FDA Antimicrobial Drugs Advisory Committee (AMDAC) on 26 Apr 2019: IM Bacitracin for staphylococcal pneumonia and empyema in infants?!

Addendum: This is the first of a series of newsletters on IM bacitracin. Go here for the next newsletter.

Dear All:

FDA has announced that on 26 April (8:30a-1:00p) it will have an Antimicrobial Drugs Advisory Committee to

• “… discuss the safety and effectiveness of bacitracin for intramuscular injection for the treatment of infants with pneumonia and empyema caused by staphylococci shown to be susceptible to the drug, which is the only approved indication for bacitracin for intramuscular injection.
• “The committee will also consider whether there are other uses for bacitracin for intramuscular injection that could be studied.
• “FDA will present background information on the regulatory history of bacitracin for intramuscular injection and information on the current use of bacitracin for intramuscular injection.”

Well, this one certainly caught me by surprise! Bacitracin? IM? Infants? I had no clue! But, it turns out that there is this one approved indication for systemic use of bacitracin. The incredibly brief USPI is here and shows that it was last updated May 2018! The label comes with this Warning:

• Nephrotoxicity: Bacitracin in parenteral (intramuscular) therapy may cause renal failure due to tubular and glomerular necrosis. Its use should be restricted to infants with staphylococcal pneumonia and empyema when due to organisms shown to be susceptible to bacitracin. It should be used only where adequate laboratory facilities are available and when constant supervision of the patient is possible.
• Renal function should be carefully determined prior to and daily during therapy. The recommended daily dose should not be exceeded and fluid intake and urinary output should be maintained at proper levels to avoid kidney toxicity. If renal toxicity occurs the drug should be discontinued. The concurrent use of other nephrotoxic drugs, particularly streptomycin, kanamycin, polymyxin B, polymyxin E (colistin), and neomycin should be avoided.

Your guess is as good as mine on the goal for this AMDAC but I’ll hazard the obvious guess that the benefit/risk ratio of this compound is not very favorable for systemic use. A brief search suggests that this product label is very, very, very old. As a first hint, I found this comment online: “Bacitracin was first isolated from Bacillus subtilis around 1943 and was approved by the FDA in 1948.” Consistent with this, we have a paper by R Koch and G Donnell entitled “Staphylococcic infections in children” and published in Calif Med 87(5): 313-316, 1957. Here is its abstract (emphasis added) and the entire .pdf is here if you want to learn more: Over 50 per cent of all staphylococcic infections are hospital-acquired. In 92 per cent of hospital-acquired infection, the organism is resistant to penicillin, and in 74 per cent to tetracycline. Chloramphenicol, bacitracin, novobiocin and erythromycin are the drugs of choice for therapy. There was good correlation between clinical response and antibiotic therapy selected on the basis of results of organism sensitivity tests done by the agar diffusion technique.Cross-resistance among the tetracyclines averaged 94 per cent. Erythromycin and magnamycin showed similar pattern. Mortality in infants less than two months old was 7.8 per cent as compared with 1.1 per cent in older children. Death was related either to pneumonia or to septicemia in the ten fatalities recorded in this series.

We need to await the briefing book to learn more! But, reading this certainly makes you think about how things have changed since the days when chloramphenicol, bacitracin, and novobiocin would appear in a list of drugs of choice! We’ve certainly benefited from having better agents … at least for now … so please get busy and go discover something new!

All best wishes, –jr

John H. Rex, MD | Chief Medical Officer, F2G Ltd. | Expert-in-Residence, Wellcome Trust. Follow me on Twitter: @JohnRex_NewAbx. See past newsletters and subscribe for the future: https://amr.solutions/blog/

Upcoming meetings of interest to the AMR community:

• 26 Mar 2019 (everywhere): First day of Harvard-sponsored course entitled “FDA and Prescription Drugs: Current Controversies in Context.” Register here.
• 26 Mar 2019 (London, UK): Sponsored by The Economist, a 1-day symposium entitled “Antimicrobial Resistance: Preventing an antibiotic apocalypse.” Register here.
• 28 Mar 2019 (everywhere, 4-5.30p GMT): GARDP-sponsored webinar entitled “Clinical development for non-developers Part 3: Antibacterial Drug Enhancer Combinations and Non-traditional Products.” Register here.
• 1 Apr 2019 (University of California, Los Angeles): Longitude Prize AMR Diagnostic Workshop and evening Lecture on the Longitude Prize. Details here.
• 8 Apr 2019 (FDA White Oak Campus): Workshop entitled “Development of Antibacterial Drugs for the Treatment of Nontuberculous Mycobacterial Disease”. Register here.
• 9 Apr 2019 (everywhere, 17:00-18:30 CEST): GARDP-sponsored webinar entitled “Mining Chemical Libraries for New Antibacterials.” Register here.
• 11-12 Apr 2019 (Amsterdam): ESGAP–SWAB (European Study Group for Antibiotic Policies – Stichting Werkgroep Antibioticabeleid) Technical Workshop on measuring quantity and quality of antimicrobial use. Register here. 
• 13-16 Apr 2019 (Amsterdam): Annual ECCMID meeting
• 16-18 Apr 2019 (Utrecht): ICOHAR, International Conference on One Health Antimicrobial Resistance. Organized by the ESCMID Study Group for Veterinary Microbiology (ESGVM).
• 24-26 Apr 2019 (Boston): Annual SHEA (Soc. for Hospital Epidemiology of America) Spring meeting
• 6-11 May 2019 (Ljubljana, Slovenia): 37th Annual Meeting of the European Society for Paediatric Infectious Diseases (ESPID). Details here.
• 20 May 2019 (everywhere): Application deadline for NIAID solicitation (HHS-NIH-NIAID-BAA2019-1) for proposals to support new vaccine or therapeutics candidates targeting antibiotic-resistant bacterial infections. Go here for more details.
• 3-6 Jun 2019 (Philadelphia): Annual BIO meeting
• 10-11 June 2019 (Research Triangle Park, NC): AMR Action Summit on R&D and Commercialization. Sponsors include the British-American Business Council, the UK Gov’t, CARB-X, the NC Biotechnology Center, and others. Details here.
• 20-24 June 2019 (San Francisco): Annual ASM Microbe meeting.
• [NEW] 10-11 Jul 2019 (Madison, WI): Tiny Earth Symposium, a teaching consortium that uses crowd-sourcing of antibiotic-producing microbes to improve undergraduate education. Details here.
• [Mark your calendar now!] 3-6 Sep 2019 (Boston). Annual ASM-ESCMID Conference on Antibiotic Development. The Bootcamp series will continue on 3 Sep with the main meeting on 4-6 Sep. Mark your calendar now and check back here for details.
• 6-8 Sep 2019 (Bilbao, Spain): 5th ESCMID conference on Vaccines. Check back here for details.
• 2-6 Oct 2019 (Washington, DC): IDSA’s annual IDWeek meeting.
• 19-27 Oct 2019 (Annecy, France): International Course on Antibiotics and Resistance (ICARe) – A soup-to-nuts intensive residential training program on all things AMR, especially R&D for new antibiotics. See this link for details.
• [Mark your calendar now!] 1-6 Mar 2020 (Il Ciocco, Tuscany, Italy): GRC on Antibacterial Discovery and Development: “Now is the time to re-boot antibiotic R&D before it’s too little, too late.” Not yet online, but the date is firm. Will share a link when it becomes available.