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Recent advances of metronidazole - A review
Abstract
Metronidazole is a nitroimidazole drug that is still being used for the treatment of various infections by anaerobes, parasites, and bacteria. It was first developed in the year 1959. It differs from the other types of antimicrobials as it has the ability to react with a large quantity of molecules. Metronidazole is a prodrug that gets toxic when it is reduced to its nitro group. Only at very low concentrations of oxygen, reduction of metronidazole into its nitro group takes place. This explains why metronidazole is highly toxic to the anaerobic microorganisms. In the present day, it is seen that the resistance rate among the various pathogens treated using metronidazole is still low. Resistance to metronidazole occurs from time to time and is generally seen during the treatment of some pathogens such as Helicobacter pylori. The working of metronidazole has almost become useless in parts around the world. This review will help give an understanding on the current status of research on metronidazole mode of action and metronidazole resistance.
... However, its mode of action is not completely understood. It has been reported that metronidazole inhibits the synthesis of deoxyribose nucleic acid (DNA) and replication in bacteria, resulting in bacterial cell death [27][28][29]. In wound treatment, metronidazole is known as an effective therapeutic agent in controlling wound odor [30]. ...
Polymer-based sponges loaded with antibacterial agents are potential wound dressings ideal for treating bacteria-infected wounds. Gelatin/poly (ethylene glycol) (PEG) sponge-based wound dressings loaded with metronidazole and Ag nanoparticles with different degrees of cross-linking were prepared, and their capability to treat infected wounds in vitro was evaluated. The degree of cross-linking of the sponges varied, and the porosity of the sponges was in the range of 15.64–91.10%. The amount of gelatin used to prepare the sponges influenced the porosity of the sponges. The sponges displayed an initial burst drug release of metronidazole followed by a sustained release profile. The sponges exhibited considerable antibacterial activity against Gram-positive and Gram-negative bacteria. The % cell viability of the sponges was in the range of 71.17–86.10%, indicating distinguished biocompatibility. The in vitro experiment showed that the sponge loaded with metronidazole, SAM2%, displayed a significant reduction of 66.68% in the scratch area compared to the sponge loaded with a combination of silver nanoparticles and metronidazole with a closure rate of 46.61% at 96 h. The promising features of the sponges indicate that they are potential wound dressings for treating infected wounds.
... More serious and rarer adverse events include numbness, peripheral neuropathy, and seizures [47]. Significantly, alcohol can interact with metronidazole in a disulfiramlike reaction that typically presents with flushing, cramping, vomiting, tachycardia, and palpitations [48,49]. To avoid this, patients should refrain from alcohol use while taking metronidazole, and 72 h following the last dose of metronidazole. ...
Background:
When prescribing antibiotics, infection eradication rates, local resistance rates, and cost should be among the most essential considerations. Helicobacter pylori is among the most common infections worldwide, and it can lead to burdensome sequela for the patient and the healthcare system, without appropriate treatment. Due to constantly fluctuating resistance rates, regimens must be constantly assessed to ensure effectiveness.
Methods:
This was a narrative review. The sources for this review are as follows: searching on PubMed, Google Scholar, Medline, and ScienceDirect; using keywords: Helicobacter pylori, Treatment Options, Clinical Practice.
Results:
Multiple antibiotics are prescribed as part of the regimen to thwart high resistance rates. This can lead to unwanted adverse reactions and adherence issues, due to the amount and timing of medication administration, which also may contribute to resistance. Single-capsule combination capsules have reached the market to ease this concern, but brand-only may be problematic for patient affordability. Due to the previously mentioned factors, effectiveness and affordability must be equally considered.
Conclusions:
This review will utilize guidelines to discuss current treatment options and give cost considerations to elicit the most effective regimen for the patient.
... For instance, the metronidazole requires to cross the cell wall as a prerequisite for its chemical activation; besides, it requires low potentials to be reduced, around −450 mV [23]. Once the metronidazole is inside the cell, it is rapidly reduced into nitroso free-radical; this chemical state is toxic and can damage the DNA molecule of anaerobic bacteria [21]. On the other hand, low potentials are not found in aerobic conditions, thus, redox potentials with positive values are avoiding the metronidazole reduction and therefore its high toxicity. ...
Metronidazole is potentially carcinogenic to humans and it has been detected in wastewaters. The Wastewater Treatment Plants using biological processes have been highly impacted by emergent compounds of recalcitrant type, and the knowledge about that issue is quite relevant. Therefore, this paper was focused on how metronidazole influences the kinetics and metabolic behavior of nitrification and heterotrophic activity on activated sludge in batch cultures. Eight concentrations of metronidazole in the range of 5 to 100 mg/L were evaluated, in presence of 2109 ± 129 mg VSS/L. The increment of initial metronidazole concentration caused a decline on COD and ammonium removal efficiencies, nitrate production yields, as well as in the substrate specific consumption rates. Metronidazole (MDZ) had a greater impact on heterotrophic activity than nitrifying activity; also, it had a greater inhibitory effect on nitrite oxidation than ammonium oxidation. The activated sludge was not able to biotransform metronidazole, however the azole compound significantly affected the physiology of it. The inhibition of ammonium oxidation was non-competitive (qmax = 120 mg NH4⁺-N consumed/gVSS-d, and Ki = 41.5 mg MDZ/L) and the initial metronidazole concentration that inhibited 50% of nitrifying activity (IC50) was 43 mg MDZ/L.
Infections especially tuberculosis caused by various bacteria including mycobacteria result in millions of lives every year, but the control of bacterial infections is challenged by the limitation of effective pharmaceuticals against drug-resistant pathogens. Nitroimidazoles belong to a group of nitroheterocyclic compounds that have broad-spectrum activity against a series of organisms such as mycobacteria, anaerobic Gram-positive and Gram-negative bacteria, and some of them have already been used in clinics or under clinical trials for the treatment of infectious diseases. In this review, we made an overview of the recent advances in nitroimidazole-containing compounds with antibacterial and antitubercular activity in the recent 20 years.
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