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Pharmaceutics May 2024Porous chitosan/hydroxyapatite (Chi-HAp) composite microspheres were prepared in an aqueous solution containing chitosan, calcium nitrate, and ammonium dihydrogen...
Porous chitosan/hydroxyapatite (Chi-HAp) composite microspheres were prepared in an aqueous solution containing chitosan, calcium nitrate, and ammonium dihydrogen phosphate by using a hydrothermal method at various temperatures. The investigation indicated that temperature significantly impacted the final product's appearance. Hydroxyapatite (HAp) coupled with dicalcium phosphate dihydrate (DCPD) flakes were obviously found at 65 and 70 °C, while the latter gradually disappeared at higher temperatures. Conversely, synthesis at 90 °C led to smaller particle sizes due to the broken chitosan chains. The microspheres synthesized at 75 °C were selected for further analysis, revealing porous structures with specific surface areas of 36.66 m/g, pores ranging from 3 to 100 nm, and pore volumes of 0.58 cm/g. Vancomycin (VCM), an antibiotic, was then absorbed on and released from the microspheres derived at 75 °C, with a drug entrapment efficiency of 20% and a release duration exceeding 20 days. The bacteriostatic activity of the VCM/composite microspheres against increased with the VCM concentration and immersion time, revealing a stable inhibition zone diameter of approximately 4.3 mm from 24 to 96 h, and this indicated the retained stability and efficacy of the VCM during the encapsulating process.
PubMed: 38931852
DOI: 10.3390/pharmaceutics16060730 -
Molecules (Basel, Switzerland) Jun 2024The discovery and investigation of new natural compounds with antimicrobial activity are new potential strategies to reduce the spread of antimicrobial resistance. The...
The discovery and investigation of new natural compounds with antimicrobial activity are new potential strategies to reduce the spread of antimicrobial resistance. The presented study reveals, for the first time, the promising antibacterial potential of two fractions from mucus with an MW < 20 kDa and an MW > 20 kDa against five bacterial pathogens- 1085, 1897, 8691, 3915, and 8754. Using de novo sequencing, 16 novel peptides with potential antibacterial activity were identified in a fraction with an MW < 20 kDa. Some bioactive compounds in a mucus fraction with an MW > 20 kDa were determined via a proteomic analysis on 12% sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE) and bioinformatics. High homology with proteins and glycoproteins was found, with potential antibacterial activity in mucus proteins named aspernin, hemocyanins, H-lectins, and L-amino acid oxidase-like protein, as well as mucins (mucin-5AC, mucin-5B, mucin-2, and mucin-17). We hypothesize that the synergy between the bioactive components determined in the composition of the fraction > 20 kDa are responsible for the high antibacterial activity against the tested pathogens in concentrations between 32 and 128 µg/mL, which is comparable to vancomycin, but without cytotoxic effects on model eukaryotic cells of . Additionally, a positive effect, by reducing the levels of intracellular oxidative damage and increasing antioxidant capacity, on cells was found for both mucus extract fractions of . These findings may serve as a basis for further studies to develop a new antibacterial agent preventing the development of antibiotic resistance.
Topics: Anti-Bacterial Agents; Mucus; Microbial Sensitivity Tests; Peptides; Enterococcus faecalis; Enterococcus faecium; Bacillus cereus; Animals; Propionibacterium acnes; Salmonella enterica
PubMed: 38930951
DOI: 10.3390/molecules29122886 -
Medicina (Kaunas, Lithuania) May 2024: Enterococci are typically found in a healthy human gastrointestinal tract but can cause severe infections in immunocompromised patients. Such infections are treated...
: Enterococci are typically found in a healthy human gastrointestinal tract but can cause severe infections in immunocompromised patients. Such infections are treated with antibiotics. This study addresses the rising concern of antimicrobial resistance (AMR) in Enterococci, focusing on the prevalence of vancomycin-resistant enterococcus (VRE) strains. : The pilot study involved 140 Enterococci isolates collected between 2021 and 2022 from two multidisciplinary hospitals (with and without local therapeutic drug monitoring protocol of vancomycin) in Latvia. Microbiological assays and whole genome sequencing were used. AMR gene prevalence with resistance profiles were determined and the genetic relationship and outbreak evaluation were made by applying core genome multi-locus sequence typing (cgMLST). : The acquired genes and mutations were responsible for resistance against 10 antimicrobial classes, including 25.0% of isolates expressing resistance to vancomycin, predominantly of the B type. Genetic diversity among and isolates was observed and seven potential outbreak clusters were identified, three of them containing sequence types ST6, ST78 and ST80. The prevalence of vancomycin resistance was highest in the hospital without a therapeutic drug-monitoring protocol and in . Notably, a case of linezolid resistance due to a mutation was documented. : The study illustrates the concerning prevalence of multidrug-resistant Enterococci in Latvian hospitals, showcasing the rather widespread occurrence of vancomycin-resistant strains. This highlights the urgency of implementing efficient infection control mechanisms and the need for continuous VRE surveillance in Latvia to define the scope and pattern of the problem, influencing clinical decision making and planning further preventative measures.
Topics: Humans; Latvia; Anti-Bacterial Agents; Pilot Projects; Enterococcus; Microbial Sensitivity Tests; Gram-Positive Bacterial Infections; Vancomycin-Resistant Enterococci; Drug Resistance, Bacterial; Multilocus Sequence Typing; Whole Genome Sequencing
PubMed: 38929467
DOI: 10.3390/medicina60060850 -
Bioengineering (Basel, Switzerland) May 2024Although the incidence of infections in orthopedic surgeries, including periprosthetic surgeries, remains low at approximately 1-2%, the number of surgeries and the...
Although the incidence of infections in orthopedic surgeries, including periprosthetic surgeries, remains low at approximately 1-2%, the number of surgeries and the incidence of drug-resistant bacteria is increasing. The cost and morbidity associated with revision surgeries are huge. More effective drug combinations and delivery methods are urgently needed. In this paper, three anti-infective drugs (vancomycin, rifampicin, and silver sulfadiazine) have been jointly and effectively electrospun in thin (0.1 mm) flexible nanofiber mats of either poly (methyl methacrylate) (PMMA) or poly (lactic-co-glycolic acid) (PLGA). The inclusion of poly (ethylene glycol) (PEG) enabled optimal drug release with a reduced water contact angle for wetting. The controlled release of these three agents from 20% PEG (/ to polymer)-blended PMMA or PLGA nanofiber mats may allow for the prophylactical prevention of implant-related infections or provide methods to treat orthopedic infections at the time of revision surgeries. These combinations of drugs provide excellent additive or synergistic antibiotic action against a broader spectrum of bacteria than each drug alone.
PubMed: 38927765
DOI: 10.3390/bioengineering11060529 -
Antibiotics (Basel, Switzerland) Jun 2024species (formerly known as ) are Gram-positive filamentous bacteria in the family Promicromonosporaceae and are more commonly found in sewage and soil. The present... (Review)
Review
species (formerly known as ) are Gram-positive filamentous bacteria in the family Promicromonosporaceae and are more commonly found in sewage and soil. The present study aimed to identify all the published cases of species infections in the literature, describe the epidemiological, clinical, and microbiological characteristics, and provide data regarding its antimicrobial resistance, treatment, and outcomes. A narrative review was performed based on a PubMed and Scopus database search. In total, 38 studies provided data on 40 patients with infections by these species. The median age of patients was 52.5 years, and 55% were male. The most common infection types were bacteremia, infective endocarditis (IE), osteoarticular infections, peritoneal dialysis-associated peritonitis, and endophthalmitis. Antimicrobial resistance to vancomycin and the combination of trimethoprim and sulfamethoxazole was minimal, and vancomycin was the most commonly used antimicrobial for treating these infections. Overall mortality was minimal for all infections, except for bacteremia and IE, which carried high mortality rates.
PubMed: 38927228
DOI: 10.3390/antibiotics13060562 -
Antibiotics (Basel, Switzerland) Jun 2024Antimicrobial peptides (AMPs) are being explored as a potential strategy to combat antibiotic resistance due to their ability to reduce susceptibility to antibiotics....
Antimicrobial peptides (AMPs) are being explored as a potential strategy to combat antibiotic resistance due to their ability to reduce susceptibility to antibiotics. This study explored whether the [RW] peptide mode of action is bacteriostatic or bactericidal using modified two-fold serial dilution and evaluating the synergism between gentamicin and [RW] against () and methicillin-resistant (MRSA) by a checkered board assay. [RW] exhibited bactericidal activity against bacterial isolates (MBC/MIC ≤ 4), with a synergistic effect with gentamicin against (FICI = 0.3) but not against MRSA (FICI = 0.75). Moreover, we investigated the mechanism of action of [RW] against MRSA by applying biophysical assays to evaluate zeta potential, cytoplasmic membrane depolarization, and lipoteichoic acid (LTA) binding affinity. [RW] at a 16 mg/mL concentration stabilized the zeta potential of MRSA -31 ± 0.88 mV to -8.37 mV. Also, [RW] at 2 × MIC and 16 × MIC revealed a membrane perturbation process associated with concentration-dependent effects. Lastly, in the presence of BODIPY-TR-cadaverine (BC) fluorescence dyes, [RW] exhibited binding affinity to LTA comparable with melittin, the positive control. In addition, the antibacterial activity of [RW] against MRSA remained unchanged in the absence and presence of LTA, with an MIC of 8 µg/mL. Therefore, the [RW] mechanism of action is deemed bactericidal, involving interaction with bacterial cell membranes, causing concentration-dependent membrane perturbation. Additionally, after 30 serial passages, there was a modest increment of MRSA strains resistant to [RW] and a change in antibacterial effectiveness MIC [RW] and vancomycin by 8 and 4 folds with a slight change in Levofloxacin MIC 1 to 2 µg/mL. These data suggest that [RW] warrants further consideration as a potential AMP.
PubMed: 38927221
DOI: 10.3390/antibiotics13060555 -
Antibiotics (Basel, Switzerland) Jun 2024Rifampicin is one of the mainstays in treating staphylococcal prosthetic joint infection (PJI). However, discontinuation due to intolerance, drug interactions, and...
Do High Doses of Multiple Antibiotics Loaded into Bone Cement Spacers Improve the Success Rate in Staphylococcal Periprosthetic Joint Infection When Rifampicin Cannot Be Employed?
Rifampicin is one of the mainstays in treating staphylococcal prosthetic joint infection (PJI). However, discontinuation due to intolerance, drug interactions, and adverse events is common. Two-stage revision surgery remains the gold standard, with the number of revision arthroplasties steadily increasing. This study aims to evaluate the effectiveness and safety of a novel two-stage revision protocol for staphylococcal prosthetic joint infection (PJI) utilizing bone cement spacers loaded with multiple high doses of antibiotics. Additionally, it seeks to analyze outcomes in patients ineligible for rifampicin treatment. A retrospective review of 43 cases of staphylococcal hip and knee prosthetic joint infections (PJIs) from 2012 to 2020 was conducted. In all instances, a commercial cement containing 1 g of gentamicin and 1 g of clindamycin, augmented with 4 g of vancomycin and 2 g of ceftazidime, was employed to cast a spacer manually after thorough surgical debridement. We report an eradication rate of 82%, with no significant differences observed ( = 0.673) between patients treated with (84%, = 19) and without rifampicin (79%, = 24). There were no disparities in positive culture rates (7%), spacer replacement (18%), or survival analysis ( = 0.514) after an average follow-up of 68 months (range 10-147) in the absence of systemic toxicity and surgical complications superimposable to those previously reported. In conclusion, two-stage revision with local high doses of ceftazidime, vancomycin, gentamicin, and clindamycin demonstrates high effectiveness in treating staphylococcal PJIs. Notably, systemic rifampicin does not influence the outcomes. This protocol, with multiple high doses of antibiotics loaded into the bone cement spacer, is presented as a viable and safe alternative for patients unsuitable for rifampicin treatment.
PubMed: 38927204
DOI: 10.3390/antibiotics13060538 -
Antibiotics (Basel, Switzerland) May 2024Staphylococcal scalded skin syndrome (SSSS) is a rare, toxin-mediated, desquamating bacterial infectious dermatosis. So far, data from Southwestern China is scarce. This...
Staphylococcal scalded skin syndrome (SSSS) is a rare, toxin-mediated, desquamating bacterial infectious dermatosis. So far, data from Southwestern China is scarce. This study aimed to investigate the clinical characteristics of SSSS patients in our hospital, the relative proportion of methicillin-resistant (MRSA) in skin and soft tissue secretions, and the drug sensitivity of to better assist dermatologists in the diagnosis and treatment of SSSS. We reviewed the demographic characteristics, clinical manifestations, treatment regimens, therapeutic efficacy, laboratory test results, drug sensitivity, and outcome data of 79 SSSS patients from January 2012 to December 2021. Statistical analysis was performed using tests and chi-square tests. Among the 79 SSSS patients, MRSA was detected in 35 (44.3%) isolates: 34 community-acquired (CA)-MRSA (97.1%) and 1 hospital-acquired (HA)-MRSA. The SSSS incidence increased annually from 2012 to 2014 and then decreased gradually after peaking in 2015. All the isolates were sensitive to vancomycin, tigecycline, linezolid, moxifloxacin, levofloxacin, and ciprofloxacin; were completely resistant to penicillin; and had low sensitivity to clindamycin and erythromycin. Interestingly, the sensitivity of MRSA to tetracycline increased annually after 2015. The resistance rates to common drugs previously used to treat SSSS increased. These findings may accelerate diagnosis and improve empirical antibiotic use, suggesting that clinicians should prescribe drugs according to antimicrobial susceptibility.
PubMed: 38927182
DOI: 10.3390/antibiotics13060516 -
Antibiotics (Basel, Switzerland) May 2024Improving local antibiotic delivery is a promising approach to improve infection control and potentially shorten systemic treatment in periprosthetic joint infection...
BACKGROUND
Improving local antibiotic delivery is a promising approach to improve infection control and potentially shorten systemic treatment in periprosthetic joint infection (PJI). This study investigates the use of an antibiotic-loaded, mouldable collagen-tricalciumphosphate composite in treatment of hip PJI.
METHODS
124 application cases in 79 patients were included from a referral centre; systemic adverse infects, local complications, and infection control were analysed.
RESULTS
In most cases, either vancomycin or meropenem were used. Pathogens were previously known in 82 (66%) cases with polymicrobial infection in 20 (25%) patients. There were no cases of hypercalcaemia. Acute kidney injure was present in 14 (11%) cases. Chronic kidney failure persisted in two cases. During a mean follow-up of 12 (SD 9.3; range 3-35) months, implant survival was achieved in 73 (92%) patients; revision due to PJI was performed in 19 cases.
CONCLUSION
Mouldable collagen-tricalciumphosphate composite bone substitute as a local antibiotic carrier in revision hip arthroplasty appears to be a valid option for local antibiotic delivery without systemic complications. Implant survival of 92% supports the hypothesis that local antibiotic therapy is an important component in the treatment of PJI.
PubMed: 38927177
DOI: 10.3390/antibiotics13060510 -
Antibiotics (Basel, Switzerland) May 2024This study conducted a quantitative meta-analysis to investigate the association of vancomycin indicators, particularly area under the curve over 24 h (AUC) and trough...
This study conducted a quantitative meta-analysis to investigate the association of vancomycin indicators, particularly area under the curve over 24 h (AUC) and trough concentrations (C), and their relationship with both nephrotoxicity and efficacy. Literature research was performed in PubMed and Web of Science on vancomycin nephrotoxicity and efficacy in adult inpatients. Vancomycin C, AUC, AUC/minimum inhibitory concentration (MIC), nephrotoxicity evaluation and treatment outcomes were extracted. Logistic regression and models were conducted, stratified by evaluation criterion for nephrotoxicity and primary outcomes for efficacy. Among 100 publications on nephrotoxicity, 29 focused on AUC and 97 on C, while of 74 publications on efficacy, 27 reported AUC/MIC and 68 reported C. The logistic regression analysis indicated a significant association between nephrotoxicity and vancomycin C (odds ratio = 2.193; 95% CI 1.582-3.442, < 0.001). The receiver operating characteristic curve had an area of 0.90, with a cut-off point of 14.55 mg/L. Additionally, 92.3% of the groups with a mean AUC within 400-600 mg·h/L showed a mean C of 10-20 mg/L. However, a subtle, non-statistically significant association was observed between the AUC and nephrotoxicity, as well as between AUC/MIC and C concerning treatment outcomes. Our findings suggest that monitoring vancomycin C remains a beneficial and valuable approach to proactively identifying patients at risk of nephrotoxicity, particularly when C exceeds 15 mg/L. C can serve as a surrogate for AUC to some extent. However, no definitive cut-off values were identified for AUC concerning nephrotoxicity or for C and AUC/MIC regarding efficacy.
PubMed: 38927164
DOI: 10.3390/antibiotics13060497