Septic Osteitis and Osteomyelitis in Foals – Are Antimicrobials Alone Enough? C

EQUINE VETERINARY EDUCATION / AE / FEBRUARY 2013 67

Clinical Commentary Septic osteitis and osteomyelitis in foals – are antimicrobials alone enough? C. Koch* and S. Witte Equine Clinic and Department of Clinical Veterinary Medicine, Vetsuisse-Faculty, University of Bern, Bern, Switzerland. *Corresponding author: email: [email protected]

Keywords: horse; foal; septic osteitis; septic osteomyelitis; medical treatment; doxycycline

Introduction fibrinogen concentrations and blood cultures, however, can The case report by Lawrence and Fraser (2013) describes the be helpful in diagnosing O/OM (Sayegh et al. 2001; Newquist successful management of 2 weanlings with septic osteitis of and Baxter 2009). the proximal sesamoid bones, using prolonged (6 weeks) Radiography is most commonly used to confirm and follow antimicrobial therapy alone. Doxycycline, an antimicrobial a septic bone lesion. Bone lysis may not be recognised with excellent bone penetration properties, was deemed radiographically until at least 4–5 days post infection, at a time essential to treatment success. In contrast to the poor when the bone has lost 30–50% or more of its mineral content outcome in previously reported cases of septic sesamoid bone (Turner 1987; Bramlage 1998; Goodrich and Nixon 2004). In osteitis, the authors were able to show the value of a cases with concurrent infarction, this time lag may be as great conservative approach over surgical debridement. The as 2–3 weeks (Wegener and Alavi 1991; Bertone 1999). question is to what extent are we able to extrapolate this to Delayed diagnosis and associated extensive lysis may result in the general treatment of septic osteitis and osteomyelitis in pathological fracture, with a negative impact on prognosis young horses? (Fig 1). Advanced imaging (magnetic resonance imaging [MRI] or computed tomography [CT]) may allow earlier recognition (Sayegh et al. 2001; Easley et al. 2011) and provide Etiopathological, clinical, and information on the extent of the lesion (Fig 2). While the diagnostic features severity of the radiographic lesion does not necessarily appear Septic osteitis (O; infection of bones lacking a medullary to affect long-term outcome (Steel et al. 1999; Kay et al. 2012), cavity) and osteomyelitis (OM) are common in foals up to age its location is more likely to determine future soundness. approximately 4 months and often involve adjacent synovial Successful elimination of infection manifests radiographically structures (Firth 1983; Neil et al. 2010). The source of bacteria, as sharp delineation of the original defect and surrounding their species and the physiological and anatomical sclerosis (Fig 3). This being said, it can take many months for a considerations that favour their growth at sites of predilection defect to regain mineral density, if at all (Lawrence and Fraser are summarised by Lawrence and Fraser (2013) and elsewhere 2013). Therefore, a positive clinical progression (decreased in the literature (Firth 1983; Brewer and Koterba 1990; Schneider swelling and lameness) and improved results of repeated et al. 1992; Vatistas et al. 1993; Hardy 2006; Neil et al. 2010). clinicopathological testing represent more important In mature horses, O/OM are usually associated with indicators of early success in treatment. penetrating injuries or previous surgical interventions. In the report by Lawrence and Fraser (2013), 2 weanlings, aged 5 and Current treatment strategies in man and equids 6 months, were affected by septic osteitis of the proximal In their ‘plea for general conservatism in the treatment of sesamoid bones (PSB). In horses of this age haematogenous septic osteomyelitis of the skull and face’ Blair and Brown seeding of bacteria remains the most likely initiating cause in (1927) remind human practitioners of an old Italian proverb the absence of external injury, although a primary septic focus that states ‘He who goes slowly goes safely; he who goes elsewhere in the body is rarely identified (Wisner et al. 1991; safely goes surely’. Unfortunately the question as to just Dabareiner et al. 2001; Witte and Rodgerson 2005; Sherman how ‘safe’ or ‘sure’ a conservative approach is, remains et al. 2006). It is assumed that the relatively convoluted blood unanswered in both human and equine medicine. supply to the axial borders of the PSB and the intersesamoidean Current treatment recommendations in the equine ligament makes them predilection sites for haematogenous veterinary literature include surgical debridement of bone as septic osteitis and desmitis in weanlings and mature equids a primary course of action to address O/OM (Goodrich and (Wisner et al. 1991; Dabareiner et al. 2001; Barr et al. 2005; Nixon 2004; Schneider 2006; McIlwraith 2007). In contrast, Sherman et al. 2006; Lawrence and Fraser 2013). treatment of the human equivalent (acute haematogenous Lameness, focal pain and swelling (oedema and effusion) osteomyelitis [AHO] in paediatric patients) appears to focus dominate the clinical picture of O/OM (Bramlage 1998). In on prolonged systemic antimicrobial therapy (Le Saux et al. cases with effusion, synovial fluid analysis as well as culture and 2002; Peltola et al. 2010). A recent prospective, randomised sensitivity testing provide valuable information (Bramlage 1998; trial investigating appropriate antimicrobial treatment Sayegh et al. 2001). With the exception of an elevated body regimens found that extensive surgical interventions are rarely temperature, there is often a paucity of signs indicating a necessary in children (Peltola et al. 2010). The exception to systemic response (Goodrich and Nixon 2004). Plasma this is the presence of an obvious abscess, from which

Fig 1: Dorsolateral-palmaromedial oblique radiograph of the right front fetlock and corresponding trans-sectional CT image at the indicated level (dotted line) of an 11-month-old Welsh Pony. The pony presented with a nonweightbearing lameness of this limb of 3 weeks’ duration. Effusion of both the digital sheath and metacarpophlangeal joint was present. The medial PSB had a large septic bone lesion, identified with conventional radiographs (arrowheads). Proximal to this, a pathological fracture of the medial PSB had occurred (arrow) as seen on CT imaging.

Fig 2: Dorsopalmar radiograph of a right front fetlock and corresponding MR image at the indicated level (dotted line) of a 12-year-old Camargue Pony presented with chronic, intermittent moderate right forelimb lameness. Lameness was abolished with intrathecal anaesthesia of the digital sheath, after which the horse showed a mild left forelimb lameness. Chronic, aseptic lytic lesions affecting the axial border of the medial PSB (arrowheads and white arrow) were present in both front limbs. purulent material is aspirated (Blyth et al. 2001; De Boeck to have inoperable lesions due to extensive physeal 2005; Goergens et al. 2005). The continued emergence of involvement or surgically inaccessible locations such as the multiresistant pathogens such as community-acquired ilium or navicular bone. A conservative approach was methicillin-resistant Staphylococcus aureus in human patients therefore elected due to the morbidity likely to result from has resulted in an increased necessity for surgical intervention surgical intervention. Rather surprisingly, therefore, 7 of these 9 (Darville and Jacobs 2004; Harik and Smeltzer 2010). Surgical foals (78%), compared with 80 of the remaining 98 foals (82%) exploration and debridement are also indicated if a patient were reported to have a successful outcome (one foal was does not respond to empiric antibiotic therapy within an subjected to euthanasia without pursuing treatment). appropriate time frame by showing persisting signs of pain Another recent report focused on the treatment of septic and fever (Stanitski 2004; Goergens et al. 2005; Harik and osteomyelitis of the patella (Kay et al. 2012). There, 6 of 8 foals Smeltzer 2010). (75%) made a full recovery. Notably, all surviving foals were Closer analysis of the data presented in reports of O/OM treated without surgical debridement of the patellar lesion, but cases in the veterinary literature (Witte and Rodgerson 2005; all received intralesional antimicrobials. Although numbers are Neil et al. 2010; Kay et al. 2012; Lawrence and Fraser 2013) small, these reports suggest that cases treated without bone allows us to consider the value of an initial conservative debridement can have an equally successful outcome when approach in the equine case with lytic bone lesions. In a compared to previous studies (Schneider et al. 1992; Vatistas retrospective study of 108 foals, medical therapy alone et al. 1993; Axon et al. 1999). Figures 3–5 are further examples was pursued in 9 (Neil et al. 2010), which were considered of cases treated successfully with antimicrobial therapy alone.

a) b)

Fig 3: Initial (a) and one month follow-up (b) lateromedial radiographic projections of the left stifle of a 4-week-old Thoroughbred foal affected with O/OM of the distal femoral physis. Note the location of the patella (due to severe femoropatellar joint effusion) and extensive lytic lesions (arrows) upon initial presentation and the sclerotic demarcation (arrowheads) after successful treatment without surgical debridement.

a) b)

Fig 4: Caudocranial radiographic projections of the left stifle of a one-month-old Warmblood colt presented for an acute mild to moderate left hindlimb lameness. OM of the lateral condyle (arrow) with concurrent synovitis of the lateral femorotibial joint was diagnosed upon initial presentation (a). Subsequent treatment involved needle lavage of the lateral femorotibial joint, intralesional and intrasynovial injection of amikacin and systemic treatment with chloramphenicol. Follow-up radiographs (b) after 2 weeks showed sclerotic demarcation (arrowheads) and relative decrease in lesion size. The treatment with oral chloramphenicol was continued for an additional 2 weeks and the foal made a full recovery.

It is important to note that the term ‘conservative’ as used in characterised, bone aspirates and/or synovial fluid samples for this commentary refers to a lack of bone debridement and in culture and sensitivity patterns should be obtained whenever no way discounts the value of lavage of adjacent synovial possible. Prior to the availability of these results, however,choice structures (whether by through-and-through needle lavage or of antibiotic should take the following into consideration: arthroscopic techniques) in order to address sepsis or simply to antimicrobial spectrum; capacity to penetrate affected tissues reduce the burden of inflammatory mediators. (including tissues with pathological milieu alteration); and commonly encountered antimicrobial resistances within the Empiric antimicrobial choice in the early hospital population. management of O/OM Enteric Gram-negative organisms appear to predominate The goal of any antimicrobial treatment regimen is to achieve in bacterial isolates from bone lesions in foals (Firth 1983; adequate tissue concentrations of an antimicrobial effective Brewer and Koterba 1990; Orsini and Kreuder 1994; Baxter in eliminating the causative infectious agent. Although the 1996; Neil et al. 2010). This is in contrast to AHO in children, most common pathogens involved in O/OM have been where S. aureus is the most commonly isolated pathogen

The role of chronicity in determining treatment and outcome Chronic septic PSB lesions in the mature equine carry a poor prognosis when treated conservatively (Wisner et al. 1991; Dabareiner et al. 2001; Barr et al. 2005). Figure 1 is evidence of the authors’ negative experience with chronic sesamoid bone infections. This case was presented after a prolonged, unsuccessful attempt at medical management. Sherman et al. (2006) reported an isolated case of fungal osteitis of the axial borders of the PSB that was successfully treated without surgical debridement. Progression (and the inherent chronicity) of an osseous infection is an important determining factor as to whether or not a conservative treatment approach is going to succeed, irrelevant of antimicrobial choice. With time, avascular necrosis develops and changes in the tissue’s chemical milieu occur. Sequestrum formation or the mere extent of the lesion will impede effective antimicrobial delivery, by whichever means. In these cases, surgical exploration for the removal of necrotic tissue and purulent material is mandatory (Fig 6). In cases with an insidious onset or a vague clinical history, it may Fig 5: Skyline radiographic projection of the left stifle of a be difficult to determine when this critical point is reached. 6-month-old American Saddlebred. The weanling presented with Advanced imaging modalities such as nuclear scintigraphy, acute left pelvic limb lameness and marked effusion of the CT or MRI (Figs 1 and 2) may guide this decision as well as the femoropatellar joint. A lytic bone lesion at the lateral aspect of the approach. Rapid referral and appropriate treatment of the patella (arrow) was present. Treatment consisted of a single cases reported by Lawrence and Fraser (2013) undoubtedly intra-articular dose of amikacin (500 mg) into the femoropatellar contributed to a positive outcome with antimicrobials alone. joint and systemic oxytetracycline for 2 weeks. Full recovery was reported. Doxycycline: spectrum of antimicrobial activity and other considerations Lawrence and Fraser (2013) were successful with their use of (Darville and Jacobs 2004; Harik and Smeltzer 2010). Thus, doxycycline. This is a semisynthetic, bacteriostatic broad-spectrum antimicrobials, in particular the combination antimicrobial that reversibly binds to the bacterial 30 s of an aminoglykoside and a b-lactam remain the first choice ribosomal unit and inhibits microbial protein synthesis. antimicrobials when treating O/OM. Amikacin is very Less antimicrobial resistance and fewer toxic effects commonly used for local antimicrobial delivery applications, (nephrotoxicity) have been reported compared to other due to its advantageous spectrum of activity for orthopaedic tetracyclines (Van Linthoudt et al. 1991; Joshi and Miller 1997). infections, and its concentration-dependent activity Its antimicrobial spectrum includes Staphylococcus spp. (Goodrich and Nixon 2004). (including S. aureus), Streptococcus spp., Escherichia coli, Pharmacokinetic properties of antimicrobials, especially Klebsiella spp., Salmonella spp., Pseudomonas spp., and bone penetration, are similar across species. Tetracyclines and anaerobic bacteria such as Bacteroides spp., Fusobacterium most aminoglycosides have excellent bone penetration spp., Clostridium spp. and Actinobacillus spp. (Ensink et al. properties and are frequently used in equine practice 1993; Joshi and Miller 1997) and it is therefore likely to be (Dowling 2004). Chloramphenicol, with its very broad spectrum efficacious against most organisms commonly isolated from of activity and outstanding penetration of bone and synovial O/OM lesions (Firth 1983; Brewer and Koterba 1990; Schneider structures, is another good choice for the treatment of O/OM. et al. 1992; Vatistas et al. 1993; Neil et al. 2010). Its application in animals, however, should be restricted to The value of tetracyclines in treating O/OM in foals is selected cases due to its association with idiosyncratic highlighted by Neil et al. 2010: Of the 107 foals for which anaemia in man (Dowling 2004). choice of systemic antimicrobial used and treatment response Regional variation in prevalence of bacteria and their ability were recorded, oxytetracycline hydrochloride (5–10 mg/kg to resist antimicrobial mechanism-of-action will influence and bwt i.v. q. 12 h) was the antimicrobial most frequently possibly restrict the choice of antimicrobial. Further, sound clinical associated with positive treatment responses. This was the examination and judgement should guide the choice of a case in 15/31 foals where it was used as the first choice specific antimicrobial protocol. An example of this is initiation of antimicrobial and in a further 24 cases where it was either used treatment with a macrolide/rifampin combination when O/OM as the second or third choice antimicrobial (Neil et al. 2010). results from extrapulmonary Rhodococcus equi infection. As Tetracyclines therefore compared favourably with all other emphasised in a recent case report by Close et al. (2010), single or combined antimicrobial choices reported in that lack of clinical improvement within 2–3 days of initiating study. antimicrobial therapy should prompt the clinician to reconsider Further, doxycycline possesses anti-catabolic effects on the choice of antimicrobials used. This holds true, even when the cartilage and synovium (Haerdi-Landerer et al. 2007; Fortier choice of antimicrobial medications is based on results of culture et al. 2010; Schnabel et al. 2011) and has been used and sensitivity analyses (Close et al. 2010). extensively in human medicine as an antimicrobial and

a) b) c)

Fig 6: Dorsopalmar radiographic projection of the right metacarpophalangeal joint of a 5-week-old foal presented with septic physitis (lateral physis). The foal showed partial clinical improvement with antimicrobial therapy. However, while only soft tissue swelling is evident on presentation (a), bone lysis was noted after one week (b, arrowheads) and progressed into the second week (c, arrow). therapeutic agent to address degenerative diseases, be expected to compensate for poor choice of antimicrobial including osteoarthritis (Breedveld et al. 1990; Golub et al. and this remains the main determinant over success when 1991; Ryan et al. 1996). These properties, together with a treating acute O/OM. As already mentioned, bone aspirates bioavailability of 70% in horses after oral administration make and/or synovial fluid samples for culture and sensitivity patterns doxycycline an excellent antimicrobial for treating O/OM in should be obtained whenever possible. Depending on the foals (Bryant et al. 2000). patient and lesion site, sampling may necessitate short-term anaesthesia. At the same time, intralesional infiltration (as well Practical considerations with regard as other methods of local antimicrobial delivery) and to duration and route of through-and-through lavage of concurrently affected synovial antimicrobial administration structures are readily performed. Finally, in cases where a primary source of infection is identified (e.g. infected umbilical Duration of treatment of AHO in human patients or O/OM in remnants) this may be addressed in the same anaesthetic equids appears to be more empiric than evidence-based. Six episode, if deemed necessary. weeks of oral treatment with doxycyline, as detailed by Lawrence and Fraser (2013), is in line with recommendations found in the human medical literature. However, a general consensus does not appear to exist and recent publications Conclusions challenge current concepts on duration and initial route In agreement with the report by Lawrence and Fraser (2013), it of administration (i.v. or oral) of antimicrobial therapy in is the authors’ opinion that a conservative initial approach, AHO (Le Saux et al. 2002). Clinical, radiographic and using systemic and local antimicrobial therapy alone, may be clinicopathological findings should guide duration of treatment warranted in cases of acute septic O/OM. Success with this in the equine patient. Assuming acceptable tolerance of approach will reduce patient morbidity and costs associated antibiotics, a period of 5–7 days following resolution of signs of with treatment. infection provides an additional margin of safety. Nonetheless, in accordance with current human medical Recent advances regarding the local delivery of guidelines, we propose the following indications for surgical antimicrobials are thought to be responsible for improved lesion debridement: failure to show clinical improvement with success rates when treating septic arthritis and O/OM in the conservative management in a timely manner (within 2–3 horse (Ducharme and Mitchell 2004; Goodrich and Nixon days); progression of a septic bone lesion (Fig 6); and 2004). Notwithstanding their positive impact in a large number evidence of abscess or sequestrum formation. of cases, their value and practicality need to be assessed on a These factors must therefore be monitored closely to assess case-by-case basis. Regional limb perfusion, for example, the response to treatment. Failure to respond not only justifies relies on a functional vasculature and the ability to effectively surgical intervention but should also prompt re-appraisal of the isolate the affected region. Such novel approaches should not current antimicrobial protocol.

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