Editors' ChoiceInfectious diseases

A shocking development

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Science Translational Medicine  23 Dec 2015:
Vol. 7, Issue 319, pp. 319ec221
DOI: 10.1126/scitranslmed.aad8029

Every year, millions of implanted medical devices—prosthetic joints, cardiac pacemakers, dialysis grafts, vascular stents, heart valves, chemotherapy ports, and more—improve patients’ well-being and even save lives. These devices, however, are prone to developing infectious biofilms, a slimy coating of living, reproducing microbes embedded in a sticky matrix of proteins, polysaccharides, and nucleic acids. Biofilms also form on human tissues, as with infective endocarditis on heart valves or chronic bronchitis in airways affected by cystic fibrosis. Some biofilm-producing bacteria, like Pseudomonas aeruginosa and Staphylococcus aureus, are notoriously difficult to eradicate; bacteria within biofilms are relatively resistant to medical therapies, usually requiring antibiotic concentrations of 1000 to 10,000 times greater than those needed to kill a solitary bacterium. Thus, surgical removal of the infected device or tissue may be necessary to clear the infection but incurs an additional risk of morbidity and mortality from the surgery itself. For biofilms that cannot be physically removed, such as those produced by Pseudomonas species in the lungs of patients with cystic fibrosis, repeated antibiotic courses are often given, with the bacterial colony invariably becoming resistant to the drug over time.

Now, Gnanadhas et al. demonstrate that they can use shock waves—high-energy mechanical pulses, traveling at supersonic speed—as an adjunct to antibiotic treatment of P. aeruginosa and S. aureus biofilms. In their experiments, the antibiotic ciprofloxacin showed minimal efficacy in eradicating these bacteria from biofilms grown on urinary catheters, commonly colonized medical devices. However, when shock waves from a hand-held generator were applied to the catheters, the bacteria became 100 to >1000-fold more sensitive to ciprofloxacin treatment.

The authors also used extracorporeal shock wave therapy together with antibiotic treatment in mouse models of P. aeruginosa pneumonia and S. aureus wound infection. They treated infected mice with whole-body shock waves, intravenous ciprofloxacin, or a combination of both. In Pseudomonas-infected mouse lungs and in the skin surrounding S. aureus–infected incisions, significant reductions in bacterial growth were seen only in mice that received shock wave therapy plus antibiotics. In the mice with Pseudomonas pneumonia, most of the mice given either shock wave therapy or ciprofloxacin died, whereas all of those treated with both modalities survived. The authors hypothesize that the shock waves disrupted the biofilm matrix and exposed embedded bacteria to antibiotic concentrations that would not normally be able to penetrate an intact biofilm.

Extracorporeal shock wave therapy is already in clinical use for the treatment of kidney stones, musculoskeletal diseases, and nonhealing wounds. Thus, its application to the eradication of infectious biofilms surrounding implanted medical devices may hold great promise as an alternative to risky surgical device removal.

D. P. Gnanadhas et al., Successful treatment of biofilm infections using shock waves combined with antibiotic therapy. Sci. Rep. 10.1038/srep17440 (2015). [Full Text]

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