вход по аккаунту


Ongoing assessment of therapy in septic arthritis.

код для вставкиСкачать
Ongoing Assessment of Therapy in Septic Arthritis
of patients with
septic arthritis, questions about treatment continue to be points of controversy.
Whether antibiotics must be instilled intraarticularly and what type of joint drainage
is required are two prime issues, still unresolved. Some physicians favor routine injections of antibiotics into the joint, as well
as systemically, and always perform open
drainage of the joint with or without continuous
Yet closed-space infections in other regions of the body, such as
the pleural or subarachnoid space, usually
are not handled in this empirical fashion.
Antibiotics in these situations are customarily administered solely by the systemic
route, and decisions about the required type
of drainage are based upon assessment of
the condition of the individual patient. Underlying this approach is abundant evidence
that antibiotics penetrate enclosed and infected body spaces and achieve bactericidal level^.^
Why is the approach to septic arthritis in
dispute? Two reasons may be advanced.
First, there is a dearth of data about the
transport of antibiotics into joints in contrast
to other body spaces.6 Consequently, some
clinicians are reluctant to abandon constant
intraarticular instillation of antibiotics and
to rely on systemic administration alone.
Second, the rapidity of joint destruction by
products of the inflammatory exudate
creates an understandable urgency in the
treatment regimen. The consequences of a
damaged joint are a constant reminder to
the patient and the physician in a way that
an adhesive pleura or thickened arachnoid
membrane is not. However, it is our contention that the basic principles that govern
treatment of closed-space infections in other
regions of the body should apply also to
the joint.
From the Arthritis-Connective Tissue Diseases
and Infectious Diseases-Hypersensitivity Sections,
Department of Medicine, Northwestern University
Medicd Center, Chicago, Illinois.
Supported in part b y USPHS Training Grant
AM-05069 and Reseurch Grant A&l-11513 from
the N a t i d Institute of Arthritis and Metabolic
Diseases, National Institutes of Health, Bethesda,
Maryland, rmd by grants-in-aid from Wyeth Laboratorfes, Radnor, Pennqllvadu, and Eli Lilly and
Co., Indianapolis, Indiana.
FRANKR. SCHMID,M.D.: Associate Professor of
Medicine, and Chief, Section of Arthritis-Connective Tissue Diseases, Department of Medicine,
Northwestern University Medical School, 303
East Chicago Avenue, Chicago, Illinois 60611 .
M.D.: Assistant Professor of
Medicine, and Chief, Infectious Disease Section,
Veterans Administration Research Hospital, Chicago, Illinois.
Reprint requests should be addressed to Dr.
Antibiotic Transport into loints
Early reports suggested that concentrations of drugs achieved intraarticularly
were suboptimal during systemic therapy.7-18However, the doses of antibiotics
used in early studies were small by present
standards, and in some instances the studies
utilized nonirdected or nonidamed joints
in which the transport of antibiotics might
be reduced. More recent evidence indicates
that bactericidal concentrations of many
antibiotics can be attained in the joint after
Studies in our laboratories30 designed to
provide information along these lines were
performed in 15 patients. Antibiotic concentrations were determined on 34 paired
and simultaneously collected specimens of
serum and synovial fluid over variable periSERUM
ods of treatment. The infections were caused
by staphylococci, gonococci, pneumococci,
streptococci, and presumed gonococcal infection. Antibiotics used included penicillin,
nafcillin, cloxacillin, cephaloridine, tetracycline, erythromycin, and lincomycin. In
25 50 100 200
all cases, levels of antibacterial activity
achieved intraarticularly were either equal
Fig. 1.-Antimicrobial activity of antibiotic to or only slightly less than those noted in
as determined by tube dilution method in the serum (Fig. 1).Further observations
synovial fluid contrasted with level in serum have been made in additional patients and
obtained at the same time. Each point repre- confirm these initial results.31 Based upon
sents the result obtained from a pair of specimens of synovial fluid and serum. Values are this information, administration of the drug
expressed as the reciprocal of that dilution of was started and usually continued by the
the specimen at which a bactericidal effect intravenous or intramuscular route. In a few
was observed.
cases following improvement in synovitis,
oral administration was substituted later to
systemic administration, provided sufficient complete therapy in the h m knowledge
dosage is
Nevertheless, the case for that intraarticular inoculation still was not
intraarticular inoculation of antibiotics con- required. Although resolution of joint effutinues to be made, even by those who have sions usually occurred within 1week, pershown that antimicrobials cross the synovial sistence of a sterile effusion was observed
membrane, because of the fear that only in in several patients. Such an effusion does
this way will large concentrations of anti- not necessarily indicate continuing active
biotic be present where they are needed.24*25 infection. In our patients, the persistence
To overcome this fear it is necessary to was considered due to underlying disease
show that systemic administration raises the (rheumatoid arthritis, tophaceous gout, and
concentration of the drug in the synovial one patient on immunosuppressive drugs
fluid above the minimal level which is bac- for renal homotransplantation). As long as
tericidal for the infecting microorganism. such effusions were present, they were asFurthermore, it must be possible to main- pirated and examined. The antibacterial
tain such bactericidal concentrations until activity of these fluids continued to be in
the microorganism is eradicated from the the same range as the serum activity.
area. With one exception, in which animals
If our experience is taken together with
were infected experimentall~,2~
no sequen- the single determinations of intraarticular
tial study of transport of antibiotics into in- drug levels reported previously by others,
fected joint fluid has been carried out to direct inoculation of antibiotics into the
show that bactericidal intraarticular con- joint space is not a prerequisite for achievcentrations can be maintained over the pro- ing adequate levels in the joint. Indeed in
longed time often required for control of some cases such local instillation results in
a chemical synovitis added to an already
( 3 4 pairs/lJ patients)
existing inflammatory p r o c e ~ sAn
. ~ addi~~~
tional reason for stressing systemic antibiotic therapy-a reason accepted by all
clinicians-is that control of infection at
points remote from the joint is often required. These extraarticular infections may
be either primary infections that led to seeding of the joint initially, or they may represent metastatic infection as a result of the
bacteremia that frequently accompanies
septic arthritisF3
Regimen for Systemic Antibiotic Therapy
The following regimen is proposed for the
routine antibiotic management of patients
with infectious arthritis. It involves close
collaboration between the clinician and the
laboratory. However, its technical aspects
are not outside the level of skill available in
the bacteriological laboratories of most
1. Examination of joint fluid should include a gram-stained smear of synovial fluid
for bacteria.
2. Culture of joint fluid and other body
fluids involved in the infectious process (including two blood cultures) should be completed prior to starting antibiotics.
3. The antibiotic selected should be administered either intramuscularly or intravenously. Oral administration at the onset
cannot be relied upon to provide prompt
and sustained effective blood levels of the
4. Joint fluid should be aspirated as often
ds it accumulates, to allow drainage and to
compare antibacterial activity of the specimen with blood specimens obtained simultaneously. This procedure naturally will be
discontinued when detectable joint fluid no
longer remains.
5. Antibacterial activity is determined by
a simple tube dilution te~hnic.3~
The validity
of this method compares favorably with
more precise but more difficult bioassay
methods utilizing agar diffusion technics.
If possible, bacteria isolated from the in-
~fected joint should serve as the best microorganism against which bactericidal levels
of the antibiotic can be determined. If the
infecting bacteria are not available, then
an appropriately sensitive laboratory strain
can be used for assay purposes.
6. Continuation of antibiotic, possibly by
the oral route, for at least 7-10 days after
all signs of joint inflammation have disappeared.
I n the series of patients noted above, this
protocol resulted in control of the infection
in all cases. Sterility of the joint fluid and
blood stream was always achieved. Dramatic clinical improvement occurred within
a week in those patients without serious
underlying disease in whom the diagnosis
was made within a few days of onset. This
was particularly true in the patients with
gonococcal arthritis.
Drainage of Joints
In addition to achieving bactericidal antibiotic levels in synovial fluid and tissues,
the removal of purulent material is of fundamental importance. The presence of
retained pus retards the action of many
antibiotics by inhibiting the rate of
growth of infecting bacteria. Slowly metabolizing bacteria can persist in pus even
in the presence of concentrations of the
drug well above the minimal bactericidal
I n addition, increased
intraarticular pressure3* and the enzymatic
products of idammation are able to erode
cartilage and b 0 n e . ~ ~ - ~ 4
As often and as soon as fluid accumulates
in the joint, it should be removed. This can
be accomplished almost always at the outset by needle aspiration. Such fluids should
be subjected to the usual methods of analysis46 as well as to determination of bactericidal activity. In deeper structures, such
as the hip, needle aspiration can be repeated
daily until fluid accumulation ceases. The
effectiveness of this approach is judged over
the course of the first EL7 days of treatment
by noting whether the volume of drainage
is decreasing and whether the character of
the fluid, as reflected in cell count, glucose
level, and other parameters, is returning toward normal. Adherence to these guidelines will decide whether closed drainage
by needle aspiration is adequate.
Persistence of effusion beyond this time,
however, may require more aggressive attempts at drai11age.3~*~6-52
Incision of the
joint space then might be necessary to remove necrotic debris and enter loculated
areas of fluid. Incision and drainage at the
onset of treatment rather than later in the
course may be advisable in infants with
septic arthritis of deeper joints, such as the
shoulder or hip, where diEculty might be
anticipated in securing proper drainage and
where the clinical signs of inflammation are
~ b s c u r e d Still
. ~ ~later
~ ~in~ the
~ ~course
the disease, it may be necessary to perform
a synovectomy and/or reconstructive procedure for a joint that has developed mechanical impairment.
This review has supported the view that
principles for optimal treatment of closedspace infections can be applied equally well
to joints as to other body areas. Analogy to
patients with lung abcess is relevant. Control of infection in and around the abcess
is achieved by systemic antibiotic therapy.
Surgical drainage is deferred unless intrabronchial drainage fails, spontaneous reabsorption does not occur, and/or fistula or
other complications develop. Later, segmental lung resection is considered if the
residual activity persists. So also with infected joints. Here the physician, however,
is in the unique position of being able to
monitor his course of action because the
site of the inflammation is usually readily
accessible. With the aid of a few simple
studies, he can make the proper decisions
in each case of septic arthritis by utilizing
sound principles of antibiotic therapy and
needle aspiration and carefully considering
what additional benefit would be achieved
by open drainage.
We wish to express our gratitude to Dr. Philip
Y. Paterson for his critical review of this manuscript and to Miss Joan Davis for her help in
the literature search.
1. Clawson, D. K., and Dunn, A. W.: Management of common bacterial infections of bones and
joints. J. Bone Joint Surg. 49A:164, 1967.
2. Compere, E. L., Metzger, W. I., and Mitra,
R. N.: The treatment of pyogenic bone and joint
infections by closed inrigation (circulation) with a
nontoxic detergent and one or more antibiotics. J.
Bone Joint Surg. 49A:614, 1967.
3. Ortiz, A. C., and Miller, W. E.: Treaiment
of a septic joint. Southern Med. J. 54:594, 1961.
4. Steindler, A.: Pyogenic arthritis. Bull. N.Y.
Acad. Med. 27:101, 1951.
5. Hoeprich, P. D., and Ward, J. R.: The
Fluids of parenteral Body Cavities. N~~ yo&,
Grune & Stratton, 1959, p. 10.
6. c,,.,jss,p. H., Ira:Changes produced in the
synovial membrane and synovial fluid by disease
(instructional course lecture). J. Bone Joint Surg.
48A:873, 1964.
7. Rammelkamp, C. H., and Keefer, C. S.: The
absorption, excretion and distribution of penicillin.
J. Clin.Invest. 22:4!25, 1943.
8. Herreil, W. E., Nichols, D. R., and Heilman,
D. H.: Penicillin. Its usefulness, limitations, diffusion and detection, with analysis of 150 cases
in which it was employed. J.A.M.A. 125:1003,
9. Bdboni, v. G.,Shapiro, 1. M., and Kydd,
D. M.: fie penetration of penicillin into joint
fluid following intramuscular administration. h e r .
J. Med. sci, 210:588, 1945.
10. Florey, M. E., and Heatley, N. G.: Systemic
of penicillin by absorption from
body cavities. Lancet 1:748, 1945.
11. M c A d a , 1. w. J . 2 DuSid, 3. P v C h a b o r ,
S. W., and McCall, A.: Penicillin treatment of
serous cavity infections. Lancet 2:843, 1945.
12. ow, E. Ma, Meads, M-9 Brown, B.9 wilmx,
c.,and Finland, Me: Penicillin levels in Serum and
in some body fluids during systemic and local
therapy. J. Lab. clin. Med. 30:809, 1945.
13. Hirsh, H. L., Feffer, H. L., and O’Neil,
C. B.: A study of the diffusion of penicillin across
serous membranes of joint cavities. J. Lab. Clin.
Med. 31:535, 1946.
14. Jones, G. B.: The behavior of penicillin in
synovial cavities. J. Bone Joint Surg. 30B:107,
15. Linsell, W. D., and Fletcher, A. P.: Laboratory and clinical experience with terramycin
hydrochloride. Brit. Med. J. 2:1190, 1950.
16. Werner, C. A., Knight, V., and McDermott,
W.: Absorption and excretion of terramycin in
humans: comparison with adeomycin and chloramphenicol. Proc. SOC. Exp. Med. Biol. 74:261,
17. Jocson, C. T.: Diffusion of antibiotics
through the synovial membrane. J. Bone Joint
Surg. 37A:l07, 1955.
18. Bogacki, B., Szulc, H., Sarnowski, M.,
Majewski, C., Kubiak, E., and Leja, Z.: The effect
of intramuscular and intra-articular administration
of penicillin and streptomycin injections in experimental bacterial infection of the knee joint.
Narzad. Ruchr. i Ortop. Polska. 25.573, 1960. In
19. Geraci, J. E., Heilman, F. R., Nichols,
D. R., Wellman, W. E., and Ross, G. T.: Some
laboratory and clinical experiences with a new
antibiotic, vancomycin. Proc. Staff Meet, Mayo
Clin. 31:564, 1956.
20. Pulaski, E. J., and Tubbs, R. S.: Inhibitory
effects of kanamycin and diffusion into various
body fluids. Antibiot. Med. Clin. Therap. 6:589,
21. Willikens, R. F., Healey, L. A., and Decker,
J. L.: Acute infectious arthritis in the aged and
chronically ill. Arch. Intern. Med. 106:354, 1960.
22. Viek, P.: Concentration of sodium nafcillin
in pathological synovial fluid. In: Antimicrobial
Agents and Chemotherapy. Ann Arbor, American
Society for Microbiology, 1962, p. 379.
23. Viek, P., and Santangelo, S. C.: Pyarthrosis:
a surgical emergency. J. Int. Coll. Surg. 37:88,
24. Balboni, V. G.: Other forms of infectious
arthritis. In: Hollander, J. (Ed.): Arthritis and
Allied Conditions (ed. 7 ) . Philadelphia, Lea &
Febiger, 1966, p. 1037.
25. Bardenheier, J. A,, 111, Morgan, H. C., and
Stamp, W. G.: Treatment and sequelae of experimentally produced septic arthritis. Surg.
Cynec. Obstet. 122:249, 1966.
26. Eli Lilly and Co.: Profile of an Antibiotic.
Indianapolis, Indiana, 1966, p. 23.
27. Rapp, G. F., CrifEth, R. S., and Hebble,
W. M.: The permeability of traumatically inflamed synovial membrane to commonly used
antibiotics. J. Bone Joint Surg. 48A:1534, 1966.
28. Drutz, D. J., Schaffner, W., Hillman, J. W.,
and Koenig, M. G.: The penetration of penicillin
and other antimicrobials into joint fluid. J. Bone
Joint Surg. 49A:1415, 1967.
29. Morgan, H. C., Stamp, W. G., and Nickel,
J. S.: Quantitative barriers of infected synovium
to penicillin. Southern Med. J. 58:710, 1965.
30. Parker, R. H., and Schmid, F. R.: Transport
of antibiotics into infected joints. Arthritis Rheum.
11:503, 1968. Abstract.
31. Parker, R. H., and Schmid, F. R.: Unpublished observations.
32. Argen, R. J., Wilson, C. H., Jr., and Wood,
P.: Suppurative arthritis. Arch. Intern. Med. 117:
661, 1988.
33. Cluff, L. E., Reynolds, R. C., Page, D. L.,
and Breckenridge, J. L.: Staphylococcal bacteremia and altered host resistance. Ann. Int. Med.
89:859, 1968.
34. Parker, R. H., Chiu, V. S. W., and Hoeprich, P. D.: Penicillin N therapy of enteric
bacillary infections. Arch. Int. Med. 111:799,
35. Eagle, H.: Experimental approach to the
problem of treatment failure with penicillin. Amer.
J. Med. 13:389, 1952.
36. Wood, W. B., and Smith, M. R.: An experimental analysis of the curative action of penicillin in acute bacterial infections. 1. The
relationship of bacterial growth rates to the antimicrobial effect of penicillin. J. Exp. Med. 103:
487, 1956.
37. Rogers, D. E.: Observations on the nature
of staphylococcal infections. Bull. N. Y. Acad.
Med. 3525, 1959.
38. Phemister, D. B.: The effect of pressure on
articular surfaces in pyogenic and tuberculous
arthridites and its bearing upon treatment. Ann.
Surg. 80:481, 1924.
39. Gaines, L. M., and Shulman, L. E.: In:
Proceedings 23rd Annual Meeting, American
Rheumatism Association. Bull. Rheum. Dis. 10:
195, 1959.
40. Lack, C. H.: Chondrolysis in arthritis. J.
Bone Joint Surg. 41B:384, 1959.
41. Ziff, M., Gribetz, H. J., and Lospalluto, J.:
Effect of leucocyte and synovial membrane extracts on cartilage mucoprotein. J. Clin. Invest.
39:405, 1960.
42. Curtiss, P. H., Jr., and Klein, L.: Destruction of articular cartilage in septic arthritis. I. In
vitro studies. J. Bone Joint Surg. 45A:797, 1963.
43. Curtiss, P. H., Jr., and Klein, L.: Destruction
of articular cartilage in septic arthritis. 11. In vivo
studies. J. Bone Joint Surg. 47A:1595, 1965.
44. Evanson, J. M., and Krane, S. M.: Studies
on collagenase from rheumatoid synovium in tissue culture. J. Clin. Invest. 47:2639, 1968.
45. Schmid, F. R., and Ogata, R. I.: Synovial
fluid evaluation in joint disease. Med. Clin. N.
h e r . 49:165, 1965.
46. Hirsh, H. L., Feffer, H. L., and Dowling,
H. F.: The treatment of bacterial arthritis with
penicillin. New Eng. J. Med. 234:853, 1946.
47. Altemeier, W. A., and Largen, T.: Antibiotic and chemotherapeutic agents in infections of
the skeletal system. J.A.M.A. 150:1462, 1952.
48. Chartier, Y., Martin, W. J., and Kelly, P. J.:
Bacterial arthritis: experiences in the treatment of
77 patients. Ann. Int. Med. 50:1462,1959.
49. Ward, J., Cohen, A. J., and Bauer, W.:
The diagnosis and therapy of acute suppurative
arthritis. Arthritis Rheum. 3:522, 1960.
50. Baitch, A.: Recent observations of acute
suppurative arthritis. Clin. Orthop. 22:157,1962.
51. Cohen, A. S., and Kim, J. C.: Acute suppurative arthritis. Mod. Trends Rheum. 1347,
52. Cobbs, C. G.,and Kaye, D.: Arthritis in infectious diseases. ch. Orthop. 57:57, 1968.
53. Obletz, B. E.: Suppurative arthritis of the
hip joint in infants. Clin. Orthop. 22:27, 1962.
54. Stetson, J. W.,DePonte, R. J., and Southwick, W. 0.: Acute septic arthritis of the hip in
children. Clin. Orthop. 56:105,168.
Без категории
Размер файла
446 Кб
septic, arthritis, assessment, therapy, ongoing
Пожаловаться на содержимое документа