Topical phage treatment shows potential, weaknesses, in small clinical trial
The results of a small clinical trial in France show that a topical treatment containing a cocktail of bacteriophages successfully reduced bacterial burden in patients with infected burn wounds, but at a significantly slower rate than standard of care. The findings appeared yesterday in The Lancet Infectious Diseases.
In the randomized phase 1/2 PhagoBurn trial—the first randomized controlled trial to investigate phage therapy—25 patients with a confirmed burn wound that was clinically infected with Pseudomonas aeruginosa were recruited from nine hospitals in France and Belgium. The participants were randomly assigned 1:1 to receive topical treatment for 7 days with a cocktail of 12 natural lytic anti-P aeruginosa bacteriophages collected from hospital sewer water (PP1131) or standard of care (1% sulfadiazine silver emulsion cream). The primary end point was median time to sustained reduction in bacterial burden in two quadrants via a four-quadrant method, assessed by use of daily swabs in all participants.
Of the patients—recruited from Jul 22, 2015, to Jan 2, 2017—13 received phage therapy and 12 received standard of care. The primary end point was reached in a median of 144 hours in the PP1131 group versus a median of 47 hours in the standard-of-care group (hazard ratio, 0.29; 95% confidence interval, 0.10 to 0.79; P = 0.018). In the PP1131 group, 6 of the 12 analyzable participants (50%) had a maximal bacterial burden versus 2 of 13 (15%) in the standard-of-care group. Adverse events were higher in the standard-of-care group (7/13, 54%) than in the PP1131 group (3/13, 23%). A follow-up study of bacteria isolated from patients whose PP1131 treatment failed showed resistance to low-phage doses.
Recruitment was stopped on Jan 2, 2017, because of concerns about patient exposure to insufficient phage concentration. On Mar 20, 2017, a data and safety monitoring board recommended stopping the trial because of the insufficient efficacy of PP1131.
The researchers say, however, that the clinically relevant reduction in bacterial burden observed in the group treated with the phage cocktail, and the smaller number of adverse events compared with standard of care, illustrate the potential of phage therapy.
"Although the effect was slower than in the control group, we found that our phage cocktail reduced bacterial burden in the infected wounds of patients with burns, one of the most difficult populations to treat, and something that, to our knowledge, has never been achieved in a human trial before," they write.
Oct 3 Lancet Infect Dis abstract
Study highlights high levels of inappropriate antibiotic prescribing in China
Chinese researchers employed actors pretending to be patients with one of three conditions that didn't require antibiotics and found that in 42% of 526 rural primary care encounters, physicians inappropriately prescribed the drugs anyway, according to a study today in the Journal of Antimicrobial Chemotherapy.
The study took place in village clinics and township health centers, the two lower tiers of China's three-tiered rural health system, in three geographically dispersed regions. The "patients" recruited for the study were trained to present cases of pulmonary tuberculosis, viral gastroenteritis, or unstable angina. The investigators also provided primary care providers with clinical vignettes to assess antibiotic prescribing habits.
The researchers found that providers inappropriately prescribed antibiotics in 221 of 526 patient visits, or 42% of the time. And compared with patient interactions, prescription rates were 29% lower in matching clinical vignettes (42% vs. 30%), suggesting practices don't always follow theoretical knowledge. Compared with vignettes assessing diagnostic and therapeutic knowledge jointly, prescribing rates were 67% lower in vignettes with the diagnosis revealed.
The authors conclude, "While a large proportion of overprescription may be due to factors such as financial incentives tied to drug sales and perceived patient demand, our findings suggest that deficits in diagnostic knowledge are a major driver of unnecessary antibiotic prescriptions."
Oct 4 J Antimicrob Chemother abstract
Point-of-care flu tests don't lower antibiotic prescribing, study finds
A meta-analysis today in Clinical Infectious Diseases of 13 studies involving point-of-care tests (POCTs) for influenza finds that they had no effect on admissions, return visits, or antibiotic prescribing but were associated with increased antiviral prescribing.
UK experts included in their review seven randomized and six non-randomized studies that involved more than 9,000 patients total. Most evidence came from pediatric emergency departments.
In randomized trials, POCTs had no effect on admissions, returning for care, or antibiotic prescribing, but they were tied to an increase in prescribing antivirals. In addition, further testing was reduced for full blood counts, blood cultures, and chest x-ray but not for urinalysis. Time in the emergency department was not changed. Fewer non-randomized studies reported these outcomes, with some findings reversed or lessened.
The researchers conclude, "Point-of-care testing for influenza influences prescribing and testing decisions, particularly for children in emergency departments."
Oct 4 Clin Infect Dis abstract
