How prescribing prophylactic antibiotics is driving AMR

Is empiric prescribing of antibiotics as prophylaxis the biggest cause of AMR?

Antimicrobial resistance (AMR) has become one of the defining healthcare threats of the twenty-first century. While public discussion often focuses on inappropriate antibiotic treatment of infections, a substantial and underappreciated contributor to AMR is the routine use of prophylactic antibiotics, particularly in elective surgical care.

Antibiotic prophylaxis has transformed modern medicine by making complex surgery safer and by reducing surgical site infections (SSIs). However, the widespread and often excessive use of prophylactic antibiotics has also created powerful evolutionary pressure favouring resistant organisms. The paradox is striking. The same drugs that enabled modern surgical care are now threatening its long-term sustainability. We have arrived at the stage where cures have become foes.

Healthcare systems increasingly face a difficult balance between preventing immediate postoperative infections and preventing long-term antimicrobial resistance. The costs associated with AMR are no longer theoretical. Hospitals are experiencing longer admissions, increased ICU occupancy, more expensive therapies, greater readmission rates, and rising mortality associated with resistant infections. Insurers and public payers are similarly facing escalating reimbursement costs, chronic disease burdens, litigation risks, and reduced efficiency across surgical pathways.

The challenge is particularly acute in elective surgery, where prophylactic antibiotics are administered to large populations of otherwise healthy patients. In many settings, prophylaxis extends beyond evidence-based recommendations, often continuing for days after surgery despite limited clinical benefit. The problem is not prophylaxis itself. Appropriate prophylaxis remains essential. The problem is unnecessary exposure, prolonged duration, excessive spectrum coverage, and poor stewardship.

The hidden cost of prolonged prophylaxis

The effectiveness of modern surgery depends heavily on reliable antibiotic prophylaxis. SSIs place a major burden on healthcare systems, and antimicrobials have enabled the development of safer patient-care pathways by reducing postoperative infection risks. However, increasing resistance threatens this protection by reducing the effectiveness of prophylactic regimens themselves.

In many hospitals, antibiotic use during surgery is extraordinarily common. Studies suggest that up to 60% of surgical patients receive postoperative antibiotics while hospitalised, and up to 50% are discharged with antibiotics after surgery. Much of this prescribing occurs in situations where evidence shows little or no benefit beyond the perioperative period.

The major stewardship problem in surgical prophylaxis is prolonged use. Numerous studies demonstrate that extending prophylaxis beyond 24 hours rarely reduces infection rates but substantially increases antimicrobial exposure. A recent systematic review found that extending surgical prophylaxis beyond recommended durations did not significantly improve infection outcomes. Yet prolonged prescribing remains common due to habit, fear of complications, medicolegal anxiety, and cultural surgical practices.

Every unnecessary antibiotic exposure creates selective pressure. Sensitive bacteria are eliminated while resistant organisms survive and proliferate. Over time, hospitals accumulate resistant strains including methicillin-resistant Staphylococcus aureus (MRSA), vancomycin-resistant enterococci (VRE), extended-spectrum beta-lactamase (ESBL) organisms, and carbapenem-resistant Enterobacterales (CRE). These organisms fundamentally alter the economics of healthcare delivery.

The hidden cost of prolonged prophylaxis

The direct financial consequences begin with longer admissions. Resistant infections require additional diagnostics, isolation facilities, expensive second-line therapies, and prolonged monitoring. A large English NHS analysis involving more than one million patients found that antimicrobial-resistant infections were associated with an additional 9.2 hospital days and approximately £3,441 additional cost per patient compared with susceptible infections. These figures likely underestimate the true burden because they do not fully capture indirect system pressures such as operating theatre delays, cancelled procedures, or downstream rehabilitation costs.

AMR also significantly increases mortality and readmission rates. Patients with resistant infections experience earlier rehospitalisation and increased long-term mortality compared with patients infected by susceptible organisms. From an insurer or payer perspective, this translates into repeat claims, increased long-term care expenditure, and reduced efficiency of bundled payment systems.

The cost implications become even larger when resistant infections occur after elective surgery. Elective procedures rely on predictable recovery pathways. Resistant postoperative infections disrupt these pathways entirely. A routine hip replacement that would normally involve a two- or three-day stay may become a multi-week admission involving revision surgery, prolonged intravenous antibiotics, rehabilitation, and intensive follow-up care. For hospitals operating under fixed reimbursement models, these complications rapidly erode margins. The reimbursement often remains fixed while treatment costs escalate dramatically.

The economic burden includes:

• Prolonged bed occupancy
• ICU utilisation
• Isolation nursing
• Infectious disease consultation
• Repeat imaging
• Revision surgery
• Expensive reserve antibiotics
• Delayed elective theatre schedules

The operational impact extends beyond the individual patient. Resistant infections create secondary effects throughout healthcare systems. Researchers examining the burden of AMR on surgery patients have highlighted that resistance may eventually alter entire surgical pathways, forcing changes in infection prevention procedures or even reducing access to surgical procedures altogether.

Hospitals already experiencing high AMR burdens frequently implement:

• Enhanced screening programmes
• Preoperative decolonisation
• Isolation protocols
• Expanded environmental cleaning
• Antimicrobial stewardship infrastructure
• Dedicated infection prevention staffing

All of these interventions carry substantial operational costs. Insurers face parallel financial pressures. Resistant infections are associated with:

• Longer claim durations
• More expensive pharmaceutical reimbursement
• Higher readmission rates
• Chronic disability costs
• Increased rehabilitation utilisation
• Greater litigation exposure

The global economic burden is enormous. A recent modelling study estimated that antibiotic resistance was associated with approximately $693bn in hospital costs globally. Another analysis estimated that inpatient care attributable to antibiotic resistance costs roughly $66bn annually worldwide, potentially exceeding $100bn depending on methodology.

Surgical prophylaxis contributes disproportionately because of the sheer volume of exposure. Millions of patients receive antibiotics prophylactically every year, many without individualised risk stratification. Even small reductions in unnecessary exposure could produce major reductions in selective resistance pressure across healthcare systems.

Why overprescribing persists

The behavioural drivers behind excessive prophylaxis are complex. Surgeons naturally fear postoperative infection because SSIs are highly visible complications with significant professional consequences. Extending antibiotics can create a false sense of security even when evidence demonstrates minimal benefit. Defensive medicine also plays a role. Some clinicians prescribe prolonged prophylaxis because they perceive the immediate risk of infection to outweigh the distant and distributed risk of AMR. However, the cumulative effect of millions of these decisions is now becoming visible.

The impact is particularly severe in orthopaedics, cardiothoracic surgery, transplant surgery, oncology surgery, and intensive care settings where resistant infections can be catastrophic. In these populations, resistance often forces the use of last-line antibiotics such as carbapenems, linezolid, daptomycin, or polymyxins. These drugs are more expensive, more toxic, and often less effective than standard prophylactic agents.

The microbiological consequences extend beyond individual patients. Antibiotic exposure disrupts the normal microbiome, facilitating colonisation by resistant organisms and opportunistic pathogens such as Clostridioides difficile. This creates secondary infection burdens that further increase healthcare costs and patient morbidity.

Importantly, AMR also threatens the future viability of elective surgery itself. Much of modern surgery assumes reliable prophylactic protection. If common prophylactic agents become ineffective, risk-benefit calculations for elective procedures may fundamentally change. Procedures currently considered routine may become substantially more dangerous. The situation resembles a slowly deteriorating infrastructure problem. The collapse is not immediate, but the reliability of the system progressively declines.

Preserving the effectiveness of modern surgery

High-performing antimicrobial stewardship programmes attempt to interrupt this trajectory through several core interventions:

• Single-dose prophylaxis protocols
• Automatic stop orders
• Procedure-specific prescribing pathways
• Culture-guided therapy
• Audit and feedback
• Surgeon-specific benchmarking
• Electronic prescribing controls
• Mandatory review at 24 hours

These programmes consistently reduce unnecessary antibiotic exposure without increasing SSI rates. The key principle is precision rather than restriction. Good stewardship is not about withholding antibiotics from patients who need them. It is about ensuring that the narrowest effective agent is used for the shortest effective duration.

In elective surgery, evidence strongly supports:

• Correct timing
• Correct dosing
• Appropriate redosing during prolonged procedures
• Discontinuation within 24 hours for most operations

When these principles are followed consistently, infection outcomes remain favourable while resistance pressure decreases substantially.

The challenge moving forward is cultural as much as scientific. Many surgical prescribing habits are deeply ingrained and reinforced through tradition rather than evidence. Changing these behaviours requires leadership, surveillance data, transparency, and system-level accountability.

Ultimately, AMR arising from prophylactic antibiotic prescribing represents a classic example of cumulative systemic risk. Individual decisions that appear rational at the bedside can collectively produce major long-term harm across healthcare systems.

Without effective stewardship, hospitals and insurers will continue absorbing escalating costs associated with resistant infections, prolonged admissions, expensive therapies, and compromised surgical safety. The sustainability of modern surgery increasingly depends not only on having antibiotics available, but on preserving their effectiveness.

If a “magic potion” prevented 90% of AMR arising from empiric prescribing decisions, what difference would that make to the world, to the costs of healthcare? Imagine a healthcare system in which a new technology, diagnostic platform, or biological intervention could prevent 90% of antimicrobial resistance generated through empiric antibiotic prescribing. Such an innovation would represent one of the most transformative developments in modern medical history.

Empiric prescribing is foundational to clinical medicine. Physicians routinely begin antibiotics before definitive microbiological confirmation because incoming critically ill patients cannot wait for laboratory results. In sepsis, meningitis, severe pneumonia, neutropenic fever, and intra-abdominal infection, delays in treatment can exponentially increase the likelihood of fatal outcomes.

The problem is that empiric prescribing is inherently probabilistic. Clinicians prescribe based on likelihood rather than certainty. To avoid undertreatment, they frequently choose broad-spectrum agents capable of covering multiple potential pathogens. This strategy saves lives but also exposes enormous numbers of patients to unnecessary antimicrobial pressure.

A transformed healthcare system

A magic potion capable of eliminating 90% of the AMR consequences arising from these empiric decisions would fundamentally alter medicine, healthcare economics, and surgical practice. The first impact would be on prescribing confidence. Clinicians could initiate early therapy without the same fear of generating resistance pressure. Broad-spectrum coverage would become less dangerous from a stewardship perspective. This would likely improve clinician willingness to treat aggressively in high-risk patients.

Second, healthcare systems would experience major economic benefits. Hospitals would likely see:

• Reduced AMR-associated admissions
• Shorter lengths of stay
• Lower ICU occupancy
• Fewer isolation requirements
• Reduced pharmacy expenditure on reserve antibiotics
• Fewer revision surgeries
• Lower infection-control costs

Elective surgery pathways would become more reliable and efficient. SSIs caused by resistant organisms would decline dramatically. This would improve:

• Operating theatre throughput
• Bed availability
• Recovery times
• Patient satisfaction
• Procedural capacity

Insurers and public payers would similarly benefit through:

• Fewer high-cost complications
• Lower readmission rates
• Reduced chronic disability claims
• Reduced rehabilitation expenditure
• Improved bundled-payment predictability

The savings could be extraordinary. Given the hundreds of billions currently associated with resistant infections globally, even partial AMR prevention could release substantial healthcare resources for other priorities.

The pharmaceutical landscape would also change significantly. Hospitals currently rely increasingly on expensive reserve antibiotics because older agents are losing effectiveness. If empiric prescribing no longer generated substantial resistance, the lifespan of existing antibiotics could be extended dramatically.

This could reduce:

• Demand for last-line agents
• Emergency antibiotic development costs
• Pharmaceutical supply instability
• Toxic salvage therapies

The implications for surgery would be particularly profound.

Modern surgery depends heavily on confidence in infection prevention. If AMR risk were dramatically reduced, surgeons could operate with far greater certainty regarding prophylactic effectiveness. High-risk procedures involving implants, prosthetics, oncology reconstruction, and transplantation would become safer over the long term.

Hospitals might even expand elective surgical capacity because infection-related bottlenecks would diminish. However, such a magic potion would also create new risks.

The limits of a magic solution

One major concern would be behavioural complacency. If clinicians believed AMR was largely solved, antibiotic overuse could paradoxically increase further. Stewardship discipline might weaken. Prescribing standards could deteriorate. Hospitals might abandon restrictive protocols, potentially generating new forms of resistance outside the potion’s protective mechanism.

Another concern is ecological adaptation. Microorganisms evolve continuously. A system that neutralised 90% of resistance selection pressure would still leave 10% remaining. Given enough exposure and enough time, resistant organisms could eventually adapt around the intervention itself.

This is one of the defining lessons of infectious disease biology: microbial evolution never fully stops. There would also remain important non-prescribing drivers of AMR, including:

• Agricultural antibiotic use
• Environmental contamination
• Poor sanitation
• International transmission
• Counterfeit medicines
• Inadequate infection prevention

Thus, the magic potion would not eliminate AMR entirely. It would instead substantially reduce one of its largest drivers. The greatest long-term impact may actually be psychological and systemic rather than microbiological.

Buying time, not eliminating resistance

Modern medicine currently operates under a growing fear that routine infections may eventually become untreatable. A successful intervention preventing most AMR from empiric prescribing would restore confidence in healthcare systems. It would protect the viability of chemotherapy, transplantation, neonatal care, intensive care medicine, and major surgery.

In many ways, it would buy time. Time for:

• New antibiotic development
• Vaccine expansion
• Precision diagnostics
• Microbiome therapeutics
• Bacteriophage therapy
• AI-guided prescribing
• Global stewardship coordination

Most importantly, it would allow medicine to transition from reactive antimicrobial use toward truly precision-based infectious disease management. The ideal future is not unlimited antibiotic freedom. It is intelligent antimicrobial precision.

Even with a hypothetical breakthrough technology, stewardship would still matter because preserving microbial susceptibility is ultimately a continuous ecological balancing act between human innovation and microbial evolution.

The difference is that healthcare systems would no longer be fighting from a position of accelerating decline. Instead, they would regain strategic control over one of the most important biological challenges in modern medicine.