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Plazomicin, an aminoglycoside, overcomes aminoglycoside modifying enzymes with in vitro potency against multidrug resistant Enterobacteriales. The exposure response relationship of plazomicin and comparator aminoglycoside amikacin was determined for Escherichia coli while for Klebsiella pneumoniae only plazomicin was tested. An in vitro pharmacokinetic (PK) model was used. Five strains of E.coli (2 meropenem resistant) and 5 strains of K.pneumoniae (2 meropenem resistant) plazomicin MICs 0.5-4mg/L were used. Antibacterial effect was assessed by changes in bacterial load and changes in bacterial population profile. The correlation between change in initial inoculum after 24h drug exposure and area under the concentration curve to MIC ratio (AUC/MIC) was good (plazomicin R ≥0.8302, amikacin R ≥0.9520). E.coli plazomicin AUC/MIC ratios for 24h static, -1 log drop, -2 log drop and -3 log drop were 36.1±18.4, 39.3±20.9, 41.2±21.9 and 44.8±24.4 respectively, and for amikacin were 49.5±12.7, 55.7±14.8, 64.1±19.2 and 73.3±25.3. K.pneumoniae plazomicin AUC/MIC ratios for 24h static, -1 log drop, -2 log drop and -3 log drop were 34.0±15.2, 46.8±27.8, 67.4±46.5 and 144.3±129.8. Plazomicin AUC/MIC ratios >66, and amikacin AUC/MIC ratios >57.7, were associated with suppression of E.coli growth on MICx4 or x8 recovery plates. The equivalent plazomicin AUC/MIC to suppress emergence of resistance with K.pneumoniae was >132. The plazomicin AUC/MIC for 24h static effect and -1 log reduction in E.coli and K.pneumoniae bacterial load was in the range 30-60. Plazomicin AUC/MIC targets aligned with those of amikacin for E.coli.
This article was published in the following journal.
Name: International journal of antimicrobial agents
The emergence of multi-drug resistant (MDR) Gram-negative pathogens has become a serious worldwide health concern. Gram-negative bacteria such as Enterobacteriaceae (Klebsiella pneumoniae, Escherichia...
Plazomicin is an aminoglycoside that was engineered to overcome aminoglycoside-modifying enzymes, which are the most common aminoglycoside resistance mechanism in Enterobacteriaceae. Because plazomici...
Plazomicin is an aminoglycoside with in vitro activity against multidrug-resistant Enterobacteriaceae. A phase 1, randomized, double-blind, crossover study assessed the potential effects of plazomicin...
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A broad-spectrum antibiotic derived from KANAMYCIN. It is reno- and oto-toxic like the other aminoglycoside antibiotics.
The proportion of survivors in a group, e.g., of patients, studied and followed over a period, or the proportion of persons in a specified group alive at the beginning of a time interval who survive to the end of the interval. It is often studied using life table methods.
An assisted reproductive technique that includes the direct handling and manipulation of oocytes and sperm to achieve fertilization in vitro.
A semi-synthetic aminoglycoside antibiotic that is used in the treatment of TUBERCULOSIS.
Naturally occurring genetic variations associated with drug response (e.g., dosage, extent and rate of metabolic processes). While these variants are not markers for GENETIC PREDISPOSITION TO DISEASE they influence PHARMACOKINETICS and pharmacodynamics and often occur on genes encoding drug metabolism enzymes and transporters (e.g., ANGIOTENSIN CONVERTING ENZYME; CYTOCHROME P-450 CYP2D6).
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Pneumonia (bronchopneumonia, lobar pneumonia and double pneumonia) is inflammation (swelling) of the tissue in one or both of your lungs. It is usually caused by an pneumococcal infection caused by bacteria called Streptococcus pneumoniae. However,...