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Ongoing assessment of therapy in septic arthritis.

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CURRENT COMMENT
Ongoing Assessment of Therapy in Septic Arthritis
By FRANKR. S ~ M I DM.D.,
,
AND RICHARD H. P-,
I
M.D.
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 .
RICHARDH. P-,
M.D.: Assistant Professor of
Medicine, and Chief, Infectious Disease Section,
Veterans Administration Research Hospital, Chicago, Illinois.
Reprint requests should be addressed to Dr.
Schmid.
N THE MANAGEMENT
ARTmuTIs
AND
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
RHEUMATLS~,VOL. 12,-No. 5 (OCTOBER1969)
529
SCHMID AND PARKER
530
/
Studies in our laboratories30 designed to
provide information along these lines were
2o01
performed in 15 patients. Antibiotic concentrations were determined on 34 paired
lo
5o
0t
1:
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
Y
,
<5
5
10
25 50 100 200
all cases, levels of antibacterial activity
SYNOVIAL FLUID
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
infection.
a chemical synovitis added to an already
( 3 4 pairs/lJ patients)
25t
I
THERAPY IN SEPTIC ARTHRITIS
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
hospitals.
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
drug.
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-
531
~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
~oncentration.3~"~
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
532
SCHMID AND PARgER
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
~
of
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.
ACKNOWLEDGMENTS
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.
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THERAPY IN SEPTIC ARTHRITIS
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