1035 ISSN 1746-0913 Future Microbiol. (2015) 10(6), 1035–1048 part of 10.2217/FMB.15.14 © 2015 Future Medicine Ltd REVIEW Development of broad-spectrum antibioflm drugs: strategies and challenges Akhilandeswarre Dharmaprakash 1 , Ramamurthy Thandavarayan 2 , Iype Joseph 3 & Sabu Thomas* ,1 1 Cholera & Biofilm Research Laboratory, Rajiv Gandhi Centre for Biotechnology, Thiruvananthapuram – 695 014, Kerala, India 2 National Institute of Cholera & Enteric Diseases (NICED), Kolkata – 700010, India 3 Pathogen Biology Program, Rajiv Gandhi Centre for Biotechnology, Thiruvananthapuram – 695 014, Kerala, India *Author for correspondence: Tel.: +91 471 252 9521, Fax: +91 471 2346333; sabu@rgcb.res.in ABSTRACT The severity of many chronic bacterial infections is mainly due to the bioflm mode of life adapted by pathogenic bacteria. The bacteria in bioflm-stage exhibit high resistance to host immune responses and antimicrobials, which complicates the treatment process and results in life threatening conditions. Most of the chronic infections are polymicrobial in nature. In order to combat the polymicrobial bioflm infections and to increase the efciency of antimicrobials, there is an urgent need for broad-spectrum antibioflm drugs. This review discusses the clinical needs and current status of broad- spectrum antibioflm drugs with special emphasis on prospective strategies and hurdles in the process of new drug discovery. KEYWORDS • bioflm • broad-spectrum antibioflm drugs • chronic infection • drug discovery • drug target identifcation • polymicrobial The perspective of chronic microbial infection is constantly changing. Two decades of research in the field have revealed that most chronic infections are due to the involvement of biofilm, where microbes exist as surface-attached communities encased in a self-produced extracellular matrix. Almost all bacterial species exhibit biofilm mode of life in nature as it protects the bacteria from hostile environments [1] . The biofilm stage is considered as a phase in the biological cycle of bacteria which significantly differ in the genetic requirements and physiology compared with their planktonic counterparts [2,3] . Microbes in biofilm stage are highly resistant to antimicrobial agents [4] and host immune responses [5] , which are correlated to the presence of extracellular polymeric matrix and physiological heterogeneity [6] . In most cases, patients treated for biofilm-related infections suffer from recurrent infections and clinicians usually adopt intensive antimicrobial treatment or surgi- cal removal of the affected area to achieve complete cure. The prolonged antibiotic treatment and surgical intervention leads to side effects and huge economic loss to the patient. According to the NIH estimates, 80% of chronic infections are due to the involvement of biofilm [7] . In the USA alone, 17 million patients are affected every year by biofilm-related infections, resulting in up to 550,000 fatalities (equal to cancer deaths), and a healthcare cost of US$94 billion [8] . The situation has created an urgent need for antibiofilm drugs that could be used as adjuvants to increase the efficacy of antibiotics for treating biofilm related infections [9] . Studies in various chronic infections have recognized many polymicrobial biofilm infections that demand the need for broad-spectrum antibiofilm drugs [10] . Several research groups have developed potential antibiofilm compounds against various human pathogens (discussed in brief under the section ‘current status of antibiofilm drug discovery’), however, most of them have a limited spectrum that makes them incompetent for treating polymicrobial infections. To the best of our knowledge, there is no antibiofilm compound For reprint orders, please contact: reprints@futuremedicine.com