Multidrug-resistant Infections Research Articles

Charge Engineering of Star-Shaped Organic Photosensitizers Enables Efficient Type-I Radicals for Photodynamic Therapy of Multidrug-Resistant Bacterial Infection.

Infection induced by multidrug-resistant bacteria is now the second most common cause of accidental death worldwide. However, identifying a high-performance strategy with good efficiency and low toxicity is still urgently needed. Antibacterial photodynamic therapy (PDT) is considered a non-invasive and efficient approach with minimal drug resistance. Whereas, the precise molecular design for highly efficient oxygen-independent type-I photosensitizers is still undefined. In this work, the regulation of the positive charge of star-shaped NIR-emissive organic photosensitizers can boost radical generation for the efficient treatment of wounds infected with multidrug-resistant bacteria. With positive charge engineering, TPAT-DNN, which has six positive charges, mainly produces hydroxyl radicals via the type-I pathway, while TPAT-DN, which has three positive charges, tends to generate singlet oxygen and superoxide radicals. For multidrug-resistant bacteria, TPAT-DNN exhibited specific killing effects on multidrug-resistant gram-positive bacteria at low concentrations, while TPAT-DN is similar antibacterial effects on both multidrug-resistant gram-negative and gram-positive bacteria. Furthermore, the efficiency and safety of TPAT-DNN for eradicating multidrug-resistant bacteria methicillin-resistant S. aureus (MRSA) infection and accelerating wound healing in an MRSA-infected mouse model are demonstrated. This work offers a new approach toward manipulating efficient type-I photosensitizers for MRSA treatment.

Pivmecillinam for Uncomplicated Acute Cystitis: A Contemporary Review.

To review the evidence and discuss use of pivmecillinam in uncomplicated acute cystitis. A literature search was conducted utilizing PubMed (from 2000 through August 2024) and ClinicalTrials.gov. Medical Subject Headings (MeSH) terms, such as mecillinam or pivmecillinam and urinary tract infections, were utilized. Additional references were identified by reviewing literature citations. Articles were limited to English language publications evaluating the efficacy or safety of pivmecillinam for urinary tract infections (UTIs) in adult populations. Data from 6 randomized controlled trials support pivmecillinam for acute uncomplicated cystitis at doses of 200 to 400 mg 3 times daily for 3 to 7 days, with more consistent clinical and bacteriologic cure observed with 400 mg doses and longer therapy durations. Clinical evaluation of 400 mg 2 to 3 times daily is available with use more common in non-US Food and Drug Administration (FDA)-approved populations, such as men, pregnancy, and multidrug resistant infections. There are limited data supporting pivmecillinam for pyelonephritis; routine use is cautioned until further clinical data are available. As resistance to first-line antimicrobials rises, the need for safe and effective treatment options remains high. Pivmecillinam represents a new therapeutic option available in the United States for outpatient management of uncomplicated acute cystitis. Pivmecillinam could be a key agent for uncomplicated acute cystitis. Utilization will likely be cost driven, but the promise of low resistance encourages the place in therapy when other agents are not susceptible to infecting uropathogens.

Ceftobiprole Medocaril: A New Fifth-Generation Cephalosporin.

The objective was to review the pharmacology, efficacy, and safety of intravenous ceftobiprole in the treatment of bloodstream infections, acute bacterial skin and skin structure infections (ABSSSIs), community-acquired pneumonia (CAP), and hospital-acquired pneumonia (HAP), or ventilator-associated pneumonia (VAP). PubMed and ClinicalTrials.gov were searched using the following terms: ceftobiprole, ceftobiprole medocaril, ceftobiprole medocaril sodium, Zevtera, and BAL5788. Articles published in English between January 1985 and August 15, 2024, related to pharmacology, safety, efficacy, and clinical trials were reviewed. Ceftobiprole has shown similar efficacy to comparator antibiotics in CAP, ABSSSIs, and bloodstream infections. Overall treatment success in patients with bacteremia was 69.8% and 68.7%; 91.3% and 88.1% with ABSSSIs and 86.6% and 87.4% with CAP in ceftobiprole and comparator groups, respectively. Finally, in the management of HAP and VAP, ceftobiprole was inferior in the VAP population. Ceftobiprole had a favorable safety profile with gastrointestinal adverse effects occurring more frequently than comparators. Clinicians have limited options to treat multidrug-resistant infections. Ceftobiprole has demonstrated efficacy against causative pathogens in specific infections including methicillin-resistant Staphylococcus aureus bacteremia (SAB), ABSSSI, and CAP and may be considered a viable alternative. However, ceftobiprole's impact on HAP, VAP, and febrile neutropenia needs to be further delineated. Ceftobiprole's broad-spectrum activity makes it a viable option for treating patients hospitalized with CAP, ABSSSI, and SAB. Further studies are needed in severely ill HAP or VAP, febrile neutropenia, and pediatric patients.

Innovative Solutions for Multidrug-resistant Organisms Infections in ICU: A Joint Efficacy Evaluation of Multi-disciplinary Team and SHEL Model (Software, Hardware, Environment, Liveware)

BackgroundThe escalating threat of Multidrug-resistant organisms (MDROs) in Intensive Care Units (ICU) demands innovative management strategies to curb the rising infection rates and associated clinical challenges. ObjectiveTo assess the effectiveness of integrating the Multi-disciplinary team (MDT) approach with the SHEL model (Software, Hardware, Environment, Liveware) in reducing MDROs infections within ICU settings. MethodsFrom January 2021 to April 2024, a prospective, randomized controlled study was conducted in the ICU of Nantong Fourth People's Hospital, enrolling 411 patients with MDROs infections. These patients were randomly assigned into three groups: the MDT group, the SHEL model group, and a combined group. The intervention lasted for four weeks, during which the effects on the MDROs detection rate, infection rate, healthcare staff's infection control execution scores, and the rationality of antibiotic use were assessed, aiming to determine the efficacy of each approach in managing MDROs in the ICU setting. ResultsThe overall infection rate of MDROs in the ICU of our hospital from 2021 to 2024 was 60.18%, with sputum infection sources accounting for 68.37% of the total sources, making it the primary source of infection. The detection rate of MOROs in the combined group was significantly higher than that in the MDT group and the SHEL group, with the SHEL group having a higher detection rate than the MDT group (P<0.05). The infection rate of MOROs in the combined group was significantly lower than that in both the MDT group and the SHEL group, with the SHEL group having a lower detection rate than the MDT group (P<0.05). The implementation scores of the combination group in standard prevention, hand hygiene, antibiotic management, and isolation measures were significantly higher than those of the MDT and SHEL groups, with the SHEL group scoring higher than the MDT group (P<0.05). The rational use of antibiotics in the combined group was also higher than in both the MDT group and the SHEL group, with the SHEL group having a higher level than the MDT group (P<0.05). ConclusionThe integrated MDT and SHEL model significantly reduced MDROs infections in ICU, improved healthcare workers' infection prevention and nursing quality, and promoted the appropriate use of antibiotics, advocating for its clinical application.

Drug Allergy Delabeling

Drug allergy labels are critical for ensuring patient safety; however, unverified labels established without a rigorous diagnostic process can lead to suboptimal medication use, treatment failures, increased adverse drug reactions, and higher healthcare costs. In particular, unconfirmed penicillin allergy labels are strongly linked to the inappropriate use of broad-spectrum antibiotics, contributing to the rise of multidrug-resistant infections. The process of drug allergy delabeling enables many patients to safely use the medication in question, thereby facilitating the appropriate use of antibiotics and reducing unnecessary avoidance. Such delabeling is particularly vital as part of antimicrobial stewardship programs, as it enhances patient outcomes while decreasing healthcare expenses. Moving forward, the development of standardized procedures, enhanced awareness among patients and healthcare providers, and the implementation of validated risk-stratification methods is essential for more accurate and efficient drug allergy delabeling. These advancements will help mitigate the adverse effects of inaccurate labels and support optimal patient care.

Assessing the Value of New Antimicrobials: Evaluations of Cefiderocol and Ceftazidime-Avibactam to Inform Delinked Payments by the NHS in England.

The UK has recently established subscription-payment agreements for two antimicrobials: cefiderocol and ceftazidime-avibactam. This article summarises the novel value assessments that informed this process and lessons learned for future pricing and funding decisions. The evaluations used decision modelling to predict population incremental net health effects (INHEs), informed by systematic reviews, evidence syntheses, national surveillance data and structured expert elicitation. Significant challenges faced during the development of the evaluations led to profound uncertainty in the estimates of INHEs. The value assessment required definition of the population expected to receive the new antimicrobials; estimating value within this heterogenous population; assessing comparative efficacy using antimicrobial susceptibility data due to the absence of relevant clinical data; and predicting population-level benefits despite poor data on current numbers of drug-resistant infections and uncertainties around emerging resistance. Though both antimicrobials offer the potential to treat multi-drug resistant infections, the benefits estimated were modest due to the rarity of true pan-resistance, low life expectancy of the patient population and difficulty of identifying and quantifying additional sources of value. Assessing the population INHEs of new antimicrobials was complex and resource intensive. Future evaluations should continue to assemble evidence relating to areas of expected usage, patient numbers over time and comparative effectiveness and safety. Projections of patient numbers could be greatly enhanced by the development of national level linked clinical, prescribing and laboratory data. A practical approach to synthesising these data would be to combine expert assessments of key parameters with a simple generic decision model.

The prevalence of optrA-carrying Enterococci in the vaginal micro-ecology of pregnant women in late pregnancy.

The colonization of Enterococcus in the female vagina leads to neonatal and pediatric enterococcal septicemia. Linezolid (LZD) is a kind of mainstream drug for treating multidrug-resistant Gram-positive infections. OptrA is the main LZD-resistance gene at Enterococci in human isolates. It is essential to explore the prevalence of optrA-carrying Enterococcus in vaginal secretions of late pregnant women and the drug resistance of optrA. From May to June 2023, this study recruited 340 volunteers in late pregnancy (35-40 weeks of pregnancy) to provide non-repetitive vaginal discharge samples. Luria-Bertani broth and florfenicol (10 µg/mL) were used to enrich bacteria. Enterococci was identified through time-of-flight mass spectrometry. Additionally, antimicrobial susceptibility, polymerase chain reaction, and next-generation sequencing assays were applied to this study. Fifty-four optrA-carrying Enterococcus strains were obtained, the proportion of the whole vagina of late pregnant women was 15.88% (54 out of 340), and Enterococcus faecalis account the highest proportion. All optrA-carrying Enterococcus were resistant to at least three drugs. Tetracycline, chloramphenicol, erythromycin, and LZD have higher bacterial resistance rates. Genetic environment analysis revealed that IS1216E, fexA, and erm(A) may synergistically exert multidrug resistance with optrA. It is necessary to strengthen the surveillance of optrA-carrying Enterococcus in pregnant women. This study provides scientific support for controlling hospital infections and managing antibiotic-resistant bacteria, and provides a scientific basis for rational clinical medication.IMPORTANCEThe disruption of cervicovaginal microbiota homeostasis is considered a key factor in causing imbalance in the microenvironment, leading to inflammation, transmission of infections, and illness. Enterococcus is considered a major cause of healthcare-related infections globally. It has resistance to multiple antimicrobial drugs, which pose significant challenges for clinical treatment. Therefore, it is crucial to assess the prevalence of optrA-carrying Enterococcus in vaginal secretions of late pregnant women and the drug resistance of optrA. This study detected 15.88% of optrA-carried Enterococci in 340 pregnant women. Furthermore, we found that optrA-carrying Enterococcus strains are highly resistant to tetracycline, chloramphenicol, erythromycin, and Linezolid. Additionally, genetic environment analysis revealed that IS1216E, fexA, and erm(A) may synergistically exert multidrug resistance with optrA. This study provides scientific support for controlling hospital infections and managing antibiotic-resistant bacteria and provides a scientific basis for rational clinical medication.

A blueprint for broadly effective bacteriophage-antibiotic cocktails against bacterial infections

Bacteriophage (phage) therapy is a promising therapeutic modality for multidrug-resistant bacterial infections, but its application is mainly limited to personalized therapy due to the narrow host range of individual phages. While phage cocktails targeting all possible bacterial receptors could theoretically confer broad coverage, the extensive diversity of bacteria and the complexity of phage-phage interactions render this approach challenging. Here, using screening protocols for identifying “complementarity groups” of phages using non-redundant receptors, we generate effective, broad-range phage cocktails that prevent the emergence of bacterial resistance. We also discover characteristic interactions between phage complementarity groups and particular antibiotic classes, facilitating the prediction of phage-antibiotic as well as phage-phage interactions. Using this strategy, we create three phage-antibiotic cocktails, each demonstrating efficacy against ≥96% of 153 Pseudomonas aeruginosa clinical isolates, including biofilm cultures, and demonstrate comparable efficacy in an in vivo wound infection model. We similarly develop effective Staphylococcus aureus phage-antibiotic cocktails and demonstrate their utility of combined cocktails against polymicrobial (mixed P. aeruginosa/S. aureus) cultures, highlighting the broad applicability of this approach. These studies establish a blueprint for the development of effective, broad-spectrum phage-antibiotic cocktails, paving the way for off-the-shelf phage-based therapeutics to combat multidrug-resistant bacterial infections.

Impact of pharmacist-led aminoglycoside stewardship: a 10-year observational study

BackgroundAminoglycosides are crucial for treating multidrug-resistant gram-negative infections and endocarditis. However, aminoglycosides are associated with significant risks of nephrotoxicity, necessitating careful dose selection and therapeutic drug monitoring. Therapeutic drug monitoring is essential for minimizing risk; however, few institutions routinely perform it. This study aimed to assess the impact of a pharmacist-driven therapeutic drug monitoring intervention on aminoglycoside usage trends and clinical outcomes.MethodsThis retrospective cohort study included 263 patients treated with aminoglycosides between 2014 and 2023. A pharmacist-led therapeutic drug monitoring intervention began in 2017, focusing on monitoring renal function, documenting patient weight, and closely managing aminoglycoside concentrations. Trends in aminoglycoside use and renal outcomes were analyzed.ResultsOver the study period, appropriate use of aminoglycosides at the time of initial prescription increased from 49 to 82% (P < 0.01). Pharmacist dosing design at initial prescription increased significantly from 21% pre-intervention to 60% post-intervention (P < 0.01). The proportion of pharmacist intervention in initial dosing design increased over time. The proportion of patients with measured aminoglycoside blood concentrations significantly increased from 53% pre-intervention to 72% post-intervention (P < 0.01). The proportion of patients who were able to manage target blood concentrations from the initial aminoglycoside dose without dose adjustments increased from 31% pre-intervention to 42% post-intervention, although the results were not significantly different (P = 0.07). The incidence rate of renal impairment remained similar (11% vs. 12%; P = 0.85), although the annual average number of cases decreased from 4.3 before the intervention to 2.5 after. Similarly, there were no significant differences in clinical efficacy before and after the intervention (65% vs. 71%; P = 0.35). Furthermore, aminoglycoside stewardship led to a 56% cost saving.ConclusionsPharmacist-led aminoglycoside stewardship significantly improved the appropriate use of aminoglycosides and decreased the associated costs. Thus, pharmacist involvement is essential for the proper use of aminoglycosides. However, many patients required aminoglycoside dose reductions despite the pharmacist’s guideline-based dosing design. Therefore, further accumulation of information on the management of aminoglycoside blood concentration may be necessary for the revision of these guidelines.

NDM-1 and KPC-3 co-producing Klebsiella pneumoniae ST512 in bronchial secretion from a patient in an intensive care unit of a Greek Tertiary Care Hospital.

This study investigated a strain of Klebsiella pneumoniae, identified as GRTHES, which exhibited extensive antibiotic resistance. The strain was resistant to all beta-lactams, including combinations withnewer agents such as meropenem/vaborbactam and imipenem/relebactam, as well as to aminoglycosides, fluoroquinolones, fosfomycin, trimethoprim-sulfamethoxazole and colistin. It remained susceptible to tigecycline. Whole-genome sequencing was performed by Ion Torrent platform on the K.pneumoniae strain. Genomic analysis revealed a genome length of 5,808,650 bp and a GC content of 56.9%. Advanced sequencing techniques and bioinformatic tools were used to assess resistance genesand plasmid replicons, highlighting the emergence of multidrug resistance and virulence traits. Thestrain carried blaNDM-1 and blaKPC-3 genes and was designated to KL107 O2afg type. Colistin resistance-associated mgrB/pmrB gene mutations were present, and the strain also harbored yersiniabactin-encoding ybt gene. Our findings provide insights into the genomic context of blaNDM-1 and blaKPC-3 carbapenemase-producing K. pneumoniae and emphasize the importance of continuous surveillance and novel therapeutic strategies to combat multidrug-resistant bacterial infections. It is the first time that an NDM-1 and KPC-3 co-producing strain of K. pneumoniae ST512 is identified in Greece. This study highlights the essential role of genomic surveillance as a proactive strategy to control the spread of carbapenemase-producing K. pneumoniae isolates, particularly when key antimicrobial resistance genes, such as blaNDM-1 and blaKPC-3, are plasmid-mediated. Detailed characterization of these isolates could reveal plasmid similarities that facilitate adaptation and transmission within and between hospitals. Although data on patient movements are limited, it is plausible that carbapenem-resistant isolate was selected to co-produce KPC and NDM through plasmid acquisition.

Evaluating the antibacterial activity of engineered phage ФEcSw endolysin against multi-drug-resistant E. coli strain Sw1

The emergence of bacteriophage-encoded endolysins hold significant promise as novel antibacterial agents, particularly against the growing threat of antibiotic-resistant bacteria. Therefore, we investigated the phage ФEcSw endolysin to enhance the lytic activity against multi-drug-resistant Escherichia coli Sw1 through site-directed mutagenesis guided by in silico identification of critical residues. A computational analysis was conducted to elucidate the protein folding pattern, identify the active domains, and recognize critical residues of ФEcSw endolysin. Structural similarity-based docking simulations were employed to identify residues potentially involved in both recognition and cleavage of the bacterial peptidoglycan (PG). Phage endolysin was amplified, cloned, expressed, and purified from phage ФEcSw. Pure Endolysin (EL) activity was subsequently validated through site-directed mutagenesis. Our studies revealed both open and closed conformations of ФEcSw endolysin within specific residue ranges (51-60 and 128-141). Notably, the active site was identified and contains the crucial catalytic residues, Glu19 and Asp34. A time-kill assay demonstrated that the Holin (HL) - EL effectively reduced E. coli Sw1 growth by 46% within 12 hours. Furthermore, treatment with HL, EL, and HL-EL significantly increased bacterial membrane permeability (11%, 74%, and 85%, respectively) within just 1 hour. Importantly, site-directed mutagenesis identified a double mutant (K19/H34) of the endolysin exhibiting the highest lytic activity compared to the wild-type and other mutants (E19D, E19K, D34E, and D34H) due to increase net charge from +3.23 to +6.29. Our findings demonstrate that phage endolysins and holins or engineered endolysin hold significant potential as therapeutic agents to combat multidrug-resistant bacterial infections.

Identification of determinants that allow maintenance of high-level fluoroquinolone resistance in Acinetobacter baumannii.

Acinetobacter baumannii is associated with multidrug-resistant infections in healthcare settings, with fluoroquinolones such as ciprofloxacin being currently ineffective. Clinical isolates largely harbor mutations in the GyrA and TopoIV fluoroquinolone targets, as well as mutations that increase expression of drug resistance-nodulation-division (RND) efflux pumps. Factors critical for maintaining fitness levels of pump overproducers are uncharacterized despite their prevalence in clinical isolates. We, here, identify proteins that contribute to the fitness of fluoroquinolone-resistant (FQR) strains overexpressing three known RND systems using high-density insertion mutagenesis. Overexpression of the AdeFGH efflux pump caused hypersensitization to defects in outer membrane homeostatic regulation, including lesions that reduced lipooligosaccharide (LOS) biosynthesis and blocked production of the major A. baumannii porin. In contrast, AdeAB pump hyperexpression, in the absence of elevated adeC expression (the outer membrane component of the pump), was relatively tolerant to loss of these functions, consistent with the outer membrane protein being the primary disruptive component. Surprisingly, overexpression of proton-transporting efflux pumps had little impact on cytosolic pH, consistent with a compensatory response to pump activity. The most striking transcriptional changes were associated with AdeFGH pump overexpression, including the activation of the phenylacetate (PAA) degradation regulon. Disruption of the PAA pathway resulted in cytosolic acidification and defective expression of genes involved in protection from oxidative stress. These results indicate that RND efflux pump overproduction is compensated by maintenance of outer membrane integrity in A. baumannii to facilitate fitness of FQR isolates.IMPORTANCEAcinetobacter baumannii is a pathogen that often causes multidrug-resistant infections in healthcare settings, presenting a threat to the efficacy of known therapeutic interventions. Fluoroquinolones such as ciprofloxacin are currently ineffective against a majority of clinical A. baumannii isolates, many of which express pumps that remove this antibiotic class from within the bacterium. Three of these pumps can be found in most clinical isolates, with one of the three often hyperproduced at all times. In this study, we identify proteins that are necessary for the fitness of pump hyperproducers. The identified proteins are necessary to stabilize the outer membrane and allow the cytoplasm to tolerate the accumulation of ions as a consequence of excess pump activity. These results point to strategies for developing therapies that combine known antibiotics with drugs that target proteins important for survival of strains hyper-expressing efflux pumps.

Ceftazidime–avibactam for the Treatment of Intra-abdominal Sepsis and Urosepsis: A Retrospective Hospital-based Study in India

Abstract Background: In India, microbial susceptibility to antibiotics has been gradually decreasing, thus making treatment of multidrug-resistant bacterial infections challenging. We aimed to assess the effectiveness of ceftazidime–avibactam in patients with intra-abdominal sepsis or urosepsis. Methods: This hospital-based, single-center retrospective study was conducted between April 2020 and March 2022 using data from inpatient records. Outcomes included inpatient mortality, clinical success/failure, and microbiological cure/failure measured on day 14/end of treatment, length of hospitalization and intensive care unit (ICU) admission, treatment and infection characteristics, recurrence within 30 days, and healthcare resource utilization. Descriptive statistics were used for data analysis. Results: Data from 46 patients (mean age = 65.2 ± 14.5 years, 73.9% male) were included. Ceftazidime–avibactam treatment was initiated within 5 days of hospitalization in 51.2% of patients. The median (range) duration of treatment was 8 (1, 20) days, and the average daily dose was 4.6 g. Inpatient and 30-day all-cause mortality rates were 41.5% and 17.1%, respectively. We observed clinical success, defined a priori, by day 14 in 58.5% of patients and microbiological cure in 61.3%. Most patients (97.0%) did not have recurrent infections. The median (range) length of hospitalization and ICU admission was 15.5 (3, 63) days and 11 (2, 63) days, respectively. Most patients (85.7%) utilized various healthcare resources during hospitalization. Conclusion: Among patients with available data, most showed clinical success (58.5%) and microbiological cure (61.3%) within 14 days of treatment initiation with ceftazidime–avibactam, with nearly no recurrence of infection, indicating treatment effectiveness in patients with intra-abdominal sepsis or urosepsis in an Indian hospital setting.

The upconversion luminescence biomonitoring and biological properties of rare earth oxide-inorganic composite microspheres enhanced by lithium

Multiple myeloma is the second most common hematologic malignant tumor, which can result in complications such as osteolytic fractures and bacterial infections. The side effects of chemotherapy limit the dosage of drugs, which can easily lead to multidrug resistance. Moreover, the dose and distribution of drugs within the body significantly influence the therapeutic efficacy of drugs. Therefore, it is highly necessary to improve multidrug resistance and bacterial infection in the treatment of multiple myeloma, repair bone defects caused by bone pain, and monitor the real-time dynamics of drugs. This work proposes a novel rare earth oxide-inorganic composite (7Li-MBGs:2Er/2Yb-0.75MTO) as a drug delivery platform for the treatment of multiple myeloma. 7Li-MBG, which have bone repair functions, serve as inorganic matrix materials, while Er2O3 and Yb2O3 act as activators and sensitizers, respectively. MTO is used as a therapeutic drug for treating myeloma. The drug release process of MTO was successfully monitored by upconversion luminescence. Cell experiments confirmed that 7Li-MBGs:2Er/2Yb-0.75MTO has a certain long-term therapeutic effect on multiple myeloma, and its mechanism of action is consistent with its drug release kinetics. Moreover, the synergistic effect of rare earth oxides, alkali metal ions and MTO endows 7Li-MBGs:2Er/2Yb-0.75MTO with high antibacterial and osteoinductive abilities, and thus playing a role in enhancing the drug resistance of infectious bacteria, preventing bacterial infection, repairing bone defects and monitoring the real-time dynamics of drug release during multiple myeloma therapy. Therefore, the 7Li-MBGs:2Er/2Yb-0.75MTO multifunctional drug delivery platform synthesized in this work provides a new idea for the treatment of multiple myeloma and biomonitoring.

Increased severity of multidrug-resistant Shigella sonnei infections in people experiencing homelessness.

Shigella sonnei has caused sexually transmitted enteric infections in men who have sex with men (MSM) in Vancouver. We recently observed a high rate of multidrug-resistant (MDR) S. sonnei bacteremia among persons experiencing homelessness (PEH). We aim to describe the wider epidemiology, clinical outcomes, and genomics of S. sonnei infections over time. A retrospective review of 163 patients with S. sonnei infections was undertaken from 2015 -2022. We collected demographic, clinical, and microbiological data over two time periods: historical (2015-2020) and recent (2021-2022). Severe shigellosis definition included hospitalization, bacteremia, or death. Whole genome sequencing was performed to identify genotype, infer relatedness, and predict antimicrobial resistance. S. sonnei infections rose from 8.3 (historical-period) to 56.5 cases/year (recent-period). Over time, the primary population characteristics associated with shigellosis shifted from MSM (45, 98%) to PEH (86,77%). The population intersection between MSM and PEH historically and recently was similar and occurred in three (6%) and ten (9%) of patients, respectively. Severe shigellosis was significantly higher in the recent compared to historical period (69 [61%] versus 7 [14%], p<0.001). A dominant clone of MDR S. sonnei, 3.6.1.1.2 (CipR.MSM5), emerged with resistance to all first and second-line agents yet with susceptibility to ceftriaxone. We observed a substantial increase in severe shigellosis and shift from sexually transmitted S. sonnei infections in MSM to likely environmental transmission among PEH. More severe disease associated with the 3.6.1.1.2 clone of MDR S. sonnei in PEH could be a result of underlying vulnerabilities of the affected population.

Eco-friendly synthesis of ZnO nanoparticles fabricated using Fioria vitifolia L. and their Biomedical Potentials

The present study aimed to environmentally friendly synthesis of ZnO NPs using Fioria vitifolia leaf extracts which provides a sustainable and green approach for production of NPs. The produced ZnO NPs were evaluated using various spectrum approaches (UV-vis, FTIR XRD, TEM and EDAX). The synthesized ZnO NPs was confirmed by UV-Visible spectroscopy exhibited a peak at 370 nm. SEM imaging revealed a flash-like and needle-like bottom morphology. Fourier-transform infrared spectroscopy (FTIR) analysis detected vibrations corresponding to alcohols, halides, and aromatics functional groups. TEM showed spherical-shaped NPs with an average diameter of 11 nm. XRD analysis exhibited distinct peaks at 2θ values of 31.7°, 34.3°, 36.2°, 47.4°, 56.6°, 62.8°, 66.4°, 67.9°, 69.1°, and 76.8°, corresponding to the crystallographic planes (100), (002), (101), (102), (110), (103), (200), (112), (201), (004), and (202) planes respectively. The antibacterial activity demonstrated significant zones of inhibition against E. coli (17±0.6 mm) and S. aureus (23.7±0.5 mm), and inhibition of biofilm formation in S. aureus and C. albicans. Additionally, S. mutans exhibited the highest sensitivity to the minimum inhibitory concentration (MIC) of ZnO NPs, with complete inhibition occurring at 7.5 μg/mL. Furthermore, antioxidant DPPH assays exhibited IC50 values of 42 μg/mL. Additionally, the anti-inflammatory properties of ZnO NPs of F. vitifolia were evaluated in-vitro using models utilizing the human red blood cells (HRBC) membrane stabilization method (MSM), and it was shown to have an MSM of 83.87% at 250 μg/mL. Furthermore, ZnO NPs exhibited anticancer activity against the MDA-MB-231 breast cancer cell line with an IC50 value of 35.50 μg/mL. Toxicological evaluation of FV-ZnO nanoparticles in zebrafish (Danio rerio) embryos indicated low toxicity at maximum concentration. These is first findings suggest that ZnO NPs synthesized from F. vitifolia leaf extracts possess significant antibacterial, antioxidant, anti-inflammatory, and anticancer properties. Additionally, their low toxicity in zebrafish embryos makes them suitable for further development in antimicrobial therapies with minimal side effects, offering a sustainable, biocompatible solution to tackle multidrug-resistant microbial infections.

Effect of Empirical Antimicrobial Therapy of Piperacillin-tazobactam Versus Carbapenems on Mortality for Patients with Sepsis from Nursing Homes.

Background Nursing home residents with a high risk of multidrug-resistant organism infection pose a complex challenge to broad-spectrum empirical antimicrobial therapy, particularly those infected with extended-spectrum β-lactamase-producing Enterobacteriaceae. The present study compared the efficacy of piperacillin-tazobactam and carbapenems as empirical antimicrobial treatments for patients with sepsis from nursing homes. Patients and Methods Using a nationwide inpatient database in Japan, we identified patients diagnosed with sepsis within two days of admission from nursing homes between 2018 and 2021. We selected patients who received intravenous piperacillin-tazobactam or carbapenems within two days of admission. In-hospital mortality was compared between the piperacillin-tazobactam and carbapenem groups using inverse probability of treatment weighting. Result We identified 8,025 eligible patients. Of these, 3,391 (42%) received piperacillin-tazobactam, and 4,634 (58%) received carbapenems within 2 days of admission. The inverse probability of treatment weighting analysis showed no significant difference in in-hospital mortality between the groups (31.6% in the piperacillin-tazobactam group and 32.8% in the carbapenem group; risk difference, 1.2%; 95% confidence interval, -3.2% to 0.9%). Conclusions Carbapenems and piperacillin-tazobactam as empirical antimicrobial therapy in patients with sepsis from nursing homes were associated with comparable in-hospital mortality rates. These findings highlight the importance of making decisions regarding broad-spectrum empirical antimicrobial therapy.

The tigecycline resistance mechanisms in Gram-negative bacilli.

Tigecycline, hailed as a pivotal agent in combating multidrug-resistant bacterial infections, confronts obstacles posed by the emergence of resistance mechanisms in Gram-negative bacilli. This study explores the complex mechanisms of tigecycline resistance in Gram-negative bacilli, with a particular focus on the role of efflux pumps and drug modification in resistance. By summarizing these mechanisms, our objective is to provide a comprehensive understanding of tigecycline resistance in Gram-negative bacilli, thereby illuminating the evolving landscape of antimicrobial resistance. This review contributes to the elucidation of current existing tigecycline resistance mechanisms and provides insights into the development of effective strategies to manage the control of antimicrobial resistance in the clinical setting, as well as potential new targets for the treatment of tigecycline-resistant bacterial infections.

Antimicrobial Peptides: The Game-Changer in the Epic Battle Against Multidrug-Resistant Bacteria.

The rapid progress of antibiotic resistance among bacteria has prompted serious medical concerns regarding how to manage multidrug-resistant (MDR) bacterial infections. One emerging strategy to combat antibiotic resistance is the use of antimicrobial peptides (AMPs), which are amino acid chains that act as broad-spectrum antimicrobial molecules and are essential parts of the innate immune system in mammals, fungi, and plants. AMPs have unique antibacterial mechanisms that offer benefits over conventional antibiotics in combating drug-resistant bacterial infections. Currently, scientists have conducted multiple studies on AMPs for combating drug-resistant bacterial infections and found that AMPs are a promising alternative to conventional antibiotics. On the other hand, bacteria can develop several tactics to resist and bypass the effect of AMPs. Therefore, it is like a battle between the bacterial community and the AMPs, but who will win? This review provides thorough insights into the development of antibiotic resistance as well as detailed information about AMPs in terms of their history and classification. Furthermore, it addresses the unique antibacterial mechanisms of action of AMPs, how bacteria resist these mechanisms, and how to ensure AMPs win this battle. Finally, it provides updated information about FDA-approved AMPs and those that were still in clinical trials. This review provides vital information for researchers for the development and therapeutic application of novel AMPs for drug-resistant bacterial infections.

Failure mode and effects analysis-based strategies for controlling multidrug-resistant organism infections in cancer patients.

In the context of advancing medical procedures, postoperative infections in cancer patients, particularly those involving multidrug-resistant organisms, have become a significant clinical concern. This study aims to comprehensively and systematically evaluate the effectiveness of infection prevention and control for multidrug-resistant organisms (MDROs) in postoperative cancer patients using Failure Mode and Effects Analysis (FMEA). This study was conducted in a tertiary A-level cancer specialty hospital in China, employing Failure Mode and Effects Analysis (FMEA) to assess the risks of hospital infections. Intervention measures were implemented for high-risk and medium-high-risk factors. Through the hospital's infection information system, data on patients who underwent surgical treatment from 2017 to 2022 were extracted. Data from 2017 to 2019 served as the control group, and data from 2020 to 2022 as the intervention group, to compare the changes in hospital infection incidence and MDRO infection incidence before and after the intervention. Categorical data were described in terms of frequency and percentage. The chi-square test was utilized for statistical inference to assess the differences in infection rates before and after the intervention. Prior to the intervention (2017-2019), the incidence rate of hospital infections was 1.66%, which decreased to 1.22% after the intervention (2020-2022), showing a statistically significant difference (χ2 = 48.83, P < 0.001). The incidence rate of MDRO infections also decreased from 1.808‰ before the intervention to 1.136‰ after the intervention, with a statistically significant difference (χ2 = 11.417, P = 0.001). This study confirms the effectiveness of the FMEA method in preventing and controlling MDRO infections in postoperative cancer patients. It highlights the practicality and value of widespread adoption of this method, particularly in the context of the COVID-19 pandemic.