SELECT AND USE MEDICATIONS
Antibiotic Classes in Primary Care
Antibiotic classes provide a framework for understanding mechanisms and predictable adverse effects. Individual agents within a class still differ in coverage, tissue penetration, interactions, and clinical usefulness.
Selection should begin with the infection and likely pathogen. The medication’s spectrum and safety profile then determine whether it is an appropriate match (Ratliff & Oliphant, 2026).
Penicillins and Beta-Lactamase Inhibitor Combinations
Beta-lactams bind penicillin-binding proteins and interfere with bacterial cell-wall synthesis. Their activity generally depends on maintaining unbound concentrations above the organism’s minimum inhibitory concentration.
Amoxicillin is useful for selected susceptible respiratory pathogens and streptococcal infections. Clavulanate inhibits certain beta-lactamases and expands coverage against some organisms that would resist amoxicillin alone. It does not overcome every resistance mechanism, and its addition increases gastrointestinal adverse effects.
Amoxicillin-clavulanate may be preferable when beta-lactamase-producing organisms are likely, such as selected cases of bacterial sinusitis or otitis media. It does not provide reliable MRSA or atypical respiratory coverage (Girand, 2026).
Cephalosporins
Cephalosporins also inhibit cell-wall synthesis. Their numbered generations are a general organizing system, but prescribing requires knowledge of the specific drug.
Cephalexin is useful for susceptible streptococci and methicillin-susceptible Staphylococcus aureus in uncomplicated skin infections. Cefuroxime and cefpodoxime have roles in selected respiratory regimens. Ceftriaxone provides a parenteral option for several infections but does not reliably cover MRSA, enterococci, or atypical respiratory pathogens.
A penicillin-allergy label should prompt clarification of the reaction, timing, and severity. Side-chain similarity and reaction phenotype matter. A remote nonspecific rash, immediate anaphylaxis, and a severe cutaneous reaction require different decisions. Low-risk histories may be eligible for structured evaluation or direct oral challenge, whereas severe delayed reactions require specialist-informed avoidance (Centers for Disease Control and Prevention [CDC], 2021; Girand, 2026; Hornecker & Biehle, 2026).
Macrolides
Azithromycin and clarithromycin bind the bacterial 50S ribosomal subunit and inhibit protein synthesis. They provide activity against atypical respiratory pathogens, but pneumococcal resistance limits their use as empiric monotherapy.
Both can contribute to QT prolongation. Clarithromycin has substantial CYP3A-mediated interaction potential; azithromycin generally has fewer metabolic interactions but still requires assessment of cardiac risk and concomitant QT-prolonging drugs.
For community-acquired pneumonia, the acceptability of macrolide monotherapy depends on local pneumococcal resistance and patient characteristics (Cappelletty, 2026).
Tetracyclines
Doxycycline inhibits protein synthesis through the 30S ribosomal subunit. It has roles in chlamydia, selected respiratory infections, and some community-associated MRSA infections.
Its usefulness for MRSA does not establish dependable streptococcal coverage for nonpurulent cellulitis. The clinical syndrome determines whether another agent is needed.
Iron, calcium, magnesium, and aluminum-containing products can reduce absorption. Counsel patients about product-specific separation, taking the medication with sufficient water, remaining upright after administration, and photosensitivity. Pregnancy and pediatric use require indication-specific assessment (Hornecker & Biehle, 2026; Smith & Honeywell, 2026).
Trimethoprim-Sulfamethoxazole
This combination blocks sequential steps in bacterial folate metabolism. It is useful for susceptible urinary pathogens and selected MRSA infections.
Important risks include hypersensitivity, severe skin reactions, marrow suppression, hyperkalemia, and interactions. Hyperkalemia risk increases with kidney dysfunction and medications such as renin-angiotensin system inhibitors or potassium-sparing diuretics.
Trimethoprim may increase serum creatinine by inhibiting tubular secretion, but a creatinine increase should still be evaluated for true kidney injury. Review renal dosing and clinically consequential interactions, including warfarin and methotrexate (Durham, 2026; Hornecker & Biehle, 2026).
Fluoroquinolones
Fluoroquinolones inhibit bacterial DNA gyrase and topoisomerase IV. Their oral bioavailability and tissue penetration can be useful in selected infections.
Agents are not interchangeable. Ciprofloxacin is not a respiratory fluoroquinolone, and moxifloxacin is not an appropriate choice for routine urinary infection.
Potential harms include tendinopathy, neuropathy, central nervous system effects, dysglycemia, QT prolongation, and Clostridioides difficile infection. These risks favor alternative agents for uncomplicated infections when an effective, safer option is available. Polyvalent cations also reduce absorption (Cappelletty, 2026; Durham, 2026).
Clindamycin
Clindamycin inhibits protein synthesis at the 50S subunit. It covers selected gram-positive organisms and anaerobes, but local resistance and inducible resistance may limit its usefulness.
When an isolate is erythromycin-resistant and apparently clindamycin-susceptible, inducible resistance testing may affect treatment selection. Its substantial C. difficile risk is an important consideration when alternatives are available (Hornecker & Biehle, 2026).
Urinary-Focused Agents
Nitrofurantoin and oral fosfomycin are useful for selected lower urinary infections. Their role depends on the infection being confined to the bladder.
Neither should be selected for pyelonephritis solely because a urine isolate is susceptible. Renal tissue exposure and systemic illness change the treatment requirement. Nitrofurantoin also requires assessment of kidney function and consideration of pulmonary, hepatic, and neurologic toxicity, especially with prolonged exposure (Durham, 2026).
Monitoring and Clinical Application
For every prescription, document the indication, relevant patient risks, regimen, expected response, and follow-up. Laboratory monitoring should reflect the medication and duration rather than be ordered indiscriminately.
A susceptible-organism report supports selection only when the agent also fits the infection site, patient, and clinical evidence.
Related YourDNP Resources
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References
Centers for Disease Control and Prevention. (2021, July 22). Penicillin allergy. https://www.cdc.gov/std/treatment-guidelines/penicillin-allergy.htm
Cappelletty, D. M. (2026). Lower respiratory tract infections. In M. A. Chisholm-Burns, P. M. Malone, J. M. Kolesar, K. C. Lee, P. B. Bookstaver, & K. R. Matthias (Eds.), Pharmacotherapy principles & practice (7th ed.). McGraw Hill.
Durham, S. H. (2026). Urinary tract infections. In M. A. Chisholm-Burns, P. M. Malone, J. M. Kolesar, K. C. Lee, P. B. Bookstaver, & K. R. Matthias (Eds.), Pharmacotherapy principles & practice (7th ed.). McGraw Hill.
Girand, H. L. (2026). Upper respiratory tract infections. In M. A. Chisholm-Burns, P. M. Malone, J. M. Kolesar, K. C. Lee, P. B. Bookstaver, & K. R. Matthias (Eds.), Pharmacotherapy principles & practice (7th ed.). McGraw Hill.
Hornecker, J. R., & Biehle, L. R. (2026). Skin and skin structure infections. In M. A. Chisholm-Burns, P. M. Malone, J. M. Kolesar, K. C. Lee, P. B. Bookstaver, & K. R. Matthias (Eds.), Pharmacotherapy principles & practice (7th ed.). McGraw Hill.
Ratliff, A., & Oliphant, C. (2026). Patient assessment, antimicrobial selection, and stewardship. In M. A. Chisholm-Burns, P. M. Malone, J. M. Kolesar, K. C. Lee, P. B. Bookstaver, & K. R. Matthias (Eds.), Pharmacotherapy principles & practice (7th ed.). McGraw Hill.
Smith, U. D., & Honeywell, M. S. (2026). Sexually transmitted infections. In M. A. Chisholm-Burns, P. M. Malone, J. M. Kolesar, K. C. Lee, P. B. Bookstaver, & K. R. Matthias (Eds.), Pharmacotherapy principles & practice (7th ed.). McGraw Hill.