Serious infection is one of the largest contributors to early mortality in myeloma. The use of antibiotic prophylaxis for newly diagnosed patients starting treatment offers an opportunity to tackle this early complication however the potential for antibiotic resistance, side effects and healthcare associated infections needs to be carefully considered.
Last month Prof Mark Drayson, Consultant Immunologist at University of Birmingham, and colleagues from the TEAMM (Tackling EArly Morbidity and Mortality in myeloma) investigation team published their findings on the largest trial to date, looking at the use of antibiotic prophylaxis with levofloxacin in newly diagnosed myeloma patients in the Lancet Oncology.
This placebo-controlled randomised trial enrolled 977 newly diagnosed patients, across 93 UK hospitals, to take either 500mg levofloxacin or placebo once daily for 12 weeks. The primary outcome was time to the first febrile episode (single oral temperature of ≥380C that required treatment with anti-infectives) or death within the 12 weeks of trial treatment. The team also looked at the carriage of specific antibiotic-resistant organisms, healthcare-associated infections, myeloma activity and immunocompetence markers every 4 weeks up until week 16, with a final follow-up for myeloma activity and immunocompetence at 1 year.
The trial demonstrated that levofloxacin prophylaxis significantly reduced first febrile episodes or deaths in the levofloxacin group (19%) compared to the placebo group (27%). Levofloxacin was well tolerated with the only detected adverse event a 1% rate of tendonitis and did not significantly increase healthcare-associated infections compared to placebo. Importantly, Drayson et al., also found that there was no increase in the carriage of C difficile, ESBL Gram-negative coliforms, or MRSA. This indicates that, at least for short fixed-term treatment of levofloxacin, concerns over acquisition of antibiotic-resistant organisms are not evident.
This large, well-conducted, supportive care study makes a strong case for the use of levofloxacin during the initial stages of myeloma treatment. However, more research is needed to define the optimal type and length of antibiotic prophylaxis and whether the benefits increase without any challenges with longer-term use.
Prof Mark Drayson commented:
“The hope is that early treatment with levofloxacin could become a standard of care for myeloma patients, reducing the risk of serious bacterial infection which affects a third of patients in the first 3 months after diagnosis.
We are now planning a randomised study in which all newly diagnosed myeloma patients receive levofloxacin for 12 weeks and are randomised to stop or continue levofloxacin to 52 weeks. We will see if these longer term strategies further reduce infections and deaths, without increasing antibiotic resistance”.