Local antibiotic delivery with gentamicin has been part of orthopaedic infection management for decades. Its persistence is striking because the scientific framing of infection has changed. Biofilm biology is now central, resistance patterns have evolved, and carrier materials have diversified. The more revealing question is not whether gentamicin can work, but why it became the default, and why that default has been so durable.
Summary
Early local antibiotic approaches existed, but reproducible delivery was the constraint, not choice of drug.
PMMA cement made local delivery practical, and gentamicin fit PMMA unusually well.
Biofilm research shifted expectations of what local antibiotics can achieve, without dislodging entrenched choices.
The durability of gentamicin appears to reflect feasibility and pathway lock-in more than extensive head-to-head comparative testing.
Why this matters
Local antibiotic delivery is used as an adjunct in orthopaedic infection surgery because dead space and poor perfusion limit the reliability of systemic antibiotics alone. That underlying surgical reality has not changed. What has changed is the knowledge base around microbial persistence and the range of available carrier concepts. When practice remains stable while underlying assumptions evolve, it becomes harder to know which parts of the pathway are evidence-driven and which are historical inheritance.
What the evidence shows
Local antibiotics were tried before PMMA, but delivery was not standardised
Before antibiotic-loaded cement, surgeons already attempted local strategies, including closed irrigation approaches using antibiotic solutions as part of managing chronic osteomyelitis and infected wounds (Compere, 1962).
These approaches reflect a consistent problem statement: after debridement, the cavity and surrounding tissue remain biologically difficult terrain for systemic therapy. What they did not offer was a simple, reproducible method for delivering a sustained local antimicrobial effect within the surgical reconstruction problem.
PMMA made local delivery practical, and gentamicin fit the material constraints
The conceptual shift was not simply “using antibiotics locally” but using a solid implantable carrier. Buchholz and Engelbrecht reported mixing antibiotics with acrylic cement in 1970, establishing the idea of PMMA as an antibiotic depot (Buchholz and Engelbrecht, 1970, cited in Hendriks et al., 2004).
Early experimental work then specifically demonstrated gentamicin release from PMMA and measurable absorption, helping define gentamicin as a workable cement-compatible agent (Wahlig and Buchholz, 1972).
By 1980, comparative studies of antibiotics and cements showed that gentamicin in Palacos could produce high and prolonged local concentrations and remain stable within the cement, reinforcing its operational attractiveness (Wahlig and Dingeldein, 1980).
In parallel, Klemm’s work made the concept surgically tangible through gentamicin-loaded PMMA beads and chains placed after debridement as a supplementary element within complex infection surgery (Klemm, 1977; Klemm, 1979).
The key point is that gentamicin’s early dominance followed from compatibility and practicality as much as from microbiological argument.
Biofilm research changed expectations of antibiotics, without undoing the path dependency
Biofilm research reframed chronic implant and bone infection by showing that bacteria in structured communities can display reduced susceptibility to antimicrobials and behave differently from planktonic bacteria (Costerton et al., 1999).
This did not make local antibiotics irrelevant, but it did shift what they could plausibly be expected to do. In practice, local gentamicin increasingly functioned as a supportive adjunct within a debridement-led strategy rather than as a standalone “biofilm eraser”.
The durability of gentamicin persisted into newer carriers, with limited comparative testing
Even as biodegradable local antibiotic carriers emerged, gentamicin often remained the loaded agent by default. Modern clinical series using gentamicin-loaded absorbable carriers describe high rates of infection control in chronic osteomyelitis when embedded in a structured surgical protocol (McNally et al., 2016).
Where the literature becomes particularly interesting is that, in at least one cohort, recurrence did not appear higher when organisms were reported intermediate or resistant to gentamicin, suggesting that susceptibility testing and local delivery context do not map cleanly onto each other (McNally et al., 2022).
This is not proof that resistance is unimportant. It is a sign that the clinical meaning of “resistant” becomes harder to interpret when exposure conditions differ drastically from systemic dosing.
Mechanisms behind the pattern
Gentamicin’s persistence is best explained as a systems story. An agent that fits PMMA well becomes easy to manufacture, standardise, teach, and regulate. Once embedded, the clinical pathway stabilises around it. When outcomes are heavily driven by debridement quality, fixation, soft tissue management, and host factors, the pressure to run head-to-head comparisons between local agents is low, even if the question remains scientifically unresolved.
Practical implications for clinical interpretation
Long-standing use is compatible with effectiveness, but does not demonstrate optimality.
Local gentamicin is best understood as part of an integrated surgical strategy rather than a separable single-variable intervention (Klemm, 1979; McNally et al., 2016).
Biofilm biology supports caution in assuming local antibiotics can compensate for inadequate debridement (Costerton et al., 1999).
When susceptibility results and clinical outcomes diverge, the issue may be context mismatch rather than laboratory error (McNally et al., 2022).
Common pitfalls
Treating “used for decades” as evidence of superiority rather than evidence of adoption and standardisation.
Assuming local gentamicin is intended to eradicate established biofilm on its own.
Interpreting systemic susceptibility breakpoints as directly predictive of local-delivery contexts.
Conflating a workable carrier-drug pairing with a biologically optimised strategy.
Closing note
Gentamicin became dominant because it solved a practical delivery problem when orthopaedic infection surgery needed a reproducible adjunct. The unresolved question is not whether this choice can work, but why it has rarely been forced to compete, given how much the underlying understanding of infection has shifted.
References
Compere EL. Treatment of osteomyelitis and infected wounds by closed irrigation with a detergent-antibiotic solution. Acta Orthop Scand. 1962;32:324–333. doi:10.3109/17453676208989589.
Buchholz HW, Engelbrecht H. Depot effects of various antibiotics mixed with Palacos resins. Der Chirurg. 1970;41(11):511–515. Cited in: Hendriks JGE, et al. Injury. 2004.
Wahlig H, Buchholz HW. Experimental and clinical studies on the release of gentamicin from bone cement. Chirurg. 1972;43(10):441–445. PMID:5084869.
Wahlig H, Dingeldein E. Antibiotics and bone cements. Experimental and clinical long-term observations. Acta Orthop Scand. 1980;51(1):49–56. doi:10.3109/17453678008990768.
Klemm K. Gentamicin-PMMA beads in treating bone and soft tissue infections. Zentralbl Chir. 1979;104(14):934–942. PMID:494865.
Klemm K. Gentamycin-PMMA beads in treating bone and soft tissue infections. Langenbecks Arch Chir. 1977;344:1–8.
Costerton JW, Stewart PS, Greenberg EP. Bacterial biofilms: a common cause of persistent infections. Science. 1999;284(5418):1318–1322. doi:10.1126/science.284.5418.1318.
McNally MA, Ferguson JY, Lau ACK, et al. Single-stage treatment of chronic osteomyelitis with an absorbable gentamicin-loaded biocomposite: a prospective series of 100 cases. Bone Joint J. 2016;98-B(9):1289–1296. doi:10.1302/0301-620X.98B9.38057.
McNally MA et al. Single-stage treatment of chronic osteomyelitis with a bioabsorbable gentamicin-loaded ceramic carrier: mid- to long-term results. Bone Joint J. 2022.