Multiple Antibiotics
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Xin Wen ◽  
Cong Shen ◽  
Jinyu Xia ◽  
Lan-Lan Zhong ◽  
Zhongwen Wu ◽  

Clostridioides difficile infections (CDI) are the leading cause of healthcare-associated diarrhea and are known to be resistant to multiple antibiotics. In the past decade, C. difficile has emerged rapidly and has spread globally, causing great concern among American and European countries.

N. E. Ballesteros-Nova ◽  
S. Sánchez ◽  
J. L. Steffani ◽  
L. C. Sierra ◽  
Z. Chen ◽  

Salmonella enterica (SE) can survive in surface waters (SuWa) and the role of non-host environments in its transmission has acquired increasing relevance. In this study, we conducted comparative genomic analyses of 172 SE isolates collected from SuWa across three months in six states of central Mexico during 2019. SE transmission dynamics were assessed using 87 experimental and 112 public isolates from Mexico collected during 2002-2019. We also studied genetic relatedness between SuWa isolates and human clinical strains collected in North America during 2005-2020. Among experimental isolates, we identified 41 SE serovars and 56 multi-locus sequence types (ST). Predominant serovars were Senftenberg (n=13), Meleagridis, Agona, and Newport (n=12 each), Give (n=10), Anatum (n=8), Adelaide (n=7), and Infantis, Mbandaka, Ohio and Typhimurium (n=6 each). We observed a high genetic diversity in the sample under study, as well as clonal dissemination of strains across distant regions. Some of these strains are epidemiologically important (ST14, ST45, ST118, ST132, ST198, and ST213), and were genotypically close to those involved in clinical cases in North America. Transmission network analysis suggests that SuWa are a relevant source of SE (0.7 source/hub ratio) and contributes to its dissemination as isolates from varied sources and clinical cases have SuWa isolates as common ancestors. Overall, the study shows SuWa act as reservoir of various SE serovars of public health significance. Further research is needed to better understand the mechanisms involved in SuWa contamination by SE, as well as develop interventions to contain its dissemination to food production settings. Study importance Surface waters are heavily used in food production worldwide. Several human pathogens can survive in these waters for long periods and disseminate to food production environments, contaminating our food supply. One of these pathogens is Salmonella enterica , a leading cause of foodborne infections, hospitalizations and deaths in many countries. This research demonstrates the role of surface waters as a vehicle for the transmission of Salmonella along food production chains. It also shows some strains circulating in surface waters are very similar to those implicated in human infections and harbor genes that confer resistance to multiple antibiotics, posing a risk to public health. The study contributes to expand our current knowledge on the ecology and epidemiology of Salmonella in surface waters.

2022 ◽  
Vol 13 (1) ◽  
Coline Plé ◽  
Heng-Keat Tam ◽  
Anais Vieira Da Cruz ◽  
Nina Compagne ◽  
Juan-Carlos Jiménez-Castellanos ◽  

AbstractEfflux transporters of the RND family confer resistance to multiple antibiotics in Gram-negative bacteria. Here, we identify and chemically optimize pyridylpiperazine-based compounds that potentiate antibiotic activity in E. coli through inhibition of its primary RND transporter, AcrAB-TolC. Characterisation of resistant E. coli mutants and structural biology analyses indicate that the compounds bind to a unique site on the transmembrane domain of the AcrB L protomer, lined by key catalytic residues involved in proton relay. Molecular dynamics simulations suggest that the inhibitors access this binding pocket from the cytoplasm via a channel exclusively present in the AcrB L protomer. Thus, our work unveils a class of allosteric efflux-pump inhibitors that likely act by preventing the functional catalytic cycle of the RND pump.

2022 ◽  
Vol 22 (1) ◽  
Shamima Nasrin ◽  
Nicolas Hegerle ◽  
Shaichi Sen ◽  
Joseph Nkeze ◽  
Sunil Sen ◽  

Abstract Background Pseudomonas aeruginosa is an opportunistic pathogen that causes a wide range of acute and chronic infections and is frequently associated with healthcare-associated infections. Because of its ability to rapidly acquire resistance to antibiotics, P. aeruginosa infections are difficult to treat. Alternative strategies, such as a vaccine, are needed to prevent infections. We collected a total of 413 P. aeruginosa isolates from the blood and cerebrospinal fluid of patients from 10 countries located on 4 continents during 2005–2017 and characterized these isolates to inform vaccine development efforts. We determined the diversity and distribution of O antigen and flagellin types and antibiotic susceptibility of the invasive P. aeruginosa. We used an antibody-based agglutination assay and PCR for O antigen typing and PCR for flagellin typing. We determined antibiotic susceptibility using the Kirby-Bauer disk diffusion method. Results Of the 413 isolates, 314 (95%) were typed by an antibody-based agglutination assay or PCR (n = 99). Among the 20 serotypes of P. aeruginosa, the most common serotypes were O1, O2, O3, O4, O5, O6, O8, O9, O10 and O11; a vaccine that targets these 10 serotypes would confer protection against more than 80% of invasive P. aeruginosa infections. The most common flagellin type among 386 isolates was FlaB (41%). Resistance to aztreonam (56%) was most common, followed by levofloxacin (42%). We also found that 22% of strains were non-susceptible to meropenem and piperacillin-tazobactam. Ninety-nine (27%) of our collected isolates were resistant to multiple antibiotics. Isolates with FlaA2 flagellin were more commonly multidrug resistant (p = 0.04). Conclusions Vaccines targeting common O antigens and two flagellin antigens, FlaB and FlaA2, would offer an excellent strategy to prevent P. aeruginosa invasive infections.

2022 ◽  
Vol 67 (4) ◽  
pp. 56-67
Gaffar Sarwar Zaman ◽  
Mohammad Y. Alshahrani ◽  
Pranab Barua ◽  
Alanoud Aladel ◽  
Forhad Akhtar Zaman ◽  

During the previous few decades, it has been seen that there is a rapid emergence of pathogens resistant to multiple antibiotics. This has now become a global crisis. Some unexplored or less explored plants also provide some antibacterial, bactericidal and antioxidant properties. The antibacterial, bactericidal effects of extracted essential oils (EEOs) of Thunbergia coccinea, Acacia polyacantha, Polygonum micrpcephallum, Abies spectabilis and Clerodendrum colebrookianum was tested in comparison with standard antibiotics. The methods chosen were disc diffusion and deduction of minimum inhibitory concentration (MIC) by microbroth dilution assays of the EEOs against the bacterial strains.The antioxidant activity was found out utilizing DPPH free radical scavenging assay, MDA, Hydrogen peroxide radical inhibition assay and Superoxide radical inhibition assay (O 2 -). Some commonly used standard antibiotics (metronidazole, amoxicillin, clarithromycin, rifampicin, clindamycin and oxacillin,) were utilized to compare the EEO antibacterial action. Clerodendrum colebrookianum (85.17 ± 3.06 µg MDA/g extract) had a reasonable MDA. Acacia polyacantha in MIC had values of 3.86 ± 0.25 to 6.20 ± 0.16. Polygonum micrpcephallum had excessive H2O2 (48.27 ± 2.4 5%). The antibacterial actions determined by the paper disc‑diffusion technique of the EEO extracted from these plants showed that most had some antibacterial actions. Also, it was seen that the bactericidal action of the EEO extracted from E. alba was most potent against S. pyogenes (4.06 ± 0.15). The extract of the plant at varying concentrations (20, 40, 60, 80 and100 mg/mL) demonstrated noteworthy (P< 0.001) anthelmintic action in an effective change when the dose was adjusted. In conclusion, most of the tested plants contain a medicinal value, which can be utilized in the future to supplement artificial medicines and cure emerging diseases that create havoc for mankind. 

Yongcui Wang ◽  
Lei Chu ◽  
Jian Ma ◽  
Guangyu Chi ◽  
Caiyan Lu ◽  

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.

2021 ◽  
Vol 10 (1) ◽  
pp. 58
Hadas Kon ◽  
Amichay Hameir ◽  
Elizabeth Temkin ◽  
Alona Keren-Paz ◽  
David Schwartz ◽  

Colistin dependent (CD) isolates are dependent on colistin for optimal growth. Here we aimed to systematically determine the emergence of CD among colistin-heteroresistant carbapenem-resistant Acinetobacter baumannii (CRAB) isolates. We also examined the phenotypic characteristics of CD and the evolution of CD strains to overt resistance. Additionally, we examined whether detection of growth in blood cultures was impaired by CD. Heteroresistant isolates, as determined by population analysis profiling, were exposed to colistin; when the colony count with colistin was significantly higher than without, isolates were suspected to be CD. CD was confirmed by Etest and growth curves. CD strains with colistin minimum inhibitory concentrations > 2 mg/L after growth in colistin-free media were considered colistin-resistant. Of the 65 heteroresistant strains tested, eight became CD after colistin exposure. These strains attained higher colony counts and growth rates with colistin vs. without, and grew adjacent to the colistin Etest strip. CD strains exhibited increased susceptibilities to multiple antibiotics compared to their parent heteroresistant strains. All CD strains tested became colistin-resistant following growth without colistin. CD strains were detected in blood culture bottles, but time to detection was significantly prolonged compared with parent strains, suggesting that CD may lead to delay in detection of CRAB bacteremia.

2021 ◽  
Jules D. P. Valentin ◽  
Hervé Straub ◽  
Franziska Pietsch ◽  
Marion Lemare ◽  
Christian H. Ahrens ◽  

AbstractPseudomonas aeruginosa biofilms exhibit an intrinsic resistance to antibiotics and constitute a considerable clinical threat. In cystic fibrosis, a common feature of biofilms formed by P. aeruginosa in the airway is the occurrence of mutants deficient in flagellar motility. This study investigates the impact of flagellum deletion on the structure and antibiotic tolerance of P. aeruginosa biofilms, and highlights a role for the flagellum in adaptation and cell survival during biofilm development. Mutations in the flagellar hook protein FlgE influence greatly P. aeruginosa biofilm structuring and antibiotic tolerance. Phenotypic analysis of the flgE knockout mutant compared to the wild type (WT) reveal increased fitness under planktonic conditions, reduced initial adhesion but enhanced formation of microcolony aggregates in a microfluidic environment, and decreased expression of genes involved in exopolysaccharide formation. Biofilm cells of the flgE knock-out mutant display enhanced tolerance towards multiple antibiotics, whereas its planktonic cells show similar resistance to the WT. Confocal microscopy of biofilms demonstrates that gentamicin does not affect the viability of cells located in the inner part of the flgE knock-out mutant biofilms due to reduced penetration. These findings suggest that deficiency in flagellar proteins like FlgE in biofilms and in cystic fibrosis infections represent phenotypic and evolutionary adaptations that alter the structure of P. aeruginosa biofilms conferring increased antibiotic tolerance.

2021 ◽  
Vol 6 ◽  
pp. 333
Ujjwol Risal ◽  
Anup Subedee ◽  
Raju Pangeni ◽  
Rakshya Pandey ◽  
Suravi Pandey ◽  

Vaccination against the virus responsible for COVID-19 has become a key in preventing mortality and morbidity related to the infection. Studies have shown that the benefits of vaccination outweigh the risks. However, there are concerns regarding serious adverse events of some vaccines,      although they are fortunately      rare. Here, we report a case of a 47-year-old female from Kathmandu who presented with high grade fever, dry cough and erythematous rash a week after exposure to the Oxford-AstraZeneca vaccine. She had hepatosplenomegaly, persistent leucocytosis, anaemia and thrombocytosis along with markedly raised inflammatory markers. Her tests for infectious causes and haematological malignancies was negative and she showed no response to multiple antibiotics. Finally, she had a dramatic response to steroids with disappearance of fever and normalization of other laboratory parameters. Hence, she was diagnosed with       Adult-onset Still’s      Disease (AOSD). She was under methotrexate and prednisolone tapering dose and doing well as at time of writing. The trigger for the disease was hypothesized to be the vaccine because of the strong temporal association.

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