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Home , Endocarditis, Infective endocarditis, Vertebral osteomyelitis

Postgrad Med J: first published as 10.1136/pgmj.70.830.885 on 1 December 1994. Downloaded from Postgrad Med J (1994) 70, 885 - 890 A) The Fellowship of Postgraduate Medicine, 1994

Osteomyelitis and infective M.E. Speechly-Dick and R.H. Swanton Department ofCardiology, The Middlesex Hospital, Mortimer Street, London WIN 8AA, UK

Summary: is thought to occur as a ofinfectious endocarditis in as many as 6% ofcases ofendocarditis. We describe this association in three patients. Osteomyelitis may be difficult to diagnose in patients with endocarditis because symptoms such as , pain and stiffness are common to both illnesses, therefore need to have a high index ofsuspicion to avoid missing this important complication. We recommend that patients with endocarditis and persistent or localized musculoskeletal symptoms should be investigated to exclude osteomyelitis. Plain radiographs can be normal in 50% of cases of osteomyelitis in the early stages or show only minor abnormalities, but bone scans are highly sensitive. We suggest that a bone scan is performed if radiography is unhelpful, since a diagnosis of osteomyelitis can effectively be excluded if the bone scan is normal. We advocate close follow-up of these patients with prolonged treatment consisting of at least 6 weeks of , and 3 months or longer of oral therapy.

Introduction We describe three cases ofosteomyelitis in patients tation there was a soft ejection systolic murmur at with endocarditis, two due to the left sternal edge radiating to the aortic area. by copyright. epidermidis and one due to . There was a tender area in the right lower lumbar Musculoskeletal symptoms are very common in area. Neurological examination was normal. patients with endocarditis and this makes it difficult Investigations revealed a haemoglobin of 12.2 g/ to determine which patients warrant investigation dl, white cell count of 28 x 109/l (of which 86% to exclude osteomyelitis. Up to 6% of all cases of were neutrophils), ESR 115 mm/hour, C-reactive endocarditis are complicated by osteomyelitis' and protein (CRP) 190 mg/I, and mean cell volume it occurs slightly more frequently in cases with (MCV) 104 fl. The chest radiograph was normal Staphylococcus aureus endocarditis.2 There is no except for a mildly enlarged and sternal wires consensus ofopinion on the length oftreatment for from previous surgery. The electrocardiogram

this condition, and we review the literature and showed sinus , left ventricular hyper- http://pmj.bmj.com/ advocate a management regime. trophy and a PR interval of 0.2 seconds. Echocar- diography revealed a normal aortic homograft with no evidence of aortic regurgitation or vegeta- Case reports tions. A diagnosis of probable Case I was made and treatment was started with intra- venous (60 mg 12 hourly) and high dose A 64 year old man was admitted because of3 weeks benzyl (1.2 g 4 hourly). Blood cultures on September 28, 2021 by guest. Protected of lumbar backache, and . Six grew a penicillin-resistant Staphylococcus epider- years earlier he had undergone a homograft aortic midis from all bottles on day 3. The antibiotic valve replacement for severe aortic regurgitation therapy was changed to flucloxacillin and gen- due to in childhood. tamicin. Thoracolumbar spine radiographs on day He was pyrexial (40TC), with a tachycardia of 2 showed extensive degenerative disease in the 120/minute and a blood pressure of 180/70 mmHg. thoracic and lumbar spine, which was especially There were no stigmata ofendocarditis. On auscul- marked at the level of L2-L3 with anterior bridg- ing osteophytes. The temperature settled and the ESR fell to 56 Correspondence: M.E. Speechly-Dick, B.Sc., M.R.C.P., but he still complained of severe back pain so a Department of Academic and Clinical , bone scan was performed (Figure 1). This sug- University College London Hospitals, Grafton Way, gested ofthe lumbar vertebrae L2 and L3. London WC1E 6DB, UK. This was confirmed by magnetic resonance imaging Accepted: 20 June 1994 of the thoracolumbar spine, which showed evi- Postgrad Med J: first published as 10.1136/pgmj.70.830.885 on 1 December 1994. Downloaded from 886 M.E. SPEECHLY-DICK & R.H. SWANTON by copyright.

Figure 1 Bone scan showing increased concentration of tracer at the level of the second lumbar (L2), which would be compatible with neoplasia or osteomyelitis. dence of osteomyelitis and at L2, and operative recovery was uneventful and after a total

ofthe surrounding soft tissue (Figure of2 months ofintravenous therapy the patient was http://pmj.bmj.com/ 2). A diagnosis of osteomyelitis secondary to discharged home on a 3 month course of oral endocarditis was made. To improve bone penetra- flucloxacillin (1 g 6 hourly) and fusidic acid tion and because of gradually deteriorating renal (500 mg 8 hourly). function fusidic acid (500 mg 8 hourly) was sub- The back pain did not recur and radiographs of stituted for gentamicin. the lumbar spine improved after 2 months. The On day 13 an aortic regurgitant murmur were discontinued after 3 months and developed. confirmed severe the patient remains well more than 2 years later. aortic regurgitation and revealed an aortic root on September 28, 2021 by guest. Protected mycotic aneurysm. The PR interval on the elec- Case 2 trocardiogram (ECG) had not changed. The patient became pyrexial again and intravenous A 65 year old man was admitted with a 2-month teicoplanin (400 mg once daily) was added to the history of anorexia, , intermittent fever, therapy. myalgia and, more recent, low thoracic and lumbar Acute developed on day 14 and backache. He had a past history of submucous emergency replacement was carried resection for a transitional cell carcinoma of the out. At surgery the valve was found to be attached bladder and was undergoing follow-up with annual to the annulus over only 1 cm ofits circumference. cystoscopies, the most recent examination being There was a large aortic root mycotic aneurysm, nearly a year earlier. which was removed, and its cavity was obliterated He was pyrexial (38°C), and looked unwell. by oversewing. The valve was replaced with a There were no stigmata of infective endocarditis. homograft because of the possible problems of There was moderate mitral regurgitation but no anticoagulation as he was a heavy drinker. Post- evidence of cardiac failure. Dental examination Postgrad Med J: first published as 10.1136/pgmj.70.830.885 on 1 December 1994. Downloaded from OSTEOMYELITIS AND ENDOCARDITIS 887

A total of 6 weeks ofintravenous antibiotics and a further 2 months of oral flucloxacillin (500 mg 6 hourly) and probenicid (500 mg 6 hourly) were given. Post-discharge follow-up was close to monitor the resolution of the endocarditis and osteomyelitis, and to follow-up the mitral regur- gitation. The mitral regurgitation gradually deteriorated and 9 months later the patient underwent a replacement. There was no evidence of a recurrence of endocarditis. Repeat thoracic spine radiographs showed gradual improvement over several months. The patient remains well 3 years later. Case 3 A 41 year old man was admitted to another hospital with a 2 month history of malaise, weight loss, night sweats and diarrhoea. He was known to Figure 2 Magnetic resonance imaging scan showing have a but had had dental discitis ofthe second lumbar vertebra (L2) with surround- treatment 3 months earlier without antibiotic pro- ing soft-tissue inflammation indicative of osteomyelitis. phylaxis. He had a history of a suppurating skin wound 2 months before. One week before admis- sion he had noticed black spots on his scalp, fingers revealed an infected left lower molar (there was no and toes. Blood cultures grew Staphylococcus history of recent dental treatment). Neurological aureus, and echocardiography showed a biscupid by copyright. examination was normal, and the spine was mobile aortic valve with vegetations on the anterior valve and non-tender. leaflet and a dilated aortic root. A diagnosis of Investigations revealed a haemoglobin of 10.2 g/ infective endocarditis was made, but despite intra- dl, a white cell count of 8.4 x 109/1 and an ESR of venous treatment with and ciprofloxa- 50 mm/hour. The chest radiograph showed car- cin, his condition continued to deteriorate haemo- diomegaly with clear fields. Echocardio- dynamically. He was then transferred to a car- graphy confirmed a dilated left ventricle with diology unit with cardiothoracic surgery facilities. volume overload, moderate mitral regurgitation On admission he was pyrexial with splinter but no vegetations on the mitral valve. Blood haemorrhages and Osler's nodes, mild splenomeg- cultures grew Staphylococcus epidermidis, which aly and early cardiac failure. Investigation revealed http://pmj.bmj.com/ was fully sensitive to penicillin. a haemoglobin of 10.4 g/dl, white cell count of A diagnosis of probable endocarditis had been 10.7 x 109 and ESR of 92 mm/hour. Echocardio- made on admission and treatment was started with graphy revealed that a fistula between the aortic intravenous penicillin (1.2 g, 4 hourly) and gen- root and the right ventricle had developed, and tamicin (80 mg, 12 hourly). When the there was severe aortic regurgitation. The antibio- results were available, intravenous flucloxacillin tics were changed to a combination of teicoplanin (500 mg, 6 hourly) was substituted for penicillin. (800 mg 12 hourly) and gentamicin (80 mg 8 The infected tooth was extracted with antibiotic hourly). (AVR) with a on September 28, 2021 by guest. Protected cover. Starr-Edwards prosthesis and patch repair of the The backache did not improve and a lateral fistula were carried out. Five days postoperatively thoracic spine radiograph was performed, which complete developed and a permanent showed slight wedging ofthe 10th thoracic vertebra WI pacemaker was inserted. He became apyrexial (T10). A subsequent bone scan revealed dense on antibiotics and made steady improvement. Two uptake of isotope at T1O, raising the possibility of weeks after surgery he developed and either malignant infiltration or infection. In view of underwent cardioversion. His renal function start- the history, a diagnosis of osteomyelitis secondary ed to deteriorate and therefore gentamicin was to infective endocarditis was made. The pain discontinued and rifampicin was added. Three gradually improved with bed rest and antibiotics. A weeks after the initial surgery, he developed repeat lateral thoracic spine radiograph 6 weeks worsening cardiac failure. Echocardiography re- later showed wedging of three vertebral bodies but vealed that the fistula between the aortic root and intact disc spaces with appearances more sugges- right ventricle was patent again, and that the patch tive of osteoporotic collapse. had come away. Surgical repair was attempted for Postgrad Med J: first published as 10.1136/pgmj.70.830.885 on 1 December 1994. Downloaded from 888 M.E. SPEECHLY-DICK & R.H. SWANTON a second time and the prosthesis was also replaced. Another large retrospective study by Meyers et Active infection was seen around the site of the al.4 of the musculoskeletal manifestations of patch closure. Two days postoperatively cardiac endocarditis examined the records of 180 cases of tamponade developed requiring emergency aspira- proven endocarditis and found an of tion. A Hickman line was inserted for the adminis- 28% ofmusculoskeletal symptoms, but they found tration of long-term antibiotics. no cases of osteomyelitis. However, there was one The patient had 6 further weeks of intravenous patient with disc-space narrowing and another therapy with teicoplanin following the second with a paravertebral , and it is possible that operation and steadily improved. He gained weight these patients had undiagnosed osteomyelitis. It and participated in active physiotherapy. He com- would have been difficult to diagnose osteomyelitis plained of mild lumbar back pain 5 weeks after in retrospect if patients were not investigated for it surgery, but there were no abnormal findings on at the time. Mansur et al.S also examined retrospec- clinical examination or on X-ray and the pain tively the incidence ofall complications ofendocar- resolved with mild analgesics. He was discharged ditis in 300 patients who presented between 1978 home with very close follow-up. Unfortunately he and 1986, and found no diagnoses ofosteomyelitis. was readmitted with a pyrexia of 40'C and severe Therefore musculoskeletal symptoms, which can back pain 2 weeks later. Samples were taken for be a prominent complaint in anyone who is unwell, culture and he was restarted on intravenous teico- are a common feature in patients with endocarditis. planin. Spinal radiographs revealed reduced height The seriousness ofthe illness and the high incidence and increased lucency of the 9th thoracic vertebra of musculoskeletal symptoms can mean that the (T9) indicating probable osteomyelitis and this was possibility of osteomyelitis is overlooked. Osteo- confirmed by a bone scan. Blood cultures probably occurs with a frequency of confirmed a recrudescence of S. aureus and approximately 6%.1 It is a well-recognized comp- echocardiography showed probable vegetations on lication of endocarditis, and is thought to be due the aortic valve, and a fistula between the aortic either to microembolism of bacteria or haemato- root and right ventricle. The patient developed genous spread. Invasive organisms such as S. severe acute pulmonary oedema and could not be aureus are thought to result in a higher incidence of by copyright. resuscitated from a . Post-mortem osteomyelitis and, for example, this diagnosis was examination showed that T9 was soft and sur- made in 9% of 35 patients with native valve rounded by purulent exudate. There was active coagulase-negative staphylococcus.2 Mansur et al.' infection in the heart but no in the liver or found that streptococci were the culprit organism . for endocarditis in 49% of 300 cases, but that there was also a high incidence ofS. aureus (20%) and S. epidermidis (5%), and all of these organisms are Discussion capable of causing osteomyelitis. Back pain in the context of positive blood

Musculoskeletal symptoms are common in infec- cultures should be taken seriously and the http://pmj.bmj.com/ tious endocarditis and this makes it difficult for the should investigate any patient with these clinician to select those patients who need inves- findings thoroughly to exclude osteomyelitis. S. tigation for osteomyelitis. Four papers specifically epidermidis is the most frequent cause of positive examined the incidence of musculoskeletal symp- blood cultures in hospital but only 6.3% of these toms in large groups ofpatients with endocarditis. are true bacteraemia.6 However, we should not Thomas et al.3 described musculoskeletal manifes- dismiss coagulase-negative staphylococci in blood tations in 32 of 108 (29.6%) patients treated for cultures as a contaminant, especially if more than infectious endocarditis. These symptoms included one sample is positive because S. aureus and S. on September 28, 2021 by guest. Protected myalgia, articular pain, aseptic arthritis, low back epidermidis account for 60-90% of cases of pain and osteomyelitis. Thirteen of these patients isolated osteomyelitis7 and approximately 30% of (12%) had spinal musculoskeletal symptoms and cases of infective endocarditis.5 there were four cases ofosteomyelitis among them. Fever, back pain and stiffness are the major Patients with endocarditis and musculoskeletal symptoms of osteomyelitis and, as described symptoms did not differ from those without symp- above, these symptoms are also very common in toms in terms ofcause ofinfection, cardiac history, endocarditis. Ifthe back pain is persistent or severe, age, sex, or coexistent clinical signs. Churchill et al.I it would seem sensible to investigate the patient for described an incidence of 44% for musculoskeletal osteomyelitis. It takes between 2 and 8 weeks from symptoms in a survey of 192 patients with endocar- the onset of osteomyelitis before there are any ditis and in 27% these symptoms were the presen- obvious abnormalities on a plain radiograph.7 ting feature. Osteomyelitis was found to be the Even then, in 50% of cases the radiographs are cause of back pain in 6% of the 192 patients; a normal early on or show changes consistent with similar result to that in the study by Thomas et al.3 degenerative arthritis only, the rest are abnormal Postgrad Med J: first published as 10.1136/pgmj.70.830.885 on 1 December 1994. Downloaded from OSTEOMYELITIS AND ENDOCARDITIS 889 and show narrowing of the disc space, sclerosis, antibiotics be given to cases of isolated osteomyel- erosion of the endplates and destruction of the itis without endocarditis and even with this regime vertebral bodies.8 Computerized tomography (CT) they experienced a relapse rate of one case in 20. may also be normal in the early stages or may They advocate surgical debridement where there is disclose a reduction in disc density, an early sign of extensive destruction of the vertebral bodies with osteomyelitis.8 Magnetic resonance imaging may sequestra and abscess formation and, of course, if reveal abnormalities earlier than either plain there are signs ofspinal cord compression. Barham radiography or CT scanning, but is not always et al."1 described a case of streptococcal endocar- available. However, radionuclide bone scans with ditis and osteomyelitis, which resolved after 5 either gallium or technetium have a very high weeks of intravenous antibiotics followed by 3 sensitivity and are the diagnostic procedure of weeks of oral amoxycillin and erythromycin. A choice if plain radiographs have been unhelpful.8'9 case of S. epidermidis endocarditis resulting in Radionuclide scanning can provide evidence of osteomyelitis at the level T9-TI0 was cured after a bone infection within 48 hours ofthe infection; the course of4 weeks ofhigh-dose intravenous fluclox- radionuclide concentrates avidly at sites of in- acillin followed by 5 months of oral amoxycillin.'2 creased blood flow and bone turnover. Therefore, In our experience of S. epidermidis endocarditis the differential diagnosis of osteomyelitis is of and osteomyelitis, successful cure can be achieved metastatic malignancy, where lesions are usually iftreatment is continued for at least 3 months. For multiple and scattered through the axial skeleton, example, case 1 had a total of 8 weeks of intra- arthritides and Paget's disease, which have typical venous therapy followed by 3 months of oral distributions, and trauma, which can be differen- flucloxacillin and fusidic acid, and case 2 had 6 tiated by the history.'" The diagnosis ofosteomyel- weeks ofintravenous therapy and 2 months oforal itis is made from the typical picture of increased flucloxacillin with probenecid. Case 3 had 10 weeks radionuclide uptake of the affected area on the ofintravenous antibiotics prior to discharge but no bone scan in association with an appropriate long-term treatment. Unfortunately, osteomyelitis clinical history. Adatepe et al.9 state that a normal was diagnosed late in case 3 and a recrudescence of bone scan excludes a diagnosis ofosteomyelitis. We endocarditis, most likely due to local reinfection by copyright. recommend that any patient in whom there is a although possibly from the bony focus, proved reasonable suspicion ofosteomyelitis should have a fatal. bone scan. In conclusion, we recommend that a diagnosis of Prolonged treatment with antibiotics is needed osteomyelitis is considered in any patient with to sterilize a bony focus, which may be a potential infective endocarditis and back pain, especially if site for reinfection in a patient with an abnormal the pain is persistent, severe or localized, and that valve. Acute haematogenous osteomyelitis can be physicians should have a high index of suspicion successfully treated with antibiotics alone unless a for this condition. These patients should be inves- late diagnosis has been made and extensive bone tigated with plain radiography and a bone scan, if necrosis has already occurred, in which case the the radiograph is normal. We also advocate that http://pmj.bmj.com/ dead bone must be surgically removed because it the treatment regime consists ofat least 6 weeks of harbours and is difficult to intravenous antibiotics, and 3 months or longer of sterilize.' outpatient oral therapy with close follow-up. Recommended antibiotic regimes range in total Patients should be encouraged to keep a tempera- length from 6 weeks to 6 months. Waldvogel et al.7 ture chart at home and any recurrence of fever or suggest that at least 6 weeks of parenteral back pain should, of course, be investigated. on September 28, 2021 by guest. Protected

References 1. Churchill, M.A., Geraci, J.E. & Hunder, G.G. Mus- 5. Mansur, A.J., Grinberg, M., Lemos de la Luz, P. & Bellotti, culoskeletal manifestations of bacterial endocarditis. Ann G. The complications of infective endocarditis. Arch Intern Intern Med 1977, 87: 754-759. Med 1992, 152: 2428-2432. 2. Etienne, J. & Eykyn, S.J. Increase in native valve endocarditis 6. Arber, N, Militianu, A., Ben-Yehuda, A. et al. Native valve caused by coagulase negative staphylococci: an Anglo- Staphylococcus epidermidis endocarditis: report of seven French clinical and microbiological study. Br Heart J 1990, cases and review of the literature. Am J Med 1991, 90: 64: 381-384. 758-762. 3. Thomas, P., Allal, J., Bontoux, D. et al. Rheumatological 7. Waldvogel, F.A. & Vasey, H. Osteomyelitis: the past decade. manifestations of infective endocarditis. Ann Rheum Dis N Engl J Med 1980, 7: 360-368. 1984, 43: 716-720. 8. Demers, C., Tremblay, M. & Lacourciere, Y. Acute vertebral 4. Meyers, O.L. & Commerford, P.J. Musculoskeletal manifes- osteomyelitis complicating sanguis endocar- tations of bacterial endocarditis. Ann Rheum Dis 1977, 36: ditis. Ann Rheum Dis 1988, 47: 333-336. 517-519. Postgrad Med J: first published as 10.1136/pgmj.70.830.885 on 1 December 1994. Downloaded from 890 M.E. SPEECHLY-DICK & R.H. SWANTON

9. Adatepe, M.H., Powell, O.M., Isaacs, G.H., Nichols, K. & 11. Barham, N.J., Flint, E.J. & Mifsud, R.P. Osteomyelitis Cefola, R. Hematogenous pyogenic vertebral osteomyelitis: complicating Streptococcus milleri endocarditis. Postgrad diagnostic value of radionuclide bone imaging. J Nucl Med Med J 1990, 66: 314-315. 1986, 11: 1680-1685. 12. Gosbell, I., Gottlieb, T. & Bradbury, R. Native valve 10. Sutton, D. Textbook of Radiology and Imaging, 5th edn. endocarditis and vertebral osteomyelitis caused by Staphylo- Churchill Livingstone, Edinburgh, 1993, pp. 46-62. coccus epidermidis. Med J Aust 1992, 156: 662. by copyright. http://pmj.bmj.com/ on September 28, 2021 by guest. Protected