Treatment Of Bacterial Infections Research Articles

Serum Pharmacokinetics and Bone Penetration of Novel Broad-Spectrum Anti-MRSA Agent Levonadifloxacin in Wistar Rats.

Objectives: Levonadifloxacin (IV) and alalevonadifloxacin (oral) are novel broad-spectrum anti-methicillin-resistant Staphylococcus aureus (S. aureus) agents based on novel benzoquinolizine core. Both are recently approved in India for the treatment of acute bacterial skin and skin structure infections, including diabetic foot infections and concurrent bacteremia. The present investigation reports the findings from preclinical pharmacokinetic (PK) studies that support the development of levonadifloxacin as a treatment option for bone and joint infections (BJIs). Methods: PK profiles of levonadifloxacin were obtained in serum, and/or various anatomical segments of femoral bone such as whole bone (WB), hard bone (HB), and bone marrow (BM) following subcutaneous administration of levonadifloxacin single doses at 50, 100, 200, and 400 mg/kg, as well as multiple doses at 200 mg/kg (BID (two times a day), 6 hours apart) for 5 days in Wistar rats. Results: The distribution of levonadifloxacin in bone was rapid, and the extent of distribution (B/S ratio; bone-to-serum area under the concentration-time curve ratio) was nearly comparable across bone segments. In single-dosage PK studies, the mean B/S ratio in WB, HB, and BM was 0.40, 0.33, and 0.34, respectively; however, in 5 days' repeated dose studies, it increased to 1.01, 1.14, and 0.61, respectively. Conclusions: On the basis of bone PK data in Wistar rat and ever-growing clinical experience in terms of safety and efficacy, levonadifloxacin has the potential to offer a well-differentiated therapy for the treatment of BJIs.

Redox-responsive degradation of antimicrobials with programmable drug release for enhanced antibacterial activity

The global crisis of antibiotic resistance has impelled the exigency to develop more effective drug delivery systems for the treatment of bacterial infection. The development of possessing high biocompatibility and targeted delivery of antimicrobials remains a persisting challenge. For programmable release of efficient antimicrobials in infection sites to enhance antibacterial activity, herein, we fabricated diselenide-bridged mesoporous organosilica nanoparticle-supported silver nanoparticles (Ag NPs) with high drug-loading capacity for the co-delivery of tobramycin (TOB) within one drug delivery system (Ag-MON@TOB (Se)). The resultant Ag-MON@TOB (Se) exhibited favorable biocompatibility due to its high stability in the physiological condition. Notably, such Ag-MON@TOB (Se) manifested a programmable structural destabilization to trigger sequential drug release in response to the oxidative stimuli within the bacterial infection microenvironment. In contradistinction to the oxidation-stable disulfide bond moieties within the framework of the nanocarrier (Ag-MON@TOB (S)), the Ag-MON@TOB (Se) with its programmed drug release behavior augmented prominent antibacterial therapy both in vitro and in vivo. This work represents a promising strategy for programmable drug release by harnessing a responsive degradable vehicle to enhance the treatment of bacterial infection.

Single-crystal structure, Hirshfeld surface and DFT analyses of chrysomycin A, a marine microbe-derived promising agent for anticancer and antimicrobial therapy

Chrysomycin A (CA) is an important Streptomyces-derived aromatic polyketide with therapeutic potential for treatment of cancer and bacterial infections. In order to prepare highly pure CA for new drug development, a simple and effective strategy to crystallize CA was firstly developed by the liquid phase diffusion method in this work. The single-crystal structure of CA and its Hirshfeld surface property analyses showed that the asymmetric unit of CA crystal consists of one CA molecule and a water in the orthorhombic space group P212121 and it has π-π interactions between benzene rings. CA crystal stacking is consolidated by three intermolecular hydrogen bonds including carbonyl/keto-C-O···H(water), naphthalene-C-O···H(water) and glycoside-O-H···O(water) and van der Waals forces. Furthermore, the HOMO-LUMO energy gap, UV-vis spectral parameters, electrostatic potential, mullliken charge and nonlinear optical properties analyzed in DFT calculations. These results pave a fundamental way for the production of CA using the feasible crystallization approach and the study of molecular mechanisms of action (MoA).

Ceftazidime with avibactam for treating severe aerobic Gram-negative bacterial infections: technology evaluation to inform a novel subscription-style payment model.

To limit the use of antimicrobials without disincentivising the development of novel antimicrobials, there is interest in establishing innovative models that fund antimicrobials based on an evaluation of their value as opposed to the volumes used. The aim of this project was to evaluate the population-level health benefit of ceftazidime-avibactam in the NHS in England, for the treatment of severe aerobic Gram-negative bacterial infections when used within its licensed indications. The results were used to inform National Institute for Health and Care Excellence guidance in support of commercial discussions regarding contract value between the manufacturer and NHS England. The health benefit of ceftazidime-avibactam was first derived for a series of high-value clinical scenarios. These represented uses that were expected to have a significant impact on patients' mortality risks and health-related quality of life. Patient-level costs and health-related quality of life of ceftazidime-avibactam under various usage scenarios compared with alternative management strategies in the high-value clinical scenarios were quantified using decision modelling. Results were reported as incremental net health effects expressed in quality-adjusted life-years, which were scaled to 20-year population in quality-adjusted life-years using infection number forecasts based on data from Public Health England. The outcomes estimated for the high-value clinical scenarios were extrapolated to other expected uses for ceftazidime-avibactam. The clinical effectiveness of ceftazidime-avibactam relative to its comparators was estimated by synthesising evidence on susceptibility of the pathogens of interest to the antimicrobials in a network meta-analysis. In the base case, ceftazidime-avibactam was associated with a statistically significantly higher susceptibility relative to colistin (odds ratio 7.24, 95% credible interval 2.58 to 20.94). The remainder of the treatments were associated with lower susceptibility than colistin (odds ratio < 1). The results were sensitive to the definition of resistance and the studies included in the analysis. In the base case, patient-level benefit of ceftazidime-avibactam was between 0.08 and 0.16 quality-adjusted life-years, depending on the site of infection and the usage scenario. There was a high degree of uncertainty surrounding the benefits of ceftazidime-avibactam across all subgroups, and the results were sensitive to assumptions in the meta-analysis used to estimate susceptibility. There was substantial uncertainty in the number of infections that are suitable for treatment with ceftazidime-avibactam, so population-level results are presented for a range of scenarios for the current infection numbers, the expected increases in infections over time, and rates of emergence of resistance. The population-level benefit varied substantially across the scenarios, from 531 to 2342 quality-adjusted life-years over 20 years. This work has provided quantitative estimates of the value of ceftazidime-avibactam within its areas of expected usage within the NHS. Given existing evidence, the estimates of the value of ceftazidime-avibactam are highly uncertain. Future evaluations of antimicrobials would benefit from improvements to NHS data linkages, research to support appropriate synthesis of susceptibility studies, and application of routine data and decision modelling to assess enablement value. No registration of this study was undertaken. This award was funded by the National Institute for Health and Care Research (NIHR) Policy Research Programme (NIHR award ref: NIHR135592), conducted through the Policy Research Unit in Economic Methods of Evaluation in Health and Social Care Interventions, PR-PRU-1217-20401, and is published in full in Health Technology Assessment; Vol. 28, No. 73. See the NIHR Funding and Awards website for further award information.

Isolation and Characterization of Lytic Bacteriophage vB_KpnP_23: A Promising Antimicrobial Candidate Against Carbapenem-Resistant Klebsiella pneumoniae

The global health threat posed by carbapenem-resistant Klebsiella pneumoniae (CRKP) is exacerbated by the limited availability of effective treatments. Bacteriophages are promising alternatives to conventional antimicrobial agents. However, current phage databases are limited. Thus, identifying and characterizing new phages could provide biological options for the treatment of multi-drug resistant bacterial infections. Here, we report the characterization of a novel lytic phage, vB_KpnP_23, isolated from hospital sewage. This phage exhibited potent activity against carbapenemase-producing CRKP strains and was characterised by an icosahedral head, a retractable tail, and a genome comprising 40,987 base pairs, with a G+C content of 51%. Capable of targeting and lysing nine different capsule types (K-types) of CRKP, including the clinically relevant ST11-K64, it demonstrated both high bacteriolytic efficiency and stability in various environmental contexts. Crucially, vB_KpnP_23 lacks virulence factors, antimicrobial resistance genes, or tRNA, aligning with the key criteria for therapeutic application. In vitro evaluation of phage-antibiotic combinations revealed a significant synergistic effect between vB_KpnP_23 and meropenem, levofloxacin, or amikacin. This synergy could lead to an 8-fold reduction in the minimum inhibitory concentration (MIC), suggesting that integrated treatments combining this phage with the aforementioned antibiotics may substantially enhance drug effectiveness. This approach not only extends the clinical utility of these antibiotics but also presents a strategic advance in combating antibiotic resistance. Specifically, it underscores the potential of phage-antibiotic combinations as a powerful tool in the treatment of infections caused by CRKP, offering a promising avenue to mitigate the public health challenges of antibiotic-resistant pathogens.

A BODIPY derivative for PDT/PTT synergistic treatment of bacterial infections

Phototherapeutic antimicrobials, including photodynamic and photothermal antimicrobials, are considered effective alternatives for antibiotic strategy due to their broad-spectrum antibacterial activity and low risk of resistance. Here, a 4,4-difluoro-4-bora-3a,4a-diaza-s-indacene (BODIPY) derivative containing triphenylamine groups was co-assembled with Pluronic F-127 (F-127) to form nanoparticles (BICF NPs). BICF NPs have excellent photodynamic and photothermal properties and are demonstrated to be effective in inhibiting and disrupting bacterial biofilms, thereby promoting the healing of subcutaneous abscesses. This work provides a new avenue for antibiotic replacement therapy.

Self-assembled near-infrared-photothermal antibacterial Hericium erinaceus β-glucan/tannic acid/Fe (III) hydrogel for accelerating infected wound healing

Bacterial infection severely hinders skin wound healing, highlighting the critical application value of developing antibacterial and anti-inflammatory hydrogel dressings. In this work, we focused on β-glucan from Hericium erinaceus as the research object, and proposed a solvent-induced combined temperature manipulation technique to trigger multilevel self-assembly of β-glucan. Furthermore, we incorporated green synthesized near-infrared photosensitizer tannic acid/iron (III) complex into the system. A hydrogel with exceptional antibacterial properties, capable of responding to near-infrared photothermal stimuli while exhibiting remarkable stiffness and structural consistency, was successfully synthesized. Under near-infrared radiation, HEBG/TA/Fe hydrogels produced local hyperthermia and exhibited excellent antibacterial activity against bacteria-infected wounds. Moreover, the HEBG/TA/Fe hydrogel demonstrates its ability to regulate cytokines by effectively inhibiting the production of inflammatory mediators TNF-α and IL-6, while simultaneously enhancing the expression of cell proliferation factor KI-67 and markers associated with angiogenesis such as CD31 and α-SMA. Notably, the results of tissue staining revealed that NIR + HEBG/TA/Fe5 hydrogel could effectively promoting granulation and vascularization, improving collagen deposition in infected wounds thereby accelerating the healing process. These findings indicate that mixed hydrogels exhibit potential as viable options for the treatment of bacterial infections.

Preliminary Study to Assess the Antioxidant and Antibacterial Activity of Extracts from the Leaves of Morelia Senegalensis (A Rich)

frican populations rely heavily on traditional medicine, which uses plants to treat human and animal diseases. However, scientific validation of this empirical knowledge concerning the efficacy, toxicity and dosage of the proposed treatments is urgently needed. The aim of this study was to evaluate the antioxidant and antibacterial activity of Morelia senegalensis leaf extracts on the 2,2-diphenyl-1-picrylhydrawyl (DPPH) radical and the (2,2’-azino-bis-(3-ethylbenzothiazoline-6-sulfonic) acid) ABTS cation radical and on four reference bacterial strains (E. coli 25922, E. coli 35218, E. faecalis 29212 and S. aureus 29213) using protocols already described in the literature. The phytochemical screening test revealed the presence of flavonoids, alkaloids, tannins, saponins, reducing compounds and sterols in Morelia senegalensis leaves. All the extracts showed antioxidant activity to varying degrees. The most active ethyl acetate (AE) extract had half-maximum inhibition concentration (IC50 )of 0.33 and 0.62 mg/mL for the ABTS and DPPH tests respectively, followed by DCM and EB extracts with IC50 of 0.86 and 0.88 mg/mL for the ABTS test respectively, while the vitamin C used as a reference was more active with IC50 of 0.04 and 0.06 mg/mL. Antibacterial activity showed inhibition diameters ranging from 7 to 16 mm depending on the concentration and strain considered. The ethyl acetate fraction was the most active on S aureus 29213 with an inhibition diameter of 16 mm at 50 mg/mL. These interesting results were confirmed by the Minimal Inhibitory Concentration inhibitory (MIC) and Minimal Bacterial Concentration (MBC) studies, which showed that all the extracts had a bactericidal effect on all the studied strains. Morelia senegalensis plant has shown promising preliminary results in the treatment of bacterial infections. Further studies are needed to isolate and characterize the secondary metabolites contained in the leaves of this plant.

Synergistic Activity of Antibiotics and Bio Active Plant Extract: Astudy Against Mdr Gram Negative Bacteria in Kirkuk City

Increasing multidrug resistance (MDR) is becoming a problematic issue worldwide. Finding alternatives to cope with this rising problem is becoming crucial for community healthcare. The present study aimed to investigate the antibacterial activityCopper oxide nanoparticles (CuONPs) synthesised using hawthorn fruit extract against different MDR gram-negative bacteria isolates. CuoNPs were synthesized from Fresh hawthorn fruits (Crataegus). The biosynthesized copper oxide nanoparticles were Characterization of the synthesised nanoparticles was performed using UV-visible spectroscopy, Scanning Electron Microscopy (SEM), Fourier-transform infrared spectroscopy (FT-IR), and X-ray diffraction (XRD) to confirm CuONP production and assess their properties. Antibacterial activity was determined by disc diffusion and the healthy diffusion method. The considerable inhibitory action of hawthorn fruit extract was observed in gram-negative bacteria isolates. Also, the green synthesised CuoNPs demonstrated remarkable antibacterial activity against two human pathogenic bacteria when combined with commercially available antibiotics. The current study suggested that CuoNPs have become an essential approach for nanobiotechnology applications in the development of antibacterial treatments for different bacterial infections, particularly for non-treatable antibiotic resistance pathogen.

Synergistic bactericidal effect of antimicrobial peptides and copper sulfide-loaded zeolitic imidazolate framework-8 nanoparticles with photothermal therapy

Antimicrobial resistance (AMR) has emerged as a significant threat to human health. Antimicrobial peptides (AMPs) have proven to be an effective strategy against antibiotic-resistant bacteria, given their capacity to swiftly disrupt microorganism membranes and alter cell morphology. A common limitation, however, lies in the inherent toxicity of many AMPs and their vulnerability to protease degradation within the body. Photothermal therapy (PTT) stands out as a widely utilized approach in combating antibiotic-resistant bacterial infections, boasting high efficiency and non-invasive benefits. To enhance the stability and antibacterial efficacy of AMPs, a novel approach involving the combination of AMPs and PTT has been proposed. This study focuses on the encapsulation of At10 (an AMP designed by our group), and copper sulfide nanoparticles (CuS NPs) within zeolitic imidazolate framework-8 (ZIF-8) to form nanocomposites (At10/CuS@ZIF-8). The encapsulated CuS NPs exhibit notable photothermal properties upon exposure to near-infrared radiation. This induces the cleavage of ZIF-8, facilitating the release of At10, which effectively targets bacterial membranes to exert its antibacterial effects. Bacteria treated with At10/CuS@ZIF-8 under light radiation exhibited not only membrane folding and intracellular matrix outflow but also bacterial fracture. This synergistic antibacterial strategy, integrating the unique properties of AMPs, CuS NPs, and pH responsiveness of ZIF-8, holds promising potential for widespread application in the treatment of bacterial infections.

Off-Label Use of Dalbavancin in Enterococcus spp. Abscess and Streptococcus pneumoniae Bacteremia Secondary to Septic Arthritis: A Retrospective Case Report

Dalbavancin, a semi-synthetic lipoglycopeptide with an extended half-life that allows for weekly dosing, is currently approved for the treatment of bacterial skin and soft tissue infections caused by susceptible gram-positive organisms. This case report discusses the successful treatment of septic arthritis with dalbavancin in a 38-year-old obese male. Septic arthritis, commonly caused by Staphylococcus aureus and Streptococcus species, was diagnosed in this patient following a mechanical fall that led to worsening shoulder pain. Given the patient’s morbid obesity and concerns about antibiotic penetration, dalbavancin 1500 mg IV biweekly was chosen for its extended half-life and ease of administration. This case underscores dalbavancin’s efficacy in managing septic arthritis in obese patients, offering a convenient alternative to traditional therapies that require a peripherally inserted central catheter (PICC line), frequent dosing, therapeutic monitoring, and prolonged hospital stays. Despite its higher cost, dalbavancin’s advantages include reduced need for PICC lines, additional staff and resources to monitor therapeutic drug levels, and fewer complications, which can offset some expenses. To our knowledge, this is the first documented case investigating the use of dalbavancin for enterococcal septic arthritis with a biweekly dosing regimen.

Construction of aptamers-modified plasmonic GO/urchin-like Au nanoparticles with enhanced photothermal performance and their efficient capture and elimination of Staphylococcus aureus

Here, aptamers-modified graphene oxide/urchin-like Au nanoparticles (Apt-GUANPs) were developed for efficient capture and photothermal therapy (PTT) of Staphylococcus aureus (S. aureus). Specifically, anisotropic UANPs were first prepared, and the excellent photothermal property was related to the localized surface plasmon resonance (LSPR) in the near infrared (NIR) region caused by sharp branching. Then GO, which was used to enhance the photothermal effect, was added and assembled into GUANPs by electrostatic action. Infrared images showed that GUANPs exhibited a stronger photothermal effect than UANPs. Under the irradiation of 808 nm laser, the photothermal conversion efficiency (η) of GUANPs was as high as 40.5 %, which was attributed to the enhanced optical response of GUANPs at 808 nm and the strong plasmonic coupling effect between tightly packed UANPs loaded on GO surfaces. Aptamers were modified on the surfaces of GUANPs for specific capture of S. aureus, with the capture efficiency of up to 72 %. Utilizing the specific capture ability of aptamers and the excellent photothermal property of GUANPs, Apt-GUANPs exhibited the strong photothermal killing ability against S. aureus. Therefore, Apt-GUANPs will be a promising and efficient photothermal agent, and will have a great application prospect in the treatment of bacterial infections in the future.

The Pharmacokinetics of Ceftazidime Following its Intravenous Administration in Dogs

Ceftazidime is a beta-lactam that is used in the treatment of bacterial infections in humans and companion animals, such as dogs and cats. It is prescribed to treat gram-negative infections, especially those caused by Pseudomonas aeruginosa. This study aimed to compare the pharmacokinetics of ceftazidime using a microbiological assay to evaluate the adequacy of the proposed dosage regimens for susceptible gram-negative bacteria. For this purpose, five healthy mongrel male dogs, with a mean age of four years and an average weight of 19.1 kg, were administered a single intravenous bolus dose of ceftazidime (20 mg/kg). Plasma concentrations were measured using a microbiological assay, and dosage regimens were established by integrating pharmacokinetics data with pharmacodynamics parameters. The results showed that ceftazidime was rapidly distributed to the peripheral tissues (0.189 L/kg), with a half-life of 1.15 hours and a clearance rate of 0.166 L/hr./kg. The results obtained from the pharmacokinetics-pharmacodynamic integration suggested 20 mg/kg q8 hours of ceftazidime for susceptible gram-negative bacteria with a Minimum Inhibitory Concentration of ≤ 8 µg/ml, and 20 mg /kg q12 hours of ceftazidime for susceptible gram-negative bacteria with a Minimum Inhibitory Concentration of ≤ 4 µg/ml. In conclusion, a mild correlation was observed between the dogs’ weight and the ceftazidime half-life, which led to an adjustment of the proposed dosage regimen to 20 mg/kg q8 hours.

Formulation Development of Mucoadhesive Vaginal Gel of Secnidazole and Voriconazole.

Purpose: Over the preceding decades, developing conventional drug delivery in to modified form has acquired importance in the pharmaceutical industry. Vaginal drug delivery system offers localized drug administration of drug and also avoids unwanted side effects of oral drug delivery. Vaginal drug delivery system has significant role in medical practice. Even though VDDS has a lot of advantages over the other routes of administration. The goal of developing the Mucoadhesive Vaginal Gel was to achieve the synergistic effect of voriconazole and secnidazole in the treatment of bacterial and fungal vaginal infections. Method: Mucoadhesive antimicrobial vaginal gel was optimised using Design expert software using Carbopol 934, HPMC K4M polymers. Result: Formulation was evaluated for various rheological parameters ,antimicrobial activity, invitro drug release and stability study. The spreadability and pH was found to be 5.5 to 7.4 cm and 4.12. Its compatible with vaginal pH. The selected optimized F8 formulation is the best formulation and the drug ratio is 2:1. and optimum gel viscosity is 1874 cps. antimicrobial study revealed that faster drug release of test formulation was compared to marketed product. It indicates as inhibition zone. Conclusion: The combination of drugs can serves as better option for treating vaginitis, compared to single drug formulation. Mucoadesion increases contact time of drug with affected area which rendered formulation more effective.

Rapid design of combination antimicrobial therapy against Acinetobacter baumannii

Treatment of serious bacterial infections with antimicrobial agents, such as antibiotics, is a major clinical challenge, because of growing bacterial resistance to multiple agents. Combination therapy (i.e. combined dosing of more than one agent) is often used for the purpose, but its systematic design remains a challenge. To address this, we recently reported a method to mathematically model bacterial response to antimicrobial agents, and to use this model for systematic design of clinically relevant combination therapy. The method relies on (a) longitudinal data of bacterial load, estimated from optical density measurements during time-kill experiments in an automated instrument, and (b) use of these data to fit a mathematical model for combination therapy design. In this work, we studied an application of the proposed method to (a) an important bacterial pathogen (Acinetobacter baumannii) and (b) two cases of antibiotic combinations (ceftazidime / amikacin and ceftazidime / avibactam) in synchronous and asynchronous dosing, not otherwise studied to date. Following the proposed method, optical density based data of bacterial load under antibiotic exposure for 20 h were used to calibrate the mathematical model and subsequently predict outcomes of various dosing regimens with clinically relevant pharmacokinetics. Representative predictions by the mathematical model were tested in vitro in a hollow fiber infection model over 120 h. Test outcomes validated these predictions. Collectively, this study both provides guidance for design of A. baumannii infection treatments with the agents studied and underscores the broader applicability of the proposed method for design of clinically relevant combination therapy.

Prophages are Infrequently Associated With Antibiotic Resistance in Pseudomonas aeruginosa Clinical Isolates.

Antimicrobial resistance (AMR) is a significant obstacle to the treatment of bacterial infections, including in the context of Pseudomonas aeruginosa infections in patients with cystic fibrosis (CF). Lysogenic bacteriophages can integrate their genome into the bacterial chromosome and are known to promote genetic transfer between bacterial strains. However, the contribution of lysogenic phages to the incidence of AMR is poorly understood. Here, in a set of 184 clinical isolates of Pseudomonas aeruginosa collected from 83 patients with CF, we evaluate the links between prophages and both genomic and phenotypic AMR associated with five anti-pseudomonal antibiotics: tobramycin, colistin, ciprofloxacin, meropenem, aztreonam, and tazobactam. We find that P. aeruginosa isolates contain on average XX +/- XX predicted prophages. There was no significant association between the number of prophages per isolate and the mean inhibitory concentration (MIC) for any of these antibiotics. We then investigate the relationship between particular prophages and AMR. We identify only a single lysogenic phage that is associated with phenotypic resistance to an antibiotic, tobramycin. Consistent with this association, we identify AMR genes associated with resistance to tobramycin in these strains and find that they are proximal to but not encoded by prophages within the bacterial genome. These findings suggest that prophages are infrequently associated with the AMR genes in clinical isolates of P. aeruginosa.

Chloramphenicol versus ceftriaxone for the treatment of pneumonia and sepsis in elderly patients with advanced dementia and functional disability. A propensity-weighted retrospective cohort study.

Sepsis and pneumonia in the elderly comprise a significant portion of medical admissions. Chloramphenicol has been used in Israel for treatment of bacterial infections, without evidence regarding its efficacy and safety. We aimed to examine whether chloramphenicol was associated with similar outcomes to ceftriaxone, for treatment of sepsis and pneumonia in the elderly with dementia and functional disability. Patients over 75, with dementia and functional disability, admitted to the internal medicine ward at Beilinson Hospital between 2011 and 2021, with community-acquired aspiration pneumonia or sepsis of undetermined source were included. Patients with mild dementia and independent in their activities of daily living were excluded. Primary outcome was 30- and 90-day all-cause mortality. A propensity-weighted multivariable model was constructed using inverse probability of treatment weighting. Results were expressed as OR with 95% CI. In total, 1558 patients were included: 512 treated with chloramphenicol and 1046 with ceftriaxone. The cohort consisted of elderly patients (mean age 87 ± 6.2 years) with comorbidities; 30- and 90-day all-cause mortality were similar [222/512 (43.3%) versus 439/1046 (41.9%) P = 0.602, and 261/512 (50.9%) versus 556/1046 (53.1%) P = 0.419, respectively]. Propensity-weighted, logistic multivariable analysis for 30- and 90-day all-cause mortality revealed similar mortality rates for chloramphenicol and ceftriaxone (OR 1.049 95% CI 0.217-1.158, OR 0.923 95% CI 0.734-1.112, respectively). In this retrospective cohort of elderly debilitated patients hospitalized with pneumonia and sepsis, we found no difference in 30- and 90-day mortality between those treated with chloramphenicol or ceftriaxone. Further studies should determine the efficacy and safety of chloramphenicol in this population.

Engineered Bacteriophage-Polymer Nanoassemblies for Treatment of Wound Biofilm Infections.

The antibacterial efficacy and specificity of lytic bacteriophages (phages) make them promising therapeutics for treatment of multidrug-resistant bacterial infections. Restricted penetration of phages through the protective matrix of biofilms, however, may limit their efficacy against biofilm infections. Here, engineered polymers were used to generate noncovalent phage-polymer nanoassemblies (PPNs) that penetrate bacterial biofilms and kill resident bacteria. Phage K, active against multiple strains of Staphylococcus aureus, including methicillin-resistant S. aureus (MRSA), was assembled with cationic poly(oxanorbornene) polymers into PPNs. The PPNs retained phage infectivity, while demonstrating enhanced biofilm penetration and killing relative to free phages. PPNs achieved 3-log10 bacterial reduction (∼99.9%) against MRSA biofilms in vitro. PPNs were then incorporated into Poloxamer 407 (P407) hydrogels and applied onto in vivo wound biofilms, demonstrating controlled and sustained release. Hydrogel-incorporated PPNs were effective in a murine MRSA wound biofilm model, showing a 1.5-log10 reduction in bacterial load compared to a 0.5 log reduction with phage K in P407 hydrogel. Overall, this work showcases the therapeutic potential of phage K engineered with cationic polymers for treating wound biofilm infections.

Isolation and Identification of Staphylococcus Aureus in Devices at a Gym in São Luís – MA

Objective: The study aimed to evaluate the presence of Staphylococcus aureus on equipment surfaces in a gym in São Luís - MA. Theoretical Framework: In recent decades, the number of gyms has increased significantly, in the search for health and good body shape. On the other hand, the presence of organic fluids deposited on the devices provides a favorable environment for pathogenic microorganisms. Method: This was an exploratory study of an experimental nature, carried out using non-probability sampling. Five pieces of equipment for collective use were analyzed. Collections were carried out with 'swabs' in places of greatest contact between users and devices. Samples were immersed in tubes with BHI broth and sent to the Federal University of Maranhão to be sown in selective culture media and incubated at 37°C for 24h, and biochemical tests were sequentially carried out. Results and Discussion: The samples were positive for Staphylococcus aureus in all the devices analyzed, which shows that the cleaning process of the devices was not being carried out efficiently, offering risks of contamination to users. Environments such as gyms have a wide distribution of microorganisms, due to the sharing of equipment and inadequate hygiene, which contribute to the transmission of diseases. Research Implications: In this context, the use of antiseptic solutions that are described in the ANVISA manuals is recommended. Originality/Value: This study contributes to the literature by expanding and strengthening the development of interdisciplinary work, with the aim of generating information about the fight, diagnosis and treatment of Bacterial Infection.

Two Novel Hydrate Salts of Norfloxacin with Phenolic Acids and Their Physicochemical Properties.

Norfloxacin (NORF) is a broad-spectrum quinolone that is widely utilized for the treatment of various bacterial infections and is considered one of the most commonly used fluoroquinolone antibiotics. However, NORF's clinical utility is limited by its poor water solubility and relatively low oral bioavailability. This study presents an optimization and synergistic enhancement approach through salt/co-crystal, aiming to maximize the biopharmaceutical properties of NORF with the use of phenolic acid. Following this strategy, two new hydrate salts of NORF with phenolic acid, namely, NORF-3,5-DBA hydrate (salt 1) and NORF-VA hydrate (salt 2), were prepared and systematically confirmed. Two hydrate salts were produced by means of the slow evaporation crystallization method, and the structures were determined through single-crystal X-ray diffraction (SCXRD). Additionally, powder X-ray diffraction (PXRD), Fourier-transform infrared (FT-IR) spectroscopy, differential scanning calorimetry (DSC), thermogravimetric analysis (TGA), and high-performance liquid chromatography (HPLC) were applied to analyze the features of the two salts. The experimental results indicated that the formation of the two salts could enhance the solubility and improve the release behavior of NORF. Interestingly, the physicochemical properties of NORF were significantly improved as a result, leading to an enhancement in its antibacterial activity. This was demonstrated by the enhanced inhibition of bacterial strains and the lower minimum inhibitory concentration values.