Discussion

Osteomyelitis of the frontal bone is a rare but devastating complication of chronic rhinosinusitis. The frontal bone is the second most common site of head and neck osteomyelitis, with the mandible most frequently affected.^{Reference Prasad, Prasad, Mouli and Agarwal5} Because of the complex craniofacial skeleton and critical neural structures that cannot be easily debrided, osteomyelitis of the fronto-ethmoid region presents particular management challenges.^{Reference Pincus, Armstrong and Thaller6}

The presentation of chronic frontal osteomyelitis, as in our cases, is often with a sinocutaneous fistula as well as pain, swelling and a low-grade fever. It can lead to complications such as meningitis, brain abscess, including Pott's puffy tumour,^{Reference Thompson, Tilak, Miller, Grayson, Cho and Woodworth7} and cavernous sinus thrombosis.^{Reference Prasad, Prasad, Mouli and Agarwal5} This is a potentially life-threatening inflammatory condition, and therefore it requires early diagnosis and management to reduce morbidity and mortality.^{Reference Masters, Trombetta, de Mesy Bentley, Boyce, Gill and Gill8}

Classical treatment of chronic frontal osteomyelitis involves surgical debridement and long-term antibiotic therapy. Other interventions include frontal sinus trephining, particularly for the initial drainage of infected material, catheter irrigation and antibiotic delivery systems. As the inflammatory process causes compression and obliteration of the vasculature, ischaemia occurs, which contributes to necrosis of the bone. Sequestra arise as a result of separation of the segments of bone devoid of blood supply. These avascular areas need to be debrided. If complete excision is not possible, these areas can continue to harbour bacteria despite antibiotic treatment, contributing to the difficulty in achieving complete resolution.^{Reference Lew and Waldvogel1,Reference Varvares, Lin, Hadlock, Azzizadeh, Gliklich and Rounds9}

The recurrence rates of chronic frontal osteomyelitis are high, resulting in significant morbidity. Additionally, given the high economic burden of current treatment, novel approaches are required.^{Reference Masters, Trombetta, de Mesy Bentley, Boyce, Gill and Gill8} The local delivery of antibiotics in the treatment of osteomyelitis has been used safely and effectively by orthopaedic surgeons for decades.^{Reference Ostermann, Seligson and Henry4} The most commonly used antibiotics are aminoglycosides, such as gentamicin and tobramycin, which are effective in the management of aerobic gram-negative bacilli and staphylococci as well as streptococci, enterococci and anaerobes.^{Reference DeCoster and Bozorgnia10}

In 1979, Klaus Klemm created gentamicin-impregnated beads. These were used to occupy dead space after debridement of infected bone. Klemm reported that in a sample of over 100 patients, a cure rate of 91.4 per cent was achieved following this treatment.^{Reference Nelson11} Hoff et al.^{Reference Hoff, Fitzgerald and Kelly12} demonstrated that the antibiotic delivery from local antibiotic beads provides significantly higher concentration levels in desired tissues than achieved by systemic therapy.^{Reference Hoff, Fitzgerald and Kelly12} Given that both S aureus and S epidermidis are known to form biofilms that act as a barrier to antibiotics, this higher concentration is of particular value.^{Reference Lew and Waldvogel1} It has been shown that concentrations 10 to 100 times that usually needed to be bactericidal are required to kill bacteria enclosed by biofilm.^{Reference Nelson11} Wahlig et al.^{Reference Wahlig, Dingeldein, Bergmann and Reuss13} showed that when polymethylmethacrylate beads with gentamicin incorporated are implanted into bone and the wound closed, the local concentrations of antibiotic achieved are 200 times those achieved with the administration of systemic antibiotic.^{Reference DeCoster and Bozorgnia10,Reference Wahlig, Dingeldein, Bergmann and Reuss13}

Several different bead compositions have been described including polymethylmethacrylate and calcium sulphate.^{Reference DeCoster and Bozorgnia10} The variations in these, including bead size and the number of beads used, all influence the local dose achieved, and further research is required to ascertain exact dosing in each scenario.

The beads, when made of polymethylmethacrylate, have classically been removed in a second stage procedure, approximately three weeks after implantation.^{Reference DeCoster and Bozorgnia10} This was based on a concern that they could act as a substratum for bacteria, particularly once drug elution has ended, and add to the development of bacterial resistance. A case report demonstrated measurable but sub-inhibitory levels of gentamicin five years after the placement of the beads with subsequent isolation of gentamicin-resistant bacteria.^{Reference Fernando, Werner, Elhaddad, Davies and Firoozabadi14} Fernando et al. tested whether polymethylmethacrylate beads required removal. They found that where the wound had healed well and where there was sufficient subcutaneous tissue to cover the beads to prevent pain, the beads could be left with no complications detected in their follow-up period of 6 months to 5 years.^{Reference Fernando, Werner, Elhaddad, Davies and Firoozabadi14} The intention in both of our cases was to leave the polymethylmethacrylate beads in-situ indefinitely. Additionally, they reported that no patients developed antibiotic resistance.^{Reference Fernando, Werner, Elhaddad, Davies and Firoozabadi14} Beads made from calcium sulphate or phosphate also exist; these biodegrade and do not require removal.^{Reference DeCoster and Bozorgnia10}

There have been reports of the use of antibiotic-impregnated beads made from polymethylmethacrylate powder and gentamicin for the treatment of infected nasal implants. Villanueva et al.^{Reference Villanueva, Martin, Martinkovich and Blomain15} used this approach in conjunction with a continuous catheter-based antibiotic irrigation system and systemic antibiotics. This enabled a two-stage procedure in removal of the beads, and reconstruction was performed after resolution of the infection.^{Reference Villanueva, Martin, Martinkovich and Blomain15}

To the best of our knowledge, there are no reported cases of antibiotic-impregnated bead use in the management of frontal osteomyelitis secondary to chronic rhinosinusitis. Given the already existing space within the frontal sinus, which is then enlarged following surgical debridement, there is an excellent cavity for the placement of the impregnated beads to facilitate local delivery of antibiotics. Antibiotic beads have the advantage of also helping through eliminating dead space.^{Reference Villanueva, Martin, Martinkovich and Blomain15} Dagum et al.^{Reference Dagum, Park, Lau and Khan16} reported the use of combined vancomycin and tobramycin-impregnated beads or cement spacers in the management of post-traumatic frontal sinus infections. The cases all occurred 1 week to 8 months after primary surgery. The patients underwent debridement, obliteration of the nasofrontal ducts and placement of impregnated beads or cement spacer followed by 4–6 weeks of parenteral antibiotics. These patients had second stage procedures for reconstruction, with removal of the beads or cement at this stage. All three patients were free of infection at 14–76 month follow up. ^{Reference Dagum, Park, Lau and Khan16}

Topical therapy also comes without the side-effects of systemic antibiotic therapy, which can include end-organ failure and gastrointestinal side effects.^{Reference Gogia, Meehan, Di Cesare and Jamali17} Eckman et al. found that locally therapeutic levels of tobramycin were associated with serum levels well below therapeutic range, with no local or systemic complications.^{Reference Eckman, Henry, Mangino and Seligson18} Given the severity of the disease in our cases, with multiple previous surgical procedures and antibiotic treatment, a belt and braces approach was adopted. The novel use of tobramycin beads formed part of triple therapy management alongside systemic treatment to maximise the chances of disease control. Evidence from orthopaedic departments suggests that antibiotic beads alone are likely to be sufficient, but further work is required to replicate this in the management of frontal osteomyelitis. Finally, there is a lower economic burden with topical therapy, especially if it helps to reduce recurrence.^{Reference Gogia, Meehan, Di Cesare and Jamali17}

Frontal osteomyelitis is a rare but potentially life-threatening condition. Despite surgical debridement and systemic antibiotic therapy, recurrence rates remain high. Antibiotic-impregnated beads offer the ability to deliver high concentrations of antibiotic locally and have been used safely in orthopaedic surgery for decades. Our cases show promising use of tobramycin beads in recalcitrant frontal osteomyelitis. We propose that antibiotic-impregnated beads should be considered as a useful adjunct in the contemporary management of frontal osteomyelitis.