Antibiotic Beads

Download as pdf or txt
Download as pdf or txt
You are on page 1of 5

Surgical Techniques

Antibiotic Beads

Thomas A. DeCoster, MD
Shahram Bozorgnia, MD
B one infection, or osteomyelitis,
can be one of the most difficult
problems confronted by the ortho-
native, the use of antibiotic-
impregnated beads as an adjunct to
other treatment offers advantages
paedic surgeon. Common causes of compared with systemic aminogly-
osteomyelitis include open frac- cosides. With the bead pouch tech-
tures, hematogenous spread of bacte- nique, the systemic levels are low,
ria to bone, and orthopaedic surgical and the systemic complications are
procedures complicated by infec- virtually eliminated, while the local
The video that accompanies tion. Assessment involves identifi- concentration, where it is needed, is
this article is “Preparation and cation of the offending organism by extremely high.3 Antibiotic beads
Use of Antibiotic-Impregnated tissue culture and sensitivity to an- also offer the benefit of management
Beads for Orthopaedic Infec- tibiotics; radiographic assessment of of dead space. They are relatively in-
tions,” available on the Orthopaedic Knowl-
the extent of the infection; clinical expensive and are easy for the sur-
edge Online Website, at http://www5.
evaluation of the patient’s general geon to insert and the patient to tol-
aaos.org/oko/jaaos/surgical.cfm
health and ability to fight infection; erate.5
and determination of the local ana-
tomic condition of the bone and soft
Indications and
Dr. DeCoster is Professor and Vice tissue.
Contraindications
Chair, Department of Orthopaedics and Treatment is individualized but
Rehabilitation, University of New Mexico generally involves prolonged use of Antibiotic beads can be used in mul-
School of Medicine, Albuquerque, NM. systemic antibiotics, surgical dé- tiple different applications. Typical
Dr. Bozorgnia is Trauma Fellow, bridement, and support of the pa- indications include prevention of in-
Department of Orthopaedics and tient’s overall health.1,2 Results are fection (eg, open fracture antibiotic
Rehabilitation, University of New Mexico generally good but are not universal- bead pouch prophylaxis), treatment
School of Medicine. ly successful. Difficulties include of established bone infection (ie,
recurrence or lack of control of in- acute and chronic osteomyelitis),
Dr. DeCoster or a member of his
fection, systemic toxicity to antibi- treatment of infected joint arthro-
immediate family has received research
or institutional support from Biomet, EBI,
otics, scar formation, and persistent plasties, dead space management in
Orthofix, Smith & Nephew, Stryker, and
nonunion of fractures.2 Other prob- patients with large soft-tissue inju-
Zimmer; has stock or stock options held lems include expense and practical ries, and chronic infected non-
in Merck and Wyeth; and has received difficulties for the patient and the unions.
royalties from Innomed. Neither surgeon, including multiple surgical Contraindications to the use of
Dr. Bozorgnia nor a member of his treatments, lengthy and frequent antibiotic bead pouches in the treat-
immediate family has received anything hospitalizations, and prolonged limb ment of open fractures include pa-
of value from or owns stock in a dysfunction. Control of infection tient hypersensitivity to specific an-
commercial company or institution eventually may be obtained, but pa- tibiotics, small wounds (for which
related directly or indirectly to the tient function still may be limited beads are not necessary), and unsal-
subject of this article. by scar, stiffness, and weakness, as vageable limbs (because beads do not
well as nonunion or malunion of the overcome massive tissue injuries).
Reprint requests: Dr. DeCoster,
fracture. Late recurrence of infection Contraindication to the use of anti-
Department of Orthopaedics and
is also a problem. biotic beads in the treatment of os-
Rehabilitation, University of New Mexico
To deliver therapeutic tissue lev- teomyelitis include patient hyper-
School of Medicine, 1127 University
Boulevard NE, Albuquerque, NM
els of parenteral antibiotics to the sensitivity to a specific antibiotic
87131.
target area, high serum levels of an- and the presence of resistant and
tibiotics must be achieved.3 These slime-forming organisms such as
J Am Acad Orthop Surg 2008;16:674- high serum levels, however, may Enterococcus. The foreign-body sur-
678 result in an increased incidence of face of the methacrylate beads them-
Copyright 2008 by the American systemic side effects such as nephro- selves is conductive to slime-
Academy of Orthopaedic Surgeons. toxicity and ototoxicity.4 As an alter- producing organisms, and the slime

674 Journal of the American Academy of Orthopaedic Surgeons


Thomas A. DeCoster, MD, and Shahram Bozorgnia, MD

barrier severely limits the efficacy of Figure 1 Figure 2


the antibiotics in controlling the in-
fection.6,7

Specific Characteristics
of Antibiotic Beads
Antibiotic-impregnated polymethyl-
methacrylate (PMMA) cement beads
are a popular modality used in con-
junction with surgical débridement
In open fractures with significant soft-
and intravenous antibiotic therapy
A string of antibiotic beads is placed tissue injuries, antibiotic beads can be
for the treatment or prophylaxis of
into the wound for dead space placed in the open wound. The soft-
orthopaedic infections. The beads tissue defect will be covered with an
management and to provide a high
vary in size, type and amount of an- concentration of local antibiotic to the adhesive, porous, polyethylene wound
tibiotic used, and type of bone ce- wound. film.
ment used. The beads can be pre-
pared in advance by molding or by
rolling by hand in the operating ci, enterococci, and anaerobes.9 of beads, followed by surgical place-
room. Among the aminoglycosides are to- ment within the débrided wound
Nonbiodegradable PMMA ce- bramycin and gentamicin. Tobramy- and in place of débrided bone (Fig-
ment is the most common carrier cin has been substituted for genta- ures 1 and 2). Following bead im-
used. To incorporate antibiotics, an- micin in the United States because it plantation, the soft tissue is closed.
tibiotic powder is mixed with the is available as a pharmaceutical- The beads allow for very high levels
powdered cement polymer before grade powder, whereas gentamicin is of antibiotic bathing of the wound
adding the methylmethacrylate liq- not. There is extensive information and also assist in fighting infection.
uid monomer. The antibiotic must on the elution patterns of aminogly- The beads occupy space, preventing
be water soluble, available as pow- cosides from beads in a variety of the accumulation of hematoma that
der, able to remain stable despite the clinical scenarios.4,10 otherwise would be a potential site
heat generated during the polymer- Vancomycin should be consid- for infection. Antibiotic beads also
ization reaction, and hypoallergenic, ered when there is a risk of resistant provide management of dead space
as well as have a broad spectrum of staphylococcal organisms, that is, by preventing the formation of scar
activity. Antibiotic release is highest methicillin-resistant Staphylococ- tissue in the bone-defect site. If in-
in the first 4 days following implan- cus aureus. Vancomycin is available fection persists, a repeat débride-
tation; the remaining elution at ther- in powder form and is not neutral- ment, culture, and antibiotic bead
apeutic concentration persists for ized by the heat of methacrylate po- exchange may be performed after
weeks to months.8 Wahlig et al3 lymerization. Effective elution of several days or weeks. Once the in-
showed that, if gentamicin-PMMA vancomycin has also been report- fection is well controlled, the beads
chains are implanted and the wound ed.11 are surgically removed. For non-
is closed, then the local concen- Bead molds are available in a va- union or a large bone void, bone graft
trations of antibiotic achieved are riety of sizes. A diameter of 8 mm is may be placed in the area that the
200 times the levels achieved with the largest and 2 mm, the smallest. beads occupied.
systemic antibiotic administration. Small-diameter beads are used in Although the antibiotic within
However, the use of the beads in an wounds of the hand and in other the beads produces a high local con-
open system or in combination with small wounds to maximize the sur- centration in the surrounding tis-
suction irrigation rapidly lowers lo- face area and antibiotic elution. sues, the systemic level of antibiot-
cal antibiotic concentrations, and Consistency in size and shape of the ic resulting from beads is low, which
the therapeutic advantage is dimin- beads also facilitates their passage minimizes complications, including
ished. Therefore, this technique is into tight spaces, including the med- renal toxicity and ototoxicity. The
not recommended. ullary canal. high local concentration of antibiot-
Aminoglycosides are the most ic reduces and often eliminates the
commonly used antibiotics in this need for intravenous antibiotics;
Surgical Technique
context. They are effective against therefore, intravenous access and
aerobic gram-negative bacilli and The technique of application of anti- compliance are not required. Osteo-
staphylococci as well as streptococ- biotic beads involves the production myelitis typically involves seques-

Volume 16, Number 11, November 2008 675


Antibiotic Beads

Figure 3 Figure 4 ing the cement away from the bot-


tom and edges of the bowl to prevent
hardening.
With a tongue depressor, forceful-
ly press the liquid cement mixture
into the bead mold (Figure 3). Quick-
ly and carefully fill all of the holes
until the entire mold is filled with
the cement mixture. It is imperative
that this step is done in less than 8
minutes, before the mixture hard-
ens. Smooth the surface of the mold
The liquid cement mixture is pressed The liquid cement mixture is pressed
by scraping off the remaining ce-
forcefully with a tongue depressor into forcefully with a cement-filled syringe
ment with a tongue depressor. Place
the bead mold. into the bead mold.
the mold on its side and let it sit for
15 minutes as the cement hardens.
tration of dead infected bone with bone cement An alternative technique for plac-
little to no blood supply. Many sys- • 20 mL of liquid monomer ing the cement into the mold holes
temic antibiotics exhibit poor pene- • Two 1.2-g vials of tobramycin is to pour 3 mL of the liquid cement
tration of bone, even when the bone powder mixture into a 10-mL syringe with
is vascularized. Hence, systemic an- • Two twisted strands of 26-gauge the plunger removed and the tip
tibiotics and blood-borne antimicro- wire capped, then replace the plunger and
bial cells may not reach the area • A cast-metal, Teflon-coated bead remove the syringe cap ( video,
of greatest need. Antibiotic beads, mold “Preparation Technique B [Sy-
however, provide high local concen- • One medium-size (approximate- ringe]”). While applying pressure,
trations of antibiotic not dependent ly 200 mL) plastic bowl use the syringe to fill each hole in
on blood supply to the bone. Neither • Tongue depressors the mold with the cement mixture.
are the antibiotics dependent on • Two 10-mL syringes Keep the syringe at a 90° angle as
bone penetration.5 • Tweezers from a suture-removal each hole is filled and apply pressure
kit to maintain a tight seal between the
• Gloves mold and the syringe (Figure 4). Ce-
Antibiotic Bead
ment should bulge into the adjacent
Preparation Technique
Technique hole. Proceed rapidly because the sy-
Bead Preparation Twist together two strands of 26- ringe technique requires the cement
The bead preparation technique gauge wire (50 turns using a hand to be in the liquid state. Four sy-
described here results in spherical, drill) ( video, “Wire-Twisting Pro- ringes typically are needed for two
uniform tobramycin-impregnated cedure”). Carefully place the wire 20-bead chains. The tip of each sy-
PMMA beads ( video, “Ingredi- into the grooves of the bead mold ringe is cut off so that the lumen
ents”). These beads can be made in and tighten the mold ( video, matches the diameter of the mold.
advance, sterilely packaged, and “Preparation Technique A [Spatu- Smooth the surface of the mold by
stored in the operating room ready la]”). A cool working environment scraping off the remaining cement
for use. Alternatively, beads can be and precooling of the mold and with a tongue depressor. Place the
prepared in the operating room at PMMA prolong the polymerization mold on its side and let it sit for 15
the time of implantation, with or time. In a medium-size plastic bowl, minutes until the cement is com-
without the use of bead molds. mix most of one package of bone ce- pletely hardened.
When this technique is used, suffi- ment (ie, 35 of 40 g) with two 1.2-g After 15 minutes, take the mold
cient time (at least 30 minutes) must vials of tobramycin powder. This al- apart and gently remove the beads
be allowed for full curing of the ce- lows a prolonged liquid phase, which by pulling the wire (Figure 5). Re-
ment to minimize toxic monomers. facilitates better bead production. move the excess cement (ie, flash-
Stir thoroughly to ensure homogene- ing) between the beads using the
Materials ity of the mixture. Pour 20 mL of liq- tweezers from the suture kit. Excess
The materials needed for the pro- uid monomer into the powder and cement in the mold also should be
duction of tobramycin-impregnated stir vigorously for about 30 seconds removed to facilitate the next use
PMMA beads are the following: until the mixture liquefies. Contin- of the mold. A pair of scissors from
• One package (40 g) of PMMA ue to stir the cement mixture, mov- a suture-removal set is the exact

676 Journal of the American Academy of Orthopaedic Surgeons


Thomas A. DeCoster, MD, and Shahram Bozorgnia, MD

Pearls
• Remove all avascular, necrotic, and contaminated tissue before applying antibiotic beads. Infection re-
sulting from inadequate débridement will not be overcome by the use of antibiotic beads.
• Beads can be made in advance and stored in the operating room.
• Thoroughly mix the bone cement with the antibiotic powder before adding the liquid monomer.
• Fill all of the holes of the mold as quickly as possible before the mixture hardens.
• An assistant is helpful.

Pitfalls
• Do not use the beads in an open system or in combination with suction irrigation because doing so pre-
vents development of effective antibiotic levels in the wound.
• Do not use the beads as an initial measure in inflamed and suppurating wounds.
• Do not use the beads in the treatment of osteomyelitis in the presence of resistant organisms or slime-
forming organisms (eg, Enterococcus) because effective elution of antibiotic is not achieved.
• Do not substitute antibiotic beads for thorough wound débridement.
• Do not insert handmade beads that are too large to fit into the medullary canal or too big to completely
fill the wound.
• Use care to produce bead chains in a timely fashion during the short available working time (8 minutes)
as the methacrylate polymerizes. Failure to do so results in wasted material and surgeon frustration. These
can be avoided by planning and relying on an assistant.
• Do not leave beads in the patient so long (>3 weeks) that removal is difficult.

width of the slots in the mold and subjected to excessive or chronic


Figure 5
thus can be used to remove residual loads. Infection resulting from inad-
cement from the mold. equate débridement will not be over-
Transfer the beads into gas- come by the use of antibiotic beads.
sterilization packages (Figure 6) and Knowledge of the effectiveness of
have them sterilized. Wash your antibiotic beads is limited. The opti-
hands and all work surfaces thor- mal dose, duration of treatment, and
oughly after working with the ce- relative efficacy of various antibiotic
ment. This same process can be per- classes are not known. Differential
formed in the operating room, using elution of antibiotics from various
sterile technique, for immediate forms of PMMA has been report-
use. ed,12,13 but the ideal carrier medium After 15 minutes, the mold is taken
is still a matter of debate. The role apart, and the beads are gently
and efficacy of absorbable beads is not removed by pulling the wire.
Complications
yet known. Local antibiotic delivery
Complications caused by the use of by pump or other mechanism is an al-
Figure 6
antibiotic beads are uncommon; ternative route of local antibiotic
however, difficulty with bead re- therapy. In addition, the efficacy of
moval can occur when the beads are beads compared with the efficacy of
left in place too long, especially in other delivery methods is not yet
the medullary canal of long bones. known.
Antibiotic beads reduce the rate of
infection in open fractures, but they
Summary
do not eliminate the risk. Beads help
to control established infections, but Antibiotic beads are an attractive
not all infections will completely re- method of treatment in the manage-
solve. A major complication is persis- ment and prevention of osteomyeli-
tent or recurrent infection. Also, spac- tis. Antibiotic beads provide high lo- The beads are transferred into gas-
ers can fragment or dislodge when cal concentrations of antibiotic at sterilization packages.

Volume 16, Number 11, November 2008 677


Antibiotic Beads

the site of infection without signifi- 2. Patzakis MJ, Harvey JP Jr, Ivler D: The loaded acrylic bone cement spacers.
cant systemic toxicity. A variety of role of antibiotics in the management J Biomed Mater Res B Appl Biomater
of open fractures. J Bone Joint Surg 2005;72:373-378.
techniques to provide local antibiot- Am 1974;56:532-541. 9. Popham GJ, Mangino P, Seligson D,
ics has been reported, including ab- 3. Wahlig H, Dingeldein E, Bergmann R, Henry SL: Antibiotic-impregnated
sorbable beads with various types of Reuss K: The release of gentamicin beads: Part II. Factors in antibiotic
antibiotics, antibiotic sticks, coated from polymethylmethacrylate beads. selection. Orthop Rev 1991;20:331-
J Bone Joint Surg Br 1978;60:270-275. 337.
nails, and coated joint spacers. Beads
4. Schentag JJ, Lasezkay G, Plant ME, 10. Walenkamp GH, Vree TB, van Rens
can be prepared in the operating Jusko WJ, Cumbo TJ: Comparative TJ: Gentamicin-PMMA beads: Phar-
room or in advance. Antibiotic beads tissue accumulation of gentamicin macokinetic and nephrotoxicological
assist in dead space management and tobramycin in patients. study. Clin Orthop Relat Res 1986;
and help facilitate the filling of bone J Antimicrob Chemother 1978;4:23- 205:171-183.
30. 11. Sasaki T, Ishibashi Y, Katano H,
voids and healing of infected non-
5. Cunningham A, Demarest G, Rosen Nagumo A, Toh S: In vitro elution of
unions. Results demonstrate im- P, DeCoster TA: Antibiotic bead pro- vancomycin from calcium phosphate
proved efficacy in the control of in- duction. Iowa Orthop J 2000;20:31- cement. J Arthroplasty 2005;20:
fection and enhanced outcomes, 35. 1055-1059.
with financial and practical sav- 6. van de Belt H, Neut D, Schenk W, van 12. Greene N, Holtom PD, Warren CA, et
Horn JR, van Der Mei HC, Busscher al: In vitro elution of tobramycin and
ings.14
HJ: Staphylococcus aureus biofilm vancomycin polymethylmethacryl-
formation on different gentamicin- ate beads and spacers from Simplex
loaded polymethylmethacrylate bone and Palacos. Am J Orthop 1998;27:
References cements. Biomaterials 2001;22:1607- 201-205.
Citation numbers printed in bold 1611. 13. Nelson CL, Griffin FM, Harrison BH,
7. Ensing GT, van Horn JR, van der Mei Cooper RE: In vitro elution character-
type indicate references published
HC, Busscher HJ, Neut D: Copal bone istics of commercially and noncom-
within the past 5 years. cement is more effective in prevent- mercially prepared antibiotic PMMA
ing biofilm formation than Palacos beads. Clin Orthop Relat Res 1992;
1. Gustilo RB, Anderson JT: Prevention R-G. Clin Orthop Relat Res 2008; 284:303-309.
of infection in the treatment of one 466:1492-1498. 14. Henry SL, Seligson D, Mangino P,
thousand and twenty-five open frac- 8. Anagnostakos K, Kelm J, Regitz T, Popham GJ: Antibiotic-impregnated
tures of long bones: Retrospective and Schmitt E, Jung W: In vitro evaluation beads: Part I. Bead implantation ver-
prospective analyses. J Bone Joint of antibiotic release from and bacteria sus systemic therapy. Orthop Rev
Surg Am 1976;58:453-458. growth inhibition by antibiotic- 1991;20:242-247.

678 Journal of the American Academy of Orthopaedic Surgeons

You might also like