Jun Kim Ph.D.

With the recent news about a woman who died from a superbug infection, antibiotics resistance has been gaining increased attention. Global leaders recently met at a UN meeting to discuss future actions on antimicrobial resistance, along with prominent figures such as Bill Gates warning us of potential threats to our health. The fact that antibiotic resistance is occurring is hardly surprising. After all, that is how evolution happens through natural selection. But the problem is excessive use of antibiotics seems to have accelerated the process. After penicillin was successfully used in 1940s, penicillin resistance soon became a significant problem by 1950s[1]. In response, new beta-lactam antibiotics were used, but the first case of methicillin-resistant Staphylococcus aureus (MRSA) was identified during that same decade[1]. According to the Centers for Disease Control and Prevention (CDC), now there are over 80,000 MRSA infections and 11,285 related deaths every year in the US.

Mechanisms behind antibiotic resistance have been studied extensively. Some bacteria can be intrinsically resistant to certain antibiotics because of structural or functional characteristics. For example, a species can be missing a molecular that the drug targets or have a cell surface membrane the drug cannot penetrate. Other types of bacteria that were initially responsive can also acquire resistance via mutations in genes or by receiving these genes from other bacteria[2]. Such mutations can reduce the concentration of the drug in the cell, modify the drug target gene by mutation, or modify the antibacterial drug.

Unnecessary use of antibiotic can promote development of antibiotic resistance by supporting genetic alterations, such as changes in gene expression, gene transfer between species, and mutagenesis[3]. Also antibiotics often remove drug sensitive competitors, because these drugs tend not to be very specific, and this leaves resistant bacteria behind to grow[4]. The healthy gut flora provides an important host defense. They inhibit overgrowth of c. difficile and other potential pathogens through competition for nutrients and intestinal niches, and induction of host immune responses. Antibiotic therapy can weaken this host defense by disrupting the indigenous gut flora, which makes the host more vulnerable to C. difficile during the treatment and during the period of microflora recovery[5].

Another important contributing factor to the rapid increase in untreatable infections is a lack of new drugs. Because of economic and regulatory obstacles pharmaceutical companies are moving away from antibiotics development. For example, because antibiotics are used for relatively short periods and are often curative, antibiotics are not as profitable as drugs that treat chronic conditions. In terms of price, antibiotics are generally at a maximum of $1000 to $3000 per course compared with cancer chemotherapy that costs tens of thousands of dollars[6]. Also, now that antibiotics resistance is becoming a widely noticed issue restrained use on antibiotics will hold the new drugs in reserve for only the worst cases to prevent development of further drug resistance[6]. Understandably, of the 18 largest pharmaceutical companies, 15 abandoned the antibiotic field[7].

It was discussed in the previous articles (here & here) that probiotics may prevent infections by providing anti-microbial agents, boosting host immune system, decreasing intestinal permeability, and competing with pathogens for space and nutrients in the host. Studies have shown that concomitant use of probiotics with antibiotics reduces the risk for antibiotic-associated symptoms. Although the extent with which probiotics directly reduce the spread of antibiotic resistance is unclear, maintaining a balanced microbiota during antibiotic use do provide opportunities for reducing the spread of resistance[8]. Most of the research conducted on antibiotic resistance has been focused on pathogenic bacteria prevalent in nosocomial settings such as hospitals and nursing home environments. However, it is also important to study the antibiotic resistance in animal food production as well as aquaculture. Therefore, using probiotics in the feed and thus improving animal health could be an important approach to reduce the spread of antibiotic resistance.

Sources

[1] Sengupta S, Chattopadhyay MK, Grossart HP: The multifaceted roles of antibiotics and antibiotic resistance in nature. Front Microbiol 2013, 4:47.

[2] Blair JMA, Webber MA, Baylay AJ, Ogbolu DO, Piddock LJV: Molecular mechanisms of antibiotic resistance. Nat Rev Micro 2015, 13:42–51.

[3] Viswanathan VK: Off-label abuse of antibiotics by bacteria. Gut Microbes 2014, 5:3–4.

[4] Read AF, Woods RJ: Antibiotic resistance management. Evol Med Public Health 2014, 2014:147.

[5] Owens RC, Jr., Donskey CJ, Gaynes RP, Loo VG, Muto CA: Antimicrobial-associated risk factors for Clostridium difficile infection. Clin Infect Dis 2008, 46 Suppl 1:S19–31.

[6] Gould IM, Bal AM: New antibiotic agents in the pipeline and how they can help overcome microbial resistance. Virulence 2013, 4:185–191.

[7] Bartlett JG, Gilbert DN, Spellberg B: Seven ways to preserve the miracle of antibiotics. Clin Infect Dis 2013, 56:1445–1450.

[8] Ouwehand AC, Forssten S, Hibberd AA, Lyra A, Stahl B: Probiotic approach to prevent antibiotic resistance. Ann Med 2016, 48:246–255.