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FDA Approved Antibacterial Drugs in 2018 and 2019

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FDA Approved Antibacterial Drugs in 2018 and 2019 DISCOVERIES 2019, Oct-Dec, 7(4): e102 DOI: 10.15190/d.2019.15 FDA Approved Antibacterial Drugs in 2018 and 2019 Focused REVIEW FDA approved antibacterial drugs: 2018-2019 Stefan Andrei1,2,3,*, Gabriela Droc,1,2,Gabriel Stefan,2,4 1Department of Anesthesia and Intensive Care, Fundeni Clinical Institute, Bucharest, Romania 2Carol Davila University of Medicine and Pharmacy, Bucharest, Romania 3Université Paris Sud XI, Faculté de Médecine, Le Kremlin-Bicêtre, France 4Dr. Davila Teaching Hospital of Nephrology, Bucharest, Romania * Corresponding authors: Stefan Andrei, MD, Department of Anesthesia and Intensive Care, Fundeni Clinical Institute, 258 Soseaua Fundeni, Bucharest, 022328, Romania; Carol Davila University of Medicine and Pharmacy, Bucharest, Romania; Université Paris Sud XI, Faculté de Médecine, 63 Rue Gabriel Péri, 94270 Le Kremlin-Bicêtre, France; [email protected] Submission: Dec. 29, 2019; Revised: Dec. 31, 2019; Accepted: Dec. 31, 2019; Published: Dec. 31, 2019; Citation: Andrei S, Droc G, Stefan G. FDA approved antibacterial drugs: 2018-2019. Discoveries 2019, October-December; 7(4); e102. DOI:10.15190/d.2019.15 ABSTRACT noninvasive Escherichia Coli-caused travelers' Bacterial resistance to existent antibiotherapy is a diarrhea. Two combinatorial strategies were perpetual internationally-recognized problem. Year approved for complicated urinary tract infections, after year, there is a continuous need for novel complicated intra-abdominal infections (imipenem, antibacterial drugs and this research and cilastatin and relebactam) and lung tuberculosis development efforts recently resulted in few new (pretomanid in combination with bedaquiline and drugs or combination of drugs proposed for the use linezolid). Lefamulin is a semisynthetic into the clinic. pleuromutilin antibiotic for community-acquired This review focuses on the novel US FDA bacterial pneumonia, while cefiderocol, a approved antibacterial agents in the last two years cephalosporin antibiotic is the last antibacterial drug (2018-2019). Plazomicin, eravacycline, sarecycline, approved in 2019, for the use in complicated urinary omadacycline, rifamycin (2018) and imipenem, tract infections. cilastatin and relebactam combination, pretomanid, Despite of these new developments, there is an lefamulin, cefiderocol (2019) are new therapeutic ongoing need and urgency to develop novel options. Plazomicin aminoglycoside antibiotic antibiotic strategies and drugs to overrun the targets Enterobacteriaceae infections, being mainly bacterial resistance to antibiotics. used for the complicated urinary tract infections. The fully synthetic fluorocycline eravacycline gained Keywords: approval for the complicated intra-abdominal FDA approved drugs, Plazomicin, Eravacycline, infections. The tetracycline-derived antibiotic Sarecycline, Omadacycline. Rifamycin, Imipenem, sarecycline might be a useful strategy for the Cilastatin and Relebactam, Pretomanid, Lefamulin, management of non-nodular moderate to severe Cefiderocol, 2018, 2019. acne, while the other tetracycline-derived antibiotic approved, omadacycline, may be used for the Abbreviations: patients with acute bacterial skin and skin structure Food and Drug Administration (FDA); European infections and community-acquired bacterial Medicines Agency (EMA); Area under the curve (AUC); New Delhi metallo-β-lactamase (NDM); Verona integron- pneumonia. The already-known RNA-synthesis encoded metallo-β-lactamase (VIM); Imipenemase (IMP); suppressor rifamycin is now also approved for Complicated intra-abdominal infections (cIAIs); www.discoveriesjournals.org/discoveries 1 FDA Approved Antibacterial Drugs in 2018 and 2019 Complicated urinary tract infections (cUTIs); Hospital Moreover, pan-resistant bacteria emergence has been acquired bacterial pneumonia (HABP); Ventilator already described9,10. Other evidences further associated bacterial pneumonia (VABP); Acute bacterial consider the non-negligible role of environmental skin and skin structure infections (ABSSI); Intravenous and agriculture-related factors11,12. (IV); Central Nervous System (CNS); Hours (h); HRZE Antibiotic stewardship has proved its (isoniazid (H), rifampicin (R), pyrazinamide (Z) and 13- ethambutol (E) antituberculosis combination). efficiency, but it has its own limits and challenges 15 . However, the quest for new efficient molecules have to continue, remaining a pillar of anti- 1. Introduction 16 multidrug resistant germs strategy . The run to overcome the rapid bacterial resistance We briefly review here the novel antibacterial started with the initial use of antibiotics. However, agents approved by the United States Food and Drug after decades of struggling in research and in clinical Administration (US FDA) during the past 2 years practice, this run is rather a marathon than a sprint. (2018 and 2019) with the hope to further encourage Despite sustained efforts, the physicians are the scientific community in continuing the continuously confronting worldwide with the threat development of new therapeutic agents for targeting of bacterial resistance1-3. The burden on public the resistance of bacteria. The recently approved health contributed to the creation and antibacterial drugs and drug combinations were implementation of strategies on rational antibiotic identified using FDA’s website (https://www. use and on limiting the spread of resistant bacteria, accessdata.fda.gov; www.fda.gov) and Center the so called antibiotic stewardship4-7. Watch’s site (https://www.centerwatch.com/drug- Other strategy in this direction is to optimize information /fda-approved-drugs/). the existing pharmaceutical arsenal, through novel We reviewed the total number of drugs and combinations and new indications8. However, the drug combinations (blue) and number of number and efficiency of these drugs is far from antibacterial drugs and drug combinations (red) covering all the existing needs and to fully combat approved by the US FDA in the past 17 years (2003- the highly adaptive bacterial microorganisms. 2019) for each individual year (Figure 1, updated Figure 1. Novel FDA-approved antibacterial and non-bacterial drugs by year (last 17 years) (updated and modified from17) www.discoveriesjournals.org/discoveries 2 FDA Approved Antibacterial Drugs in 2018 and 2019 and modified from17). There is a clear upward trend pyelonephritis), caused by susceptible Escherichia in terms of the number of antibacterial drugs coli, Klebsiella pneumoniae, Proteus mirabilis or approved by year. Enterobacter cloacae18,19. To the date of this review, 9 antibacterial drugs Plazomicin is supplied as single-dose vials in an or combination of drugs were approved for 2018 and amount of 500 mg/10 mL plazomicin base19. 2019, from a total of 107 introduced molecules. In Administration recommendations can be found in 2018, the 5 approved antibacterial drugs or Table 1 and its dosage is personalized based on the combinations of drugs represented 8.4% of the total renal function and/or therapeutic monitoring of the of 59 new drugs, while in 2019 the 4 new single or drug, if available19. Plazomicin might be of value in combination of antibacterial drugs represented patients that have resistance to their primary 8.33% of the 48 approved molecules. This represents treatment options or who are allergic to beta-lactam a significant increase from the previous years antibiotics. (Figure 1), since the number of antibacterial drugs The most important adverse events reported or regimens in the past two years has doubled as with plazomicin are: nephrotoxicity (but lower compared to the two previous years. incidence of nephrotoxicity than colistin), diarrhea, We identified 9 novel FDA approved hypertension, headache, nausea, vomiting, antibacterial drugs: plazomicin aminoglycoside hypotension20. antibiotic, the fully synthetic fluorocycline Plazomicin showed to be non-inferior to eravacycline, tetracycline-derived antibiotics meropenem within the EPIC non-inferiority trial in sarecycline and omadacycline, RNA synthesis treatment of cUTIs and even demonstrated superior suppressor rifamycin, two combinatorial strategies microbiological eradication (81.7% versus 70.1%; (imipenem (carbapenem antibiotic), cilastatin and 95% confidence interval (CI) 2.7-25.7)21. relebactam and pretomanid (nitroimidazole) in Plazomicin-based combinations also demonstrated combination with bedaquiline and linezolid), the decreased disease-complications and mortality when semisynthetic pleuromutilin antibiotic lefamulin and compared to colistin-based combination in the cefiderocol, a cephalosporin antibiotic (Tables 1 & CARE trial (23.5% versus 50%; 90% CI -0.7 to 2). These drugs are briefly discussed by FDA- 51.2)20. approval year in the next section. 2.2 Eravacycline 2. FDA approved antibacterial drugs (2018-2019) Eravacycline dihydrochloride (Xerava) is a fully synthetic bacteriostatic fluorocycline and a 2.1 Plazomicin tetracycline-class antibacterial agent that binds Plazomicin sulfate (Zemdri) is a semisynthetic bacterial 30S ribosomal subunit. Compared to other aminoglycoside bactericidal antibiotic drug, acting tetracyclines, it has two structural substitutions in asimilar manner to other aminoglycosides, by which makes the drug working on certain strains of suppressing the 30S bacterial ribosomal subunit. Gram-positive and Gram-negative bacteria that Noteworthy, while other aminoglycosides can be usually have tetracycline-specific resistance inactivated by aminoglycoside-modifying enzymes, mechanisms. Noteworthy, eravacycline
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