Treatment Of MRSA Infections Research Articles

Pharmacokinetics and safety of daptomycin administered subcutaneously in healthy volunteers: a single-blinded randomized crossover trial.

Daptomycin stands as a key IV antibiotic in treating MRSA infections. However, patients facing challenges with difficult venous access require alternative administration routes. This study aimed to evaluate the pharmacokinetic (PK) profile and safety of subcutaneous (SC) daptomycin. In a two-period, two-treatment, single-blind crossover Phase I trial (ClinicalTrials.gov NCT04434300), participants with no medical history received daptomycin (10 mg/kg) both IV and SC in a random order, with a minimum 2 week washout period together with matched placebo (NaCl 0.9%). Blood samples collected over 24 h facilitated PK comparison. Monte Carlo simulations assessed the PTA for various dosing regimens. Adverse events were graded according to Common Terminology Criteria for Adverse Events(CTCAE) v5.0. Twelve participants (aged 30.9 ± 24.4 years; 9 male,75%) were included. SC daptomycin exhibited delayed (median Tmax 0.5 h for IV versus 4 h for SC) and lower peak concentration than IV (Cmax = 132.2 ± 16.0 μg/mL for IV versus 57.3 ± 8.6 μg/mL for SC; P < 0.001). SC AUC0-24 (937.3 ± 102.5 μg·h/mL) was significantly lower (P = 0.005) than IV AUC0-24 (1056.3 ± 123.5 μg·h/mL) but was deemed bioequivalent. PTA demonstrated target AUC0-24 attainment for 100% of simulated individuals, for both 8 and 10 mg/kg/24 h SC regimens. Adverse events (AEs) related to SC daptomycin were more frequent than for SC placebo (25 versus 13, P = 0.016). No serious AEs were reported. Single-dose SC daptomycin infusion proved to be safe, exhibiting a bioequivalent AUC0-24 compared with the IV route. The SC route emerges as a potential and effective alternative when IV administration is not possible.

The mechanism of MRSA drug tolerance and the comparison between vancomycin and daptomycin in the treatment of MRSA infections

The mechanism of MRSA drug tolerance and the comparison between vancomycin and daptomycin in the treatment of MRSA infections

Comparative effectiveness and safety of six antibiotics in treating MRSA infections: A network meta-analysis

ObjectivesThis study conducted a network meta-analysis comparing linezolid, teicoplanin, daptomycin, tigecycline, and ceftaroline fosamil with vancomycin for treating MRSA-related diseases, addressing the lack of comprehensive evaluations in existing research on antibiotic therapy for MRSA infections. MethodsWe systematically searched databases including PubMed, Embase, Web of Science, the Cochrane Librar up to August 22, 2023. All eligible randomized controlled trials of the six antibiotics were included in the NMA, and their effectiveness and safety were compared across various MRSA-related diseases. Categorical data were used for the odds ratio (OR), and continuous data were used for mean difference (SMD). The surface under the cumulative ranking (SUCRA) was employed to evaluate the incidence rate. ResultsAccording to SUCRA results, daptomycin was the most effective treatment (73.0%) in bloodstream infections. In pulmonary infections and skin and soft tissue infections, linezolid out-performed other antibiotics in effectiveness rate (90.6% and 86.3%), microbial killing rate (93.3% and 93.1%). Vancomycin showed lower adverse reactions than teicoplanin, with less hepatotoxicity compared to linezolid and tigecycline. Linezolid had higher thrombocytopenia risk but lower nephrotoxicity risk than others. Vancomycin was less effective in microbial killing rates than linezolid across various infections. ConclusionThe present research suggests that in pulmonary infections and skin and soft tissue infections, linezolid may be a better option for treating MRSA-related diseases. However, caution is warranted due to the association of linezolid with thrombocytopenia. Trial registrationOur study protocol was registered with the International Prospective Register of SystematicReviews (PROSPERO); Registration number: CRD42024535142.

Design, Synthesis, Biological Evaluation, and Molecular Docking Studies of Pleuromutilin Derivatives Containing Thiazole.

In this study, we designed and synthesized a series of pleuromutilin derivatives containing thiazole. The in vitro antimicrobial efficacy of these synthesized compounds was examined by using four strains. Compared with tiamulin (MIC = 0.25 μg/mL), compound 14 exhibited potency in inhibiting MRSA growth (MIC = 0.0625 μg/mL) in these derivatives. Meanwhile, the time-killing kinetics further demonstrated that compound 14 could efficiently inhibit the MRSA growth. After exposure at 4 × MIC, the postantibiotic effect (PAE) of compound 14 was 1.29 h. Additionally, in thigh-infected mice, compound 14 exhibited a more potent antibacterial efficacy (-1.78 ± 0.28 log10 CFU/g) in reducing MRSA load compared to tiamulin (-1.21 ± 0.23 log10 CFU/g). Moreover, the MTT assay on RAW 264.7 cells demonstrated that compound 14 (8 μg/mL) had no significant cytotoxicity. Docking studies indicated the strong affinity of compound 14 toward the 50S ribosomal subunit, with a binding free energy of -9.63 kcal/mol. Taken together, it could be deduced that compound 14 was a promising candidate for treating MRSA infections.

Metabolic remodeling by RNA polymerase gene mutations is associated with reduced β-lactam susceptibility in oxacillin-susceptible MRSA.

The emergence of oxacillin-susceptible methicillin-resistant Staphylococcus aureus (OS-MRSA) strains has created new challenges for treating MRSA infections. These strains can become resistant to β-lactam antibiotics through chromosomal mutations, including those in the RNA polymerase (RNAP) genes such as rpoBC, leading to treatment failure. This study investigated the mechanisms underlying reduced β-lactam susceptibility in four rpoBC mutants of OS-MRSA. The results showed that rpoBC mutations caused RNAP transcription dysfunction, leading to an intracellular accumulation of ribonucleotides and precursors of peptidoglycan as well as wall teichoic acid. This, in turn, caused thickening of the cell wall and ultimately resulted in decreased susceptibility to β-lactam in OS-MRSA. These findings provide insights into the mechanisms of antibiotic resistance in OS-MRSA and highlight the importance of continued research in developing effective treatments to combat antibiotic resistance.

Design and synthesis of potential pyrrole-coupled carboxamide derivatives as an anti-superbug MRSA agent

A series of new pyrrole-coupled carboxamide derivatives had been synthesized and amply characterized by various techniques, viz FTIR, 1H-NMR, 13C-NMR, and LCMS. All these compounds had undergone evaluation for their PASS, BBB, pharmacophore model, ADME, and bioactive score. The antibacterial properties of all the derivatives were examined and compound 5i demonstrated strong antibacterial activity against MRSA. A membrane damage investigation supported by SEM pictures, cellular content leakage, potassium efflux, and bacterial respiration suppression showed that compound 5i had anti-MRSA properties. A good binding score of -9.11 was found for compound 5i against the MRSA protein 6FTB in an in silico molecular docking analysis, compared to a score of -10.25 for streptomycin. Based on these findings, compound 5i can be further studied in order to develop it as a drug to treat MRSA infections.

Effect of Resveratrol and Curcumin on Gene Expression of Methicillin-Resistant Staphylococcus aureus (MRSA) Toxins.

Staphylococcus aureus is an opportunistic pathogen that can lead to a number of potentially terrible community- and hospital-acquired illnesses. Among the diverse set of virulence factors that S. aureus possesses, secreted toxins play a particularly preeminent role in defining its virulence. In this work, we aimed to facilitate the development of novel strategies utilizing natural compounds to lower S. aureus's toxin production and consequently enhance therapeutic approaches. Two natural polyphenols, resveratrol (RSV) and curcumin (CUR), were tested for their effect on reducing toxin gene production of MRSA isolates. Fifty clinical MRSA isolates were gathered from Riyadh and Jeddah. Molecular screening of toxin genes (sea, seb, sec, sed, seh, lukF, and lukS) harbored by MRSA was performed. Sub-inhibitory concentrations of RSV (50 μg/ml) and CUR (20 μg/ml) were determined to study their effect on the gene expression MRSA's toxin genes. Our findings revealed the presence of the tested genes in MRSA isolates, with lukF being the most prevalent gene and seh the least detected gene. We found that RSV reduced the relative expression of toxin genes, sea, seb, lukF, and lukS, respectively, while CUR decreased the relative expression of sea and seb genes in the examined isolates. Regarding lukF and lukS, CUR downregulated the expression of both genes in some isolates and upregulated the expression in other isolates. From these results, we concluded that RSV and CUR could be used as alternative therapeutic approaches to treat MRSA infections through reducing toxin production.

Progress in the Prevalence, Classification and Drug Resistance Mechanisms of Methicillin-Resistant Staphylococcus aureus.

Staphylococcus aureus is a common human pathogen with a variety of virulence factors, which can cause multiple infectious diseases. In recent decades, due to the constant evolution and the abuse of antibiotics, Staphylococcus aureus was becoming more resistant, the infection rate of MRSA remained high, and clinical treatment of MRSA became more difficult. The genetic diversity of MRSA was mainly represented by the continuous emergence of epidemic strains, resulting in the constant changes of epidemic clones. Different classes of MRSA resulted in different epidemics and resistance characteristics, which could affect the clinical symptoms and treatments. MRSA had also spread from traditional hospitals to community and livestock environments, and the new clones established a relationship between animals and humans, promoting further evolution of MRSA. Since the resistance mechanism of MRSA is very complex, it is important to clarify these resistance mechanisms at the molecular level for the treatment of infectious diseases. We firstly described the diversity of SCCmec elements, and discussed the types of SCCmec, its drug resistance mechanisms and expression regulations. Then, we described how the vanA operon makes Staphylococcus aureus resistant to vancomycin and its expression regulation. Finally, a brief introduction was given to the drug resistance mechanisms of biofilms and efflux pump systems. Analyzing the resistance mechanism of MRSA can help study new anti-infective drugs and alleviate the evolution of MRSA. At the end of the review, we summarized the treatment strategies for MRSA infection, including antibiotics, anti-biofilm agents and effluxpump inhibitors. To sum up, here we reviewed the epidemic characteristics of Staphylococcus aureus, summarized its classifications, drug resistance mechanisms of MRSA (SCCmec element, vanA operon, biofilm and active efflux pump system) and novel therapy strategies, so as to provide a theoretical basis for the treatment of MRSA infection.

Generation of monoclonal antibodies against PBP2a to improve diagnosis and potential treatment of MRSA infections

Background: MRSA is a type of MDR bacterium. All around the world, it leads to significant nosocomial and community-acquired diseases. The discovery of fresh ideas is very important because there are so few effective treatments for MRSA infections. PBP2a is a great candidate for the development of MRSA-specific Mabs. Aim: The purpose of this study was to create murine Mabs against PBP2a in order to enhance MRSA laboratory detection and possibly treatment. Methods: Anti-PBP2a MAb was tested for biodistribution, therapeutic, and preventative effects in comparison to vancomycin. After receiving anti-PBP2a MAb therapy, biodistribution was assessed between 12 and 96 hours later. Results: During the observation timepoints, the majority of the generated MAb stayed in the serum and just a tiny fraction was found in the kidneys, lungs, and spleen. A prophylactic experiment in mice given the lethal dosage 50 (LD50) found that treated animals with anti-PBP2a MAb had a greater survival rate than the control group. In a therapeutic experiment, one dosage of anti-PBP2a MAb reduced bacterial load in the kidneys similarly to the group treated with five doses of vancomycin, and a combination therapy with anti-PBP2a MAb and vancomycin was more effective than either drug used alone. Conclusion: The findings of this study suggested that an anti-PBP2a MAb may be extremely useful in the creation of innovative diagnostic tools and promising treatments for preventative and therapeutic measures against MRSA infections.

Antimicrobial resistance profile of methicillin-resistant Staphylococcus aureus isolates in children reported from the ISPED surveillance of bacterial resistance, 2016-2021.

Methicillin-resistant Staphylococcus aureus (MRSA) poses a serious threat to public health worldwide. In December 2015, the Infectious Disease Surveillance of Pediatrics (ISPED) program was organized to monitor bacterial epidemiology and resistance trends in children. This retrospective study was conducted from January 2016-December 2021 on patients at eleven ISPED-group hospitals. From 2016-2021, a total of 13024 MRSA isolates were obtained from children. The most common age group for patients with MRSA infection was less than 3 years old, and newborns were an important group affected by MRSA infection. MRSA was most commonly isolated from the lower respiratory, an abscess, a secretion, or blood in neonates and from the lower respiratory, an abscess, or the upper respiratory in non-neonates. All isolates were susceptible to vancomycin and linezolid and resistant to penicillin; additionally, 76.88%, 54.97%, 22.30%, 5.67%, 5.14%, 3.63%, and 1.42% were resistant to erythromycin, clindamycin, tetracycline, levofloxacin, sulfamethoxazole-trimethoprim (TMP-SMX), gentamicin, and rifampin, respectively. Between 2016 and 2021, a significant increase was seen in the levofloxacin- and TMP-SMX-resistance rates (from 5.45% to 7.14% and from 4.67% to 6.50%, respectively) among MRSA isolates, along with a significant decrease in the rates of resistance to erythromycin (from 82.61% to 68.08%), clindamycin (from 60.95% to 46.82%), tetracycline (from 25.37% to 17.13%), gentamicin (from 4.53% to 2.82%), and rifampin (from 1.89% to 0.41%). The antibiotic-resistance rates varied among MRSA isolated from different sources. Because of the high antibiotic resistance rate to clindamycin, this antibiotic is not recommended for empirical treatment of MRSA infections, especially in osteomyelitis.

(Digital Presentation) A Disposable Chip Sensor for the Detection of Vancomycin: Studying the Long-Term Stability

Vancomycin is one of the most important anti-bacterial drugs for the treatment of MRSA infection. Continuous monitoring is commonly recommended as it has a low therapeutic window, which is often limited by the equipment cost, and the technical skills required for modern TDM techniques such as HP-LCs and immunoassays. As a result, a cost-effective and quick detection solution for Vancomycin TDM is critical. We have already reported a successful vancomycin sensor on a ceramic base, a paper base, and a PET (polyethylene terephthalate) base, in our previous works 1,2. However, the long-term stability of the sensor for the clinical trial is very important. Therefore, this study focused on the improvement of the stability of the sensor.The PET chip is composed of a PET base on which the silver wiring was printed using an inkjet printer. It contains two holes for electrodes with a 2.0 mm diameter for the counter electrode and a 1.0 mm diameter for the working electrode. The chip also comprises a circular reservoir of diameter 8 mm. VCM imprinted poly(methylene bisacrylamide-co-methacrylic acid-co-Allylaminocarboxypropyonic-3-ferrocene) was grafted on graphite particle surface by a procedure similar to our previous work. This grafted graphite was mixed with a) silicon oil (MIPsi ), and b) paraffin oil (MIPpff ) to make a paste to use as the sensing material. The viscosity of both the oils was the same. We performed the chronoamperometric analysis with a VCM sample solution (0-60 µgmL-1, in phosphate buffer) filled in the sample reservoir.The chronoamperometric analysis time was 15 seconds for each sample. Current obtained at the 10th second was recorded to obtain the calibration curve. The change in current at 10s demonstrated strong linearity with the VCM concentration in both MIPsi and MIPpff , indicating good linearity with the change in current at 10s. Furthermore, this result was obtained using a "single-use" chip, which implies that each concentration was measured using a separate chip. MIPsi and MIPpff were both sensitive to vancomycin. However, when the sensor was packed and kept for 3 days, the MIPsi sensor lost its sensitivity completely. Sensor with the working electrode made of MIPpff, however, retained their sensitivity. MIPpff was further packed and kept for 10 days to have a deeper insight into the effect of binder oil on the long-term stability of the sensor and the sensor was still found to be sensitive. From the results of this study, it can be concluded that a stable sensor that can sensitively detect vancomycin can be made using paraffin oil as the binder oil. References Aaryashree, A., Takeda, Y., Yoshimi, Y., Hatano, A. & Kida, M. A Disposable Vancomycin Sensor Using Molecularly Imprinted Carbon Paste on a Ceramic Chip. in ECS Meeting s vols MA2020-02 3332–3332 (2020).Aaryashree et al. A “Single-Use” Ceramic-Based Electrochemical Sensor Chip Using Molecularly Imprinted Carbon Paste Electrode. Sensors 20, 5847 (2020).

Modification of the immune response by bacteriophages alters methicillin-resistant Staphylococcus aureus infection

There is an urgent need to develop phage therapies for multidrug-resistant bacterial infections. However, although bacteria have been shown to be susceptible to phage therapy, phage therapy is not sufficient in some cases. PhiMR003 is a methicillin-resistant Staphylococcus aureus phage previously isolated from sewage influent, and it has demonstrated high lytic activity and a broad host range to MRSA clinical isolates in vitro. To investigate the potential of phiMR003 for the treatment of MRSA infection, the effects of phiMR003 on immune responses in vivo were analysed using phiMR003-susceptible MRSA strains in a mouse wound infection model. Additionally, we assessed whether phiMR003 could affect the immune response to infection with a nonsusceptible MRSA strain. Interestingly, wounds infected with both susceptible and nonsusceptible MRSA strains treated with phiMR003 demonstrated decreased bacterial load, reduced inflammation and accelerated wound closure. Moreover, the infiltration of inflammatory cells in infected tissue was altered by phiMR003. While the effects of phiMR003 on inflammation and bacterial load disappeared with heat inactivation of phiMR003. Transcripts of proinflammatory cytokines induced by lipopolysaccharide were reduced in mouse peritoneal macrophages. These results show that the immune modulation occurring as a response to the phage itself improves the clinical outcomes of phage therapy.

N-Acetyl Cysteine in combination with vancomycin or linezolid for biofilm eradication of methicillin-resistant Staphylococcus aureus (MRSA)

Antibiotics are challenging to deliver because MRSA can build biofilms. In Indonesia, the major parenteral antibiotics for treating MRSA infections are Vancomycin and Linezolid. Because NAC can degrade the biofilm matrix, it is believed that combining it with antibiotics will improve its capacity to destroy MRSA biofilms. An experiment was done at RSUD Dr. Soetomo Surabaya's Clinical Microbiology Laboratory in June 2022. The biofilm-forming bacteria studied were MRSA clinical isolates. The antibiotics utilized were Vancomycin (2 g/mL), Linezolid (4 g/mL), and NAC (8 mg/mL). A biofilm assay microtiter test was also carried out to see how drug exposure affected the biofilm that had grown. Biofilm eradication was observed when comparing the mass yield and biofilm metabolism after treatment to the control. According to the study's findings, using a combination of NAC with Vancomycin or Linezolid was superior to using NAC, Vancomycin, or Linezolid alone. There was no apparent difference between the two combinations, however. The combination of NAC and Vancomycin had the same effect on eliminating MRSA biofilms as the combination of NAC and Linezolid.

Platelets Inhibit Methicillin-Resistant Staphylococcus aureus by Inducing Hydroxyl Radical-Mediated Apoptosis-Like Cell Death.

ABSTRACTMethicillin-resistant Staphylococcus aureus (MRSA) is one of the most common drug-resistant bacteria and poses a significant threat to human health. Due to the emergence of multidrug resistance, limited drugs are available for the treatment of MRSA infections. In recent years, platelets have been reported to play important roles in inflammation and immune responses, in addition to their functions in blood hemostasis and clotting. We and other researchers have previously reported that platelets can inhibit Staphylococcus aureus growth. However, it remained unclear whether platelets have the same antibacterial effect on drug-resistant strains. In this study, we hypothesized that platelets may also inhibit the growth of MRSA; the results confirmed that platelets significantly inhibited the growth of MRSA in vitro. In a murine model of MRSA infection, we found that a platelet transfusion alleviated the symptoms of MRSA infection; in contrast, depletion of platelets aggravated infective symptoms. Moreover, we observed an overproduction of hydroxyl radicals in MRSA following platelet treatment, which induced apoptosis-like death of MRSA. Our findings demonstrate that platelets can inhibit MRSA growth by promoting the overproduction of hydroxyl radicals and inducing apoptosis-like death.IMPORTANCE The widespread use of antibiotics has led to the emergence of drug-resistant bacteria, particularly multidrug-resistant bacteria. MRSA is the most common drug-resistant bacterium that causes suppurative infections in humans. As only a limited number of drugs are available to treat the infections caused by drug-resistant pathogens, it is imperative to develop novel and effective biological agents for treating MRSA infections. This is the first study to show that platelets can inhibit MRSA growth in vitro and in vivo. Our results revealed that platelets enhanced the production of hydroxyl radicals in MRSA, which induced a series of apoptosis hallmarks in MRSA, including DNA fragmentation, chromosome condensation, phosphatidylserine exposure, membrane potential depolarization, and increased intracellular caspase activity. These findings may further our understanding of platelet function.

External Validation of a Vancomycin Population Pharmacokinetic Model and Developing a New Dosage Regimen in Neonates.

Vancomycin is the drug of choice in the treatment of MRSA infections. In a published vancomycin population pharmacokinetic study on neonates in Singapore healthcare institutions, it was found that vancomycin clearance was predicted by weight, postmenstrual age, and serum creatinine. The aim of this study was to externally validate the vancomycin population pharmacokinetic model to develop a new dosage regimen in neonates, and to compare this regimen with the existing institutional and NeoFax® dosage regimens. A retrospective chart review of neonates who received vancomycin therapy and therapeutic drug monitoring was conducted. The median prediction error percentage was calculated to assess bias, while the median absolute prediction error percentage and the root mean squared error percentage were calculated to assess precision. The new dosage regimen was developed using Monte Carlo simulation. A total of 20 neonates were included in the external validation dataset. Eighteen of them were premature, with a median gestational age of 27.7 (25.9-31.5) weeks and postmenstrual age of 30.5 (27.3-34.3) weeks at the point of vancomycin initiation. No apparent systematic bias was found in the predictions of the model. The external validation performed in the current study found the model to be generally unbiased. Our new vancomycin dosage regimen was able to achieve target trough concentrations and area under the curve (AUC24) at a greater proportion as compared to existing institutional and NeoFax® dosage regimens. The pharmacokinetic model built in the previous study can be used to conduct reliable population simulations of our Asian neonatal population in Singapore. The new dosage regimen was able to achieve target trough concentrations and AUC24 better than existing institutional and NeoFax® dosage regimens.

Nitric-Oxide-Releasing aza-BODIPY: A New Near-Infrared J-Aggregate with Multiple Antibacterial Modalities.

The development of near-infrared (NIR) J-aggregates has received increasing attention due to their broad applications. Here, we report the nitrosation of an amine-containing aza-BODIPY precursor (BDP-NH2 ), affording the first nitric oxide (NO)-releasing NIR J-aggregate (BDP-NO). The introduction of N-nitrosamine moieties efficiently inhibits the aromatic interactions of BDP-NH2 , which instead promotes the formation of J-aggregates within micellar nanoparticles with a remarkable bathochromic shift of ≈109 nm to the NIR window (820 nm). Interestingly, the NO release and photothermal conversion efficiency (PTCE) can be delicately tuned by the loading contents of BDP-NO within micellar nanoparticles, thereby enabling multiple antibacterial modalities by exploring either NO release, photothermal therapy (PTT), or both. We demonstrate the combination of NO and PTT can elevate antibacterial activity while attenuating PTT-associated inflammation for the in vivo treatment of MRSA infection.

Nitric‐Oxide‐Releasing aza‐BODIPY: A New Near‐Infrared J‐Aggregate with Multiple Antibacterial Modalities

AbstractThe development of near‐infrared (NIR) J‐aggregates has received increasing attention due to their broad applications. Here, we report the nitrosation of an amine‐containing aza‐BODIPY precursor (BDP‐NH2), affording the first nitric oxide (NO)‐releasing NIR J‐aggregate (BDP‐NO). The introduction ofN‐nitrosamine moieties efficiently inhibits the aromatic interactions ofBDP‐NH2, which instead promotes the formation of J‐aggregates within micellar nanoparticles with a remarkable bathochromic shift of ≈109 nm to the NIR window (820 nm). Interestingly, the NO release and photothermal conversion efficiency (PTCE) can be delicately tuned by the loading contents ofBDP‐NOwithin micellar nanoparticles, thereby enabling multiple antibacterial modalities by exploring either NO release, photothermal therapy (PTT), or both. We demonstrate the combination of NO and PTT can elevate antibacterial activity while attenuating PTT‐associated inflammation for the in vivo treatment of MRSA infection.

Berberine: Best Alternative Medicine Insight Abating Global Challenges for Treatment of MRSA Infections - Response to Comments of Savita V Jadhav [Response to Letter

Berberine: Best Alternative Medicine Insight Abating Global Challenges for Treatment of MRSA Infections - Response to Comments of Savita V Jadhav [Response to Letter

Oxygen-Tolerant Photoredox Catalysis Triggers Nitric Oxide Release for Antibacterial Applications.

Photoredox catalysis has emerged as a robust tool for chemical synthesis. However, it remains challenging to implement photoredox catalysis under physiological conditions due to the complex microenvironment and the quenching of photocatalyst by biologically relevant molecules such as oxygen. Here, we report that UV-absorbing N,N'-dinitroso-1,4-phenylenediamine derivatives can be selectively activated by fac-Ir(ppy)3 photocatalyst within micellar nanoparticles under visible light irradiation (e.g., 500 nm) through photoredox catalysis in aerated aqueous solutions to form quinonediimine (QDI) residues with concomitant release of NO. Notably, the formation of QDI derivatives can actively scavenge the reactive oxygen species generated by fac-Ir(ppy)3 , thus avoiding oxygen quenching of the photocatalyst. Further, we exemplify that the oxygen-tolerant photoredox catalysis-mediated NO release can not only kill planktonic bacteria in vitro but also efficiently treat MRSA infections in vivo.

Oxygen‐Tolerant Photoredox Catalysis Triggers Nitric Oxide Release for Antibacterial Applications

AbstractPhotoredox catalysis has emerged as a robust tool for chemical synthesis. However, it remains challenging to implement photoredox catalysis under physiological conditions due to the complex microenvironment and the quenching of photocatalyst by biologically relevant molecules such as oxygen. Here, we report that UV‐absorbingN,N′‐dinitroso‐1,4‐phenylenediamine derivatives can be selectively activated byfac‐Ir(ppy)3photocatalyst within micellar nanoparticles under visible light irradiation (e.g., 500 nm) through photoredox catalysis in aerated aqueous solutions to form quinonediimine (QDI) residues with concomitant release of NO. Notably, the formation of QDI derivatives can actively scavenge the reactive oxygen species generated byfac‐Ir(ppy)3, thus avoiding oxygen quenching of the photocatalyst. Further, we exemplify that the oxygen‐tolerant photoredox catalysis‐mediated NO release can not only kill planktonic bacteria in vitro but also efficiently treat MRSA infections in vivo.