Plazomicin
Plazomicin Uses, Dosage, Side Effects, Food Interaction and all others data.
Developed by Achaogen biopharmaceuticals, plazomicin is a next-generation aminoglycoside synthetically derived from Sisomicin. The structure of plazomicin was established via appending hydroxylaminobutyric acid to Sisomicin at position 1 and 2-hydroxyethyl group at position 6' . It was designed to evade all clinically relevant aminoglycoside-modifying enzymes, which contribute to the main resistance mechanism for aminoglycoside therapy . However, acquired resistance of aminoglycosides may arise through over expression of efflux pumps and ribosomal modification by bacteria, which results from amino acid or rRNA sequence mutations . Like other aminoglycosides, plazomicin is ineffective against bacterial isolates that produce 16S rRNA methyltransferases . Plazomicin mediates the antibacterial activity against pathogens including carbapenem-resistant (CRE) and extended-spectrum beta-lactamase (ESBL) producing Enterobacteriaceae. It mediates the antibacterial activity by binding to bacterial 30S ribosomal subunit and inhibiting protein synthesis . On June 28th, 2018, plazomicin sulfate was approved by the FDA for use in adult patients for the treatment of complicated urinary tract infections (cUTI) including Pyelonephritis. It is marketed as Zemdri and is administered via once-daily intravenous infusion.
Plazomicin exerts its antibacterial activity in a dose-dependent manner with a post-antibiotic effect ranging from 0.2 to 2.6 hours at 2X MIC against Enterobacteriaceae, as demonstrated by in vitro studies . In clinical trials comprising of hospitalized adult patients with cUTI (including pyelonephritis), resolution or improvement of clinical cUTI symptoms and a microbiological outcome of eradication were observed at day 5 following the first dose administration of plazomicin . Plazomicin has shown to elicit nephrotoxic, ototoxic, and neuromuscular blocking effects. In clinical trials, it did not induce any clinically relevant QTc-prolonging effects .
| Trade Name | Plazomicin |
| Availability | Prescription only |
| Generic | Plazomicin |
| Plazomicin Other Names | Plazomicin |
| Related Drugs | amoxicillin, doxycycline, ciprofloxacin, ceftriaxone, levofloxacin, Augmentin |
| Weight | 50mg/ml, |
| Type | Intravenous Solution, Intravenous |
| Formula | C25H48N6O10 |
| Weight | Average: 592.691 Monoisotopic: 592.34319177 |
| Protein binding | The extent of plasma protein binding in humans is approximately 20% . The degree of protein binding was concentration-independent across the range tested in vitro (5 to 100 mcg/mL) . |
| Groups | Approved, Investigational |
| Therapeutic Class | |
| Manufacturer | |
| Available Country | United States |
| Last Updated: | September 19, 2023 at 7:00 am |
Uses
Plazomicin is an aminoglycoside antibiotic used to treat complicated urinary tract infections.
Plazomicin is indicated for the treatment of patients 18 years of age or older with Complicated Urinary Tract Infections (cUTI) including Pyelonephritis, who have limited or no alternative treatment options. It should only be used to treat infections that are proven or strongly suspected to be caused by susceptible microorganisms .
Plazomicin is also used to associated treatment for these conditions: Complicated Urinary Tract Infection, Pyelonephritis
How Plazomicin works
Plazomicin exerts a bactericidal action against susceptible bacteria by binding to bacterial 30S ribosomal subunit . Aminoglycosides typically bind to the ribosomal aminoacyl-tRNA site (A-site) and induce a conformational change to further facilitate the binding between the rRNA and the antibiotic . This leads to codon misreading and mistranslation of mRNA during bacterial protein synthesis .
Plazomicin demonstrates potency against Enterobacteriaceae, including species with multidrug-resistant phenotypes such as carbapenemase-producing bacteria and isolates with resistance to all other aminoglycosides . Its antibacterial activity is not inhibited by aminoglycoside modifying enzymes (AMEs) produced by bacteria, such as acetyltransferases (AACs), phosphotransferases (APHs), and nucleotidyltransferases (ANTs) . Plazomicin was shown to be effective against Enterobacteriaceae in presence of some beta-lactamases . In clinical settings and in vivo, bacteria shown to be susceptible toward plazomicin include Escherichia coli, Klebsiella pneumoniae, Proteus mirabilis, and Enterobacter cloacae . Other aerobic bacteria that may be affected by plazomicin are Citrobacter freundii, Citrobacter koseri, Enterobacter aerogenes, Klebsiella oxytoca, Morganella morganii, Proteus vulgaris, Providencia stuartii, and Serratia marcescens .
Toxicity
In case of suspected overdose, plazomicin therapy should be discontinued with initiation of supportive care. Maintenance of glomerular filtration and careful monitoring of renal function is recommended. Hemodialysis may be used to facilitate drug elimination, and this may be especially clinically useful in patients with compromised renal function .
Food Interaction
No interactions found.Plazomicin Disease Interaction
Major: neuromuscular blockade, ototoxicity, renal dysfunction, colitisModerate: hepatic impairment
Volume of Distribution
The mean (±SD) volume of distribution is 17.9 (±4.8) L in healthy adults and 30.8 (±12.1) L in cUTI patients .
Elimination Route
Administration of 15 mg/kg plazomicin by 30-minute IV infusion resulted in peak plasma concentrations of 73.7 ± 19.7 μg/mL in healthy adult subjects and 51.0 ± 26.7 μg/mL in patients with complicated urinary tract infections (cUTI) . The area under the curve (AUC) were 257 ± 67.0 μg.h/mL in healthy adults and 226 ± 113 μg.h/mL in cUTI patients .
Half Life
The mean (±SD) half-life of plazomicin was 3.5 h (±0.5) in healthy adults with normal renal function receiving 15 mg/kg plazomicin via intravenous infusion .
Clearance
Following administration of 15 mg/kg plazomicin by 30-minute IV infusion, the mean (±SD) total body clearance in healthy adults and cUTI patients is 4.5 (±0.9) and 5.1 (±2.01) L/h, respectively .
Elimination Route
Plazomicin predominantly undergoes renal excretion, where 56% of the total administered drug was recovered in the urine within 4 hours following a single 15 mg/kg IV dose of radiolabeled plazomicin in healthy subjects. About less than 0.2% and 89.1% of the total drug were recovered within 168 hours in feces and urine, respectively .
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