The crisis of no new antibiotics--what is the way forward?

Antibiotic use not only underpins modern medicine, but has brought huge changes to the world, especially in expectations of survival of children into adulthood. The theme of World Health Day, 2011, was "antimicrobial resistance: no action today and no cure tomorrow". The demise of antibacterial drug discovery brings the spectre of untreatable infections. To prevent this crisis immediate action is needed and a new initiative, Antibiotic Action, has been launched. By bringing together communities who need these drugs with academia, health-care professionals, and pharmaceutical companies, this initiative aims to strengthen and enhance academic-industrial partnerships, bring about revision of costly and laborious processes of licensing and regulation of new antibiotics, and address the economics of antimicrobial drugs (cost of use vs profit). A global alliance for antibiotic drug discovery and development would provide a platform for these initiatives.

[1]  N. Thomson,et al.  Complete Sequence and Molecular Epidemiology of IncK Epidemic Plasmid Encoding blaCTX-M-14 , 2011, Emerging infectious diseases.

[2]  P. De Wals,et al.  Pneumonia After Implementation of the Pneumococcal Conjugate Vaccine Program in the Province of Quebec, Canada , 2008, The Pediatric infectious disease journal.

[3]  Christophe Corre,et al.  Identification of a bioactive 51-membered macrolide complex by activation of a silent polyketide synthase in Streptomyces ambofaciens , 2011, Proceedings of the National Academy of Sciences.

[4]  A. Clatworthy,et al.  Targeting virulence: a new paradigm for antimicrobial therapy , 2007, Nature Chemical Biology.

[5]  S. Levy,et al.  Antibacterial resistance worldwide: causes, challenges and responses , 2004, Nature Medicine.

[6]  V. Fischetti,et al.  Bacteriophage lysins as effective antibacterials. , 2008, Current opinion in microbiology.

[7]  J. Coast,et al.  Strategies to contain the emergence of antimicrobial resistance: a systematic review of effectiveness and cost-effectiveness , 2002, Journal of health services research & policy.

[8]  L. Greene,et al.  Impact of antibiotic resistance , 2011, BMJ : British Medical Journal.

[9]  Christopher M Thomas,et al.  A Natural Plasmid Uniquely Encodes Two Biosynthetic Pathways Creating a Potent Anti-MRSA Antibiotic , 2011, PloS one.

[10]  Brad Spellberg,et al.  Combating antimicrobial resistance: policy recommendations to save lives. , 2011, Clinical infectious diseases : an official publication of the Infectious Diseases Society of America.

[11]  G Kahlmeter,et al.  Escherichia coli and Staphylococcus aureus: bad news and good news from the European Antimicrobial Resistance Surveillance Network (EARS-Net, formerly EARSS), 2002 to 2009. , 2011, Euro surveillance : bulletin Europeen sur les maladies transmissibles = European communicable disease bulletin.

[12]  Elias Mossialos,et al.  Stoking the antibiotic pipeline , 2010, BMJ : British Medical Journal.

[13]  C. Baron.  Antivirulence drugs to target bacterial secretion systems. , 2010, Current opinion in microbiology.

[14]  N. Woodford,et al.  Emergence of a new antibiotic resistance mechanism in India, Pakistan, and the UK: a molecular, biological, and epidemiological study , 2010, The Lancet. Infectious diseases.

[15]  S. Projan,et al.  Why is big Pharma getting out of antibacterial drug discovery? , 2003, Current opinion in microbiology.

[16]  J. Frère,et al.  Treatment of health-care-associated infections caused by Gram-negative bacteria: a consensus statement. , 2008, The Lancet. Infectious diseases.

[17]  Bala Hota,et al.  Hospital and societal costs of antimicrobial-resistant infections in a Chicago teaching hospital: implications for antibiotic stewardship. , 2009, Clinical infectious diseases : an official publication of the Infectious Diseases Society of America.

[18]  S. Levy,et al.  Novel anti-infection agents: small-molecule inhibitors of bacterial transcription factors. , 2007, Bioorganic & medicinal chemistry letters.

[19]  C. Nathan,et al.  The profit problem in antibiotic R&D , 2005, Nature Reviews Drug Discovery.

[20]  D. Pompliano,et al.  Nat. Rev. Drug Disc. , 2007 .

[21]  H. Goossens,et al.  Society's failure to protect a precious resource: antibiotics , 2011, The Lancet.

[22]  W. Schaffner,et al.  Sustained reductions in invasive pneumococcal disease in the era of conjugate vaccine. , 2010, The Journal of infectious diseases.

[23]  M. M. Rahman,et al.  Medicinal plant extracts with efflux inhibitory activity against Gram-negative bacteria. , 2011, International journal of antimicrobial agents.

[24]  I. Okeke,et al.  Diagnostics as essential tools for containing antibacterial resistance. , 2011, Drug resistance updates : reviews and commentaries in antimicrobial and anticancer chemotherapy.

[25]  P Huovinen,et al.  The effect of changes in the consumption of macrolide antibiotics on erythromycin resistance in group A streptococci in Finland. Finnish Study Group for Antimicrobial Resistance. , 1997, The New England journal of medicine.

[26]  A. White.  Effective antibacterials: at what cost? The economics of antibacterial resistance and its control. , 2011, The Journal of antimicrobial chemotherapy.

[27]  M. M. Rahman,et al.  Natural and synthetic compounds such as trimethoprim behave as inhibitors of efflux in Gram-negative bacteria. , 2010, The Journal of antimicrobial chemotherapy.

[28]  D. Barlocco.  Muraglitazar (Bristol-Myers Squibb/Merck). , 2005, Current opinion in investigational drugs.

[29]  J. Bartlett,et al.  Bad bugs, no drugs: no ESKAPE! An update from the Infectious Diseases Society of America. , 2009, Clinical infectious diseases : an official publication of the Infectious Diseases Society of America.

[30]  Regulatory opportunities to encourage technology solutions to antibacterial drug resistance. , 2011, The Journal of antimicrobial chemotherapy.

[31]  K. Bostian,et al.  Practical applications and feasibility of efflux pump inhibitors in the clinic--a vision for applied use. , 2006, Biochemical pharmacology.

[32]  D. Livermore.  Discovery research: the scientific challenge of finding new antibiotics. , 2011, The Journal of antimicrobial chemotherapy.

[33]  O. Cars,et al.  The global need for effective antibiotics-moving towards concerted action. , 2011, Drug resistance updates : reviews and commentaries in antimicrobial and anticancer chemotherapy.

[34]  Qijing Zhang,et al.  Sensitization of Campylobacter jejuni to fluoroquinolone and macrolide antibiotics by antisense inhibition of the CmeABC multidrug efflux transporter. , 2009, The Journal of antimicrobial chemotherapy.

[35]  J. Mecsas,et al.  Small Molecule Inhibitors of LcrF, a Yersinia pseudotuberculosis Transcription Factor, Attenuate Virulence and Limit Infection in a Murine Pneumonia Model , 2010, Infection and Immunity.

[36]  V. Ricci,et al.  Exploiting the Role of TolC in Pathogenicity: Identification of a Bacteriophage for Eradication of Salmonella Serovars from Poultry , 2010, Applied and Environmental Microbiology.

[37]  D. Pompliano,et al.  Drugs for bad bugs: confronting the challenges of antibacterial discovery , 2007, Nature Reviews Drug Discovery.

[38]  D. Hung,et al.  Productive steps toward an antimicrobial targeting virulence. , 2009, Current opinion in microbiology.

[39]  H. D. de Melker,et al.  Effects of Pneumococcal Conjugate Vaccine 2 Years after Its Introduction, the Netherlands , 2010, Emerging infectious diseases.

[40]  N. Chan-Tompkins.  Multidrug-Resistant Gram-Negative Infections , 2011, Critical care nursing quarterly.

[41]  J. Hughes,et al.  Preserving the lifesaving power of antimicrobial agents. , 2011, JAMA.

[42]  L. Rice.  Rapid diagnostics and appropriate antibiotic use. , 2011, Clinical infectious diseases : an official publication of the Infectious Diseases Society of America.

[43]  Bonnie L Bassler,et al.  A strategy for antagonizing quorum sensing. , 2011, Molecular cell.

[44]  L. Berti,et al.  Geraniol Restores Antibiotic Activities against Multidrug-Resistant Isolates from Gram-Negative Species , 2009, Antimicrobial Agents and Chemotherapy.

[45]  R. Wise.  The urgent need for new antibacterial agents. , 2011, The Journal of antimicrobial chemotherapy.