Antibiotics: Experimental
Experimental antibiotics refer to antibiotics currently undergoing clinical trials, those awaiting FDA approval, or those approved by the FDA but not yet available to the public. This area of research is crucial in addressing the growing challenge of antibiotic resistance, which complicates treatment and increases the burden on healthcare systems. Among the notable experimental antibiotics are ceftobiprole and ceftaroline, both belonging to the fifth generation of cephalosporins. Ceftobiprole is still awaiting FDA approval but shows promise for treating a wide range of bacteria, including MRSA. Ceftaroline, on the other hand, has been approved for specific infections, including skin and bacterial pneumonia, and has demonstrated a good safety profile.
Another significant candidate is fidaxomicin, which targets Clostridium difficile infections and has shown efficacy comparable to the standard treatments of metronidazole and vancomycin. The development of these experimental antibiotics highlights the need for targeted therapies that can effectively combat specific bacterial infections while minimizing the risk of resistance. As research advances, the potential impact of these antibiotics on public health will become clearer, emphasizing the importance of continued innovation in antibiotic development.
Antibiotics: Experimental
Definition
Experimental antibiotics are antibiotics under study in clinical trials, antibiotics awaiting U.S. Food and Drug Administration (FDA) approval, and antibiotics that have been approved by the FDA but are not available to the public.
Ceftaroline and Ceftobiprole
Two new cephalosporin antibiotics comprise what is termed “fifth-generation cephalosporins”: ceftobiprole and ceftaroline. Ceftobiprole is fifth-generation broad-spectrum cephalosporin awaiting FDA approval. In studies, ceftobiprole has shown broad coverage of gram-positive and gram-negative bacteria (both aerobes and anaerobes), including activity against methicillin-resistant Staphylococcus aureus (MRSA) and Pseudomonas. Its mechanism of action is similar to other cephalosporins.
Because of the broad-spectrum nature of ceftobiprole, many experts believe it may be utilized as empirical treatment in hospital settings in cases when antibiotic treatment needs to be started before culture and sensitivity results are complete. Two phase-three studies looked at ceftobiprole for the treatment of skin and complicated skin-structure infections. In these two published phase-three clinical trials, study subjects received a 500 milligram (mg) dose intravenously, every eight hours or every twelve hours; this dosage was compared with a 1 gram (g) dose of vancomycin given every twelve hours (with or without ceftazidime at 1 g every eight hours). Combined, more than fifteen hundred study subjects were enrolled in the trials. In both trials, ceftobiprole was found to be noninferior to the comparator with a similar adverse-effect profile.
Additional phase-three trials were conducted for the indication of hospital- and community-acquired pneumonia and in persons with fever and neutropenia after chemotherapy. Adverse events were similar between treatment groups in both trials. Additionally, ceftobiprole has been studied for endocarditis, orthopedic infections, and pneumonia. The most common adverse events reported in clinical trials, most classified as mild to moderate, include gastrointestinal upset and headache. The FDA has not approved ceftobiprole, and it has requested additional clinical trials be completed by the manufacturer.
Ceftaroline is a broad-spectrum cephalosporin with a mechanism of action similar to other beta-lactams. It provides coverage of gram-positive, gram-negative, and anaerobic bacteria. Importantly, it displays gram-positive activity against most pathogens, including MRSA. Ceftaroline has been approved for two indications: acute bacterial skin and skin-structure infections and community-acquired bacterial pneumonia (CABP).
Two phase-three trials were conducted to investigate ceftaroline for the indication of moderate to severe CABP requiring treatment with intravenous antibiotics. Two additional phase-three trials investigated ceftaroline for the treatment of complicated skin and skin-structure infections. In clinical trials, the most common adverse events (reported in less than 2 percent of study subjects) were diarrhea, nausea, and rash. Overall, the medication was well tolerated and had adverse-event rates similar to comparator treatments.
Fidaxomicin
Fidaxomicin is a novel, narrow-spectrum macrocyclic antibiotic that targets bacterial RNA (ribonucleic acid) polymerase studied in clinical trials for Clostridium difficile infection. Fidaxomicin has been studied in phase-three clinical trials in adults with C. difficile infection. The two compounds most often, and almost exclusively, used for the treatment of C. difficile infection are oral metronidazole and oral vancomycin. Study subjects were randomized to receive either fidaxomicin 200 milligrams (mg) twice daily or standard therapy with oral vancomycin 125 mg four times daily. More than six hundred persons were enrolled, and the study found fidaxomicin to be noninferior to treatment with vancomycin.
One of the proposed benefits of this therapy is its minimal systemic absorption; also, it does not affect most normal gut flora. Additionally, its spectrum of action (no gram-negative coverage and some gram-positive coverage) means it is highly specific for C. difficile. In two phase-three trials, fidaxomicin was given orally at 200 mg every twelve hours for ten days and was found to be noninferior in terms of clinical cure rates.
Other Experimental Antibiotics
Throughout the 2010s and 2020s, numerous experimental antibiotics were discovered by scientists. Many of these antibiotics showed potential for medical treatments when tested in laboratory conditions. In 2023, Pfizer showed that its experimental antibiotic combination, featuring the experimental antibiotic aztreonam-avibactam and several existing antibiotics, could fight intra-abdominal infections and hospital-acquired pneumonia. In 2024, the antibiotic zosurabalpin was shown to successfully fight the Gram-negative bacterium carbapenem-resistant Acinetobacter baumannii (CRAB). It had been more than fifty years since the FDA approved a new class of antibiotics that targets this class of bacteria.
Impact
Antibiotic resistance results in longer times to eradicate pathogens, more frequent clinical failures, and a heavy burden on the healthcare system. The importance of using targeted antibiotics and of decreasing unwarranted widespread use of antibiotics is critical to curbing antibiotic resistance and to maintaining the efficacy of available therapies.
Experimental antibiotics can be designed to target a broad spectrum of bacteria, such as the newer fifth-generation cephalosporins, or they can be niche antibiotics with a narrow spectrum, such as fidaxomicin for C. difficile infection. The significance of these and other antibiotics undergoing clinical trials will be fully analyzable once they are widely available.
Bibliography
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Louie, Thomas J., et al. “Fidaxomicin Versus Vancomycin for Clostridium difficile Infection.” New England Journal of Medicine 364 (2011): 422-431.
Noel, G. J., et al. “A Randomized, Double-Blind Trial Comparing Ceftobiprole Medocaril with Vancomycin plus Ceftazidime for the Treatment of Patients with Complicated Skin and Skin-Structure Infections.” Clinical Infectious Diseases 46, no. 5 (2008): 647-655.
"Pfizer Says Its Experimental Antibiotic Combo Can Treat Some Superbug Infections." Reuters, 1 June 2023, www.reuters.com/business/healthcare-pharmaceuticals/pfizer-says-its-experimental-antibiotic-combo-can-treat-some-superbug-infections-2023-06-01/. Accessed 3 Feb. 2025.
Sanford, Jay P., et al. The Sanford Guide to Antimicrobial Therapy. 18th ed. Sperryville, Va.: Antimicrobial Therapy, 2010.
Steed, Molly E., and Michael J. Rybak. “Ceftaroline: A New Cephalosporin with Activity Against Resistant Gram-Positive Pathogens.” Pharmacotherapy 30, no. 4 (2010): 375-389.