Efficacy of Aminomethyl Spectinomycins against Complex Upper Respiratory Tract Bacterial Infections

被引:0
作者
Iverson, Amy [1 ]
Meyer, Christopher J. [2 ]
Vogel, Peter [3 ]
Waidyarachchi, Samanthi [2 ,4 ]
Das, Nisha [2 ]
Bruhn, David F. [2 ]
Poole, Aaron [1 ]
Butler, Michelle M. [4 ]
Bowlin, Terry L. [4 ]
Lee, Richard E. [2 ]
Rosch, Jason W. [1 ]
机构
[1] St Jude Childrens Res Hosp, Dept Infect Dis, 332 N Lauderdale St, Memphis, TN 38105 USA
[2] St Jude Childrens Res Hosp, Dept Chem Biol & Therapeut, 332 N Lauderdale St, Memphis, TN 38105 USA
[3] St Jude Childrens Res Hosp, Vet Pathol Core, 332 N Lauderdale St, Memphis, TN 38105 USA
[4] Microbiotix Inc, Worcester, MA USA
基金
美国国家卫生研究院;
关键词
Haemophilus influenzae; Streptococcus pneumoniae; otitis media; STREPTOCOCCUS-PNEUMONIAE; OTITIS-MEDIA; MIDDLE-EAR; ANTIBIOTICS; PROTEIN; SURFACE; AGENTS;
D O I
10.1128/AAC.02096-18
中图分类号
Q93 [微生物学];
学科分类号
071005 ; 100705 ;
摘要
The most frequent ailment for which antibiotics are prescribed is otitis media (ear infections), which is most commonly caused by Haemophilus influenzae, Moraxella catarrhalis, and Streptococcus pneumoniae. Treatment of otitis media is complicated by the fact that the bacteria in the middle ear typically form biofilms, which can be recalcitrant to antibiotic treatment. Furthermore, bacterial respiratory infections can be greatly exacerbated by viral coinfection, which is particularly evidenced by the synergy between influenza and S. pneumoniae. In this study, we sought to ascertain the in vivo efficacy of aminomethyl spectinomycin lead 1950, an effective antibacterial agent both in vitro and in vivo against Streptococcus pneumoniae in the context of complex respiratory infections and acute otitis media. A single dose of 1950 significantly reduced bacterial burden in the respiratory tract for all three pathogens, even when species were present in a coinfection model. Additionally, a single dose of 1950 effectively reduced pneumococcal acute otitis media from the middle ear. The agent 1950 also proved efficacious in the context of influenza-pneumococcal super infection. These data further support the development of this family of compounds as potential therapeutic agents against the common causes of complex upper respiratory tract infections and acute otitis media.
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页数:11
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共 29 条
[1]   A steric block in translation caused by the antibiotic spectinomycin [J].
Borovinskaya, Maria A. ;
Shoji, Shinichiro ;
Holton, James M. ;
Fredric, Kurt ;
Cate, Jamie H. D. .
ACS CHEMICAL BIOLOGY, 2007, 2 (08) :545-552
[2]   Aminomethyl spectinomycins as therapeutics for drug-resistant respiratory tract and sexually transmitted bacterial infections [J].
Bruhn, David F. ;
Waidyarachchi, Samanthi L. ;
Madhura, Dora B. ;
Shcherbakov, Dimitri ;
Zheng, Zhong ;
Liu, Jiuyu ;
Abdelrahman, Yasser M. ;
Singh, Aman P. ;
Duscha, Stefan ;
Rathi, Chetan ;
Lee, Robin B. ;
Belland, Robert J. ;
Meibohm, Bernd ;
Rosch, Jason W. ;
Boettger, Erik C. ;
Lee, Richard E. .
SCIENCE TRANSLATIONAL MEDICINE, 2015, 7 (288)
[3]   Functional insights from the structure of the 30S ribosomal subunit and its interactions with antibiotics [J].
Carter, AP ;
Clemons, WM ;
Brodersen, DE ;
Morgan-Warren, RJ ;
Wimberly, BT ;
Ramakrishnan, V .
NATURE, 2000, 407 (6802) :340-348
[4]   New Patterns in the Otopathogens Causing Acute Otitis Media Six to Eight Years After Introduction of Pneumococcal Conjugate Vaccine [J].
Casey, Janet R. ;
Adlowitz, Diana G. ;
Pichichero, Michael E. .
PEDIATRIC INFECTIOUS DISEASE JOURNAL, 2010, 29 (04) :304-309
[5]   Pharmacokinetics and pharmacodynamics of antibiotics in otitis media [J].
Craig, WA ;
Andes, D .
PEDIATRIC INFECTIOUS DISEASE JOURNAL, 1996, 15 (03) :255-259
[6]   The microbiologic and immunologic basis for recurrent otitis media in children [J].
Faden, H .
EUROPEAN JOURNAL OF PEDIATRICS, 2001, 160 (07) :407-413
[7]   Antibiotics for Emerging Pathogens [J].
Fischbach, Michael A. ;
Walsh, Christopher T. .
SCIENCE, 2009, 325 (5944) :1089-1093
[8]   Antibiotic Prescription Rates for Acute Respiratory Tract Infections in US Ambulatory Settings [J].
Grijalva, Carlos G. ;
Nuorti, J. Pekka ;
Griffin, Marie R. .
JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION, 2009, 302 (07) :758-766
[9]   Direct detection of bacterial Biofilms on the middle-ear mucosa of children with chronic otitis media [J].
Hall-Stoodley, Luanne ;
Hu, Fen Ze ;
Gieseke, Armin ;
Nistico, Laura ;
Nguyen, Duc ;
Hayes, Jay ;
Forbes, Michael ;
Greenberg, David P. ;
Dice, Bethany ;
Burrows, Amy ;
Wackym, P. Ashley ;
Stoodley, Paul ;
Post, J. Christopher ;
Ehrlich, Garth D. ;
Kerschner, Joseph E. .
JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION, 2006, 296 (02) :202-211
[10]   A LARGE, ANTIGENICALLY CONSERVED PROTEIN ON THE SURFACE OF MORAXELLA-CATARRHALIS IS A TARGET FOR PROTECTIVE ANTIBODIES [J].
HELMINEN, ME ;
MACIVER, I ;
LATIMER, JL ;
KLESNEYTAIT, J ;
COPE, LD ;
PARIS, M ;
MCCRACKEN, GH ;
HANSEN, EJ .
JOURNAL OF INFECTIOUS DISEASES, 1994, 170 (04) :867-872