A desiccated dual-species subaerial biofilm reprograms its metabolism and affects water dynamics in limestone.

Understanding the impact of sessile communities on underlying materials is of paramount importance in stone conservation. Up until now, the critical role of subaerial biofilms (SABs) whether they are protective or deteriorative remains unclear, especially under desiccation. The interest in desiccated SABs is raised by the prediction of an increase in drought events in the next decades that will affect the Mediterranean regions' rich stone heritage as never before. Thus, the main goal of this research is to study the effects of desiccation on both the biofilms' eco-physiology and its impacts on the lithic substrate. To this end, we used a dual-species model system composed of a phototroph and a chemotroph to simulate biofilm behavior on stone heritage. We found that drought altered the phototroph-chemotroph balance and enriched the biofilm matrix with proteins and DNA. Desiccated SABs underwent a shift in metabolism to fermentation and a decrease in oxidative stress. Additionally, desiccated SABs changed the water-related dynamics (adsorption, evaporation, and wetting properties) in limestone. Water absorption experiments showed that desiccated SABs protected the stone from rapid water uptake, while a thermographic survey indicated a delay in water evaporation. Spilling-drop tests revealed a change in the wettability of the stone-SAB interface, which affected the water transport properties of the stone. Finally, desiccated SABs reduced stone swelling in the presence of water vapor. The biodeteriorative and bioprotective implications of desiccated SABs on the stone were ultimately assessed.

Oncology clinical trial disruption during the COVID-19 pandemic: a COVID-19 and cancer outcomes study.

BACKGROUND: COVID-19 disproportionately impacted patients with cancer as a result of direct infection, and delays in diagnosis and therapy. Oncological clinical trials are resource-intensive endeavors that could be particularly susceptible to disruption by the pandemic, but few studies have evaluated the impact of the pandemic on clinical trial conduct. PATIENTS AND METHODS: This prospective, multicenter study assesses the impact of the pandemic on therapeutic clinical trials at two large academic centers in the Northeastern United States between December 2019 and June 2021. The primary objective was to assess the enrollment on, accrual to, and activation of oncology therapeutic clinical trials during the pandemic using an institution-wide cohort of (i) new patient accruals to oncological trials, (ii) a manually curated cohort of patients with cancer, and (ii) a dataset of new trial activations. RESULTS: The institution-wide cohort included 4756 new patients enrolled to clinical trials from December 2019 to June 2021. A major decrease in the numbers of new patient accruals (-46%) was seen early in the pandemic, followed by a progressive recovery and return to higher-than-normal levels (+2.6%). A similar pattern (from -23.6% to +30.4%) was observed among 467 newly activated trials from June 2019 to June 2021. A more pronounced decline in new accruals was seen among academically sponsored trials (versus industry sponsored trials) (P < 0.05). In the manually curated cohort, which included 2361 patients with cancer, non-white patients tended to be more likely taken off trial in the early pandemic period (adjusted odds ratio: 2.60; 95% confidence interval 1.00-6.63), and substantial pandemic-related deviations were recorded. CONCLUSIONS: Substantial disruptions in clinical trial activities were observed early during the pandemic, with a gradual recovery during ensuing time periods, both from an enrollment and an activation standpoint. The observed decline was more prominent among academically sponsored trials, and racial disparities were seen among people taken off trial.

Shock wave propagation along the central retinal blood vessels.

Retinal haemorrhage is often observed following brain injury. The retinal circulation is supplied (drained) by the central retinal artery (vein) which enters (leaves) the eye through the optic nerve at the optic disc; these vessels penetrate the nerve immediately after passing through a region of cerebrospinal fluid (CSF). We consider a theoretical model for the blood flow in the central retinal vessels, treating each as multi-region collapsible tubes, where we examine how a sudden change in CSF pressure (mimicking an injury) drives a large amplitude pressure perturbation towards the eye. In some cases, this wave can steepen to form a shock. We show that the region immediately proximal to the eye (within the optic nerve where the vessels are strongly confined by the nerve fibres) can significantly reduce the amplitude of the pressure wave transmitted into the eye. When the length of this region is consistent with clinical measurements, the CSF pressure perturbation generates a wave of significantly lower amplitude than the input, protecting the eye from damage. We construct an analytical framework to explain this observation, showing that repeated rapid propagation and reflection of waves along the confined section of the vessel distributes the perturbation over a longer lengthscale.

Risk factors for chronic biofilm-related infection associated with implanted medical devices.

BACKGROUND: The use of implanted medical devices is associated with a small but clinically important risk of foreign body infection. A key question is: why do some patients develop chronic infection associated with an implanted device, but most do not? AIMS: The literature on patient-specific risk factors for chronic infections associated with five types of implants was surveyed to glean clues about the etiology of these infections. SOURCES: Data were collected from 47 articles through calendar year 2017 for five categories of device-related infections: cardiovascular implantable electronic devices (CIEDs), hernia meshes, prosthetic hip and knee joints, prosthetic shoulder joints and breast implants. CONTENT: Important risk factors include immunomodulation/steroid therapy, diabetes, smoking, and renal disease/haemodialysis-findings that point to a critical role of a compromised innate immune response in determining vulnerable subpopulations. IMPLICATIONS: A model of biofilm-related device infection is presented that posits defects in the innate immune response both systemically and locally, in the immediate vicinity of an abiotic biomaterial. The limitations of in vitro and animal models of chronic device-related infections are discussed in this context as are implications for research and clinical practice.

Paired methods to measure biofilm killing and removal: a case study with Penicillin G treatment of Staphylococcus aureus biofilm.

Biofilms are microbial aggregates that show high tolerance to antibiotic treatments in vitro and in vivo. Killing and removal are both important in biofilm control, therefore methods that measure these two mechanisms were evaluated in a parallel experimental design. Kill was measured using the single tube method (ASTM method E2871) and removal was determined by video microscopy and image analysis using a new treatment flow cell. The advantage of the parallel test design is that both methods used biofilm covered coupons harvested from a CDC biofilm reactor, a well-established and standardized biofilm growth method. The control Staphylococcus aureus biofilms treated with growth medium increased by 0·6 logs during a 3-h contact time. Efficacy testing showed biofilms exposed to 400 µmol l-1 penicillin G decreased by only 0·3 logs. Interestingly, time-lapse confocal scanning laser microscopy revealed that penicillin G treatment dispersed the biofilm despite being an ineffective killing agent. In addition, no biofilm removal was detected when assays were performed in 96-well plates. These results illustrate that biofilm behaviour and impact of treatments can vary substantially when assayed by different methods. Measuring both killing and removal with well-characterized methods will be crucial for the discovery of new anti-biofilm strategies. SIGNIFICANCE AND IMPACT OF THE STUDY: Biofilms are tolerant to antimicrobial treatments and can lead to persistent infections. Finding new anti-biofilm strategies and understanding their mode-of-action is therefore of high importance. Historically, antimicrobial testing has focused on measuring the decrease in viability. While kill data are undeniably important, measuring biofilm disruption provides equally useful information. Starting with biofilm grown in the same reactor, we paired assessment of biofilm removal using a new treatment-flow-cell and real-time microscopy with kill data collected using the single tube method (ASTM E2871). Pairing these two methods revealed efficient biofilm removal properties of Penicillin G which were not detected during efficacy testing.

Borealis-1: a randomized, first-line, placebo-controlled, phase II study evaluating apatorsen and chemotherapy for patients with advanced urothelial cancer.

BACKGROUND: Five-year survival of patients with inoperable, advanced urothelial carcinoma treated with the first-line chemotherapy is 5%-15%. We assessed whether the Hsp27 inhibitor apatorsen combined with gemcitabine plus cisplatin (GC) could improve overall survival (OS) in these patients. PATIENTS AND METHODS: This placebo-controlled, double-blind, phase II trial randomized 183 untreated urothelial carcinoma patients (North America and Europe) to receive GC plus either placebo (N = 62), 600 mg apatorsen (N = 60), or 1000 mg apatorsen (N = 61). In the experimental arm, treatment included loading doses of apatorsen followed by up to six cycles of apatorsen plus GC. Patients receiving at least four cycles could continue apatorsen monotherapy as maintenance until progression or unacceptable toxicity. The primary end point was OS. RESULTS: OS was not significantly improved in the single or combined 600- or 1000-mg apatorsen arms versus placebo [hazard ratio (HR), 0.86 and 0.90, respectively]. Exploratory study of specific statistical modeling showed a trend for improved survival in patients with baseline poor prognostic features treated with 600 mg apatorsen compared with placebo (HR = 0.72). Landmark analysis of serum Hsp27 (sHsp27) levels showed a trend toward survival benefit for poor-prognosis patients in 600- and 1000-mg apatorsen arms who achieved lower area under the curve sHsp27 levels, compared with the placebo arm (HR = 0.45 and 0.62, respectively). Higher baseline circulating tumor cells (≥5 cells/7.5 ml) was observed in patients with poor prognosis in correlation with poor survival. Treatment-emergent adverse events were manageable and more common in both apatorsen-treatment arms. CONCLUSIONS: Even though apatorsen combined with standard chemotherapy did not demonstrate a survival benefit in the overall study population, patients with poor prognostic features might benefit from this combination. Serum Hsp27 levels may act as a biomarker to predict treatment outcome. Further exploration of apatorsen in poor-risk patients is warranted.

A phase I dose-escalation study of apatorsen (OGX-427), an antisense inhibitor targeting heat shock protein 27 (Hsp27), in patients with castration-resistant prostate cancer and other advanced cancers.

BACKGROUND: Heat shock protein 27 (Hsp27) is a chaperone protein that regulates cell survival via androgen receptor and other signaling pathways, thereby mediating cancer progression. Apatorsen (OGX-427) is a 2'-methoxyethyl-modified antisense oligonucleotide that inhibits Hsp27 expression. This study evaluated the safety profile and recommended phase II dosing of apatorsen in patients with advanced cancer. PATIENTS AND METHODS: Patients with castration-resistant prostate (CRPC), breast, ovary, lung, or bladder cancer were enrolled to this phase I dose-escalation study. Apatorsen was administered i.v. weekly in 21-day cycles following 3 loading doses and over 5 dose levels (200-1000 mg). Apatorsen plasma concentrations, circulating tumor cells (CTCs) and CTC Hsp27 expression, and serum Hsp27 levels were evaluated. RESULTS: Forty-two patients were accrued, of which 52% had CRPC. Patients were heavily pretreated, with 57% having had ≥3 prior chemotherapy regimens. During the loading dose/cycle 1 and overall study period, 93% and 100% of patients (N = 42) experienced treatment-related adverse events, respectively; most were grade 1-2 and included chills, pruritus, flushing, prolonged aPTT, lymphopenia, and anemia. One patient experienced a dose-limiting toxicity at the 600 mg dose level (intracranial hemorrhage in a previously undiagnosed brain metastasis). A maximum tolerated dose was not defined. Apatorsen Cmax increased proportionally with dose. Decreases in tumor markers and declines in CTCs were observed, with a prostate-specific antigen decline >%50% occurring in 10% of patients with CRPC; 29/39 assessable patients (74%) had reductions from ≥5 CTC/7.5 ml at baseline to <5 CTC/7.5 ml post-treatment. Twelve patients had stable measurable disease as best response. CONCLUSIONS: Apatorsen was tolerated at the highest dose evaluated (1000 mg). Single-agent activity was suggested by changes in tumor markers, CTC, and stable measurable disease. Phase II studies evaluating apatorsen are underway. CLINICALTRIALSGOV ID: NCT00487786.

Diffusive transport through a model host-biofilm system.

Free-living biofilms have been subject to considerable attention, and basic physical principles for them are generally accepted. Many host-biofilm systems, however, consist of heterogeneous mixtures of aggregates of microbes intermixed with host material and are much less studied. Here we analyze a key property, namely reactive depletion, in such systems and argue that two regimes are possible: (1) a homogenizable mixture of biofilm and host that in important ways acts effectively like a homogeneous macrobiofilm and (2) a distribution of separated microbiofilms within the host with independent local microenvironments.

A combined network model for membrane fouling.

Membrane fouling during particle filtration occurs through a variety of mechanisms, including internal pore clogging by contaminants, coverage of pore entrances, and deposition on the membrane surface. Each of these fouling mechanisms results in a decline in the observed flow rate over time, and the decrease in filtration efficiency can be characterized by a unique signature formed by plotting the volumetric flux, Q^, as a function of the total volume of fluid processed, V^. When membrane fouling takes place via any one of these mechanisms independently the Q^V^ signature is always convex downwards for filtration under a constant transmembrane pressure. However, in many such filtration scenarios, the fouling mechanisms are inherently coupled and the resulting signature is more difficult to interpret. For instance, blocking of a pore entrance will be exacerbated by the internal clogging of a pore, while the deposition of a layer of contaminants is more likely once the pores have been covered by particulates. As a result, the experimentally observed Q^V^ signature can vary dramatically from the canonical convex-downwards graph, revealing features that are not captured by existing continuum models. In a range of industrially relevant cases we observe a concave-downwardsQ^V^ signature, indicative of a fouling rate that becomes more severe with time. We derive a network model for membrane fouling that accounts for the inter-relation between fouling mechanisms and demonstrate the impact on the Q^V^ signature. Our formulation recovers the behaviour of existing models when the mechanisms are treated independently, but also elucidates the concave-downward Q^V^ signature for multiple interactive fouling mechanisms. The resulting model enables post-experiment analysis to identify the dominant fouling modality at each stage, and is able to provide insight into selecting appropriate operating regimes.

Identification of peptides derived from the human antimicrobial peptide LL-37 active against biofilms formed by Pseudomonas aeruginosa using a library of truncated fragments.

Persistent Pseudomonas aeruginosa infections are a major cause of morbidity and mortality in cystic fibrosis (CF) patients and are linked to the formation of a biofilm. The development of new biofilm inhibition strategies is thus a major challenge. LL-37 is the only human antimicrobial peptide derived from cathelicidin. The effects on the P. aeruginosa PAO1 strain of synthetic truncated fragments of this peptide were compared with the effects of the original peptide. Fragments of LL-37 composed of 19 residues (LL-19, LL13-31, and LL7-25) inhibited biofilm formation. The strongest antibiofilm activity was observed with the peptides LL7-37 and LL-31, which decreased the percentage of biomass formation at a very low concentration. Some peptides were also active on the bacteria within an established biofilm. LL7-31, LL-31, and LL7-37 increased the uptake of propidium iodide (PI) by sessile bacteria. The peptide LL7-37 decreased the height of the biofilm and partly disrupted it. The peptides active within the biofilm had an infrared spectrum compatible with an α-helix. LL-37, but not the peptides LL7-31 and LL7-37, showed cellular toxicity by permeabilizing the eukaryotic plasma membrane (uptake of ethidium bromide and release of lactate dehydrogenase [LDH]). None of the tested peptides affected mitochondrial activity in eukaryotic cells. In conclusion, a 25-amino-acid peptide (LL7-31) displayed both strong antimicrobial and antibiofilm activities. The peptide was even active on cells within a preformed biofilm and had reduced toxicity toward eukaryotic cells. Our results also suggest the contribution of secondary structures (α-helix) to the activity of the peptides on biofilms.

Development and application of a polymicrobial, in vitro, wound biofilm model.

AIMS: The goal of this investigation was to develop an in vitro, polymicrobial, wound biofilm capable of supporting the growth of bacteria with variable oxygen requirements. METHODS AND RESULTS: The strict anaerobe Clostridium perfringens was isolated by cultivating wound homogenates using the drip-flow reactor (DFR), and a three-species biofilm model was established using methicillin-resistant Staphylococcus aureus (MRSA), Pseudomonas aeruginosa and Cl. perfringens in the colony-drip-flow reactor model. Plate counts revealed that MRSA, Ps. aeruginosa and Cl. perfringens grew to 7·39 ± 0·45, 10·22 ± 0·22 and 7·13 ± 0·77 log CFU per membrane, respectively. The three-species model was employed to evaluate the efficacy of two antimicrobial dressings, Curity™ AMD and Acticoat™, compared to sterile gauze controls. Microbial growth on Curity™ AMD and gauze was not significantly different, for any species, whereas Acticoat™ was found to significantly reduce growth for all three species. CONCLUSIONS: Using the colony-DFR, a three-species biofilm was successfully grown, and the biofilms displayed a unique structure consisting of distinct layers that appeared to be inhabited exclusively or predominantly by a single species. SIGNIFICANCE AND IMPACT OF THE STUDY: The primary accomplishment of this study was the isolation and growth of an obligate anaerobe in an in vitro model without establishing an artificially anaerobic environment.

An in vitro model for the growth and analysis of chronic wound MRSA biofilms.

AIMS: To develop an in vitro model (Colony/drip-flow reactor - C/DFR) for the growth and analysis of methicillin-resistant Staphylococcus aureus (MRSA) biofilms. METHODS AND RESULTS: Using the C/DFR model, biofilms were grown on the top of polycarbonate filter membranes inoculated with a clinical isolate of MRSA, placed on absorbent pads in the DFR and harvested after 72 h. The biofilms varied from 256 to 308 µm in thickness with a repeatability standard deviation of 0·22. Testing of antimicrobial agents was also performed where C/DFR biofilms were grown in parallel with conventional colony biofilms. A saline solution (control), 1% silver sulfadiazine solution, and 0·25% Dakin's solution were used to treat the biofilms for 15 min. Microscopic evaluation of biofilm morphology and thickness was conducted. The Dakins solution in both models produced statistically significantly higher log reductions than silver sulfadiazine treatment. CONCLUSIONS: The C/DFR biofilms were thick and repeatable and exhibited higher resistance to Dakins solution than the treated colony biofilms. SIGNIFICANCE AND IMPACT OF THE STUDY: The C/DFR can be used as a tool for examining complex biofilm physiology as well as for performing comparative experiments that test wound care products and novel antimicrobials.

In vitro efficacy of bismuth thiols against biofilms formed by bacteria isolated from human chronic wounds.

AIMS: The purpose of this study was to evaluate the antimicrobial efficacy of thirteen bismuth thiol preparations for bactericidal activity against established biofilms formed by two bacteria isolated from human chronic wounds. METHODS: Single species biofilms of a Pseudomonas aeruginosa or a methicillin-resistant Staphylococcus aureus were grown in either colony biofilm or drip-flow reactors systems. Biofilms were challenged with bismuth thiols, antibiotics or silver sulfadiazine, and log reductions were determined by plating for colony formation. CONCLUSIONS: Antibiotics were ineffective or inconsistent against biofilms of both bacterial species tested. None of the antibiotics tested were able to achieve >2 log reductions in both biofilm models. The 13 different bismuth thiols tested in this investigation achieved widely varying degrees of killing, even against the same micro-organism in the same biofilm model. For each micro-organism, the best bismuth thiol easily outperformed the best conventional antibiotic. Against P. aeruginosa biofilms, bismuth-2,3-dimercaptopropanol (BisBAL) at 40-80 µg ml⁻¹ achieved > 7·7 mean log reduction for the two biofilm models. Against MRSA biofilms, bismuth-1,3-propanedithiol/bismuth-2-mercaptopyridine N-oxide (BisBDT/PYR) achieved a 4·9 log reduction. SIGNIFICANCE AND IMPACT OF THE STUDY: Bismuth thiols are effective antimicrobial agents against biofilms formed by wound bacteria and merit further development as topical antiseptics for the suppression of biofilms in chronic wounds.

Occupational exposure to dusts and risk of renal cell carcinoma.

BACKGROUND: Occupational exposures to dusts have generally been examined in relation to cancers of the respiratory system and have rarely been examined in relation to other cancers, such as renal cell carcinoma (RCC). Although previous epidemiological studies, though few, have shown certain dusts, such as asbestos, to increase renal cancer risk, the potential for other occupational dust exposures to cause kidney damage and/or cancer may exist. We investigated whether asbestos, as well as 20 other occupational dust exposures, were associated with RCC risk in a large European, multi-center, hospital-based renal case-control study. METHODS: General occupational histories and job-specific questionnaires were reviewed by occupational hygienists for subject-specific information. Odds ratios (ORs) and 95% confidence intervals (95% CIs) between RCC risk and exposures were calculated using unconditional logistic regression. RESULTS: Among participants ever exposed to dusts, significant associations were observed for glass fibres (OR: 2.1; 95% CI: 1.1-3.9), mineral wool fibres (OR: 2.5; 95% CI: 1.2-5.1), and brick dust (OR: 1.5; 95% CI: 1.0-2.4). Significant trends were also observed with exposure duration and cumulative exposure. No association between RCC risk and asbestos exposure was observed. CONCLUSION: Results suggest that increased RCC risk may be associated with occupational exposure to specific types of dusts. Additional studies are needed to replicate and extend findings.

Characterization of a modified rotating disk reactor for the cultivation of Staphylococcus epidermidis biofilm.

AIMS: The purpose of this study was to develop a system that would allow biofilms to be cultivated under strictly defined conditions in terms of dissolved oxygen, fluid shear and to assess whether the method was suitable for the detection of respiratory activity stratification in biofilm samples. METHODS: The system is a modified version a commercially available laboratory biofilm reactor and incorporates a number of features such as the provision of defined levels of dissolved oxygen, constant average shear, enhanced gas-liquid mass transfer, aseptic operation and the ability to remove biofilm for ex situ analysis during or after continuous cultivation. CONCLUSIONS: The system was shown to be effective for the characterization of the effects of dissolved oxygen on a pure culture of Staphylococcus epidermidis. The versatility of the system offers the potential for cultivating pure culture biofilm in defined, controlled conditions and facilitates a range of analyses that can be performed ex situ. SIGNIFICANCE AND IMPACT OF THE STUDY: The ability to provide strict regulation of environmental conditions and enhanced transfer of oxygen to the biofilm during cultivation are important, first because oxygen is known to regulate biofilm development in several micro-organisms and second because many conventional biofilm cultivation systems may not provide adequate oxygen supply to the biofilm.

Biofilm maturity studies indicate sharp debridement opens a time- dependent therapeutic window.

OBJECTIVE: To investigate the hypothesis that newly formed wound biofilms (or bioburdens) are more susceptible to antimicrobial treatment. METHOD: Four separate and distinct models were performed by four separate biofilm research laboratories to evaluate the resistance of biofilms to antimicrobial treatments over time. These included a drip-flow biofilm model along with a hydrodebridement study, a porcine skin punch biopsy ex vivo model, a mouse chronic wound model and clinical longitudinal debridement study. RESULTS: All four models showed that, within the first 24 hours, the biofilm community was more susceptible to the selected antibiotics, and after maturing for up to 48 hours became increasingly tolerant. In each model, there was at least a 24-hour period in which the biofilms were more resistant to antibiotics. Each of the models utilised showed a significant decrease in the resistance of the biofilm/ burden to gentamicin for up to 24 hours with a confidence interval of at least 95%. The resistance increased in each of the models by 48 hours and reached original resistance levels by 72 hours. CONCLUSION: These data suggest the principles of biofilm-based wound care, along with the use of serial debridement to continually remove mature biofilm, followed by biofilm wound management strategies, including topical antibiotics while the bioburden is still immature and more susceptible, are valid.

Senescence can explain microbial persistence.

It has been known for many years that small fractions of persister cells resist killing in many bacterial colony-antimicrobial confrontations. These persisters are not believed to be mutants. Rather it has been hypothesized that they are phenotypic variants. Current models allow cells to switch in and out of the persister phenotype. Here, a different explanation is suggested for persistence, namely senescence. Using a mathematical model including age structure, it is shown that senescence provides a natural explanation for persistence-related phenomena, including the observations that the persister fraction depends on growth phase in batch culture and dilution rate in continuous culture.

Ultrasonically controlled release of ciprofloxacin from self-assembled coatings on poly(2-hydroxyethyl methacrylate) hydrogels for Pseudomonas aeruginosa biofilm prevention.

Indwelling prostheses and subcutaneous delivery devices are now routinely and indispensably employed in medical practice. However, these same devices often provide a highly suitable surface for bacterial adhesion and colonization, resulting in the formation of complex, differentiated, and structured communities known as biofilms. The University of Washington Engineered Biomaterials group has developed a novel drug delivery polymer matrix consisting of a poly(2-hydroxyethyl methacrylate) hydrogel coated with ordered methylene chains that form an ultrasound-responsive coating. This system was able to retain the drug ciprofloxacin inside the polymer in the absence of ultrasound but showed significant drug release when low-intensity ultrasound was applied. To assess the potential of this controlled drug delivery system for the targeting of infectious biofilms, we monitored the accumulation of Pseudomonas aeruginosa biofilms grown on hydrogels with and without ciprofloxacin and with and without exposure to ultrasound (a 43-kHz ultrasonic bath for 20 min daily) in an in vitro flow cell study. Biofilm accumulation from confocal images was quantified and statistically compared by using COMSTAT biofilm analysis software. Biofilm accumulation on ciprofloxacin-loaded hydrogels with ultrasound-induced drug delivery was significantly reduced compared to the accumulation of biofilms grown in control experiments. The results of these studies may ultimately facilitate the future development of medical devices sensitive to external ultrasonic impulses and capable of treating or preventing biofilm growth via "on-demand" drug release.