Multidrug-resistant Acinetobacter Baumannii Research Articles

Comparative genomics and characterization of a multidrug-resistant Acinetobacter baumannii VRL-M19 isolated from a crowded setting in India

A crowded vegetable market serves as a mass gathering, posing a potential risk for infection transmission. In this study, we isolated a multidrug-resistant Acinetobacter baumannii strain, VRL-M19, from the air of such a market and conducted comparative genomics and phenotypic characterization. Antimicrobial susceptibility testing, genome sequencing using Illumina HiSeq X10, and pan-genome analysis with 788 clinical isolates identified core, accessory, and unique drug-resistant determinants. Mutational analysis of drug-resistance genes, virulence factor annotation, in vitro pathogenicity assessment, subsystem analysis, Multilocus sequence typing, and whole genome phylogenetic analysis were performed. VRL-M19 exhibited multidrug resistance with 69 determinants, and analysis across 788 clinical isolates and 350 Indian isolates revealed more accessory genes (52 out of 69) in the Indian isolates. Multiple mutations were observed in drug target modification genes, and the strain was identified as a moderate biofilm-former with 55 virulence factors. Whole genome phylogenetics indicated a close relationship between VRL-M19 and clinical A. baumannii strains. In conclusion, our comprehensive study suggests that VRL-M19 is a multidrug-resistant, potential pathogen with biofilm-forming capabilities, closely associated with clinical A. baumannii strains.

Characterization of a novel bacteriophage endolysin (LysAB1245) with extended lytic activity against distinct capsular types associated with Acinetobacter baumannii resistance.

Capsular polysaccharides are considered as major virulence factors associated with the ability of multidrug-resistant (MDR) Acinetobacter baumannii to cause severe infections. In this study, LysAB1245, a novel bacteriophage-encoded endolysin consisting of a lysozyme-like domain from phage T1245 was successfully expressed, purified, and evaluated for its antibacterial activity against distinct capsular types associated with A. baumannii resistance. The results revealed a broad spectrum activity of LysAB1245 against all clinical MDR A. baumannii isolates belonging to capsular type (KL) 2, 3, 6, 10, 47, 49, and 52 and A. baumannii ATCC 19606. At 2 h following the treatment with 1.7 unit/reaction of LysAB1245, more than 3 log reduction in the numbers of bacterial survival was observed. In addition, LysAB1245 displayed rapid bactericidal activity within 30 min (nearly 3 log CFU/mL of bacterial reduction). Thermostability assay indicated that LysAB1245 was stable over a broad range of temperature from 4 to 70°C, while pH sensitivity assay demonstrated a wide range of pH from 4.5 to 10.5. Furthermore, both minimal inhibitory concentration (MIC) and minimal bactericidal concentration (MBC) of LysAB1245 against all MDR A. baumannii isolates and A. baumannii ATCC 19606 were 4.21 μg/mL (0.1 unit/reaction). Conclusively, these results suggest that LysAB1245 possesses potential application for the treatment of nosocomial MDR A. baumannii infections.

Pneumonija prouzrokovana Acinetobacter baumanii tokom mehaničke ventilacije usled infekcije kovidom 19 - epidemiološke i kliničke karakteristike i terapija

Less than 3% of people who get infected with COVID-19 need hospital treatment. However, up to one-third of the hospitalized patients with COVID-19 require invasive mechanical ventilation. Ventilator-associated pneumonia (VAP), caused by the multidrug-resistant Acinetobacter baumannii (A. baumannii), is an emerging infection in the intensive care units and can have fatal consequences for those patients who already have critical COVID-19. Countries of the Balkan peninsula have an exceptionally high prevalence of invasive carbapenem-resistant Acinetobacter spp in the hospital setting. Diagnosing this type of pneumonia is a challenging process. Furthermore, treatment complexities arise because of multidrug resistance. Novel therapeutic agents, such as sulbactam/durlobactam and zosurabalpin could be the new therapeutic opportunity for A. baumannii-induced VAP. Antimicrobial resistance of A. baumannii is not entirely understood, although several mechanisms have been identified. To adequately manage VAP it is important to isolate causative agents, have awareness of the resistance pattern, carefully dispense antibiotics, and identify risk factors. In this review, we discuss epidemiological characteristics, pathophysiological mechanisms, clinical presentation and diagnosis, as well as the current and novel treatments of A. baumannii-induced VAP.

The Effect of Citric and Ascorbic Acids as Anti-Biofilm and Anti-Capsular Agents on Multidrug-Resistant Acinetobacter baumannii

Objective: Acinetobacter baumannii (A. baumannii) is an opportunistic bacterium with multiple virulence factors, including capsule and biofilm, and is known for its high drug resistance. Anti-virulence natural substances have been suggested as novel alternatives to conventional antibiotics. We aimed to evaluate the effect of citric and ascorbic acids as anti-biofilm and anti-capsular agents against multidrug-resistant (MDR) A. baumannii clinical isolates. Materials and Methods: Twenty-eight A. baumannii MDR isolates were collected from different clinical sources. The minimum inhibitory concentration (MIC) of each agent was estimated. Biofilm formation and capsule were investigated phenotypically in the absence and presence of both agents at ½ and ¼ MICs. The presence of 14 adhesive and nonadhesive virulence genes was investigated. Results: Phenotypically, all the isolates were biofilm producers and were capsulated. The MIC of citric acid ranged from 1.25 to 2.5 mg/mL, while that of ascorbic acid was 3 mg/mL for all isolates. Both agents showed significant reduction in biofilm and capsular thinning. Ascorbic acid showed a dose-dependent effect in both biofilm reduction and capsule thinning unlike citric acid. Four genes, papG23, sfa1, fyuA, and cvaC, were absent among all isolates, while iutA was present in 100% of isolates. Other genes showed different distributions among the isolates. These virulence genes were not correlated to the anti-biofilm effect of both agents. Ascorbic acid was observed to have a better effect than citric acid. This can provide a clue for a better treatment regimen including ascorbic acid against MDR A. baumannii infections.

Transcriptomic analysis reveals zinc-mediated virulence and pathogenicity in multidrug-resistant Acinetobacter baumannii.

Acinetobacter baumannii is a gram-negative bacterium well known for its multidrug resistance and connection to nosocomial infections under ESKAPE pathogens. This opportunistic pathogen is ubiquitously associated with nosocomial infections, posing significant threats within healthcare environments. Its critical clinical symptoms, namely, meningitis, urinary tract infections, bloodstream infections, ventilator-associated pneumonia, and pneumonia, catalyze the imperative demand for innovative therapeutic interventions. The proposed research focuses on delineating the role of Zinc, a crucial metallo-binding protein and micronutrient integral to bacterial metabolism and virulence, to enhance understanding of the pathogenicity of A. baumannii. RNA sequencing and subsequent DESeq2 analytical methods were used to identify differential gene expressions influenced by zinc exposure. Exploiting the STRING database for functional enrichment analysis has demonstrated the complex molecular mechanisms underlying the enhancement of pathogenicity prompted by Zinc. Moreover, hub genes like gltB, ribD, AIL77834.1, sdhB, nuoI, acsA_1, acoC, accA, accD were predicted using the cytohubba tool in Cytoscape. This investigation underscores the pivotal role of Zinc in the virulence of A. baumannii elucidates the underlying molecular pathways responsible for its pathogenicity. The research further accentuates the need for innovative therapeutic strategies to combat A. baumannii infections, particularly those induced by multidrug-resistant strains.

Inhibitory effect of selenium nanoparticles on the biofilm formation of multidrug-resistant Acinetobacter baumannii

Background/Aim: Treatment of infections caused by biofilm-producing multidrug-resistant (MDR) pathogens represents a huge global problem due to primary antimicrobial multi-resistance enhanced by reduced penetration of antibiotics in the biofilm-embedded bacteria. The aim of this study was to determine the capacity of biofilm production among MDR Acine-tobacter baumannii (A. baumannii) isolates obtained from different clinical specimens and to evaluate the inhibitory effect of selenium nanoparticles (SeNPs) coated with cationic polymer cetyltrimethylammonium bromide (CTAB) on the biofilm formation. Methods: Antimicrobial effect of antibiotics (meropenem, imipenem, gentamicin, amikacin, ciprofloxacin, levofloxacin and trimethoprim-sulfa-methoxazole) was determined by disk-diffusion assay, while sensitivity to colistin was determined with E test. All 60 isolates were tested on biofilm production in microtiter plates with crystal violet dye. Minimal biofilm inhib-itory concentration (MBIC) of SeNPs was tested in order to prevent biofilm formation in microtiter plates. Results: All tested clinical isolates were classified as MDR (n = 60) and extensively drug-resistant (XDR, n = 60). Out of the total 60 isolates, 55 isolates (92 %) showed the ability for biofilm formation, with the majority of them classified as strong (42 %) and moderate (42 %) biofilm producers. MBIC values of SeNPs for 55 biofilm-producing isolates ranged from 0.07 to 1.25 mg/mL. Strong biofilm producers had statistically higher MBIC (0.15 mg/mL) in correlation to other biofilm-producing isolates (0.07 mg/ mL). There was no correlation between invasiveness of isolates with biofilm production and MBIC values. Conclusion: Presented results are very promising and interesting especially in nanotechnology and medical fields, while SeNPs with the addition of cationic surfactant inhibit biofilm formation of MDR A. baumannii clinical isolates.

Can risk factors and risk scores help predict colonization and infection in multidrug-resistant gram-negative bacteria?

Antimicrobial resistance (AMR) is positioning as one of the most relevant threats to global public health and threatens the effective treatment of an ever-growing number of bacterial infections in various healthcare settings, particularly in acute care and surgical units, as well as in the community. Among multidrug-resistant (MDR) gram-negative bacteria (MDRGNB), Enterobacterales, Pseudomonas aeruginosa, and Acinetobacter baumannii require special attention, since they account for most of the mortality associated with bacterial infections and are often MDR. It is clear that there is an important global variation in antibiotic resistance profiles among MDRGNB species. Extended-spectrum β-lactamase-producing Enterobacterales, carbapenem-resistant Enterobacterales, DTR-P. aeruginosa, and MDR-A. baumannii are the focus of this review. Here, we summarize a series of relevant studies on risk factors associated with colonization and infection with these MDRGNB. Likewise, we offer a comparative overview of those studies providing scoring systems to predict the risk of infection with these MDR pathogens, and their pros and cons. Despite the variable accuracy of published risk factors for predicting colonization or infection with MDRGNB, these scores are valuable tools that may help anticipate colonization and infection among those colonized. More importantly, they may help reduce unnecessary use of broad-spectrum antimicrobials and guiding the selection of an optimal treatment.

Practical synthesis of isoindolines yields potent colistin potentiators for multidrug-resistant Acinetobacter baumannii.

An efficient and practical one-pot synthesis of isoindolines from readily available starting materials was achieved under mild conditions by implementing an isoindole umpolung strategy. A variety of isoindolines were prepared with good to excellent yields. Biological screens of these identified compounds demonstrated that they are potent potentiators of colistin for multi-drug resistant Acinetobacter baumannii.

Characterization of genes involved in the iron acquisition system of multidrug-resistant Acinetobacter baumannii.

The high prevalence of virulence-associated genes observed in Acinetobacter baumannii isolates underscores the pathogenic potential of this bacterium. The presence of these genes confers enhanced survival, evasion of host defenses, and increased virulence. In this study, we investigate the presence and distribution of genes associated with virulence and assess the antimicrobial susceptibility patterns in clinical isolates of A. baumannii. This research focused on examining the 50 multi-drugs resistant (MDR) strains that were included in this investigation. The identification of these strains was validated using Oxa-51. The presence of the BauA and BasD genes was determined through conventional PCR techniques. The results derived from Oxa-51 PCR confirmed the identification of all 50 selected strains of A. baumannii. Additionally, both the BauA and BasD genes were successfully identified in 82% of the MDR strains. Moreover, the varying antibiotic resistance patterns highlight the challenge in treating A. baumannii infections effectively. Strategies such as combination therapy, antimicrobial stewardship, and infection control measures should be considered to combat this multidrug-resistant pathogen.

Outbreak of Multidrug-resistant Acinetobacter baumannii in a Tertiary Health Center from Northwestern Nigeria.

In spite of its global notoriety and WHO alarm, Acinetobacter baumannii is still an understudied critical-priority pathobiont in Nigeria. We characterized its antimicrobial susceptibility profile and resistance genes during an outbreak. This cross-sectional study involved collection of patients' urine samples and swabs from unit staff's hands and ward environments for the identification of A. baumannii strains using standard morphologic and biochemical methods. The disk diffusion method was used to assess the antimicrobial susceptibility profile of the isolates with the production of extended-spectrum beta-lactamases (ESBLs) confirmed by the combined disk test screening method. Characterization of the resistance genes of the ESBL producers was carried out using polymerase chain reaction polymerase chain reaction technique. A. MDR strains of A. baumannii harboring blaSHV and blaTEM genes were recovered from clinical and environmental sources during the outbreak, which was contained with preventive measures recommended.

Phenotypic and Molecular Characterization of Hypervirulent and Multidrug-Resistant Acinetobacter baumannii Isolated from ICU Respiratory Infections.

The emergence of hypervirulent strains of Acinetobacter baumannii poses a significant threat in intensive care units (ICU). This study aimed to molecularly characterize hypervirulent A. baumannii strains isolated from ICU patients with respiratory infections. Six strains were isolated from ICU patients over one month. Isolates were identified by phenotypic characterization biochemical properties and 16s RNA sequencing. Antibiotic susceptibility testing was conducted followed by resistance genes detection by PCR. MLST, and PFGE were employed to analyse clonal relationships among strains. Plasmid replicon typing and plasmid transmission frequencies were determined. The isolated strains exhibited diverse clinical manifestations, including acute respiratory distress syndrome (ARDS). Antibiotic susceptibility testing revealed multidrug-resistance phenotype. Molecular analysis revealed a complex genetic landscape of antibiotic resistance genes, including ESBLs and carbapenemases, as well as virulence genes such as ompA, csuE, and exoS. The multiple sequence types indicating genetic diversity among the strains as ST1512, ST622, and ST149 (each type two isolates). Plasmid characterization revealed the presence of diverse replicon types associated with multidrug resistance. This study provides comprehensive insights into the phenotypic, molecular, and epidemiological characteristics of hypervirulent A. baumannii outbark in ICU.

A thermosensitive hydrogel formulation of phage and colistin combination for the management of multidrug-resistant Acinetobacter baumannii wound infections.

Chronic skin wounds are often associated with multidrug-resistant bacteria, impeding the healing process. Bacteriophage (phage) therapy has been revitalized as a promising strategy to counter the growing concerns of antibiotic resistance. However, phage monotherapy also faces several application drawbacks, such as a narrow host spectrum, the advent of resistant phenotypes and poor stability of phage preparations. Phage-antibiotic synergistic (PAS) combination therapy has recently been suggested as a possible approach to overcome these shortcomings. In the present study, we employed a model PAS combination containing a vB_AbaM-IME-AB2 phage and colistin to develop stable wound dressings of PAS to mitigate infections associated with Acinetobacter baumannii. A set of thermosensitive hydrogels were synthesized with varying amounts of Pluronic® F-127 (PF-127 at 15, 17.5 and 20 w/w%) modified with/without 3 w/w% hydroxypropyl methylcellulose (HPMC). Most hydrogel formulations had a gelation temperature around skin temperature, suitable for topical application. The solidified gels were capable of releasing the encapsulated phage and colistin in a sustained manner to kill bacteria. The highest bactericidal effect was achieved with the formulation containing 17.5% PF-127 and 3% HPMC (F5), which effectively killed bacteria in both planktonic (by 5.66 log) and biofilm (by 3 log) states and inhibited bacterial regrowth. Good storage stability of F5 was also noted with negligible activity loss after 9 months of storage at 4 °C. The ex vivo antibacterial efficacy of the F5 hydrogel formulation was also investigated in a pork skin wound infection model, where it significantly reduced the bacterial burden by 4.65 log. These positive outcomes warrant its further development as a topical PAS-wound dressing.

Phage-encoded depolymerases as a strategy for combating multidrug-resistant Acinetobacter baumannii.

Acinetobacter baumannii, a predominant nosocomial pathogen, represents a grave threat to public health due to its multiple antimicrobial resistance. Managing patients afflicted with severe infections caused by multiple drug-resistant A. baumannii is particularly challenging, given the associated high mortality rates and unfavorable prognoses. The diminishing efficacy of antibiotics against this superbug underscores the urgent necessity for novel treatments or strategies to address this formidable issue. Bacteriophage-derived polysaccharide depolymerase enzymes present a potential approach to combating this pathogen. These enzymes target and degrade the bacterial cell's exopolysaccharide, capsular polysaccharide, and lipopolysaccharide, thereby disrupting biofilm formation and impairing the bacteria's defense mechanisms. Nonetheless, the narrow host range of phage depolymerases limits their therapeutic efficacy. Despite the benefits of these enzymes, phage-resistant strains have been identified, highlighting the complexity of phage-host interactions and the need for further investigation. While preliminary findings are encouraging, current investigations are limited, and clinical trials are imperative to advance this treatment approach for broader clinical applications. This review explores the potential of phage-derived depolymerase enzymes against A. baumannii infections.

Drug Repurposing against Anhydro-N-acetylmuramic Acid Kinase of Multi-Drug Resistant Acinetobacter baumannii: An in Silico Approach

ABSTRACT: Acinetobacter baumannii, a gram-negative coccobacillus is accountable for different nosocomial diseases. It has been enlisted in the ‘critical’ category in WHO published list depending on the urgency for novel drug development as it becomes multidrug resistant (MDR). The aim of this study was to find a drug which can be repurposed against any drug target of these bacteria and thus the time and cost required for typical drug development procedure can be bypassed. In this study, Anhydro-N-acetylmuramic acid kinase (AnmK) of Acinetobacter baumannii was analyzed to be a good drug target which is responsible for the structural integrity of the cell wall of these bacteria. The expression probability of the protein is high with 0.916. PROTPARAM analysis shows that it is a thermostable, non polar protein with molecular weight of 41.7 kDa and pI in the acidic range. The structure prediction was done with SWISS-MODEL (with 46.71% identity with the template) and was found reliable with 91.8% amino acid in allowable region. This predicted structure was used for dug repurposing in which drugs are screened from ZINC15 database (containing FDA approved drug) to find their effective binding (if any) with this protein. PyRx software was used for the docking process which found Ergotamine as the most promising repurposed drug in terms of binding energy(-10.5 kcal/mole) and vina score(-10.3 kcal/mole). Molecular Dynamics Simulation shows that binding of this drug with the protein target is stable over picoseconds time scale.

Detection of Multidrug-Resistant Acinetobacter baumannii among Gram-Negative Bacteria Isolated from Clinical Samples

Detection of Multidrug-Resistant Acinetobacter baumannii among Gram-Negative Bacteria Isolated from Clinical Samples

In vitro activity of cefiderocol and comparator antibiotics against multidrug-resistant non-fermenting Gram-negative bacilli.

This study evaluated the in vitro activity of cefiderocol, ceftazidime/avibactam, and aztreonam/avibactam against clinically important multidrug-resistant non-fermenting Gram-negative bacilli. Bacteraemic isolates of 126 multidrug-resistant Acinetobacter baumannii (MDRAB), 110 imipenem-resistant Pseudamoas aeruginosa [including 14 difficult-to-treat resistant P. aeruginosa (DTRPA)], 45 beta-lactam-non-susceptible Burkholderia cepacia complex (BCC), 47 levofloxacin or trimethoprim/sulfamethoxazole-non-susceptible Stenotrophomonas maltophilia and 22 ciprofloxacin-non-susceptible Elizabethkingia spp. collected between 2019 and 2021 were subjected to MIC determination for cefiderocol, ceftazidime/avibactam and aztreonam/avibactam. The MIC50/90s of cefiderocol for drug-resistant A. baumannii, P. aeruginosa, BCC, S. maltophilia and Elizabethkingia spp. were 0.25/2, 0.25/1, ≤0.06/≤0.06, ≤0.06/0.25 and >32/>32 mg/L, respectively. Cefiderocol inhibited 94.4% (119/126) of MDRAB, 100% of imipenem-resistant P. aeruginosa, 100% of DTRPA and 100% of BCC at an MIC ≤4 mg/L, and 97.9% (46/47) of S. maltophilia at ≤1 mg/L. Ceftazidime/avibactam inhibited 76.4% (84/110) of imipenem-resistant P. aeruginosa, 21.4% (3/14) of DTRPA and 68.9% (31/45) of BCC at an MIC ≤8 mg/L. Aztreonam/avibactam had MIC50/90s of 16/>32, 8/16 and 4/8 mg/L for imipenem-resistant P. aeruginosa, BCC and S. maltophilia, respectively. At ≤8 mg/L, aztreonam/avibactam inhibited 7.1% (1/14) of DTRPA and 93.6% (44/47) of S. maltophilia isolates. Elizabethkingia spp. demonstrated high MICs for cefiderocol, ceftazidime/avibactam and aztreonam/avibactam, with all MIC50s and MIC90s > 32 mg/L. Cefiderocol may serve as an alternative treatment for multidrug-resistant A. baumannii, P. aeruginosa, BCC and S. maltophilia when other antibiotics have been ineffective or intolerable. The role of ceftazidime/avibactam and aztreonam/avibactam in the management of BCC or S. maltophilia infections warrants further investigation.

Exploring Roles of the Polysaccharide Capsule in Pathogenesis of Hypervirulent Acinetobacter baumannii Clinical Isolate Lac-4.

The frequently multidrug-resistant bacterial pathogen Acinetobacter baumannii is a leading cause of nosocomial infections, including ventilator-associated pneumonia, such that the World Health Organization and US Centers for Disease Control and Prevention have declared it a top priority candidate for novel drug development. Nearly all clinical A. baumannii strains express a thick surface polysaccharide capsule that protects against desiccation, host defenses, and disinfectants. In this study, we investigated the contribution of the polysaccharide capsule to virulence caused by the A. baumannii clinical isolate Ab Lac-4, which is rare in its ability to cause pneumonia and disseminated sepsis in healthy mice. We assessed the role of the capsule in wildtype Lac-4 (WT) by generating a premature stop codon in wza, which codes for the polysaccharide export protein. The wza# mutant was hypersensitive to killing by complement, whole blood, and healthy human neutrophils compared to WT and a revertant mutant (wza-Rev). Furthermore, the wza# mutant was highly attenuated in murine sepsis and unable to disseminate from the lungs during pneumonia. This study reinforces the capsule as a key contributor to Ab Lac-4 hypervirulence.

Pandrug-resistant Acinetobacter baumannii from different clones and regions in Mexico have a similar plasmid carrying the blaOXA-72 gene.

Multidrug-resistant Acinetobacter baumannii is a common hospital-acquired pathogen. The increase in antibiotic resistance is commonly due to the acquisition of mobile genetic elements carrying antibiotic resistance genes. To comprehend this, we analyzed the resistome and virulome of Mexican A. baumannii multidrug-resistant isolates. Six clinical strains of A. baumannii from three Mexican hospitals were sequenced using the Illumina platform, the genomes were assembled with SPAdes and annotated with Prokka. Plasmid SPAdes and MobRecon were used to identify the potential plasmid sequences. Sequence Type (ST) assignation under the MLST Oxford scheme was performed using the PubMLST database. Homologous gene search for known virulent factors was performed using the virulence factor database VFDB and an in silico prediction of the resistome was conducted via the ResFinder databases. The six strains studied belong to different STs and clonal complexes (CC): two strains were ST208 and one was ST369; these two STs belong to the same lineage CC92, which is part of the international clone (IC) 2. Another two strains were ST758 and one was ST1054, both STs belonging to the same lineage CC636, which is within IC5. The resistome analysis of the six strains identified between 7 to 14 antibiotic resistance genes to different families of drugs, including beta-lactams, aminoglycosides, fluoroquinolones and carbapenems. We detected between 1 to 4 plasmids per strain with sizes from 1,800 bp to 111,044 bp. Two strains from hospitals in Mexico City and Guadalajara had a plasmid each of 10,012 bp pAba78r and pAba79f, respectively, which contained the bla OXA-72 gene. The structure of this plasmid showed the same 13 genes in both strains, but 4 of them were inverted in one of the strains. Finally, the six strains contain 49 identical virulence genes related to immune response evasion, quorum-sensing, and secretion systems, among others. Resistance to carbapenems due to pAba78r and pAba79f plasmids in Aba pandrug-resistant strains from different geographic areas of Mexico and different clones was detected. Our results provide further evidence that plasmids are highly relevant for the horizontal transfer of antibiotic resistance genes between different clones of A. baumannii.

The impact of environmental cleaning protocol featuring PX-UV in reducing the incidence of multidrug-resistant gram-negative healthcare-associated infection and colonization in intensive care units in Thailand.

In this quasi-experimental study, implementing PX-UV to the standard environmental cleaning protocol was associated with a reduction in the overall incidence of multidrug-resistant (MDR) gram-negative organisms (P = .01) and MDR Acinetobacter baumannii (P = .001) in intervention intensive care units. However, the intervention did not reduce patient length of stay and 30-day mortality.

Fe3O4 NPs-encapsulated metal-organic framework/enzyme hybrid nanoreactor for drug-resistant bacterial elimination via enhanced chemodynamictherapy

As a potential tool for combating bacterial infections, chemodynamic therapy (CDT), which utilizes the highly toxic hydroxyl radical (•OH), has shown tremendous promise. Its antibacterial efficacy, however, is compromised by insufficient H2O2 levels and a near-neutral pH at infection sites. Herein, a glucose-fueled and H2O2 self-supplying •OH nanogenerator (GOx-Fe3O4@MIL) based on cascade catalytic reactions is successfully constructed by immobilizing glucose oxidase (GOx) on the surface of Fe3O4 NPs-encapsulated MIL88B–NH2. MIL88B–NH2 (MIL NPs), a peroxidase-mimicking enzyme, immobilizes and protects GOx while synergistically enhancing the CDT effect of Fe3O4 NPs. GOx can continuously convert glucose into gluconic acid and H2O2. The former reduces the pH value to approximately 4, at which point Fe3O4@ MIL NPs exhibit the highest reaction activity. The continually produced H2O2 is used for subsequent catalysis of activated Fe3O4 @MIL NPs to generate highly toxic •OH for antibacterial applications, avoiding the direct use of relatively high concentrated and toxic H2O2. In vitro and in vivo results indicate that the designed self-activated nanoreactor can significantly inhibit methicillin-resistant Staphylococcus aureus (MRSA) and multidrug-resistant Acinetobacter baumannii (MDR-AB) growth with negligible biotoxicity.