Synergistic effects of sulopenem in combination with cefuroxime or durlobactam against Mycobacterium abscessus.

Mycobacterium abscessus (Mab) affects patients with immunosuppression or underlying structural lung diseases such as cystic fibrosis (CF). Additionally, Mab poses clinical challenges due to its resistance to multiple antibiotics. Herein, we investigated the synergistic effect of dual ß-lactams [sulopenem and cefuroxime (CXM)] or the combination of sulopenem and CXM with ß-lactamase inhibitors [BLIs-avibactam (AVI) or durlobactam (DUR)]. The sulopenem-CXM combination yielded low minimum inhibitory concentration (MIC) values for 54 clinical Mab isolates and ATCC19977 (MIC50 and MIC90 ≤0.25 µg/mL). Similar synergistic effects were observed in time-kill studies conducted at concentrations achievable in clinical settings. Sulopenem-CXM outperformed monotherapy, yielding ~1.5 Log10 CFU/mL reduction during 10 days. Addition of BLIs enhanced this antibacterial effect, resulting in an additional reduction of CFUs (~3 Log10 for sulopenem-CXM and AVI and ~4 Log10 for sulopenem-DUR). Exploration of the potential mechanisms of the synergy focused on their interactions with L,D-transpeptidases (Ldts; LdtMab1-LdtMab4), penicillin-binding-protein B (PBP B), and D,D-carboxypeptidase (DDC). Acyl complexes, identified via mass spectrometry analysis, demonstrated the binding of sulopenem with LdtMab2-LdtMab4, DDC, and PBP B and CXM with LdtMab2 and PBP B. Molecular docking and mass spectrometry data suggest the formation of a covalent adduct between sulopenem and LdtMab2 after the nucleophilic attack of the cysteine residue at the ß-lactam carbonyl carbon, leading to the cleavage of the ß-lactam ring and the establishment of a thioester bond linking the LdtMab2 with sulopenem. In conclusion, we demonstrated the biochemical basis of the synergy of sulopenem-CXM with or without BLIs. These findings potentially broaden the selection of oral therapeutic agents to combat Mab. IMPORTANCE: Treating infections from Mycobacterium abscessus (Mab), particularly those resistant to common antibiotics like macrolides, is notoriously difficult, akin to a never-ending struggle for healthcare providers. The rate of treatment failure is even higher than that seen with multidrug-resistant tuberculosis. The role of combination ß-lactams in inhibiting L,D-transpeptidation, the major peptidoglycan crosslink reaction in Mab, is an area of intense investigation, and clinicians have utilized this approach in the treatment of macrolide-resistant Mab, with reports showing clinical success. In our study, we found that cefuroxime and sulopenem, when used together, display a significant synergistic effect. If this promising result seen in lab settings, translates well into real-world clinical effectiveness, it could revolutionize current treatment methods. This combination could either replace the need for more complex intravenous medications or serve as a "step down" to an oral medication regimen. Such a shift would be much easier for patients to manage, enhancing their comfort and likelihood of sticking to the treatment plan, which could lead to better outcomes in tackling these tough infections. Our research delved into how these drugs inhibit cell wall synthesis, examined time-kill data and binding studies, and provided a scientific basis for the observed synergy in cell-based assays.

Durlobactam, a Diazabicyclooctane ß-Lactamase Inhibitor, Inhibits BlaC and Peptidoglycan Transpeptidases of Mycobacterium tuberculosis.

Peptidoglycan synthesis is an underutilized drug target in Mycobacterium tuberculosis (Mtb). Diazabicyclooctanes (DBOs) are a class of broad-spectrum ß-lactamase inhibitors that also inhibit certain peptidoglycan transpeptidases that are important in mycobacterial cell wall synthesis. We evaluated the DBO durlobactam as an inhibitor of BlaC, the Mtb ß-lactamase, and multiple Mtb peptidoglycan transpeptidases (PonA1, LdtMt1, LdtMt2, LdtMt3, and LdtMt5). Timed electrospray ionization mass spectrometry (ESI-MS) captured acyl-enzyme complexes with BlaC and all transpeptidases except LdtMt5. Inhibition kinetics demonstrated durlobactam was a potent and efficient DBO inhibitor of BlaC (KI app 9.2 ± 0.9 µM, k2/K 5600 ± 560 M-1 s-1) and similar to clavulanate (KI app 3.3 ± 0.6 µM, k2/K 8400 ± 840 M-1 s-1); however, durlobactam had a lower turnover number (tn = kcat/kinact) than clavulanate (1 and 8, respectively). KI app values with durlobactam and clavulanate were similar for peptidoglycan transpeptidases, but ESI-MS captured durlobactam complexes at more time points. Molecular docking and simulation demonstrated several productive interactions of durlobactam in the active sites of BlaC, PonA1, and LdtMt2. Antibiotic susceptibility testing was conducted on 11 Mtb isolates with amoxicillin, ceftriaxone, meropenem, imipenem, clavulanate, and durlobactam. Durlobactam had a minimum inhibitory concentration (MIC) range of 0.5-16 µg/mL, similar to the ranges for meropenem (1-32 µg/mL) and imipenem (0.5-64 µg/mL). In ß-lactam + durlobactam combinations (1:1 mass/volume), MICs were lowered 4- to 64-fold for all isolates except one with meropenem-durlobactam. This work supports further exploration of novel ß-lactamase inhibitors that target BlaC and Mtb peptidoglycan transpeptidases.

Particle separator with vortex claw: an efficient and new technology.

Despite facing many challenges, the exploration of using natural forces and mechanisms besides gravity to enhance particle settling has never ceased. A novel particle separator design, which utilizes multiple vortexes to enhance particle settling, was proposed in this study. The basic principle is using the fluid's energy to generate small swirling currents in a specially designed vortex claw generator. These currents bring suspended particles from the rapid and turbulent inflow to relatively quiet water regions, separating them from the main flows and reducing their travel distance to the wall. To verify the new separator design's performance, comparison studies were carried out in the laboratory using physical models. The results showed that the new design had much higher particle capture rates for the same inflow rates and tested particle sizes. Most importantly, it was able to effectively remove small particles, and particle capture rates were much less affected by fluctuations in inflow rates. Since most existing particle separators failed to perform well under large inflow rates, these characteristics make the new design stand out from other separators. Due to its special structure, its treatment capacity can also be easily increased without changing its horizontal separator size.

Predicting Peak Productivity in Urologic Medicare Practice via Work-Relative Value Units.

OBJECTIVE: To explore factors associated with productivity in urologic practice. Work-relative value units (wRVUs), the basis for Center for Medicare & Medicaid Services (CMS) and private payer reimbursements, commonly serve to estimate physician productivity. Limited data describes which practice factors predict increased wRVU productivity. METHODS: The 2017 and 2018 CMS databases were retrospectively queried for urologic Medicare provider demographics and procedural/service details. Medical school graduation year was used to estimate years in practice and generation (Millennial, Gen X, Baby Boomer, or Post-War). Treated patients' demographics were obtained. Adjusted and unadjusted linear mixed models were performed to predict wRVU production. RESULTS: Included were 6773 Medicare-participating urologists across the United States. Millennials produced 1115 wRVUs per year, while Gen X and Baby Boomers produced significantly more (1997 and 2104, respectively, P <.01). Post-War urologists produced numerically more (1287, P = .88). In adjusted analyses, predictors of Medicare wRVU productivity included female and pelvic medicine and reconstructive surgery (exponentiated beta estimate (ß) 1.46, 95% CI 1.32-1.60), men's health (ß 1.22, 95% CI 1.13-1.32), and oncologic subspecialization (ß 1.08, 95% CI 1.02-1.14), female gender (ß 0.87, 95% CI 0.82-0.92), wRVUs generated from inpatient procedures (ß 1.08, 95% CI 1.06-1.09) and office visits (ß 0.88, 95% CI 0.87-0.89), and the level of education (ß 1.10, 95% CI 1.07-1.14) and percent impoverished patients (ß 0.85, 95% CI 0.83-0.88) in provider's practice zip code. CONCLUSION: Urologic experience, specialization, demographics, practice patterns, and patient demographics are significantly associated with wRVU productivity in Medicare settings. Further work should incorporate quality metrics into wRVUs and ensure patient demographics do not affect reimbursement.

The burden of RSV, hMPV, and PIV amongst hospitalized adults in the United States from 2016 to 2019.

BACKGROUND: Respiratory syncytial virus (RSV), human metapneumovirus (hMPV), and parainfluenza virus (PIV) hospitalize many people yearly. Though severe lower respiratory tract disease has been described in children, the elderly, and the immunocompromised, there is a gap in our understanding of RSV, hMPV, and PIV in hospitalized adults. We sought to evaluate the association of RSV, hMPV, and PIV with severe respiratory disease requiring noninvasive or mechanical ventilation and death in hospitalized adults in the United States. METHODS: We conducted a retrospective, pooled, cross-sectional study of general medicine hospitalizations in the United States from 2016 to 2019 using the National Inpatient Sample published by the Agency for Healthcare Quality and Research. We used multivariable Poisson regression to estimate the likelihood of severe respiratory disease or death. We used linear regression to estimate the mean difference in length of stay for those hospitalized with and without a respiratory virus. RESULTS: We found that RSV (incidence rate ratio [IRR]: 1.68, 95% confidence interval [CI]: 1.61-1.74, p < .001), hMPV (IRR: 1.82, 95% CI: 1.71-1.93, p < .001), and PIV (IRR: 1.81, 95% CI: 1.68-1.94, p < .001) were independently associated with severe respiratory disease, even after adjustment. Additionally, we found the presence of a respiratory virus prolonged hospitalizations by (0.79 ± 0.27 days, p < .003) for RSV, (0.88 ± 0.28 days, p < .002) for hMPV, and (1.43 ± 0.30 days, p < .001) for PIV. CONCLUSIONS: RSV, hMPV, and PIV have a significant burden on hospitalized adults, even without classic risk factors.

The Updated Mouse Universal Genotyping Array Bioinformatic Pipeline Improves Genetic QC in Laboratory Mice.

The MiniMUGA genotyping array is a popular tool for genetic QC of laboratory mice and genotyping of samples from most types of experimental crosses involving laboratory strains, particularly for reduced complexity crosses. The content of the production version of the MiniMUGA array is fixed; however, there is the opportunity to improve array's performance and the associated report's usefulness by leveraging thousands of samples genotyped since the initial description of MiniMUGA in 2020. Here we report our efforts to update and improve marker annotation, increase the number and the reliability of the consensus genotypes for inbred strains and increase the number of constructs that can reliably be detected with MiniMUGA. In addition, we have implemented key changes in the informatics pipeline to identify and quantify the contribution of specific genetic backgrounds to the makeup of a given sample, remove arbitrary thresholds, include the Y Chromosome and mitochondrial genome in the ideogram, and improve robust detection of the presence of commercially available substrains based on diagnostic alleles. Finally, we have made changes to the layout of the report, to simplify the interpretation and completeness of the analysis and added a table summarizing the ideogram. We believe that these changes will be of general interest to the mouse research community and will be instrumental in our goal of improving the rigor and reproducibility of mouse-based biomedical research.

Pharmacokinetics and Pharmacodynamics of Etripamil, an Intranasally Administered, Fast-Acting, Nondihydropyridine Calcium Channel Blocker.

Etripamil, a fast-acting nondihydropyridine L-type calcium channel blocker, is under investigation for potential self-administration for the acute treatment of supraventricular tachyarrhythmias in a medically unsupervised setting. We report detailed pharmacokinetics and pharmacodynamics of intranasally administered etripamil in healthy adults from 2 Phase 1, randomized, double-blind studies: Study MSP-2017-1096 (sequential dose-escalation, crossover study design, n = 64) and NODE-102 (single dose, 4-way crossover study, n = 24). Validated bioanalytical assays determined plasma concentrations of etripamil and its inactive metabolite. Noncompartmental pharmacokinetic parameters were calculated. Pharmacodynamic parameters were determined for PR interval, blood pressure, and heart rate. Etripamil was rapidly absorbed intranasally, with time to maximal plasma concentration of 5-8.5 minutes, corresponding to a rapid greater than 10% increase in mean maximum PR interval from baseline within 4-7 minutes of doses of 60 mg or greater. Following peak plasma concentrations, systemic etripamil levels declined rapidly within the first 15 minutes following dosing and decreased more gradually thereafter. PR interval prolongation greater than 10% from baseline was generally sustained for about 45 minutes at doses of 60 mg or greater. The mean terminal half-life ranged from about 1.5 hours with 60 mg to about 2.5-3 hours for the 70- and 105-mg doses. Etripamil was generally well tolerated without symptomatic hypotension. Adverse events were primarily mild to moderate and related to the administration site; no serious adverse events or episodes of atrioventricular block occurred. Intranasal etripamil administration, at doses of 60 mg or greater, produced rapidly occurring slowing of atrioventricular nodal conduction with a limited duration of effect without hemodynamic or electrocardiographic safety signals in healthy volunteers.

Analyzing the influence of expanding multispecialty adoption of robotic surgery on robotic urologic care: A decade-long assessment of two Canadian academic hospitals.

INTRODUCTION: Most robot-assisted surgery (RAS) systems in Canada are donor-funded, with constraints on implementation and access due to significant costs, among other factors. Herein, we evaluated the impact of the growing multispecialty use of RAS on urologic RAS access and outcomes in the past decade. METHODS: We conducted a retrospective review of all RAS performed by different surgical specialties in two high-volume academic hospitals between 2010 and 2019 (prior to the COVID pandemic). The assessed outcomes included the effect of increased robot access over the years on annual robotic-assisted radical prostatectomy (RARP) volumes, surgical waiting times (SWT), and pathologically positive surgical margins (PSM). Data were collected and analyzed from the robotic system and hospital databases. RESULTS: In total, six specialties (urology, gynecology, general, cardiac, thoracic, and otorhinolaryngologic surgery) were included over the study period. RAS access by specialty doubled since 2010 (from three to six). The number of active robotic surgeons tripled from seven surgeons in 2010 to 20 surgeons in 2019. Moreover, there was a significant drop in average case volume, from a peak of 40 cases in 2014 to 25 cases in 2019 (p=0.02). RARP annual case volume followed a similar pattern, reaching a maximum of 166 cases in 2014, then declining to 137 cases in 2019. The mean SWT was substantially increased from 52 days in 2014 to 73 days in 2019; however, PSM rates were not affected by the reduction in surgical volumes (p<0.05). CONCLUSIONS: Over the last decade, RAS access by specialty has increased at two Canadian academic centers due to growing multispecialty use. As there was a fixed, single-robotic system at each of the hospital centers, there was a substantial reduction in the number of RAS performed per surgeon over time, as well as a gradual increase in the SWT. The current low number of available robots and unsustainable funding resources may hinder universal patient access to RAS.

The global distribution of special needs dentistry across dental school curricula.

INTRODUCTION: Special needs dentistry (SND) is an emerging dental specialty, with ongoing developments in education and clinical practice focused towards the tailored management of individuals with special needs (SN). Patients with SN have a higher prevalence of oral diseases and unmet dental needs compared to the general population. Although inadequate training and experience in managing patients with SN has been highlighted as a significant barrier to accessing care, there is limited data about the extent of SND teaching at the entry-to-practice or higher levels. METHODS: This work is the first to map SND curricula globally, across 180 countries and 1265 dental schools. RESULTS: Although 74.62% of dental schools were found in developing economies, the distribution of programs that reported SND in their courses was highly skewed towards developed countries. In terms of advanced degrees, beyond basic entry-to-practice training, the USA delivered 60% of the SND programs, followed by Canada (15.56%), UK (13.33%), and Australia (8.89%). The term SND appeared in 33.95% of entry-to-practice level program curricula and was less commonly used in transitioning economies. Only 112 SND-specialized practitioners enter the workforce globally each year from developed economies, and all but three advanced degrees are found in G7 countries. CONCLUSION: By exploring the impact of economic status on its distribution, this paper highlighted the lack of SND representation in dental curricula, especially amongst programs in transitioning or developing economies. Education of both general dentists and specialists is critical as a collaborative effort is needed to manage the growing population of patients with SN.

Single-Port vs Multiport Robot-Assisted Partial Nephrectomy: A Meta-Analysis.

Background: Several centers have reported their experience with single-port robot-assisted partial nephrectomy (SP-RAPN); however, it is uncertain if utilization of this platform represents an improvement in outcomes compared to multiport robot-assisted partial nephrectomy (MP-RAPN). To evaluate this, we performed a meta-analysis to compare the perioperative, oncological, and functional outcomes between SP-RAPN and MP-RAPN. Methods: For relevant articles, three electronic databases, including PubMed, Scopus, and Web of Science, were searched from their inception until January 1, 2023. A meta-analysis has been reported in line with Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) 2020 and assessing the methodological quality of systematic reviews (AMSTAR) guidelines. The odds ratio (OR) and weighted mean difference (MD) were applied for the comparison of dichotomous and continuous variables with 95% confidence intervals (CI). Results: Of the 374 retrieved abstracts, 29 underwent full-text review, and 8 studies were included in the final analysis, comprising a total cohort of 1007 cases of RAPN (453 SP-RAPN cases and 554 MP-RAPN cases). Compared to MP-RAPN, the SP-RAPN group had a significantly longer ischemia time (MD = 4.6 minutes, 95% CI 2.8 to 6.3, p < 0.001), less estimated blood loss (MD = -12.4 mL, 95% CI -24.6 to -0.3, p = 0.045), higher blood transfusion rate (OR = 2.97, 95% CI 1.33 to 6.65, p = 0.008), and higher postoperative estimated glomerular filtration rate (eGFR) at 6 months (MD = 4.9 mL/min, 95% CI 0.2 to 9.7, p = 0.04). There was no significant difference in other outcomes between the two approaches, including the intraoperative complication, overall postoperative complication, minor postoperative complication (Clavien-Dindo I - II), major postoperative complication (Clavien-Dindo III-V), conversion to radical nephrectomy, pain score on day #1, pain score on discharge, morphine milligram equivalent usage, hospital stay, positive surgical margins, and postoperative eGFR. Conclusions: SP-RAPN represents an emerging technique using a novel platform. Initial studies have demonstrated that SP-RAPN is a safe and feasible approach to performing partial nephrectomy, although with inferior outcomes for ischemia time and blood transfusion rates. Further studies will be necessary to define the best usage of SP-RAPN within the surgeon's armamentarium.

Ablative minimally invasive surgical therapies for benign prostatic hyperplasia: A review of Aquablation, Rezum, and transperineal laser prostate ablation.

INTRODUCTION: Benign prostatic hyperplasia (BPH) is one of the most common diseases affecting men and can present with bothersome lower urinary tract symptoms (LUTS). Historically, transurethral resection of the prostate (TURP) has been considered the gold standard in the treatment of LUTS due to BPH. However, TURP and other traditional options for the surgical management of LUTS secondary to BPH are associated with high rates of sexual dysfunction. In the past decade, several novel technologies, including Aquablation therapy, convective water vapor therapy (Rezum), and transperineal prostate laser ablation (TPLA), have demonstrated promising evidence to be safe and effective while preserving sexual function. METHODS: In this review, we discuss three ablative minimally invasive surgeries: Aquablation, Rezum, and TPLA. We review their techniques, safety, as well as perioperative and functional outcomes. We go into further detail regarding sexual function after these ablative minimally invasive surgical therapies. RESULTS: Aquablation is a surgeon-guided, robot-executed, heat-free ablative waterjet procedure with sustained functional outcomes at 5 years while having no effect on sexual activity. Rezum is an innovative office-based, minimally invasive surgical option for BPH that delivers convective water vapor energy into prostate adenoma to ablate obstructing tissue. Rezum leads to significant improvements in Qmax, IPSS while preserving sexual function. TPLA is another office-based technology which uses a diode laser source to produce thermoablation. It leads to improvement in Qmax, IPSS, and QoL while preserving ejaculatory function. CONCLUSIONS: Overall, ablative minimally invasive surgical therapies have demonstrated excellent safety and efficacy profiles while preserving sexual function. These modalities should be discussed with patients to ensure informed and shared decision-making. Ablative minimally invasive surgical therapies may be particularly interesting to patients who value the preservation of their sexual function.

Personalized Numerical Cardiovascular Model with Weight Growth for Evaluating Pediatric Left Ventricular Assist Devices: Derivation from an Experimental Mock Circulatory Loop.

Pediatric patients with heart failure have limited treatment options because of a shortage of donor hearts and compatible left ventricular assist devices (LVADs). To address this issue, our group is developing an implantable pediatric LVAD for patients weighing 5-20 kg, capable of accommodating different physiological hemodynamic conditions as patients grow. To evaluate LVAD prototypes across a wide range of conditions, we developed a numerical cardiovascular model, using data from a mock circulatory loop (MCL) and patient-specific elastance functions. The numerical MCL was validated against experimental MCL results, showing good agreement, with differences ranging from 0 to 11%. The numerical model was also tested under left heart failure conditions and showed a worst-case difference of 16%. In an MCL study with a pediatric LVAD, a pediatric dataset was obtained from the experimental MCL and used to tune the numerical MCL. Then, the numerical model simulated LVAD flow by using an HQ curve obtained from the LVAD's impeller. When the numerical MCL was validated against the experimental MCL, hemodynamic differences ranged between 0 and 9%. These findings suggest that the numerical model can replicate various physiological conditions and impeller designs, indicating its potential as a tool for developing and optimizing pediatric LVADs.

Prospective Multicenter Evaluation of Pain Before and After Removal of Nonobstructing Renal Calculi: A CoRE Initiative.

PURPOSE: Flank pain associated with stone disease is typically caused by a stone that obstructs urine flow. However, it is plausible that nonobstructing kidney stones may still cause pain. We performed a multicenter, observational trial to evaluate whether treatment of small nonobstructing calyceal stones improves pain and kidney stone-specific health-related quality of life. MATERIALS AND METHODS: Patients aged 18 years or older with nonobstructing renal stone(s) up to 10 mm in longest diameter and moderate to severe pain were recruited. All participants completed 3 questionnaires: the Brief Pain Inventory (BPI), the Patient-Reported Outcomes Measurement Information System pain interference form 6a, and the Wisconsin Stone Quality of Life questionnaire. Thereafter, all participants underwent ureteroscopy for renal stone treatment. All 3 questionnaires were repeated at 2, 6 to 8, and at 12 weeks postprocedure. The primary outcomes were change in preoperative to 12-week postoperative mean BPI score and worst BPI pain score. RESULTS: A total of 43 patients with nonobstructing kidney stones and associated flank pain were recruited. All stones were removed. Preoperatively, BPI scores for mean pain and worst pain were 5.5 and 7.2, respectively which decreased to 1.8 and 2.8 respectively at 12 weeks postoperatively. Wisconsin Stone Quality of Life questionnaire mean score increased from 70.4 to 115.3 at 12 weeks postoperatively. A total of 86% and 69% of patients had at least a 20% and 50% reduction in their mean pain scores, respectively. CONCLUSIONS: This study determined that patients benefit significantly from the removal of calyceal nonobstructing kidney stones for at least 12 weeks with a reduction in pain and an increase in quality of life. Therefore, surgical removal of these stones in this patient population should be offered as a treatment option.

Hemodynamic Effect of a Fontan Assist Device on a Numerical Fontan Circulatory Model under Various Medication Scenarios.

Patients with single-ventricle heart disease and failing Fontan circulation represent the largest and most rapidly growing subgroup of adults with congenital heart disease referred for transplant assessment. Few clinical therapies are available for improving Fontan hemodynamics. Mechanical circulatory support devices have been used successfully in the clinical setting to assist the single ventricle, but no device is currently available to support the subpulmonary circulation. A subpulmonary pump could be used to support patients with failing Fontan circulation by mitigating chronic venous hypertension and restoring normal physiology. Our group designed a Fontan assist device (FAD) to augment right-heart (subpulmonary) flow and decrease venous pressures. To ensure that our FAD could achieve target hemodynamic parameters, we developed a numerical Fontan circulatory model to evaluate the interaction between the cardiovascular system and the FAD. To ensure that the circulatory model can mimic real-world clinical conditions, we investigated the effects of various medications in the FAD loop. Results showed that the FAD can significantly increase cardiac output in Fontan patients and can create a pressure difference between the pulmonary arteries and venae cavae. Further, the systemic venous pressure can be significantly reduced by using the FAD plus diuretic treatment. The downstream pulmonary artery pressure can be increased by augmenting the FAD with vasodilator treatment, diuretic treatment, or both.Clinical Relevance- This work supports FAD development by providing a method for studying human cardiovascular effects under various hemodynamic scenarios.

Case Commentary: Another prong of attack? Topical antibiotic instillation with negative pressure wound therapy for nontuberculous mycobacterial skin and soft tissue infections.

Nontuberculous mycobacteria (NTM) skin infections remain therapeutically challenging. Given the diversity in infections, host responses, and antimicrobials, clinical guidelines are often built on case series and observational studies. In this commentary, we respond to a paper by Stemkens et al. that introduces an emerging strategy: adjunctive negative pressure wound therapy with instillation and dwell time combined with topical antibiotics for refractory NTM skin and soft tissue infections. We delve into the primary considerations surrounding this innovative approach.