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Pharmacy Practice in Focus: Health Systems
Pharmacists ensure responsible antibiotic use, combating resistance through tailored therapies.
Image credit: Vitalii Vodolazskyi | stock.adobe.com
Pharmacists play a critical role in the management of antibiotics, particularly as antibiotic resistance continues to rise. Understanding the spectrum of antibiotics, narrow- or broad-spectrum, is essential for pharmacists to make informed decisions in both empirical and definitive therapy. This knowledge enables pharmacists to select the most appropriate treatment for infections, monitor patient outcomes, and adjust therapy as needed. Failure to appropriately target the causative pathogen can lead to increased resistance, treatment failures, and adverse outcomes.
Antibiotics transformed human health by reducing mortality from severe infections, marking their discovery as one of the most impactful scientific medical advancements.1,2 Clinically, the antibiotic spectrum of activity, which defines bacterial pathogen targets and elimination capabilities, is the key to their efficacy.
Antibiotics are classified as broad-spectrum or narrow-spectrum based on their ability to treat different bacterial groups.3 Narrow-spectrum antibiotics treat only very specific bacterial strains, whereas broad-spectrum antibiotics can target a larger range of pathogens.3,4 Understanding the antibiotic’s spectrum is crucial to determine its use as empirical or definitive therapy in clinical practice, but to do so, we need to understand how bacteria are further classified.
Gram-positive bacteria, including species such as Staphylococcus aureus, Streptococcus pneumoniae, and Enterococcus faecium, are clinically significant pathogens that can cause a variety of infections. Gram-positive bacteria have far thicker cell walls than those of gram-negative bacteria, providing structural integrity and protection. This thick peptidoglycan layer is vital for the survival of these organisms, making them a primary target for antibiotics such as β-lactams, which inhibit cell wall synthesis.5-7 In 1995, gram-positive organisms accounted for 62% of all bloodstream infections (BSIs), increasing to 76% by 2000, whereas gram-negative organisms were responsible for 22% and 14% of BSIs in these years, respectively.8-10
The development of antibiotic resistance in gram-positive bacteria is the explanation for this phenomenon. Resistance mechanisms arise primarily through 2 strategies: enzymatic degradation via the production of β-lactamases or by reducing the affinity and susceptibility of their target sites.11-13 According to the 2019 Antibiotic Resistance Threat Report, methicillin-resistant S aureus caused 323,700 infections in hospitalized patients, resulting in 10,000 deaths and a financial burden of $1.7 billion in health care costs. Further, vancomycin-resistant enterococci emerged in the 1990s due to widespread vancomycin use, with over 70% of E faecium now resistant to vancomycin, a foundational antibiotic for these infections.8 Despite ongoing efforts, many gram-positive strains remain resistant, as illustrated in the Figure, which highlights the various antibiotics used against these organisms. It is notable to mention here that cephalosporins lack activity against Enterococcus species due to expression of low-affinity penicillin-binding proteins.14
C difficile, Clostrioides difficile; CFP, cefoperazone; CRE, carbapenem-resistant Enterobacterales; CTX, cerebrotendinous xanthomatosis; ESBL, extended-spectrum β-lactamases; IDSA, Infectious Diseases Society of America; MRSA, methicillin-resistant Staphylococcus aureus; PCN, penicillin; pip/tazo, piperacillin and tazobactam; S maltophilia, Stenotrophomonas maltophilia; SMX/TMP, sulfamethoxazole and trimethoprim; VRE, vancomycin-resistant enterococci.
Antibiotics are not listed in any particular order. This chart is for educational reference. It is not all-inclusive. It is intended as an educational tool to guide practitioners in understanding antibiotic spectrum. Clinical judgment and reference to specific guidelines are essential for optimal therapy selection.
Gram-negative bacteria, such as Escherichia coli, Pseudomonas aeruginosa, and Klebsiella pneumoniae, have a more complex cell envelope, including an outer membrane that acts as a barrier to many antibiotics.15,16 This membrane contributes to the intrinsic resistance of gram-negative bacteria.15,16 Gram-negative bacteria are responsible for a wide array of infections, including urinary tract infections, pneumonia, and bacteremia.7,17
The rising prevalence of antimicrobial resistance among gram-negative bacteria is a critical challenge in clinical practice, which leads to the continual development of novel antibiotics and therapeutic approaches. New resistant strains, specifically those resistant to carbapenems, have emerged and are creating treatment challenges.1,8 Carbapenem-resistant Enterobacterales (CRE) species are often resistant to multiple drug classes, such as β-lactams, fluoroquinolones, and aminoglycosides, owing to the production of carbapenemases—enzymes that degrade carbapenems—combined with porin alterations and efflux pumps.19,20 As a result, treatment options for these resistant strains are limited. However, agents such as ceftazidime-avibactam (Avycaz; AbbVie) and ceftolozane-tazobactam (Zerbaxa; Merck) have proven ef fective against certain carbapenemase-producing strains.19-21 Developing antibiotics that target CRE has become a major focus in the drug development industry.
Gram-negative resistant organisms have become increasingly difficult to treat over the years. Due to this, the Infectious Diseases Society of America releases guidance on the treatment of antimicrobial-resistant gram-negative infections annually.23,24 The Figure illustrates various antibiotics used to combat infections caused by other gram-negative bacteria.
Anaerobes, such as Bacteroides fragilis and Clostridium species, are significant causes in infections in hypoxic environments, such as deep tissue infections or abscesses. Anaerobes play a critical role in various environments, including the human gut, where they contribute to digestion and overall gut health.9 However, they can also become pathogenic, particularly in hypoxic environments such as chronic wounds, where they contribute to persistent infections that are challenging to treat.9 Understanding the metabolic pathways and oxygen tolerance mechanisms of anaerobes is essential for developing effective treatments for infections caused by these organisms.10 Gradually, more resistant strains of anaerobic bacteria are being reported.8 Clostridium perfringens has shown significant resistance to penicillin and clindamycin (Cleocin; Pfizer).11 Over a 13-year study, susceptibility of C perfringens to clindamycin decreased from 91% to 60% whereas penicillin susceptibility dropped from 82.1% to 65.9%.11 Common antibiotics used to treat anaerobic infections include metronidazole (Flagyl; Pfizer), clindamycin, β-lactam/β-lactamase inhibitor combinations, and carbapenems. The Figure illustrates the current medications used to treat infections caused by Clostridium and other anaerobic bacteria.
Atypical bacteria lack conventional cell walls, making β-lactam antibiotics ineffective. Atypical bacteria are not readily classified by traditional Gram staining methods and exhibit unique characteristics that distinguish them from typical bacteria.22,23 Some atypical bacteria, including Mycoplasma pneumoniae, Chlamydia pneumoniae, and Legionella pneumophila, can function as obligate or facultative intracellular pathogens.22,23 Therefore, their ability to reside within host cells makes them more challenging to detect and treat.22,23
Atypical bacteria are difficult to culture using standard laboratory techniques.22,23 Because atypical bacteria are often resistant to β-lactam antibiotics, drugs of choice for these bacteria are macrolides, tetracyclines, and fluoroquinolones.22,23
Antibiotics are lifesaving medications but their effectiveness is threatened by increasing antibiotic resistance. This emphasizes how crucial it is to use antibiotics cautiously to reduce the risk of resistance development. Pharmacists play a pivotal role in the management of bacterial infections through antibiotic stewardship, ensuring that antibiotics are used responsibly and effectively. As medication experts, pharmacists are tasked with overseeing the proper selection, dosing, and duration of antibiotic therapy, tailoring these decisions to the individual patient’ s needs. It is important for pharmacists to know the spectrum of activity of antibiotics to ensure appropriate empiric therapy is selected based on classic pathogens and recognize gaps in antibiotic coverage, should the patient’s status continue to decline.
From an interprofessional perspective, pharmacists play a crucial role in educating both health care providers and patients about the proper use of antibiotics. Pharmacists ensure that antibiotics are not overused, misused, or abused, which is critical in preventing resistance. This education encompasses understanding when antibiotics are necessary and how they should be taken, and the consequences of inappropriate use.
Moreover, pharmacists are actively involved in monitoring antibiotic therapy. This includes tracking adverse effects, interactions, and resistance patterns to ensure that treatment is still safe and effective. They analyze patient-specific factors, such as age, comorbidities, and renal function, to adjust therapy as needed. Additionally, pharmacists stay informed about emerging resistance data, enabling them to suggest prompt modifications to treatment regimens based on the latest evidence. Their interventions not only improve individual patient outcomes but also contribute to the broader goal of reducing antibiotic resistance on a population level.
The spectrum of antibiotics is an important topic due to more agents coming to market, ongoing overuse of broad-spectrum antibiotics, and the array of empiric treatment options with patient-specific factors and sensitivity results when available. Sensitivity results may not be available for days, so pharmacists knowing if the identified pathogen is even covered the current antibiotic is vital.
Kardarius Byes Felton is a class of 2025 PharmD candidate at William Carey University School of Pharmacy in Biloxi, Mississippi. He has interests in infectious disease.
Ron Welch, PharmD, BCPS, BCIDP, is a clinical lead pharmacy specialist at Baptist Memorial Hospital-Golden Triangle in Columbus, Mississippi.
Victoria Byerly, PharmD, is a clinical pharmacist at Methodist Dallas Medical Center in Texas.
Antibiotic resistance is progressively compromising the efficacy of antibiotics, even though they were pivotal in transforming modern medicine. Complex bacterial mechanisms, like those found in gram-positive, gram-negative, and atypical bacteria, are the source of this resistance and call for cautious, customized treatment approaches. In order to ensure appropriate usage, prevent misuse, and modify therapy in light of patient-specific characteristics and developing resistance data, antibiotic stewardship is essential. Personalized and evidence-based treatment is necessary to support the effectiveness of antibiotics, and pharmacists are at the forefront of therapeutic management and education. Knowing the antibiotic spectrum of coverage is crucial for pharmacists to ensure the selection of the most appropriate therapy, optimize treatment efficacy, and minimize the risk of antibiotic resistance.
