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Pronunciation | pla" zoe mye' sin |
Trade names | Zemdri |
Other names | ACHN-490, 6'-(Hydroxylethyl)-1-(HABA)-sisomicin |
AHFS/Drugs.com | Monograph |
MedlinePlus | a618037 |
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Routes of administration | Intravenous |
Drug class | Aminoglycoside |
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Chemical and physical data | |
Formula | C25H48N6O10 |
Molar mass | 592.691 g·mol−1 |
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Plazomicin, sold under the brand name Zemdri, is an aminoglycoside antibiotic used to treat complicated urinary tract infections. [2] As of 2019 it is recommended only for those in whom alternatives are not an option. [2] It is given by injection into a vein. [2]
Common side effects include kidney problems, diarrhea, nausea, and blood pressure changes. [2] Other severe side effects include hearing loss, Clostridioides difficile-associated diarrhea, anaphylaxis, and muscle weakness. [2] Use during pregnancy may harm the baby. [2] Plazomicin works by decreasing the ability of bacteria to make protein. [2]
Plazomicin was approved for medical use in the United States in 2018. [3] [4] It is on the World Health Organization's List of Essential Medicines. [5]
Plazomicin is approved by the U.S. Food and Drug Administration (FDA) for adults with complicated urinary tract infections, including pyelonephritis, caused by Escherichia coli , Klebsiella pneumoniae , Proteus mirabilis , or Enterobacter cloacae , in patients who have limited or no alternative treatment options. Zemdri is an intravenous infusion, administered once daily. [6] [7] [8] [9] The FDA declined approval for treating bloodstream infections due to lack of demonstrated effectiveness. [3] The lack of demonstrated effectiveness was not so much about the antibiotic itself being ineffective so much as the low enrollment rate for the study. Studies using mouse models however, showed a high survival rate. [10]
Plazomicin has been reported to demonstrate in vitro synergistic activity when combined with daptomycin or ceftobiprole versus methicillin-resistant Staphylococcus aureus, vancomycin-resistant S. aureus and against Pseudomonas aeruginosa when combined with cefepime, doripenem, imipenem or piperacillin/tazobactam. [11] It also demonstrates potent in vitro activity versus carbapenem-resistant Acinetobacter baumannii . [12] Plazomicin was found to be noninferior to meropenem. [13] [14]
The drug was developed by the biotech company Achaogen. In 2012, the U.S. Food and Drug Administration granted fast track designation for the development and regulatory review of plazomicin. [15] The FDA approved plazomicin for adults with complicated UTIs and limited or no alternative treatment options in 2018. [6] Achaogen was unable to find a robust market for the drug, and declared bankruptcy a few months later. [16] As part of the bankruptcy process, the rights to plazomicin were sold to Cipla USA, who currently markets ZEMDRI. [17] There is no generic plazomicin currently available in the US market. [18]
It is derived from sisomicin by appending a hydroxy-aminobutyric acid substituent at position 1 and a hydroxyethyl substituent at position 6'. [19] [11] The latter makes it impervious to acetylation (deactivation) by Aminoglycoside Acetyltransferase 6'-N- Type Ib (AAC(6')-Ib), the most prevalent AAC enzyme. [20]
Plazomicin is the international nonproprietary name (INN). [21]
A urinary tract infection (UTI) is an infection that affects a part of the urinary tract. Lower urinary tract infections may involve the bladder (cystitis) or urethra (urethritis) while upper urinary tract infections affect the kidney (pyelonephritis). Symptoms from a lower urinary tract infection include suprapubic pain, painful urination (dysuria), frequency and urgency of urination despite having an empty bladder. Symptoms of a kidney infection, on the other hand, are more systemic and include fever or flank pain usually in addition to the symptoms of a lower UTI. Rarely, the urine may appear bloody. Symptoms may be vague or non-specific at the extremities of age.
Ertapenem, sold under the brand name Invanz, is a carbapenem antibiotic medication used for the treatment of infections of the abdomen, the lungs, the upper part of the female reproductive system, and the diabetic foot.
Klebsiella pneumoniae is a Gram-negative, non-motile, encapsulated, lactose-fermenting, facultative anaerobic, rod-shaped bacterium. It appears as a mucoid lactose fermenter on MacConkey agar.
Amoxicillin/clavulanic acid, also known as co-amoxiclav or amox-clav, sold under the brand name Augmentin, among others, is an antibiotic medication used for the treatment of a number of bacterial infections. It is a combination consisting of amoxicillin, a β-lactam antibiotic, and potassium clavulanate, a β-lactamase inhibitor. It is specifically used for otitis media, streptococcal pharyngitis, pneumonia, cellulitis, urinary tract infections, and animal bites. It is taken by mouth or by injection into a vein.
Meropenem, sold under the brand name Merrem among others, is an intravenous carbapenem antibiotic used to treat a variety of bacterial infections. Some of these include meningitis, intra-abdominal infection, pneumonia, sepsis, and anthrax.
Cefixime, sold under the brand name Suprax among others, is an antibiotic medication used to treat a number of bacterial infections. These infections include otitis media, strep throat, pneumonia, urinary tract infections, gonorrhea, and Lyme disease. For gonorrhea typically only one dose is required. In the United States it is a second-line treatment to ceftriaxone for gonorrhea. It is taken by mouth.
Carbapenems are a class of very effective antibiotic agents most commonly used for treatment of severe bacterial infections. This class of antibiotics is usually reserved for known or suspected multidrug-resistant (MDR) bacterial infections. Similar to penicillins and cephalosporins, carbapenems are members of the beta-lactam antibiotics drug class, which kill bacteria by binding to penicillin-binding proteins, thus inhibiting bacterial cell wall synthesis. However, these agents individually exhibit a broader spectrum of activity compared to most cephalosporins and penicillins. Furthermore, carbapenems are typically unaffected by emerging antibiotic resistance, even to other beta-lactams.
Norfloxacin, sold under the brand name Noroxin among others, is an antibiotic that belongs to the class of fluoroquinolone antibiotics. It is used to treat urinary tract infections, gynecological infections, inflammation of the prostate gland, gonorrhea and bladder infection. Eye drops were approved for use in children older than one year of age.
Amikacin is an antibiotic medication used for a number of bacterial infections. This includes joint infections, intra-abdominal infections, meningitis, pneumonia, sepsis, and urinary tract infections. It is also used for the treatment of multidrug-resistant tuberculosis. It is used by injection into a vein using an IV or into a muscle.
Fosfomycin, sold under the brand name Monurol among others, is an antibiotic primarily used to treat lower urinary tract infections. It is not indicated for kidney infections. Occasionally it is used for prostate infections. It is generally taken by mouth.
Omadacycline, sold under the brand name Nuzyra, is a broad spectrum antibiotic medication belonging to the aminomethylcycline subclass of tetracycline antibiotics. In the United States, it was approved in October 2018, for the treatment of community-acquired bacterial pneumonia and acute skin and skin structure infections.
Eravacycline is a synthetic halogenated tetracycline class antibiotic by Tetraphase Pharmaceuticals. It is closely related to tigecycline. It has a broad spectrum of activity including many multi-drug resistant strains of bacteria. Phase III studies in complicated intra-abdominal infections (cIAI) and complicated urinary tract infections (cUTI) were recently completed with mixed results. Eravacycline was granted fast track designation by the FDA and is currently available in USA.
Ceftolozane/tazobactam, sold under the brand name Zerbaxa, (Merck) is a fixed-dose combination antibiotic medication used for the treatment of complicated urinary tract infections and complicated intra-abdominal infections in adults. Ceftolozane is a cephalosporin antibiotic, developed for the treatment of infections with gram-negative bacteria that are resistant to conventional antibiotics. It was studied for urinary tract infections, intra-abdominal infections and ventilator-associated bacterial pneumonia.
Ceftazidime/avibactam, sold under the brand name Avycaz among others, is a fixed-dose combination medication composed of ceftazidime, a cephalosporin antibiotic, and avibactam, a β-lactamase inhibitor. It is used to treat complicated intra-abdominal infections, urinary tract infections, and pneumonia. It is only recommended when other options are not appropriate. It is given by infusion into a vein.
Vaborbactam (INN) is a non-β-lactam β-lactamase inhibitor discovered by Rempex Pharmaceuticals, a subsidiary of The Medicines Company. While not effective as an antibiotic by itself, it restores potency to existing antibiotics by inhibiting the β-lactamase enzymes that would otherwise degrade them. When combined with an appropriate antibiotic it can be used for the treatment of gram-negative bacterial infections.
ESKAPE is an acronym comprising the scientific names of six highly virulent and antibiotic resistant bacterial pathogens including: Enterococcus faecium, Staphylococcus aureus, Klebsiella pneumoniae, Acinetobacter baumannii, Pseudomonas aeruginosa, and Enterobacter spp. The acronym is sometimes extended to ESKAPEE to include Escherichia coli. This group of Gram-positive and Gram-negative bacteria can evade or 'escape' commonly used antibiotics due to their increasing multi-drug resistance (MDR). As a result, throughout the world, they are the major cause of life-threatening nosocomial or hospital-acquired infections in immunocompromised and critically ill patients who are most at risk. P. aeruginosa and S. aureus are some of the most ubiquitous pathogens in biofilms found in healthcare. P. aeruginosa is a Gram-negative, rod-shaped bacterium, commonly found in the gut flora, soil, and water that can be spread directly or indirectly to patients in healthcare settings. The pathogen can also be spread in other locations through contamination, including surfaces, equipment, and hands. The opportunistic pathogen can cause hospitalized patients to have infections in the lungs, blood, urinary tract, and in other body regions after surgery. S. aureus is a Gram-positive, cocci-shaped bacterium, residing in the environment and on the skin and nose of many healthy individuals. The bacterium can cause skin and bone infections, pneumonia, and other types of potentially serious infections if it enters the body. S. aureus has also gained resistance to many antibiotic treatments, making healing difficult. Because of natural and unnatural selective pressures and factors, antibiotic resistance in bacteria usually emerges through genetic mutation or acquires antibiotic-resistant genes (ARGs) through horizontal gene transfer - a genetic exchange process by which antibiotic resistance can spread.
Meropenem/vaborbactam, sold under the brand name Vabomere among others, is a combination medication used to treat complicated urinary tract infections, complicated abdominal infections, and hospital-acquired pneumonia. It contains meropenem, a beta-lactam antibiotic, and vaborbactam, a beta-lactamase inhibitor. It is given by injection into a vein.
Cefiderocol, sold under the brand name Fetcroja among others, is an antibiotic used to treat complicated urinary tract infections when no other options are available. It is indicated for the treatment of multi-drug-resistant Gram-negative bacteria including Pseudomonas aeruginosa. It is given by injection into a vein.
Imipenem/cilastatin/relebactam, sold under the brand name Recarbrio(Merck), is a fixed-dose combination medication used as an antibiotic. In 2019, it was approved for use in the United States for the treatment of complicated urinary tract and complicated intra-abdominal infections. It is administered via intravenous injection.
Nacubactam is an investigational β-lactamase inhibitor being developed for the treatment of infections caused by carbapenem-resistant Enterobacteriaceae (CRE). It belongs to the diazabicyclooctane (DBO) class of compounds and exhibits a dual mechanism of action. Nacubactam inhibits serine β-lactamases, including classes A and C and some class D enzymes, while also directly inhibiting penicillin-binding protein 2 (PBP2) in Enterobacteriaceae. This unique profile allows nacubactam to both protect partner β-lactam antibiotics from degradation and exert direct antibacterial effects. As of 2024, nacubactam is undergoing clinical trials in combination with other β-lactam antibiotics such as meropenem, cefepime, and aztreonam for the treatment of complicated urinary tract infections and other serious bacterial infections caused by multidrug-resistant pathogens.
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