Nav: Home

Antibiotic identified that reduces infection risk in young leukemia patients

September 14, 2017

St. Jude Children's Research Hospital researchers have identified an antibiotic that significantly reduced the odds of infections in children starting treatment for acute lymphoblastic leukemia (ALL) without an apparent increase in antibiotic resistance. The research appears today in the journal Clinical Infectious Diseases.

The study was the largest yet focused on the safety and efficacy of proactive antibiotic therapy to prevent infections in pediatric ALL patients during induction therapy. These early weeks of chemotherapy often lead to a drop in white blood cells known as neutropenia that leaves patients at risk for life-threatening infections that can delay cancer treatment. Nationwide, up to 4 percent of young ALL patients die from treatment-related infections.

"This research provides the first major evidence supporting targeted use of antibacterial prophylaxis for at-risk pediatric ALL patients, particularly use of the broad-spectrum antibiotic levofloxacin," said lead author Joshua Wolf, M.D., an assistant member of the St. Jude Department of Infectious Diseases. The findings have been incorporated into Total Therapy XVII, the current St. Jude clinical trial for children and adolescents newly diagnosed with ALL.

Researchers reported that preventive therapy with levofloxacin or other antibiotics reduced the odds of infection, including fevers and bloodstream infections, by 70 percent or more in ALL patients with neutropenia during induction therapy. Levofloxacin also reduced patients' odds of antibiotic-associated infection with Clostridium difficile by 95 percent or more. Hospital-acquired C. difficile infection is associated with a nearly seven-fold increased risk of death in children.

Levofloxacin reduced patient exposure to front-line antibiotics like vancomycin and cefepime. These antibiotics are needed if patients develop infections during therapy. Researchers said the reduced exposure might explain why levofloxacin reduced odds of infection with C. difficile. A.ntibiotic treatment is a risk factor for C. difficile infection.

"Prophylactic antibiotic therapy with levofloxacin is routine for at-risk adult ALL patients, but it has remained controversial in children," Wolf said. "Until this study, evidence supporting the safety and efficacy of prophylactic antibiotic therapy in children with ALL has been sparse."

Physicians have also worried that proactive antibiotic treatment in children would promote drug resistance, particularly to antibiotics needed to treat life-threatening infection in patients who become infected.

The study included 344 St. Jude patients enrolled in the St. Jude Total XVI clinical trial for patients newly diagnosed with ALL. Patients were enrolled from 2007 to 2016. Until July 2014, patients received prophylactic antibiotic therapy at the discretion of their physicians. Beginning in August 2014, hospital treatment guidelines changed to recommend prophylactic levofloxacin therapy during induction therapy for ALL patients who develop neutropenia expected to last at least seven days.

Wolf and his colleagues used the change to compare infection rates and other questions in 173 patients who received no preventive antibiotics; 69 patients treated prophylactically with levofloxacin; and 102 patients who received other prophylactic antibiotics, typically cefepime, ciprofloxacin or vancomycin, alone or in combination. Researchers did not include patients with infections that began prior to or early in induction therapy. Investigators also used a statistical method called propensity score-weighting to control for differences among the patient groups.

Researchers reported that patients with neutropenia who received any prophylactic therapy were far less likely than those who did not to develop fever, documented or likely infections, or bloodstream infections.

In contrast, reductions in C. difficile infections occurred only in levofloxacin-treated patients. Levofloxacin belongs to the fluoroquinolone family of antibiotics, which animal studies have suggested might reduce the risk of infection with C. difficile compared with other antibiotics. Levofloxacin was associated with reduced exposure to other antibiotics, including antibiotics that were essential for treatment if infections did occur. The reduction in exposure to other antibiotics may partly explain why C. difficile infections declined in levofloxacin-treated patients, Wolf said.

Meanwhile, antibiotic resistance did not significantly increase despite greater use of levofloxacin to prevent infections. "We are cautiously optimistic that any impact of levofloxacin on antibacterial resistance will be balanced by the reduction in use of other antibiotics, but long-term monitoring antibiotic resistance patterns in young ALL patients will be needed to prove this," Wolf said.

-end-

The senior author is Sima Jeha, M.D., a member of the St. Jude Department of Oncology. The other authors are Li Tang, Patricia Flynn, Ching-Hon Pui, Aditya Gaur, Yilun Sun, Hiroto Inaba, Tracy Stewart, Randall Hayden and Hana Hakim, all of St. Jude.

The study was funded in part by grants (CA21765, CA3640126S1, GM92666) from the National Institutes of Health and ALSAC, the fundraising and awareness organization of St. Jude.

St. Jude Children's Research Hospital

Related Antibiotics Articles:

Antibiotics promote resistance on experimental croplands
Canadian researchers have generated both novel and existing antibiotic resistance mechanisms on experimental farmland, by exposing the soil to specific antibiotics.
Why antibiotics fail
UCSB biologists correct a flaw in the way bacterial susceptibility to these drugs is tested.
Fungi have enormous potential for new antibiotics
Fungi are a potential goldmine for the production of pharmaceuticals.
Antibiotics can boost bacterial reproduction
The growth of bacteria can be stimulated by antibiotics, scientists at the University of Exeter have discovered.
Last-line antibiotics are failing
The ECDC's latest data on antimicrobial resistance and consumption shows that in 2015, antibiotic resistance continued to increase for most bacteria and antibiotics under surveillance.
Two antibiotics fight bacteria differently than thought
Two widely prescribed antibiotics -- chloramphenicol and linezolid -- may fight bacteria in a different way from what scientists and doctors thought for years, University of Illinois at Chicago researchers have found.
Preserving the power of antibiotics
News release describes efforts to address inappropriate antibiotic prescribing in emergency departments and urgent-care centers nationwide, which a JAMA study published this past May found rates as high as 50 percent for acute respiratory infections in US emergency departments.
Antibiotics could be cut by up to one-third, say dairy farmers
Nine in 10 dairy farmers participating in a new survey from the Royal Association of British Dairy Farmers (RADBF) say that the farming industry must take a proactive lead in the battle against antibiotic resistance.
Antibiotics may be inappropriate for uncomplicated diverticulitis
Antibiotics are advised in most guidelines on diverticulitis, which arises when one or more small pouches in the digestive tract become inflamed or infected.
New book on Antibiotics and Antibiotic Resistance from CSHLPress
'Antibiotics and Antibiotic Resistance' from CSHLPress examines the major classes of antibiotics, together with their modes of action and mechanisms of resistance.

Best Science Podcasts 2017

We have hand picked the best science podcasts for 2017. Sit back and enjoy new science podcasts updated daily from your favorite science news services and scientists.
Now Playing: Radiolab

Radiolab Presents: Anna in Somalia
This week, we are presenting a story from NPR foreign correspondent Gregory Warner and his new globe-trotting podcast Rough Translation. Mohammed was having the best six months of his life - working a job he loved, making mixtapes for his sweetheart - when the communist Somali regime perp-walked him out of his own home, and sentenced him to a lifetime of solitary confinement.  With only concrete walls and cockroaches to keep him company, Mohammed felt miserable, alone, despondent.  But then one day, eight months into his sentence, he heard a whisper, a whisper that would open up a portal to - of all places and times - 19th century Russia, and that would teach him how to live and love again. 
Now Playing: TED Radio Hour

Future Consequences
From data collection to gene editing to AI, what we once considered science fiction is now becoming reality. This hour, TED speakers explore the future consequences of our present actions. Guests include designer Anab Jain, futurist Juan Enriquez, biologist Paul Knoepfler, and neuroscientist and philosopher Sam Harris.