Site Infection Research Articles

Evaluation of hospital-onset bacteraemia and fungaemia in the USA as a potential healthcare quality measure: a cross-sectional study

BackgroundHospital-onset bacteraemia and fungaemia (HOB) is being explored as a surveillance and quality metric. The objectives of the current study were to determine sources and preventability of HOB in hospitalised...

Epidemiology of Chlamydia trachomatis and Repeat Positivity Following Detection in New York State.

In New York State, excluding New York City, chlamydia remains a persistent health concern. Our aim was to characterize chlamydia epidemiology and identify groups at higher risk of repeat positivity to inform targeted public health interventions. We analyzed demographic and clinical data of laboratory-confirmed chlamydia cases in New York State from 2015 to 2019. Repeat positivity was defined as a second positive chlamydia test within 31 to 365days of the initial positive test. We compared characteristics of individuals with single and repeat positivity and evaluated associations with repeat positivity using multivariable logistic regression models. During the study period, 176273 individuals were diagnosed with chlamydia, with 17253 experiencing repeat positivity. Repeat positivity was more common among individuals assigned female at birth. Key predictors of repeat positivity among females included non-Hispanic Black (adjusted odds ratio [aOR]: 1.33; 95% confidence interval [CI], 1.27-1.40) race/ethnicity, ages 13 to 19 (aOR: 1.62; 95% CI, 1.55-1.69), prior sexually transmitted infection (STI) diagnosis (aOR: 1.24; 95% CI, 1.18-1.31), symptomatic examination (aOR: 1.07; 95% CI, 1.02-1.13), and county/community (aOR: 1.10; 95% CI, 1.05-1.15) or private/public (aOR: 1.18; 95% CI, 1.11-1.25) provider. Among males, predictors included non-Hispanic Black (aOR: 1.57; 95% CI, 1.45-1.70) race/ethnicity, ages 13 to 19 (aOR: 1.27; 95% CI, 1.17-1.38), HIV coinfection (aOR: 1.30; 95% CI, 1.10-1.54), prior STI diagnosis (aOR: 1.31; 95% CI, 1.20-1.43), extragenital infection site (aOR: 2.59; 95% CI, 2.27-2.95), symptomatic examination (aOR: 1.21; 95% CI, 1.12-1.31), and county/community health (aOR: 1.09; 95% CI, 1.02-1.17) provider. Our findings provide valuable insights for sexual health interventions to prevent chlamydia transmission and recurrence. Prioritizing resources for prevention interventions and tailored sexual health promotion among non-Hispanic Black individuals is crucial. Additionally, targeted STI prevention efforts are needed for males who have sex with men and those initially diagnosed with extragenital infection. Research is warranted on STI prevention among people living with HIV or at high risk of HIV infection. Strengthening prevention strategies through Expedited Partner Therapy and sexual health education for individuals at risk of repeat positivity could enhance prevention efforts.

The Interactions of the Complement System with Human Cytomegalovirus.

The complement system is an evolutionarily ancient component of innate immunity that serves as an important first line of defense against pathogens, including viruses. In response to infection, the complement system can be activated by three distinct yet converging pathways (classical, lectin, and alternative) capable of engaging multiple antiviral host responses to confront acute, chronic, and recurrent viral infections. Complement can exert profound antiviral effects via multiple mechanisms including the induction of inflammation and chemotaxis to sites of infection, neutralization/opsonization of viruses and virally infected cells, and it can even shape adaptive immune responses. With millions of years of co-evolution and the ability to establish life-long infections, herpesviruses have evolved unique mechanisms to counter complement-mediated antiviral defenses, thus enabling their survival and replication within humans. This review aims to comprehensively summarize how human herpesviruses engage with the complement system and highlight our understanding of the role of complement in human cytomegalovirus (HCMV) infection, immunity, and viral replication. Herein we describe the novel and unorthodox roles of complement proteins beyond their roles in innate immunity and discuss gaps in knowledge and future directions of complement and HCMV research.

Florfenicol core–shell composite nanogels as oral administration for efficient treatment of bacterial enteritis

To reduce the bitterness of florfenicol, avoid its degradation by gastric acid, and enhance its antibacterial activity against Escherichia coli by targeting and slowly releasing drugs at the site of intestinal infection, with pectin as an anion carrier and chitosan oligosaccharides (COS) as a cationic carrier, florfenicol-loaded COS@pectin core nanogels were self-assembled by electrostatic interaction and then encapsulated in sodium carboxymethylcellulose (CMCNa) shell nanogels through the complexation of CMCNa and Ca2+ to prepare florfenicol core–shell composite nanogels in this study. The florfenicol core–shell composite nanogels were investigated for their formula choice, physicochemical characterization, pH-responsive performances, antibacterial activity, therapeutic efficacy, and in vitro and in vivo biosafety studies. The results indicated that the optimized formula was 0.6 g florfenicol, 0.79 g CMCNa, 0.30 g CaCl2, 0.05 g COS, and 0.10 g pectin, respectively. In addition, the mean particle diameter, polydispersity index, zeta potential, loading capacity, and encapsulation efficiency were 124.0 ± 7.2 nm, –22.9 ± 2.5 mV, 0.42 ± 0.03, 43.4 % ± 3.1 %, and 80.5 % ± 3.4 %, respectively. The appearance, lyophilized mass, resolvability, scanning electron microscopy (SEM), transmission electron microscopy (TEM), powder X-ray diffraction (PXRD), and fourier transform infrared (FTIR) showed that the florfenicol core–shell composite nanogels were successfully prepared. Florfenicol core–shell composite nanogels had satisfactory stability, rheology, and pH-responsiveness, which were conducive to avoid degradation by gastric acid and achieve targeted and slow release at intestinal infection sites. More importantly, florfenicol core–shell composite nanogels had excellent antibacterial activity against Escherichia coli, a satisfactory therapeutic effect, and good palatability. In vitro and in vivo biosafety studies suggested the great promise of florfenicol core–shell composite nanogels. Therefore, the prepared florfenicol core–shell composite nanogels may be helpful for the treatment of bacterial enteritis as a biocompatible oral administration.

Drug metabolism of ciprofloxacin, ivacaftor, and raloxifene by Pseudomonas aeruginosa cytochrome P450 CYP107S1

Drug metabolism is one of the main processes governing the pharmacokinetics and toxicity of drugs via their chemical biotransformation and elimination. In humans, the liver, enriched with cytochrome P450 (CYP) enzymes, plays a major metabolic and detoxification role. The gut microbiome and its complex community of microorganisms can also contribute to some extent to drug metabolism. However, during an infection when pathogenic microorganisms invade the host, our knowledge of the impact on drug metabolism by this pathobiome remains limited. The intrinsic resistance mechanisms and rapid metabolic adaptation to new environments often allow the human bacterial pathogens to persist, despite the many antibiotic therapies available. Here, we demonstrate that a bacterial CYP enzyme, CYP107S1, from Pseudomonas aeruginosa, a predominant bacterial pathogen in cystic fibrosis (CF) patients, can metabolize multiple drugs from different classes. CYP107S1 demonstrated high substrate promiscuity and allosteric properties much like human hepatic CYP3A4. Our findings demonstrated binding and metabolism by the recombinant CYP107S1 of fluoroquinolone antibiotics (ciprofloxacin and fleroxacin), a CF transmembrane conductance regulator potentiator (ivacaftor), and a SERM antimicrobial adjuvant (raloxifene). Our in vitro metabolism data were further corroborated by molecular docking of each drug to the heme active site using a CYP107S1 homology model. Our findings raise the potential for microbial pathogens modulating drug concentrations locally at the site of infection, if not systemically, via CYP-mediated biotransformation reactions. To our knowledge, this is the first report of a CYP enzyme from a known bacterial pathogen that is capable of metabolizing clinically utilized drugs.

Etiological analysis of ocular herpes virus infection.

To do the etiological analysis of ocular herps virus infection, revealing the pathogen species and the distribution of different virus types within the eye. Samples were collected from 2017 to 2021 at the Department of Ophthalmology, Peking University Third Hospital and tested using real-time PCR for common ocular viruses: herpes simplex virus 1 (HSV-1), cytomegalovirus (CMV), varicella-zoster virus (VZV) and Epstein-Barr virus (EBV). The pathogenesis of the different viruses was classified and analyzed according to the site of infection. Viral PCR detections were performed on 3627 samples collected over the 5-years and 649 (17.89%) samples contained one or more of the viruses tested. The overall detection rate of CMV was highest at 9.93%. Of all sample types, aqueous humor was the most common (1752 cases), of which 340 were positive (19.41% positive rate). Corneal samples were the next most common, with 1481 cases and 250 positive results (16.88% positive rate). CMV positivity was higher in aqueous humor and corneal samples than other viruses; vitreous body had the highest positive rate at 36.36% (20/55), among which 18 cases were VZV positive. Distribution of virus types differed among infection sites, with CMV the most common virus type detected in the cornea and aqueous humor, while VZV was the most common virus detected in the vitreous body.

Microbial Composition of Extracted Dental Alveoli in Dogs with Advanced Periodontitis.

Periodontitis is a serious gum infection that damages the soft tissue and destroys the bone supporting the teeth. The aim of the study was to investigate the microbiota using traditional microbiology plating and metagenomic sequencing of extracted tooth alveoli in dogs with severe periodontitis. Isolation of culturable microorganisms was performed as part of bacteriological testing to provide bacteriological diagnosis to veterinary surgeons. Metagenomic sequencing was performed using shotgun sequencing on the Illumina HiSeq system platform. The most prevalent species at sites of periodontal infection detected by metagenomic sequencing were Porphyromonas gulae, Prevotella spp., Tannerella forsythia, Porphyromonas crevioricanis, Porphyromonas cangingivalis, and Bacteroides heparinolyticus. Pasteurella, Streptococcus, and Neisseria were the most frequently isolated culturable bacteria from infected sites detected by traditional microbiologic methods. Metagenomic data revealed that these three genera accounted for only 1.6% of all microbiota at the sites of infection. Antimicrobial resistance patterns of the isolated bacteria included resistance to ampicillin, doxycycline, sulfamethoxazole-trimethoprim, ciprofloxacin, colistin, cefotaxime, and chloramphenicol. Antimicrobial-resistant genes detected using shotgun sequencing also showed resistance to aminoglycosides and macrolides. Dogs with periodontal infections carry bacteria that can cause bite infections in humans as well as multi-resistant isolates. Therefore, treatment and prophylaxis or periodontal disease of dogs is important from a One Health perspective.

Bed occupancy and nosocomial infections in the intensive care unit: A retrospective observational study in a tertiary hospital

Background. Healthcare-associated infections (HAI) are a major problem globally, contributing to prolonged hospital admissions and poor outcomes. Objective. To examine HAI incidence and risk factors in an intensive care unit (ICU) during high v. low occupancy periods. Methods. This retrospective, descriptive analysis investigated HAI incidence among adult patients admitted to the ICU at Chris Hani Baragwanath (CHBH) during a high (H2019) and low (L2020) occupancy. Data were extracted from the clinical records of 440 eligible patients. Results. We found an increased risk of HAI during H2019 compared with L2020 (relative risk (RR) 1.42, 95% confidence interval (CI) 1.03 - 1.94). The overall frequency density of HAI was 25/1 000 ICU days. There was no difference in the distribution of the site of infection (blood v. other) (p=0.27) or bacterial category (Gram stain) (p=0.62). Five organisms accounted for 89% of pathogens: Klebsiella (26%), Staphylococcus (21%), Acinetobacter (16%), Candida (16%) and Enterobacter (10%). The incidence of multidrug-resistant/extensively drug-resistant (MDR/XDR) organisms was 4.2-fold higher (95% CI 1.3 - 13.4) during H2019 compared with L2020. Logistic regression analysis revealed two independent predictors of nosocomial infection: ICU length of stay (odds ratio (OR) 1.12, 95% CI 1.02 - 1.22) and intercostal drain duration in days (OR 1.27, 95% CI 1.09 - 1.47). Conclusion. High occupancy in the ICU was associated with an increased risk of HAI and a greater incidence of MDR and XDR pathogens. Increasing ICU length of stay and invasive device duration were independent predictors of HAI.

Multiple impacts of the COVID-19 pandemic and antimicrobial stewardship on antimicrobial resistance in nosocomial infections: an interrupted time series analysis.

The emergency response to the COVID-19 pandemic may disrupt hospital management activities of antimicrobial resistance (AMR). This study aimed to determine the changing AMR trend over the period in China when stringent COVID-19 response measures were implemented. This retrospective study was conducted in a designated hospital for COVID-19 patients in Guangzhou, China from April 2018 to September 2021. The prevalence of 13 antimicrobial-resistant bacteria was compared before and after the COVID-19 responses through Chi-square tests. Interrupted time series (ITS) models on the weekly prevalence of AMR were established to determine the changing trend. Controlled ITS models were performed to compare the differences between subgroups. A total of 10,134 isolates over 1,265 days were collected. And antimicrobial-resistant strains presented in 38.6% of the testing isolates. The weekly AMR prevalence decreased by 0.29 percentage point (95% CI [0.05-0.80]) after antimicrobial stewardship (AMS) policy, despite an increase in the prevalence of penicillin-resistant Streptococcus pneumoniae (from 0/43 to 15/43, p < 0.001), carbapenem-resistant Escherichia coli (from 20/1254 to 41/1184, p = 0.005), and carbapenem-resistant Klebsiella pneumoniae (from 93/889 to 114/828, p = 0.042). And the changing trend did not vary by gender (male vs. female), age (<65 vs. ≥65 years), service setting (outpatient vs. inpatient), care unit (ICU vs. non-ICU), the primary site of infection (Lung vs. others), and Gram type of bacteria (positive vs. negative). The response to COVID-19 did not lead to an increase in overall AMR; however, it appears that management strategy on the prudent use of antimicrobials likely contributed to a sizable long-term drop. The frequency of several multidrug-resistant bacteria continues to increase after the COVID-19 epidemic. It is crucial to continue to monitor AMR when COVID-19 cases have surged in China after the relaxation of restriction measures.

Enhancing the efficacy of fluconazole against Leishmania major: Formulation and evaluation of FLZ-nanoemulsions for topical delivery

BackgroundCutaneous Leishmaniasis (CL) remains a significant public health concern, particularly in the tropical and subtropical regions. Present treatment options for CL such as Fluconazole (FLZ) face limitations, including low solubility and bioavailability. This study aimed to address these challenges by investigating the use of nano-emulsions (NEs) to enhance the efficacy of FLZ against Leishmania major(L.major). Materials and methodsFLZ-NEs were formulated with oleic acid, Tween-20, and ethanol using low-energy emulsification at various surfactant/co-surfactant ratios. Subsequently, a comprehensive analysis was conducted to assess the physicochemical characteristics of the samples. This analysis encompassed stability, zeta potential, pH, viscosity, refractive index, and droplet size. We then studied the anti-parasitic properties of these optimized FLZ-NEs both in vitro and in vivo. ResultsThe selected nano-emulsion (NE) formulation (2 % oleic acid, 20 % Tween 20, 10 % ethyl alcohol) showcased desirable properties like small droplet size (10.51 ± 0.24 nm), low dispersity (0.19 ± 0.03), and zeta potential value (- 0.41 ± 0.17 mV), key for stability and targeted drug delivery. This optimal formulation translated into remarkable efficacy. In vitro, FLZ-NEs demonstrated a threefold increase in their ability to combat promastigotes and a remarkable thirtyfold increase in their ability to combat amastigotes. Additionally, they demonstrated a ninefold advantage in their ability to specifically target parasites within infected macrophages, thereby attacking the infection site. These promising in vitro results translated into improved outcomes in vivo. Compared to other chemicals studied, FLZ-NE-treated mice showed decreased disease severity, weight growth, and quicker ulcer healing. It was further supported by histopathological research, which showed reduced tissue damage linked to Leishmania infection. ConclusionThese findings show the potential of nanotechnology-based drug delivery in improving anti-leishmanial treatment.

Design and evaluation of composite films for in situ synthesis and antibacterial activity of allicin vapour

Although allicin has potent antibiotic properties, its low stability, which is responsible for its persistent biological activity, has posed a significant challenge to its practical application in modern medicine. To harness the healing benefits of this phytochemical, known by humans for thousands of years, we propose a controlled in situ synthesis of allicin vapour near the site of infection. Considering the critical need for novel approaches to prevent pandemic scenarios caused by MDR bacteria, we suggest encapsulating and physically separating allicin precursors (substrate alliin and enzyme alliinase) in alginate-based films and spray-dried chitosan microparticles. The mechanical properties of the hydrogel films of various compositions were evaluated, as well as their ability to protect the encapsulated alliinase against thermal stress and control the overall rate of allicin release upon hydration. Furthermore, the non-contact antibacterial efficacy of free alliin/alliinase reaction mixture (aqueous solution) and three compartmentalised configurations, i.e. film-solution, film-particles, and double-film, were tested against selected bacterial strains, i.e. E. coli, S. epidermidis, and S. aureus. The results indicate that the formation of allicin vapour using the proposed compartmentalised systems addresses allicin’s stability issues and provides better control over the rate of allicin production. The observed antibacterial effect was comparable with directly formed allicin using higher initial amounts of both substances, which is given by diffusion limitations associated with encapsulation. These findings illustrate the potential of compartmentalised systems in developing nature-based wound dressings for infection prevention and promoting healing.

Comparison of clinical features of septic shock in children with hematological malignancies versus children without malignant tumors

Objective: To investigate the clinical features of septic shock in children with hematological malignancies compared with those without malignant tumor in the pediatric intensive care unit (PICU). Methods: This retrospective study enrolled children with septic shock at the PICU of Capital Institute of Pediatrics' Children's Hospital from June 2015 to July 2022. According to the presence of hematological malignancies, patients were divided into the hematological malignancies group and without malignant tumor group. Clinical data were compared between the two groups, and logistic regression analysis was used to identify related factors for mortality. Results: A total of 164 children (97 males and 67 females) with a median age of 3.6 (interquartile range 0.8, 7.8) years were enrolled, including 75 (45.7%) patients with hematological malignancies and 89 (54.3%) patients without malignant tumors. Patients in the hematological malignancies group were older [6.0(3.6, 9.4) years vs 1.2 (0.4, 4.3) years, P<0.001] and more experienced hospital-acquired infections [48.0%(36/75) vs 21.3%(19/89),P=0.001], compared with patients without malignant tumors. Surgical emergencies were more frequent in patients without malignant tumors (32.6% vs 14.7%, P=0.013). Patients with hematological malignancies mainly had blood stream infections (58.7%), with Gram-negative bacilli (46.7%), meanwhile, patients without malignant tumors more experienced Gram-positive cocci infections (22.5%) of the respiratory system (40.4%) or digestive system (28.1%). There were significant differences regarding the infection sites (P<0.001) and pathogens (P=0.001). The types of antibacterial agents (P<0.001) and the frequency of noradrenaline (P=0.013) used in patients with hematological malignancies were significantly higher than those without malignant tumors. Patients with hematological malignancies had a higher incidence of multiple organ dysfunction (MODS) [100.0%(75/75) vs 80.9%(72/89), P<0.001] and higher 28-day mortality [34.8%(23/66) vs 19.0%(15/79),P=0.048]. Multivariate logistic regression analysis showed that Pediatric Critical Illness Score (PCIS) was an independent factor for death (odds ratio, OR=1.387, 95%CI: 1.161-1.657, P<0.001) in patients with hematological malignancies, and PCIS (OR=1.419, 95%CI: 1.140-1.767, P=0.002) and the 6-hour lactate clearance rate (OR=65.857, 95%CI: 2.953-1 468.638, P=0.008) were independent factors for death in patients without malignant tumors. Conclusions: Children with hematological malignancies were older, more frequently experienced bloodstream infections, and had a higher incidence of MODS and higher 28-day mortality. PCIS is related to poor prognosis of septic shock in children.

Biofilm dispersal patterns revealed using far-red fluorogenic probes.

Bacteria frequently colonize niches by forming multicellular communities called biofilms. To explore new territories, cells exit biofilms through an active process called dispersal. Biofilm dispersal is essential for bacteria to spread between infection sites, yet how the process is executed at the single-cell level remains mysterious. Here, we characterize dispersal at unprecedented resolution for the global pathogen Vibrio cholerae. To do so, we first developed a far-red cell-labeling strategy that overcomes pitfalls of fluorescent protein-based approaches. We reveal that dispersal initiates at the biofilm periphery and ~25% of cells never disperse. We define novel micro-scale patterns that occur during dispersal, including biofilm compression and the formation of dynamic channels. These patterns are attenuated in mutants that reduce overall dispersal or that increase dispersal at the cost of homogenizing local mechanical properties. Collectively, our findings provide fundamental insights into the mechanisms of biofilm dispersal, advancing our understanding of how pathogens disseminate.

Neutrophilic Myocarditis: Insights from a Forensic Centre's Retrospective Study.

Neutrophilic myocarditis often stems from bacterial or fungal infections, and it is typically detectable through blood cultures or analyses of the primary infection site. However, research specifically addressing the morphological features of acute myocarditis in complex sepsis cases is scarce, with existing studies primarily dating back to the pre-antibiotic era. This study constitutes a retrospective and descriptive analysis encompassing 22 forensic cases. We collected data from forensic reports emphasising clinical details, disease history, gross observations, and histopathological findings. The results show that using positive-air-pressure ventilation could be related to cardiac inflammation (45.45%, 10/22). Despite large-spectrum antibiotic therapy, the blood samples were positive for Staphylococcus aureus (MRSA strain), Klebsiella pneumoniae (ESBL strain), Acinetobacter baumannii, and Pseudomonas aeruginosa. Colonies developed in the myocardium of 36% of the patients (8/22), where 4 of them had septic emboli. Fungal myocarditis accompanied bacterial infections (2/8) and were unsuspected clinically. Background changes, such as interstitial fibrosis and arteriosclerosis, were associated with a greater degree of inflammation and septic embolism. Neutrophilic myocarditis in patients with emerging sepsis is linked to fatal virulent infections, where bacteria and/or fungi contaminate and impair the myocardium syncytium. Prolonged hospitalisation and positive-air-pressure ventilation may be a risk factor for this condition and needs further research.

Impact of Growth Conditions on High-Throughput Identification of Repurposing Drugs for Pseudomonas aeruginosa Cystic Fibrosis Lung Infections.

Pseudomonas aeruginosa lung infections in cystic fibrosis (CF) patients represent a therapeutic challenge due to antibiotic resistance. Repurposing existing drugs is a promising approach for identifying new antimicrobials. A crucial factor in successful drug repurposing is using assay conditions that mirror the site of infection. Here, the impact of growth conditions on the anti-P. aeruginosa activity of a library of 3386 compounds was evaluated. To this, after 24 h exposure, the survival rate of CF P. aeruginosa RP73 planktonic cells was assessed spectrophotometrically under "CF-like" (artificial CF sputum, pH 6.8, 5% CO2) and enriched (Tryptone Soya Broth, pH 7.2, and aerobiosis) conditions. Among non-antibiotic compounds (n = 3127), 13.4% were active regardless of growth conditions, although only 3.2% had comparable activity; 4% and 6.2% were more active under CF-like or enriched conditions, respectively. Interestingly, 22.1% and 26.6% were active exclusively under CF-like and enriched conditions, respectively. Notably, 7 and 12 hits caused 100% killing under CF-like and enriched conditions, respectively. Among antibiotics (n = 234), 42.3% were active under both conditions, although only 18.4% showed comparable activity; 9.4% and 14.5% were more active under CF-like and enriched conditions, respectively. Interestingly, 23% and 16.6% were active exclusively under CF-like and enriched conditions, respectively. Sulphonamides showed higher activity under CF-like conditions, whereas tetracyclines, fluoroquinolones, and macrolides were more effective under enriched settings. Our findings indicated that growth conditions significantly affect the anti-P. aeruginosa activity of antibiotics and non-antibiotic drugs. Consequently, repurposing studies and susceptibility tests should be performed under physicochemical conditions that the pathogen tackles at the site of infection.

Dual tobramycin and docosahexaenoic acid loaded nanoemulsions combating Pseudomonas aeruginosa-induced pulmonary infection

Pseudomonas aeruginosa (P. aeruginosa) typically forms biofilms in vivo, which exhibit high resistance and complicate eradication efforts. Additionally, persistent inflammation and excessive oxidative stress can lead to severe lung dysfunction, facilitating bacterial colonization and infection. Herein, we prepared oil-in-water (O/W) nanoemulsions (TD-αT NEs) by using PEG5k-block-PCL5k and α-tocopherol to encapsulate tobramycin (TOB). To enhance TOB’s drug load, a hydrophobic ion pair (TDIP) composed of TOB and docosahexaenoic acid (DHA) was pre-prepared. TD-αT NEs was not only easily prepared and aerosolized, but stable in both physics and chemistry. The negatively charged TD-αT NEs facilitated penetration through mucus, reaching infection sites. Subsequently, TD-αT NEs permeated biofilms due to their small size and released drugs via lipase-triggered carrier dissociation, aiding in eradicating internal bacteria within biofilms (with a 16-fold reduction in CFU vs. free TOB group). TD-αT NEs simultaneously exerted superior anti-inflammatory effects, reducing levels of pro-inflammatory cytokines (NO, IL-6, IL-8, and TNF-α) while increasing the level of anti-inflammatory cytokine (IL-10). It was achieved through the upregulation of PPAR-γ and downregulation of NF-κB signaling, thus mitigating the lung damage. In addition, TD-αT NEs demonstrated strong antioxidant activity, alleviating the oxidative stress induced by P. aeruginosa. Notably, when administered via inhalation, TD-αT NEs significantly reduced the lung bacterial burden, lung inflammation, and oxidative stress in vivo compared to TOB solution. TD-αT NEs could prove beneficial in treating chronic pulmonary infections induced by P. aeruginosa through a comprehensive strategy, specifically enhancing biofilm eradication, reducing inflammation, and alleviating oxidative stress.

Association of mucoadhesive polymeric matrices and liposomes for local delivery of miconazole: A new approach for the treatment of oral candidiasis

Since the local treatment of oral candidiasis usually requires long-term administration of the antifungal drug, an ideal dosage form should be able to maintain the drug release over an extended period, assuring an adequate concentration at the infection site. In this context, we have considered the possibility of a buccal delivery of miconazole nitrate (MN) by mucoadhesive polymeric matrices. The loading of the antifungal drug in a hydrophilic matrix was made possible by taking advantage of the amphiphilic nature of liposomes (LP).The MN-loaded LP were prepared by a thin film evaporation method followed by extrusion, while solid matrices were obtained by freeze-drying a suspension of the LP in a polymeric solution based on chitosan (CH), sodium hyaluronate (HYA), or hydroxypropyl methylcellulose (HPMC).MN-loaded LP measured 284.7 ± 20.1 nm with homogeneous size distribution, adequate drug encapsulation efficiency (86.0 ± 3.3 %) and positive zeta potential (+47.4 ± 3.3). CH and HYA-based formulations almost completely inhibited C. albicans growth after 24 h, even if the HYA-based one released a higher amount of the drug. The CH-based matrix also provided the best mucoadhesive capacity and therefore represents the most promising candidate for the local treatment of oral candidiasis.

White light-driven enhanced cerium-doped carbon dots activity to combat multidrug-resistant bacterial infection

Infections caused by multidrug-resistant (MDR) bacteria are increasing and becoming an urgent global health crisis. The discovery and development of novel antibacterial agents to combat MDR are highly desirable. Here, we report the fabrication of cerium-doped carbon dots (CeCDs) with a simple hydrothermal method, which exhibit intrinsic broad efficacy against MDR bacteria including clinical isolates while maintaining low cytotoxicity and hemolytic effects. Importantly, the antibacterial activity of CeCDs is dramatically improved owing to the generation of reactive oxygen species (ROS) upon white light irradiation. Comprehensive analyses revealed that the CeCDs can penetrate the bacterial wall, disrupt the cell membrane, and prevent the biofilm formation, possibly hindering the bacterial resistance development. And the interaction of CeCDs with lipopolysaccharide (LPS) may contribute to the higher activity against Gram-negative bacteria strains. The treatment of CeCDs in a murine skin infection model can significantly reduce the number of bacteria on infected sites and accelerate wound healing by irradiation with light. Overall, CeCDs show great promise as low-cost and efficient antibacterial agents for chronic wounds and may be served as a powerful weapon to fight against the growing threat of MDR bacterial infection.

Outbreak of Feline Sporotrichosis with Zoonotic Potential in the Seventh Health District of Maceió-AL.

Sporotrichosis is a mycosis with zoonotic potential caused by species of Sporothrix. Once thought rare in northeastern Brazil, the disease has recently been spreading, leading to an emergency health issue. In this paper, we describe an outbreak of feline sporotrichosis in the Seventh Health District of Maceió-AL. We collected samples from 23 domiciled and non-domiciled felines without regard for age, breed, sex, and neutering state. Skin samples were analyzed cytologically under a light microscope and seeded onto Sabouraud dextrose agar at 25 °C for from 15 to 30 days. Fifteen of the twenty-three cats with suspected skin lesions were positive for Sporothrix spp. on either cytological or microbiological evaluation. Most of the infected cats were male, young adults, non-neutered, with free access to external areas, and living in environments with poor sanitation, a high population density, and an accumulation of garbage and organic matter. Three owners were bitten or scratched by infected cats and subsequently developed suspicious cutaneous lesions suggestive of sporotrichosis. The epidemiological features of feline sporotrichosis in the outbreaks of Maceió seemed to share similarities with the data obtained from outbreaks in current hyperendemic areas. Identifying geographical sites of infection and providing compulsory notification of the disease is essential for avoiding an epidemic in Alagoas.

The Efficacy of Antibiotic-Loaded Calcium Sulfate Beads (Stimulan) in Patients with Hip Arthroplasty Infections.

Background: Given the increasing rate of infections following hip arthroplasty, one of the current options is the application of a biocomposite at the site of the infection. One of the products used is Stimulan, a completely resorbable calcium sulfate, designed to treat acute and chronic infections. This biocomposite has a controlled purity, is easy to mix with liquid, powder, and antibiotics, and can be applied directly to the site of infection, or it can be injected. Methods: We analyzed data from 76 patients, who were admitted to the County Clinical Hospital of Emergency "St. Apostol Andrei" in Galati during January 2017-September 2023, with a diagnosis of infection associated with hip arthroplasty. Results: In 69.73% of cases (52 patients), we decided to keep the implant in place. In this subgroup, Stimulan was applied in 26 cases (57.78%). Of these, 100% were cured-compared to the subgroup in which Stimulan was not applied, where this percentage was lower. All patients underwent chemical and mechanical toileting, and for 24 patients (20.27%), it was necessary to ablate the implant with or without the application of Stimulan, then reimplantation of the prosthesis. Conclusions: The patients with Stimulan had a longer average length of hospitalization, almost half of them required intervention in two periods, and a quarter required the implantation of spacers. However, the cure rate was higher, only in three people could we not control the infection, and there was no death. This study confirms the effectiveness of the treatment when using a biocomposite in addition to the classical treatment for both acute and chronic cases.