In Vitro Antibacterial Activity of Metformin Against Gram-Positive and Gram-Negative Bacteria Associated with Diabetic Wounds

Abstract

Objective: This study aimed to determine the in vitro antibacterial activity of metformin hydrochloride against reference strains of Pseudomonas aeruginosa, Staphylococcus aureus, Escherichia coli, and Enterococcus faecalis associated with diabetic wound infections. Methods: P. aeruginosa ATCC 27853, S. aureus ATCC 25923, E. coli ATCC 25922, and E. faecalis ATCC 29212 were used. The antibacterial activity of metformin hydrochloride was evaluated using agar well diffusion and broth microdilution methods. Minimum bactericidal concentrations were determined by subculturing samples from wells without visible bacterial growth onto Mueller–Hinton agar. The experiments were performed in three technical replicates. Results: No measurable inhibition zone was observed for any of the tested strains in the agar well diffusion assay. The minimum inhibitory concentration was 64 mg/mL for P. aeruginosa, S. aureus, and E. coli and 128 mg/mL for E. faecalis. The minimum bactericidal concentration was 128 mg/mL for P. aeruginosa and E. coli and greater than 128 mg/mL for S. aureus and E. faecalis. Conclusion: Metformin hydrochloride exhibited species-dependent antibacterial activity. A bactericidal endpoint was achieved for P. aeruginosa and E. coli, whereas no definitive bactericidal endpoint was reached for the Gram-positive strains within the tested concentration range. These findings demonstrate that the antibacterial activity of metformin may vary according to the evaluation method and provide preliminary data for investigating its potential in local or controlled-release systems.

Keywords

• Drug repurposing
• metformin
• minimum inhibitory concentration
• minimum bactericidal concentration
• broth microdilution
• Gram-negative microorganisms

Project Number

1919B012472944

Ethical Statement

Ethics committee approval was not required for this in vitro study.

Metforminin Diyabetik Yaralarla İlişkili Gram-Pozitif ve Gram-Negatif Bakteriler Üzerindeki İn Vitro Antibakteriyel Etkinliği

Abstract

Amaç: Bu çalışmada, diyabetik yara enfeksiyonlarıyla ilişkili Pseudomonas aeruginosa, Staphylococcus aureus, Escherichia coli ve Enterococcus faecalis referans suşlarına karşı metformin hidroklorürün in vitro antibakteriyel aktivitesinin belirlenmesi amaçlanmıştır. Yöntem: Çalışmada P. aeruginosa ATCC 27853, S. aureus ATCC 25923, E. coli ATCC 25922 ve E. faecalis ATCC 29212 suşları kullanılmıştır. Metformin hidroklorürün antibakteriyel aktivitesi agar kuyu difüzyon ve sıvı mikrodilüsyon yöntemleri kullanılarak değerlendirilmiştir. Minimum bakterisidal konsantrasyonlar, görünür bakteriyel üreme gözlenmeyen kuyucuklardan alınan örneklerin Mueller–Hinton agara pasajlanmasıyla belirlenmiştir. Deneyler üç teknik tekrarlı olarak gerçekleştirilmiştir. Bulgular: Agar kuyu difüzyon deneyinde test edilen suşların hiçbirinde ölçülebilir bir inhibisyon zonu gözlenmemiştir. Minimum inhibitör konsantrasyon P. aeruginosa, S. aureus ve E. coli için 64 mg/mL, E. faecalis için ise 128 mg/mL olarak belirlenmiştir. Minimum bakterisidal konsantrasyon P. aeruginosa ve E. coli için 128 mg/mL, S. aureus ve E. faecalis için ise 128 mg/mL’den yüksek bulunmuştur. Sonuç: Metformin hidroklorür, türe bağlı antibakteriyel aktivite göstermiştir. P. aeruginosa ve E. coli için bakterisidal sonlanım noktasına ulaşılırken, test edilen konsantrasyon aralığında Gram-pozitif suşlar için kesin bir bakterisidal sonlanım noktası belirlenememiştir. Bu bulgular, metforminin antibakteriyel aktivitesinin kullanılan değerlendirme yöntemine göre değişebileceğini göstermekte ve lokal veya kontrollü salım sistemlerindeki potansiyelinin araştırılmasına yönelik ön veriler sunmaktadır.

Keywords

• İlacın yeniden konumlandırılması
• metformin
• minimum inhibitör konsantrasyon
• minimum bakterisidal konsantrasyon
• sıvı mikrodilüsyon
• Gram-negatif mikroorganizmalar

Project Number

1919B012472944

Ethical Statement

Bu in vitro çalışma için etik kurul onayı gerekli değildi.

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