By Learnmore Edwin Zvada
The accidental discovery of penicillin by Sir Alexander Fleming back in 1928 was a game-changer for the medical profession. This ‘miracle drug’ became a torchbearer for antimicrobial chemotherapy, thus significantly reducing morbidity and improving the general quality of life amongst other pros. However, as Fleming warned in his Nobel acceptance speech in 1945, underdosing antibiotics may prompt the development of mutant bacteria that are resistant to conventional therapy.
To some extent, this got spurred by empiric antibiotic therapy, where antibiotic treatment is initiated without the presence of microbiological findings or susceptibility tests, and this is often guided by past clinical experience (Robinson & Grace, 2017). Empiric antibiotic therapy is useful and has been for quite some time since it provides prophylaxis against potential infections and sometimes provides timely interventions in cases where microbiological results may take longer to be available.
Empirical Therapy With Broad Spectrum Antibiotics
Broad-spectrum antibiotics are the class of antibiotics used in empiric treatment where a group of bacteria is suspected rather than a single bacterial species. Microbiological diagnosis may yield results after several days, and delaying initiation of therapy may potentiate higher mortality. In many situations, there is simply no provision for an accurate diagnosis. In the diagnosis of infectious diseases, there are key features that have to be established, and these are; the site of infection, host factors, and microbiological diagnosis, if possible. Determining the etiological agents through microbiological diagnosis is critical because it warrants definitive antibiotic therapy. Broad-spectrum antibiotics have a higher tendency to select for antibiotic resistance when compared to standard antibiotic treatment.
Another challenge that arises from using broad-spectrum antibiotics is that they have a detrimental effect on the human microbiome or normal flora, which may end up predisposing an individual to a whole host of other infections. For instance, many antibiotics on the market get administered orally, and they pass through the gastrointestinal tract. However, according to research, gut microbiota may develop resistance genes after only seven days of therapy, and these can still be detected two years after they first appeared (Francino, 2016).
Escherichia coli, a common bacterium that is part of the gut microbiota, is implicated in conditions such as gastric ulcers. If it develops resistance against antibiotics, conventional antibiotic therapy will no longer be effective. Data reports suggest that broad-spectrum antibiotics can potentially affect about 30% of the gut microbiota, giving rise to a myriad of pathogenic states.
Current WHO guidelines recommend empiric therapy for most bacterial infections. However, there is a need to revise the policies and develop new therapeutic regimens that have less potential to promote drug-resistance in bacteria. Infections are seldom medical emergencies; therefore, empiric selection of antibiotics is often uncalled-for.
As aforementioned, there is a need for rapid molecular diagnosis so that clinicians may use definitive antibiotic therapy, which is targeted at a specific etiological agent (Leekha et al., 2011). Once microbiological results are availed, the clinician can narrow the spectrum of the antibiotics, thus optimizing therapeutic outcomes. Quality patient care requires that treatment be as specific and timely as possible so that the patient may not be unnecessarily exposed to a given drug’s adverse effects. Newer diagnosis methods that can differentiate between closely related bacterial species and provide information on antibiotic susceptibility of the etiologic agent are needed.
Back To The Drawing Board?
Conventional methods of detecting bacteria include culture methods, microscopy, biochemical tests, immunoassays, and molecular techniques. However, these traditional methods are being replaced by newer diagnosis methods, which in some cases are simply an upgrade of conventional methods of diagnosis. These methods include nucleic acid-based amplification technologies (NAATs) using polymerase chain reaction (PCR) and other molecular diagnostic methods (Tsalik et al., 2018).
In addition to that, the diagnostic methods should be easy to interpret and provide results as quickly as possible with high sensitivity and precision. Medical diagnosis plays a pivotal role in influencing treatment modalities in clinical settings. However, there is also a need to develop point-of-care testing devices that can be used in remote settings such as rural areas where there are few or no microbiological laboratories.
In rural areas across most African countries, antibiotic treatment is mainly empiric, given the lack of proper diagnosis resources. Although there is a lack of data to attest to this assertion, it can be theorized that there is a rise in cases of drug-resistant pathogenic strains in rural Africa. Again, this points to the need for more affordable and accessible diagnostic devices for infections such as cholera and typhoid, which often prove problematic in most developing countries where there are poor sanitation and unsafe water.
Technology comes in handy in coming up with new and improved diagnostic methods. Nanotechnology is one such area that has the potential to yield novel diagnostic devices and methods. The use of Nanotechnology in cancer has been widely researched. Of note is the innovative approach of theranostics, which in basic terms is the use of nanosized agents that can provide both diagnosis and therapy.(Hapuarachchige & Artemov, 2020).
The use of theranostics in bacterial infections can help direct a drug-conjugated nanocarrier to the specific infection site where it can deliver its payload, thus avoiding the accumulation of the drug in a non-target area. The use of a smaller size of the drug lowers the dose administered. Consequently, this action reduces the duration and frequency of therapy.
Clinicians must become prudent and judicious in the use of antibiotics or antimicrobials. Everyone who at some point will handle antibiotics, from the drug developer to the final consumer, needs to be fully equipped with enough knowledge with regards to antimicrobial use (AMU) and antimicrobial resistance (AMR). The ignorance of these two phenomena’s impact can prove disastrous for the entire healthcare system and the world at large. However, improved diagnostic methods can also add to the fight against AMR’s gains by influencing the shift from unnecessary antibiotic therapy to definitive antibiotic therapy.
1. Francino M. P. (2016). Antibiotics and the Human Gut Microbiome: Dysbioses and Accumulation of Resistances. Frontiers in microbiology, 6, 1543. https://doi.org/10.3389/fmicb.2015.01543
2. Hapuarachchige, S., & Artemov, D. (2020). Theranostic Pretargeting Drug Delivery and Imaging Platforms in Cancer Precision Medicine. Frontiers In Oncology, 10. https://doi.org/10.3389/fonc.2020.01131
3. Leekha, S., Terrell, C. L., & Edson, R. S. (2011). General principles of antimicrobial therapy. Mayo Clinic Proceedings, 86(2), 156–167. https://doi.org/10.4065/mcp.2010.0639
4. Robinson, B., & Grace, C. (2017). Empiric Antibiotic Selection – Infectious Disease and Antimicrobial Agents. Antimicrobe.org. Retrieved 1 October 2020, from http://www.antimicrobe.org/e62.asp.
5. Tsalik, E. L., Bonomo, R. A., & Fowler, V. G., Jr (2018). New Molecular Diagnostic Approaches to Bacterial Infections and Antibacterial Resistance. Annual review of medicine, 69, 379–394. https://doi.org/10.1146/annurev-med-052716-030320