Cephalosporins currently in early clinical trials for the treatment of bacterial infections

被引:12
作者
Long, Timothy E. [1 ]
Williams, Justin T. [2 ,3 ]
机构
[1] Marshall Univ, Sch Pharm, Dept Pharmaceut Sci & Res, Huntington, WV 25755 USA
[2] Marshall Univ, Sch Pharm, Dept Pharm Practice Adm & Res, Huntington, WV 25755 USA
[3] St Marys Hosp, Huntington, WV 25702 USA
关键词
antibacterial; ceftolozane; cephalosporin; Enterobacteriaceae; MRSA; Pseudomonas; beta-lactam; IN-VITRO ACTIVITY; GRAM-NEGATIVE BACTERIA; PSEUDOMONAS-AERUGINOSA; CEFTAZIDIME-AVIBACTAM; CEFTAROLINE FOSAMIL; BETA-LACTAMASES; CEFTOLOZANE-TAZOBACTAM; ANTIMICROBIAL ACTIVITY; VIVO ACTIVITIES; EFFLUX PUMPS;
D O I
10.1517/13543784.2014.930127
中图分类号
R9 [药学];
学科分类号
1007 ;
摘要
Introduction: Healthcare-associated infections caused by multi-drug resistant bacteria remain a major cause of worldwide mortality. With the recent approval of agents such as hetero-resistant cocci (i.e., ceftaroline, ceftobiprole, telavancin) for the treatment of Gram-positive infections by and drugs like fidaxomicin for treating Clostridium difficile, present-day research on antibacterials has largely shifted to developing interventions for diseases caused by Gram-negative bacilli. Cephalosporins have gained significant interest as antipseudomonals to be used in hospitals for treating device-and procedure-associated infections. With extended-spectrum activity against many enterobacterial pathogens, the introduction of new antipseudomonal cephalosporin-based treatments will mark a significant advancement in the management of hospital-borne diseases. Areas covered: The following review examines the present-day status of investigational cephalosporins currently in preclinical, Phase I and Phase II stage development. The article focuses specifically on treatments used for healthcare-associated infections due to Gram-negative bacteria. Expert opinion: There is an urgent need for new antimicrobials to treat nosocomial infections due to multi-drug resistant Gram-negative bacteria. The impending approvals of antipseudomonal cephalosporins co-formulated with a beta-lactamase inhibitor will allow clinicians to treat more hetero-resistant infections with cephalosporins, while avoiding the use of more toxic agents such as colistin. The growing interest in developing new beta-lactamase inhibitor combinatorial treatments with approved beta-lactam antibiotics is anticipated to decrease the number of novel cephalosporins entering clinical trials this decade.
引用
收藏
页码:1375 / 1387
页数:13
相关论文
共 59 条
  • [1] In vitro activity of avibactam (NXL104) in combination with β-lactams against Gram-negative bacteria, including OXA-48 β-lactamase-producing Klebsiella pneumoniae
    Aktas, Z.
    Kayacan, C.
    Oncul, O.
    [J]. INTERNATIONAL JOURNAL OF ANTIMICROBIAL AGENTS, 2012, 39 (01) : 86 - 89
  • [2] Ceftobiprole: a novel cephalosporin with activity against Gram-positive and Gram-negative pathogens, including methicillin-resistant Staphylococcus aureus (MRSA)
    Barboura, April
    Schmidt, Stephan
    Rand, Kenneth H.
    Derendorf, Hartmut
    [J]. INTERNATIONAL JOURNAL OF ANTIMICROBIAL AGENTS, 2009, 34 (01) : 1 - 7
  • [3] In vitro activity of AVE1330A, an innovative broad-spectrum non-β-lactam β-lactamase inhibitor
    Bonnefoy, A
    Dupuis-Hamelin, C
    Steier, V
    Delachaume, C
    Seys, C
    Stachyra, T
    Fairley, M
    Guitton, M
    Lampilas, M
    [J]. JOURNAL OF ANTIMICROBIAL CHEMOTHERAPY, 2004, 54 (02) : 410 - 417
  • [4] 10 x '20 Progress-Development of New Drugs Active Against Gram-Negative Bacilli: An Update From the Infectious Diseases Society of America
    Boucher, Helen W.
    Talbot, George H.
    Benjamin, Daniel K., Jr.
    Bradley, John
    Guidos, Robert J.
    Jones, Ronald N.
    Murray, Barbara E.
    Bonomo, Robert A.
    Gilbert, David
    [J]. CLINICAL INFECTIOUS DISEASES, 2013, 56 (12) : 1685 - 1694
  • [5] Updated Functional Classification of β-Lactamases
    Bush, Karen
    Jacoby, George A.
    [J]. ANTIMICROBIAL AGENTS AND CHEMOTHERAPY, 2010, 54 (03) : 969 - 976
  • [6] Contemporary Diversity of β-Lactamases among Enterobacteriaceae in the Nine US Census Regions and Ceftazidime-Avibactam Activity Tested against Isolates Producing the Most Prevalent β-Lactamase Groups
    Castanheira, Mariana
    Farrell, Sarah E.
    Krause, Kevin M.
    Jones, Ronald N.
    Sader, Helio S.
    [J]. ANTIMICROBIAL AGENTS AND CHEMOTHERAPY, 2014, 58 (02) : 833 - 838
  • [7] Cebrik D, 2013, ICAAC ANN M DENV CO
  • [8] Chen M, 2008, Cephalosporin compounds comprising a C3 thio-methyl moiety substituted with. N-containing heterocyclic group, and a C7 thiourea acetamido group, their preparations and uses thereof, Patent No. [US20080182836 A1, 20080182836]
  • [9] Cho YL, 2013, Patent No. [US20130178455 A1, 20130178455]
  • [10] In Vivo Activities of Ceftolozane, a New Cephalosporin, with and without Tazobactam against Pseudomonas aeruginosa and Enterobacteriaceae, Including Strains with Extended-Spectrum β-Lactamases, in the Thighs of Neutropenic Mice
    Craig, W. A.
    Andes, D. R.
    [J]. ANTIMICROBIAL AGENTS AND CHEMOTHERAPY, 2013, 57 (04) : 1577 - 1582