Activity Of Amikacin Research Articles

N-Acetyl Cysteine and Vitamin C Modulate the Antibiotic Efficacy Against Escherichia coli Cells.

Supplements with their own beneficial effect on hosts are consumed by us. N-acetyl cysteine (NAC) and Vitamin C (Vit C) are antioxidants and supplements, consumed for their beneficial properties. The present investigation evaluates the effect of their antioxidant property on antibiotic efficacy against Escherichia coli cells from different physiological states, including exponential and stationary-phase, cell aggregates, and in-vitro stress-induced persister cells. Survival was measured in cfu/mL by cfu (colony-forming unit) counting, with efficacy determined by log-fold change in survival by comparing CFUs in antibiotics alone and antibiotic + antioxidant combinations. Fluoroquinolones in the presence of NAC reduced ∼1 log CFUs of log-phase and persister cells, while Vit C reduced CFUs (∼1-3-log increase) of cells from all physiological states. Aminoglycosides results were inconclusive; streptomycin's activity declined (∼1-3-log increase in survival), whereas amikacin's activity potentiated (∼1-log reduction in cfu/mL). Rifampicin's showed reduced activity (∼2-3 log increase in survival) with Vit C in all the states and a ∼1-2 log increase with NAC, especially in cell aggregates and persisters. Beta-lactams activity showed variability, with amoxicillin and ampicillin not being influenced, but ceftriaxone showed significant reduction of efficacy (∼2-3-log increase in survival) in all the treatments. The findings suggest that the overall impact of antioxidants on antibiotic efficacy varies depending on the antibiotic class.

In vitro antibacterial effect of fosfomycin combination therapy against colistin-resistant Klebsiella pneumoniae.

ObjectivesColistin is still a “last-resort” antibiotic used to manage human infections due to multidrug-resistant (MDR) Klebsiella pneumoniae. However, colistin-resistant K. pneumoniae (CR-Kp) isolates emerged a decade ago and had a worldwide distribution. The purpose of this study was to evaluate the genetic data of CR-Kp and identify the antibacterial activity of fosfomycin (FM) alone and in combination with amikacin (AMK) or colistin (COL) against CR-Kp in vitro.MethodsThree clinical CR-Kp isolates from three patients were collected. Whole-genome sequencing and bioinformatics analysis were performed. The Pharmacokinetics Auto Simulation System 400, by simulating human pharmacokinetics in vitro, was employed to simulate FM, AMK, and COL alone and in combination. Different pharmacodynamic parameters were calculated for determining the antimicrobial effect.ResultsWhole-genome sequencing revealed that none of the three isolates contain mcr gene and that no insertion was found in pmrAB, phoPQ, or mgrB genes. We found the antibacterial activity of AMK alone was more efficient than FM or COL against CR-Kp. The area between the control growth and antibacterial killing curves of FM (8 g every 8 hours) combined with AMK (15 mg/kg once daily) was higher than 170 LogCFU/mL·h−1. In addition, the area between the control growth and antibacterial killing curves of FM (8 g every 8 hours) combined with COL (75,000 IU/kg every12 hours) was higher than that of monotherapies (>100 LogCFU/mL·h−1 vs <80 LogCFU/mL·h−1).ConclusionFM (8 g every 8 hours) combined with AMK (15 mg/kg once daily) was effective at maximizing bacterial killing against CR-Kp.

Activity of Plazomicin against Enterobacteriaceae Isolates Collected in the United States Including Isolates Carrying Aminoglycoside-Modifying Enzymes Detected by Whole Genome Sequencing

BackgroundPlazomicin (PLZ) is a next-generation aminoglycoside (AMG) stable against aminoglycoside-modifying enzymes (AME) that completed Phase 3 studies for complicated urinary tract infections and serious infections due to carbapenem-resistant Enterobacteriaceae (ENT). We evaluated the activity of PLZ and AMGs against ENT collected in US hospitals during 2016.MethodsA total of 2,097 ENT were susceptibility (S) tested by CLSI reference broth microdilution methods. E. coli, Klebsiella spp. Enterobacter spp., and P. mirabilis isolates displaying non-S MICs (CLSI criteria) for gentamicin (GEN), amikacin (AMK), and/or tobramycin (TOB) were submitted to WGS, de novo assembly and screening for AME genes.ResultsAgainst ENT, PLZ was more active than all 3 clinically available AMGs (Table). PLZ and AMK activities were stable regardless of the infection type; however, differences were observed for GEN and TOB. Bloodstream isolates displayed higher GEN MICs when compared with the other infection sites. TOB activity varied 4-fold, being higher for bloodstream and pneumonia infections and lower for skin/soft tissue and other/unknown specimens. Against 198 isolates carrying 1 or more AME-encoding genes detected among 208 AMG-non-S isolates, the activity of PLZ was 8- to 16-fold greater when compared with the activity of AMK and at least 16-fold higher than the activity of GEN or TOB.ConclusionPLZ was active against ENT isolates from US hospitals regardless of infection type. PLZ displayed activity against isolates carrying AME genes that represent 12.0% of selected species. AME-carrying isolates were considerably more resistant to AMK, GEN, and TOB, highlighting the potential value of PLZ to treat infections caused by these organisms.This project has been funded under BARDA Contract No. HHSO100201000046C.Disclosures M. Castanheira, Achaogen: Research Contractor, Research grant; L. M. Deshpande, Achaogen: Research Contractor, Research grant; C. M. Hubler, Achaogen: Research Contractor, Research grant; R. E. Mendes, Achaogen: Research Contractor, Research grant; A. W. Serio, Achaogen: Employee, Salary; K. M. Krause, Achaogen: Employee, Salary; R. K. Flamm, Achaogen: Research Contractor, Research grant

Resistance to amikacin and gentamicin among Gram-negative bloodstream isolates in a university hospital between 1989 and 1994

OBJECTIVE: To characterize antimicrobial resistance patterns to amikacin (AN) and gentamicin (GM) among Gram-negative bloodstream isolates and to determine the possible relationship between use of AN and GM and the occurrence of antibiotic resistance during a 6-year period. METHODS: Standard media and techniques of isolation and identification were used. Antimicrobial susceptibility testing was performed with the disk diffusion method and API rapid ATB E strips. Data on consumption of aminoglycosides were collected by the central hospital pharmacy and were expressed as daily defined doses. RESULTS: One thousand nine hundred and four bloodstream isolates were tested for AN and GM susceptibility between 1989 and 1994. Activities of AN and GM remained high during the study period against most isolates of Gram-negative bacteria. No relationship could be observed between the use of AN/GM and the rate of AN/GM resistance. Nosocomial Gram-negative bloodstream isolates showed a higher degree of resistance towards both AN (3.9% of all nosocomial isolates) and GM (7.9%) than community-acquired isolates (1.8% toward AN and 3.1% towards GM, respectively). There was a significant increase (P=0.004) in the risk of GM resistance in patients with nosocomial Gram-negative bacteremia detected more than 14 days after admission. The proportion of GM-susceptible Pseudomonas aeruginosa isolates decreased linearly from 97% for infections acquired between day 3 and day 10 following admission to 80% for bacteremia developing 30 days or more after admission (P=0.008). CONCLUSIONS: AN and GM remain highly active antimicrobial drugs for treatment of GNB in times of growing resistance to cephalosporins and fluoroquinolones.

Synergistic Activity of Trimethoprim and Amikacin Against Gram-Negative Bacilli

The in vitro effect of trimethoprim on the inhibitory and bactericidal activity of amikacin against 20 strains each of Klebsiella pneumoniae and Serratia marcescens, 15 strains of Escherichia coli, and 10 strains of Pseudomonas aeruginosa was examined by the checkerboard technique in microtiter plates. Trimethoprim had a synergistic effect on the inhibitory and bactericidal activity of amikacin against the majority of non-pseudomonas strains tested. The mean +/- standard deviation fractional inhibitory concentration indexes were 0.59 +/- 0.19 for the Klebsiella strains, 0.48 +/- 0.18 for the Serratia strains, and 0.60 +/- 0.22 for the E. coli strains tested. Respective mean +/- standard deviation fractional bactericidal concentration indexes for these organisms were 0.55 +/- 0.17, 0.54 +/- 0.29, and 0.61 +/- 0.22. A total of 40% of the Klebsiella strains, 80% of the Serratia strains, and 46% of the E. coli strains had a fractional inhibitory concentration equal to or less than 0.25 for both of these antimicrobial agents and were considered to be synergistically inhibited by the combination. By applying this criterion to bactericidal activity, synergy was demonstrated against 50, 65, and 46% of these strains, respectively. All of the Enterobacteriaceae tested were inhibited by clinically achievable concentrations of trimethoprim and amikacin. Antagonism was not demonstrated with any of the organisms tested. Trimethoprim had no antibacterial effect on the Pseudomonas strains and did not alter amikacin's activity against these bacteria.