Treatment of MRSA Infection: Where are We?

Adila      Nazli; Wenlan      Tao; Hengyao      You; Xiaoli      He; Yun      He
doi:10.2174/0109298673249381231130111352
Abstract

Staphylococcus aureus is a leading cause of septicemia, endocarditis, pneumonia, skin and soft tissue infections, bone and joint infections, and hospital-acquired infections. In particular, methicillin-resistant Staphylococcus aureus (MRSA) is associated with high morbidity and mortality, and continues to be a major public health problem. The emergence of multidrug-resistant MRSA strains along with the wide consumption of antibiotics has made anti-MRSA treatment a huge challenge. Novel treatment strategies (e.g., novel antimicrobials and new administrations) against MRSA are urgently needed. In the past decade, pharmaceutical companies have invested more in the research and development (R&D) of new antimicrobials and strategies, spurred by favorable policies. All research articles were collected from authentic online databases, including Google Scholar, PubMed, Scopus, and Web of Science, by using different combinations of keywords, including ‘anti-MRSA’, ‘antibiotic’, ‘antimicrobial’, ‘clinical trial’, ‘clinical phase’, clinical studies’, and ‘pipeline’. The information extracted from articles was compared to information provided on the drug manufacturer’s website and Clinical Trials.gov (https://clinicaltrials.gov/) to confirm the latest development phase of anti-MRSA agents. The present review focuses on the current development status of new anti-MRSA strategies concerning chemistry, pharmacological target(s), indications, route of administration, efficacy and safety, pharmacokinetics, and pharmacodynamics, and aims to discuss the challenges and opportunities in developing drugs for anti-MRSA infections.
Keywords: MRSA, multidrug resistance, antibiotics, antimicrobial, clinical trials, pharmacokinetics, effectiveness, safety.
« Previous Next »
[1]
Walsh, L.; Johnson, C.N.; Hill, C.; Ross, R.P. Efficacy of phage- and bacteriocin-based therapies in combatting nosocomial MRSA infections. Front. Mol. Biosci.,  2021, 8(4), 654038.
 [http://dx.doi.org/10.3389/fmolb.2021.654038] [PMID: 33996906]

[2]
Diekema, D.J.; Climo, M. Preventing MRSA infections. JAMA,  2008, 299(10), 1190-1192.
 [http://dx.doi.org/10.1001/jama.299.10.1190] [PMID: 18334697]

[3]
Harkins, C.P.; Pichon, B.; Doumith, M.; Parkhill, J.; Westh, H.; Tomasz, A.; de Lencastre, H.; Bentley, S.D.; Kearns, A.M.; Holden, M.T.G. Methicillin-resistant Staphylococcus aureus emerged long before the introduction of methicillin into clinical practice. Genome Biol.,  2017, 18(1), 130-141.
 [http://dx.doi.org/10.1186/s13059-017-1252-9] [PMID: 28724393]

[4]
Morell, E.A.; Balkin, D.M. Methicillin-resistant Staphylococcus aureus: A pervasive pathogen highlights the need for new antimicrobial development. Yale J. Biol. Med.,  2010, 83(4), 223-233.
 [PMID: 21165342]

[5]
Shanmuganathan, V.A.; Armstrong, M.; Buller, A.; Tullo, A.B. External ocular infections due to methicillin-resistant Staphylococcus aureus (MRSA). Eye (Lond.),  2005, 19(3), 284-291.
 [http://dx.doi.org/10.1038/sj.eye.6701465] [PMID: 15375372]

[6]
Villegas-Estrada, A.; Lee, M.; Hesek, D.; Vakulenko, S.B.; Mobashery, S. Co-opting the cell wall in fighting methicillin-resistant Staphylococcus aureus: Potent inhibition of PBP 2a by two anti-MRSA β-lactam antibiotics. J. Am. Chem. Soc.,  2008, 130(29), 9212-9213.
 [http://dx.doi.org/10.1021/ja8029448] [PMID: 18582062]

[7]
El Amin, N.M.; Faidah, H.S. Methicillin-resistant Staphylococcus aureus in the Western region of Saudi Arabia: Prevalence and antibiotic susceptibility pattern. Ann. Saudi Med.,  2012, 32(5), 513-516.
 [http://dx.doi.org/10.5144/0256-4947.2012.513] [PMID: 22871621]

[8]
Chatterjee, S.S.; Ray, P.; Aggarwal, A.; Das, A.; Sharma, M. A community-based study on nasal carriage of Staphylococcus aureus. Indian J. Med. Res.,  2009, 130(6), 742-748.
 [PMID: 20090137]

[9]
Stefani, S.; Chung, D.R.; Lindsay, J.A.; Friedrich, A.W.; Kearns, A.M.; Westh, H.; MacKenzie, F.M. Meticillin-resistant Staphylococcus aureus (MRSA): Global epidemiology and harmonisation of typing methods. Int. J. Antimicrob. Agents,  2012, 39(4), 273-282.
 [http://dx.doi.org/10.1016/j.ijantimicag.2011.09.030] [PMID: 22230333]

[10]
von Eiff, C.; Becker, K.; Machka, K.; Stammer, H.; Peters, G. Nasal carriage as a source of Staphylococcus aureus bacteremia. N. Engl. J. Med.,  2001, 344(1), 11-16.
 [http://dx.doi.org/10.1056/NEJM200101043440102] [PMID: 11136954]

[11]
Clarridge, J.E., III; Harrington, A.T.; Roberts, M.C.; Soge, O.O.; Maquelin, K. Impact of strain typing methods on assessment of relationship between paired nares and wound isolates of methicillin-resistant Staphylococcus aureus. J. Clin. Microbiol.,  2013, 51(1), 224-231.
 [http://dx.doi.org/10.1128/JCM.02423-12] [PMID: 23135945]

[12]
Lakhundi, S.; Zhang, K. Methicillin-resistant Staphylococcus aureus: Molecular characterization, evolution, and epidemiology. Clin. Microbiol. Rev.,  2018, 31(4), e00020-18.
 [http://dx.doi.org/10.1128/CMR.00020-18] [PMID: 30209034]

[13]
David, M.Z.; Cadilla, A.; Boyle-Vavra, S.; Daum, R.S. Replacement of HA-MRSA by CA-MRSA infections at an academic medical center in the midwestern United States, 2004-5 to 2008. PLoS One,  2014, 9(4), e92760.
 [http://dx.doi.org/10.1371/journal.pone.0092760] [PMID: 24755631]

[14]
Bean, H.D.; Zhu, J.; Sengle, J.C.; Hill, J.E. Identifying methicillin-resistant Staphylococcus aureus (MRSA) lung infections in mice via breath analysis using secondary electrospray ionization-mass spectrometry (SESI-MS). J. Breath Res.,  2014, 8(4), 041001-41001.
 [http://dx.doi.org/10.1088/1752-7155/8/4/041001] [PMID: 25307159]

[15]
Tenover, F.; Biddle, J.W.; Lancaster, M.V. Increasing resistance to vancomycin and other glycopeptides in Staphylococcus aureus. Emerg. Infect. Dis.,  2001, 7(2), 327-332.
 [http://dx.doi.org/10.3201/eid0702.010237] [PMID: 11294734]

[16]
Shrivastava, S.; Shrivastava, P.; Ramasamy, J. World health organization releases global priority list of antibiotic-resistant bacteria to guide research, discovery, and development of new antibiotics. J. Med. Society,  2018, 32(1), 76-77.
 [http://dx.doi.org/10.4103/jms.jms_25_17]

[17]
Bassetti, M.; Del Puente, F.; Magnasco, L.; Giacobbe, D.R. Innovative therapies for acute bacterial skin and skin-structure infections (ABSSSI) caused by methicillin-resistant Staphylococcus aureus : Advances in phase I and II trials. Expert Opin. Investig. Drugs,  2020, 29(5), 495-506.
 [http://dx.doi.org/10.1080/13543784.2020.1750595] [PMID: 32242469]

[18]
French, G.L. Bactericidal agents in the treatment of MRSA infections--the potential role of daptomycin. J. Antimicrob. Chemother.,  2006, 58(6), 1107-1117.
 [http://dx.doi.org/10.1093/jac/dkl393] [PMID: 17040922]

[19]
Zeller, J.L.; Burke, A.E.; Glass, R.M. MRSA Infections. JAMA,  2007, 298(15), 1826-1826.
 [http://dx.doi.org/10.1001/jama.298.15.1826] [PMID: 17940240]

[20]
Wilcox, M.H.; Hall, J.; Pike, H.; Templeton, P.A.; Fawley, W.N.; Parnell, P.; Verity, P. Use of perioperative mupirocin to prevent methicillin-resistant Staphylococcus aureus (MRSA) orthopaedic surgical site infections. J. Hosp. Infect.,  2003, 54(3), 196-201.
 [http://dx.doi.org/10.1016/S0195-6701(03)00147-6] [PMID: 12855234]

[21]
Hsu, D.I.; Hidayat, L.K.; Quist, R.; Hindler, J.; Karlsson, A.; Yusof, A.; Wong-Beringer, A. Comparison of method-specific vancomycin minimum inhibitory concentration values and their predictability for treatment outcome of meticillin-resistant Staphylococcus aureus (MRSA) infections. Int. J. Antimicrob. Agents,  2008, 32(5), 378-385.
 [http://dx.doi.org/10.1016/j.ijantimicag.2008.05.007] [PMID: 18701261]

[22]
Kurosu, M.; Siricilla, S.; Mitachi, K. Advances in MRSA drug discovery: Where are we and where do we need to be? Expert Opin. Drug Discov.,  2013, 8(9), 1095-1116.
 [http://dx.doi.org/10.1517/17460441.2013.807246] [PMID: 23829425]

[23]
Weis, F.; Beiras-Fernandez, A.; Schelling, G. Daptomycin, a lipopeptide antibiotic in clinical practice. Curr. Opin. Investig. Drugs,  2008, 9(8), 879-884.
 [PMID: 18666036]

[24]
Tedesco, K.L.; Rybak, M.J. Daptomycin. Pharmacotherapy,  2004, 24(1), 41-57.
 [http://dx.doi.org/10.1592/phco.24.1.41.34802] [PMID: 14740787]

[25]
Enoch, D.A.; Bygott, J.M.; Daly, M.L.; Karas, J.A. Daptomycin. J. Infect.,  2007, 55(3), 205-213.
 [http://dx.doi.org/10.1016/j.jinf.2007.05.180] [PMID: 17629567]

[26]
Patel, J.B.; Jevitt, L.A.; Hageman, J.; McDonald, L.C.; Tenover, F.C. An association between reduced susceptibility to daptomycin and reduced susceptibility to vancomycin in Staphylococcus aureus. Clin. Infect. Dis.,  2006, 42(11), 1652-1653.
 [http://dx.doi.org/10.1086/504084] [PMID: 16652325]

[27]
Kishor, K.; Dhasmana, N.; Kamble, S.; Sahu, R. Linezolid induced adverse drug reactions-an update. Curr. Drug Metab.,  2015, 16(7), 553-559.
 [http://dx.doi.org/10.2174/1389200216666151001121004] [PMID: 26424176]

[28]
Stein, G.E.; Wells, E.M. The importance of tissue penetration in achieving successful antimicrobial treatment of nosocomial pneumonia and complicated skin and soft-tissue infections caused by methicillin-resistant Staphylococcus aureus : Vancomycin and linezolid. Curr. Med. Res. Opin.,  2010, 26(3), 571-588.
 [http://dx.doi.org/10.1185/03007990903512057] [PMID: 20055750]

[29]
Greer, N.D. Tigecycline (Tygacil): The first in the glycylcycline class of antibiotics. Proc. Bayl. Univ. Med. Cent.,  2006, 19(2), 155-161.
 [http://dx.doi.org/10.1080/08998280.2006.11928154] [PMID: 16609746]

[30]
Frei, C.R.; Miller, M.L.; Lewis, J.S., II; Lawson, K.A.; Hunter, J.M.; Oramasionwu, C.U.; Talbert, R.L. Trimethoprim-sulfamethoxazole or clindamycin for community-associated MRSA (CA-MRSA) skin infections. J. Am. Board Fam. Med.,  2010, 23(6), 714-719.
 [http://dx.doi.org/10.3122/jabfm.2010.06.090270] [PMID: 21057066]

[31]
Goldstein, E.J.C.; Proctor, R.A. Role of folate antagonists in the treatment of methicillin-resistant Staphylococcus aureus infection. Clin. Infect. Dis.,  2008, 46(4), 584-593.
 [http://dx.doi.org/10.1086/525536] [PMID: 18197761]

[32]
Kollef, M.H. Limitations of vancomycin in the management of resistant staphylococcal infections. Clin. Infect. Dis.,  2007, 45(3)(Suppl. 3), S191-S195.
 [http://dx.doi.org/10.1086/519470] [PMID: 17712746]

[33]
Bassetti, M.; Peghin, M.; Castaldo, N.; Giacobbe, D.R. The safety of treatment options for acute bacterial skin and skin structure infections. Expert Opin. Drug Saf.,  2019, 18(8), 635-650.
 [http://dx.doi.org/10.1080/14740338.2019.1621288] [PMID: 31106600]

[34]
Jevitt, L.A.; Smith, A.J.; Williams, P.P.; Raney, P.M.; McGowan, J.E., Jr; Tenover, F.C. In vitro activities of Daptomycin, Linezolid, and Quinupristin-Dalfopristin against a challenge panel of Staphylococci and Enterococci, including vancomycin-intermediate staphylococcus aureus and vancomycin-resistant Enterococcus faecium. Microb. Drug Resist.,  2003, 9(4), 389-393.
 [http://dx.doi.org/10.1089/107662903322762833] [PMID: 15000746]

[35]
Sakoulas, G.; Alder, J.; Thauvin-Eliopoulos, C.; Moellering, R.C., Jr; Eliopoulos, G.M. Induction of daptomycin heterogeneous susceptibility in Staphylococcus aureus by exposure to vancomycin. Antimicrob. Agents Chemother.,  2006, 50(4), 1581-1585.
 [http://dx.doi.org/10.1128/AAC.50.4.1581-1585.2006] [PMID: 16569891]

[36]
Arbeit, R.D.; Maki, D.; Tally, F.P.; Campanaro, E.; Eisenstein, B.I. The safety and efficacy of daptomycin for the treatment of complicated skin and skin-structure infections. Clin. Infect. Dis.,  2004, 38(12), 1673-1681.
 [http://dx.doi.org/10.1086/420818] [PMID: 15227611]

[37]
Aikawa, N.; Kusachi, S.; Mikamo, H.; Takesue, Y.; Watanabe, S.; Tanaka, Y.; Morita, A.; Tsumori, K.; Kato, Y.; Yoshinari, T. Efficacy and safety of intravenous daptomycin in Japanese patients with skin and soft tissue infections. J. Infect. Chemother.,  2013, 19(3), 447-455.
 [http://dx.doi.org/10.1007/s10156-012-0501-9] [PMID: 23085743]

[38]
Quinn, D.K.; Stern, T.A. Linezolid and serotonin syndrome. Prim. Care Companion J. Clin. Psychiatry,  2009, 11(6), 353-356.
 [http://dx.doi.org/10.4088/PCC.09r00853] [PMID: 20098528]

[39]
Van Wart, S.A.; Cirincione, B.B.; Ludwig, E.A.; Meagher, A.K.; Korth-Bradley, J.M.; Owen, J.S. Population pharmacokinetics of tigecycline in healthy volunteers. J. Clin. Pharmacol.,  2007, 47(6), 727-737.
 [http://dx.doi.org/10.1177/0091270007300263] [PMID: 17519399]

[40]
Murchison, A. Quinupristin–dalfopristin: A streptogramin antibiotic. Prim. Care Update Ob Gyns,  2002, 9(5), 176-177.
 [http://dx.doi.org/10.1016/S1068-607X(02)00113-0]

[41]
Eliopoulos, G.M.; Eliopoulos, G.M. Quinupristin-dalfopristin and linezolid: Evidence and opinion. Clin. Infect. Dis.,  2003, 36(4), 473-481.
 [http://dx.doi.org/10.1086/367662] [PMID: 12567306]

[42]
Ma, H.; Cheng, J.; Peng, L.; Gao, Y.; Zhang, G.; Luo, Z. Adjunctive rifampin for the treatment of Staphylococcus aureus bacteremia with deep infections: A meta-analysis. PLoS One,  2020, 15(3), e0230383.
 [http://dx.doi.org/10.1371/journal.pone.0230383] [PMID: 32191760]

[43]
Dryden, M.; Zhang, Y.; Wilson, D.; Iaconis, J.P.; Gonzalez, J. A Phase III, randomized, controlled, non-inferiority trial of ceftaroline fosamil 600 mg every 8 h versus vancomycin plus aztreonam in patients with complicated skin and soft tissue infection with systemic inflammatory response or underlying comorbidities. J. Antimicrob. Chemother.,  2016, 71(12), 3575-3584.
 [http://dx.doi.org/10.1093/jac/dkw333] [PMID: 27585969]

[44]
Corey, G.R.; Wilcox, M.; Talbot, G.H.; Friedland, H.D.; Baculik, T.; Witherell, G.W.; Critchley, I.; Das, A.F.; Thye, D. Integrated analysis of CANVAS 1 and 2: Phase 3, multicenter, randomized, double-blind studies to evaluate the safety and efficacy of ceftaroline versus vancomycin plus aztreonam in complicated skin and skin-structure infection. Clin. Infect. Dis.,  2010, 51(6), 641-650.
 [http://dx.doi.org/10.1086/655827] [PMID: 20695801]

[45]
Blumenthal, K.G.; Kuhlen, J.L., Jr; Weil, A.A.; Varughese, C.A.; Kubiak, D.W.; Banerji, A.; Shenoy, E.S. Adverse drug reactions associated with ceftaroline use: A 2-center retrospective cohort. J. Allergy Clin. Immunol. Pract.,  2016, 4(4), 740-746.
 [http://dx.doi.org/10.1016/j.jaip.2016.03.008] [PMID: 27130709]

[46]
Smieja, M. Current indications for the use of clindamycin: A critical review. Can. J. Infect. Dis.,  1998, 9(1), 22-28.
 [http://dx.doi.org/10.1155/1998/538090] [PMID: 22346533]

[47]
Geric, B.; Rupnik, M.; Gerding, D.N.; Grabnar, M.; Johnson, S. Distribution of Clostridium difficile variant toxinotypes and strains with binary toxin genes among clinical isolates in an American hospital. J. Med. Microbiol.,  2004, 53(9), 887-894.
 [http://dx.doi.org/10.1099/jmm.0.45610-0] [PMID: 15314196]

[48]
Miller, L.G.; Daum, R.S.; Creech, C.B.; Young, D.; Downing, M.D.; Eells, S.J.; Pettibone, S.; Hoagland, R.J.; Chambers, H.F. Clindamycin versus trimethoprim-sulfamethoxazole for uncomplicated skin infections. N. Engl. J. Med.,  2015, 372(12), 1093-1103.
 [http://dx.doi.org/10.1056/NEJMoa1403789] [PMID: 25785967]

[49]
Crellin, E.; Mansfield, K.E.; Leyrat, C.; Nitsch, D.; Douglas, I.J.; Root, A.; Williamson, E.; Smeeth, L.; Tomlinson, L.A. Trimethoprim use for urinary tract infection and risk of adverse outcomes in older patients: Cohort study. BMJ,  2018, 360, k341.
 [http://dx.doi.org/10.1136/bmj.k341] [PMID: 29438980]

[50]
Talan, D.A.; Mower, W.R.; Krishnadasan, A.; Abrahamian, F.M.; Lovecchio, F.; Karras, D.J.; Steele, M.T.; Rothman, R.E.; Hoagland, R.; Moran, G.J. Trimethoprim–sulfamethoxazole versus placebo for uncomplicated skin abscess. N. Engl. J. Med.,  2016, 374(9), 823-832.
 [http://dx.doi.org/10.1056/NEJMoa1507476] [PMID: 26962903]

[51]
Shorr, A.F.; Lodise, T.P.; Corey, G.R.; De Anda, C.; Fang, E.; Das, A.F.; Prokocimer, P. Analysis of the phase 3 ESTABLISH trials of tedizolid versus linezolid in acute bacterial skin and skin structure infections. Antimicrob. Agents Chemother.,  2015, 59(2), 864-871.
 [http://dx.doi.org/10.1128/AAC.03688-14] [PMID: 25421472]

[52]
Wilson, A.P.R. Comparative safety of teicoplanin and vancomycin. Int. J. Antimicrob. Agents,  1998, 10(2), 143-152.
 [http://dx.doi.org/10.1016/S0924-8579(98)00025-9] [PMID: 9716291]

[53]
Boucher, H.W.; Wilcox, M.; Talbot, G.H.; Puttagunta, S.; Das, A.F.; Dunne, M.W. Once-weekly dalbavancin versus daily conventional therapy for skin infection. N. Engl. J. Med.,  2014, 370(23), 2169-2179.
 [http://dx.doi.org/10.1056/NEJMoa1310480] [PMID: 24897082]

[54]
Bouza, E.; Valerio, M.; Soriano, A.; Morata, L.; Carus, E.G.; Rodríguez-González, C.; Hidalgo-Tenorio, M.C.; Plata, A.; Muñoz, P.; Vena, A.; Alvarez-Uria, A.; Fernández-Cruz, A.; Nieto, A.A.; Artero, A.; Allende, J.M.B.; Morell, E.B.; Candel-González, F.J.; Castelo, L.; Cobo, J.; del Carmen Gálvez Contreras, M.; Fernández, R.G.; Horcajada, J.P.; Guisado-Vasco, P.; Losa, J.E.; Hervás, R.; Iftimie, S.M.; Mejías, M.E.J.; Jover, F.; Ferreiro, J.L.L.; Serrano, A.B.L.; Malmierca, E.; Masiá, M.; Sempere, M.R.O.; Nieto, A.R.; Rodriguez-Pardo, D.; Alvarez, S.J.R.; San Juan, R.; Cepeda, C.S.; Berrocal, M.A.S.; Sobrino, B.; Sorlí, L. Dalbavancin in the treatment of different gram-positive infections: A real-life experience. Int. J. Antimicrob. Agents,  2018, 51(4), 571-577.
 [http://dx.doi.org/10.1016/j.ijantimicag.2017.11.008] [PMID: 29180276]

[55]
Stryjewski, M.E.; Graham, D.R.; Wilson, S.E.; O’Riordan, W.; Young, D.; Lentnek, A.; Ross, D.P.; Fowler, V.G.; Hopkins, A.; Friedland, H.D.; Barriere, S.L.; Kitt, M.M.; Corey, G.R. Telavancin versus vancomycin for the treatment of complicated skin and skin-structure infections caused by gram-positive organisms. Clin. Infect. Dis.,  2008, 46(11), 1683-1693.
 [http://dx.doi.org/10.1086/587896] [PMID: 18444791]

[56]
Graham, D.R.; Talan, D.A.; Nichols, R.L.; Lucasti, C.; Corrado, M.; Morgan, N.; Fowler, C.L. Once-daily, high-dose levofloxacin versus ticarcillin-clavulanate alone or followed by amoxicillin-clavulanate for complicated skin and skin-structure infections: A randomized, open-label trial. Clin. Infect. Dis.,  2002, 35(4), 381-389.
 [http://dx.doi.org/10.1086/341026] [PMID: 12145720]

[57]
Nicodemo, A.C.; Robledo, J.A.; Jasovich, A.; Neto, W. A multicentre, double-blind, randomised study comparing the efficacy and safety of oral levofloxacin versus ciprofloxacin in the treatment of uncomplicated skin and skin structure infections. Int. J. Clin. Pract.,  1998, 52(2), 69-74.
 [http://dx.doi.org/10.1111/j.1742-1241.1998.tb11567.x] [PMID: 9624783]

[58]
Vick-Fragoso, R.; Hernández-Oliva, G.; Cruz-Alcázar, J.; Amábile-Cuevas, C.F.; Arvis, P.; Reimnitz, P.; Bogner, J.R.; Group, S.S. Efficacy and safety of sequential intravenous/oral moxifloxacin vs intravenous/oral amoxicillin/clavulanate for complicated skin and skin structure infections. Infection,  2009, 37(5), 407-417.
 [http://dx.doi.org/10.1007/s15010-009-8468-x] [PMID: 19768381]

[59]
Smith, K.; Leyden, J.J. Safety of doxycycline and minocycline: A systematic review. Clin. Ther.,  2005, 27(9), 1329-1342.
 [http://dx.doi.org/10.1016/j.clinthera.2005.09.005] [PMID: 16291409]

[60]
Hershberger, E.; Donabedian, S.; Konstantinou, K.; Zervos, M.J.; Eliopoulos, G.M. Quinupristin-dalfopristin resistance in gram-positive bacteria: Mechanism of resistance and epidemiology. Clin. Infect. Dis.,  2004, 38(1), 92-98.
 [http://dx.doi.org/10.1086/380125] [PMID: 14679454]

[61]
Yamaoka, T. The bactericidal effects of anti-MRSA agents with rifampicin and sulfamethoxazole-trimethoprim against intracellular phagocytized MRSA. J. Infect. Chemother.,  2007, 13(3), 141-146.
 [http://dx.doi.org/10.1007/s10156-007-0521-Z] [PMID: 17593499]

[62]
Saravolatz, L.D.; Pawlak, J.; Johnson, L.; Bonilla, H.; Saravolatz, L.D., II; Fakih, M.G.; Fugelli, A.; Olsen, W.M. In vitro activities of LTX-109, a synthetic antimicrobial peptide, against methicillin-resistant, vancomycin-intermediate, vancomycin-resistant, daptomycin-nonsusceptible, and linezolid-nonsusceptible Staphylococcus aureus. Antimicrob. Agents Chemother.,  2012, 56(8), 4478-4482.
 [http://dx.doi.org/10.1128/AAC.00194-12] [PMID: 22585222]

[63]
Nilsson, A.C.; Janson, H.; Wold, H.; Fugelli, A.; Andersson, K.; Håkangård, C.; Olsson, P.; Olsen, W.M. LTX-109 is a novel agent for nasal decolonization of methicillin-resistant and -sensitive Staphylococcus aureus. Antimicrob. Agents Chemother.,  2015, 59(1), 145-151.
 [http://dx.doi.org/10.1128/AAC.03513-14] [PMID: 25331699]

[64]
Giuliani, A.; Rinaldi, A.C. Beyond natural antimicrobial peptides: Multimeric peptides and other peptidomimetic approaches. Cell. Mol. Life Sci.,  2011, 68(13), 2255-2266.
 [http://dx.doi.org/10.1007/s00018-011-0717-3] [PMID: 21598022]

[65]
Méndez-Samperio, P. Peptidomimetics as a new generation of antimicrobial agents: Current progress. Infect. Drug Resist.,  2014, 7, 229-237.
 [http://dx.doi.org/10.2147/IDR.S49229] [PMID: 25210467]

[66]
Mercer, D.K.; O’Neil, D.A. Innate inspiration: Antifungal peptides and other immunotherapeutics from the host immune response. Front. Immunol.,  2020, 11, 2177-2205.
 [http://dx.doi.org/10.3389/fimmu.2020.02177] [PMID: 33072081]

[67]
Isaksson, J.; Brandsdal, B.O.; Engqvist, M.; Flaten, G.E.; Svendsen, J.S.M.; Stensen, W. A synthetic antimicrobial peptidomimetic (LTX 109): Stereochemical impact on membrane disruption. J. Med. Chem.,  2011, 54(16), 5786-5795.
 [http://dx.doi.org/10.1021/jm200450h] [PMID: 21732630]

[68]
Jiang, Y.; Chen, Y.; Song, Z.; Tan, Z.; Cheng, J. Recent advances in design of antimicrobial peptides and polypeptides toward clinical translation. Adv. Drug Deliv. Rev.,  2021, 170, 261-280.
 [http://dx.doi.org/10.1016/j.addr.2020.12.016] [PMID: 33400958]

[69]
Saravolatz, L.D.; Pawlak, J.; Martin, H.; Saravolatz, S.; Johnson, L.; Wold, H.; Husbyn, M.; Olsen, W.M. Postantibiotic effect and postantibiotic sub-MIC effect of LTX-109 and mupirocin on Staphylococcus aureus blood isolates. Lett. Appl. Microbiol.,  2017, 65(5), 410-413.
 [http://dx.doi.org/10.1111/lam.12792] [PMID: 28802058]

[70]
Koo, H.B.; Seo, J. Antimicrobial peptides under clinical investigation. Pept. Sci. (Hoboken),  2019, 111(5), e24122.
 [http://dx.doi.org/10.1002/pep2.24122]

[71]
Xu, Z.Q.; Flavin, M.T.; Flavin, J. Combating multidrug-resistant gram-negative bacterial infections. Expert Opin. Investig. Drugs,  2014, 23(2), 163-182.
 [http://dx.doi.org/10.1517/13543784.2014.848853] [PMID: 24215473]

[72]
Rakesh, K.P.; Marichannegowda, M.H.; Srivastava, S.; Chen, X.; Long, S.; Karthik, C.S.; Mallu, P.; Qin, H.L. Combating a master manipulator: Staphylococcus aureus immunomodulatory molecules as targets for combinatorial drug discovery. ACS Comb. Sci.,  2018, 20(12), 681-693.
 [http://dx.doi.org/10.1021/acscombsci.8b00088] [PMID: 30372025]

[73]
Kowalski, R.P.; Romanowski, E.G.; Yates, K.A.; Mah, F.S. An independent evaluation of a novel peptide mimetic, brilacidin (PMX30063), for ocular anti-infective. J. Ocul. Pharmacol. Ther.,  2016, 32(1), 23-27.
 [http://dx.doi.org/10.1089/jop.2015.0098] [PMID: 26501484]

[74]
Li, J.; Koh, J.J.; Liu, S.; Lakshminarayanan, R.; Verma, C.S.; Beuerman, R.W. Membrane active antimicrobial peptides: Translating mechanistic insights to design. Front. Neurosci.,  2017, 11, 73-91.
 [http://dx.doi.org/10.3389/fnins.2017.00073] [PMID: 28261050]

[75]
Boucher, H.W.; Talbot, G.H.; Benjamin, D.K., Jr; Bradley, J.; Guidos, R.J.; Jones, R.N.; Murray, B.E.; Bonomo, R.A.; Gilbert, D. 10 x ’20 Progress--development of new drugs active against gram-negative bacilli: An update from the Infectious Diseases Society of America. Clin. Infect. Dis.,  2013, 56(12), 1685-1694.
 [http://dx.doi.org/10.1093/cid/cit152] [PMID: 23599308]

[76]
Wang, M.; Odom, T.; Cai, J. Challenges in the development of next-generation antibiotics: Opportunities of small molecules mimicking mode of action of host-defense peptides. Expert Opin. Ther. Pat.,  2020, 30(5), 303-305.
 [http://dx.doi.org/10.1080/13543776.2020.1740683] [PMID: 32149532]

[77]
Mercer, D.K.; O’Neil, D.A. Peptides as the next generation of anti-infectives. Future Med. Chem.,  2013, 5(3), 315-337.
 [http://dx.doi.org/10.4155/fmc.12.213] [PMID: 23464521]

[78]
Tillotson, G.S.; Theriault, N. New and alternative approaches to tackling antibiotic resistance. F1000Prime Rep.,  2013, 5, 51-60.
 [http://dx.doi.org/10.12703/P5-51] [PMID: 24381727]

[79]
McCool, R.; Gould, I.M.; Eales, J.; Barata, T.; Arber, M.; Fleetwood, K.; Glanville, J.; Kauf, T.L. Systematic review and network meta-analysis of tedizolid for the treatment of acute bacterial skin and skin structure infections caused by MRSA. BMC Infect. Dis.,  2017, 17(1), 39.
 [http://dx.doi.org/10.1186/s12879-016-2100-3] [PMID: 28061827]

[80]
Jorgensen, D.; Scott, R.; O’Riordan, W.; Tack, K. A randomized, double-blind study comparing single-dose and short-course brilacidin to daptomycin in the treatment of acute bacterial skin & skin structure infections (ABSSSI 25th European Congress of Clinical Microbiology and Infectious Diseases (ECCMID),  2015, pp. 25-28.

[81]
Takahashi, Y.; Igarashi, M. Destination of aminoglycoside antibiotics in the ‘post-antibiotic era’. J. Antibiot. (Tokyo),  2018, 71(1), 4-14.
 [http://dx.doi.org/10.1038/ja.2017.117] [PMID: 29066797]

[82]
Singh, G.S. Carbohydrates in Drug Discovery and Development.Carbohydrate-based antibiotics: Opportunities and challenges, 1st ed.; Elsevier Academic Press: Amsterdam, 2006, pp. 523-559.

[83]
Lakota, E.A.; Sato, N.; Koresawa, T.; Kondo, K.; Bhavnani, S.M.; Ambrose, P.G.; Rubino, C.M. Population pharmacokinetic analyses for arbekacin after administration of ME1100 inhalation solution. Antimicrob. Agents Chemother.,  2019, 63(8), e00267-19.
 [http://dx.doi.org/10.1128/AAC.00267-19] [PMID: 31182524]

[84]
Koulenti, D.; Xu, E.; Song, A.; Sum Mok, I.Y.; Karageorgopoulos, D.E.; Armaganidis, A.; Tsiodras, S.; Lipman, J. Emerging treatment options for infections by multidrug-resistant gram-positive microorganisms. Microorganisms,  2020, 8(2), 191-231.
 [http://dx.doi.org/10.3390/microorganisms8020191] [PMID: 32019171]

[85]
AB Naafs, M. The antimicrobial peptides: Ready for clinical trials. Biomed. J. Sci. Tech. Res.,  2018, 7(4), 6038-6042.
 [http://dx.doi.org/10.26717/BJSTR.2018.07.001536]

[86]
Appelbaum, P.C. 2012 and beyond: Potential for the start of a second pre-antibiotic era? J. Antimicrob. Chemother.,  2012, 67(9), 2062-2068.
 [http://dx.doi.org/10.1093/jac/dks213] [PMID: 22687888]

[87]
de Souza Mendes, C.; de Souza Antunes, A. Pipeline of known chemical classes of antibiotics. Antibiotics (Basel),  2013, 2(4), 500-534.
 [http://dx.doi.org/10.3390/antibiotics2040500] [PMID: 27029317]

[88]
Peric, M.; Jacobs, M.R.; Appelbaum, P.C. Antianaerobic activity of a novel fluoroquinolone, WCK 771, compared to those of nine other agents. Antimicrob. Agents Chemother.,  2004, 48(8), 3188-3192.
 [http://dx.doi.org/10.1128/AAC.48.8.3188-3192.2004] [PMID: 15273148]

[89]
Liapikou, A.; Cillóniz, C.; Torres, A. Investigational drugs in phase I and phase II clinical trials for the treatment of community-acquired pneumonia. Expert Opin. Investig. Drugs,  2017, 26(11), 1239-1248.
 [http://dx.doi.org/10.1080/13543784.2017.1385761] [PMID: 28952384]

[90]
Jabes, D. The antibiotic R&D pipeline: An update. Curr. Opin. Microbiol.,  2011, 14(5), 564-569.
 [http://dx.doi.org/10.1016/j.mib.2011.08.002] [PMID: 21873107]

[91]
Lipsky, B.A.; Tsai, C.Y.; Chang, L.W.; Chang, Y.T.; Hsu, M.C. WITHDRAWN: Nemonoxacin treatment of patients with diabetic foot infection: A pilot study. J. Microbiol. Immunol. Infect.,  2019, 72, 397-404.
 [http://dx.doi.org/10.1016/j.jmii.2019.05.015]

[92]
O’Riordan, W.; Tiffany, C.; Scangarella-Oman, N.; Perry, C.; Hossain, M.; Ashton, T.; Dumont, E. Efficacy, safety, and tolerability of Gepotidacin (GSK2140944) in the treatment of patients with suspected or confirmed gram-positive acute bacterial skin and skin structure infections. Antimicrob. Agents Chemother.,  2017, 61(6), e02095-16.
 [http://dx.doi.org/10.1128/AAC.02095-16] [PMID: 28373199]

[93]
Jeong, J.W.; Jung, S.J.; Lee, H.H.; Kim, Y.Z.; Park, T.K.; Cho, Y.L.; Chae, S.E.; Baek, S.Y.; Woo, S.H.; Lee, H.S.; Kwak, J.H. In vitro and in vivo activities of LCB01-0371, a new oxazolidinone. Antimicrob. Agents Chemother.,  2010, 54(12), 5359-5362.
 [http://dx.doi.org/10.1128/AAC.00723-10] [PMID: 20855730]

[94]
Vuong, C.; Yeh, A.J.; Cheung, G.Y.C.; Otto, M. Investigational drugs to treat methicillin-resistant Staphylococcus aureus. Expert Opin. Investig. Drugs,  2016, 25(1), 73-93.
 [http://dx.doi.org/10.1517/13543784.2016.1109077] [PMID: 26536498]

[95]
Cho, Y.S.; Lim, H.S.; Lee, S.H.; Cho, Y.L.; Nam, H.; Bae, K.S. Pharmacokinetics, pharmacodynamics, and tolerability of single-dose oral LCB01-0371, a novel oxazolidinone with broad-spectrum activity, in healthy volunteers. ntimicrob. Antimicrob. Agents Chemother.,  2018, 62(7), e00451-18.
 [http://dx.doi.org/10.1128/AAC.00451-18]

[96]
Carvalhaes, C.G.; Duncan, L.R.; Wang, W.; Sader, H.S. In vitro activity and potency of the novel Oxazolidinone Contezolid (MRX-I) tested against Gram-positive clinical isolates from US and Europe. Antimicrob. Agents Chemother.,  2020, 64(11), e01195-20.
 [http://dx.doi.org/10.1128/AAC.01195-20] [PMID: 32778552]

[97]
Li, Y.G.; Wang, J.X.; Zhang, G.N.; Zhu, M.; You, X.F.; Hu, X.X.; Zhang, F.; Wang, Y.C. Antibacterial activity and structure− activity relationship of a series of newly synthesized Pleuromutilin derivatives. Chem. Biodivers.,  2019, 16(2), e1800560.
 [http://dx.doi.org/10.1002/cbdv.201800560] [PMID: 30467968]

[98]
Pucci, M.J.; Bush, K. Investigational antimicrobial agents of 2013. Clin. Microbiol. Rev.,  2013, 26(4), 792-821.
 [http://dx.doi.org/10.1128/CMR.00033-13] [PMID: 24092856]

[99]
Paukner, S.; Riedl, R. Pleuromutilins: Potent drugs for resistant bugs—mode of action and resistance. Cold Spring Harb. Perspect. Med.,  2017, 7(1), a027110.
 [http://dx.doi.org/10.1101/cshperspect.a027110] [PMID: 27742734]

[100]
Jones, J.A.; Virga, K.G.; Gumina, G.; Hevener, K.E. Recent advances in the rational design and optimization of antibacterial agents. MedChemComm,  2016, 7(9), 1694-1715.
 [http://dx.doi.org/10.1039/C6MD00232C] [PMID: 27642504]

[101]
Giacobbe, D.R.; De Rosa, F.G.; Del Bono, V.; Grossi, P.A.; Pea, F.; Petrosillo, N.; Rossolini, G.M.; Tascini, C.; Tumbarello, M.; Viale, P.; Bassetti, M. Ceftobiprole: Drug evaluation and place in therapy. Expert Rev. Anti Infect. Ther.,  2019, 17(9), 689-698.
 [http://dx.doi.org/10.1080/14787210.2019.1667229] [PMID: 31553250]

[102]
Parkes, A.L.; Yule, I.A. Hybrid antibiotics – clinical progress and novel designs. Expert Opin. Drug Discov.,  2016, 11(7), 665-680.
 [http://dx.doi.org/10.1080/17460441.2016.1187597] [PMID: 27169483]

[103]
Blais, J.; Lewis, S.R.; Krause, K.M.; Benton, B.M. Antistaphylococcal activity of TD-1792, a multivalent glycopeptide-cephalosporin antibiotic. Antimicrob. Agents Chemother.,  2012, 56(3), 1584-1587.
 [http://dx.doi.org/10.1128/AAC.05532-11] [PMID: 22203585]

[104]
Leuthner, K.D.; Vidaillac, C.; Cheung, C.M.; Rybak, M.J. In vitro activity of the new multivalent glycopeptide-cephalosporin antibiotic TD-1792 against vancomycin-nonsusceptible Staphylococcus isolates. Antimicrob. Agents Chemother.,  2010, 54(9), 3799-3803.
 [http://dx.doi.org/10.1128/AAC.00452-10] [PMID: 20585126]

[105]
Hegde, S.S.; Okusanya, O.O.; Skinner, R.; Shaw, J.P.; Obedencio, G.; Ambrose, P.G.; Blais, J.; Bhavnani, S.M. Pharmacodynamics of TD-1792, a novel glycopeptide-cephalosporin heterodimer antibiotic used against Gram-positive bacteria, in a neutropenic murine thigh model. Antimicrob. Agents Chemother.,  2012, 56(3), 1578-1583.
 [http://dx.doi.org/10.1128/AAC.05382-11] [PMID: 22155835]

[106]
Itoh, H.; Tokumoto, K.; Kaji, T.; Paudel, A.; Panthee, S.; Hamamoto, H.; Sekimizu, K.; Inoue, M. Total synthesis and biological mode of action of WAP-8294A2: A menaquinone-targeting antibiotic. J. Org. Chem.,  2018, 83(13), 6924-6935.
 [http://dx.doi.org/10.1021/acs.joc.7b02318] [PMID: 29019678]

[107]
Kato, A.; Nakaya, S.; Ohashi, Y.; Hirata, H.; Fujii, K.; Harada, K. WAP-8294A2, a novel anti-MRSA antibiotic produced by Lysobacter sp. J. Am. Chem. Soc.,  1997, 119(28), 6680-6681.
 [http://dx.doi.org/10.1021/ja970895o]

[108]
Kato, A.; Hirata, H.; Ohashi, Y.; Fujii, K.; Mori, K.; Harada, K. A new anti-MRSA antibiotic complex, WAP-8294A II. Structure characterization of minor components by ESI LCMS and MS/MS. J. Antibiot. (Tokyo),  2011, 64(5), 373-379.
 [http://dx.doi.org/10.1038/ja.2011.9] [PMID: 21326252]

[109]
Ling, J.; Zhu, R.; Laborda, P.; Jiang, T.; Jia, Y.; Zhao, Y.; Liu, F. LbDSF, the Lysobacter brunescens quorum sensing system diffusible signalling factor, regulates anti-xanthomonas XSAC biosynthesis, colony morphology, and surface motility. Front. Microbiol.,  2019, 10, 1230-1244.
 [http://dx.doi.org/10.3389/fmicb.2019.01230] [PMID: 31275253]

[110]
Hafkin, B.; Kaplan, N.; Murphy, B. Efficacy and safety of AFN-1252, the first Staphylococcus-specific antibacterial agent, in the treatment of acute bacterial skin and skin structure infections, including those in patients with significant comorbidities. Antimicrob. Agents Chemother.,  2016, 60(3), 1695-1701.
 [http://dx.doi.org/10.1128/AAC.01741-15] [PMID: 26711777]

[111]
Butler, M.S.; Paterson, D.L. Antibiotics in the clinical pipeline in October 2019. J. Antibiot. (Tokyo),  2020, 73(6), 329-364.
 [http://dx.doi.org/10.1038/s41429-020-0291-8] [PMID: 32152527]

[112]
Fisher, C.R.; Schmidt-Malan, S.M.; Ma, Z.; Yuan, Y.; He, S.; Patel, R. In vitro activity of TNP-2092 against periprosthetic joint infection–associated staphylococci. Diagn. Microbiol. Infect. Dis.,  2020, 97(3), 115040-115065.
 [http://dx.doi.org/10.1016/j.diagmicrobio.2020.115040] [PMID: 32354459]

[113]
Motley, M.P.; Banerjee, K.; Fries, B.C. Monoclonal antibody-based therapies for bacterial infections. Curr. Opin. Infect. Dis.,  2019, 32(3), 210-216.
 [http://dx.doi.org/10.1097/QCO.0000000000000539] [PMID: 30950853]

[114]
Peck, M.; Rothenberg, M.E.; Deng, R.; Lewin-Koh, N.; She, G.; Kamath, A.V.; Carrasco-Triguero, M.; Saad, O.; Castro, A.; Teufel, L.; Dickerson, D.S.; Leonardelli, M.; Tavel, J.A. A phase 1, randomized, single-ascending-dose study to investigate the safety, tolerability, and pharmacokinetics of DSTA4637S, an anti-Staphylococcus aureus thiomab antibody-antibiotic conjugate, in healthy volunteers. Antimicrob. Agents Chemother.,  2019, 63(6), e02588-18.
 [http://dx.doi.org/10.1128/AAC.02588-18] [PMID: 30910894]

[115]
Fernandes, P.; Pereira, D. Efforts to support the development of fusidic acid in the United States. Clin. Infect. Dis.,  2011, 52(7)(Suppl. 7), S542-S546.
 [http://dx.doi.org/10.1093/cid/cir170] [PMID: 21546632]

[116]
Shukla, M.; Soni, I.; Dasgupta, A.; Chopra, S. Drugs under preclinical and clinical testing for the treatment of infections caused due to Staphylococcus aureus.  An update, in infectious diseases and your health.,  (1st ed.. ) 2018, , 239-255.

[117]
Biedenbach, D.J.; Rhomberg, P.R.; Mendes, R.E.; Jones, R.N. Spectrum of activity, mutation rates, synergistic interactions, and the effects of pH and serum proteins for fusidic acid (CEM-102). Diagn. Microbiol. Infect. Dis.,  2010, 66(3), 301-307.
 [http://dx.doi.org/10.1016/j.diagmicrobio.2009.10.014] [PMID: 20159376]

[118]
Noeske, J.; Huang, J.; Olivier, N.B.; Giacobbe, R.A.; Zambrowski, M.; Cate, J.H.D. Synergy of streptogramin antibiotics occurs independently of their effects on translation. Antimicrob. Agents Chemother.,  2014, 58(9), 5269-5279.
 [http://dx.doi.org/10.1128/AAC.03389-14] [PMID: 24957822]

[119]
Liapikou, A.; Torres, A. Emerging drugs on methicillin-resistant Staphylococcus aureus. Expert Opin. Emerg. Drugs,  2013, 18(3), 291-305.
 [http://dx.doi.org/10.1517/14728214.2013.813480] [PMID: 23848400]

[120]
Pankuch, G.A.; Lin, G.; Clark, C.; Appelbaum, P.C. Time-kill activity of the streptogramin NXL 103 against gram-positive and -negative bacteria. Antimicrob. Agents Chemother.,  2011, 55(4), 1787-1791.
 [http://dx.doi.org/10.1128/AAC.01159-10] [PMID: 21245439]

[121]
Politano, A.D.; Sawyer, R.G. NXL-103, a combination of flopristin and linopristin, for the potential treatment of bacterial infections including community-acquired pneumonia and MRSA. Curr. Opin. Investig. Drugs,  2010, 11(2), 225-236.
 [PMID: 20112172]

[122]
Lepak, A.J.; Parhi, A.; Madison, M.; Marchillo, K.; VanHecker, J.; Andes, D.R. In vivo pharmacodynamic evaluation of an FtsZ Inhibitor, TXA-709, and its active metabolite, TXA-707, in a murine neutropenic thigh infection model. Antimicrob. Agents Chemother.,  2015, 59(10), 6568-6574.
 [http://dx.doi.org/10.1128/AAC.01464-15] [PMID: 26259789]

[123]
Theuretzbacher, U.; Bush, K.; Harbarth, S.; Paul, M.; Rex, J.H.; Tacconelli, E.; Thwaites, G.E. Critical analysis of antibacterial agents in clinical development. Nat. Rev. Microbiol.,  2020, 18(5), 286-298.
 [http://dx.doi.org/10.1038/s41579-020-0340-0] [PMID: 32152509]

[124]
Stephens, L.J.; Werrett, M.V.; Sedgwick, A.C.; Bull, S.D.; Andrews, P.C. Antimicrobial innovation: A current update and perspective on the antibiotic drug development pipeline. Future Med. Chem.,  2020, 12(22), 2035-2065.
 [http://dx.doi.org/10.4155/fmc-2020-0225] [PMID: 33169622]

[125]
Kaul, M.; Mark, L.; Zhang, Y.; Parhi, A.K.; Lyu, Y.L.; Pawlak, J.; Saravolatz, S.; Saravolatz, L.D.; Weinstein, M.P.; LaVoie, E.J.; Pilch, D.S. TXA709, an FtsZ-targeting benzamide prodrug with improved pharmacokinetics and enhanced in vivo efficacy against methicillin-resistant Staphylococcus aureus. Antimicrob. Agents Chemother.,  2015, 59(8), 4845-4855.
 [http://dx.doi.org/10.1128/AAC.00708-15] [PMID: 26033735]

[126]
Naderer, O.J.; Dumont, E.; Zhu, J.; Kurtinecz, M.; Jones, L.S. Single-dose safety, tolerability, and pharmacokinetics of the antibiotic GSK1322322, a novel peptide deformylase inhibitor. Antimicrob. Agents Chemother.,  2013, 57(5), 2005-2009.
 [http://dx.doi.org/10.1128/AAC.01779-12] [PMID: 23403431]

[127]
Corey, R.; Naderer, O.J.; O’Riordan, W.D.; Dumont, E.; Jones, L.S.; Kurtinecz, M.; Zhu, J.Z. Safety, tolerability, and efficacy of GSK1322322 in the treatment of acute bacterial skin and skin structure infections. Antimicrob. Agents Chemother.,  2014, 58(11), 6518-6527.
 [http://dx.doi.org/10.1128/AAC.03360-14] [PMID: 25136015]

[128]
Alm, R.A.; Lahiri, S.D. Narrow-spectrum antibacterial agents—benefits and challenges. Antibiotics (Basel),  2020, 9(7), 418-426.
 [http://dx.doi.org/10.3390/antibiotics9070418] [PMID: 32708925]

[129]
Page, J.E.; Walker, S. Natural products that target the cell envelope. Curr. Opin. Microbiol.,  2021, 61, 16-24.
 [http://dx.doi.org/10.1016/j.mib.2021.02.001] [PMID: 33662818]

[130]
Traczewski, M.M.; Ambler, J.E.; Schuch, R. Determination of MIC quality control parameters for Exebacase, a novel lysin with anti-staphylococcal activity. J. Clin. Microbiol.,  2021, 59(7), e03117-20.
 [http://dx.doi.org/10.1128/JCM.03117-20] [PMID: 33910968]

[131]
Watson, A.; Oh, J.T.; Sauve, K.; Bradford, P.A.; Cassino, C.; Schuch, R. Antimicrobial activity of exebacase (lysin CF-301) against the most common causes of infective endocarditis. Antimicrob. Agents Chemother.,  2019, 63(10), e01078-19.
 [http://dx.doi.org/10.1128/AAC.01078-19] [PMID: 31332073]

[132]
Kim, N.H.; Park, W.B.; Cho, J.E.; Choi, Y.J.; Choi, S.J.; Jun, S.Y.; Kang, C.K.; Song, K.H.; Choe, P.G.; Bang, J.H.; Kim, E.S.; Park, S.W.; Kim, N.J.; Oh, M.; Kim, H.B. Effects of phage endolysin SAL200 combined with antibiotics on Staphylococcus aureus infection. Antimicrob. Agents Chemother.,  2018, 62(10), e00731-18.
 [http://dx.doi.org/10.1128/AAC.00731-18] [PMID: 30038042]

[133]
Caflisch, K.M.; Patel, R. Implications of bacteriophage-and bacteriophage component-based therapies for the clinical microbiology laboratory. J. Clin. Microbiol.,  2019, 57(8), e00229-19.
 [http://dx.doi.org/10.1128/JCM.00229-19] [PMID: 31092596]

[134]
Jun, S.Y.; Jung, G.M.; Yoon, S.J.; Youm, S.Y.; Han, H.Y.; Lee, J.H.; Kang, S.H. Pharmacokinetics of the phage endolysin-based candidate drug SAL 200 in monkeys and its appropriate intravenous dosing period. Clin. Exp. Pharmacol. Physiol.,  2016, 43(10), 1013-1016.
 [http://dx.doi.org/10.1111/1440-1681.12613] [PMID: 27341401]

[135]
Channabasappa, S.; Chikkamadaiah, R.; Durgaiah, M.; Kumar, S.; Ramesh, K.; Sreekanthan, A.; Sriram, B. Efficacy of chimeric ectolysin P128 in drug-resistant Staphylococcus aureus bacteraemia in mice. J. Antimicrob. Chemother.,  2018, 73(12), 3398-3404.
 [http://dx.doi.org/10.1093/jac/dky365] [PMID: 30215762]

[136]
ClinicalTrials.gov. Safety & efficacy of an antibacterial protein molecule applied topically to the nostrils of volunteers and patients.   Available From: https://clinicaltrials.gov/ct2/show/NCT01746654

[137]
Bagnoli, F. Staphylococcus aureus toxin antibodies: Good companions of antibiotics and vaccines. Virulence,  2017, 8(7), 1037-1042.
 [http://dx.doi.org/10.1080/21505594.2017.1295205] [PMID: 28267417]

[138]
Varshney, A.K.; Kuzmicheva, G.A.; Lin, J.; Sunley, K.M.; Bowling, R.A., Jr; Kwan, T.Y.; Mays, H.R.; Rambhadran, A.; Zhang, Y.; Martin, R.L.; Cavalier, M.C.; Simard, J.; Shivaswamy, S. A natural human monoclonal antibody targeting Staphylococcus Protein A protects against Staphylococcus aureus bacteremia. PLoS One,  2018, 13(1), e0190537.
 [http://dx.doi.org/10.1371/journal.pone.0190537] [PMID: 29364906]

[139]
Falcó, V.; Burgos, J.; Papiol, E.; Ferrer, R.; Almirante, B. Investigational drugs in phase I and phase II clincial trials for the treatment of hospital-acquired pneumonia. Expert Opin. Investig. Drugs,  2016, 25(6), 653-665.
 [http://dx.doi.org/10.1517/13543784.2016.1168803] [PMID: 26998623]

[140]
Wang-Lin, S.; Balthasar, J. Pharmacokinetic and pharmacodynamic considerations for the use of monoclonal antibodies in the treatment of bacterial infections. Antibodies (Basel),  2018, 7(1), 5-25.
 [http://dx.doi.org/10.3390/antib7010005] [PMID: 31544858]

[141]
Vignon, P.; Laterre, P.F.; Daix, T.; François, B. New agents in development for sepsis: Any reason for hope? Drugs,  2020, 80(17), 1751-1761.
 [http://dx.doi.org/10.1007/s40265-020-01402-z] [PMID: 32951149]

[142]
Tabor, D.E.; Yu, L.; Mok, H.; Tkaczyk, C.; Sellman, B.R.; Wu, Y.; Oganesyan, V.; Slidel, T.; Jafri, H.; McCarthy, M.; Bradford, P.; Esser, M.T. Staphylococcus aureus alpha-toxin is conserved among diverse hospital respiratory isolates collected from a global surveillance study and is neutralized by monoclonal antibody MEDI4893. Antimicrob. Agents Chemother.,  2016, 60(9), 5312-5321.
 [http://dx.doi.org/10.1128/AAC.00357-16] [PMID: 27324766]

[143]
François, B.; Jafri, H.S.; Chastre, J.; Sánchez-García, M.; Eggimann, P.; Dequin, P.F.; Huberlant, V.; Viña Soria, L.; Boulain, T.; Bretonnière, C.; Pugin, J.; Trenado, J.; Hernandez Padilla, A.C.; Ali, O.; Shoemaker, K.; Ren, P.; Coenjaerts, F.E.; Ruzin, A.; Barraud, O.; Timbermont, L.; Lammens, C.; Pierre, V.; Wu, Y.; Vignaud, J.; Colbert, S.; Bellamy, T.; Esser, M.T.; Dubovsky, F.; Bonten, M.J.; Goossens, H.; Laterre, P.F.; Chochrad, D.; Dive, A.; Foret, F.; Simon, M.; Spapen, H.; Creteur, J.; Bouckaert, Y.; Biston, P.; Bourgeois, M.; Novacek, M.; Vymazal, T.; Svoboda, P.; Pachl, J.; Sramek, V.; Hanauer, M.; Hruby, T.; Balik, M.; Suchy, T.; Lepape, A.; Argaud, L.; Dailler, F.; Desachy, A.; Guitton, C.; Mercat, A.; Meziani, F.; Navellou, J-C.; Robert, R.; Souweine, B.; Tadie, J-M.; Maamar, A.; Annane, D.; Tamion, F.; Gros, A.; Nseir, S.; Schwebel, C.; Francony, G.; Lefrant, J-Y.; Schneider, F.; Gründling, M.; Motsch, J.; Reill, L.; Rolfes, C.; Welte, T.; Cornely, O.; Bloos, F.; Deja, M.; Schmidt, K.; Wappler, F.; Meier-Hellmann, A.; Komnos, A.; Bekos, V.; Koulouras, V.; Soultati, I.; Baltopoulos, G.; Filntisis, G.; Zakynthinos, E.; Zakynthinos, S.; Pnevmatikos, I.; Krémer, I.; Szentkereszty, Z.; Sarkany, A.; Marjanek, Z.; Moura, P.; Pintado Delgado, M.C.; Montejo González, J.C.; Ramirez, P.; Torres Marti, A.; Valia, J.C.; Lorente, J.; Loza Vazquez, A.; De Pablo Sanchez, R.; Escudero, D.; Ferrer Roca, R.; Pagani, J-L.; Maggiorini, M. Efficacy and safety of suvratoxumab for prevention of Staphylococcus aureus ventilator-associated pneumonia (SAATELLITE): A multicentre, randomised, double-blind, placebo-controlled, parallel-group, phase 2 pilot trial. Lancet Infect. Dis.,  2021, 21(9), 1313-1323.
 [http://dx.doi.org/10.1016/S1473-3099(20)30995-6] [PMID: 33894131]

[144]
Jacobs, M.R.; Appelbaum, P.C. Nadifloxacin: A quinolone for topical treatment of skin infections and potential for systemic use of its active isomer, WCK 771. Expert Opin. Pharmacother.,  2006, 7(14), 1957-1966.
 [http://dx.doi.org/10.1517/14656566.7.14.1957] [PMID: 17020421]

[145]
Lautre, C.; Sharma, S.; Sahu, J.K. Chemistry, biological properties and analytical methods of Levonadifloxacin:A review. Crit. Rev. Anal. Chem.,  2020, 50, 1-9.
 [PMID: 33307757]

[146]
Baliga, S.; Mamtora, D.K.; Gupta, V.; Shanmugam, P.; Biswas, S.; Mukherjee, D.N.; Shenoy, S. Assessment of antibacterial activity of levonadifloxacin against contemporary gram-positive clinical isolates collected from various Indian hospitals using disk-diffusion assay. Indian J. Med. Microbiol.,  2020, 38(3-4), 307-312.
 [http://dx.doi.org/10.4103/ijmm.IJMM_20_307] [PMID: 33154240]

[147]
Veeraraghavan, B.; Bakthavatchalam, Y.D.; Manesh, A.; Lal, B.; Swaminathan, S.; Ansari, A.; Subbareddy, K.; Rangappa, P.; Choudhuri, A.H.; Nagvekar, V.; Mehta, Y.; Appalaraju, B.; Baveja, S.; Baliga, S.; Shenoy, S.; Bhardwaj, R.; Kongre, V.; Dattatraya, G.S.; Verma, B.; Mukherjee, D.N.; Gupta, S.; Shanmugam, P.; Iravane, J.; Mishra, S.R.; Barman, P.; Chopra, S.; Hariharan, M.; Surpam, R.; Pratap, R.; Turbadkar, D.; Taklikar, S. India-discovered levonadifloxacin & alalevonadifloxacin: A review on susceptibility testing methods, CLSI quality control and breakpoints along with a brief account of their emerging therapeutic profile as a novel standard-of-care. Indian J. Med. Microbiol.,  2023, 41(3), 71-80.
 [http://dx.doi.org/10.1016/j.ijmmb.2022.11.005] [PMID: 36509611]

[148]
Rodvold, K.A.; Gotfried, M.H.; Chugh, R.; Gupta, M.; Yeole, R.; Patel, A.; Bhatia, A. Intrapulmonary pharmacokinetics of Levonadifloxacin following oral administration of Alalevonadifloxacin to healthy adult subjects. Antimicrob. Agents Chemother.,  2018, 62(3), e02297-17.
 [http://dx.doi.org/10.1128/AAC.02297-17] [PMID: 29263070]

[149]
Jones, T.; Johnson, S.; DiMondi, V.P.; Wilson, D.T. Focus on JNJ-Q2, a novel fluoroquinolone, for the management of community-acquired bacterial pneumonia and acute bacterial skin and skin structure infections. Infect. Drug Resist.,  2016, 9, 119-128.
 [http://dx.doi.org/10.2147/IDR.S105620] [PMID: 27354817]

[150]
Covington, P.; Davenport, J.M.; Andrae, D.; O’Riordan, W.; Liverman, L.; McIntyre, G.; Almenoff, J. Randomized, double-blind, phase II, multicenter study evaluating the safety/tolerability and efficacy of JNJ-Q2, a novel fluoroquinolone, compared with linezolid for treatment of acute bacterial skin and skin structure infection. Antimicrob. Agents Chemother.,  2011, 55(12), 5790-5797.
 [http://dx.doi.org/10.1128/AAC.05044-11] [PMID: 21947389]

[151]
Chang, L-W.; Hsu, M-C.; Zhang, Y-Y. Nemonoxacin (Taigexyn®): A new non-fluorinated Quinolone. Staphylococcus and Streptococcus, 1st ed.; Elsevier: Amsterdam, 2019, pp. 1-95.

[152]
Kocsis, B.; Domokos, J.; Szabo, D. Chemical structure and pharmacokinetics of novel quinolone agents represented by avarofloxacin, delafloxacin, finafloxacin, zabofloxacin and nemonoxacin. Ann. Clin. Microbiol. Antimicrob.,  2016, 15(1), 34-42.
 [http://dx.doi.org/10.1186/s12941-016-0150-4] [PMID: 27215369]

[153]
Cheng, S.L.; Wu, R.G.; Chuang, Y.C.; Perng, W.C.; Tsao, S.M.; Chang, Y.T.; Chang, L.W.; Hsu, M.C. Integrated safety summary of phase II and III studies comparing oral nemonoxacin and levofloxacin in community-acquired pneumonia. J. Microbiol. Immunol. Infect.,  2019, 52(5), 743-751.
 [http://dx.doi.org/10.1016/j.jmii.2018.11.006] [PMID: 30616912]

[154]
Lai, C.C.; Lee, K.Y.; Lin, S.W.; Chen, Y.H.; Kuo, H.Y.; Hung, C.C.; Hsueh, P.R. Nemonoxacin (TG-873870) for treatment of community-acquired pneumonia. Expert Rev. Anti Infect. Ther.,  2014, 12(4), 401-417.
 [http://dx.doi.org/10.1586/14787210.2014.894881] [PMID: 24579813]

[155]
Adam, H.J.; Laing, N.M.; King, C.R.; Lulashnyk, B.; Hoban, D.J.; Zhanel, G.G. In vitro activity of nemonoxacin, a novel non fluorinated quinolone, against 2,440 clinical isolates. Antimicrob. Agents Chemother.,  2009, 53(11), 4915-4920.
 [http://dx.doi.org/10.1128/AAC.00078-09] [PMID: 19738018]

[156]
Liu, Y.; Zhang, Y.; Wu, J.; Zhu, D.; Sun, S.; Zhao, L.; Wang, X.; Liu, H.; Ren, Z.; Wang, C.; Xiu, Q.; Xiao, Z.; Cao, Z.; Cui, S.; Yang, H.; Liang, Y.; Chen, P.; Lv, Y.; Hu, C.; Lv, X.; Liu, S.; Kuang, J.; Li, J.; Wang, D.; Chang, L. A randomized, double-blind, multicenter Phase II study comparing the efficacy and safety of oral nemonoxacin with oral levofloxacin in the treatment of community-acquired pneumonia. J. Microbiol. Immunol. Infect.,  2017, 50(6), 811-820.
 [http://dx.doi.org/10.1016/j.jmii.2015.09.005] [PMID: 26748734]

[157]
Aoki, H.; Ke, L.; Poppe, S.M.; Poel, T.J.; Weaver, E.A.; Gadwood, R.C.; Thomas, R.C.; Shinabarger, D.L.; Ganoza, M.C. Oxazolidinone antibiotics target the P site on Escherichia coli ribosomes. Antimicrob. Agents Chemother.,  2002, 46(4), 1080-1085.
 [http://dx.doi.org/10.1128/AAC.46.4.1080-1085.2002] [PMID: 11897593]

[158]
Cho, Y.S.; Lim, H.S.; Cho, Y.L.; Nam, H.S.; Bae, K.S. Multiple-dose safety, tolerability, pharmacokinetics, and pharmacodynamics of oral LCB01-0371 in healthy male volunteers. Clin. Ther.,  2018, 40(12), 2050-2064.
 [http://dx.doi.org/10.1016/j.clinthera.2018.10.007] [PMID: 30420289]

[159]
Egorova, A.; Jackson, M.; Gavrilyuk, V.; Makarov, V. Pipeline of anti Mycobacterium abscessus small molecules: Repurposable drugs and promising novel chemical entities. Med. Res. Rev.,  2021, 41(4), 2350-2387.
 [http://dx.doi.org/10.1002/med.21798] [PMID: 33645845]

[160]
Shetye, G.S.; Franzblau, S.G.; Cho, S. New tuberculosis drug targets, their inhibitors, and potential therapeutic impact. Transl. Res.,  2020, 220(4), 68-97.
 [http://dx.doi.org/10.1016/j.trsl.2020.03.007] [PMID: 32275897]

[161]
Cho, Y.S.; Lim, H.S.; Han, S.; Yoon, S.K.; Kim, H.; Cho, Y.L.; Nam, H.S.; Bae, K.S. Single-dose intravenous safety, tolerability, and pharmacokinetics and absolute bioavailability of LCB01-0371. Clin. Ther.,  2019, 41(1), 92-106.
 [http://dx.doi.org/10.1016/j.clinthera.2018.11.009] [PMID: 30559004]

[162]
Cho, Y.L.; Jang, J. Development of delpazolid for the treatment of tuberculosis. Appl. Sci. (Basel),  2020, 10(7), 2211.
 [http://dx.doi.org/10.3390/app10072211]

[163]
Gao, X.; Zhao, W.; Huo, F.; Jiang, G.; Dong, L.; Zhao, L.; Wang, F.; Yu, X.; Huang, H. In vitro efficacy comparison of Linezolid, Tedizolid, Sutezolid and Delpazolid against rapid growing Mycobacteria isolated in Beijing, China. BioRxiv, 2020.

[164]
Kaku, N.; Morinaga, Y.; Takeda, K.; Kosai, K.; Uno, N.; Hasegawa, H.; Miyazaki, T.; Izumikawa, K.; Mukae, H.; Yanagihara, K. Efficacy and pharmacokinetics of ME1100, a novel optimized formulation of arbekacin for inhalation, compared with amikacin in a murine model of ventilator-associated pneumonia caused by Pseudomonas aeruginosa. J. Antimicrob. Chemother.,  2017, 72(4), 1123-1128.
 [PMID: 27999047]

[165]
Bhagwat, S.S.; Nandanwar, M.; Kansagara, A.; Patel, A.; Takalkar, S.; Chavan, R.; Hariharan, P.; Yeole, R.; Deshpande, P.; Bhavsar, S.; Bhatia, A.; Ahdal, J.; Jain, R.; Patel, M. Levonadifloxacin, a novel broad-spectrum anti-MRSA benzoquinolizine quinolone agent: Review of current evidence. Drug Des. Devel. Ther.,  2019, 13, 4351-4365.
 [http://dx.doi.org/10.2147/DDDT.S229882] [PMID: 31920285]

[166]
Wu, X.; Zhang, J.; Guo, B.; Zhang, Y.; Yu, J.; Cao, G.; Chen, Y.; Zhu, D.; Ye, X.; Wu, J.; Shi, Y.; Chang, L.; Chang, Y.; Tsai, C. Pharmacokinetics and pharmacodynamics of multiple-dose intravenous nemonoxacin in healthy Chinese volunteers. Antimicrob. Agents Chemother.,  2015, 59(3), 1446-1454.
 [http://dx.doi.org/10.1128/AAC.04039-14] [PMID: 25534726]

[167]
Negash, K.; Andonian, C.; Felgate, C.; Chen, C.; Goljer, I.; Squillaci, B.; Nguyen, D.; Pirhalla, J.; Lev, M.; Schubert, E.; Tiffany, C.; Hossain, M.; Ho, M. The metabolism and disposition of GSK2140944 in healthy human subjects. Xenobiotica,  2016, 46(8), 683-702.
 [http://dx.doi.org/10.3109/00498254.2015.1112933] [PMID: 26586303]

[168]
Choi, Y.; Lee, S.W.; Kim, A.; Jang, K.; Nam, H.; Cho, Y.L.; Yu, K.S.; Jang, I.J.; Chung, J.Y. Safety, tolerability and pharmacokinetics of 21 day multiple oral administration of a new oxazolidinone antibiotic, LCB01-0371, in healthy male subjects. J. Antimicrob. Chemother.,  2018, 73(1), 183-190.
 [http://dx.doi.org/10.1093/jac/dkx367] [PMID: 29069400]

[169]
Eckburg, P.B.; Ge, Y.; Hafkin, B. Single-and multiple-dose study to determine the safety, tolerability, pharmacokinetics, and food effect of oral MRX-I versus Linezolid in healthy adult subjects. Antimicrob. Agents Chemother.,  2017, 61(4), e02181-16.
 [http://dx.doi.org/10.1128/AAC.02181-16] [PMID: 28167545]

[170]
Yang, D.; Chen, L.; Lai, L.; Ren, M.; Zhang, G.; Pan, Z.; Fang, B. Research on pharmacokinetics and bioavailability of pleuromutilin derivative BC-7013 in chickens. Zhongguo Nongye Daxue Xuebao,  2015, 36(4), 26-31.

[171]
Zeitlinger, M.; Schwameis, R.; Burian, A.; Burian, B.; Matzneller, P.; Müller, M.; Wicha, W.W.; Strickmann, D.B.; Prince, W. Simultaneous assessment of the pharmacokinetics of a pleuromutilin, lefamulin, in plasma, soft tissues and pulmonary epithelial lining fluid. J. Antimicrob. Chemother.,  2016, 71(4), 1022-1026.
 [http://dx.doi.org/10.1093/jac/dkv442] [PMID: 26747098]

[172]
Schmitt-Hoffmann, A.; Roos, B.; Schleimer, M.; Sauer, J.; Man, A.; Nashed, N.; Brown, T.; Perez, A.; Weidekamm, E.; Kovács, P. Single-dose pharmacokinetics and safety of a novel broad-spectrum cephalosporin (BAL5788) in healthy volunteers. Antimicrob. Agents Chemother.,  2004, 48(7), 2570-2575.
 [http://dx.doi.org/10.1128/AAC.48.7.2570-2575.2004] [PMID: 15215110]

[173]
Stryjewski, M.E.; Potgieter, P.D.; Li, Y.P.; Barriere, S.L.; Churukian, A.; Kingsley, J.; Corey, G.R. TD-1792 versus vancomycin for treatment of complicated skin and skin structure infections. Antimicrob. Agents Chemother.,  2012, 56(11), 5476-5483.
 [http://dx.doi.org/10.1128/AAC.00712-12] [PMID: 22869571]

[174]
Kaplan, N.; Hafkin, B. 2014. Preclinical pharmacokinetics and efficacy of Debio 1450 (Previously AFN-1720), a prodrug of the Staphylococcocal-specific Antibiotic Debio 1452 (Previously AFN-1252). In: 24th European Congress of Clinical Microbiology and Infectious Diseases (ECCMID). 2014.

[175]
Morgan, A.; Cofer, C.; Stevens, D.L. Iclaprim: A novel dihydrofolate reductase inhibitor for skin and soft tissue infections. Future Microbiol.,  2009, 4(2), 131-144.
 [http://dx.doi.org/10.2217/17460913.4.2.131] [PMID: 19257839]

[176]
Weiss, W.; Pulse, M.; Nguyen, P.; Ma, Z.  In vivo efficacy of dual-action molecule TNP-2092 in mouse H. pylori infection model as compared to triple therapies and distribution within the gastric mucosal layer. In: American Society of Microbiology General Meeting, Poster. 2016, pp. 460

[177]
Zhou, C.; Lehar, S.; Gutierrez, J.; Rosenberger, C.M.; Ljumanovic, N.; Dinoso, J.; Koppada, N.; Hong, K.; Baruch, A.; Carrasco-Triguero, M.; Saad, O.; Mariathasan, S.; Kamath, A.V. Pharmacokinetics and pharmacodynamics of DSTA4637A: A novel THIOMAB™ antibody antibiotic conjugate against Staphylococcus aureus in mice. MAbs,  2016, 8(8), 1612-1619.
 [http://dx.doi.org/10.1080/19420862.2016.1229722] [PMID: 27653831]

[178]
Still, J.G.; Clark, K.; Degenhardt, T.P.; Scott, D.; Fernandes, P.; Gutierrez, M.J. Pharmacokinetics and safety of single, multiple, and loading doses of fusidic acid in healthy subjects. Clin. Infect. Dis.,  2011, 52(7)(Suppl. 7), S504-S512.
 [http://dx.doi.org/10.1093/cid/cir174] [PMID: 21546627]

[179]
Pankuch, G.A.; Hoellman, D.; Bryskier, A.; Lowther, J.; Appelbaum, P.C. Effects of various media on the activity of NXL103 (formerly XRP 2868), a new oral streptogramin, against Haemophilus influenzae. Antimicrob. Agents Chemother.,  2006, 50(11), 3914-3916.
 [http://dx.doi.org/10.1128/AAC.00587-06] [PMID: 17065630]

[180]
Andes, D.; Craig, W.A. Pharmacodynamics of a new streptogramin, XRP 2868, in murine thigh and lung infection models. Antimicrob. Agents Chemother.,  2006, 50(1), 243-249.
 [http://dx.doi.org/10.1128/AAC.50.1.243-249.2006] [PMID: 16377693]

[181]
Naderer, O.J.; Jones, L.S.; Zhu, J.; Kurtinecz, M.; Dumont, E. Safety, tolerability, and pharmacokinetics of oral and intravenous administration of GSK1322322, a peptide deformylase inhibitor. J. Clin. Pharmacol.,  2013, 53(11), 1168-1176.
 [http://dx.doi.org/10.1002/jcph.150] [PMID: 23907665]

[182]
Cassino, C.; Murphy, M.; Boyle, J.; Rotolo, J.; Wittekind, M. Results of the first in human study of lysin CF-301 evaluating the safety, tolerability and pharmacokinetic profile in healthy volunteers proceedings of the 26th European congress of clinical microbiology and infectious diseases, Amsterdam, The Netherlands, 2016.
 [http://dx.doi.org/10.26226/morressier.56ebbf52d462b80296c97eca]

[183]
Jun, S.Y.; Jang, I.J.; Yoon, S.; Jang, K.; Yu, K.S.; Cho, J.Y.; Seong, M.W.; Jung, G.M.; Yoon, S.J.; Kang, S.H. Pharmacokinetics and tolerance of the phage endolysin-based candidate drug SAL200 after a single intravenous administration among healthy volunteers. Antimicrob. Agents Chemother.,  2017, 61(6), e02629-16.
 [http://dx.doi.org/10.1128/AAC.02629-16] [PMID: 28348152]

[184]
Hariharan, S.; Keelara, S.; Paul, V.D.; Sriram, B.; Vipra, A.A.; Balganesh, T. Phage therapy—bacteriophage and phage-derived products as anti-infective drugs. Drug discovery targeting drug-resistant bacteria, 1st ed.; Elsevier: Amsterdam, 2020, pp. 301-359.

[185]
Rupp, M.E.; Stecher, M.; Mckinnon, J.; Jung, N.; Huynh, T. Pharmacokinetics of a novel monoclonal antibody targeting Staphylococcal Protein A in patients hospitalized with S. aureus bacteremia. Open Forum Infect. Dis.,  2016, 3(1)(Suppl. 1), 1985.
 [http://dx.doi.org/10.1093/ofid/ofw172.1533]

[186]
François, B.; Mercier, E.; Gonzalez, C.; Asehnoune, K.; Nseir, S.; Fiancette, M.; Desachy, A.; Plantefève, G.; Meziani, F.; de Lame, P.A.; Laterre, P.F. Safety and tolerability of a single administration of AR-301, a human monoclonal antibody, in ICU patients with severe pneumonia caused by Staphylococcus aureus: First-in-human trial. Intensive Care Med.,  2018, 44(11), 1787-1796.
 [http://dx.doi.org/10.1007/s00134-018-5229-2] [PMID: 30343314]

[187]
Yu, X-Q.; Robbie, G.J.; Wu, Y.; Esser, M.T.; Jensen, K.; Schwartz, H.I.; Bellamy, T.; Hernandez-Illas, M.; Jafri, H.S. Safety, tolerability, and pharmacokinetics of MEDI4893, an investigational, extended-half-life, anti-Staphylococcus aureus alpha-toxin human monoclonal antibody, in healthy adults. Antimicrob. Agents Chemother.,  2016, 61(1), 1020-1036.
 [PMID: 27795368]

[188]
Reddy, D.S.; Sinha, A.; Kumar, A.; Saini, V.K. Drug re-engineering and repurposing: A significant and rapid approach to tuberculosis drug discovery. Arch. Pharm. (Weinheim),  2022, 355(11), 2200214.
 [http://dx.doi.org/10.1002/ardp.202200214] [PMID: 35841594]

[189]
Bae, I.G.; Tonthat, G.T.; Stryjewski, M.E.; Rude, T.H.; Reilly, L.F.; Barriere, S.L.; Genter, F.C.; Corey, G.R.; Fowler, V.G., Jr Presence of genes encoding the panton-valentine leukocidin exotoxin is not the primary determinant of outcome in patients with complicated skin and skin structure infections due to methicillin-resistant Staphylococcus aureus: Results of a multinational trial. J. Clin. Microbiol.,  2009, 47(12), 3952-3957.
 [http://dx.doi.org/10.1128/JCM.01643-09] [PMID: 19846653]

[190]
Wang, W.; Voss, K.M.; Liu, J.; Gordeev, M.F. Nonclinical evaluation of antibacterial oxazolidinones Contezolid and Contezolid Acefosamil with low serotonergic neurotoxicity. Chem. Res. Toxicol.,  2021, 34(5), 1348-1354.
 [http://dx.doi.org/10.1021/acs.chemrestox.0c00524] [PMID: 33913699]

[191]
Wu, J.; Cao, G.; Wu, H.; Chen, Y.; Guo, B.; Wu, X.; Yu, J.; Ni, K.; Qian, J.; Wang, L.; Wu, J.; Wang, Y.; Yuan, H.; Zhang, J.; Xi, Y. Evaluation of the effect of Contezolid (MRX-I) on the corrected QT interval in a randomized, double-blind, placebo-and positive-controlled crossover study in healthy Chinese volunteers. Antimicrob. Agents Chemother.,  2020, 64(6), e02158-19.
 [http://dx.doi.org/10.1128/AAC.02158-19] [PMID: 32229495]

[192]
Michalska, K.; Gruba, E.; Bocian, W.; Cielecka-Piontek, J. Enantioselective recognition of radezolid by cyclodextrin modified capillary electrokinetic chromatography and electronic circular dichroism. J. Pharm. Biomed. Anal.,  2017, 139, 98-108.
 [http://dx.doi.org/10.1016/j.jpba.2017.01.041] [PMID: 28279932]

[193]
Kaur, M.; Rai, J.; Randhawa, G.K. Recent advances in antibacterial drugs. Int. J. Appl. Basic Med. Res.,  2013, 3(1), 3-10.
 [http://dx.doi.org/10.4103/2229-516X.112229] [PMID: 23776832]

[194]
Silverberg, N.; Block, S. Uncomplicated skin and skin structure infections in children: Diagnosis and current treatment options in the United States. Clin. Pediatr. (Phila.),  2008, 47(3), 211-219.
 [http://dx.doi.org/10.1177/0009922807307186] [PMID: 18354031]

[195]
Eyal, Z.; Matzov, D.; Krupkin, M.; Paukner, S.; Riedl, R.; Rozenberg, H.; Zimmerman, E.; Bashan, A.; Yonath, A. A novel pleuromutilin antibacterial compound, its binding mode and selectivity mechanism. Sci. Rep.,  2016, 6(1), 39004.
 [http://dx.doi.org/10.1038/srep39004] [PMID: 27958389]

[196]
Goethe, O.; Heuer, A.; Ma, X.; Wang, Z.; Herzon, S.B. Antibacterial properties and clinical potential of pleuromutilins. Nat. Prod. Rep.,  2019, 36(1), 220-247.
 [http://dx.doi.org/10.1039/C8NP00042E] [PMID: 29979463]

[197]
Yi, Y.; Fu, Y.; Dong, P.; Qin, W.; Liu, Y.; Liang, J.; Shang, R. Synthesis and biological activity evaluation of novel heterocyclic pleuromutilin derivatives. Molecules,  2017, 22(6), 996.
 [http://dx.doi.org/10.3390/molecules22060996] [PMID: 28617344]

[198]
Li, Y.G.; Wang, J.X.; Zhang, G.N.; Zhu, M.; You, X.F.; Wang, Y.C.; Zhang, F. Design, synthesis, and biological activity evaluation of a series of pleuromutilin derivatives with novel C14 side chains. Bioorg. Med. Chem. Lett.,  2020, 30(7), 126969.
 [http://dx.doi.org/10.1016/j.bmcl.2020.126969] [PMID: 32014384]

[199]
Veve, M.P.; Wagner, J.L. Lefamulin: Review of a promising novel pleuromutilin antibiotic. Pharmacotherapy,  2018, 38(9), 935-946.
 [http://dx.doi.org/10.1002/phar.2166] [PMID: 30019769]

[200]
Mercuro, N.J.; Veve, M.P. Clinical utility of Lefamulin: If not now, when? Curr. Infect. Dis. Rep.,  2020, 22(9), 25.
 [http://dx.doi.org/10.1007/s11908-020-00732-z] [PMID: 32834786]

[201]
Zhanel, G.G.; Deng, C.; Zelenitsky, S.; Lawrence, C.K.; Adam, H.J.; Golden, A.; Berry, L.; Schweizer, F.; Zhanel, M.A.; Irfan, N.; Bay, D.; Lagacé-Wiens, P.; Walkty, A.; Mandell, L.; Lynch, J.P., III; Karlowsky, J.A. Lefamulin: A novel oral and intravenous pleuromutilin for the treatment of community-acquired bacterial pneumonia. Drugs,  2021, 81(2), 233-256.
 [http://dx.doi.org/10.1007/s40265-020-01443-4] [PMID: 33247830]

[202]
Koulenti, D.; Xu, E.; Yin Sum Mok, I.; Song, A.; Karageorgopoulos, D.E.; Armaganidis, A.; Lipman, J.; Tsiodras, S. Novel antibiotics for multidrug-resistant gram-positive microorganisms. Microorganisms,  2019, 7(10), 386-390.
 [http://dx.doi.org/10.3390/microorganisms7100386] [PMID: 31554342]

[203]
Anderson, S.D.; Gums, J.G. Ceftobiprole: An extended-spectrum anti-methicillin-resistant Staphylococcus aureus cephalosporin. Ann. Pharmacother.,  2008, 42(6), 806-816.
 [http://dx.doi.org/10.1345/aph.1L016] [PMID: 18477729]

[204]
Zhanel, G.G.; Lam, A.; Schweizer, F.; Thomson, K.; Walkty, A.; Rubinstein, E.; Gin, A.S.; Hoban, D.J.; Noreddin, A.M.; Karlowsky, J.A. Ceftobiprole. A review of a broad spectrum and anti-MRSA cephalosporin.  Am. J. Clin. Dermatol.,  2008, 9(4), 245-254.
 [http://dx.doi.org/10.2165/00128071-200809040-00004] [PMID: 18572975]

[205]
Noel, G.J.; Strauss, R.S.; Amsler, K.; Heep, M.; Pypstra, R.; Solomkin, J.S. Treatment of complicated skin and skin structure infections caused by gram-positive bacteria with Ceftobiprole: Results of a double-blind, randomized trial. Antimicrob. Agents Chemother.,  2007, 52, 37-44.
 [http://dx.doi.org/10.1128/AAC.00551-07] [PMID: 17954698]

[206]
Noel, G.J.; Bush, K.; Bagchi, P.; Ianus, J.; Strauss, R.S. A randomized, double-blind trial comparing ceftobiprole medocaril with vancomycin plus ceftazidime for the treatment of patients with complicated skin and skin-structure infections. Clin. Infect. Dis.,  2008, 46(5), 647-655.
 [http://dx.doi.org/10.1086/526527] [PMID: 18225981]

[207]
Bhavnani, S.M.; Hammel, J.P.; Lakota, E.A.; Safir, M.C.; VanScoy, B.D.; Nagira, Y.; Rubino, C.M.; Sato, N.; Koresawa, T.; Kondo, K.; Ambrose, P.G. Pharmacokinetic-pharmacodynamic target attainment analyses to support dose selection for ME1100, an Arbekacin inhalation solution. Antimicrob. Agents Chemother.,  2020, 64(10), e02367-19.
 [http://dx.doi.org/10.1128/AAC.02367-19] [PMID: 32661000]

[208]
Chavan, R.; Zope, V.; Chavan, N.; Shaikh, J.; Patil, K.; Yeole, R.; Bhagwat, S.; Patel, M. Assessment of in vitro inhibitory effects of novel anti MRSA benzoquinolizine fluoroquinolone WCK 771 (levonadifloxacin) and its metabolite on human liver cytochrome P450 enzymes. Xenobiotica,  2020, 50(10), 1149-1157.
 [http://dx.doi.org/10.1080/00498254.2020.1756007] [PMID: 32283993]

[209]
Mason, J.W.; Chugh, R.; Patel, A.; Gutte, R.; Bhatia, A. Electrocardiographic effects of a supratherapeutic dose of WCK 2349, a benzoquinolizine fluoroquinolone. Clin. Transl. Sci.,  2019, 12(1), 47-52.
 [http://dx.doi.org/10.1111/cts.12594] [PMID: 30369076]

[210]
Yuan, J.; Mo, B.; Ma, Z.; Lv, Y.; Cheng, S.L.; Yang, Y.; Tong, Z.; Wu, R.; Sun, S.; Cao, Z.; Wu, J.; Zhu, D.; Chang, L.; Zhang, Y.; Zhao, L.; Wang, X.; Wang, X.; Wang, D.; Li, X.; Peng, Y.; Liang, Y.; Liu, H.; Xiao, Z.; Lv, X.; Wu, S.; Dai, Y.; Huang, Y.; Hu, Z.; Qiu, C.; Li, X.; Zhang, S.; Li, W.; Liu, S.; Shi, Y.; Xiong, C.; Kuang, J.; Xiu, Q.; Cui, S.; Li, J.; Lin, Q.; Huang, W.; Wan, Y.; Qimanguli; Shen, C.; Xiao, Y.; Wu, X.; Chuang, Y.C.; Perng, W.C.; Tsao, S-M.; Hsu, J-Y.; Wang, C-C.; Wang, J-H.; Yeh, P-F.; Lin, H-H.; Kuo, P.H.; Lin, M-S.; Su, W-J. Safety and efficacy of oral nemonoxacin versus levofloxacin in treatment of community-acquired pneumonia: A phase 3, multicenter, randomized, double-blind, double-dummy, active-controlled, non-inferiority trial. J. Microbiol. Immunol. Infect.,  2019, 52(1), 35-44.
 [http://dx.doi.org/10.1016/j.jmii.2017.07.011] [PMID: 30181096]

[211]
Wu, J.; Wu, H.; Wang, Y.; Chen, Y.; Guo, B.; Cao, G.; Wu, X.; Yu, J.; Wu, J.; Zhu, D.; Guo, Y.; Yuan, H.; Hu, F.; Zhang, J. Tolerability and pharmacokinetics of Contezolid at therapeutic and supratherapeutic doses in healthy Chinese subjects, and assessment of Contezolid dosing regimens based on pharmacokinetic/pharmacodynamic analysis. Clin. Ther.,  2019, 41(6), 1164-1174.e4.
 [http://dx.doi.org/10.1016/j.clinthera.2019.04.025] [PMID: 31126694]

[212]
Bassetti, M.; Righi, E. Safety profiles of old and new antimicrobials for the treatment of MRSA infections. Expert Opin. Drug Saf.,  2016, 15(4), 467-481.
 [http://dx.doi.org/10.1517/14740338.2016.1142528] [PMID: 26764972]

[213]
Goldberg, L.; Das, A. Efficacy and safety of iv-to-oral lefamulin, a pleuromutilin antibiotic, for treatment of communityacquired bacterial pneumonia: The phase 3 LEAP 1 Trial. Clin. Infect. Dis.,  2019, 69, 1856-1867.
 [http://dx.doi.org/10.1093/cid/ciz090] [PMID: 30722059]

[214]
Overcash, J.S.; Kim, C.; Keech, R.; Gumenchuk, I.; Ninov, B.; Gonzalez-Rojas, Y.; Waters, M.; Simeonov, S.; Engelhardt, M.; Saulay, M.; Ionescu, D.; Smart, J.I.; Jones, M.E.; Hamed, K.A. Ceftobiprole compared with Vancomycin plus Aztreonam in the treatment of acute bacterial skin and skin structure infections: Results of a Phase 3, randomized, double-blind trial (TARGET). Clin. Infect. Dis.,  2021, 73(7), e1507-e1517.
 [http://dx.doi.org/10.1093/cid/ciaa974] [PMID: 32897367]

[215]
Schiebel, J.; Chang, A.; Shah, S.; Lu, Y.; Liu, L.; Pan, P.; Hirschbeck, M.W.; Tareilus, M.; Eltschkner, S.; Yu, W.; Cummings, J.E.; Knudson, S.E.; Bommineni, G.R.; Walker, S.G.; Slayden, R.A.; Sotriffer, C.A.; Tonge, P.J.; Kisker, C. Rational design of broad spectrum antibacterial activity based on a clinically relevant enoyl-acyl carrier protein (ACP) reductase inhibitor. J. Biol. Chem.,  2014, 289(23), 15987-16005.
 [http://dx.doi.org/10.1074/jbc.M113.532804] [PMID: 24739388]

[216]
Wittke, F.; Vincent, C.; Chen, J.; Heller, B.; Kabler, H.; Overcash, J.S.; Leylavergne, F.; Dieppois, G. Afabicin, a first-in-class anti-staphylococcal antibiotic, in the treatment of acute bacterial skin and skin structure infections: Clinical non-inferiority to vancomycin/linezolid. Antimicrob. Agents Chemother.,  2020, 64(10), e00250-20.
 [http://dx.doi.org/10.1128/AAC.00250-20] [PMID: 32747361]

[217]
Yendewa, G.A.; Griffiss, J.M.; Jacobs, M.R.; Fulton, S.A.; O’Riordan, M.A.; Gray, W.A.; Proskin, H.M.; Winkle, P.; Salata, R.A. A two-part phase 1 study to establish and compare the safety and local tolerability of two nasal formulations of XF-73 for decolonisation of Staphylococcus aureus: A previously investigated 0.5 mg/g viscosified gel formulation versus a modified formulation. J. Glob. Antimicrob. Resist.,  2020, 21, 171-180.
 [http://dx.doi.org/10.1016/j.jgar.2019.09.017] [PMID: 31600598]

[218]
Krievins, D.; Brandt, R.; Hawser, S.; Hadvary, P.; Islam, K. Multicenter, randomized study of the efficacy and safety of intravenous iclaprim in complicated skin and skin structure infections. Antimicrob. Agents Chemother.,  2009, 53(7), 2834-2840.
 [http://dx.doi.org/10.1128/AAC.01383-08] [PMID: 19414572]

[219]
TAXIS. Our Pipeline. 2022. Available From: https://www.taxispharma.com/research development/our-pipeline/

[220]
Huynh, T.; Stecher, M.; Mckinnon, J.; Jung, N.; Rupp, M.E. Safety and tolerability of 514G3, a true human anti-protein a monoclonal antibody for the treatment of S. aureus bacteremia. Open Forum Infect. Dis.,  2016, 3(1)(Suppl. 1), 1354.
 [http://dx.doi.org/10.1093/ofid/ofw172.1057]

[221]
Schneider, T.; Müller, A.; Miess, H.; Gross, H. Cyclic lipopeptides as antibacterial agents – Potent antibiotic activity mediated by intriguing mode of actions. Int. J. Med. Microbiol.,  2014, 304(1), 37-43.
 [http://dx.doi.org/10.1016/j.ijmm.2013.08.009] [PMID: 24119568]

[222]
Chen, X.; Li, S.; Yu, L.; Miller, A.; Du, L. Systematic optimization for production of the anti- MRSA antibiotics WAP -8294A in an engineered strain of Lysobacter enzymogenes. Microb. Biotechnol.,  2019, 12(6), 1430-1440.
 [http://dx.doi.org/10.1111/1751-7915.13484] [PMID: 31520522]

[223]
Butler, M.S.; Cooper, M.A. Antibiotics in the clinical pipeline in 2011. J. Antibiot. (Tokyo),  2011, 64(6), 413-425.
 [http://dx.doi.org/10.1038/ja.2011.44] [PMID: 21587262]

[224]
Moir, D.T.; Opperman, T.J.; Butler, M.M.; Bowlin, T.L. New classes of antibiotics. Curr. Opin. Pharmacol.,  2012, 12(5), 535-544.
 [http://dx.doi.org/10.1016/j.coph.2012.07.004] [PMID: 22841284]

[225]
Farrell, D.J.; Robbins, M.; Rhys-Williams, W.; Love, W.G. In vitro activity of XF-73, a novel antibacterial agent, against antibiotic-sensitive and -resistant gram-positive and gram-negative bacterial species. Int. J. Antimicrob. Agents,  2010, 35(6), 531-536.
 [http://dx.doi.org/10.1016/j.ijantimicag.2010.02.008] [PMID: 20346634]

[226]
Sakr, A.; Brégeon, F.; Rolain, J.M.; Blin, O. Staphylococcus aureus nasal decolonization strategies: A review. Expert Rev. Anti Infect. Ther.,  2019, 17(5), 327-340.
 [http://dx.doi.org/10.1080/14787210.2019.1604220] [PMID: 31012332]

[227]
Laue, H.; Weiss, L.; Bernardi, A.; Hawser, S.; Lociuro, S.; Islam, K. In vitro activity of the novel diaminopyrimidine, iclaprim, in combination with folate inhibitors and other antimicrobials with different mechanisms of action. J. Antimicrob. Chemother.,  2007, 60(6), 1391-1394.
 [http://dx.doi.org/10.1093/jac/dkm409] [PMID: 17962215]

[228]
Kohlhoff, S.A.; Sharma, R. Iclaprim. Expert Opin. Investig. Drugs,  2007, 16(9), 1441-1448.
 [http://dx.doi.org/10.1517/13543784.16.9.1441] [PMID: 17714029]

[229]
Sincak, C.A.; Schmidt, J.M. Iclaprim, a novel diaminopyrimidine for the treatment of resistant gram-positive infections. Ann. Pharmacother.,  2009, 43(6), 1107-1114.
 [http://dx.doi.org/10.1345/aph.1L167] [PMID: 19435963]

[230]
Ma, Z.; Lynch, A.S. Development of a dual-acting antibacterial agent (TNP-2092) for the treatment of persistent bacterial infections. J. Med. Chem.,  2016, 59(14), 6645-6657.
 [http://dx.doi.org/10.1021/acs.jmedchem.6b00485] [PMID: 27336583]

[231]
Nazli, A.; He, D.; Xu, H.; Wang, Z-P.; He, Y. A comparative insight on the newly emerging rifamycins: Rifametane, Rifalazil, TNP-2092 and TNP-2198. Curr. Med. Chem.,  2021, 28, 1-30.
 [PMID: 34365945]

[232]
Park, H.S.; Yoon, Y.M.; Jung, S.J.; Kim, C.M.; Kim, J.M.; Kwak, J.H. Antistaphylococcal activities of CG400549, a new bacterial enoyl-acyl carrier protein reductase (FabI) inhibitor. J. Antimicrob. Chemother.,  2007, 60(3), 568-574.
 [http://dx.doi.org/10.1093/jac/dkm236] [PMID: 17606482]

[233]
You, I.; Kariyama, R.; Zervos, M.J.; Kumon, H.; Chow, J.W. In-vitro activity of arbekacin alone and in combination with vancomycin against gentamicin- and methicillin-resistant Staphylococcus aureus. Diagn. Microbiol. Infect. Dis.,  2000, 36(1), 37-41.
 [http://dx.doi.org/10.1016/S0732-8893(99)00104-2] [PMID: 10744365]

[234]
Patel, M.V.; De Souza, N.J.; Gupte, S.V.; Jafri, M.A.; Bhagwat, S.S.; Chugh, Y.; Khorakiwala, H.F.; Jacobs, M.R.; Appelbaum, P.C. Antistaphylococcal activity of WCK 771, a tricyclic fluoroquinolone, in animal infection models. Antimicrob. Agents Chemother.,  2004, 48(12), 4754-4761.
 [http://dx.doi.org/10.1128/AAC.48.12.4754-4761.2004] [PMID: 15561853]

[235]
Farrell, D.J.; Liverman, L.C.; Biedenbach, D.J.; Jones, R.N. JNJ-Q2, a new fluoroquinolone with potent In vitro activity against Staphylococcus aureus, including methicillin- and fluoroquinolone-resistant strains. Antimicrob. Agents Chemother.,  2011, 55(7), 3631-3634.
 [http://dx.doi.org/10.1128/AAC.00162-11] [PMID: 21555765]

[236]
Farrell, D.J.; Robbins, M.; Rhys-Williams, W.; Love, W.G. Investigation of the potential for mutational resistance to XF-73, retapamulin, mupirocin, fusidic acid, daptomycin, and vancomycin in methicillin-resistant Staphylococcus aureus isolates during a 55-passage study. Antimicrob. Agents Chemother.,  2011, 55(3), 1177-1181.
 [http://dx.doi.org/10.1128/AAC.01285-10] [PMID: 21149626]

[237]
Remy, J.M.; Tow-Keogh, C.A.; McConnell, T.S.; Dalton, J.M.; DeVito, J.A. Activity of delafloxacin against methicillin-resistant Staphylococcus aureus: Resistance selection and characterization. J. Antimicrob. Chemother.,  2012, 67(12), 2814-2820.
 [http://dx.doi.org/10.1093/jac/dks307] [PMID: 22875850]

[238]
Noviello, S.; Huang, D.B.; Corey, G.R. Iclaprim: A differentiated option for the treatment of skin and skin structure infections. Expert Rev. Anti Infect. Ther.,  2018, 16(11), 793-803.
 [http://dx.doi.org/10.1080/14787210.2018.1536545] [PMID: 30317894]

[239]
Li, Z.; Liu, Y.; Wang, R.; Li, A. Antibacterial activities of nemonoxacin against clinical isolates of Staphylococcus aureus: An in vitro comparison with three fluoroquinolones. World J. Microbiol. Biotechnol.,  2014, 30(11), 2927-2932.
 [http://dx.doi.org/10.1007/s11274-014-1720-2] [PMID: 25129332]

[240]
Flamm, R.K.; Farrell, D.J.; Rhomberg, P.R.; Scangarella-Oman, N.E.; Sader, H.S. Gepotidacin (GSK2140944) In vitro activity against gram-positive and gram-negative bacteria.  Antimicrob. Agents Chemother.,  2017, 61(7), e00468-17.
 [http://dx.doi.org/10.1128/AAC.00468-17] [PMID: 28483959]

[241]
McGhee, P.; Clark, C.; Credito, K.; Beachel, L.; Pankuch, G.A.; Appelbaum, P.C.; Kosowska-Shick, K. In vitro activity of fusidic acid (CEM-102, sodium fusidate) against Staphylococcus aureus isolates from cystic fibrosis patients and its effect on the activities of tobramycin and amikacin against Pseudomonas aeruginosa and Burkholderia cepacia. Antimicrob. Agents Chemother.,  2011, 55(5), 2417-2419.
 [http://dx.doi.org/10.1128/AAC.01672-10] [PMID: 21343445]

[242]
Sader, H.; Rhomberg, P.; Duncan, L.; Flamm, R.  In vitro activity and potency of the novel oxazolidinone MRX-I tested against contemporary clinical isolates of Gram-positive bacteria. American Society for Microbiology (ASM Microbe), 2017.

[243]
Lawrence, L.; Danese, P.; DeVito, J.; Franceschi, F.; Sutcliffe, J. In vitro activities of the Rx-01 oxazolidinones against hospital and community pathogens. Antimicrob. Agents Chemother.,  2008, 52(5), 1653-1662.
 [http://dx.doi.org/10.1128/AAC.01383-07] [PMID: 18316525]

[244]
O’Dwyer, K.; Hackel, M.; Hightower, S.; Hoban, D.; Bouchillon, S.; Qin, D.; Aubart, K.; Zalacain, M.; Butler, D. Comparative analysis of the antibacterial activity of a novel peptide deformylase inhibitor, GSK1322322. Antimicrob. Agents Chemother.,  2013, 57(5), 2333-2342.
 [http://dx.doi.org/10.1128/AAC.02566-12] [PMID: 23478958]

[245]
Heidtmann, C.V.; Voukia, F.; Hansen, L.N.; Sørensen, S.H.; Urlund, B.; Nielsen, S.; Pedersen, M.; Kelawi, N.; Andersen, B.N.; Pedersen, M.; Reinholdt, P.; Kongsted, J.; Nielsen, C.U.; Klitgaard, J.K.; Nielsen, P. Discovery of a potent adenine–benzyltriazolo–pleuromutilin conjugate with pronounced antibacterial activity against MRSA. J. Med. Chem.,  2020, 63(24), 15693-15708.
 [http://dx.doi.org/10.1021/acs.jmedchem.0c01328] [PMID: 33325700]

[246]
Sader, H.S.; Biedenbach, D.J.; Paukner, S.; Ivezic-Schoenfeld, Z.; Jones, R.N. Antimicrobial activity of the investigational pleuromutilin compound BC-3781 tested against Gram-positive organisms commonly associated with acute bacterial skin and skin structure infections. Antimicrob. Agents Chemother.,  2012, 56(3), 1619-1623.
 [http://dx.doi.org/10.1128/AAC.05789-11] [PMID: 22232289]

[247]
Nair, S.; Desai, S.; Poonacha, N.; Vipra, A.; Sharma, U. Antibiofilm activity and synergistic inhibition of Staphylococcus aureus biofilms by bactericidal protein P128 in combination with antibiotics. Antimicrob. Agents Chemother.,  2016, 60(12), 7280-7289.
 [http://dx.doi.org/10.1128/AAC.01118-16] [PMID: 27671070]

[248]
Iqbal, Z.; Seleem, M.N.; Hussain, H.I.; Huang, L.; Hao, H.; Yuan, Z. Comparative virulence studies and transcriptome analysis of Staphylococcus aureus strains isolated from animals. Sci. Rep.,  2016, 6(1), 35442.
 [http://dx.doi.org/10.1038/srep35442] [PMID: 27739497]

[249]
Giacobbe, D.R.; Labate, L.; Vena, A.; Bassetti, M. Potential role of new-generation antibiotics in acute bacterial skin and skin structure infections. Curr. Opin. Infect. Dis.,  2021, 34(2), 109-117.
 [http://dx.doi.org/10.1097/QCO.0000000000000708] [PMID: 33395093]

[250]
Temme, J.S.; Butler, D.L.; Gildersleeve, J.C. Anti-glycan antibodies: Roles in human disease. Biochem. J.,  2021, 478(8), 1485-1509.
 [http://dx.doi.org/10.1042/BCJ20200610] [PMID: 33881487]

[251]
Lehar, S.M.; Pillow, T.; Xu, M.; Staben, L.; Kajihara, K.K.; Vandlen, R.; DePalatis, L.; Raab, H.; Hazenbos, W.L.; Hiroshi Morisaki, J.; Kim, J.; Park, S.; Darwish, M.; Lee, B.C.; Hernandez, H.; Loyet, K.M.; Lupardus, P.; Fong, R.; Yan, D.; Chalouni, C.; Luis, E.; Khalfin, Y.; Plise, E.; Cheong, J.; Lyssikatos, J.P.; Strandh, M.; Koefoed, K.; Andersen, P.S.; Flygare, J.A.; Wah Tan, M.; Brown, E.J.; Mariathasan, S. Novel antibody-antibiotic conjugate eliminates intracellular S. aureus. Nature,  2015, 527(7578), 323-328.
 [http://dx.doi.org/10.1038/nature16057] [PMID: 26536114]

[252]
Staben, L.R.; Koenig, S.G.; Lehar, S.M.; Vandlen, R.; Zhang, D.; Chuh, J.; Yu, S.F.; Ng, C.; Guo, J.; Liu, Y.; Fourie-O’Donohue, A.; Go, M.; Linghu, X.; Segraves, N.L.; Wang, T.; Chen, J.; Wei, B.; Phillips, G.D.L.; Xu, K.; Kozak, K.R.; Mariathasan, S.; Flygare, J.A.; Pillow, T.H. Targeted drug delivery through the traceless release of tertiary and heteroaryl amines from antibody–drug conjugates. Nat. Chem.,  2016, 8(12), 1112-1119.
 [http://dx.doi.org/10.1038/nchem.2635] [PMID: 27874860]

[253]
Panchal, G.; Pandit, R.; Trailokya, A.; Sharma, A. Arbekacin-a novel antibiotic for critical infections. J. Assoc. Physicians India,  2019, 67(7), 93-97.
 [PMID: 31559785]

[254]
Singh, S.B.; Kaelin, D.E.; Wu, J.; Miesel, L.; Tan, C.M.; Meinke, P.T.; Olsen, D.B.; Lagrutta, A.; Wei, C.; Liao, Y.; Peng, X.; Wang, X.; Fukuda, H.; Kishii, R.; Takei, M.; Yajima, M.; Shibue, T.; Shibata, T.; Ohata, K.; Nishimura, A.; Fukuda, Y. Structure activity relationship of pyridoxazinone substituted RHS analogs of oxabicyclooctane-linked 1,5-naphthyridinyl novel bacterial topoisomerase inhibitors as broad-spectrum antibacterial agents (Part-6). Bioorg. Med. Chem. Lett.,  2015, 25(17), 3636-3643.
 [http://dx.doi.org/10.1016/j.bmcl.2015.06.057] [PMID: 26141771]

[255]
Shang, R.; Liu, Y.; Xin, Z.; Guo, W.; Guo, Z.; Hao, B.; Jianping, L. Synthesis and antibacterial evaluation of novel pleuromutilin derivatives. Eur. J. Med. Chem.,  2013, 63, 231-238.
 [http://dx.doi.org/10.1016/j.ejmech.2013.01.048] [PMID: 23501109]

[256]
Scheeren, T.W.L. Ceftobiprole medocaril in the treatment of hospital-acquired pneumonia. Future Microbiol.,  2015, 10(12), 1913-1928.
 [http://dx.doi.org/10.2217/fmb.15.115] [PMID: 26573022]

[257]
Yum, J.H.; Kim, C.K.; Yong, D.; Lee, K.; Chong, Y.; Kim, C.M.; Kim, J.M.; Ro, S.; Cho, J.M. In vitro activities of CG400549, a novel FabI inhibitor, against recently isolated clinical staphylococcal strains in Korea. Antimicrob. Agents Chemother.,  2007, 51(7), 2591-2593.
 [http://dx.doi.org/10.1128/AAC.01562-06] [PMID: 17420210]

[258]
Rautio, J.; Kärkkäinen, J.; Sloan, K.B. Prodrugs – Recent approvals and a glimpse of the pipeline. Eur. J. Pharm. Sci.,  2017, 109, 146-161.
 [http://dx.doi.org/10.1016/j.ejps.2017.08.002] [PMID: 28782609]

[259]
Ross, J.E.; Flamm, R.K.; Jones, R.N. Initial broth microdilution quality control guidelines for Debio 1452, a FabI inhibitor antimicrobial agent. Antimicrob. Agents Chemother.,  2015, 59(11), 7151-7152.
 [http://dx.doi.org/10.1128/AAC.01690-15] [PMID: 26324261]

[260]
Schneider, P.; Hawser, S.; Islam, K. Iclaprim, a novel diaminopyrimidine with potent activity on trimethoprim sensitive and resistant bacteria. Bioorg. Med. Chem. Lett.,  2003, 13(23), 4217-4221.
 [http://dx.doi.org/10.1016/j.bmcl.2003.07.023] [PMID: 14623005]

[261]
Surur, A.S.; Sun, D. Macrocycle-antibiotic hybrids: A path to clinical candidates. Front Chem.,  2021, 9, 659845.
 [http://dx.doi.org/10.3389/fchem.2021.659845] [PMID: 33996753]

[262]
De Rosa, M.; Verdino, A.; Soriente, A.; Marabotti, A. The odd couple (s): An overview of beta-lactam antibiotics bearing more than one pharmacophoric group. Int. J. Mol. Sci.,  2021, 22(2), 617-638.
 [http://dx.doi.org/10.3390/ijms22020617] [PMID: 33435500]

[263]
 Lemaire, S.; Van Bambeke, F.; Tulkens, P.M. Contrasting effect of acidic pH on the batericidal activities of CEM-102 (fusidic acid) vs. linezolid and clindamycin towards Staphylococcus aureus, 49th Interscience conference on antimicrobial agents and chemotherapy (ICAAC), San Francisco, California, Sep 12-15, 2009.

[264]
Marinelli, F.; Genilloud, O. Antimicrobials: New and old molecules in the fight against multi-resistant bacteria, 1st ed; Springer Science & Business Media: Berlin, 2013. 

[265]
Kaur, G.; Pavadai, E.; Wittlin, S.; Chibale, K. 3D-QSAR modeling and synthesis of new fusidic acid derivatives as antiplasmodial agents. J. Chem. Inf. Model.,  2018, 58(8), 1553-1560.
 [http://dx.doi.org/10.1021/acs.jcim.8b00105] [PMID: 30040885]

[266]
Clinicaltrials.gov. Oral sodium fusidate (CEM-102) versus oral linezolid for the treatment of acute bacterial skin and skin structure infections. 2019. Available From: https://clinicaltrials.gov/ct2/show/NCT02570490

[267]
Clinicaltrials.gov. Comparative study of NXL103 versus Linezolid in Adults with Acute Bacterial Skin and Skin Structure Infections (ABSSSI). 2018. Available From: https://clinicaltrials.gov/ct2/show/NCT00949130

[268]
Cai, L.; Seiple, I.B.; Li, Q. Modular chemical synthesis of streptogramin and lankacidin antibiotics. Acc. Chem. Res.,  2021, 54(8), 1891-1908.
 [http://dx.doi.org/10.1021/acs.accounts.0c00894] [PMID: 33792282]

[269]
Tracxn. Biocidium. 2016. Available From: https://tracxn.com/d/companies/biocidium/__A1AwtbyuPpFosPFzBrVDoWk6tH1IzPhIJlK_Tt94OiE

[270]
Vander Elst, N.; Linden, S.B.; Lavigne, R.; Meyer, E.; Briers, Y.; Nelson, D.C. Characterization of the bacteriophage-derived endolysins PlySs2 and PlySs9 with in vitro lytic activity against bovine mastitis Streptococcus uberis. Antibiotics (Basel),  2020, 9(9), 621-635.
 [http://dx.doi.org/10.3390/antibiotics9090621] [PMID: 32961696]

[271]
Swift, S.M.; Sauve, K.; Cassino, C.; Schuch, R. Exebacase is active in vitro in pulmonary surfactant and is efficacious alone and synergistic with Daptomycin in a mouse model of lethal Staphylococcus aureus lung infection. Antimicrob. Agents Chemother.,  2021, 65(9), e02723-20.
 [http://dx.doi.org/10.1128/AAC.02723-20] [PMID: 34228536]

[272]
Bamberger, D.M. Bacteremia and endocarditis due to methicillin-resistant Staphylococcus aureus: The potential role of daptomycin. Ther. Clin. Risk Manag.,  2007, 3(4), 675-684.
 [PMID: 18472990]

[273]
Rasmussen, R.V.; Fowler, V.G., Jr; Skov, R.; Bruun, N.E. Future challenges and treatment of Staphylococcus aureus bacteremia with emphasis on MRSA. Future Microbiol.,  2011, 6(1), 43-56.
 [http://dx.doi.org/10.2217/fmb.10.155] [PMID: 21162635]

[274]
 Fowler, V.; Das, A.; Lipka, J.; Schuch, R.; Cassino, C. Exebacase (lysin CF-301) improved clinical responder rates in methicillin-resistant Staphylococcus aureus bacteremia and endocarditis compared to standard of care antibiotics alone in a first-in-patient phase 2 study. In European congress of clinical microbiology and infectious diseases,  Amsterdam, Netherland, 2019.

[275]
Clinicaltrials.gov. Safety, efficacy and pharmacokinetics of CF-301 vs. placebo in addition to antibacterial therapy for treatment of S. Aureus Bacteremia. 2021. Available From: https://clinicaltrials.gov/ct2/show/NCT03163446

[276]
Clinicaltrials.gov. Expanded access study of exebacase in COVID-19 patients with persistent MRSA bacteremia. 2022. Available From: https://clinicaltrials.gov/ct2/show/NCT04597242

[277]
Rello, J.; Parisella, F.R.; Perez, A. Alternatives to antibiotics in an era of difficult-to-treat resistance: New insights. Expert Rev. Clin. Pharmacol.,  2019, 12(7), 635-642.
 [http://dx.doi.org/10.1080/17512433.2019.1619454] [PMID: 31092053]

[278]
Huang, D.B.; Sader, H.S.; Rhomberg, P.R.; Gaukel, E.; Borroto-Esoda, K. Anti-staphylococcal lysin, LSVT-1701, activity: In vitro susceptibility of Staphylococcus aureus and coagulase-negative staphylococci (CoNS) clinical isolates from around the world collected from 2002 to 2019. Diagn. Microbiol. Infect. Dis.,  2021, 101(3), 115471-115477.
 [http://dx.doi.org/10.1016/j.diagmicrobio.2021.115471] [PMID: 34280671]

[279]
François, B.; Barraud, O.; Jafri, H.S. Antibody-based therapy to combat Staphylococcus aureus infections. Clin. Microbiol. Infect.,  2017, 23(4), 219-221.
 [http://dx.doi.org/10.1016/j.cmi.2017.02.035] [PMID: 28274770]

[280]
GlobeNewswire. XBiotech announces top-line results for 514G3 antibody therapy in serious Staphylococcus aureus infections. 2017. Available From: https://www.globenewswire.com/news-release/2017/04/03/953500/0/en/XBiotech-Announces-Top-Line-Results-for-514G3-Antibody-Therapy-in-Serious-Staphylococcus-aureus-Infections.html

[281]
Clinicaltrials.gov. A study of the safety and efficacy of 514g3 in subjects hospitalized with bacteremia due to Staphylococcus aureus. 2017. Available From: https://clinicaltrials.gov/ct2/show/NCT02357966

[282]
Hageman, J.C.; Uyeki, T.M.; Francis, J.S.; Jernigan, D.B.; Wheeler, J.G.; Bridges, C.B.; Barenkamp, S.J.; Sievert, D.M.; Srinivasan, A.; Doherty, M.C.; McDougal, L.K.; Killgore, G.E.; Lopatin, U.A.; Coffman, R.; MacDonald, J.K.; McAllister, S.K.; Fosheim, G.E.; Patel, J.B.; McDonald, L.C. Severe community-acquired pneumonia due to Staphylococcus aureus, 2003-04 influenza season. Emerg. Infect. Dis.,  2006, 12(6), 894-899.
 [http://dx.doi.org/10.3201/eid1206.051141] [PMID: 16707043]

[283]
Mayor, A.; Chesnay, A.; Desoubeaux, G.; Ternant, D.; Heuzé-Vourc’h, N.; Sécher, T. Therapeutic antibodies for the treatment of respiratory tract infections—current overview and perspectives. Vaccines (Basel),  2021, 9(2), 151-172.
 [http://dx.doi.org/10.3390/vaccines9020151] [PMID: 33668613]

[284]
Vanamala, K.; Tatiparti, K.; Bhise, K.; Sau, S.; Scheetz, M.H.; Rybak, M.J.; Andes, D.; Iyer, A.K. Novel approaches for the treatment of methicillin-resistant Staphylococcus aureus: Using nanoparticles to overcome multidrug resistance. Drug Discov. Today,  2021, 26(1), 31-43.
 [http://dx.doi.org/10.1016/j.drudis.2020.10.011] [PMID: 33091564]

[285]
Hall-Stoodley, L.; Costerton, J.W.; Stoodley, P. Bacterial biofilms: From the natural environment to infectious diseases. Nat. Rev. Microbiol.,  2004, 2(2), 95-108.
 [http://dx.doi.org/10.1038/nrmicro821] [PMID: 15040259]

[286]
Salem, A.H.; Elkhatib, W.F.; Noreddin, A.M. Pharmacodynamic assessment of vancomycin–rifampicin combination against methicillin resistant Staphylococcus Aureus biofilm: A parametric response surface analysis. J. Pharm. Pharmacol.,  2010, 63(1), 73-79.
 [http://dx.doi.org/10.1111/j.2042-7158.2010.01183.x] [PMID: 21155818]

[287]
Dube, D.; Agrawal, G.P.; Vyas, S.P. Tuberculosis: From molecular pathogenesis to effective drug carrier design. Drug Discov. Today,  2012, 17(13-14), 760-773.
 [http://dx.doi.org/10.1016/j.drudis.2012.03.012] [PMID: 22480870]

[288]
Li, J.; Zhang, K.; Ruan, L.; Chin, S.F.; Wickramasinghe, N.; Liu, H.; Ravikumar, V.; Ren, J.; Duan, H.; Yang, L.; Chan-Park, M.B. Block copolymer nanoparticles remove biofilms of drug-resistant gram-positive bacteria by nanoscale bacterial debridement. Nano Lett.,  2018, 18(7), 4180-4187.
 [http://dx.doi.org/10.1021/acs.nanolett.8b01000] [PMID: 29902011]

[289]
Mikkaichi, T.; Yeaman, M.R.; Hoffmann, A.; Group, M.S.I. Identifying determinants of persistent MRSA bacteremia using mathematical modeling. PLOS Comput. Biol.,  2019, 15(7), e1007087.
 [http://dx.doi.org/10.1371/journal.pcbi.1007087] [PMID: 31295255]

[290]
Grassi, L.; Di Luca, M.; Maisetta, G.; Rinaldi, A.C.; Esin, S.; Trampuz, A.; Batoni, G. Generation of persister cells of Pseudomonas aeruginosa and Staphylococcus aureus by chemical treatment and evaluation of their susceptibility to membrane-targeting agents. Front. Microbiol.,  2017, 8, 1917-1929.
 [http://dx.doi.org/10.3389/fmicb.2017.01917] [PMID: 29046671]

[291]
Kim, W.; Hendricks, G.L.; Tori, K.; Fuchs, B.B.; Mylonakis, E. Strategies against methicillin-resistant Staphylococcus aureus persisters. Future Med. Chem.,  2018, 10(7), 779-794.
 [http://dx.doi.org/10.4155/fmc-2017-0199] [PMID: 29569952]

[292]
Pacios, O.; Blasco, L.; Bleriot, I.; Fernandez-Garcia, L.; González Bardanca, M.; Ambroa, A.; López, M.; Bou, G.; Tomás, M. Strategies to combat multidrug-resistant and persistent infectious diseases. Antibiotics (Basel),  2020, 9(2), 65-68.
 [http://dx.doi.org/10.3390/antibiotics9020065] [PMID: 32041137]

[293]
Hageman, J.C.; Liedtke, L.A.; Sunenshine, R.H.; Strausbaugh, L.J.; McDonald, L.C.; Tenover, F.C. Management of persistent bacteremia caused by methicillin-resistant Staphylococcus aureus: A survey of infectious diseases consultants. Clin. Infect. Dis.,  2006, 43(5), e42-e45.
 [http://dx.doi.org/10.1086/506568] [PMID: 16886141]

[294]
Moellering, R.C., Jr MRSA: The first half century. J. Antimicrob. Chemother.,  2012, 67(1), 4-11.
 [http://dx.doi.org/10.1093/jac/dkr437] [PMID: 22010206]

[295]
Butler, M.S.; Blaskovich, M.A.; Cooper, M.A. Antibiotics in the clinical pipeline in 2013. J. Antibiot. (Tokyo),  2013, 66(10), 571-591.
 [http://dx.doi.org/10.1038/ja.2013.86] [PMID: 24002361]

[296]
Livermore, D.M. Introduction: The challenge of multiresistance. Int. J. Antimicrob. Agents,  2007, 29(Suppl. 3), S1-S7.
 [http://dx.doi.org/10.1016/S0924-8579(07)00158-6] [PMID: 17659208]

[297]
Barrett, J.F. MRSA – what is it, and how do we deal with the problem? Expert Opin. Ther. Targets,  2005, 9(2), 253-265.
 [http://dx.doi.org/10.1517/14728222.9.2.253] [PMID: 15934914]
Rights & Permissions Print Cite
Article Metrics
87
1
Journal Information
For Authors
For Editors
For Reviewers
Explore Articles
Open Access
Open Access Articles
For Visitors
DOI https://dx.doi.org/10.2174/0109298673249381231130111352	Print ISSN 0929-8673
Publisher Name Bentham Science Publisher	Online ISSN 1875-533X
Current Medicinal Chemistry

Treatment of MRSA Infection: Where are We?

Abstract

Advances in Medicinal Chemistry: From Cancer to Chronic Diseases.

Approaches to the Treatment of Chronic Inflammation

Cellular and Molecular Mechanisms of Non-Infectious Inflammatory Diseases: Focus on Clinical Implications

Chalcogen-modified nucleic acid analogues

Current Medicinal Chemistry

Treatment of MRSA Infection: Where are We?

Abstract

Call for Papers in Thematic Issues

Advances in Medicinal Chemistry: From Cancer to Chronic Diseases.

Approaches to the Treatment of Chronic Inflammation

Cellular and Molecular Mechanisms of Non-Infectious Inflammatory Diseases: Focus on Clinical Implications

Chalcogen-modified nucleic acid analogues

Related Journals

Related Books

Related Articles
