The Story to be Told...

The Story of Intralesional Antibiotics

The foundations of surgical antibiotic prophylaxis were well-established by the 1970s. These principles state that an adequate concentration of the prophylactic antibiotic must be present in both the serum and the wound tissue when bacteria is inoculated into the wound by a surgical procedure. The concentration of the protein-free active fraction that can diffuse into the dermal interstitial space from the vascular compartments is critical for successful antibiotic prophylaxis. The standard delivery modes, i.e., intravenous, intramuscular, and topical have not changed in 50 years. 

In the late 1970s, a group of dedicated general surgeons from the United Kingdom,1 followed by surgeons in Greece2,3 and Spain4, began a journey to optimize the delivery of antibiotics for surgical antibiotic prophylaxis (SAP). Dr Pollock and Greenall1 (Scarborough Hospital in North Yorkshire) advocated placing antibiotics directly into the wound during surgery. Although no needle was used to deliver antibiotics, this technique was termed intra-incisional. The rationale and groundwork for direct needle intralesional injection of antibiotics is attributed to Taylor5 and others at the Manchester Royal Infirmary. He advocated that the antibiotic would be more effective if injected directly into the sidewall of the abdominal cavity. 

Taylor,5,6 Armstrong, and Reeves6 were the first to publish in support of pre-incisional injection of an antibiotic, followed closely by Rodriguez et al.4 from Spain, Porteous7 in Scotland, and Dillon8 from the United States. These surgeons advocated using a 20 ml syringe containing a local antibiotic injection 10 minutes before an operation. They used a 22-gauge spinal needle inserted into the muscle, fat, and skin of the intended incision, depositing the antibiotic directly.

The report by Dillon identified 34 legs that were at risk for amputation due to peripheral arterial insufficiency, osteomyelitis, and soft tissue infections in ischemic diabetic legs. The author utilized local antibiotic injections and stated, “Of the 34 legs, 31 were spared amputation. Pain was lessened or relieved in all lesions within a few days of the local injections of antibiotics.” The walking capacity also improved in many patients. This report signifies the importance of local antibiotic therapy beyond its use in general surgery.8

In 1984, Tanner published a letter titled, “Is preoperative intra-incisional intra-parietal injection of antibiotics the ideal mode of administration as prophylaxis in abdominal surgery?” 9The author stated that on a theoretical basis, this approach would appear to be the ideal mode of antibiotics, producing very high levels of antibiotics present in the wound at the time of potential contamination.” It was noted that adequate serum levels were obtained to minimize the risk of serious systemic complications.

Clinical trials followed throughout the 1980s and 1990s, with John Zitelli, Robert Griego,10,11 and David Brodland11 spearheading the direct delivery of antibiotics in dermatologic surgery. Their initial work, utilizing nafcillin, was published in 1998.10 This group now has more than 12,000 cases of intra-incisional delivery in cutaneous surgery with an infection rate of less than 1%.

The Guidelines

Despite positive results from clinical trials, the published guidelines do not reflect the efficacy, benefits, and recommendations of local antibiotic delivery. This is primarily due to a lack of commercial products available globally. The lack of commercially available products has forced surgeons to compound their own antibiotic solutions. There is a lack of data on optimizing the concentration of the various antibiotic solutions. In the United States, laws prevent physicians from compounding antibiotic solutions. Nevertheless, in the best interest of their patients, physicians still managed to utilize this novel technology as an off-label use with no reimbursement.

A Worldwide Shift

The worldwide shift for intra incisional antibiotic delivery is upon us. This technique has more potential for reducing antimicrobial resistance than any other current proposal to fight the global AMR crisis. SAP accounts for at least 15% of the antibiotics used globally; reducing this should substantially impact antimicrobial resistance. The toxicities of antibiotics and the damage to the human microbiome from the routine use of common antibiotics is now a threat to all mankind. We have the novel delivery method, the clinical trials, the data, and the ability to assist surgeons in their quest to optimize surgical antibiotic prophylaxis.
  1. M J Greenall, J E Atkinson, Mary Evans, A V Pollock. (1981) Single dose antibiotic prophylaxis of surgical wound sepsis: which route of administration is best? A controlled clinical trial of intra-incisional against intravenous cephaloridine. Journal of Antimicrobial Chemotherapy. Vol 7, 223-227
  2. George E Chalkiadakis, MD; Constantin Gonnianakis, MD; Aristidis Tsatsakis, PhD, et al. (1995) Preincisional Single-Dose Ceftriaxone for the Prophylaxis of Surgical Wound Infection. Am Jour of Surg. Vol 170 (October) 353-355.
  3. Petrakis Vrachassotakis, A Tsatsakis, G Chalkiadakis. (1998) Prospective Study of preincisional single-dose ceftriaxone in reducing postoperative wound infection in high risk of infection patients. Euro Rev Med Pharmacol Sci. Vol 2(3-4): 141-145
  4. J R Barbero Rodriguez, E L Marino, M J Otero, et al. (1984) Concentrations of Cefmetazole in Plasma and Tissue Resulting from Peri-Incisional Administration Before Appendectomy. Antimicrobial Agents and Chemotherapy. p. 787-788.
  5. TV Taylor, DL Dawson, M DE Silva, et al. (1985) Preoperative intraincisonal cefamandole reduces wound infection and postoperative inpatient stay in upper abdominal surgery. Annals of the Royal College of Surgeons of England. Vol 67. 235-237.
  6. CP Armstrong, T V Taylor, D S Reeves. (1982) Pre-incisional intraparietal injection of cephamandole: a new approach to wound infection prophylaxis. Br J Surg. Aug ; 69(8); 459-460.
  7. C Porteous, P M Davidson, D Rawluk, M Brown, et al. (1985) Peri-incisional mezlocillin versus rectal-metronidazole for wound infection prophylaxis. Journal of Hospital Infection. Vol 6. 413-418.
  8. R S Dillon. (1986) Successful Treatment of Osteomyelitis and Soft Tissue Infections in Ischemic Diabetic Legs by Local Antibiotic Injections and the End-diastolic Pneumatic Compression Boot. Ann Surg. (December) 643-649.
  9. A G Tanner. (1984) Is pre-operative intra-incisional intra-parietal injection of antibiotics the ideal mode of administration as prophylaxis in abdominal surgery? Jour of Antimicrob Chemother. (April) Vol 13 (4) 305-308.
  10. R D Griego, J A Zitelli. (1998) Intra-Incisional Prophylactic Antibiotics for Dermatologic Surgery. Arch Dermatol. (June) Vol 134: 688-692.
  11. M J Huether, R D Griego, D Brodland, J Zitelli. (2002) Clindamycin for Intraincisional Antibiotic Prophylaxis in Dermatologic Surgery. Arch Dermatol. (Sept) Vol 138: 1145-1148.

Binary Pharmaceuticals develops accessible and affordable antibiotic delivery platforms in the interest of public health. 

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