International Journal of Infectious Diseases 14 (2010) e752e758

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International Journal of Infectious Diseases

journal homepage: www.elsevier.com/locate/ijid

Review

Duration of post-surgical antibiotics in chronic osteomyelitis: empiric or evidence-based?

Rachid Haidar *, Asdghig Der Boghossian, Bisharah Atiyeh
Department of Surgery, American University of Beirut Medical Center, PO Box 11-0236, Riad El Solh, 1107 2020, Beirut, Lebanon

A R T I C L E I N F O

S U M M A R Y

Article history: Received 24 October 2009 Received in revised form 24 December 2009 Accepted 17 January 2010 Corresponding Editor: Vikas Trivedi, Meerut, India Keywords: Chronic osteomyelitis Debridement Muscle aps Antibiotic treatment Empiric Review

Chronic osteomyelitis is a relatively common infection and is often a lifelong disease. Traditionally, osteomyelitis has been treated with 46 weeks of parenteral antibiotics after denitive debridement surgery. Antibiotic-impregnated cement beads have also been used as adjuvant therapy for chronic osteomyelitis. However, this time frame of antibiotic treatment has no documented superiority over other time intervals, and there is no evidence that prolonged parenteral antibiotics will penetrate the necrotic bone. There is no solid evidence in the medical literature to support the continuous use of long duration antibiotic treatment for chronic osteomyelitis. A small number of comparative trials on the treatment of chronic osteomyelitis have been published. Also, the type of surgical procedures practiced in the past in treating chronic osteomyelitis and the lack of effective muscle ap application might have contributed to the prolonged antibiotic treatment. And although the surgical approach to the treatment of chronic osteomyelitis has advanced markedly, still the same duration of antibiotic treatment is adopted. In this review we question the continuous and traditional use of long-term antibiotic treatment for chronic osteomyelitis in spite of the advances in surgical treatment using aps. The medical literature, including studies in animals and humans, was searched for evidence to support the use of short courses of antibiotics. We hope this review will provoke the initiation of animal studies and clinical trials assessing the use of short courses of antibiotics for chronic osteomyelitis. 2010 International Society for Infectious Diseases. Published by Elsevier Ltd. All rights reserved.

1. Introduction From the time of the famous painting, The Gross Clinic by T. Eakins, until today, considerable advancements have been made for the surgical treatment of chronic osteomyelitis. However, the lack of aseptic concepts at that time can be equated with the current lack of denite guidelines regarding the duration of antibiotic therapy. Most physicians have prescribed prolonged courses of antibiotics in treating chronic osteomyelitis. This has been traditionally adopted, though it is not based on strong evidence. And although the surgical techniques in treating chronic osteomyelitis have advanced considerably, still the duration of antibiotic treatment has not decreased. In this review we question the continuous and traditional use of long-term antibiotic treatment for chronic osteomyelitis in spite of the advances in surgical treatment using aps. The medical literature was searched for evidence in animal and human studies to support the use of short courses of antibiotics. We hope this review will provoke the initiation of animal studies and clinical

trials assessing the use of short courses of antibiotics for chronic osteomyelitis. Chronic osteomyelitis is an osseous infection that has progressed to bone necrosis and sequestrum formation.13 Pathologic features of chronic osteomyelitis are the presence of necrotic bone and the exudation of polymorphonuclear leukocytes joined by large numbers of lymphocytes, histiocytes, and occasionally plasma cells.3 Symptoms are usually vague and the history might include chronic pain, chills, and low-grade fever. The physical examination might reveal local swelling and drainage. Diagnosis of chronic osteomyelitis is based on medical history, laboratory ndings, and different imaging techniques.4 Laboratory tests may reveal a normal leukocyte count but elevated erythrocyte sedimentation rate (ESR) and C-reactive protein (CRP) levels. The imaging modalities used for detecting the infection include Xray, computed tomography (CT) scan, and magnetic resonance imaging (MRI). Technetium-99m labeled leukocyte imaging helps eliminate differential diseases, and bone cultures guide the antimicrobial drug choice.1 2. Treatment of osteomyelitis Treatment of osteomyelitis in the long bones requires a multidomain intervention incorporating specic surgical approaches

* Corresponding author. Tel.: +961 3310877; fax: +961 1366384. E-mail address: rh00@aub.edu.lb (R. Haidar).

1201-9712/$36.00 see front matter 2010 International Society for Infectious Diseases. Published by Elsevier Ltd. All rights reserved. doi:10.1016/j.ijid.2010.01.005

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followed by extensive antibiotic therapy.1 The standard surgical procedure can be summarized as two basic steps, namely debridement and obliteration of the subsequent dead space by soft tissue. Other techniques such as removal of hardware or fracture stabilization may be used when necessary for a better functional and therapeutic outcome.1 3. Debridement

Nonetheless, recent data show that optimal vascularization of any ap is the most important characteristic to provide efcient coverage of dead space and to ensure success of treatment following adequate debridement.13,15 It is worth noting that muscle aps may conform better than fasciocutaneous aps to cavities and thus may be superior in obliterating dead spaces. 5. Antibiotic treatment

Debridement has been the forefront management protocol in osteomyelitis.5 It includes excision of all sequestra along with any infected bone or soft tissue,2 followed by obliteration of residual dead space. However, the involucrum may be preserved because it is viable bone; periosteum stripping and cortex resection are carefully approached to prevent unnecessary loss of vascularization and stability.6 The delineation of involucrum, inammation, and its penetration can be planned pre-operatively based on standard radiographs, CT scan, MRI or bone scan.5 However, the nal margin of debridement is determined by the surgeon intraoperatively5 by the paprika sign,3 demonstrated by interspersed pin-pointed bleeding noted on the well-vascularized viable bone.6 The degree of tissue to be removed can be decided beforehand to follow wide excision in a compromised host but marginal excision in otherwise healthy patients.7 Insufcient debridement is correlated with a high recurrence rate in chronic osteomyelitis,2 where the failure/recurrence rate may reach 30%.5 To decrease the recurrence rate, the management of chronic osteomyelitis of the long bones sometimes requires segmental resection, application of external xator, and immediate or delayed metaphyseal corticotomy. Thus, the quality and extent of debridement is a crucial step towards successful management.8 Adequately performed aggressive debridement reduces the microbial load,9 eradicates dead sections, and rescues healthy viable segments,3 but it also leaves behind a signicant dead space of bone and soft tissue.6 4. Soft tissue coverage The avascular dead space resulting from debridement promotes persistence of the infection.3 Therefore, it is necessary to properly manage this space8 in order to prevent recurrence2 and sustain bone integrity.3 Obliteration of the dead space is achieved with durable vascularized soft tissues3 that may be local, if adequate and not severely scarred, or distant, either pedicled or free.8 These aps range from the simplest skin aps9 for small space coverage3 to fasciocutaneous and muscular aps9 for bulk coverage.3 Softtissue aps improve local blood ow and antibiotic delivery.8 As early as 1946, Stark demonstrated that for the treatment of chronic osteomyelitis, rotating local muscles into post-debridement cavities resulted in an 84% success rate compared to only 43% when local aps were not rotated.10 Subsequently, the superiority of axial muscle aps over random-pattern skin aps was demonstrated.10,11 Today, muscle aps are considered to be the best option for reconstructing chronic osteomyelitic wounds,12,13 with the latissimus dorsi and rectus abdominis being the most common muscles used in free-transfer procedures.14 The advantages of a muscle ap can be attributed to its good blood ow, antibiotic release, and oxygen tension.12 However, muscle aps have certain drawbacks: the functional donor-site morbidity14 and their bulk, which might not be highly aesthetic.12 Fasciocutaneous aps may avoid these problems;12 however, their utilization for the treatment of osteomyelitis has been limited, with conicting outcomes. Experimental results revealed the superiority of muscle aps in reducing bacterial growth even though fasciocutaneous aps showed a more robust early increase in oxygen tension.14

The surgical procedure may include or be preceded by biopsy harvesting for planning the antibiotic treatment. Once the microbial agent is identied by culture, the broad-spectrum antibiotic initiated post-operatively is changed according to the culture and sensitivity results.15 It should be noted that in chronic osteomyelitis, bone and non-bone specimens might vary drastically in their microbiology; hence, microbiological studies of the bone should be considered for any therapeutic approach.15,16 Further management will be dictated by the patients status, clinical response, and risk of adverse effects.17 Concerning the duration of treatment for chronic long-bone osteomyelitis in adults, intravenous administration of antibiotics for 46 weeks is a widely used protocol.17,18 However, the duration of therapy remains empiric.1 This is because there are no clinical studies or documented records indicating the superiority of the 46-week course of antibiotics over other durations.19,20 6. Antibiotic-impregnated cement beads In the 1970s, antibiotic-impregnated bone cement was introduced as local antibacterial therapy to treat infected arthroplasties.21 Since then, antibiotic-impregnated beads have been developed to treat local infections of bone and soft tissue. The advantage of antibiotic-containing beads is that the beads ll dead space produced by debridement and they provide local antibiotic concentrations that are much greater than the minimum inhibitory concentration for most pathogens isolated in orthopedic infections.22,23 The local release of antibiotics accomplished with antibiotic-impregnated beads avoids the potential systemic adverse effects.22,24,25 Compared with systemic antibiotic therapy, the incidence of nephrotoxic, ototoxic, and hypersensitivity reactions with antibiotic-impregnated beads is signicantly diminished.22,26,27 The effectiveness of local antibiotic administration using antibiotic-impregnated beads in the treatment of osteomyelitis has been widely demonstrated. Korkusuz et al. reported on the effectiveness of antibiotic-impregnated beads in the treatment of osteomyelitis in a rat model.28 In another chronic osteomyelitis model, the efcacy of gentamicin bead treatment was comparable to treatment with systemic antibiotics.29 Other investigators have obtained good results in other animal models.30,31 Most of the data reported in the literature support the safe usage of antibiotic-impregnated beads.23,29,32 These antibiotic beads have been used in the treatment of chronic osteomyelitis, mostly as a supplement to systemic antibiotic treatment.33,34 There was no recurrence in 12 treated patients. One study reported 26 patients with chronic osteomyelitis treated with radical debridement, irrigation, vancomycin-impregnated beads and systemic antibiotics.32 The results were satisfactory in all patients, who were ambulatory and had returned to their pretreatment activity level or better at last follow-up.32 A study from Germany reported a high cure rate (91.4%) in a group of 128 patients treated for different manifestations of chronic osteomyelitis.25 In vivo models comparing the efcacy of antibiotic-impregnated cement beads to systemic antibiotics are lacking. For the time being, antibiotic-impregnated beads are effective supplements to

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Table 1 Animal studies on the treatment of osteomyelitis Reference Salgado et al. 2006 [14] Norden et al. 1980 [35] Norden 1983 [36] Norden and Shaffer 1982 [37] Mader and Wilson 1983 [38] Rissing et al. 1985 [39] Nelson et al. 1990 [40] Dart and Hodgson 1996 [41] Monzon et al. 2001 [42] Shirtliff et al. 2001 [43] Kadry et al. 2004 [44] Yin et al. 2005 [45] Disease case Osteomyelitis of lower extremity of goat Staphylococcal chronic osteomyelitis in rabbit Staphylococcal osteomyelitis Chronic osteomyelitis in rabbit, Pseudomonas aeruginosa Staphylococcal osteomyelitis in rabbit Staphylococcal chronic osteomyelitis in rat Chronic Pseudomonas aeruginosa osteomyelitis in rat Chronic osteomyelitis in horse Staphylococcal chronic osteomyelitis in rat Staphylococcal chronic osteomyelitis in rabbit Chronic staphylococcal osteomyelitis in rabbits Methicillin-resistant Staphylococcus aureus osteomyelitis Antibiotic treatment Cefazolin Rifampin and trimethoprim Rifampin, sisomicin, and cephalothin Azlocillin and tobramycin Cefamandole or cephalothin Oxacillin or ceftriaxone Subcutaneous ceftazidime alone or in combination with tobramycin Penicillin and gentamicin Cefuroxime, vancomycin, tobramycin or ciprooxacin Levooxacin and nafcillin Ciprooxacin and vancomycin (liposomal form of the combination) Subcutaneous tigecycline or vancomycin with or without oral rifampin Antibiotic duration 5 days 7, 14, 28 days 14 days 14, 28 days 28 days 14, 28 days 14 days 10 days 21 days 28 days 14 days 28 days

debridement and systemic antibiotics in the treatment of softtissue infections and chronic osteomyelitis. 7. Materials and methods The medical databases of PubMed, Medline, and Embase were searched for literature on treatment modalities of chronic osteomyelitis (MeSH term) in the lower extremities; hence acute, maxillofacial, and vertebral osteomyelitis entries were excluded, as were those of diabetic foot. Later, the search was combined with antibacterial agents (MeSH term)/antibiotic. The medical literature was reviewed for articles published between 1955 and 2008. All entries in the English language were scanned for related information and the most appropriate references included in this manuscript. Those related to animal studies are summarized in Table 1 and those related to human studies are summarized in Table 2. We wished to update the reader and the orthopedic surgeon on what has been documented in the literature concerning the treatment of chronic osteomyelitis, evaluating whether there is any evidence supporting certain durations of antibiotic treatment. 8. Results and discussion 8.1. Animal studies Starting in the 1970s, animal studies were undertaken in order to determine the appropriate duration of antibiotic treatment for osteomyelitis (Table 1).14,3545 Rabbit models of chronic osteomyelitis indicated that clindamycin administered for 28 days was effective in treating the bone infection, while 4-week courses of penicillin and cephalosporin were not sufcient for adequate therapy.35 On the other hand, these single-antibiotic studies were contradicted by the combination-drug studies showing therapy success with courses shorter than 4 weeks.35 One study in rabbits revealed that staphylococcal osteomyelitis treated with the combination of rifampin, sisomicin, and cephalothin had a lower percentage of positive bone cultures than when rifampin was given alone or in combination with other antibiotics.36 Furthermore, lower rates of positive culture were obtained with 7-, 14-, and 28day treatment modalities. It is worth mentioning that the therapy was started 14 days after the induction of infection, the cultures were done after 70 days of treatment, and no surgical procedure was attempted in that study.36 Another study conducted a few years later by the same investigator indicated that rabbits

receiving the combination of rifampin, sisomicin, and cephalothin for only 14 days recovered from staphylococcal osteomyelitis.37 Studies on the angiogenesis and blood ow in osteomyelitic bone are scarce. In a recent study by Herzog et al., blood ow in the fractured tibia of rabbits was studied after introducing the muscle ap. A rise in perfusion rate was noticed in the cortical lid within the rst week after local muscle ap transfer.46 Another study on goats illustrated that the osteomyelitic bones reconstructed with a very well-vascularized ap, being of muscle or non-muscle origin, were able to recover with only 5 days post-operative antibiotic administration.14 Although healing in chronic osteomyelitis will depend on the rapidity of revascularization, which is linked to angiogenesis, researchers have still not conducted studies to assess this notion. Studies on angiogenesis and revascularization are needed to understand this concept in chronic osteomyelitis and to explore what factors might speed up this process, eventually leading to rapid healing and shorter courses of antibiotic treatment. 8.2. Human studies After an extensive search of the literature on osteomyelitis, all studies using a short-term antibiotic course (314 days), irrespective of the outcome, are summarized in Table 2.4767 We have not included studies using the traditional 6-week antibiotic regimens because these studies have been extensively reviewed by many investigators in the medical literature.68,69 Most of the reviewed studies showed good results in treating chronic osteomyelitis. The therapy duration might be shortened depending on the administration route of the drug. Treatment failure can be attributed to many factors. For example, a study on patients suffering from infectious diseases included as part of its population a small set of six chronic osteomyelitis cases.68 These patients were treated for 1124 days (average of 15 treatment days) post-operatively (hardware removal, stabilization of nonunion and bone graft, when indicated) with cefoxitin, with a good response in four of the cases. Failure was due to the retained metal wire and the non-union of the femur, which facilitated the persistence of infection.68 By 1968, Bicks book reviewing 25 years of experience with antibiotic treatment led him to conclude that it was invaluable for eliminating osteomyelitis-related septicemia and abscesses, but that chronic bone infection could only be cured with surgery.36 Thus, it is fully established that without proper surgical intervention and debridement, the treatment failure rate in chronic osteomyelitis is high, irrespective of the duration of the antibiotic

Table 2 Chronic osteomyelitis cases of the lower extremities treated with short term antibiotics reported in the literature Reference Geddes et al. 1964 [47] Grondin et al. 1965 [48] Cases 5 patients, osteomyelitis of tibia or femur 6 patients with chronic osteomyelitis of lower extremities (2 tibia, 3 femur) 2 patients with chronic osteomyelitis (femur and intermedullary nail) 5 patients Surgical procedure Antibiotics used Lincomycin Drainage and graft for 2 cases Lincomycin Antibiotic duration 4, 7, 18 weeks for 3 patients and 1 week for 2 patients Average of 17.4 days (530 days) Outcome 3 patients recovered; failure in 2 5 patients responded

Nettles et al. 1969 [49]

Debridement and saucerization for 1 patient Debridement (3 cases), pin removal (1 case), skin graft (1 case)

Cephalothin or tetracycline

23 weeks

Good in all

Edmondson 1973 [50]

Oral therapy group: lincomycin and clindamycin alternately also gentamicin Parenteral group: clindamycin

Oral group: maximum of 32 days Parenteral group: maximum of 11 days

Oral therapy: pathogen cleared in 1 case but both cases showed good response Parenteral group: pathogen clearance and good response in all cases All were cured Cured (21 and 34 months follow-up) 4 patients were cured, 1 improved, 1 failed 12 cases healed with a follow-up of 26 months Relapse twice in the same patient after 34 months Follow-up: 3/11/12/32 months Follow-up for 3 months, 6 patients improved

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McCloskey 1977 [51] Fass 1978 [52]

3 patients 2 cases of femur osteomyelitis

Wound aspiration (1 case, not-specied) Surgery (not clearly described) Debridement and curettage in all patients 3 cases treated with debridement, 1 with muscle ap, and 1 with omentum ap and skin graft Debridement of wound infections and curettage

Cefoxitin Cefazolin and cephalexin

Schurman and Dillingham 1979 [53] Green and Ripley 1984 [54]

6 patients 14 patients with chronic osteomyelitis (12 tibia, 1 ulna, 1 radius) 4 patients had chronic osteomyelitis of tibia

Cefoxitin Penicillin or cephalosporin parenterally then orally Cefsulodin 4 g/day with ampicillin (for Enterococcus) or 8 g/day (2 cases) Aztreonam and penicillin for one patient; cloxacillin for the 2nd patient Ampicillin and sulbactam with/without gentamicin, or clindamycin with gentamicin or clindamycin alone (1) 1 g of sulbactam and 2 g of ampicillin q3d (2) Cefotaxime 2 g q3d Antibiotic type not specied Fosfomycin

12 days Case 1: 46 days iv followed by 22 days oral Case 2: 14 days iv Average 15 days (range 1124) Parenteral for 12.2 days (328 days) and oral for 76 days (0150 days) 42 days (2 cases), 26 days (1 case) and 17 days (1 case)

Pottage et al. 1984 [55]

Romero-Vivas et al. 1985 [56]

2 patients with chronic osteomyelitis

Reinhardt et al. 1986 [57]

14 osteomyelitis cases

744 days (the exact period is not known as the patients were part of a group with other infections) 27 days (942 days)

All had satisfactory clinical responses

fer et al. 1986 [58] Lo

(1) 2 chronic osteomyelitis (2) 1 chronic osteomyelitis 47 cases of chronic osteomyelitis 60 patients with chronic post-traumatic

Both groups treated for 2 weeks

(1) Both cases cured (2) Patient relapsed Mean follow-up of 2.5 years: 40 successes (85%) Mean follow-up of 37 months (753 months); outcome was very good in 54.7%, good in 3.8% and satisfactory in 15.1%

Knopp et al. 1987 [59] Meibner et al. 1989 [60]

15 latissimus dorsi muscle myocutaneous and 32 local aps

35 days 528 days (mean 13.9 days)

Gentry and Rodriguez 1990 [61]

osteomyelitis with 43 tibia and 13 femur cases 67 patients with chronic bone osteomyelitis (tibia and femur) 33 patients with chronic gunshot osteomyelitis 26 patients with chronic osteomyelitis

Surgical debridement and removal of metallic material Radical surgical intervention, debridement, irrigation and drainage Debridement or vascular repair or both when needed

Ciprooxacin vs. broad spectrum cephalosporin Lincomycin and gentamicin

Shcherbin et al. 1990 [62]

Average 56 days (2896 days) for ciprooxacin; 47 days (877 days) for iv regimen 722 days

Greenberg 1990 [63]

Teicoplanin

Range 113 days

Follow-up: 12 months; success rate 77% with ciprooxacin vs. 79% with the iv regimen Follow-up for 4 years showed 3 relapses out of 26 operated patients All improved but further assessment was not done

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27 chronic osteomyelitis cases of lower extremities 16 cases of chronic osteomyelitis (9 cases involving the tibia) 65 patients with chronic osteomyelitis

7 patients with osteomyelitis Chronic osteomyelitis of bula

regimen.8,36 This trend can be attributed to the underlying pathology of the disease. In chronic osteomyelitis, the sustained suppurative infection of the bone results in tissue necrosis and vascular collapse. The ischemia exacerbates the bone necrosis and parts of the infected bone lacking blood supply become separated into certain foci called sequestra.2 Antibiotics and the inammatory cells of the host are unable to reach these avascular envelopes causing chronic disease,2 unless there is surgical manipulation through debridement, drainage, and soft tissue coverage. Additionally, the surgical procedure helps in diminishing the microbial load, eradicating the unviable tissues, and revitalizing the dead space with healthy softtissue and neovascularization. The enhanced blood perfusion to the bone improves the bioavailability of the antimicrobial drug and certain physiological contributors, consequently ghting the infection and promoting tissue healing.2 Hence the importance of the revascularization timeline in estimating the duration of antibiotic use. Muscle ap versus control group studies in chronic osteomyelitis showed better blood ow, increased antibiotic release, and decreased bacterial count in the muscle ap group.12 Recent advances in surgical technology and microsurgery have rened the ap harvest14 and developed its hemodynamics,12 allowing the reestablishment of a blood supply earlier than what was previously expected. Since revascularization or blood supply is a major factor in determining the antibiotic treatment duration, it is generally proposed that the proper surgical intervention can help not only reduce the failure rate but also shorten the duration of antibiotic therapy. Recently, Rubino et al. reported the case of a woman with chronic osteomyelitis in the lower extremities that was treated with intravenous antibiotics for only 2 weeks following radical excision and obliteration of the dead space with a propeller ap. She recovered with no relapse within a year.12 Further studies indicating short-term antibiotic treatment of osteomyelitis are summarized in Table 2. Therefore, shorter duration of antimicrobial treatment with emphasis on thorough debridement and well-vascularized ap coverage might be a possible alternative guideline for treating chronic osteomyelitis in the lower extremities. Of course further studies are necessary to build a scientic basis for the management of the precise duration of antibiotics in the light of enhanced surgical intervention. These studies should focus on blood ow and revascularization of bone following ap introduction, in order to instigate clinical studies regarding treatment of chronic osteomyelitis with shorter antibiotic regimens following enhanced surgical intervention. 9. Conclusions Chronic osteomyelitis is a relatively common infection and is often a lifelong disease. Despite all of the advances in antibiotic and operative treatment, osteomyelitis remains difcult to treat. This is because bacteria can elude host defense mechanisms by hiding intracellularly and by developing a protective slimy coat. By acquiring a very slow metabolic rate, bacteria become less sensitive to antibiotics. For all the above reasons, operative treatment is considered whenever possible. Osteomyelitis has traditionally been treated with 46 weeks of parenteral antibiotics after denitive debridement surgery. However, this time frame has no documented superiority over other time intervals, and there is no evidence that prolonged parenteral antibiotics will penetrate the necrotic bone. A small number of comparative trials on the treatment of chronic osteomyelitis have been published. However, most of the studies have involved relatively few patients and have not been randomized. It should be added here that the type of surgical procedures practiced in

Mean follow-up of 7.4 years with 89% success rate Cured (mean follow-up of 2 years) Follow-up of 25 years with success rate up to 76% Culture-specic antibiotics 1014 days Post-operative antibiotics Debridement and ap coverage Surgical intervention: debridement and foreign body removal

Outcome

Antibiotics used

Cases

Radical excision and propeller ap coverage iv, intravenous; q3d, every 3 days. Finney et al. 2005 [67] Rubino et al. 2009 [12]

Surgical procedure

Debridement and muscle ap

Guelinckx and Sinsel 1995 [65]

Table 2 (Continued )

Anthony et al. 1991 [64]

Galanakis et al. 1997 [66]

Reference

Alternating among ciprooxacin, ooxacin and peoxacin Daptomycin Meropenem

12 days: intravenously for 5 days and orally for 1 week Ciprooxacin 17210 days, ooxacin 17235 days and peoxacin 44210 days Average 29 days (842 days) 15 days

Antibiotic duration

All patients were cured No recurrence at 12 months

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the past in treating chronic osteomyelitis and the lack of effective muscle ap application might have contributed to the prolonged antibiotic treatment. And although the surgical approach in treating chronic osteomyelitis has advanced markedly, the same duration of antibiotic treatment is still adopted. Properly designed studies are needed to ascertain the optimal duration of antibiotic treatment for patients with chronic osteomyelitis. Also more studies are needed to clarify the role of angiogenesis in the treatment of chronic osteomyelitis. Conict of interest No conict of interest to declare. References
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