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Is a negative gram stain in suspected septic arthritis sufficient to rule out septic arthritis

Three Part Question

In [adults with suspected arthritis] is [a negative Gram stain of the joint aspirate ]sufficient [to rule out septic arthritis]

Clinical Scenario

A 30 year old Nurse presents to the ED with two day history of a hot, swollen joint. She reports no prior knee swelling and no recent trauma or knee surgery, illegal drug use, rash, uvetis or risky sexual behavior. On examination, she is afebrile and has a left knee effusion. Her WBC, ESR and CRP are all raised. The joint aspirate reports a negative gram stain. You wonder if negative gram stain is enough to rule out septic arthritis?

Search Strategy

Multifile search using OVID – Medline (1950-2008), Embase (1980-2008), CINHAL (1982-2008), Cochrane ({[exp.Infectious Arthritis OR hot OR septic OR septic] AND [exp. Gram stain OR gram stain$.mp] AND [exp Synovial Fluid OR aspirate$.mp OR synovialfluid$.mp]}) Limited to Humans, English Language and Adults

Search Outcome

The following number of articles were identified from each of the databases: Medline 20 citations, Embase 22 citations, CINAL 0 citations, Cochrane 1 citations. Duplicates and irrelevant titles removed from 43 articles leaving a total of 8 relevant articles.

Relevant Paper(s)

Author, date and country Patient group Study type (level of evidence) Outcomes Key results Study Weaknesses
Daniel C, et al
49 culture positive synovial fluid aspirates in an ED in an urban tertiary care center Case Series (Level 3) Gram stainNegative in 27/49 (55%;95%CI, 37-74%)Imperfect Gold standard*
Nausha A, et al.
116 patients from a tertiary care hospital identified by the ICD 711 as having SARetrospective Cohort (Level 3) Gram Stain78/116(67.2%) had a gram stain done 26/78 (33.3%) stained positive for a specific organism and 52/78 (66.7%) inconclusiveSmall sample. Narrow definition of SA.
Faraj A, et al
22 patients of who had arthroscopic lavage following a provisional diagnosis of SA who later were all found to have culture proven SACase Series (Level 3) Gram StainSensitivity 45% Specificity 100%Case Series. Small sample. No confidence intervals
Margaretten ME, et al.
Fourteen studies involving 6242 patients, of whom 653 diagnosed with SA and met all respective inclusion criteria.Systematic Review (Level 1)Gram StainSeven studies identified that reported sensitivities of 29-50%[1-5]No confidence intervals. Imperfect gold standard*
McCutchan, et al.
41 patients diagnosed with SA on a positive culturesCase Series(Level 3)Gram StainPositiveCase Series. Small Sample


There is no evidence to suggest that a gram stain is sensitive enough to rule out septic arthritis such that a negative gram stain should not be taken as evidence to rule out SA.[1-8] This is supported by studies that have noted the absence of gram stain with a positive culture.[Mc Cutchan, Daniel] Most of the studies of the value of gram stain have been case series, therefore specificity is often not calculated. In the one retrospective study that looked at patients undergoing arthroscopic lavage following a provisional diagnosis of SA, specificity was calculated as 100%. [Faraj] A positive gram stain can therefore rule in (Spin) SA.

Editor Comment


Clinical Bottom Line

A negative gram stain is not sufficiently sensitive to rule out septic arthritis. A positive gram stain is sufficient to rule in SA. *Imperfect Gold Standard –gram stain (sensitivity 29-50%) and culture (sensitive-82%)[Margaretten].


  1. Daniel C, et al. How sensitive is the synovial fluid white blood cell count in diagnosing septic arthritis? American Journal of Emergency Medicine. 2007;749-752
  2. Nausha A, et al Septic arthritis in a tertiary care hospital Journal of Pakistan Medical Association
  3. Faraj A, et al. Gram staining in the diagnosis of septic arthritis Acia Orthopadica Belgica 2002;388-391
  4. Margaretten et al. Does the Adult Patient have Septic Arthritis? JAMA 2008;1478-1488
  5. McCutchan HJ, et al. Synovial leukocytosis in infectious arthritis. Clinical Orthopaedics and Related Research . 2002;388-391
  6. Soderquist B. Bacterial or Crystal –associated Arthritis? Discriminating Ability of Serum Inflammatory Markers. Scandinavian Journal of Infectious Diseases. 1998;30:591-596
  7. Krey PR. Synovial fluid leukocytosis :a study of extremes. American Journal of Medicine. 1979;67:436-442.
  8. Korekangas P. Synovial fluid in bacterial arthritis vs. reactive arthritis and rheumatoid arthritis in the adult knee. Scandinavian Journal of Rheumatology. 1992;21:283-2886.