Local antibiotic delivery with gentamicin has been part of orthopaedic infection management for decades. Gentamicin is still used despite major advances in the understanding of biofilm-associated infection and the development of new carrier materials. Biofilm biology is now central, and carrier materials have diversified. Gentamicin became the default local antibiotic because its properties suited PMMA and because products, surgical techniques and clinical experience developed around that combination.
Summary
Early local antibiotic approaches existed, but reproducible delivery was the constraint, not the choice of drug.
PMMA cement made local delivery practical, and gentamicin fitted PMMA unusually well.
Biofilm research clarified the limits of antibiotic treatment, but gentamicin continued to be used in established local-delivery systems.
Gentamicin’s continued use is supported by feasibility, established products and clinical experience, while direct comparisons with other local antibiotics are limited.
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 (Metsemakers et al., 2020). That underlying surgical reality has not changed. What has changed is the knowledge base around microbial persistence and the range of available carrier concepts. Gentamicin’s widespread use reflects both published clinical experience and the early standardisation of gentamicin-loaded PMMA.
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 addressed the difficulty of achieving adequate antibiotic exposure in poorly perfused tissue and residual cavities after debridement. They did not provide a simple implantable carrier capable of sustained antibiotic release within the treated defect.
PMMA made local delivery practical, and gentamicin fitted the material constraints
PMMA introduced a solid implantable carrier for local antibiotic delivery. Buchholz and Engelbrecht reported mixing antibiotics with acrylic cement in 1970, establishing the idea of PMMA as an antibiotic depot (Buchholz and Engelbrecht, 1970).
Early experimental work specifically demonstrated gentamicin release from PMMA, helping to establish gentamicin as a workable cement-compatible agent (Wahlig and Buchholz, 1972).
By 1980, studies of antibiotics and cements had shown that gentamicin in Palacos produced high and prolonged local concentrations and remained stable within the cement (Wahlig and Dingeldein, 1980).
Klemm subsequently used gentamicin-loaded PMMA beads and chains after debridement as an adjunct in the surgical treatment of bone and soft-tissue infection (Klemm et al., 1977; Klemm, 1979).
Gentamicin’s early dominance followed from compatibility and practicality as much as from microbiological argument.
Biofilm research clarified the limits of antibiotic treatment
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”.
Gentamicin continued to be used in newer carriers, with limited comparative testing
As biodegradable local antibiotic carriers emerged, gentamicin was also incorporated into these newer systems. 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).
In one cohort, recurrence was not significantly more frequent when organisms showed intermediate or high-grade resistance 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 became established through its use in PMMA beads, chains and spacers. Compatibility with PMMA supported reproducible manufacture, standardisation and clinical use. Outcomes in bone infection also depend on debridement, fixation, soft-tissue management and host factors, which makes the independent effect of the selected local antibiotic difficult to determine. High-quality clinical evidence on local antibiotic therapy is limited (Hake et al., 2015).
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 that local antibiotics can compensate for inadequate debridement (Costerton et al., 1999; Metsemakers et al., 2020).
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. Gentamicin has extensive clinical use, but direct evidence that it is superior to other antibiotics for local delivery is limited.
References
Buchholz HW, Engelbrecht H. [Depot effects of various antibiotics mixed with Palacos resins]. Chirurg. 1970;41(11):511–515.
Compere EL. Treatment of osteomyelitis and infected wounds by closed irrigation with a detergent-antibiotic solution. Acta Orthop Scand. 1962;32:324–333.
Costerton JW, Stewart PS, Greenberg EP. Bacterial biofilms: a common cause of persistent infections. Science. 1999;284(5418):1318–1322.
Hake ME, Young H, Hak DJ, Stahel PF, Hammerberg EM, Mauffrey C. Local antibiotic therapy strategies in orthopaedic trauma: practical tips and tricks and review of the literature. Injury. 2015;46(8):1447–1456.
Klemm K, Dingeldein E, Wahlig H. Gentamycin-PMMA-Kugeln für die lokale Infekttherapie. Langenbecks Arch Chir. 1977;345:639.
Klemm K. [Gentamicin-PMMA beads in treating bone and soft-tissue infections]. Zentralbl Chir. 1979;104(14):934–942.
McNally MA, Ferguson JY, Lau ACK, Diefenbeck M, Scarborough M, Ramsden AJ, Atkins BL. Single-stage treatment of chronic osteomyelitis with a new absorbable, gentamicin-loaded, calcium sulphate/hydroxyapatite biocomposite: a prospective series of 100 cases. Bone Joint J. 2016;98-B(9):1289–1296.
McNally MA, Ferguson JY, Scarborough M, Ramsden A, Stubbs DA, Atkins BL. Mid- to long-term results of single-stage surgery for patients with chronic osteomyelitis using a bioabsorbable gentamicin-loaded ceramic carrier. Bone Joint J. 2022;104-B(9):1095–1100.
Metsemakers WJ, Fragomen AT, Moriarty TF, Morgenstern M, Egol KA, Zalavras C, Obremskey WT, Raschke M, McNally MA. Evidence-based recommendations for local antimicrobial strategies and dead space management in fracture-related infection. J Orthop Trauma. 2020;34(1):18–29.
Wahlig H, Buchholz HW. [Experimental and clinical studies on the release of gentamicin from bone cement]. Chirurg. 1972;43(10):441–445.
Wahlig H, Dingeldein E. Antibiotics and bone cements: experimental and clinical long-term observations. Acta Orthop Scand. 1980;51(1):49–56.