Breast implant spacers for the treatment of periprosthetic breast implant infections

Abstract

The present disclosure provides improved devices and methods to treat periprosthetic breast implant infections.

Claims

1. A breast implant spacer comprising an acrylic cement impregnated with an antibiotic, antifungal, bacteriostatic or bacteriocidal agent, selected from vancomycin, tobramycin, voriconazole, gentamicin, erythromycin, oxacillin, cloxacillin, methicillin, lincomycin, ampicillin, colistin, clindamycin, a cephalosporin, amphotericin B, fluconazole, copper-nitride, metallic silver, or any combination thereof, wherein the cement is formed into the shape of a breast implant and comprises a porous structure effective to allow a therapeutic amount of the antibiotic, antifungal, bacteriostatic or bacteriocidal agent, or a combination thereof to diffuse out of the spacer into contact with the surrounding tissue when the spacer is implanted in a human during use.

2. The breast implant spacer of claim 1, comprising a bacteriocidal or antifungal agent selected from vancomycin, tobramycin, voriconazole or a combination thereof.

3. The breast implant spacer of claim 2, wherein the breast implant spacer releases said bacteriocidal or antifungal agent or combination thereof to achieve a local concentration of up to 100 times the mean inhibitory concentration for a released agent when implanted into a human breast.

4. The breast implant spacer of claim 1, wherein the acrylic cement comprises polymethylmethacrylate, a methylmethacrylate-styrene copolymer or a methylmethacrylate-methacrylate copolymer.

5. The breast implant spacer of claim 1 comprising a plurality of segments connected by a wire, a spring or one or more pins.

6. The breast implant spacer of claim 1 wherein the acrylate cement is coated onto a template.

7. An antibiotic breast implant spacer for use in treatment of an infection associated with a surgically reconstructed breast, said implant comprising an implantable device molded in the shape of a breast implant and comprising one or more leachable antibiotic agents effective to treat said infection when implanted into a human breast.

8. The antibiotic breast implant spacer of claim 7, wherein the infection is a bacterial infection.

9. The antibiotic breast implant spacer of claim 7, wherein said infection is methocillin resistant Staphlococcus aureus.

10. The antibiotic breast implant spacer of claim 7, wherein the infection is a fungal infection.

11. The antibiotic breast implant spacer of claim 7, wherein said leachable antibiotic agent is vancomycin, tobramycin, voriconazole or a combination thereof.

12. The antibiotic breast implant spacer of claim 7, comprising polymethylmethacrylate, a methylmethacrylate-styrene copolymer or a methylmethacrylate-methacrylate copolymer.

13. The antibiotic breast implant spacer of claim 7, comprising a plurality of segments connected by a wire, a spring or one or more pins.

14. The antibiotic breast implant spacer of claim 13, wherein one or more of said plurality of segments comprises a suture hole.

15. A method of treating a periprosthetic breast implant infection comprising removing a breast implant from an infected breast, and replacing the removed breast implant with an antibiotic breast implant spacer of claim 7 and leaving the spacer in place for a time effective to achieve a local concentration of up to 100 times the mean inhibitory concentration of an antibiotic agent.

16. The method of claim 15, wherein the effective time is from 4 to 7 weeks.

17. The method of claim 15 further comprising concomitant oral or intravenous administration of an antibiotic, or a combination of oral and intravenous administration thereof.

Description

BRIEF DESCRIPTION OF THE SEVERAL VIEWS OF THE DRAWINGS

(1) The following drawings form part of the present specification and are included to further demonstrate certain aspects of the present invention. The invention may be better understood by reference to one or more of these drawings in combination with the detailed description of specific embodiments presented herein.

(2) FIG. 1. A side view of an embodiment of a four segment articulated antibiotic spacer of the present disclosure.

(3) FIG. 2. A top view of an embodiment of a six segment articulated antibiotic spacer of the present disclosure.

(4) FIG. 3. A perspective view of an embodiment of a segmented, spring loaded antibiotic spacer of the present disclosure.

(5) FIG. 4. A perspective view of an embodiment of a mold base and mold insert used to form an antibiotic spacer of the present disclosure.

(6) FIG. 5. A side view of an embodiment of a mold base and a mold spacer used to form an antibiotic spacer of the present disclosure.

(7) FIG. 6. A top view of an embodiment of a mold base used to form an antibiotic spacer of the present disclosure.

(8) FIG. 7. A side view of an embodiment of a mold base used to form an antibiotic spacer of the present disclosure.

(9) FIG. 8. A top view of an embodiment of an injectable mold used to form an antibiotic spacer of the present disclosure.

(10) FIG. 9. A side view of an embodiment of an injectable mold used to form an antibiotic spacer of the present disclosure.

DETAILED DESCRIPTION OF THE INVENTION

(11) The present disclosure is directed to improved devices and methods to treat periprosthetic breast implant infections. The present disclosure specifically addresses the formulation, preparation and use of antibiotic spacers that approximate the volume and shape of the existing breast implant. In general the antibiotic spacers comprise a cement, such as a bone cement, and an antibiotic, antifungal, bacteriostatic or bacteriocidal agent, or any combination thereof In certain embodiments the antibiotic spacers comprise a plurality of connected segments. In further embodiments the antibiotic spacers could be formed by coating at least a portion of metallic or plastic template with a cement and an antibiotic, antifungal, bacteriostatic or bacteriocidal agent.

(12) FIG. 1 shows a side view of one embodiment of an antibiotic spacer 100 of the present disclosure. In this embodiment antibiotic spacer 100 is comprised of four segments, 101, 102, 103 and 104, which are connected by pivot pins 110 and 111 such that the segments 101, 102, 103 and 104 can rotate on the pivot pins 110 and 111 to form a generally circular shape (see FIG. 2). Each of segments 101, 102, 103 and 104 are comprised of a cement, such as a bone cement, that is impregnated with one or more antibiotics. The skilled artisan will appreciate that in such embodiments the number of segments is not important, and can vary from 2 to 8 or more (not shown) depending upon the particular requirements of the spacer. In addition, the segments can be connected with a single pivot pin (not shown). The dimensions of the antibiotic spacer can vary, depending upon the particular application, but in general the diameter can range between about 9 cm and about 16 cm, the height (or projection) can range between about 3 cm and about 8 cm, and the thickness can range between about 5 mm and about 1 cm.

(13) A number of different materials can be used to fabricate pivot pins 110 and 111, including, but not limited to, a polymer such as ultra-high molecular weight polyethylene, high density polyethylene, acetal homopolymer (DELRIN), polyetheretherketone (PEEK), acetal polyoxymethylene (POM) copolymer (CELCON, ULTRAFORM, ACETRON GP), acrylonitrile butadiene styrene (ABS), fluorinated ethylene propylene (FEP), polytetrafluoroethylene (PTFE) linked to mica (FLUOROSINT), PTFE (TEFLON), ethylene tetrafluoroethylene (ETFE; TEFZEL), polyphenylene sulfide (PPS; FORTRON), polyphenylsulfone (PPSU; RADEL), polyethyleneimine (PEI), polysulfone (PSU; ULTRASON S), polyethersulfone (PES; ULTRASON E), polycarbonate (PC), poly(p-phenylene oxide) (PPO), acrylic cement (which is certain instances can be loaded with an antibiotic), or metal, such as stainless steel, titanium or cobalt chromium, or any combination thereof.

(14) A number of different cements or combination of cements can be used to fabricate the antibiotic spacer. In general, such cements or combination of cements are solid enough to maintain the shape of the breast implant throughout most or all of the procedure, while at the same time porous enough to allow a sufficient or therapeutically effective amount of antibiotic (or combination of antibiotics) to diffuse from the cement to treat or cure the infection. For example cements that can be used include, but are not limited to, bone cements, such as a poly-methyl-methacrylate (PMMA) cement, including those produced under the trade names Generation 4, CMW1, CMW2, CMW3, Zimmer Dough Type, Zimmer LVC, SMARTSET MV, SMARTSET GMV, or SMARTSET GHV, a MMA-styrene copolymer cement, including those produced under the trade names Stryker Simplex P or Zimmer OSTEOBOND, or an MMA-methyl acrylate copolymer cement, including those produced under trade name Cobalt G-HV, Cobalt HV, or PALACOS R.

(15) A number of different antibiotic, antifungal, bacteriostatic or bacteriocidal agents, or any combination thereof, can be used in the antibiotic spacer. In general, such antibiotic, antifungal, bacteriostatic or bacteriocidal agents, or combination thereof, are stable enough to withstand the heat generated during the curing of the cement (or combination of cements) used to fabricate the antibiotic spacer. The choice of antibiotic, antifungal, bacteriostatic or bacteriocidal agent for the spacer may depend upon the source of an actual infection or potential infection, and include, but is not limited to, vancomycin, tobramycin, voriconazole gentamicin, erythromycin, oxacillin, cloxacillin, methicillin, lincomycin, ampicillin, colistin, clindamycin, a cephalosporin, amphotericin B, fluconazole, copper-nitride, metallic silver, or any combination thereof

(16) FIG. 2 shows a top view of another embodiment of an antibiotic spacer 200 of the present disclosure. In this embodiment antibiotic spacer 200 is comprised of six segments, 201, 202, 203, 204, 205 and 206, which are connected by pivot pin 210 such that the segments 201, 202, 203, 204, 205 and 206 can rotate on the pivot pin 210 to form a generally circular shape. Also shown are suture holes 221, 222, 223 and 224, which are connected by sutures 225 and 226. The skilled artisan will appreciate that in such embodiments the number of suture holes is not important, and can vary from 1 to 4 or more (not shown) depending upon the particular requirements of the spacer. In addition, the suture holes can be connected with wire or any other suitable material (not shown).

(17) FIG. 3 shows a perspective view of another embodiment of an antibiotic spacer 300 of the present disclosure. In this embodiment antibiotic spacer 300 is comprised of a plurality of segments 301 that are connected by a spring 310. The skilled artisan will appreciate that in such embodiments the size and number of segments 301, the total length of the spring 310, as well as the distance between the segments 301 on the spring 310 can vary as described herein above depending upon the particular needs of the patient. In certain embodiments (not shown) the segments 301 can be connected by one or more wires, for example wires comprising stainless steel, DFT, titanium or a titanium alloy, tantalum, a copper-manganese, copper-nickel, nickel-chromium or quaternary resistance alloy (i.e., BALCO 120, INCOLOY alloy 800), a mechanical alloy (i.e., MONEL 400), an austenitic nickel-chromium based superalloy (i.e., ICONEL) or a HASTELLOY corrosion-resistant superalloy, or wires fabricated from a shape-memory alloy. The most common types of shape-memory alloys are the copper-zinc-aluminum-nickel, copper-aluminum-nickel, and nickel-titanium (NiTi) alloys, but shape-memory alloys can also be created by alloying zinc, copper, gold and iron.

(18) FIG. 4 shows a perspective view of an embodiment of a mold base 400 and mold plunger 401 used to form an embodiment of an antibiotic spacer of the present disclosure. In this embodiment the mold base 400 has a cut-out or indentation having a concave surface 400a that approximates the shape of the breast implant (not shown) from the patient, and the mold plunger 401 comprises a handle 402, a head 403, and a plurality of projections 404 connected to the head 404, which can vary in length depending upon the desired thickness of the antibiotic spacer. To form an antibiotic spacer using the mold shown in FIG. 4, the desired amount of a mixture of cement and antibiotic(s) (not shown) is poured onto the concave surface 400a of the mold base 400 to reach the desired thickness of the antibiotic spacer, and the mold plunger 401 is inserted into the cement/antibiotic(s) mixture. Once the cement/antibiotic(s) mixture hardens, cures or sets to form the antibiotic spacer, the plunger 401 is removed from the antibiotic spacer, and the antibiotic spacer is removed from the concave surface 400a of the mold base 400. In certain embodiments the antibiotic spacer thus formed can be cut into a plurality of segments prior to use.

(19) Any suitable material can be used to form the mold base 400 and plunger 401, including, but not limited to, medical grade plastic or silicone, such as DOW CORNING SILASTIC Q7-4780 or any other 80 durometer silicone, ultra-high molecular weight polyethylene, high density polyethylene, PEEK, acetal homopolymer (DELRIN), or acetal polyoxymethylene (POM) copolymer (CELCON, ULTRAFORM, ACETRON GP). In general the material used to form the mold base 400 and plunger 401 should be flexible to ease removal of the hardened or cured antibiotic spacer, but solid enough to maintain its shape when the cement/antibiotic mixture is added to the mold base 400, and the plunger 401 is inserted into the cement/antibiotic mixture. In addition the material should not react adversely with the cement/antibiotic mixture, or cause breakdown of the cement or the antibiotic in the mixture.

(20) FIG. 5 shows a side view of the embodiment of a mold base 400 and a mold plunger 401 shown in FIG. 4, which can be used to form an embodiment of an antibiotic spacer of the present disclosure. Once again, the mold base 400 has a concave surface 400a that approximates the shape of the breast implant (not shown) from the patient, and the mold plunger 401 comprises a handle 402, a head 403, and a plurality of projections 404 connected to the head 404, which can vary in length depending upon the desired thickness of the antibiotic spacer.

(21) FIG. 6 shows a top view of an embodiment of a mold base 500 used to form an embodiment of an antibiotic spacer of the present disclosure. The mold base 500 defines a cut-out portion 500a, which in this embodiment is generally circular in shape. In other embodiments (not shown) the cut-out portion can have a generally triangular, square, or rectangular shape, or any other shape desired to construct an antibiotic spacer of the present disclosure. The mold base 500 also comprises a plurality (in this embodiment seven) pegs or projections 501, which are used to form holes for sutures or wires. The skilled artisan will appreciate that in such embodiments the number of pegs or projections 501 is not important, and can vary from 0, 1, 2, 3, 4, 5 or 6 or more (not shown) depending upon the particular requirements of the spacer. To form an antibiotic spacer using the mold shown in FIG. 6, the desired amount of a mixture of cement and antibiotic(s) (not shown) is poured into the cut-out portion 500a of the mold base 500 to reach the desired thickness of the antibiotic spacer. Once the cement/antibiotic(s) mixture hardens, cures or sets to form the antibiotic spacer, the antibiotic spacer is removed from the cut-out portion 500a of the mold base 500. In certain embodiments the antibiotic spacer thus formed can be cut into a plurality of segments prior to use.

(22) FIG. 7 shows a side view of an embodiment of a mold base used to form an antibiotic spacer of the present disclosure. Once again, the mold base 500 has a cut-out portion 500a and a plurality of pegs or projections 501. Although the bottom of the cut-out portion 500a is flat in this embodiment, the bottom can be concave in further embodiments of the disclosure (not shown).

(23) FIG. 8 shows a top view of an embodiment of an injectable mold 600 used to form an embodiment of an antibiotic spacer of the present disclosure. Mold 600 comprises two threaded injection/fill ports 601 two air efflux ports 602 and a fill port 603 with a fitting 604 (in this embodiment a luer-lock fitting) that is connected to the internal bladder (not shown in FIG. 8; see FIG. 9). This embodiment of the injectable mold 600 is generally circular in shape, although in alternative embodiments (not shown) the injectable mold can generally triangular, square or rectangular in shape, or any other desired shape. Any suitable material can be used to form the injectable mold 600, including, but not limited to, medical grade plastic or silicone, such as DOW CORNING SILASTIC Q7-4780 or any other 80 durometer silicone.

(24) FIG. 9 shows a side view of the embodiment of the injectable mold shown in FIG. 8, which can be used to form an embodiment of an antibiotic spacer of the present disclosure. Once again mold 600 comprises two threaded injection/fill ports 601 two air efflux ports 602 and a fill port 603 with a fitting 604 (in this embodiment a luer-lock fitting) that is connected to the internal bladder 606. Internal bladder can be filled with any suitable material to define the shape of the antibiotic spacer, including, but not limited to, water, saline, silicone, air or nitrogen. Also shown in FIG. 9 are septations 605 that prevent movement of the internal bladder 606 with respect to the mold 600. To form an antibiotic spacer using the mold 600, the desired amount of a mixture of cement and antibiotic(s) (not shown) is poured or pumped into one of the injection/fill ports 601, and fluid or gas is added to the internal bladder 606 to reach the desired thickness of the antibiotic spacer. Once the cement/antibiotic(s) mixture hardens, cures or sets to form the antibiotic spacer, the antibiotic spacer is removed from the mold 600 by sharply incising the silicone outer layer, leaving the inner bladder intact. In certain embodiments the antibiotic spacer thus formed can be cut into a plurality of segments prior to use.

(25) The following example is included to demonstrate preferred embodiments of the invention. It should be appreciated by those of skill in the art that the techniques disclosed in the example which follows represent techniques discovered by the inventor to function well in the practice of the invention, and thus can be considered to constitute preferred modes for its practice. However, those of skill in the art should, in light of the present disclosure, appreciate that many changes can be made in the specific embodiments which are disclosed and still obtain a like or similar result without departing from the spirit and scope of the invention. The present invention is not to be limited in scope by the specific embodiments described herein, which are intended as single illustrations of individual aspects of the invention, and functionally equivalent methods and components are within the scope of the invention. Indeed, various modifications of the invention, in addition to those shown and described herein, will become apparent to those skilled in the art from the foregoing description. Such modifications are intended to fall within the scope of the appended claims.

EXAMPLE 1

(26) Antibiotic impregnated spacers provide a new and effective method for treating periprosthetic breast implant infections. The patient is returned to the operating room for removal of the infected implant and debridement. An antibiotic impregnated spacer fashioned to replicate the shape and volume of the removed breast implant is inserted. The spacer is composed of polymethymethacrylate and contains all or combinations of vancomycin, tobramycin and voriconazole. After the implant is inserted the access incision is closed. Over a period of 4 weeks the implant will release its antibiotic load achieving local concentrations up to and exceeding 100 times the MIC (mean inhibitory concentration). The supra-physiologic antibiotic concentration is highly bactericidal yet produces minimal systemic absorption avoiding nephrotoxicity and ototoxicity. In addition to managing local infection the spacer maintains the shape and volume of the breast avoiding the need for repeat expansion in the reconstructed breast and reducing the potential for disfiguring contracture in cases of cosmetic augmentation. The spacer is used in conjunction with systemic antibiotic therapy. After a 6-12 week period the patient is returned to the operating room for removal of the spacer and insertion of a permanent breast implant.

(27) A female who underwent bilateral simple mastectomy followed by uncomplicated expander-implant breast reconstruction was chosen to test the antibiotic impregnated spacer. Fourteen months after the initial surgery the patient underwent bilateral nipple reconstruction complicated by development of swelling, pain and erythema of the right breast. She was returned to the operating room where irrigation and debridement was performed. Cultures were obtained and the original implant was cleansed and replaced. Operative cultures demonstrated Methocillin Resistant Staphlococcus Auerus (MRSA) and she received a course of culture specific intravenous antibiotics. Despite this intervention the infection recurred and she was returned to the operating room for removal of the implant, debridement and insertion of an antibiotic spacer containing vancomycin and tobramycin. Repeat cultures again demonstrated MRSA. She received a short course of intravenous antibiotics followed by a 4 week course of oral antibiotics. During the 7.sup.th postoperative week the patient was returned to surgery for removal of the spacer and insertion of a permanent breast implant. The patient has been followed for 18 months and no sign of recurrent infection or capsular contraction has developed. The overall aesthetics of the reconstruction are good and the treatment at this juncture can be deemed a success.

(28) All of the compositions and/or methods disclosed and claimed herein can be made and executed without undue experimentation in light of the present disclosure. While the compositions and methods of this invention have been described in terms of preferred embodiments, it will be apparent to those of skill in the art that variations may be applied to the compositions and/or methods and in the steps or in the sequence of steps of the method described herein without departing from the concept, spirit and scope of the invention. More specifically, it will be apparent that certain agents which are both chemically and physiologically related may be substituted for the agents described herein while the same or similar results would be achieved. All such similar substitutes and modifications apparent to those skilled in the art are deemed to be within the spirit, scope and concept of the invention as defined by the appended claims.