Non-gonococcal infectious arthritis: A retrospective study

Journal of Infection (I987) I4, I3-2o

Non-gonococcal

infectious arthritis: a retrospective study

K. A. E. Meijers,* B. A. C. D i j k m a n s , * J. H e r m a n s , t P. J. v a n den Broek~ a n d A. Cats*

* Department of Rheumatology, t Department of Medical Statistics, Department of Infectious Diseases, University Hospital, Leiden, The Netherlands Accepted for publication 22 June I986 Summary In a retrospective study the outcome of non-gonococcal infectious arthritis was evaluated in 76 adult patients admitted to the Leiden University Hospital between I97o and x984. The mortality rate was Iz %, and complete recovery was achieved in only ~9 of the 76 patients (25 %). Each of the following had a significantly unfavourable influence on the residual joint function: duration of infection more than ~4 days, female sex, presence of rheumatoid arthritis, and presence of a joint prosthesis.

Introduction T h e availability of antibacterial therapy during the last few decades has greatly i m p r o v e d the o u t c o m e of m a n y infections and infectious diseases. T h e frequency of infectious arthritis, however, has not decreased during the last two or three decades. 1-4 T h i s disease remains important in terms of b o t h mortality and residual joint deformity. ~ M a n y reports mention the presence of various diseases and their treatment as increasing the risk of infectious arthritis (Table I). 3-6 Admission to the University Hospital, Leiden of a large n u m b e r of patients for non-gonococcal infectious arthritis over a period of I4 years p r o v i d e d material for a retrospective study. T h e p u r p o s e of this study was to evaluate the influence of various factors on the end-result of treated infectious arthritis.

Material and methods F o r entrance into this study, patients admitted to the D e p a r t m e n t of R h e u matology or seen b y the consultant rheumatologist b e t w e e n I97o and I984 had to satisfy two criteria: (I) a clinical picture consistent with synovitis and (z) the isolation of a micro-organism from the synovial fluid (SF). All patients, except two, were Caucasians of D u t c h origin living in and around the city of Leiden. O f the two non-Caucasians neither was k n o w n to have haemoglobinopathy. N o n e of those studied was k n o w n to be addicted to drugs or to alcohol. T h e patients were treated as soon as the diagnosis was suspected, cultures having been p e r f o r m e d on SF, blood, and, if possible, material from the suspected p o r t - o f - e n t r y of infection. Because at that time the invading micro-organism was usually not yet known, patients were treated initially as Correspondence to: Dr K. A, E. Meijers, Department of Rheumatology, University Hospital, B.O. 9600, ~3oo RC Leiden, The Netherlands. oi63-4453/87/oioox3 +08 $02.00/0

© I987 The British Society for the Study of Infection

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K. A. E. M E I J E R S

ET AL,

Table I Possible predisposing conditions and treatment in 76 patients with non-gonococcal infectious arthritis

No. of patients Apparently healthy R h e u m a t o i d a r t h r i t i s (RA) R A + diabetes mellitus Diabetes mellitus Collagen diseases Miscellaneous Miscellaneous

+

IO 43 2 3 7 io

Prednisone and/or cytostatic drugs

Joint prosthesis

-I2

-xo

--

--

-7 3

I -I

I

i

76

23

--

diabetes mellitus Total

I2

a rule with 6 g cloxacillin daily intravenously a n d / o r 7"5 m g / k g body weight kanamycin twice daily intravenously, kidney function being taken into account. This regimen was modified as soon as the identity of the micro-organism and its susceptibility were known. Antibacterial therapy was continued for 6-IZ weeks, depending on the clinical response. T h e patients infected by a mycobacterium were treated with antituberculous drugs for 9-r2 months. Pus in the infected joints was aspirated daily for up to 7 days. If this did not lead to sufficient improvement, surgical drainage was performed. F r o m the very beginning, the joints were kept in a proper position by splinting a n d / o r traction. Careful physiotherapy was applied, first with passive and later with active movement. T h e clinical records of all patients were reviewed. T h e following were considered as possibly having had an influence on the final outcome: duration of the disease, age, sex, the presence and type of underlying disease, the presence of a prosthesis, treatment with prednisone a n d / o r cytostatic drugs, the species of the causative micro-organism, the kind and n u m b e r of affected joints, positive Gram-staining of SF and a positive blood culture as well as leucocyte counts of peripheral blood and SF. T h e final function of the joint was scored as cured or not cured by one of us (K. A. E. M). Those whose joints were not cured included patients with moderately impaired (limited but not complete loss of movement) or seriously impaired (complete loss of movement) joint function. Ability for work was not taken into account for scoring the repair of joint function since employment depends on underlying diseases and social factors. Statistical analysis was performed with Student's t-test, x2 tests, and stepwise discriminant analysis.

Non-gonococcal infectious arthritis

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Table 11 Affected joints in 76 patients with non-gonococcal infectious arthritis No. of Percent joints infected affected joints

Joint Hip Knee Metacarpophalangeal joint Wrist Sternoclavicularjoint Elbow Shoulder Ankle Metatarsophalangeal joint Total

i2 40 4 9 3 Io 12 4 5 99

i6 53 5 i2 4 13 16 5 7

Results Patients' characteristics

During the period of study, 76 patients were seen (age range: I4-86 years), 4I males (54%; age range: I4-79 years) and 35 females (46%; age range: I4-86 years). T h e patients seen up to I978 have been described elsewhere. 7 T h e annual rate of infection was roughly constant. T e n of the 76 patients were apparently healthy; the others suffered from various underlying diseases, 45 (59%) of them from rheumatoid arthritis (RA) and two of those also from diabetes mellitus (Table I). Twenty-three of the 76 patients were on prednisone and/or a cytostatic drug. Infected prosthetic joints were present in I2 patients. Four patients had a total hip prosthesis, six RA patients had a total knee prosthesis, one RA patient had a Swanson prosthesis in a metacarpophalangeal joint, and one patient had a pin after fracture of the hip. D u r a t i o n o f disease

T h e time between the first symptoms and diagnosis was shorter than I4 days in 5I patients (67%), called here the early admission group. T h e other 25 patients, for whom this interval was longer (at most 9 months), formed the late admission group. Joints

Almost all joints may become infected, but the knees are involved most often, followed by the hips and shoulders (Table II). Sixty patients (79%) had monarthritis, i I had two infected joints, four had three, and one patient had six. P o r t o f e n t r y o f the m i c r o - o r g a n i s m s

The port of entry could be identified in 51 patients. Skin lesions were the most common site, i.e. in 32 patients (42 %). In I3 patients (I7 %) joints had become infected via a respiratory, urogenital, or intestinal infection and in six patients

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K.A.E. MEIJERS E T A L .

Table I I I Micro-organisms cultured from synovial fluid of 76 patients Micro-organism

No. (%)

Staphylococcus aureus Staphylococcus epidermidis Streptococcus species Streptococcus pneumoniae Listeria monocytogenes Salmonella agona Escherichia coli Pseudomonas aeruginosa Serratia marcescens Bacteroides species + others Mycobacterium species Cryptococcus neoformans

47 (62) 6 (8) 8 (I I) 2 (3) I (I) I (I) 2 (3) I (I) I (I) 3 (4) 6 (8) I (I )

Mixed flora Two patients: Staphylococcus aureus and anaerobic micro-organism. One patient: Staphylococcus aureus and Mycobacterium kansasii.

(8 %) via intra-articular injections. In 25 patients the port of entry remained Unknown. Laboratory data

Gram-staining of SF was revealing in 49 cases (65 %) and gave the first indication o f the species of the invading micro-organism. W h e n Gram-staining was unhelpful and bacteria could not be cultured, Z i e h l - N e e l s e n staining was p e r f o r m e d ; this stain was applied in seven cases, and gave positive results in two of them. T h e frequency of occurrence of the micro-organisms in question is shown in Table I I I , from which it may be seen that Staphylococcus aureus was cultured the most often, followed by Streptococcus spp. and Staphylococcus epidermidis. T h e incidence of Gram-negative aerobic bacteria was 6 %. M y c o bacteria were present in six patients, in four of t h e m being Mycobacterium tuberculosis and in the other two Mycobacterium kansasii or Mycobacterium terrae. T h r e e of these six patients were taking oral glucocorticosteroids; one of t h e m was found to have overt p u l m o n a r y tuberculosis. In the four patients with M . tuberculosis infection, haematogenous spread seems to have been the most likely mechanism. I n two patients, infection with the atypical m y c o bacteria developed after intra-articular corticosteroid injections in the knee. Blood cultures were p e r f o r m e d on 70 patients and were positive in 22 (31%) o f them, all but one being in the early treatment group. L e u c o c y t e counts were p e r f o r m e d on 24 specimens of SF. In 20 o f t h e m the count was higher than 20 × I09/1; the highest n u m b e r was I25 x IO9/1 and the lowest 4 x Io9/1. T h e n u m b e r o f leucocytes in the peripheral blood ranged between 4 and I8 x Io9/1; the count lay below IO x io9/1 in 47 patients.

Non-gonococcal infectious arthritis

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Table IV Results of treatment in 76 patients with non-gonococcal infectious

arthritis two of whom were lost to follow-up Joint status Died No. of patients RA Other diseases or 'healthy' Duration of disease < I4days < 7 days > I4 days Age range (years) Mean S.D.

Survived

9 (I2%) 65 (85%) 9 35 -3o

cured

not cured

P

I9 4 I5

46 31 15

0"002*

25

9(I2%) 8 -51-85 66

42(550/0) 3I 23 (3I %) I4-86 55

I7 I3 2 I4-76 46

I2

I6

I8"8

6 (8%)

35 (46%)

I6

19

3 (4%) 2

30 (40%) 9

3 --

27 9

2I

0"02*

I7-86 58 13

Sex M

F Prosthesis

0"004*

* g 2 test.

Treatment T w o of the 76 patients could not be f u r t h e r evaluated. N i n e (12 ~o) died soon after diagnosis; all of these suffered f r o m RA, eight died of septicaemia within I week after admission and one of cardiac insufficiency due to infectious endocarditis 3 weeks after t r e a t m e n t began (Table IV). T h e causative microorganism of all nine patients who died was a Gram-positive coccus; in five, Staphylococcus aureus, in two, Streptococcus spp. and in two, Streptococcus

pneumoniae. State o f joint Joint function recovered in I9 of the 65 surviving patients (Table IV). Recovery was complete in only four of the 35 surviving patients with RA. O f the remaining 31 R A patients, 16 had moderately and 15 severely limited joint function. Statistical analysis disclosed that the final outcome was significantly worse in the patients with R A t h a n in the others (P = o.ooz). T h i r t y patients had no u n d e r l y i n g joint disease; in half of t h e m joint function was good after the infection. T h e presence of these diseases had no influence on the final state of the joint. In five patients infection recurred in the same joint, the interval to relapse ranging f r o m a few days to 2 years. Other factors T h e cured and n o n - c u r e d groups did not differ as to positive blood cultures and SF Gram-staining. Statistical analysis with the chi-squared test, comparing each single group of bacteria (Staphylococcus aureus, Staphylococcus epidermidis, Streptococcus spp. G r a m - n e g a t i v e bacteria and Mycobacterium

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K. A. E. MEIJERS E T A L .

spp.) with that of the other micro-organisms, disclosed that the species of micro-organism was of no importance for recovery of joint function, except with respect to the slightly but not significantly (P = 0.2) more destructive effect of the mycobacteria. Concomitant therapy with prednisone a n d / o r immunosuppressive drugs had no influence on the final outcome of joint function. T h e higher the number of leucocytes in the SF, the more favourable the outcome for the joint (P = o'o3). T h e chance of recovery of function was lower for the wrist and shoulder than for the other joints, but this difference is not statistically significant. T h e presence of a prosthesis had an unfavourable prognosis: in all but two of the nine surviving patients the prosthesis had to be removed. Duration o f Disease

Among the 5 r early admissions, nine patients died and 17 completely recovered (Table IV). Of the 25 late admissions, two of whom were lost for follow-up, none died and two completely recovered. T h e difference between cured and non-cured joints is statistically significant, early admission giving a better outcome (P = o.o2). Age

Infectious arthritis affected those of all ages in adults but those who died were all more than 50 years of age (Table IV). Although the mean age of the group with a cured joint is slightly less than that in the group without cure, the influence of age on the final function of an infected joint proved to be negligible. Sex

Six of the 4I males died and three of the 35 females (Table IV). Recovery of function of the infected joint was significantly poorer in females than in males (P = 0"oo4). Although many of the female patients had RA as well, statistical analysis showed that the poorer prognosis was attributable to both sex and RA.

Discussion

T h e main conclusion drawn from the present study is that infectious arthritis still has a high mortality (I2 % ) and high residual impairment of joint function (6I % of the total group had impaired function of the affected joint). Recovery of function was unfavourably influenced by lateness of admission to hospital among the survivors, the presence of RA or a joint prosthesis, and female sex. Goldenberg and Cohen ~ saw a higher rate (67 %) of complete remission when treatment was started within 7 days after the onset of the infection. This marked divergence from our findings cannot be explained by our later cut-off point for early admission, since our rate of cure comes to 33 % when calculated for their cut-offpoint. As major factors influencing the prognosis unfavourably, Rosenthal and colleagues 1° found the-presence of a prosthesis, longer duration of disease, and impaired host resistance. T h e 76 adult patients with nongonococcal infections arthritis in the present series had been treated in a 6oo-bed hospital over a period of I4 years. Our frequency of about five infections annually agrees with previous reports ~-8, 10. 11 and shows that the

Non-gonococcal infectious arthritis

I9

incidence of infectious arthritis has remained unaltered during the last few decades.a, 7 Recently, a higher incidence due to drug abuse in a large city has been reported. 12 Points of similarity between earlier reports and our series are a higher incidence in patients more than 50 years of age, a male preponderance, the distribution of the infected j o i n t s - (the knee joint being the most frequently involved) and Staphylococcus aureus as the responsible microorganism, predominating. 3-7, 10-12 Infectious arthritis is generally thought to be due to haematogenous spread of bacteria. Blood cultures were positive in 2I (40%) of the 5I patients admitted to hospital early and one of those admitted late. In I4 of those with positive blood cultures the port of entry was the skin and in i2 cases the invading micro-organism was a Staphylococcus spp. In half of the total series, including the RA patients, the skin was the most likely port of entry; other authors refer more often to sites such as the urogenital tract. 1° T h e invading micro-organism can also reach the joint by extension from an infected site in the vicinity; it can also be implanted in the joint during an intra-articular injection. T h e percentage of patients with aerobic Gram-negative bacteria in the present series is small, contrary to previous reports. 5. 10 This difference may be due to the absence of children, drug abusers, and alcoholics in our series and which was not the case in other studies, z, 10 It was somewhat surprising that the species of micro-organism proved of no importance for the recovery of joint function except for the more destructive effect of the mycobacteria. Goldenberg and Cohen 5 considered the Gram-negative infections to be more destructive; but Rosenthal and colleagues' findings 11 agree with ours. It is less surprising that more than 50% of the patients who died suffered from infections with Staphylococcus aureus. It must be kept in mind that bacterial arthritis in a patient with RA is dangerous.tS-2° T h e incidence in several studies on RA patients ranges from o'3 to 3 o/0.19 Diagnosis may be difficult because the clinical picture may resemble a flare-up of the rheumatoid synovitis. T h e mortality due to this complication in RA is high; the 20% in our RA group accords approximately with the 30 % mentioned in earlier reports29 T h e loss of joint function is also high; only four of our 45 RA patients had a cured joint. Joint prostheses are often used in RA patients but when they become infected the prognosis is unfavourable. One intriguing question is why infectious arthritis arises so often in RA patients. It has been suggested that chemotaxis of the polymorphonuclear (PMN) leucocytes of patients with RA is impaired. 21 Even so, impairment of P M N leucocyte function was not found in recent work on the phagocytosis and intra-cellular killing of micro-organisms by leucocytes in the SF of RA patients. 22 Furthermore, it is conceivable that in infected RA joints bacteria are concealed in small niches and are therefore less accessible to phagocytosing leucocytes than they would be in a normal joint. From the present results it is clear that despite the availability of new antibacterial agents and a better understanding of the influence of major factors on the outcome, infectious arthritis is still a disease with a high mortality and a high rate of joint impairment. (The authors are greatly indebted to Marian Rusman for secretarial help.)

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K . A . E . MEIJERS E T A L .

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