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

Antimicrobial Agents and Chemotherapy

Volumn 61, Issue 6, 2017, Pages

  O'riordan, William ^a   Tiffany, Courtney ^b   Scangarella Oman, Nicole ^b   Perry, Caroline ^b   Hossain, Mohammad ^b   Ashton, Teri ^b   Dumont, Etienne ^b  

^a Study Site   (United States)

^b GLAXOSMITHKLINE   (United States)

Author keywords

ABSSSI; Antibacterial agent; Antimicrobial safety; Efficacy; Gepotidacin; Phase 2 study; Skin infections

Indexed keywords

ALANINE AMINOTRANSFERASE; ASPARTATE AMINOTRANSFERASE; GAMMA GLUTAMYLTRANSFERASE; GEPOTIDACIN; ACENAPHTHENE DERIVATIVE; ANTIINFECTIVE AGENT; FUSED HETEROCYCLIC RINGS;

ACUTE BACTERIAL SKIN AND SKIN STRUCTURE INFECTION; ADULT; ALANINE AMINOTRANSFERASE BLOOD LEVEL; AREA UNDER THE CURVE; ARTICLE; ASPARTATE AMINOTRANSFERASE BLOOD LEVEL; BACTERIAL SKIN DISEASE; BACTERIUM ISOLATE; BLOOD CULTURE; BODY MASS; CELLULITIS; DIARRHEA; DOUBLE BLIND PROCEDURE; DRUG BLOOD LEVEL; DRUG EFFICACY; DRUG SAFETY; DRUG TOLERABILITY; EXTRAVASATION; FEMALE; FLATULENCE; GAMMA GLUTAMYL TRANSFERASE BLOOD LEVEL; GASTROESOPHAGEAL REFLUX; HEADACHE; HUMAN; IN VITRO STUDY; INTENTION TO TREAT ANALYSIS; LYMPHADENOPATHY; MAJOR CLINICAL STUDY; MALE; METHICILLIN RESISTANT STAPHYLOCOCCUS AUREUS; MIDDLE AGED; MIGRAINE; MINIMUM INHIBITORY CONCENTRATION; MULTICENTER STUDY; NAUSEA; OPEN STUDY; OPTIMAL DRUG DOSE; PHASE 2 CLINICAL TRIAL; PLASMA CONCENTRATION-TIME CURVE; PRIORITY JOURNAL; PRURITUS; RANDOMIZED CONTROLLED TRIAL; SIDE EFFECT; SKIN ABSCESS; SKIN STRUCTURE INFECTION; TREATMENT RESPONSE; VOMITING; WOUND INFECTION; CLINICAL TRIAL; CONTROLLED STUDY; DRUG EFFECTS; GRAM POSITIVE BACTERIUM; MICROBIOLOGY; PATHOGENICITY;

ACENAPHTHENES; ADULT; ANTI-BACTERIAL AGENTS; FEMALE; GRAM-POSITIVE BACTERIA; HETEROCYCLIC COMPOUNDS, 3-RING; HUMANS; MALE; MIDDLE AGED; SKIN DISEASES, BACTERIAL;

EID: 85019709513     PISSN: 00664804     EISSN: 10986596     Source Type: Journal    
DOI: 10.1128/AAC.02095-16     Document Type: Article

References (17)

1. Suaya JA, Mera RM, Cassidy A, O'Hara P, Amrine-Madsen H, Burstin S, Miller LG. 2014. Incidence and cost of hospitalizations associated with Staphylococcus aureus skin and soft tissue infections in the United States from 2001 through 2009. BMC Infect Dis 14:296. https://doi.org/10.1186/1471-2334-14-296.
2. Hersh AL, Chambers HF, Maselli JH, Gonzales R. 2008. National trends in ambulatory visits and antibiotic prescribing for skin and soft-Tissue infections. Arch Intern Med 168:1585-1591. https://doi.org/10.1001/archinte.168.14.1585.
3. Kaye KS, Patel DA, Stephens JM, Khachatryan A, Patel A, Johnson K. 2015. Rising United States hospital admissions for acute bacterial skin and skin structure infections: Recent trends and economic impact. PLoS One 10:e0143276. https://doi.org/10.1371/journal.pone.0143276.
4. Pfuntner A, Wier LM, Stocks C. 2013. Most frequent conditions in U.S. hospitals, 2011. Statistical brief 162. Healthcare Cost and Utilization Project (HCUP) statistical briefs. Agency for Healthcare Policy and Research, Rockville, MD. http://www.hcup-us.ahrq.gov/reports/statbriefs/sb162.pdf. Accessed 1 June 2016.
5. Moran GJ, Abrahamian FM, LoVecchio F, Talan DA. 2013. Acute bacterial skin infections: developments since the 2005 Infectious Diseases Society of America (IDSA) guidelines. J Emerg Med 44:e397-e412. https://doi.org/10.1016/j.jemermed.2012.11.050.
6. Dryden MS. 2010. Complicated skin and soft tissue infection. J Antimicrob Chemother 65(Suppl 3):iii35-iii44. https://doi.org/10.1093/jac/dkq302.
7. Johnson J, Khoie T, Shurland S, Kreisel K, Stine OC, Roghmann M-C. 2007. Skin and soft tissue infections caused by methicillin-resistant Staphylococcus aureus USA300 clone. Emerg Infect Dis 13:1195-1200. https://doi.org/10.3201/eid1308.061575.
8. Fridkin SK, Hageman JC, Morrison M, Sanza LT, Como-Sabetti K, Jernigan JA, Harriman K, Harrison LH, Lynfield R, Farley MM. 2005. Methicillinresistant Staphylococcus aureus disease in three communities. N Engl J Med 352:1436 -1444. https://doi.org/10.1056/NEJMoa043252.
9. Wilcox MH. 2009. The tide of antimicrobial resistance and selection. Int J Antimicrob Agents 34(Suppl 3):S6 -S10. https://doi.org/10.1016/S0924-8579(09)70550-3.
10. Falcone M, Concia E, Giusti M, Mazzone A, Santini C, Stefani S, Violi F. 2016. Acute bacterial skin and skin structure infections in internal medicine wards: old and new drugs. Intern Emerg Med 11:637- 648. https://doi.org/10.1007/s11739-016-1450-6.
11. Bax BD, Chan PF, Eggleston DS, Fosberry A, Gentry DR, Gorrec F, Giordano I, Hann MM, Hennessy A, Hibbs M, Huang J, Jones E, Jones J, Brown KK, Lewis CJ, May EW, Saunders MR, Singh O, Spitzfaden CE, Shen C, Shillings A, Theobald AJ, Wohlkonig A, Pearson ND, Gwynn MN. 2010. Type IIA topoisomerase inhibition by a new class of antibacterial agents. Nature 466:935-940. https://doi.org/10.1038/nature09197.
12. Biedenbach DJ, Bouchillon SK, Hackel M, Miller LA, Scangarella-Oman NE, Jakielaszek C, Sahm DF. 2016. In vitro activity of gepotidacin, a novel triazaacenaphthylene bacterial topoisomerase inhibitor, against a broad spectrum of bacterial pathogens. Antimicrob Agents Chemother 60: 1918-1923. https://doi.org/10.1128/AAC.02820-15.
13. 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. 2016. The metabolism and disposition of GSK2140944 in healthy human subjects. Xenobiotica 46:683-702. https://doi.org/10.3109/00498254.2015.1112933.
14. Tiffany CA, Hossain M, McDonald M, Dumont EF. 2015. The effect of gepotidacin (GSK2140944), a novel triazaacenaphthylene bacterial topoisomerase inhibitor, on cardiac repolarization parameters, abstr 515. Abstr 115th Gen Meet Am Soc Microbiol. American Society for Microbiology, Washington, DC.
15. Tiffany CA, Hossain M, McDonald M, Dumont EF. 2014. Safety and pharmacokinetics of single escalating IV doses of GSK2140944, a novel bacterial topoisomerase inhibitor, abstr 2611. Abstr 54th Intersci Conf Antimicrob Agents Chemother. American Society for Microbiology, Washington, DC.
16. Tiffany CA, Hossain M, McDonald M, Patel A, Lerman S, Patel P, Widdowson KL, Dumont EF. 2013. Safety and pharmacokinetics of single escalating oral doses of GSK2140944, a novel bacterial topoisomerase inhibitor, abstr F-1218. Abstr 53rd Intersci Conf Antimicrob Agents Chemother. American Society for Microbiology, Washington, DC.
17. Bulik CC, Okusanya ÓO, Lakota EA, Forrest A, Bhavnani SM, Hoover JL, Andes DR, Ambrose PG. 2017. Pharmacokinetic-pharmacodynamic evaluation of gepotidacin against Gram-positive organisms using data from murine infection models. Antimicrob Agents Chemother 61:e00115-16. https://doi.org/10.1128/AAC.00115-16.