Antibiotics, once the forefront and quintessence of modern medicine, are unfortunately progressing at a pace that has been superseded by the advent of new antibiotic resistance mechanisms poised by bacteria. Before the time of antibiotics, countless deaths occurred due to rampant infections caused by the myriad of diseases that people were often exposed to. Ancient civilizations would conjure up concoctions made from various medicinal herbs and/or invoke the power of greater deities to aid in then recovery of their affected. However, it wasn’t until 1928 that Alexander Fleming discovered penicillin adventitiously via a mold spore in a petri dish of bacteria. This was the most important milestone in the 20th century as we now officially had a surefire cure against gram-positive infections common to man. Thus, the road was paved for the exponential increase in the discovery and innovation of numerous new antibiotics of various mechanisms and classes. As part of this endeavor for a refresher course in antibiotics and their functions, I have designed this thread to encompass the topics of antibiotic classifications, antibiotic resistance, and the antibiotic usage guidelines established by the Infectious Diseases Society of America (IDSA).
To start off it is vital to know the mechanism by which antibiotics work. The primary target of antibiotics is to affect a unique characteristic of the bacteria cell that isn’t coincidentally also on the human cell; in this way, the potential of inhibiting or destroying the bacteria is maximized while also ensuring that the body isn’t harmed in that process. Usually, the most vital difference is the fact that bacteria have a cell wall that encapsulates all the necessary cell components necessary to bacteria survival. Next, the enzymes present in bacteria cells are slightly different compared to human cell enzymes, along with different ribosome sizes. Therefore, it would make sense for antibiotics to be designed to target these specific differences in cell components in order to avoid toxicity; and, as a result, antibiotics that aren’t as selective, as you’ll see later, will have unfavorable side effects to the body.
To simplify things a little bit, we will divide antibiotics into two major categories: bactericidal and bacteriostatic.
Bactericidal antibiotics impose a direct action on the bacteria by either killing or lysing the cell, resulting in complete cell destruction. To do so, they target biochemical pathways involved in cell wall assembly in order to produce a compromised cell wall with missing or altered components. Then, subsequent bacteria cell divisions will produce weaker cell walls that eventually lead to the complete failure of the cell wall to protect and uphold the integrity of the bacteria. These cells then lyse and die and can no longer replicate. Bactericidal antibiotics can then be divided further into those that utilize a concentration-dependent kill vs. those that utilize a time-dependent kill. We will talk more about this later on in the thread. These types of antibiotics are typically reserved for serious infections that need the effect of a bactericidal antibiotic in order to completely clear the infection, e.g. infections in the immunocompromised or meningitis.
Bacteriostatic antibiotics, on the other hand, do not directly kill the bacteria and instead only inhibit the bacteria from reproducing. These antibiotics are ones that you have to take for the full course of therapy, otherwise the potential for relapse will be high as the effects of bacteriostasis are reversible. These antibiotics target nucleic acid and protein synthesis, which are required in the replication process. By effectively slowing down bacterial growth, they allow the host immune system to ramp up enough to destroy the bacteria.
In this next part, I will list out the antibiotics belonging to each group.
References:
1) Calhoun C, Wermuth HR, Hall GA. Antibiotics. [Updated 2021 Jun 8]. In: StatPearls [Internet]. Treasure Island (FL): StatPearls Publishing; 2022 Jan-. Available from https://www.ncbi.nlm.nih.gov/books/NBK535443/
2) Ribeiro da Cunha B, Fonseca LP, Calado CRC. Antibiotic Discovery: Where Have We Come from, Where
Do We Go?. Antibiotics (Basel). 2019;8(2):45. Published 2019 Apr 24. doi:10.3390/antibiotics8020045
3) American Chemical Society International Historic Chemical Landmarks. Discovery and Development of
Penicillin. http://www.acs.org/content/acs/en/education/whatischemistry/landmarks/flemingpenicillin.html
1. Diagnosis and Susceptibility Testing: Before initiating antibiotic therapy, it's essential to accurately diagnose the infection and identify the causative pathogen. This often involves collecting specimens for culture and sensitivity testing to determine which antibiotics are effective against the specific bacteria or fungi causing the infection. Rapid diagnostic tests may also be utilized to expedite the identification of pathogens and guide antibiotic selection.
2. Empiric Therapy: In many cases, antibiotic treatment must be initiated empirically based on clinical suspicion before microbiological results are available. Empiric therapy aims to cover the most likely pathogens based on the patient's clinical presentation, site of infection, and local epidemiology. Antibiotic choice should consider factors such as the severity of illness, risk factors for antibiotic resistance, and potential adverse effects.
3. De-escalation and Targeted Therapy: Once microbiological data becomes available, antibiotic therapy should be reassessed, and adjustments made based on susceptibility results. De-escalation involves narrowing the antibiotic spectrum to the most appropriate agent(s) based on susceptibility testing, minimizing unnecessary broad-spectrum antibiotic use. Targeted therapy allows for more precise treatment of the identified pathogen, optimizing efficacy while reducing the risk of antibiotic resistance and adverse effects.
4. Duration of Therapy: The duration of antibiotic therapy varies depending on factors such as the type and severity of infection, the patient's clinical response, and the presence of complicating factors (e.g., immunocompromised status, foreign bodies). Antibiotic courses are typically tailored to the individual patient, with a focus on achieving clinical resolution while minimizing the development of antibiotic resistance and adverse effects. Shorter courses of antibiotics are often preferred when appropriate to reduce the risk of complications and antibiotic-associated adverse events.
5. Intravenous versus Oral Therapy: In severe infections or when the patient is unable to tolerate oral medications, intravenous (IV) antibiotics may be administered initially. Once the patient's condition stabilizes and oral intake is feasible, transitioning to oral antibiotics can facilitate early discharge from the hospital and reduce the risk of complications associated with prolonged IV therapy. Oral antibiotics with bioequivalent IV formulations are often preferred to streamline the transition from parenteral to oral therapy.
6. Antibiotic Stewardship: Antibiotic stewardship programs play a crucial role in optimizing antibiotic use in the hospital setting. These programs promote judicious antibiotic prescribing practices, monitor antibiotic use and resistance patterns, provide education and feedback to healthcare providers, and implement interventions to improve antibiotic prescribing practices. By promoting appropriate antibiotic use, stewardship programs help mitigate the development of antibiotic resistance, reduce healthcare costs, and improve patient outcomes.
In summary, treating infections with antibiotics in a hospital setting requires a systematic approach that integrates diagnostic testing, empirical therapy, targeted therapy, and antibiotic stewardship principles. By following evidence-based guidelines and optimizing antibiotic use, healthcare providers can effectively manage infections while minimizing the emergence of antibiotic resistance and reducing the risk of adverse effects for patients.