU/mL) of MRSA isolate. Then mice received 300 mg/kg body weight of the plant extracts daily for seven days. The efficacy of plant extracts was evaluated by general health, mortality rate, gross lesion, and histopathology study of inoculated mice. Only ten plants showed activities against different MDR bacteria with inhibitory zones ranging from (8 to 22 mm) in diameter. Of the ten medicinal plant extracts, and Aloysia citrodora showed the highest activities against MRSA and Camellia sinensis MSSA isolates, with MIC values ranging from 0.5 to 1.5 mg/mL, followed by Hibiscus sabdariffa, Thymus vulgaris, and Glycyrrhiza glabra. Furthermore, the extract of the effective plants showed low toxicity against Vero and fibroblasts cell lines, along with inhibitory activities to erythrocytes membrane disruption. The in vivo study demonstrated that Camellia sinensis showed significant activity against MRSA infections in mice. The results validate that these plants are effective and safe antibacterial agents against multidrug-resistance bacteria, and have the potential to be utilized as an alternative to antibiotics for the treatment of bacterial infections.

Antibiotics ◽  
2020 ◽  
Vol 9 (10) ◽  
pp. 688
Shashi B. Kumar ◽  
Shanvanth R. Arnipalli ◽  
Ouliana Ziouzenkova

Antibiotics have been used as essential therapeutics for nearly 100 years and, increasingly, as a preventive agent in the agricultural and animal industry. Continuous use and misuse of antibiotics have provoked the development of antibiotic resistant bacteria that progressively increased mortality from multidrug-resistant bacterial infections, thereby posing a tremendous threat to public health. The goal of our review is to advance the understanding of mechanisms of dissemination and the development of antibiotic resistance genes in the context of nutrition and related clinical, agricultural, veterinary, and environmental settings. We conclude with an overview of alternative strategies, including probiotics, essential oils, vaccines, and antibodies, as primary or adjunct preventive antimicrobial measures or therapies against multidrug-resistant bacterial infections. The solution for antibiotic resistance will require comprehensive and incessant efforts of policymakers in agriculture along with the development of alternative therapeutics by experts in diverse fields of microbiology, biochemistry, clinical research, genetic, and computational engineering.

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