Public Health Threat: Rise of Antibiotic Resistance

Antimicrobial resistance (AMR) is defined as the microorganisms’ (bacteria /viruses/fungi)ability to grow and replicate in presence of antimicrobial agents that once inhibited theirgrowth & kill them. Antimicrobial agents include antibiotics, antifungals, antivirals,disinfectants, food preservatives, etc. Antibiotic resistance occurs when bacteria adapt toantibiotics and grow in their presence. It is a rising and ongoing thread for public health allover the world as it means that the infectious diseases would no longer be treated withantibiotics that were once effective against them. AMR’s major consequences in patients areprolonged hospital stay, high morbidity and mortality.

When Alexander Fleming discovered penicillin, the world’s first antibiotic, in 1928; it was abreakthrough to treat bacterial infections. But little did we know that we were fighting alosing battle against bacteria’s ability to mutate & adapt to changing circumstances. Morethan 150 antibiotics have been developed since the discovery of penicillin. The drugsbecoming readily available and easy to afford led to their misuse by humans over the years.This includes not finishing the course of antibiotics, overusing them, not taking them at thesame time of the day or using them for viral infections such as flu.

Major antibiotic groups are: Penicillins, cephalosporins, fluoroquinolones, aminoglycosides, monobactams, carbapenems and macrolides. Their mechanisms of action include interfering with cell wall synthesis, inhibiting protein/nucleic acid synthesis or inhibiting metabolic pathways.

Bacteria showing antimicrobial resistance can be multidrug-resistant (MDR), extensivelydrug-resistant (XDR) or pan-drug resistant (PDR). MDR organisms are non-susceptible to atleast one antibiotic in three or more antibiotic groups. XDR organisms are non-susceptible toat least one antibiotic in all but two or fewer antibiotic groups. PDR organisms are non-susceptible to all agents in all antibiotic groups. In bacterial level, driving forces for AMR aremutations and horizontal gene transfers. Antibiotic resistance could be intrinsic or acquired.

Based on the level of their threat, CDC (Centers for Disease Control and Prevention) listed antibiotic-resistant microbes in three classes as given with examples below (it is not an exhaustive list):

Urgent threats: Carbapenem-resistant Acinetobacter, Clostridioides difficile, Carbapenem-resistant Enterobacteriaceae (CRE), Drug-resistant Neisseria gonorrhoeae

Serious threats: Drug-resistant Campylobacter, Extended spectrum β-lactamase producing Enterobacteriaceae (ESBLs), Vancomycin-resistant Enterococcus (VRE), Multidrug-resistant Pseudomonas aeruginosa

Concerning threats: Erythromycin-resistant Group A Streptococcus and Clindamycin-resistant Group B Streptococcus

Below is an example of a fully susceptible environmental P. aeruginosa strain tested against twelve antibiotics by disc-diffusion assay when compared to MDR clinical P. aeruginosa strain. It can be seen in image A.1 &; A.2 that antibiotics were effective on inhibiting bacterial growth as opposed to image B.1 &; B.2, where no or little inhibition zones are formed as MDR bacteria grew in presence of antibiotics.

Figure 1 . Fully sensitive antibiotic testing profile of P. aeruginosa (A.1 & A.2) as opposed to MDR P. aeruginosa (B.1 & B.2). Antibiotics tested: Meropenem, imipenem, piperacillin, piperacillin–tazobactam, amikacin, ceftazidime, cefepime, ciprofloxacin, tobramycin, aztreonam, gentamicin and ticarcillin – clavulanic acid. Image credit: Yetiş Ö. (2023) UCL PhD thesis (https://discovery.ucl.ac.uk/id/eprint/10182829/)

National action plans to combat antibiotic resistance are in place now and there is so much we can do at the individual level. It is challenging to discover novel antibiotics with the current knowledge we have so we need to use the ones already in place wisely. We should not underestimate AMR emergence. Remember, as we continue to develop in science; bacteria will continue to develop resistance mechanisms, too…

References:
1. Yetiş, Ö. The role of hospital water in the transmission of Pseudomonas aeruginosa infection in immunosuppressed patients: Impact of interventions on healthcare water systems, epidemiological characterisation of risk factors for nosocomial bacteraemia and its relationship to reservoirs in the hospital environment using longitudinal sampling, case control studies and whole-genome-sequencing.. Doctoral thesis, UCL (University College London). (UCL (University College London), 2023).
2. Dadgostar, P. Antimicrobial resistance: implications and costs. Infect. Drug Resist. 12, 3903–3910 (2019).
3. Tang, K. W. K., Millar, B. C. & Moore, J. E. Antimicrobial Resistance (AMR). Br. J. Biomed. Sci. 80, 11387 (2023).
4. Magiorakos, A. P. et al. Multidrug-resistant, extensively drug-resistant and pandrug- resistant bacteria: An international expert proposal for interim standard definitions for acquired resistance. Clin. Microbiol. Infect. 18, 268–281 (2012).Magiorakos, A. P. et al. Multidrug-resistant, extensively drug-resistant and pandrug-resistant bacteria: An international expert proposal for interim standard definitions foracquired resistance. Clin. Microbiol. Infect. 18, 268–281 (2012).
5. CDC. Antibiotic Resistance Threats in The United States 2019. Cdc 10, (2019).