Analgesics and Dentistry: Addressing the Silent Driver of Resistance

By Ayesha Khan, MD, MBA

Antimicrobial resistance (AMR) is a critical global health crisis, ranked by the WHO among the top ten threats to humanity. A 2019 Lancet analysis attributed 1.27 million deaths worldwide to bacterial AMR—exceeding those from HIV/AIDS and malaria.

Dentistry is a significant contributor to outpatient antibiotic use: U.S. dentists issue nearly 25 million prescriptions annually (≈10% of total), with similar 7–10% rates across Europe. Alarmingly, CDC data suggests that up to 80% of dental prescriptions are inappropriate, often for conditions better managed operatively.

Beyond antibiotic misuse, growing evidence implicates non-antibiotic medications—including widely used analgesics such as ibuprofen, acetaminophen/paracetamol, and diclofenac—in shaping bacterial behavior and potentially fostering resistance. As these agents are commonly prescribed or recommended for postoperative pain, their role as hidden drivers of AMR warrants critical attention within dental practice.

Linking Analgesics to Antibiotic Resistance

Although analgesics are not designed to exert antibacterial activity, experimental data demonstrate that certain agents can influence microbial survival and adaptability in indirect ways:

Modulation of Efflux Pumps: A 2025 study in npj Antimicrobials and Resistance demonstrated that exposure of Escherichia coli and Staphylococcus aureus to sub-therapeutic concentrations of NSAIDs may induce expression of efflux pumps and stress response pathways. The in vitro investigation demonstrated that ibuprofen at clinically relevant concentrations led to a two- to fourfold increase in the minimal inhibitory concentrations (MICs) of fluoroquinolones against E. coli. The proposed mechanism involves competitive inhibition of bacterial DNA gyrase binding, leading to selection of resistant mutants. Though modeled in vitro, these findings suggest that common over-the-counter analgesics may accelerate resistance under antibiotic pressure, particularly in polypharmacy settings.

Induction of Oxidative Stress Responses: Acetaminophen, when metabolized, can generate reactive oxygen species and alter bacterial stress pathways. This phenomenon aligns with prior evidence that certain NSAIDs activate stress regulons (e.g., MarA), upregulate AcrAB-TolC, and elevate MICs across drug classes.

Biofilm Formation: Certain NSAIDs have been observed to affect quorum sensing and biofilm production. Enhanced biofilm formation can shield bacteria from antibiotic penetration, promoting tolerance.

Horizontal Gene Transfer: There is emerging evidence that non-antibiotic pharmaceuticals may increase bacterial membrane permeability or DNA uptake, thereby facilitating horizontal gene transfer of resistance determinants. Although research is ongoing, these findings suggest that analgesic prescribing may have unforeseen ecological consequences.

What Does This Mean in a Dental Setting?

1) Analgesia remains first-line—but pair it with procedure-first care, not reflex antibiotics

The CDC and ADA’s evidence-based guideline (2019) advises against routine antibiotic use for most pulpal and periapical conditions, especially in immunocompetent adults, recommending instead definitive dental interventions (e.g., pulpotomy, pulpectomy, nonsurgical root canal therapy, or incision and drainage) combined with over-the-counter analgesics such as acetaminophen and/or ibuprofen. Reserve antibiotics for systemic involvement (fever, malaise) or spreading infection. This approach already minimizes unnecessary antibiotic exposure; the new data provide additional incentive to avoid casual antibiotic–analgesic co-exposure.

2) Choose analgesics judiciously

NSAIDs (e.g., ibuprofen 400–600 mg every 6–8 hours) in combination with acetaminophen (500–1000 mg every 6 hours, mindful of maximum daily dose) provide superior pain relief after routine dental surgery than opioids, with fewer adverse effects. However, prolonged or unnecessary use of NSAIDs may select for resistant organisms in the gut and oral flora; therefore, prescribe the lowest effective dose for the shortest feasible duration.

3) Be mindful of timing and necessity when antibiotics are indicated

Dentists rarely prescribe fluoroquinolones like ciprofloxacin, but the mechanistic pathways noted—efflux pump up-regulation and mutation under stress—are not drug-class specific and could conceptually influence responses to other antibiotics. If antibiotics are warranted (e.g., cellulitis, systemic signs), document indication, microbiologic target, narrow spectrum, and shortest effective duration; schedule a 72-hour reassessment and instruct discontinuation 24 hours after symptom resolution when appropriate.

4) Screen and document antibiotic allergies thoroughly

Approximately 10% of patients report a penicillin allergy, yet over 90% of them are not truly allergic upon testing. Mislabeling often drives use of clindamycin, which carries a high risk of C. difficile infection and contributes disproportionately to resistance. When possible, verify allergy status and consider alternative penicillin-class antibiotics if safe.

5) Keep efficacy high while avoiding polypharmacy pitfalls

Counsel patients to avoid unnecessary additional OTCs (e.g., decongestants, sedatives) that can contribute to polypharmacy, and not to self-start leftover antibiotics. Review the patient’s medication list (including OTCs). The 2025 npj data showed amplified resistance when multiple non-antibiotic meds were combined with antibiotics—common in older adults. Coordinate with the patient’s physician when complexity is high.

6) Educate patients

A 2018 Journal of the American Dental Association survey found that 42% of dentists felt pressured by patients to prescribe antibiotics. Patients may expect antibiotics for a toothache or post-operative discomfort. Clear communication about the viral versus bacterial nature of conditions, the role of local treatment, and the efficacy of non-antibiotic analgesia is essential. Incorporating evidence-based guidelines—such as those from the American Dental Association (2019), which recommend against antibiotics for most pulpal and periapical conditions—strengthens clinical decision-making and fosters patient trust. In practice, this may involve explaining that a properly performed extraction plus ibuprofen/acetaminophen often controls pain and swelling as effectively as antibiotics, without contributing to resistance.

The Path Forward

The intersection between analgesic prescribing and antimicrobial resistance adds a new dimension to the stewardship responsibilities of dental practitioners. While the direct contribution of non-antibiotic analgesics such as ibuprofen and acetaminophen to resistance remains under investigation, the available evidence suggests these drugs can influence bacterial physiology in ways that may indirectly encourage resistance.

Dentists can play a pivotal role in mitigating this threat by adhering to evidence-based prescribing guidelines, promoting alternatives to systemic antibiotics where appropriate, and engaging patients in shared decision-making about pain control strategies. Moreover, incorporating discussions of non-antibiotic drug effects into continuing professional development will strengthen our collective capacity to deliver effective, sustainable, and safe care.

References:

1. Chen H, Sapula SA, Turnidge J, Venter H. The effect of commonly used non-antibiotic medications on antimicrobial resistance development in E. coli. npj Antimicrobials and Resistance. Published Aug 25, 2025.
2. ADA clinical guideline: Antibiotics for Dental Pain and Swelling (2019) and CDC/ADA stewardship summary.
3. Non-antibiotic pharmaceuticals and conjugative transfer at community scale. Microbiome (2022).
4. Background on NSAIDs and efflux-mediated cross-resistance. FEMS Microbiology Letters (2018).
5. Global burden of AMR (Lancet 2022; WHO fact sheet 2023).
6. Ramanathan, S., Yan, C. H., Hubbard, C., Calip, G. S., Sharp, L. K., Evans, C. T., ... & Suda, K. J. (2023). Changes in antibiotic prescribing by dentists in the United States, 2012–2019. Infection Control & Hospital Epidemiology, 44(11), 1725-1730.
7. Al-Khatib, A., & AlMohammad, R. A. (2022). Dentists’ habits of antibiotic prescribing may be influenced by patient requests for prescriptions. International Journal of Dentistry, 2022(1), 5318753.

Author: Ayesha Khan, MD, MBA, is a registered physician, former research fellow, and enthusiastic blogger. With a wide range of articles published in renowned newspapers and scientific journals, she covers topics such as nutrition, wellness, supplements, medical research, and alternative medicine. Currently serving as the Vice President of Social Communications and Strategy at Renaissance, Ayesha brings her expertise and strategic mindset to drive impactful initiatives. Follow her blog for insightful content on healthcare advancements and empower yourself with knowledge.