Non–anti-infective Effects of Antimicrobials and Their Clinical Applications

Abstract

Antimicrobial agents are undoubtedly one of the key advances in the history of modern medicine and infectious diseases, improving the clinical outcomes of infection owing to their inhibitory effects on microbial growth. However, many antimicrobial agents also have biological activities stemming from their interactions with host receptors and effects on host inflammatory responses and other human or bacterial cellular biological pathways. These result in clinical uses of antimicrobial drugs that are distinct from their direct bacteriostatic or bactericidal properties. We reviewed the published literature regarding non-anti-infective therapeutic properties and proposed clinical applications of selected antimicrobials, specifically, macrolides, tetracyclines, sulfonamides, and ketoconazole. The clinical applications reviewed were varied, and we focused on uses that were clinically relevant (in terms of importance and burden of disease) and where published evidence exists. Such uses include chronic inflammatory pulmonary and skin disorders, chronic periodontitis, gastrointestinal dysmotility, rheumatoid arthritis, and cancer. Most of these potential therapeutic uses are not Food and Drug Administration approved. Clinicians need to weigh the use of antimicrobial agents for their non-anti-infective benefits, considering potential adverse effects and long-term effect on microbial resistance.

Non Antimicrobial Effects of Antibacterial Agents

“…Alzheimer hastalığı ile ilgili olarak tetrasiklinler (özellikle minosiklin) hastalığın gelişmesinde kilit rolü olan betaamiloid proteinini azaltarak etkilerini göstermektedirler [43,44] . Minosiklinin nöroprotektif etkisini, mikrogliyal aktivasyonu indüklemesi, proenflamatuvar sitokinlerin "down-regülasyonu" ve mitokondriyal geçirgenliğin kontrolünü sağlaması ile gösterdiği düşünülmektedir.…”

“…Makrolidler ayrıca lökotrien B oluşumunu ve oksidan üretimini azaltarak nötrofil fonksiyonunu etkiler. Bir yandan da nötrofil migrasyonu için gerekli olan MMP ve adezyon moleküllerini bloke eder [43] .…”

“…Bunun yanında eritromisinin Th1'den Th2'ye dönüşümü inhibe etme, T lenfosit apoptozunu arttırma ve T lenfosit proliferosyonunu inhibe etme gibi özellikleri de bildirilmiştir [43] . Astmada oluşan enflamasyonu engellemek için uzun süredir üzerinde çalışmalar yapılmaktadır.…”

Corticosteroids as a therapy for bacterial keratitis: an evidence-based review of ‘who, when and why’

“…These bacterial products are cytotoxic for several host cell types, causing damage to the epithelial and stromal tissue during bacterial keratitis 18. While some antibiotics (especially the tetracycline and macrolide classes) are thought to have intrinsic anti-inflammatory activity,19 it is also likely that the diminution of inflammation with effective antibiotic use is primarily related to a combination of inhibition of toxin synthesis and eradication of the organisms producing the toxins.…”

Exploring novel AEDs from drugs used for treatment of non-epileptic disorders

“…But most of the experimental subjects are cell or animal models. If rapamycin is used to treat epileptic patients clinically which often require several years, the safety of the drug need to be considered, more clinical trials are needed and clinicians need to consider potential adverse effects and longterm effect on microbial resistance [16].…”