Novobiocin

Bone or joint infection due to Staphylococcus lugdunensis is rare, there being only a small number of case reports in the literature.1-9 In six cases, infection was either a local complication of recent surgery2-4 or associated with an underlying prosthetic joint.7,8 However, in other reports, particularly relating to vertebral osteomyelitis5,8,9 and an epidural abscess,6 there were no apparent risk factors. These cases demonstrate that bone and joint infection due to S. lugdunensis may be associated with severe clinical manifestations and therapeutic difficulties. Furthermore, the bacteriological diagnosis may prove elusive due to the potential for S. lugdunensis to be misidentified.

To illustrate this point, an unusual case of infective discitis due to S. lugdunensis is described in a patient who similarly had no apparent risk factors. In this patient, the diagnosis of S. lugdunensis bacteraemia was missed, and the subsequent diagnosis of S. lugdunensis infective discitis delayed by six months, due to the lack of a laboratory screening strategy to distinguish S. lugdunensis from other coagulase-negative staphylococci (CNS) isolated from blood culture.

In addition, recommendations for laboratory procedures to avoid such misdiagnoses are discussed.

A 73-year-old woman with severe osteoarthritis underwent corrective foot surgery in July 2000. Apart from penicillin allergy, she was otherwise well. Four weeks later she presented with diffuse low back pain, constipation and painful retention of urine. She was afebrile and general examination was normal. Her erythrocyte sedimentation rate (ESR) and C-reactive protein (CRP) were both elevated at 138 mm/hr and 231 µg/mL, respectively.

She was treated for five days with intravenous cefuroxime for a presumed urinary tract infection. At the time of admission, however, urine culture was negative but a penicillin-sensitive CNS (clumping factor- and protein A-negative; Pro-Lab Diagnostics, Canada) was isolated from two separate blood culture sets. The CNS isolates had similar antibiograms but were not speciated because they were thought to reflect skin contamination.

A plain X-ray at presentation demonstrated degenerative changes at multiple levels within the lumbar spine, with loss of disc height at L4/L5; however, the vertebral endplates were well preserved. Subsequently, a magnetic resonance imaging (MRI) scan of the lumbosacral spine showed high signal within the L4/L5 intervertebral disc, which was of reduced height.

Disc degeneration most commonly leads to loss of hydration and therefore low signal on the T2 weighted images. The appearance of high signal within this disc raised the suspicion of discitis. Minimal enhancement after gadolinium was demonstrated, however, and therefore the appearances were thought clinically to be most likely due to degenerative changes.

The patient was re-admitted six months later with a five-day history of severe low back pain. ESR and CRP remained elevated at 100 mm/hr and 97 ng/mL, respectively. A repeat MRI examination of the lumbosacral spine showed extensive marrow signal abnormality within the L4 and L5 vertebral bodies, with extensive enhancement within the L4 and L5 vertebral bodies and within the peripheral margin of the L4 / L5 disc and adjacent endplates.

A lumbar spine X-ray obtained prior to computed tomography (CT)-guided biopsy now demonstrated illdefined lytic destruction of the vertebral endplates around the L4/L5 disc, with features in keeping with infective discitis and osteomyelitis. CT-guided bone biopsies of the L4/L5 intervertebral disc space and superior endplate of L5 both yielded penicillin-sensitive CNS (clumping factor- and protein A-negative). Isolates were identified as S. lugdunensis by API 20 Staph (bioMérieux, SA, France), and were confirmed by the Division of Hospital Infection, Public Health Laboratory Service, London.

Antibiotic profiles of the S. lugdunensis isolates and the previous penicillin-sensitive CNS grown from blood cultures were identical. All strains were sensitive to penicillin, erythromycin, clindamycin, gentamicin, fusidic acid, tetracycline, rifampicin, ciprofloxacin, chloramphenicol and vancomycin.

Following the biopsy procedure, blood culture was repeated and this grew S. epidermidis (penicillin- and fusidic acid-resistant), which was considered to be a contaminant. The patient was treated with clindamycin for a total of four weeks and made a good clinical recovery. There was no clinical evidence of infective endocarditis and an echocardiogram showed no abnormality. Two months later her CRP had returned to normal.

S. lugdunensis is a CNS named after the Latin name for Lyon, the French city where it was first described in 1988. It is characterised by a failure to produce free tube coagulase with rabbit and bovine plasma, but is clumping (fibrinogen affinity) factor- and ornithine decarboxylase (ODC)-positive.10 Isolates are typically penicillin-sensitive.1-9,11,12

S. lugdunensis has been associated most commonly with skin and soft-tissue infection, including abscess formation.11 It is also an important cause of infective endocarditis, often attacking native valves, and follows an aggressive course.12-14 The clinical picture, therefore, can be similar to S. aureus infection, particularly as there may not be an obvious portal of entry. A single case of S. lugdunensis meningitis following ventriculostomy has also been reported recently.15 S. lugdunensis has also been linked to brain abscess, peritonitis and vascular prosthetic infections.1

In the case reported here, S. lugdunensis bacteraemia probably occurred following foot surgery. The subsequent infective discitis with vertebral osteomyelitis is typical of haematogenous spread. The penicillin-sensitive CNS originally isolated from blood culture showed an identical extended antibiogram to the S. lugdunensis strains cultured from intervertebral disc and bone-marrow biopsies. Unfortunately, they were not available for further examination when the patient was re-admitted. If further identification tests had been undertaken when the blood culture CNS were first isolated, it is likely that the patient would have avoided the prolonged delay in diagnosis.

Few laboratories have screening strategies in place to distinguish S. lugdunensis simply from other blood culture CNS because infection is so rare. In a study of 258 CNS in blood cultures, S. lugdunensis accounted for only 1.1% of true bacteraemic isolates and 1.6% of contaminants. The most common species were S. epidermidis, S. hominis and S. haemolyticus.16

In an earlier study of 978 tube coagulase-negative staphylococcal isolates from blood culture, no strains of S. lugdunensis were found.11 Similarly, a 20-year review of 89 staphylococcal isolates from patients with bacterial endocarditis identified S. lugdunensis in only four cases.17

Nevertheless, in view of the clinical importance of S. lugdunensis infection, a variety of screening strategies have been proposed, including tests for pyrrolidomylarylamidase (PYR), ODC, alkaline phosphatase and maltose/marmose fermentation.11,18,19 For clumping factor-positive CNS, only PYR and ODC are required to identify S. lugdunensis. If clumping factor-negative, then an additional fermentation test is required for confirmation.

Although these tests are available as commercial media, they may prove expensive because CNS are the most frequently isolated bacteria from blood culture sets. Therefore, their suitability in busy diagnostic laboratories is questionable. However, the recently introduced 'ID staphylococcus ring' (Mast Diagnostics, UK), which incorporates tests for novobiocin and desferrioxamine sensitivity with p-nitro phenol phosphate, is a promising alternative. Although requiring further evaluation, it is designed to distinguish simply the main CNS pathogens (S. epidermidis, S. saprophyticus, S. haemolyticus and S. lugdunensis), and therefore may provide an alternative screening system.

Clumping factor-positive, tube coagulase-negative staphylococci clearly warrant further follow-up because S. lugdunensis and S. scheiferi are the most likely species. However, as demonstrated in the case study presented here, clumping factor alone cannot be relied upon because the test is not 100% positive (87% from human plasma, 73% from rabbit plasma) for S. lugdunensis strains.18

Furthermore, the ability of commercial reagents widely used in diagnostic laboratories to detect staphylococcal clumping factor have also not been specifically evaluated against S. lugdunensis strains. Similarly, ODC is not a unique characteristic for S. lugdunensis as mis-identifications due to weakly positive results in some cases of S. haemolyticus isolates have been reported.18

Most case reports of S. lugdunensis infection have been due to [beta]-lactamase-negative, penicillin-sensitive strains. This is a relatively unusual characteristic for CNS. In our own laboratory, only 5% of CNS from blood culture exhibit penicillin sensitivity. Hence, the routine speciation of penicillin-sensitive CNS may prove to be a simple screening strategy to distinguish S. lugdunenis from other CNS isolated from blood culture.

However, in view of occasional reports of penicillin resistance and, more recently, oxacillin resistance linked to the mecA gene,20 we suggest that all CNS repeatedly isolated from blood culture or predominant growths from deep tissue samples should be identified to species level.

References

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18 Leung MJ, Nuttall N, Mezur M et al. Case of Staphylococcus schleifen endocarditis and a simple scheme to identify clumping factor positive staphylococci. J Clin Microbiol 1999; 37: 3353-6.

19 Schritzler N, Meilicke R, Conrads G, Frank D, Haase G. Staphylococcus lugdunensis: report of a case of peritonitis and an easy-to-perform screening strategy. J Clin Microbiol 1998; 36: 812-3.

20 Tee WSN, Yen Soh S, Lin R, Loo LH. Staphylococcus lugdunensis carrying the mecA gene causes catheter-associated bloodstream infection in premature neonate. J Clin Microbiol 2003; 41: 519-20.

R. P. D. COOKE*, S.E. JAMES[dagger] and D.E. SALLOMI[double dagger]

* Departments of Medical Microbiology, [dagger] Orthopaedic Surgery and [double dagger] Radiology, District General Hospital, Eastbourne, East Sussex BN21 2UD

Correspondence to: Dr RPD Cooke

Email: richard.cooke@esht.nhs.uk

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