More Like this

1. Probing the Fate of Different Structures of Beta-Lactam Antibiotics: Hydrolysis, Mineral Capture, and Influence of Organic Matter

   https://doi.org/10.1021/acsearthspacechem.1c00064  

   Klein, A.R.; Sarri, E.; Kelch, S.E.; Basinski, J.J.; Vaidya, S.; Aristilde, L. (June 2021, ACS earth and space chemistry)

   Beta-lactam antibiotics, which are used extensively in human and veterinary applications, are commonly detected in surface waters. To examine how the distinct structures of different generations of beta-lactam antibiotics can influence their persistence or degradation in environmental aqueous media, we examined the fate of two penams (amoxicillin and cloxacillin) and two cephems (cephalexin and ceftriaxone) at pH 5.0 and pH 7.0. By contrast to the lack of hydrolysis of the penam antibiotics at both pHs, we observed hydrolysis of cephalexin at pH 7.0 (t1/2 = 12 d) and ceftriaxone at pH 5.0 (t1/2 = 2.8 d). Using high-performance liquid chromatography coupled with a diode array detector or a high-resolution mass spectrometer, we were able to confirm thiotriazinone and 3-desacetyl cefotaxime as major hydrolysis products of ceftriaxone, and propose the hydrolytic cleavage of the benzene and cephem moieties from cephalexin. In addition, we studied the effects of smectite clay particles suspended in solutions without or with dissolved organic matter. The adsorption capacity of the clay was 4- to 9-fold higher at pH 7.0 than at pH 5.0. Subsequent X-ray diffraction analysis revealed that the antibiotic adsorption was not within the clay interlayer nanopores but occurred primarily on the external clay surfaces. The addition of dissolved organic matter interfered with the adsorption of a cephem antibiotic (ceftriaxone) on the clay, but the adsorption of a penam antibiotic (amoxicillin) remained unaffected. We employed molecular modeling simulations to probe the mechanisms of adsorption on the mineral surface. Our findings offer new insights on how the compound structures can dictate different fates of the beta-lactam class of antibiotics in environmental media. 

   more » « less
2. Janus Paper‐Based Wound Dressings for Effective Exudate Absorption and Antibiotic Delivery

   https://doi.org/10.1002/adem.202301422  

   Gao, Yang; Elhadad, Anwar; Choi, Seokheun (December 2023, Advanced Engineering Materials)

   Traditional hydrophilic wound dressings, while common, fail to effectively drain wound exudate, creating conditions favorable for bacterial growth. Similarly, newer Janus‐type dressings with hydrophobic‐hydrophilic properties also fall short, as their hydrophobic side causes excessive dryness by pulling biofluids from the wound, disrupting moisture balance. Additionally, embedding antibiotics in dressings at fixed concentrations, regardless of the infection type, reduces effectiveness and contributes to the growing problem of antibiotic resistance. In response, a single‐layered Janus paper wound dressing, designed for efficient exudate absorption and precise antibiotic delivery, is developed. The approach differs from traditional Janus‐type dressings; a hydrophilic layer is placed directly against the wound for better moisture management, while antibiotics are applied through the hydrophobic layer. To further enhance exudate management, the hydrophilic section with four extra absorbent pads is extended. The dressing's antibiotic efficacy and dosage are tailored based on antibiotic susceptibility testing, ensuring targeted treatment. The selected antibiotic is manually added but automatically delivered directly to the wound bed. The in vitro and ex vivo evaluations, using bacterial cultures on agar and porcine skin assays, respectively, confirm the dressing's superior exudate drainage and its ability to inhibit pathogen growth and reproduction, marking a significant advancement in wound care. 

   more » « less
3. Potential impact of annual vaccination with reformulated COVID-19 vaccines: Lessons from the US COVID-19 scenario modeling hub

   https://doi.org/10.1371/journal.pmed.1004387  

   Jung, Sung-mok; Loo, Sara L; Howerton, Emily; Contamin, Lucie; Smith, Claire P; Carcelén, Erica C; Yan, Katie; Bents, Samantha J; Levander, John; Espino, Jessi; et al (April 2024, PLOS Medicine)

   MacPherson, Peter (Ed.)

   BackgroundCoronavirus Disease 2019 (COVID-19) continues to cause significant hospitalizations and deaths in the United States. Its continued burden and the impact of annually reformulated vaccines remain unclear. Here, we present projections of COVID-19 hospitalizations and deaths in the United States for the next 2 years under 2 plausible assumptions about immune escape (20% per year and 50% per year) and 3 possible CDC recommendations for the use of annually reformulated vaccines (no recommendation, vaccination for those aged 65 years and over, vaccination for all eligible age groups based on FDA approval). Methods and findingsThe COVID-19 Scenario Modeling Hub solicited projections of COVID-19 hospitalization and deaths between April 15, 2023 and April 15, 2025 under 6 scenarios representing the intersection of considered levels of immune escape and vaccination. Annually reformulated vaccines are assumed to be 65% effective against symptomatic infection with strains circulating on June 15 of each year and to become available on September 1. Age- and state-specific coverage in recommended groups was assumed to match that seen for the first (fall 2021) COVID-19 booster. State and national projections from 8 modeling teams were ensembled to produce projections for each scenario and expected reductions in disease outcomes due to vaccination over the projection period.From April 15, 2023 to April 15, 2025, COVID-19 is projected to cause annual epidemics peaking November to January. In the most pessimistic scenario (high immune escape, no vaccination recommendation), we project 2.1 million (90% projection interval (PI) [1,438,000, 4,270,000]) hospitalizations and 209,000 (90% PI [139,000, 461,000]) deaths, exceeding pre-pandemic mortality of influenza and pneumonia. In high immune escape scenarios, vaccination of those aged 65+ results in 230,000 (95% confidence interval (CI) [104,000, 355,000]) fewer hospitalizations and 33,000 (95% CI [12,000, 54,000]) fewer deaths, while vaccination of all eligible individuals results in 431,000 (95% CI: 264,000–598,000) fewer hospitalizations and 49,000 (95% CI [29,000, 69,000]) fewer deaths. ConclusionsCOVID-19 is projected to be a significant public health threat over the coming 2 years. Broad vaccination has the potential to substantially reduce the burden of this disease, saving tens of thousands of lives each year. 

   more » « less
4. Development of the computational antibiotic screening platform (CLASP) to aid in the discovery of new antibiotics

   https://doi.org/10.1039/D0SM02035D  

   Dai, Yinghui; Ma, Huilin; Wu, Meishan; Welsch, Tory Alane; Vora, Soor Rajiv; Ren, Dacheng; Nangia, Shikha (January 2021, Soft Matter)

   null (Ed.)

   Bacterial colonization of biotic and abiotic surfaces and antibiotic resistance are grand challenges with paramount societal impacts. However, in the face of increasing bacterial resistance to all known antibiotics, efforts to discover new classes of antibiotics have languished, creating an urgent need to accelerate the antibiotic discovery pipeline. A major deterrent in the discovering of new antibiotics is the limited permeability of molecules across the bacterial envelope. Notably, the Gram-negative bacteria have nutrient specific protein channels (or porins) that restrict the permeability of non-essential molecules, including antibiotics. Here, we have developed the Computational Antibiotic Screening Platform (CLASP) for screening of potential drug molecules through the porins. The CLASP takes advantage of coarse grain (CG) resolution, advanced sampling techniques, and a parallel computing environment to maximize its performance. The CLASP yields comprehensive thermodynamic and kinetic output data of a potential drug molecule within a few hours of wall-clock time. Its output includes the potential of mean force profile, energy barrier, the rate constant, and contact analysis of the molecule with the pore-lining residues, and the orientational analysis of the molecule in the porin channel. In our first CLASP application, we report the transport properties of six carbapenem antibiotics—biapenem, doripenem, ertapenem, imipenem, meropenem, and panipenem—through OccD3, a major channel for carbapenem uptake in Pseudomonas aeruginosa . The CLASP is designed to screen small molecule libraries with a fast turnaround time to yield structure–property relationships to discover antibiotics with high permeability. The CLASP will be freely distributed to enable accelerated antibiotic drug discovery. 

   more » « less
5. The air-gap PAD: a roll-to-roll-compatible fabrication method for paper microfluidics

   https://doi.org/10.1039/d2lc01164f  

   Roller, Rachel M.; Rea, Angela; Lieberman, Marya (March 2023, Lab on a Chip)

   Paper-based analytical devices (PADs) offer a low-cost, user-friendly platform for rapid point-of-use testing. Without scalable fabrication methods, however, few PADs make it out of the academic laboratory and into the hands of end users. Previously, wax printing was considered an ideal PAD fabrication method, but given that wax printers are no longer commercially available, alternatives are needed. Here, we present one such alternative: the air-gap PAD. Air-gap PADs consist of hydrophilic paper test zones, separated by “air gaps” and affixed to a hydrophobic backing with double-sided adhesive. The primary appeal of this design is its compatibility with roll-to-roll equipment for large-scale manufacturing. In this study, we examine design considerations for air-gap PADs, compare the performance of wax-printed and air-gap PADs, and report on a pilot-scale roll-to-roll production run of air-gap PADs in partnership with a commercial test-strip manufacturer. Air-gap devices performed comparably to their wax-printed counterparts in Washburn flow experiments, a paper-based titration, and a 12-lane pharmaceutical screening device. Using roll-to-roll manufacturing, we produced 2700 feet of air-gap PADs for as little as $0.03 per PAD. 

   more » « less