Researchers use bacteria-eating viruses in the treatment of complex lung infections

Scientists from the University of California San Diego School of Medicine and the University of Pittsburgh have conducted the largest case series of patients who received bacteriophage treatment for antibiotic-resistant infections.

The team used bacteria-eating viruses to treat 20 complicated and antibiotic-resistant lung infections. As per the encouraging results they shared, the subjects have shown no negative side effects, and more than half of them had favorable clinical results.

Non-tuberculous mycobacteria (NTM) are a class of bacteria that occasionally cause lung infections. People who have cystic fibrosis or any other chronic disorders that damage or destroy the bronchi in the lungs are more prone to get NTM infections. Treating NTM infections, however, is challenging due to bacterial resistance to antibiotics.

Using bacteria-eating viruses

Bacteriophages are a kind of virus that evolved to target and eradicate particular bacterial species or strains. Since their first identification in the early 20th century, antibiotic-resistant bacteria have increased in prevalence, and more research has been done on them to ascertain their medical potential.

The use of phage therapy is limited due to the fact that each phage species targets and destroys only one bacterial species and the current armamentarium of the phages that are known to be therapeutically useful is relatively small. Therefore, phage therapy applications are limited to experimental therapies, where all other feasible options have failed.

The new study included 20 subjects with complex, antibiotic-resistant mycobacterial infections. All of the patients had varying underlying conditions, such as cystic fibrosis (CF), an inherited and progressive disease that causes severe damage to the lungs and other organs.

The research team screened 200 patients with symptomatic lung disease in order to detect bacterial strains that can be defenseless against phages and identified 55 strains.

The 20 trial participants received phages intravenously, via nebulizer aerosolization, or by employing both techniques twice a day for an average of six months. Nevertheless, some patients had shorter or longer therapy depending on their clinical or microbiological response.

No adverse impact

The final results have shown that 11 out of these 20 subjects showed some improvements in symptoms or reduced the presence of bacteria, while five patients had inconclusive outcomes and four displayed no response. On the other hand, none of the patients showed any negative side effects as a reaction to phage therapy.

“Given the complexity and great variation of these patients and their individual conditions, it is not possible to draw any broad conclusions, except that phage treatment of mycobacterial infections shows promise and should be explored further, especially for treating patients with few or no other good options,” said Constance Benson, MD, professor of medicine and global public health at UC San Diego School of Medicine.

“In phages, evolution has produced an effective killer of bacteria, one that offers enormous potential in the worldwide fight against antibiotic resistance. This paper is a glimpse of what might and can be. It starts with NTM infections, but the number of antibiotic-resistant bacterial species out there is large and growing. This is another step, an important one, in a fight that will likely never end,” adds co-author Robert Schooley, MD, professor of medicine and an infectious disease expert at UC San Diego School of Medicine.

Abstract:

Background: Non-tuberculous Mycobacterium (NTM) infections, particularly Mycobacterium abscessus, are increasingly common among patients with cystic fibrosis and chronic bronchiectatic lung diseases. Treatment is challenging due to intrinsic antibiotic resistance. Bacteriophage therapy represents a potentially novel approach. Relatively few active lytic phages are available and there is great variation in phage susceptibilities among M. abscessus isolates, requiring personalized phage identification.

Methods: Mycobacterium isolates from 200 culture-positive patients with symptomatic disease were screened for phage susceptibilities. One or more lytic phages were identified for 55 isolates. Phages were administered intravenously, by aerosolization, or both to 20 patients on a compassionate use basis and patients were monitored for adverse reactions, clinical and microbiologic responses, the emergence of phage resistance, and phage neutralization in serum, sputum, or bronchoalveolar lavage fluid.

Results: No adverse reactions attributed to therapy were seen in any patient regardless of the pathogen, phages administered, or the route of delivery. Favorable clinical or microbiological responses were observed in 11 patients. Neutralizing antibodies were identified in serum after initiation of phage delivery intravenously in eight patients, potentially contributing to lack of treatment response in four cases but were not consistently associated with unfavorable responses in others. Eleven patients were treated with only a single phage, and no phage resistance was observed in any of these.

Conclusions: Phage treatment of Mycobacterium infections is challenging due to the limited repertoire of therapeutically useful phages, but favorable clinical outcomes in patients lacking any other treatment options support continued development of adjunctive phage therapy for some mycobacterial infections.

The results of the study were recently published in the journal Clinical Infectious Diseases.