zoliflodacin (pending FDA approval)

Action and Spectrum

Actions and spectrum: 

Action:  

zoliflodacin belongs to a class of antibiotics known as spiropyrimidinetriones. It works by inhibiting the bacterial DNA replication process through inhibition of the enzyme DNA gyrase. DNA gyrase is crucial for the proper coiling and replication of bacterial DNA, and its inhibition disrupts bacterial cell division and leads to bacterial death. 

Spectrum:  

zoliflodacin has shown its activity against Neisseria gonorrhoeae, including the strains that are resistant to other commonly used antibiotics such as fluoroquinolones. Neisseria gonorrhoeae is a bacterium responsible for gonorrhea, a sexually transmitted infection. The spectrum of activity is primarily focused on gram-negative bacteria. 

Drug Interaction

Adverse Reaction

N/A 

Black Box Warning

Black Box Warning: 

There is no specific black box warning associated with zoliflodacin. 

Contraindication / Caution

Contraindication/Caution: 

Contraindication: 

• Hypersensitivity: zoliflodacin may be contraindicated in individuals with known hypersensitivity or allergic reaction to drug or its components. 
• Pediatric Population: The safety and efficacy of zoliflodacin in pediatric populations may not have been established, and its use in certain age groups could be contraindicated. 
• Pregnancy and Breastfeeding: zoliflodacin may have contraindications in pregnant or breastfeeding individuals due to potential risks to the fetus or infant.

Caution: 

• Renal Impairment: zoliflodacin may require dose adjustments or careful monitoring in patients with renal impairment. 
• Hepatic Impairment: Caution may be needed in patients with hepatic impairment, and dose adjustments or monitoring may be necessary. 

Comorbidities: 

• Cardiovascular Conditions: Consider the cardiovascular status of patients, especially if there are concerns about potential effects on the cardiovascular system. 
• Neurological Disorders: Exercise caution in individuals with pre-existing neurological conditions, as some antibiotics may have neurological side effects. 
• Immunocompromised States: Evaluate the use of zoliflodacin in immunocompromised individuals, as their ability to fight infections may be compromised. 

Pregnancy / Lactation

Pregnancy consideration: pregnancy category: not assigned 

Lactation: excreted into human milk: unknown   

Pregnancy category: 

• Category A: well-controlled and Satisfactory studies show no risk to the fetus in the first or later trimester. 
• Category B: there was no evidence of risk to the fetus in animal studies, and there were not enough studies on pregnant women. 
• Category C: there was evidence of risk of adverse effects in animal reproduction studies, and no adequate evidence in human studies must take care of potential risks in pregnant women.   
• Category D: adequate data with sufficient evidence of human fetal risk from various platforms, but despite the potential risk, and used only in emergency cases for potential benefits. 
• Category X: Drugs listed in this category outweigh the risks over benefits. Hence these categories of drugs need to be avoided by pregnant women. 
• Category N: There is no data available for the drug under this category. 

Pharmacology

Pharmacology: 

zoliflodacin is an investigational antibiotic designed to address bacterial infections, particularly those caused by Neisseria gonorrhoeae. It belongs to the spiropyrimidinetrione class of antibiotics and exerts its pharmacological action by inhibiting the bacterial enzyme DNA gyrase. This inhibition disrupts the process of DNA replication and cell division in bacteria, leading to bacterial cell death. zoliflodacin demonstrates a spectrum of activity against Neisseria gonorrhoeae, including strains that may be resistant to other commonly used antibiotics.  

Pharmacodynamics: 

• Inhibition of DNA Gyrase: zoliflodacin inhibits the activity of DNA gyrase, a bacterial enzyme responsible for introducing negative supercoils into the bacterial DNA helix during replication. This process is essential for proper DNA replication and cell division in bacteria. 
• Disruption of DNA Replication: By inhibiting DNA gyrase, zoliflodacin disrupts the normal progression of DNA replication. This disruption hinders the bacteria’s ability to replicate their genetic material accurately. 
• Bactericidal Activity: zoliflodacin’s interference with DNA gyrase results in a bactericidal effect, causing the death of the bacterial cells. This mechanism makes it effective in eliminating susceptible strains of bacteria. 
• Activity Against Neisseria gonorrhoeae: zoliflodacin has demonstrated activity against Neisseria gonorrhoeae, the bacterium responsible for gonorrhea. This includes strains that may exhibit resistance to other commonly used antibiotics.

Pharmacokinetics: 

Absorption 

zoliflodacin is administered through oral or parenteral routes. Oral absorption involves the drug entering the bloodstream through the gastrointestinal tract.  

Distribution 

zoliflodacin is expected to distribute throughout the body after absorption. The drug may reach various tissues and body fluids, including those where Neisseria gonorrhoeae infections may be present. 

Metabolism 

The metabolism of zoliflodacin may involve hepatic processes. The liver is often a key organ for drug metabolism. 

Elimination and excretion 

zoliflodacin and its metabolites are eliminated from the body primarily through renal excretion. The kidneys play a major role in filtering the drug from the blood and excreting it in urine. Biliary excretion and fecal elimination might also contribute to the overall excretion process. 

Adminstartion

Administration: 

N/A 

Patient Information Leaflet

Patient information leaflet 

Generic Name: zoliflodacin 

Pronounced: (ZOH-lih-FLOH-duh-sin)  

Why do we use zoliflodacin? 

It is an investigational antibiotic designed to target bacterial infections, particularly those caused by Neisseria gonorrhoeae, which is the bacterium responsible for gonorrhea. The potential uses of zoliflodacin, if it receives regulatory approval, would be in the treatment of gonorrhea infections. Gonorrhea is a sexually transmitted infection (STI) that can affect various parts of the body, including the genital tract, rectum, and throat.