The antibiotic pipeline: reviving research and development and speeding drugs to market

Luepke, Katherine H.; Mohr, John

doi:10.1080/14787210.2017.1308251

Cited by 67 publications

(55 citation statements)

References 25 publications

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“…In recent years, there has been both a surge in antibiotic resistance (ABR) (European Centre for Disease Prevention and Control (ECDC), 2017; Okeke et al, 2005; World Health Organization (WHO), 2014) and a decline in the rate of new antibiotic development (Luepke and Mohr, 2017;Spellberg et al, 2004). ABR poses a significant risk in terms of mortality and economic burden worldwide.…”

Section: Introductionmentioning

confidence: 99%

Antibiotic resistance in Bangladesh: A systematic review

Ahmed

Rabbi

Sultana

2019

International Journal of Infectious Diseases

149

125

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Background: Antibiotic resistance (ABR) is a worldwide problem and Bangladesh is a major contributor to this owing to its poor healthcare standards, along with the misuse and overuse of antibiotics. This systematic review was conducted to summarize the present scenario of ABR in Bangladesh, to identify gaps in surveillance, and to provide recommendations based on the findings. Methods: Google Scholar, PubMed, and Bangladesh Journals Online were searched using relevant keywords to identify articles related to ABR in Bangladesh published between 2004 and 2018. Inclusion or exclusion was based on a predefined set of criteria. The resistance of a bacterium to a given drug was presented as the median resistance (MR) and interquartile range (IQR). Results: Forty-six articles were included in this systematic review. Antimicrobial susceptibility testing was performed by disk diffusion method in 82.6% of studies, while the Clinical and Laboratory Standards Institute (CLSI) guidelines were followed in 78.3%. Data regarding the susceptibility testing method, guidelines for interpretation, and source of infection (hospital/community) were absent in 10.9%, 19.6%, and 73.9% of the studies, respectively. A high prevalence of resistance was detected in most tested pathogens, and many of the common first-line drugs were mostly ineffective. Resistance to carbapenems was low in most cases. The presence of extended-spectrum beta-lactamase (ESBL)-producing organisms was indicated by the high resistance to beta-lactams. Methicillin-resistant Staphylococcus aureus (MRSA) was identified in four studies. Three studies reported vancomycin susceptibility of enterococci, and the median susceptibility was 100%. Streptococcus pneumoniae exhibited high susceptibility to penicillin (MR 4%). Resistance data were available from only six out of the 64 districts of Bangladesh. Conclusions: A high prevalence of resistance to most antibiotics was detected, along with major gaps in surveillance and information gaps in the methodological data of the studies (susceptibility testing method, guidelines for susceptibility interpretation, source of infection). Based on the findings, we recommend appropriate initiatives to monitor and control the use of antibiotics, as well as nationwide surveillance following standardized methodologies.

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Section: Introductionmentioning

confidence: 99%

Antibiotic resistance in Bangladesh: A systematic review

Ahmed

Rabbi

Sultana

2019

International Journal of Infectious Diseases

149

125

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“…T he alarming threat of antimicrobial resistance has emerged as a worldwide problem, where the evolution of resistant microbes has seemingly outpaced the development of new antibiotics (1,2).The rapid spread and dissemination of resistanceencoding genes among pathogens further exacerbate the problem, resulting in an ever-increasing rate of antimicrobial-resistant bacterial infections (3)(4)(5). Infections caused by Gram-negative bacilli (GNB) are arguably more difficult to treat since they are intrinsically resistant to many antibiotics and therefore often have limited options for therapy (6,7).…”

mentioning

confidence: 99%

The Anthelmintic Drug Niclosamide Synergizes with Colistin and Reverses Colistin Resistance in Gram-Negative Bacilli

Domalaon

Silva

Kumar

et al. 2019

Antimicrob Agents Chemother

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There is an urgent need for new therapies to overcome antimicrobial resistance especially in Gram-negative bacilli (GNB). Repurposing old U.S. Food and Drug Administration-approved drugs as complementary agents to existing antibiotics in a synergistic combination presents an attractive strategy. Here, we demonstrate that the anthelmintic drug niclosamide selectively synergized with the lipopeptide antibiotic colistin against colistin-susceptible but more importantly against colistin-resistant GNB, including clinical isolates that harbor the mcr-1 gene. Breakpoints for colistin susceptibility in resistant Gram-negative bacilli were reached in the presence of 1 g/ml (3 M) niclosamide. Reversal of colistin resistance was also observed in combinations of niclosamide and polymyxin B. Enhanced bacterial killing was evident for the combination, in comparison to colistin monotherapy, against resistant Pseudomonas aeruginosa, Acinetobacter baumannii, Klebsiella pneumoniae, Escherichia coli, and Enterobacter cloacae. Accumulating evidence in the literature, along with our results, strongly suggests the potential for the combination of niclosamide and colistin to treat colistin-resistant Gram-negative bacillary infections. Our finding is significant since colistin is an antibiotic of last resort for multidrugresistant Gram-negative bacterial infections that are nonresponsive to conventional treatments. With the recent global dissemination of plasmid-encoded colistin resistance, the addition of niclosamide to colistin therapy may hold the key to overcome colistin resistance.

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“…The drug development process is as expensive as it is long, and pharmaceutical companies hesitate to invest in antibiotics when the odds are against them. Furthermore, antibiotics are consumed in short regimes, should be overseen by strict stewardship programs, and are vulnerable to the emergence of resistance, all of which can severely diminish the revenues a company receives (22). It is even believed that newly marketed antibiotics will be outpaced by the high rate at which antibiotic-resistant bacteria are emerging, highlighting the need for novel therapeutics (23).…”

Section: From the Golden Age To The Dry Pipelinementioning

confidence: 99%

Phage Therapy in the Postantibiotic Era

2019

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SUMMARY Antibiotic resistance is arguably the biggest current threat to global health. An increasing number of infections are becoming harder or almost impossible to treat, carrying high morbidity, mortality, and financial cost. The therapeutic use of bacteriophages, viruses that infect and kill bacteria, is well suited to be part of the multidimensional strategies to combat antibiotic resistance. Although phage therapy was first implemented almost a century ago, it was brought to a standstill after the successful introduction of antibiotics. Now, with the rise of antibiotic resistance, phage therapy is experiencing a well-deserved rebirth. Among the admittedly vast literature recently published on this topic, this review aims to provide a forward-looking perspective on phage therapy and its role in modern society. We cover the key points of the antibiotic resistance crisis and then explain the biological and evolutionary principles that support the use of phages, their interaction with the immune system, and a comparison with antibiotic therapy. By going through up-to-date reports and, whenever possible, human clinical trials, we examine the versatility of phage therapy. We discuss conventional approaches as well as novel strategies, including the use of phage-antibiotic combinations, phage-derived enzymes, exploitation of phage resistance mechanisms, and phage bioengineering. Finally, we discuss the benefits of phage therapy beyond the clinical perspective, including opportunities for scientific outreach and effective education, interdisciplinary collaboration, cultural and economic growth, and even innovative use of social media, making the case that phage therapy is more than just an alternative to antibiotics.

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The antibiotic pipeline: reviving research and development and speeding drugs to market

Cited by 67 publications

References 25 publications

Antibiotic resistance in Bangladesh: A systematic review

Antibiotic resistance in Bangladesh: A systematic review

The Anthelmintic Drug Niclosamide Synergizes with Colistin and Reverses Colistin Resistance in Gram-Negative Bacilli

Phage Therapy in the Postantibiotic Era

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