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once the forefront and quintessence of modern medicine, are unfortunately progressing at a pace that has been superseded by the advent of new antibiotic resistance mechanisms poised by bacteria.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
An Overview of Hospital Acquired Pneumonia (HAP):
Hospital-acquired pneumonia (HAP) is defined as pneumonia that develops more than 48 hours after a patient is admitted to the hospital. This category includes both hospital acquired pneumonia (HAP) and ventilator-associated pneumonia (VAP).
Some risk factors include older age, chronic lung disease, depressed consciousness, aspiration, agents that increase gastric pH (H2 blockers, antacids, proton pump inhibitors, previous antibiotic exposure (especially broad spectrum), prolonged intubation, paralysis, total opioid exposure, etc. Furthermore, additional risk factors include immunosuppressive populations such as those with AIDS, organ transplant recipient, chronic steroid usage, and hyperglycemia with blood glucose >180 mg/dL in hospitalized patients.
Most common pathogens include streptococcus pneumoniae, haemophilus influenzae, enteric gram-negatives (E.Coli, Klebsiella, Proteus), ESBL- producing organisms, and pseudomonas species. Risk factors for MDR pathogens (including Pseudomonas aeruginosa, other gram-negative bacilli and methicillin-resistant S. aureus (MRSA) include intravenous (IV) antibiotic use within the previous 90 days, septic shock at the time of VAP, acute respiratory distress syndrome (ARDS) preceding VAP, >5 of hospitalization prior to the occurrence of VAP, and acute renal replacement therapy prior to VAP onset.
Additionally, risk factors for MRSA include treatment in a unit in which >20% of S. Aureus isolates associated with HAP are methicillin resistant, treatment in a unit in which the prevalence of MRSA is not known, colonization with and/ or prior isolation of MRSA on culture at any body site (especially the respiratory tract).
A clinical presentation of Hospital Acquired Pneumonia (HAP) can be described as fever, cough, shortness of breath and increased sputum production and an elevated white blood cell count. Clinical manifestations vary based on the causative pathogen and patients health status. Lab abnormalities include leukocytosis (WBC >11,000 cells/uL or leukopenia (WBC < 4,000 cells/uL), bandemia (>10% bands or immature white blood cells), and septic shock (may cause multi-organ dysfunction (elevated BUN, creatinine, liver enzymes, INR, acidosis, thrombocytopenia). Imaging may convey new or progressive consolidation or infiltrates, sputum cultures for bacterial pneumonia portray moderate WBC counts with positive Gram stain and culture results, two sets of blood cultures are recommended for VAP; 15% of patients may have bacteremia, and bronchoscopy or other invasive cultures should be considered for severe pneumonia not responding to empiric regimens.
Treatment Overview:
The selection of therapy for hospital-acquired pneumonia (HAP) is based on several criteria, including the patient's history of colonization with or prior isolation of multidrug-resistant (MDR) gram-negative bacilli. Patients without such a history may be treated with Piperacillin-tazobactam or Cefepime. Additionally, if MRSA risk factors are present, anti-MRSA therapy should be initiated. For patients without a history of colonization with or prior isolation of MDR gram-negative bacilli and no prior culture history of carbapenemase-resistant pathogens, options include Ceftazidime-avibactam, Ceftolozane-tazobactam, Impipenem-cilastatin-relebactam, and Meropenem-vaborbactam. Patients with no prior culture history of carbapenamase- resistant pathogens may also be treated with Meropenem or Imipenem-cilastatin.
To continue with the treatment for HAP, patients with risk factors for mortality and no prior culture history of carbapenemase-resistant pathogens can be treated with Meropenem or Imipenem-cilastatin, in addition to one of the following: Vancomycin or Linezolid. On the other hand, patients presenting with risk factors for mortality and carbapenemase-resistant pathogens may be treated with Ceftazidime-avibactam, Ceftolozane-tazobactam, Imipenem-cilastatin-relebactam, or Meropenem-vaborbactam, along with one of the following Vancomycin or Linezolid. Typically, Vancomycin therapy involves administering 15-20 mg/kg every 8 to 12 hours for most patients with normal kidney function, while Linezolid is typically administered at 600 mg IV every 12 hours.
Supportive Care & Conclusion:
Supportive care is crucial in the management of hospital-acquired pneumonia (HAP). This includes maintaining proper hydration, ensuring adequate nutrition, and providing supplemental oxygen as needed to maintain optimal oxygen levels.
As pharmacists, it is essential to spread education and awareness regarding pneumococcal and influenza vaccinations. Pneumococcal vaccination is recommended for all patients aged 65 years and older, as well as those with specific risk factors, such as chronic heart, lung, and liver diseases, immunocompromised conditions, and impaired splenic function. Additionally, encouraging smoking cessation and fall prevention are key strategies in reducing the risk and severity of HAP.
References:
BrozekHospital-acquired and ventilator-associated pneumonia (HAP/VAP). https://www.idsociety.org/practice-guideline/hap_vap/
UpToDate. (n.d.). UpToDate. https://www.uptodate.com/contents/treatment-of-hospital-acquired-and-ventilator-associated-pneumonia-in-adults