Re-establishing the utility of tetracycline-class antibiotics for current challenges with antibiotic resistance

Abstract

The progressive increase in antibiotic resistance in recent decades calls for urgent development of new antibiotics and antibiotic stewardship programs to help select appropriate treatments with the goal of minimising further emergence of resistance and to optimise clinical outcomes. Three new tetracycline-class antibiotics, eravacycline, omadacycline, and tigecycline, have been approved within the past 15 years, and represent a new era in the use of tetracyclines. These drugs overcome the two main mechanisms of acquired tetracycline-class resistance and exhibit a broad spectrum of in vitro activity against gram-positive, gram-negative, anaerobic, and atypical pathogens, including many drug-resistant strains. We provide an overview of the three generations of tetracycline-class drugs, focussing on the efficacy, safety, and clinical utility of these three new third-generation tetracycline-class drugs. We also consider various scenarios of unmet clinical needs where patients might benefit from re-engagement with tetracycline-class antibiotics including outpatient treatment options, patients with known β-lactam antibiotic allergy, reducing the risk of Clostridioides difficile infection, and their potential as monotherapy in polymicrobial infections while minimising the risk of any potential drug-drug interaction. KEY MESSAGES The long-standing safety profile and broad spectrum of activity of tetracycline-class antibiotics made them a popular choice for treatment of various bacterial infections; unfortunately, antimicrobial resistance has limited the utility of the early-generation tetracycline agents. The latest generation of tetracycline-class antibiotics, including eravacycline, tigecycline, and omadacycline, overcomes the most common acquired tetracycline resistance mechanisms. Based on in vitro characteristics and clinical data, these newer tetracycline agents provide an effective antibiotic option in the treatment of approved indications in patients with unmet clinical needs – including patients with severe penicillin allergy, with renal or hepatic insufficiency, recent Clostridioides difficile infection, or polymicrobial infections, and those at risk of drug–drug interactions.

In Vitro Antimicrobial Activities of Tigecycline, Eravacycline, Omadacycline, and Sarecycline against Rapidly Growing Mycobacteria

“…New or repurposed antibiotics with good efficacy and safety are the major route to solving this dilemma. Several novel tetracycline-class antibiotics have been applied to treat infections in recent years, while either in vitro or in vivo activity data for these tetracyclines against different RGM species remain scarce ( 27 – 29 ). Limited studies have evaluated the in vitro activities of ERC and OMC against a few clinical isolates of M. abscessus complex ( 30 , 31 ), whereas no such evaluation has been performed for SAC.…”

Multimodal imaging appearance including cinematic rendering of renal malakoplakia in a patient with E. coli bacteremia

“…After obtaining the biopsy results, treatment options were weighed including administration of antibiotics with intracellular penetration capabilities due to the macrophage dysfunction associated with malakoplakia. Tigecycline was chosen due to the resistance profile of the patient's bacterial isolate and the mechanism of resistance compared to the other tetracyclines [14] . Ceftriaxone was also used to treat the patient as bacterial cultures showed sensitivity to this medication.…”

Study of Electrospun Membranes Composed of PCL and Tilapia-Skin Collagen with Tetracycline or Chloramphenicol in Contact with Human Skin Fibroblasts for Wound Dressing Treatment

“…As most of the wound infections or biofilms are polymicrobial, it is recommended to manage them with wide-spectrum antibiotics. Tetracycline is a favorable drug with antimicrobial properties versus Gram-negative and Gram-positive bacteria, is easily absorbed in all tissues, and has been widely used in the treatment of animal and human infections due to its efficiency, low side effects, and affordable cost . On the other hand, chloramphenicol is a broad-spectrum antibiotic that exhibits activity against a wide range of bacteria.…”