scholarly journals Rapid heuristic inference of antibiotic resistance and susceptibility by genomic neighbor typing

2018 ◽  
Author(s):  
Karel Břinda ◽  
Alanna Callendrello ◽  
Kevin C. Ma ◽  
Derek R MacFadden ◽  
Themoula Charalampous ◽  
...  

AbstractSurveillance of drug-resistant bacteria is essential for healthcare providers to deliver effective empiric antibiotic therapy. However, traditional molecular epidemiology does not typically occur on a timescale that could impact patient treatment and outcomes. Here we present a method called ‘genomic neighbor typing’ for inferring the phenotype of a bacterial sample by identifying its closest relatives in a database of genomes with metadata. We show that this technique can infer antibiotic susceptibility and resistance for both S. pneumoniae and N. gonorrhoeae. We implemented this with rapid k-mer matching, which, when used on Oxford Nanopore MinION data, can run in real time. This resulted in determination of resistance within ten minutes (sens/spec 91%/100% for S. pneumoniae and 81%/100% N. gonorrhoeae from isolates with a representative database) of sequencing starting, and for clinical metagenomic sputum samples (75%/100% for S. pneumoniae), within four hours of sample collection. This flexible approach has wide application to pathogen surveillance and may be used to greatly accelerate appropriate empirical antibiotic treatment.

Antibiotics ◽  
2021 ◽  
Vol 10 (6) ◽  
pp. 712
Author(s):  
Ali Salama ◽  
Ammar Almaaytah ◽  
Rula M. Darwish

(1) Background: Antimicrobial resistance represents an urgent health dilemma facing the global human population. The development of novel antimicrobial agents is needed to face the rising number of resistant bacteria. Ultrashort antimicrobial peptides (USAMPs) are considered promising antimicrobial agents that meet the required criteria of novel antimicrobial drug development. (2) Methods: Alapropoginine was rationally designed by incorporating arginine (R), biphenylalanine (B), and naproxen to create an ultrashort hexapeptide. The antimicrobial activity of alapropoginine was evaluated against different strains of bacteria. The hemolytic activity of alapropoginine was also investigated against human erythrocytes. Finally, synergistic studies with antibiotics were performed using the checkerboard technique and the determination of the fractional inhibitory index. (3) Results: Alapropoginine displayed potent antimicrobial activities against reference and multi-drug-resistant bacteria with MIC values of as low as 28.6 µg/mL against methicillin-resistant S. aureus. Alapropoginine caused negligible toxicity toward human red blood cells. Moreover, the synergistic studies showed improved activities for the combined conventional antibiotics with a huge reduction in their antimicrobial concentrations. (4) Conclusions: The present study indicates that alapropoginine exhibits promising antimicrobial activity against reference and resistant strains of bacteria with negligible hemolytic activity. Additionally, the peptide displays synergistic or additive effects when combined with several antibiotics.


2021 ◽  
pp. 126958
Author(s):  
Campista-León Samuel ◽  
López-Espinoza José Uriel ◽  
Garcia-Guerrero Joel Tohevaris ◽  
Alfonso-Corrado Cecilia ◽  
Clark-Tapia Ricardo ◽  
...  

2009 ◽  
Vol 11 (8) ◽  
pp. 645-649 ◽  
Author(s):  
Lynelle R. Johnson ◽  
Philip H. Kass

Empiric antibiotic therapy is often employed to treat feline chronic rhinosinusitis (CRS), however, collection of samples for culture should result in improved antibiotic selection and development of less antibacterial resistance. This study evaluated the effect of sampling method on culture results in 44 cats and found that aerobic and anaerobic cultures were positive significantly more often from nasal flush samples than from tissue biopsy samples. Frequency of positive Mycoplasma species culture did not differ between the two sampling methodologies, although results were discordant in eight sample pairs. Mycoplasma species were cultured from flush samples only in three cats and from biopsy samples only in five cats. These results suggest that a nasal flush sample is adequate for determining the presence of bacterial organisms in feline nasal disease, however, failure to culture Mycoplasma species from a nasal flush must be interpreted with caution.


2012 ◽  
Vol 33 (4) ◽  
pp. 416-420 ◽  
Author(s):  
Megan E. Davis ◽  
Deverick J. Anderson ◽  
Michelle Sharpe ◽  
Luke F. Chen ◽  
Richard H. Drew

This study aimed to determine the feasibility of using likelihood of inadequate therapy (LIT), a parameter calculated by using pathogen frequency and in vitro susceptibility for determination of appropriate empiric antibiotic therapy for primary bloodstream infections. Our study demonstrates that LIT may reveal differences in traditional antibiograms.


2019 ◽  
Vol 4 ◽  
pp. 140
Author(s):  
Quentin J. Leclerc ◽  
Nichola R. Naylor ◽  
Alexander M. Aiken ◽  
Francesc Coll ◽  
Gwenan M. Knight

Background: Antibiotics are most often prescribed empirically, meaning that they are used to treat infection syndromes prior to identification of the causative bacteria and their susceptibility to antibiotics. The effectiveness of antibiotic therapies is now compromised by the emergence and spread of antibiotic-resistant bacteria. Guidelines on empiric antibiotic therapy are a key component of effective clinical care for infection syndromes, as treatment needs to be informed by knowledge of likely aetiology and bacterial resistance patterns. Methods: We used open-access antimicrobial resistance (AMR) surveillance datasets, including the newly available ATLAS dataset from Pfizer, to derive a composite index of antibiotic resistance for common infection syndromes. Results: We developed a framework that integrated data on antibiotic prescribing guidelines, aetiology of infections, access to and cost of antibiotics, with antibiotic susceptibilities from global AMR surveillance datasets to create an empirical prescribing index. The results are presented in an interactive web app to allow users to visualise underlying resistance rates to first-line empiric antibiotics for their infection syndromes and countries of interest. Conclusions: We found that whilst an index for empiric antibiotic therapy based on resistance data can technically be created, the ATLAS dataset in its current form can only inform on a limited number of infection syndromes. Other open-access AMR surveillance datasets (ECDC Surveillance Atlas, CDDEP ResistanceMap and WHO GLASS datasets) are largely limited to bacteraemia-derived specimens and cannot directly inform treatment of other infection syndromes. With improving data availability on international rates of AMR and better understanding of infection aetiology, our approach may prove useful for informing empiric prescribing decisions in settings with limited local AMR surveillance data. Syndrome-level resistance could be a more clinically relevant measure of resistance to inform on the appropriateness of empiric antibiotic therapies at the country-level.


2021 ◽  
Vol 99 (4) ◽  
pp. 22-28
Author(s):  
I. B. Viktorova ◽  
V. N. Zimina ◽  
I. V. Dadyka ◽  
I. V. Аndreeva ◽  
I. A. Golovina ◽  
...  

The objective: to study the frequency and nature of community-acquired pneumonia (CAP) in HIV patients.Subjects and methods: The continuous longitudinal retrospective study of all cases of respiratory diseases among HIV patients (n = 185), who received in-patient treatment in the therapy department.Results. CAP was diagnosed in 38.4% (n = 71) of patients and it was the most frequent respiratory disease among HIV patients. The median CD4 count in CAP made 197.5 cells/μL, 9.1% of patients received antiretroviral therapy before hospital admission. 74.7% of CAP patients (n = 53) had lesions disseminated to several lobes. Laboratory parameters revealed in severe CAP (leukocytosis > 12 × 109/L, leukopenia < 4.0 × 109/L and thrombocytopenia < 100 × 1012/L) were associated with the degree of immunodeficiency and did not depend on the infiltration dissemination (p > 0.05). Bacteremia in CAP was detected in 20.8% of patients and it was associated with the failure of standard empiric antibiotic therapy (p < 0.05). 9.9% of CAP patients (n = 7) were diagnosed with polymicrobial infection. Lethal outcomes of CAP were recorded in 5.6% of cases (n = 4), all with severe immunosuppression (the median of CD4 count was 5 cells/μL), 2 cases had bilateral subtotal CAP and 2 suffered from polymicrobial infection.


2019 ◽  
Vol 14 ◽  
Author(s):  
Nicolò Capsoni ◽  
Pietro Bellone ◽  
Stefano Aliberti ◽  
Giovanni Sotgiu ◽  
Donatella Pavanello ◽  
...  

Background: Although previous studies showed an increasing prevalence of infections due to multi-drug resistant (MDR) bacteria in the community, specific data on sepsis are lacking. We aimed to assess prevalence, risk factors and outcomes of patients with sepsis due to MDR bacteria. Methods: An observational, retrospective study was conducted on consecutive adult patients coming from the community and admitted to the Policlinico Hospital, Milan, Italy, with a diagnosis of sepsis between January 2011 and December 2015. Primary study outcome was in-hospital mortality. Results: Among 518 patients, at least one MDR bacteria was isolated in 88 (17%). ESBL+ Enterobacteriaceae were the most prevalent MDR bacteria (9.7%) followed by MRSA (3.9%). Independent risk factors for sepsis due to MDR bacteria were septic shock (OR: 2.2; p = 0.002) and hospitalization in the previous 90 days (OR: 2.3; p = 0.003). Independent risk factors for sepsis due to ESBL+ bacteria were hospitalization in the previous 90 days (OR: 2.1; p = 0.02) and stroke (OR: 2.1; p = 0.04). A significantly higher mortality was detected among patients with vs. without MDR bacteria (40.2% vs. 23.1% respectively, p = 0.001). Independent risk factors for mortality among patients with sepsis were coagulation dysfunction (OR: 3.2; p = 0.03), septic shock (OR: 3.2; p = 0.003), and isolation of a MDR bacteria (OR: 4.6; p < 0.001). Conclusion: In light of the prevalence and impact of MDR bacteria causing sepsis in patients coming from the community, physicians should consider ESBL coverage when starting an empiric antibiotic therapy in patients with specific risk factors, especially in the presence of septic shock.


2021 ◽  
Vol 22 (11) ◽  
pp. 5472
Author(s):  
Mauricio Osorio ◽  
Marcela Carvajal ◽  
Alejandra Vergara ◽  
Estefania Butassi ◽  
Susana Zacchino ◽  
...  

Prenylated flavonoids are an important class of naturally occurring flavonoids with important biological activity, but their low abundance in nature limits their application in medicines. Here, we showed the hemisynthesis and the determination of various biological activities of seven prenylated flavonoids, named 7–13, with an emphasis on antimicrobial ones. Compounds 9, 11, and 12 showed inhibitory activity against human pathogenic fungi. Compounds 11, 12 (flavanones) and 13 (isoflavone) were the most active against clinical isolated Staphylococcus aureus MRSA, showing that structural requirements as prenylation at position C-6 or C-8 and OH at positions C-5, 7, and 4′ are key to the antibacterial activity. The combination of 11 or 12 with commercial antibiotics synergistically enhanced the antibacterial activity of vancomycin, ciprofloxacin, and methicillin in a factor of 10 to 100 times against drug-resistant bacteria. Compound 11 combined with ciprofloxacin was able to decrease the levels of ROS generated by ciprofloxacin. According to docking results of S enantiomer of 11 with ATP-binding cassette transporter showed the most favorable binding energy; however, more studies are needed to support this result.


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