Development of Gentamicin Resistance During Treatment of Escherichia coli Ventilator-Associated Pneumonia in a Neonate

2020 ◽  
pp. 089719002094012
Author(s):  
Brandi D. Newby

A neonate born at 25 + 1/7 weeks developed ventilator-associated pneumonia at 29 + 3/7 weeks post-menstrual age with Escherichia coli that was originally sensitive to gentamicin. After 3 days of treatment with gentamicin, the minimum inhibitory concentration (MIC) changed from less than 1 mg/L to more than 16 mg/L. It appears that suboptimal gentamicin dosing led to the development of gentamicin resistance. As the patient was not improving clinically, the antibiotics were changed once the gentamicin resistance was identified. To minimize resistance and treatment failure, clinicians should consider the patient-specific pharmacokinetic parameters, achieved peak level, and the amount of time the gentamicin level will remain below the MIC of the organism being treated.

2021 ◽  
Vol 21 (1) ◽  
Author(s):  
Abdulkader Masri ◽  
Naveed Ahmed Khan ◽  
Muhammad Zarul Hanifah Md Zoqratt ◽  
Qasim Ayub ◽  
Ayaz Anwar ◽  
...  

Abstract Backgrounds Escherichia coli K1 causes neonatal meningitis. Transcriptome studies are indispensable to comprehend the pathology and biology of these bacteria. Recently, we showed that nanoparticles loaded with Hesperidin are potential novel antibacterial agents against E. coli K1. Here, bacteria were treated with and without Hesperidin conjugated with silver nanoparticles, and silver alone, and 50% minimum inhibitory concentration was determined. Differential gene expression analysis using RNA-seq, was performed using Degust software and a set of genes involved in cell stress response and metabolism were selected for the study. Results 50% minimum inhibitory concentration with silver-conjugated Hesperidin was achieved with 0.5 μg/ml of Hesperidin conjugated with silver nanoparticles at 1 h. Differential genetic analysis revealed the expression of 122 genes (≥ 2-log FC, P< 0.01) in both E. coli K1 treated with Hesperidin conjugated silver nanoparticles and E. coli K1 treated with silver alone, compared to untreated E. coli K1. Of note, the expression levels of cation efflux genes (cusA and copA) and translocation of ions, across the membrane genes (rsxB) were found to increase 2.6, 3.1, and 3.3- log FC, respectively. Significant regulation was observed for metabolic genes and several genes involved in the coordination of flagella. Conclusions The antibacterial mechanism of nanoparticles maybe due to disruption of the cell membrane, oxidative stress, and metabolism in E. coli K1. Further studies will lead to a better understanding of the genetic mechanisms underlying treatment with nanoparticles and identification of much needed novel antimicrobial drug candidates.


2020 ◽  
Vol 10 (1) ◽  
Author(s):  
Bálint Ármin Pataki ◽  
◽  
Sébastien Matamoros ◽  
Boas C. L. van der Putten ◽  
Daniel Remondini ◽  
...  

Abstract It is important that antibiotics prescriptions are based on antimicrobial susceptibility data to ensure effective treatment outcomes. The increasing availability of next-generation sequencing, bacterial whole genome sequencing (WGS) can facilitate a more reliable and faster alternative to traditional phenotyping for the detection and surveillance of AMR. This work proposes a machine learning approach that can predict the minimum inhibitory concentration (MIC) for a given antibiotic, here ciprofloxacin, on the basis of both genome-wide mutation profiles and profiles of acquired antimicrobial resistance genes. We analysed 704 Escherichia coli genomes combined with their respective MIC measurements for ciprofloxacin originating from different countries. The four most important predictors found by the model, mutations in gyrA residues Ser83 and Asp87, a mutation in parC residue Ser80 and presence of the qnrS1 gene, have been experimentally validated before. Using only these four predictors in a linear regression model, 65% and 93% of the test samples’ MIC were correctly predicted within a two- and a four-fold dilution range, respectively. The presented work does not treat machine learning as a black box model concept, but also identifies the genomic features that determine susceptibility. The recent progress in WGS technology in combination with machine learning analysis approaches indicates that in the near future WGS of bacteria might become cheaper and faster than a MIC measurement.


2020 ◽  
Vol 12 (1) ◽  
pp. 71-75
Author(s):  
A.M. Aliyu ◽  
S.J. Oluwafemi ◽  
S. Kasim

All over the world, hundreds of plants have been identified based on researchers and experimental evidence as good sources of medicinal agents. The bioactive components (phytochemicals) of both the seeds and pulp of Cola milleni were extracted using ethanol as solvent. The bioactive components detected were alkaloids, tanins, saponins, cardiac glycosides, carbohydrates, sterols, resins and terpenes while Flavonoids, anthraquinones, anthracyanides and phenol were not detected for both the seed and pulps. Antimicrobial activity of the ethanol extract (Seed and pulp) against Staphylococcus aureus, Escherichia coli and Penicillium notatum was carried out using standard techniques. Staphylococcus aureus had the highest zone of inhibition for pulp having a range of 9.7mm±0.58mm - 19.7mm±2.52mm while Penicllium notatum had the least with 0.00mm. S.aureus also had the highest zone of inhibition range of 14.3mm±2.08mm - 21.3mm±1.53mm for the seed extract while penicillium had the least inhibition range of 5.0mm±1.00mm - 5.7mm±0.58. E.coli showed the highest minimum inhibitory concentration with ethanol extract of the pulp (160mg/ml) while penicillium notatum was not reactive. The minimum inhibitory concentration of seed against penillium notatum was the highest (160mg/ml) while staphylococcus aureus showed the lowest of 40mg/ml. The antimicrobial activity is as a result of the presence of phytochemicals detected, which suggest the use of the plant for the treatment of diseases caused by these organisms. Key words: Cola millenii, Phytochemical, Antimicrobial activity, Bacteria, Fungi


2008 ◽  
Vol 58 (4) ◽  
pp. 937-944 ◽  
Author(s):  
J. H. Cunningham ◽  
C. Cunningham ◽  
B. Van Aken ◽  
L.-S. Lin

Disinfection kinetics has been well established for selected antimicrobial agents on isolated bacterial strains. Due to the difficulties of culturing most bacteria, the majority of these studies have been limited to readily cultivable microorganisms of a single type or family. This study explores the feasibility of using flow cytometry for characterising the disinfection kinetics and minimum inhibitory concentration (MIC) of an Escherichia coli culture and a microbial consortium. The proposed method relies on fluorescent dye molecules to indicate the morphological and physiological status of numerous individual cells. Biocides of varying effectiveness and inactivation mechanisms (chlorine, iodine, and silver) were used to evaluate this novel application. Using pseudo-first-order kinetics, the coefficients of specific lethality of chlorine and iodine on Escherichia coli were 4.71 and 3.78×10−3 L mg−1 min−1 and MIC of silver ion was between 60 and 80 μg L−1. The coefficients of specific lethality of chlorine and iodine on the microbial consortium were 4.96 and 8.89×10−3 L mg−1 min−1 and MIC of silver ion was between 40 and 60 μg L−1. This method can be used to provide a rapid and consistent way of determining disinfection kinetics and MICs for pure and mixed bacterial cultures and can potentially be used to examine water and wastewater disinfection efficiency. However, caution should be used to ensure that the physiological and morphological status characterised by cytodyes is a result of the inactivation mechanisms of the disinfectants evaluated.


DICP ◽  
1989 ◽  
Vol 23 (6) ◽  
pp. 456-460
Author(s):  
Michael N. Dudley ◽  
Hilary D. Mandler ◽  
Kenneth H. Mayer ◽  
Stephen H. Zinner

Serum inhibitory and bactericidal titers were measured in nine healthy volunteers following single iv doses of ciprofloxacin 100, 150, and 200 mg. The median peak serum bactericidal titer (5 minutes following completion of a 30-minute infusion) against two highly susceptible strains of Escherichia coli ranged between 1:64 and 1:1024 and titers exceeded 1:8 for six hours for all dose levels. The bactericidal titers against two strains of Pseudomonas aeruginosa and a methicillin-resistant strain of Staphylococcus aureus were considerably lower, the median peak being 1:2 at all dose levels. Measured inhibitory and bactericidal titers at five minutes and one hour postinfusion were significantly greater than those predicted (measured serum ciprofloxacin concentration to minimum inhibitory concentration [MIC] or minimum bactericidal concentration [MBC]) for only one strain of E. coli. Intravenous doses of ciprofloxacin 100–200 mg produce high and sustained serum bactericidal titers against highly susceptible bacteria; considerably lower levels of activity are seen against bacteria having higher MICs and MBCs but still considered susceptible to the drug.


2018 ◽  
Author(s):  
Mehdi Snoussi ◽  
John Paul Talledo ◽  
Nathan-Alexander Del Rosario ◽  
Bae-Yeun Ha ◽  
Andrej Košmrlj ◽  
...  

AbstractAntimicrobial peptides (AMPs) are broad spectrum antibiotics that selectively target bacteria. Here we investigate the activity of human AMP LL37 againstEscherichia coliby integrating quantitative, population and single-cell level experiments with theoretical modeling. Our data indicate an unexpected, rapid absorption and retention of a large number of LL37 byE. colicells upon the inhibition of their growth, which increases the chance of survival for the rest of population. Cultures with high-enough cell density exhibit two distinct subpopulations: a non-growing population that absorb peptides and a growing population that survive owing to the sequestration of the AMPs by others. A mathematical model based on this binary picture reproduces the rather surprising behaviors ofE. colicultures in the presence of LL37, including the increase of the minimum inhibitory concentration with cell density (even in dilute cultures) and the extensive lag in growth introduced by sub-lethal dosages of LL37.


2019 ◽  
Vol 21 (6) ◽  
pp. 280-283
Author(s):  
Farshad Kakian ◽  
Behnam Zamanzad ◽  
Abolfazle Gholipour ◽  
Kiarash Zamanzad

Background and aims: Carbapenems are the final-line treatments for multidrug-resistant, gram-negative infections. The patterns of resistance to carbapenems among hospital bacterial pathogens vary widely across different hospitals in a country. Considering that Escherichia coli is one of the most important causes of nosocomial infections, it is essential to study its drug resistance. Methods: In this descriptive-analytical study, a total of 80 samples of E. coli isolated from inpatients with urinary tract infections (UTIs) were collected in different wards (i.e., women, urology, infectious, and ICU) of Shahrekord hospitals. After the diagnosis and confirmation of bacteria by standard bacteriological methods, their sensitivity to imipenem and meropenem was investigated by the antibiogram (diskdiffusion) method. Then, the minimum inhibitory concentration (MIC) was determined by the E-test strip according to the Clinical and Laboratory Standards Institute (CLSI) standard. Results: In this study, resistance to meropenem and imipenem by antibiogram (disc diffusion) was observed in 21 (25.26%) and 20 (25%) of the isolates, respectively. Twenty isolates had MIC ≥4 μg/mL for meropenem, 13 isolates demonstrated MIC≥4 μg/mL for imipenem, and 14 isolates had 1≤MIC<4 μg/mL and were semi-sensitive. Conclusion: In general, E. coli had significant resistance to carbapenems. Therefore, rapid and accurate identification of these strains can be a major step to the treatment and control of these strains and prevention of the spread of the resistance.


2017 ◽  
Vol 14 (1) ◽  
Author(s):  
Samuel Hager ◽  
Ellen Jensen ◽  
Timothy Johnson ◽  
David Mitchell

Bacteria are quick to adapt and evolve, especially under the effects of selective pressures from chemical antibiotics. In addition, bacteria may develop resistance to antibiotics from multiple classes simultaneously, making their eradication from the human body particularly challenging. This study aims to demonstrate that bacterial multiple-drug resistance can be developed and retained in a laboratory setting. Escherichia coli B was grown in tryptic soy broth in the presence of a small, increasing concentration of streptomycin. This exposure resulted in a strain of E. coli, which had an increased minimum inhibitory concentration (MIC) towards streptomycin, or “resistance.” This resistant strain was then grown in like manner in nalidixic acid and then penicillin G. The result was a strain that became resistant to streptomycin and nalidixic acid, and increasingly resistant to nalidixic acid after penicillin G exposure. Additionally, the bacteria retained resistance to streptomycin and nalidixic acid even after exposure to those chemicals ceased. Genome sequencing and comparison to E. coli B reference strain REL606 revealed the emergence of point mutations with each exposure to an antibiotic. Of particular interest is a mutation associated with the appearance of nalidixic acid resistance. Base pair 4,553,488 was changed from adenine to guanine, resulting in a change from aspartate to glycine in the protein helicase. Previous studies have not indicated mutations to this locus as nalidixic acid resistance conferring. Thus, this mutation may be a novel mutation conferring E. coli B nalidixic acid resistance. Since the region of the mutated helicase is functionally undefined, a mechanism is not apparent. Further research needs to be done to confirm this hypothesis and illuminate a mechanism. KEYWORDS: Bacteria; Escherichia coli; Evolution; Antibiotic Resistance; Nalidixic Acid; Streptomycin; Point Mutation; Single-nucleotide Polymorphism; Helicase; Minimum Inhibitory Concentration


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