Advertisement

Blogs

Medication Shortages – Boning Up on Antibiotics

By Kelly Kampschmidt posted 10-02-2011 21:09

  

The recent shortage of tobramycin powder for injection has left several people wondering what other antibiotics can be added to bone cement.  Tobramycin powder for injection is often added to bone cement during orthopedic procedures.  The cement can be used to affix a prosthetic joint or it can be used to create a spacer.  The indication determines how much antibiotic can be added to the cement.  Antibiotic impregnated bone cement helps to attain high concentrations of antibiotics at the site of infection. 

In an effort to be proactive against drug shortages, the drug information department at Northwestern Memorial Hospital was asked to investigate the shortage of tobramycin powder for injection and come up with an alternative plan.  A PubMed search was completed to obtain review articles and primary literature related to this topic.  The following chart was created to communicate the findings to the medical staff.    

General guidelines to follow:

  • For prophylaxis, a low dose of antibiotic-loaded bone cement (≤1g of antibiotic per batch of cement) should be used1
  • For treatment, a high dose of antibiotic-loaded bone cement (>1g of antibiotic per batch of cement) should be used1
  • Adding more than 8g of antibiotic powder to cement weakens the cement2
  • Adding liquid antibiotics to cement weakens the cement2
  • If using cement for prosthesis fixation, more than 4.5g of antibiotic powder should not be used1

ANTIBIOTIC

DOSE

EVIDENCE

Amphotericin B

100-150mg/40g cement1

Dose provided in a review article, but evidence behind use is not known

Aztreonam

4g/40g cement3

Hsieh et al used aztreonam 4g with vancomycin 4g mixed in 40g PMMA cement for treatment of infected hip implants.  In 45 patients there were no signs of re-infection during follow up period of 33.1 months.3

Cefazolin

4.5g/40g cement5

Use is not recommended.  Showed unfavorable characteristics in dogs.5

Cefotaxime

2g/80g cement6

Koo et al used 2g vancomycin, 2g gentamicin, and 2g cefotaxime in 80g PMMA cement for treatment of infected THA.  21 of 22 patients were treated successfully.6

Cefuroxime

2g/40g cement7

Chiu et al used 2g cefuroxime in 40g Simplex P cement as prophylaxis in 340 primary TKA’s.  No deep infections occurred in patients that received cefuroxime in bone cement. 7

Ciprofloxacin

6g/40g cement5

Use is not recommended.  Showed unfavorable characteristics in dogs.5

Clindamycin

4-8g/40g cement5

Clindamycin demonstrated high seroma, granulation tissue, and bone concentrations in dogs.5

Heat stable4

Commercially available only as a liquid in the United States

Co-trimoxazole

                    

Heat stable4 Evidence behind use is not known

Commercially available only as a liquid in the United States

Colistin

 

Heat stable4

Inability to elute from PMMA matrix8 therefore should not be used

Dicloxacillin

 

Heat stable4 Evidence behind use is not known

Erythromycin

1-6g/40g cement

Has good bacterial spectrum, rarely causes allergies, and has good elution from cement8

Heat stable4

Gentamicin

1-2g/40g cement

Koo et al used 2g vancomycin, 2g gentamicin, and 2g cefotaxime in 80g PMMA cement for treatment of infected THA. 21 of 22 patients were treated successfully.6

Srivastav et al used 1g gentamicin in 40g CMWI cement for prophylaxis of TJA.  Infection rate was reported at 0.91% which is lower than 1-2% seen in most studies.9

Water soluble, heat stable and bactericidal8

Commercially available only as a liquid in the United States

Methacillin

 

Heat stable4 Evidence behind use is not known

Oxacillin

 

Heat stable4 Evidence behind use is not known

Rifampin

 

Inability to elute from PMMA matrix8 therefore should not be used

Tetracycline

 

Heat stable4

Inability to elute from PMMA matrix8 therefore should not be used

Ticarcillin

12g/40g cement5

Showed unfavorable characteristics in dogs5

Tobramycin

1-5g/40g cement

Maris et al used 1.2-4.8g tobramycin and 1-2g vancomycin per 40g of Palacos-R bone cement.  Showed tobramycin doses of 3.6mg increased elution of tobramycin and vancomycin10

Water soluble, heat stable and bactericidal8

Vancomycin

2-8g/40g cement

Koo et al used 2g vancomycin, 2g gentamicin, and 2g cefotaxime in 80g PMMA cement for treatment of infected THA. 21 of 22 patients were treated successfully.6

Maris et al used 1.2-4.8g tobramycin and 1-2g vancomycin per 40g of Palacos-R bone cement.  Showed tobramycin doses of 3.6mg increased elution of tobramycin and vancomycin10

Hsieh et al used aztreonam 4g with vancomycin 4g mixed in 40g PMMA cement for treatment of infected hip implants.  In 45 patients there were no signs of re-infection during follow up period of 33.1 months.3

COMMERCIALLY AVAILABLE PRODUCTS

Approved as a medical device for fixation of prosthesis to living bone for use in the second stage of a two-stage revision for total joint arthroplasty.

Simplex P with tobramycin

Stryker

1g/40g cement

 http://www.nordic.stryker.com/st-index-down/st_pag_medic-home/st_pag_portfolio-info/st_pag_reconstructive-products/st_pag_cement-products/st-pag-reconstructive_products-bonecement-simplex_p-tobramycin.htm?wa=2

Palacos G with Gentamicin

Heraues

0.5g/40g cement

http://heraeus-medical.com/en/produkte_1/primaerendoprothetik/palacosrg_1/palacosrg.aspx

SmartSet GHV Bone Cement

(Gentamicin)

Depuy Orthopedics

1g/40g cement

http://www.depuy.com/healthcare-professionals/product-details/smartset-ghv-gentamicin-bone-cement?s=search_1313421320511466&i=3&consulta=t&keyword=&company=247&specialty=0&category=0&focus=355&family=0&sorting=title&sorting_type=asc&page=1&per_page=5

 

SmartSet GMV Bone Cement

(Gentamicin)

 

Depuy Orthopedics

1g/40g cement

http://www.depuy.com/healthcare-professionals/product-details/smartset-gmv-gentamicin-bone-cement?s=search_131342155823982&i=4&consulta=t&keyword=&company=247&specialty=0&category=0&focus=355&family=0&sorting=title&sorting_type=asc&page=1&per_page=5

Cobalt G HV Bone Cement

(Gentamicin)

Biomet INC

0.5g/40g cement

http://www.biomet.com/orthopedics/productDetail.cfm?category=7&product=250

Cobalt G MV Bone Cement

(Gentamicin)

Biomet INC

0.5g/40g cement

http://www.biomet.com/orthopedics/productDetail.cfm?category=7&product=255

Several other products exist outside of the United States. 

 

The following link will direct to you PubMed search results on this topic

http://www.ncbi.nlm.nih.gov/pubmed?term=%22Anti-Bacterial%20Agents%22%5BMesh%5D%20AND%20%22Bone%20Cements%22%5BMAJR%5D%20AND%20%22humans%22%5BMeSH%20Terms%5D

References:

  1. Hanssen AD, Spangehl MJ. Practical applications of antibiotic-loaded bone cement for treatment of infected joint replacements. Clin Orthop Relat Res. 2004;427:79-85.
  2. Hsieh PH, Chen LH, Chen CH, et al.  Two-stage revision hip arthroplasty for infection with a custom-made, antibiotic-loaded, cement prosthesis as an interim spacer.  J Trauma.  2004;56(6):1247-52. 
  3. Hsieh PH, Chang YH, Chen SH, Ueng SW, Shih CH. High concentration and bioactivity of vancomycin and aztreonam eluted from Simplex cement spacers in two-stage revision of infected hip implants: a study of 46 patients at an average follow-up of 107 days. J Ortho Res. 2006;24(8):1615-21.
  4. Bourne RB. Prophylactic use of antibiotic bone cement: an emerging standard – in the affirmative. J Arthroplasty. 2004;19(4):69-72
  5. Adams K, Couch L, Cierny G, Calhoun J, Mader JT. In vitro and in vivo evaluation of antibiotic diffusion from antibiotic-impregnated polymethylmethacrylate beads. Clin Orthop Relat Res. 1992;278:244-52.
  6. Koo KH, Yang JW, Cho SH, et al.  Impregnation of vancomycin, gentamicin, and cefotaxime in a cement spacer for two-stage cementless reconstruction in infected total hip arthroplasty. J Arthroplasty. 2001;16(7):882-92.
  7. Chiu FY, Chen CM, Lin CF, Lo WH. Cefuroxime-impregnated cement in primary total knee arthroplasty: a prospective, randomized study of three hundred and forty knees.  J Bone Joint Surg Am. 2002;84A(5):759-62
  8. Popham GJ, Mangino P, Seligson D, Henry SL. Antibiotic-impregnated beads. Part II: Factors in antibiotic selection. Orthop Rev. 1991;20(4):331-7.
  9. Srivastav AK, Nadkarni B, Srivastav S, et al. Prophylactic use of antibiotic-loaded bone cement in primary total knee arthroplasty: Justified or not? Indian J Orthop. 2009;43(3):259-63.
  10. Marsi BA, Duncan CP, Beauchamp CP. Long-term elution of antibiotics from bone-cement: an in vitro study using the prosthesis of antibiotic-loaded acrylic cement (PROSTALAC) system.  J Arthroplasty. 1998;13(3):331-8.


#DrugShortages
1 comment
2931 views

Permalink

Comments

Angela Powell
07-12-2012 09:05

Did you see any data for daptomycin?