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International Journal of Nanomedicine 2024This research was to innovate a nanozyme-based therapeutic strategy that combines aggregation-induced emission (AIE) photosensitizers with copper nanozymes. This...
PURPOSE
This research was to innovate a nanozyme-based therapeutic strategy that combines aggregation-induced emission (AIE) photosensitizers with copper nanozymes. This approach is designed to address the hypoxic conditions often found in bacterial infections and aims to boost the effectiveness of photodynamic therapy (PDT) by ensuring sufficient oxygen supply for reactive oxygen species (ROS) generation.
METHODS
Our approach involved the synthesis of dihydroxyl triphenyl vinyl pyridine (DHTPY)-Cu@zoledronic acid (ZOL) nanozyme particles. We initially synthesized DHTPY and then combined it with copper nanozymes to form the DHTPY-Cu@ZOL composite. The nanozyme's size, morphology, and chemical properties were characterized using various techniques, including dynamic light scattering, transmission electron microscopy, and X-ray photoelectron spectroscopy. We conducted a series of in vitro and in vivo tests to evaluate the photodynamic, antibacterial, and wound-healing properties of the DHTPY-Cu@ZOL nanozymes, including their oxygen-generation capacity, ROS production, and antibacterial efficacy against methicillin-resistant Staphylococcus aureus (MRSA).
RESULTS
The DHTPY-Cu@ZOL exhibited proficient HO scavenging and oxygen generation, crucial for enhancing PDT in oxygen-deprived infection environments. Our in vitro analysis revealed a notable antibacterial effect against MRSA, suggesting the nanozymes' potential to disrupt bacterial cell membranes. Further, in vivo studies using a diabetic rat model with MRSA-infected wounds showed that DHTPY-Cu@ZOL markedly improved wound healing and reduced bacterial presence, underscoring its efficacy as a non-antibiotic approach for chronic infections.
CONCLUSION
Our study suggests that DHTPY-Cu@ZOL is a highly promising approach for combating antibiotic-resistant microbial pathogens and biofilms. The biocompatibility and stability of these nanozyme particles, coupled with their improved PDT efficacy position them as a promising candidate for clinical applications.
Topics: Photochemotherapy; Animals; Methicillin-Resistant Staphylococcus aureus; Copper; Anti-Bacterial Agents; Photosensitizing Agents; Wound Infection; Staphylococcal Infections; Reactive Oxygen Species; Imidazoles; Pyridines; Rats; Wound Healing; Male; Humans; Rats, Sprague-Dawley
PubMed: 38919773
DOI: 10.2147/IJN.S458520 -
South Asian Journal of Cancer Apr 2024Ramakrishna Pai Jakribettu Surgical site infections (SSIs) in head and neck cancer (HNC) patients can significantly affect the outcome of the surgery. Appropriate...
Ramakrishna Pai Jakribettu Surgical site infections (SSIs) in head and neck cancer (HNC) patients can significantly affect the outcome of the surgery. Appropriate antimicrobial prophylaxis is needed for prevention of SSI. To study the causative agents causing SSI among the HNC patients and their drug resistance pattern. This was a retrospective study. The antibiotic suspectibility pattern of the aerobic bacteria isolated from the wound infection in the patients underwent surgery for head and neck cancer, admitted from January 2015 to December 2016 were added in the study. The demographic details of patients, pathogens isolated, and their antimicrobial susceptibility were collected, entered into Microsoft Excel, and statistical analysis was done as per percentage of isolates and drug resistance. A total of 130 culture-positive pus samples were included in the study. The majority of the samples were from males (71.5%), one-third of the patients belonged to the sixth decade of their life. Buccal mucosa and tongue were the common cancer in the head and neck region. The common gram-negative pathogens were sp. and sp. and and sp. among the gram-positive bacteria. Methicillin-resistant isolation rate was noted to be as high as 64.28%. High levels of resistance to aminopenicillins, third generation cephalosporins, co-trimoxazole and fluoroquinolones among the gram-negative pathogens. Anti-MRSA drugs such as vancomycin, linezolid, and teicoplanin resistance was not seen among . The resistance pattern among the pathogens isolated from SSI in HNC patients is alarming. So, implementation of strict infection control practices to prevent SSI rather than treating them with high end antimicrobials is the best option.
PubMed: 38919662
DOI: 10.1055/s-0043-1763282 -
Iranian Journal of Public Health Mar 2024Hospital refrigerators as essential food storage can be important source of food contamination. We aimed to investigate the frequency and antibiotic susceptibility of...
BACKGROUND
Hospital refrigerators as essential food storage can be important source of food contamination. We aimed to investigate the frequency and antibiotic susceptibility of the pathogenic bacteria in three hospital refrigerators in Tehran.
METHODS
This study was performed on 254 samples, collected from 60 refrigerators of the various wards of three hospitals, A, B, and C, in Tehran, Iran from 2020 to 2021. Following isolation and identification of isolates, the antibiotic susceptibility pattern was determined. PCR-based assays were used to screen the presence of antibiotic resistance genes of resistant isolates.
RESULTS
From 254 collected samples, 236 samples (92.9%) were contaminated. Most strains were isolated from refrigerators with poorly cleaned, temperatures above 8 °C in non-critical wards. Most bacteria belonging to Enterobacteriaceae (68.8%), followed by (11.9%), and (10.6%), while the frequency of non-Enterobacteriaceae isolates was 8.9%. The highest antibiotic resistant bacteria were in extended spectrum beta-lactamase (ESBL) 9.7%, vancomycin-resistant enterococci (VRE) 5.3%, methicillin-resistant (MRSE) 0.4%, and methicillin-resistant (MRSA) 0.4%, respectively. The , , and genes were found only in 10% of Enterobacteriaceae isolates. The gene was found in all non-Enterobacteriaceae isolates. The and genes were detected in antibiotic-resistant and .
CONCLUSION
Our findings suggests major concern about cross-contamination and the emergence of antibiotic-resistant isolates as a potential health threat with hospital refrigerators origin. More attention to hospital refrigerators cleaning is necessary to prevent foodborne diseases and nosocomial infections.
PubMed: 38919309
DOI: 10.18502/ijph.v53i3.15150 -
The Permanente Journal Jun 2024Wrist (TB) complex osteomyelitis is rare, with polymicrobial TB osteomyelitis even more uncommon. The authors describe an unusual case of polymicrobial TB wrist...
Wrist (TB) complex osteomyelitis is rare, with polymicrobial TB osteomyelitis even more uncommon. The authors describe an unusual case of polymicrobial TB wrist osteomyelitis. The case patient presented with a 2.5-year history of 2 insidiously growing nodules on his wrist. He underwent debridement, and tissue cultures grew methicillin-resistant , , and, later, TB complex. He was started on vancomycin, rifampin, isoniazid, pyrazinamide, and ethambutol with improvement in symptoms. This case emphasizes the importance of a broad differential and thorough workup for atypical presentations of osteomyelitis. Diagnosis of uncommon etiologies is essential for definitive treatment.
PubMed: 38919054
DOI: 10.7812/TPP/24.025 -
Antimicrobial Resistance and Infection... Jun 2024Methicillin-resistant Staphylococcus aureus (MRSA) is one of the leading causes of mortality due to bacterial antimicrobial resistance. While S. aureus is common in skin...
BACKGROUND
Methicillin-resistant Staphylococcus aureus (MRSA) is one of the leading causes of mortality due to bacterial antimicrobial resistance. While S. aureus is common in skin and soft tissue infections (SSTI) in Africa, data on MRSA rates are scarce and reports vary widely across the continent (5%-80%). In this study, we describe the proportion of MRSA causing SSTI in Lambaréné, Gabon, over an 11-year period.
METHODS
We retrospectively analyzed data from 953 bacterial specimens collected from inpatients and outpatients with SSTI at the Albert Schweitzer Hospital, Lambaréné, Gabon, between 2009 and 2019. We determined temporal changes in the prevalence of MRSA and identified risk factors for SSTI with MRSA.
RESULTS
68% of all specimens with bacterial growth yielded S. aureus (n = 499/731), of which 7% (36/497) with antimicrobial susceptibility testing were identified as MRSA. Age above 18 years, admission to the surgical ward, and deep-seated infections were significantly associated with MRSA as the causative agent. After an initial decline from 7% in 2009, there was a marked increase in the proportion of MRSA among all S. aureus from SSTI from 3 to 20% between 2012 and 2019. The resistance rate to erythromycin was significantly higher in MRSA than in methicillin-susceptible S. aureus (73% vs. 10%), and clindamycin resistance was detected exclusively in MRSA isolates (8%).
CONCLUSION
The increasing proportion of MRSA causing SSTI over the 11-year period contrasts with many European countries where MRSA is on decline. Continuous surveillance of MRSA lineages in the hospital and community along with antibiotic stewardship programs could address the increasing trend of MRSA.
Topics: Humans; Methicillin-Resistant Staphylococcus aureus; Gabon; Soft Tissue Infections; Retrospective Studies; Male; Female; Adult; Adolescent; Middle Aged; Anti-Bacterial Agents; Young Adult; Microbial Sensitivity Tests; Prevalence; Child; Risk Factors; Staphylococcal Skin Infections; Staphylococcal Infections; Child, Preschool; Aged; Infant
PubMed: 38918863
DOI: 10.1186/s13756-024-01426-0 -
BMC Infectious Diseases Jun 2024CKD patients on hemodialysis (HD) with Staphylococcus aureus (SA) bacteremia present high morbidity, mortality and increased risk of MRSA. Vancomycin is the antibiotic...
Impact of Vancomycin trough levels monitoring on uncomplicated methilcillin-resistant Staphylococcus aureus bacteremia in chronic kidney disease on hemodialysis, retrospective cohort.
BACKGROUND
CKD patients on hemodialysis (HD) with Staphylococcus aureus (SA) bacteremia present high morbidity, mortality and increased risk of MRSA. Vancomycin is the antibiotic of choice in these cases, it has a narrow therapeutic margin and inadequate dosage generates a risk of toxicity, therefore, the recommendation is to dosage it through serum levels.
METHODS
This is a retrospective cohort study in 3 hospitals of third level of complexity in the city of Medellin in which there were differences in the measurement and implementation of vancomycin25 dosage based on trough levels (VL) in patients with chronic kidney disease on hemodialysis (CKD- HD) with uncomplicated bacteremia based infection by methilcillin-resistant Staphyloccocus aureus (MRSA). The primary outcome was the composite of hospital mortality, clinical response (fever, hemodynamic instability and altered consciousness), complications associated with bacteremia, or bacteriological response failure (positive cultures at first week follow-up) at 7 days. The composite variables were analyzed individually as secondary outcomes.
RESULTS
The main unadjusted outcome (OR 1.3, CI 0.6 - 2.7) and adjusted for age, Charlson index, loading dose, initial dose, dosing frequency and MIC to vancomycin (OR 1.2, CI 0.5 - 2.7). Regarding adjusted secondary outcomes: clinical response (OR 1.4 CI 0.3 - 5.8), death (OR 1.3 CI 0.3 - 4.6) and complications (OR 0.9, CI 0.37 - 2.2).
CONCLUSIONS
We conclude that the measurement of trough levels in patients with HD-CKD does not modify the composite outcome. The main limitation is the sample size and type of study, randomized control trials may be required to confirm the results presented.
Topics: Humans; Vancomycin; Retrospective Studies; Bacteremia; Staphylococcal Infections; Male; Renal Dialysis; Female; Renal Insufficiency, Chronic; Aged; Methicillin-Resistant Staphylococcus aureus; Middle Aged; Anti-Bacterial Agents; Aged, 80 and over; Microbial Sensitivity Tests
PubMed: 38918705
DOI: 10.1186/s12879-024-08984-z -
Therapeutic Drug Monitoring Jun 2024In neonatal and pediatric intensive care units, Gram-positive infections are a significant cause of morbidity and mortality. The increase in infections caused by...
Development and Validation of a High-Performance Liquid Chromatography With Ultraviolet Detection Method to Facilitate Therapeutic Monitoring of Teicoplanin Using Dried Blood Spots.
BACKGROUND
In neonatal and pediatric intensive care units, Gram-positive infections are a significant cause of morbidity and mortality. The increase in infections caused by methicillin-resistant Staphylococcus aureus and methicillin-resistant coagulase-negative Staphylococci have led to the increased use of glycopeptides, which treat invasive infections caused by Gram-positive organisms, particularly those resistant to beta-lactam antibiotics. Teicoplanin has bacteriostatic activity against Gram-positive bacteria, but its pharmacokinetics in children is highly variable, with most children failing to reach target levels at the recommended dose. This study aimed to develop a cost-effective method for determining concentrations using dried blood spot (DBS).
METHODS
A method to determine the concentrations of teicoplanin in 20 µL blood or plasma using the Whatman 903 Protein Saver filter was evaluated. High-performance liquid chromatography with ultraviolet detection high-performance liquid chromatography with ultraviolet/vis was used, with internal standard ketoconazole. In addition, a method to quantify teicoplanin using 50 µL of liquid plasma was established to compare the results with the values obtained by DBS and dried plasma methods.
RESULTS
The method was successfully developed and validated for 20 µL DBS. Furthermore, 50 µL of plasma was used to quantify teicoplanin with a lower limit of quantification of 10 mg/L. Precision and accuracy ranged from 2.3% to 10.7% and 95%-114.2%, respectively. A consistent factor (1.15) was used to calculate teicoplanin plasma concentrations from whole blood, indicating the reliability of the DBS method for therapeutic drug monitoring of teicoplanin.
CONCLUSIONS
A simple, reliable, and cost-effective method using high-performance liquid chromatography with ultraviolet/vis was established to determine pediatric teicoplanin concentrations in both small plasma sample volumes and whole blood using DBS, and an accurate correlation factor for estimating teicoplanin plasma concentrations from DBS was identified. This method is suitable for the use in pediatrics.
PubMed: 38917389
DOI: 10.1097/FTD.0000000000001202 -
Clinical Infectious Diseases : An... Jun 2024Staphylococcus aureus bacteraemia (SAB) is a clinically heterogeneous disease. The ability to identify sub-groups of patients with shared traits (sub-phenotypes) is an...
BACKGROUND
Staphylococcus aureus bacteraemia (SAB) is a clinically heterogeneous disease. The ability to identify sub-groups of patients with shared traits (sub-phenotypes) is an unmet need that could allow patient stratification for clinical management and research. We aimed to test the hypothesis that clinically-relevant sub-phenotypes can be reproducibly identified amongst patients with SAB.
METHODS
We studied three cohorts of hospitalised adults with monomicrobial SAB: a UK retrospective observational study (Edinburgh cohort, n=458), the UK ARREST randomised trial (n=758), and the Spanish SAFO randomised trial (n=214). Latent class analysis was used to identify sub-phenotypes using routinely-collected clinical data, without considering outcomes. Mortality and microbiologic outcomes were then compared between sub-phenotypes.
RESULTS
Included patients had predominantly methicillin-susceptible SAB (1366/1430,95.5%). We identified five distinct, reproducible clinical sub-phenotypes: (A) SAB associated with older age and comorbidity, (B) nosocomial intravenous catheter-associated SAB in younger people without comorbidity, (C) community-acquired metastatic SAB, (D) SAB associated with chronic kidney disease, and (E) SAB associated with injection drug use. Survival and microbiologic outcomes differed between the sub-phenotypes. 84-day mortality was highest in sub-phenotype A, and lowest in B and E. Microbiologic outcomes were worse in sub-phenotype C. In a secondary analysis of the ARREST trial, adjunctive rifampicin was associated with increased 84-day mortality in sub-phenotype B and improved microbiologic outcomes in sub-phenotype C.
CONCLUSIONS
We have identified reproducible and clinically-relevant sub-phenotypes within SAB, and provide proof-of-principle of differential treatment effects. Through clinical trial enrichment and patient stratification, these sub-phenotypes could contribute to a personalised medicine approach to SAB.
PubMed: 38916975
DOI: 10.1093/cid/ciae338 -
Microbiology Spectrum Jun 2024Bacteremia is associated with significant morbidity and mortality. The emergence of bacteria with antimicrobial resistance (AMR) has further exacerbated the poor...
UNLABELLED
Bacteremia is associated with significant morbidity and mortality. The emergence of bacteria with antimicrobial resistance (AMR) has further exacerbated the poor outcomes associated with bacteremia. The Taiwan Surveillance of Antimicrobial Resistance (TSAR) program was established in 1998 to monitor bacterial epidemiology and antimicrobial resistance trends across all patient types and age groups. Between 2002 and 2020, a total of 14,539 non-duplicate bacteremia isolates were collected biennially from 29 hospitals during the months of July-September as part of the TSAR program. The three most common bacteremia agents were (31%), (13.6%), and (12.7%) overall. However, there was a steady increase in the proportions of and isolated from bacteremia cases (both < 0.001), while the proportions of spp. decreased. Regarding antimicrobial resistance, there was a notable increase in rates of third-generation cephalosporin and fluoroquinolone non-susceptibility among and , while the rates of carbapenem non-susceptibility were elevated but remained milder in these two species, especially in . Of concern is the alarming increase in vancomycin resistance among , rising from 10.0% in 2004 to 47.7% in 2020. In contrast, the prevalence of methicillin-resistant has remained stable at 51.2% overall. In conclusion, , with increasing third-generation cephalosporin and fluoroquinolone resistance, is the predominant cause of bacteremia in Taiwan during the 18-year surveillance. The escalating proportion of in bacteremia, coupled with a concurrent upsurge in vancomycin resistance, presents a therapeutic challenge in the recent decade.
IMPORTANCE
AMR surveillance not only enables the identification of regional variations but also supports the development of coordinated efforts to combat AMR on a global scale. The TSAR has been a biennial, government-endorsed, multicenter study focusing on pathogens isolated from inpatients and outpatients in Taiwan hospitals since 1998. Our report presents an 18-year comprehensive analysis on blood isolates in the 2002-2020 TSAR program. The study highlights an alarming increase in the proportion of causing bacteremia accompanied by elevated vancomycin resistance. It is worth noting that this trend differs from the observations in the United States and China. Understanding the composition of bacteria causing bacteremia, along with their prevalence of antimicrobial resistance, holds significant importance in establishing healthcare and research priorities. Additionally, this knowledge serves as a critical factor in evaluating the effectiveness of preventive interventions.
PubMed: 38916365
DOI: 10.1128/spectrum.00608-24 -
Microbiology Spectrum Jun 2024Methicillin-resistant (MRSA) bacteremia is a serious clinical challenge with high mortality rates. Antibiotic combination therapy is currently used in cases of...
Methicillin-resistant (MRSA) bacteremia is a serious clinical challenge with high mortality rates. Antibiotic combination therapy is currently used in cases of persistent infection; however, the limited development of new antibiotics will likely increase the need for combination therapy, and better methods are needed for identifying effective combinations for treating persistent bacteremia. To identify pairwise combinations with the most consistent potential for benefit compared to monotherapy with a primary anti-MRSA agent, we conducted a systematic study with an high-throughput methodology. We tested daptomycin and vancomycin each in combination with gentamicin, rifampicin, cefazolin, and oxacillin, and ceftaroline with daptomycin, gentamicin, and rifampicin. Combining cefazolin with daptomycin lowered the daptomycin concentration required to reach 95% growth inhibition (IC) for all isolates tested and lowered daptomycin IC below the sensitivity breakpoint for five out of six isolates that had daptomycin minimum inhibitory concentrations at or above the sensitivity breakpoint. Similarly, vancomycin ICs were decreased when vancomycin was combined with cefazolin for 86.7% of the isolates tested. This was a higher percentage than was achieved by adding any other secondary antibiotic to vancomycin. Adding rifampicin to daptomycin or vancomycin did not always reduce ICs and failed to produce synergistic interaction in any of the isolates tested; the addition of rifampicin to ceftaroline was frequently synergistic and always lowered the amount of ceftaroline required to reach the IC. These analyses rationalize further evaluation of three drug pairs for MRSA bacteremia: daptomycin+cefazolin, vancomycin+cefazolin, and ceftaroline+rifampicin.IMPORTANCEBloodstream infections caused by methicillin-resistant (MRSA) have a high mortality rate despite the availability of vancomycin, daptomycin, and newer antibiotics including ceftaroline. With the slow output of the antibiotic pipeline and the serious clinical challenge posed by persistent MRSA infections, better strategies for utilizing combination therapy are becoming increasingly necessary. We demonstrated the value of a systematic high-throughput approach, adapted from prior work testing antibiotic combinations against tuberculosis and other mycobacteria, by using this approach to test antibiotic pairs against a panel of MRSA isolates with diverse patterns of antibiotic susceptibility. We identified three antibiotic pairs-daptomycin+cefazolin, vancomycin+cefazolin, and ceftaroline+rifampicin-where the addition of the second antibiotic improved the potency of the first antibiotic across all or most isolates tested. Our results indicate that these pairs warrant further evaluation in the clinical setting.
PubMed: 38916355
DOI: 10.1128/spectrum.00976-24