Plazomicin, sold under the brand name Zemdri, is an

aminoglycoside antibiotic Aminoglycoside is a medicinal and bacteriologic category of traditional Gram-negative antibacterial medications that inhibit protein synthesis and contain as a portion of the molecule an amino-modified glycoside (sugar). The term can also refer ...

used to treat complicated

urinary tract infections A urinary tract infection (UTI) is an infection that affects part of the urinary tract. When it affects the lower urinary tract it is known as a bladder infection (cystitis) and when it affects the upper urinary tract it is known as a kidney ...

. As of 2019 it is recommended only for those in whom alternatives are not an option. It is given by

injection into a vein Intravenous therapy (abbreviated as IV therapy) is a medical technique that administers fluids, medications and nutrients directly into a person's vein. The intravenous route of administration is commonly used for rehydration or to provide nutrie ...

. Common side effects include

kidney problems Kidney failure, also known as end-stage kidney disease, is a medical condition in which the kidneys can no longer adequately filter waste products from the blood, functioning at less than 15% of normal levels. Kidney failure is classified as eit ...

diarrhea Diarrhea, also spelled diarrhoea, is the condition of having at least three loose, liquid, or watery bowel movements each day. It often lasts for a few days and can result in dehydration due to fluid loss. Signs of dehydration often begin wi ...

, nausea, and blood pressure changes. Other severe side effects include

hearing loss Hearing loss is a partial or total inability to Hearing, hear. Hearing loss may be present at birth or acquired at any time afterwards. Hearing loss may occur in one or both ears. In children, hearing problems can affect the ability to Language ...

, ''Clostridium difficile''-associated diarrhea,

anaphylaxis Anaphylaxis is a serious, potentially fatal allergic reaction and medical emergency that is rapid in onset and requires immediate medical attention regardless of use of emergency medication on site. It typically causes more than one of the follow ...

, and muscle weakness. Use during pregnancy may harm the baby. Plazomicin works by decreasing the ability of bacteria to make protein. Plazomicin was approved for medical use in the United States in 2018. It is on the

World Health Organization's List of Essential Medicines The WHO Model List of Essential Medicines (aka Essential Medicines List or EML), published by the World Health Organization (WHO), contains the medications considered to be most effective and safe to meet the most important needs in a health ...

Medical uses

Plazomicin is approved by the U.S.

Food and Drug Administration The United States Food and Drug Administration (FDA or US FDA) is a List of United States federal agencies, federal agency of the United States Department of Health and Human Services, Department of Health and Human Services. The FDA is respon ...

(FDA) for adults with complicated urinary tract infections, including

pyelonephritis Pyelonephritis is inflammation of the kidney, typically due to a bacterial infection. Symptoms most often include fever and flank tenderness. Other symptoms may include nausea, burning with urination, and frequent urination. Complications may ...

, caused by ''

Escherichia coli ''Escherichia coli'' (),Wells, J. C. (2000) Longman Pronunciation Dictionary. Harlow ngland Pearson Education Ltd. also known as ''E. coli'' (), is a Gram-negative, facultative anaerobic, rod-shaped, coliform bacterium of the genus ''Escher ...

'', ''

Klebsiella pneumoniae ''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. Although found in the normal flora of the mouth ...

'', ''

Proteus mirabilis ''Proteus mirabilis'' is a Gram-negative, facultatively anaerobic, rod-shaped bacterium. It shows swarming motility and urease activity. ''P. mirabilis'' causes 90% of all ''Proteus'' infections in humans. It is widely distributed in soil and ...

'', or ''

Enterobacter cloacae ''Enterobacter cloacae'' is a clinically significant Gram-negative, facultatively-anaerobic, rod-shaped bacterium. Microbiology In microbiology labs, ''E. cloacae'' is frequently grown at 30 °C on nutrient agar or at 35 °C in tr ...

'', in patients who have limited or no alternative treatment options. Zemdri is an intravenous infusion, administered once daily. The FDA declined approval for treating bloodstream infections due to lack of demonstrated effectiveness. 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. Plazomicin has been reported to demonstrate ''in vitro'' synergistic activity when combined with

daptomycin Daptomycin, sold under the brand name Cubicin among others, is a lipopeptide antibiotic used in the treatment of systemic and life-threatening infections caused by Gram-positive organisms. Daptomycin was removed from the World Health Organiza ...

ceftobiprole Ceftobiprole (Zevtera/Mabelio) is a fifth-generation cephalosporin for the treatment of hospital-acquired pneumonia (excluding ventilator-associated pneumonia) and community-acquired pneumonia. It is marketed by Basilea Pharmaceutica in the Unit ...

versus methicillin-resistant ''Staphylococcus aureus'', vancomycin-resistant ''S. aureus'' and against ''

Pseudomonas aeruginosa ''Pseudomonas aeruginosa'' is a common encapsulated, gram-negative, aerobic–facultatively anaerobic, rod-shaped bacterium that can cause disease in plants and animals, including humans. A species of considerable medical importance, ''P. aerugi ...

'' when combined with

cefepime Cefepime is a fourth-generation cephalosporin antibiotic. Cefepime has an extended spectrum of activity against Gram-positive and Gram-negative bacteria, with greater activity against both types of organism than third-generation agents. A 2007 ...

doripenem Doripenem (Doribax, Finibax) is an antibiotic drug in the carbapenem class. It is a beta-lactam antibiotic drug able to kill ''Pseudomonas aeruginosa''. Doripenem can be used for bacterial infections such as: complex abdominal infections, pneumon ...

imipenem Imipenem (trade name Primaxin among others) is an intravenous β-lactam antibiotic discovered by Merck scientists Burton Christensen, William Leanza, and Kenneth Wildonger in the mid-1970s. Carbapenems are highly resistant to the β-lactamase enzy ...

piperacillin/tazobactam Piperacillin/tazobactam, sold under the brand name Zosyn among others, is a combination medication containing the antibiotic piperacillin and the β-lactamase inhibitor Beta-lactamases, (β-lactamases) are enzymes () produced by bacteri ...

. It also demonstrates potent ''in vitro'' activity versus carbapenem-resistant ''

Acinetobacter baumannii ''Acinetobacter baumannii'' is a typically short, almost round, rod-shaped ( coccobacillus) Gram-negative bacterium. It is named after the bacteriologist Paul Baumann. It can be an opportunistic pathogen in humans, affecting people with compromi ...

''. Plazomicin was found to be noninferior to meropenem.

History

The drug was developed by the biotech company Achaogen. In 2012, the U.S. Food and Drug Administration granted

fast track The fast track is an informal English term meaning "the quickest and most direct route to achievement of a goal, as in competing for professional advancement". By definition, it implies that a less direct, slower route also exists. Fast track or F ...

designation for the development and regulatory review of plazomicin. The FDA approved plazomicin for adults with complicated UTIs and limited or no alternative treatment options in 2018. Achaogen was unable to find a robust market for the drug, and declared bankruptcy a few months later. A generic version is manufactured by

Cipla Cipla Limited (stylized as Cipla) is an Indian multinational pharmaceutical company, headquartered in Mumbai. Cipla primarily develops medicines to treat respiratory disease, cardiovascular disease, arthritis, diabetes, depression and many oth ...

USA.

Synthesis

It is derived from sisomicin by appending a hydroxy-aminobutyric acid substituent at position 1 and a hydroxyethyl substituent at position 6'. The latter makes it impervious to acetylation (deactivation) by Aminoglycoside Acetyltransferase 6'-N- Type Ib (AAC(6')-Ib), the most prevalent AAC enzyme.

Names

Plazomicin is the international nonproprietary name (INN).

References

External links