Tackling Early Morbidity and Mortality in Myeloma: Assessing the benefit of antibiotic prophylaxis and its effect on healthcare associated infections

There is a high risk of infection in patients with impaired immune function including those with low numbers of white blood cells (often a result of cancer treatment), reflux nephropathy, absent spleen, HIV and chronic lung disease. Giving these patients Antibiotic Prophylaxis (AP) - antibiotics given to prevent infection - is common evidence based practice in the NHS. But the studies that established the benefit of AP in these patients were before the current rise in healthcare associated infections, such as Clostridium difficile (C Diff). C diff is a bacterium found in low numbers in the gut of a small proportion of healthy adults. When the normal intestinal bacteria are killed off by antibiotics, outgrowths of antibiotic resistant C diff can cause severe illness. There were 36,095 cases of C diff associated diarrhoea in the UK in 2008-2009 with a substantial proportion resulting in death. This along with the increase in other health care associated infections like MRSA has made doctors and patients question the net benefits of preventive antibiotics. Thus there is an urgent need to study the risks of AP therapy with respect to its effect on carriage rates of S. aureus (including methicillin resistant forms - MRSA), C. difficile and ESBL (extended spectrum beta lactamase) coliforms and the risk of developing an infection from carriage of those organisms. Myeloma is a cancer of bone marrow plasma cells arising in 4000 UK patients per year. Myeloma causes very low immunity, with serious infections in a quarter of patients and 5% of patients dying from infection within 12 weeks of diagnosis. About half of patients with myeloma are not given AP because of lack of studies to assess benefit and fear it will cause health care associated infection. Thus there is an urgent need for the effect of antibiotic prophylaxis on Healthcare-associated infections to be studied in a randomised trial. A trial of antibiotic prophylaxis in a group of immunosuppressed patients who are likely to benefit from the antibiotic, and are mostly outpatients, provides an ideal platform to perform a longitudinal study of colonisation and subsequent patterns of infection with antibiotic resistant organisms. This information will inform rational decision making about the risks and benefits of antibiotic chemoprophylaxis, not only in myeloma, but also in other conditions where prolonged antibiotics are indicated. This study will assess risks, benefits and cost effectiveness of antibiotic prophylaxis using levofloxacin (a commonly used quinolone antibacterial agent) in newly diagnosed symptomatic myeloma by a prospective, multi-centre, randomized, double-blind, placebo-controlled trial. The trial will recruit patients from about 100 district general and teaching hospitals most of whom already participate in trials of anti-myeloma therapy. The trial centre will randomly allocate 440 myeloma patients to receive antibiotic treatment (levofloxacin one tablet a day) and 440 patients to receive a placebo for 12 weeks. Patients will be monitored for fevers and other evidence of infections, myeloma response and hospital admission. 4 weekly samples of stools and nasal swabs will monitor for carriage of antibiotic resistant organisms as well as monitoring for invasive infection by health care associated infections. The trial team consists of specialists with expertise in clinical trials, immunity, health care associated infections and microbiology, myeloma, health economics and patient advocacy. A safety committee will monitor the results closely and terminate the trial early if there are any safety concerns.