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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 -
Antibiotics (Basel, Switzerland) May 2024Street food may be a vehicle of antibiotic-resistant bacteria (ARB) and antibiotic resistance genes (ARGs) to humans. Foods contaminated with ARB entail serious problems... (Review)
Review
Street food may be a vehicle of antibiotic-resistant bacteria (ARB) and antibiotic resistance genes (ARGs) to humans. Foods contaminated with ARB entail serious problems or challenges in the fields of medical care, animal husbandry, food industry, and public health worldwide. The objectives of this systematic review were to identify and evaluate scientific reports associated with ARB isolated from various street foods. "Preferred reporting items for systematic reviews and meta-analysis" (PRISMA) guidelines were followed. The bibliographic material covers a period from January 2015 to April 2024. Six electronic scientific databases were searched individually for full-text articles; only those papers that met the inclusion and exclusion criteria were selected. Seventeen papers were included in this systematic review. This study highlighted the wide distribution of ARB resistant to β-lactams and other antibiotics, posing significant health risks to consumers. High resistance levels were observed for antibiotics such as ampicillin, ceftriaxone, and tetracycline, while some antibiotics, such as ceftazidime, clavulanic acid, cefoperazone, cotrimoxazole, doxycycline, doripenem, fosfomycin, vancomycin, and piperacillin-tazobactam, demonstrated 100% susceptibility. The prevalence of ARB in street foods varied between 5.2% and 70.8% among different countries. The multiple resistance of various bacteria, including , , , and , to multiple classes of antibiotics, as well as environmental factors contributing to the spread of antibiotic resistance (AR), emphasize the urgent need for comprehensive approaches and coordinated efforts to confront antimicrobial resistance (AMR) under the "One Health" paradigm.
PubMed: 38927148
DOI: 10.3390/antibiotics13060481 -
Clinical Microbiology and Infection :... Jun 2024To estimate risk factors for AKI and the effect of AKI on mortality in Staphylococcus aureus bacteremia, while taking into account recurrent AKI episodes, competing...
OBJECTIVES
To estimate risk factors for AKI and the effect of AKI on mortality in Staphylococcus aureus bacteremia, while taking into account recurrent AKI episodes, competing risks, time-varying variables and time-varying effects.
METHODS
We performed an unplanned analysis using data from a multicenter cohort study of patients with SAB. Primary outcome was cumulative incidence of AKI, according to KDIGO definitions.
RESULTS
We included 453 patients in this study of whom 194 (43%) patients experienced one or more AKI episodes. Age (HR 1.013, 95% CI 1.001 - 1.024), Charlson comorbidity index (HR 1.07, 95% CI 1.01 - 1.14), prior chronic kidney disease (HR 1.76, 95% CI 1.28 - 2.42), septic shock (HR 3.28, 95% CI 2.31 - 4.66), persistent bacteremia (HR 1.53, 95% CI 1.08 - 2.17) and vancomycin therapy (HR 1.80, 95% CI 1.05 - 3.09) were independently associated with AKI, but flucloxacillin, cefazolin, rifampicin and aminoglycoside therapy were not. After adjustment for confounders and immortal time bias, AKI was associated with an increased risk of 90-day mortality (HR 4.26, 95% CI 2.91 - 6.23).
CONCLUSIONS
Incidence of AKI in SAB is high and a substantial proportion of patients develops recurrent episodes of AKI after recovery. AKI is specifically linked to the use of vancomycin and not to anti-staphylococcal penicillins. Clinical outcome of patients with SAB complicated by AKI is worse than previously estimated.
PubMed: 38925460
DOI: 10.1016/j.cmi.2024.06.017 -
The Science of the Total Environment Jun 2024In response to the rapid emergence and dissemination of antimicrobial resistant bacteria (ARB) and genes (ARGs), integrated surveillance systems are needed to address...
In response to the rapid emergence and dissemination of antimicrobial resistant bacteria (ARB) and genes (ARGs), integrated surveillance systems are needed to address antimicrobial resistance (AMR) within the One Health Era. Wastewater analyses enable biomarker monitoring at the sewershed level, offering timely insights into pathogen circulation and ARB/ARGs trends originating from different compartments. During two consecutive epidemic waves of the COVID-19 pandemic in Portugal, taxonomic and functional composition of raw urban wastewater from two wastewater treatment plants (WWTPs) representing one million in equivalent population, located in the main urban areas of the country, were profiled by shotgun metagenomics. Hospital wastewater from two central hospitals located in the WWTPs catchment areas were also sequenced. The resistome and virulome were profiled using metagenomic assemblies without taxonomic constraint, and then specifically characterized for ESKAPE pathogens. Urban and hospital wastewater exhibited specific microbiota signatures, Pseudomonadota dominated in the first and Bacteroidota in the latter. Correlation network analyses highlighted 85 (out of top 100) genera co-occurring across samples. The most frequent ARGs were classified in the multidrug, tetracyclines, and Macrolides, Lincosamides, Streptogramins (MLS) classes. Links established between AMR determinants and bacterial hosts evidenced that the diversity and abundance of ARGs is not restricted to ESKAPE, being also highly predominant among emergent enteropathogens, like Aeromonas and Aliarcobacter, or in the iron (II) oxidizer Acidovorax. The Aliarcobacter genus accumulated high abundance of sulphonamides and polymyxins ARGs, while Acinetobacter and Aeromonas hosted the highest abundance of ARGs against beta-lactams. Other bacteria (e.g. Clostridioides, Francisella, Vibrio cholerae) and genes (e.g. vanA-type vancomycin resistance) of public health interest were detected, with targeted monitoring efforts being needed to establish informative baseline data. Altogether, results highlight that wastewater monitoring is a valuable component of pathogen and AMR surveillance in healthy populations, providing a community-representative snapshot of public health trends beyond priority pathogens.
PubMed: 38925382
DOI: 10.1016/j.scitotenv.2024.174272 -
Hemodialysis International.... Jun 2024Few studies have reported the application of vacuum-sealing drainage of infected dialysis vascular access wounds. Herein, we present a case of buttonhole-related...
Few studies have reported the application of vacuum-sealing drainage of infected dialysis vascular access wounds. Herein, we present a case of buttonhole-related arteriovenous fistula infection treated with vacuum-sealing drainage. A 53-year-old female hemodialysis patient was hospitalized with an inflamed arteriovenous fistula. The patient underwent non-tunneled catheterization for dialysis and was treated with moxifloxacin and vancomycin for staphylococcal infection. On Day 3, the skin overlying the inflamed fistula was ulcerated, resulting in severe hemorrhage. Emergency surgery was performed along with vacuum-sealing drainage for fistula reconstruction. Vacuum-sealing drainage accelerated the recovery of the wound without complications. No further access complications occurred during over a 3-year follow-up.
PubMed: 38924346
DOI: 10.1111/hdi.13164 -
Infectious Diseases and Therapy Jun 2024Methicillin-resistant Staphylococcus aureus (MRSA) infections are a serious threat to public health. Vancomycin (VAN) remains the primary treatment for these infections,...
Characterizing Day 1 Area Under the Curve Following Vancomycin Loading Dose Administration in Adult Hospitalized Patients Using Non-Trapezoidal Linear Pharmacokinetic Equations: A Retrospective Observational Study.
INTRODUCTION
Methicillin-resistant Staphylococcus aureus (MRSA) infections are a serious threat to public health. Vancomycin (VAN) remains the primary treatment for these infections, and achieving the recommended area under the curve (AUC) target has been linked to improved clinical outcomes. The current VAN therapeutic monitoring guidelines recommend a loading dose (LD) of 20-35 mg/kg to rapidly attain targeted VAN exposures within 24 h of therapy. However, there is a paucity of data describing the impact of VAN LD on day 1 area under the curve (AUC). This study aims to employ pharmacokinetic (PK) equations to calculate and describe the AUC following a VAN LD of 20 mg/kg.
METHODS
This was a retrospective study of adult patients who were loaded with VAN 20 mg/kg, received ≥ 48 h of treatment, and had two consecutive serum VAN levels collected within 24 h. Linear, non-trapezoidal PK equations and two post-infusion VAN levels were used to calculate AUC. Therapeutic AUC was defined as 400-600 mg/l*h.
RESULTS
Among 123 included patients, the median age was 46 years (IQR 36, 62), 54% (67/123) of the patients had a body mass index (BMI) ≥ 30 kg/m and 27% (33/123) were admitted to the intensive care unit (ICU). Following a LD of 20 mg/kg, 50% (61/123) of the patients met the therapeutic AUC, while 22% (27/123) of the patients were subtherapeutic, and 28% (35/123) were supratherapeutic. Compared with patients who achieved therapeutic AUC, patients with subtherapeutic AUC were more likely to be younger (44 vs. 37 years old) and have a BMI ≥ 30 kg/m (67 vs. 52%). In contrast, patients with supratherapeutic AUC were more likely to be older (64 vs. 44 years old) and to have chronic kidney disease diagnosis (23 vs. 7%) when compared to patients who achieved a therapeutic AUC CONCLUSIONS: Only 50% of patients achieve the target AUC following a VAN 20 mg/kg LD, with younger, heavier patients underexposed and older patients with renal impairment overexposed, suggesting that different dosing strategies are needed for these populations.
PubMed: 38922527
DOI: 10.1007/s40121-024-01004-2 -
Biomacromolecules Jun 2024Polymeric drugs containing up to 60% by weight of the antibiotic vancomycin were synthesized based on dextran carriers activated with epichlorohydrin. Vancomycin was...
Polymeric drugs containing up to 60% by weight of the antibiotic vancomycin were synthesized based on dextran carriers activated with epichlorohydrin. Vancomycin was covalently bound, involving the primary amino group of the molecule through the hydroxypropyl radical to the C6 position of the anhydroglucose units of the dextran main chain. Covalent binding is necessary to prevent spontaneous release of the antibiotic from the gel, thereby reducing the risk of bacterial multiresistance. Antibacterial depot gels were obtained from those polymers, containing up to 17.5% by weight of polysaccharide with a cross-linking density of = 3-5 nodes per macromolecule for the deposition of another type of drugs not covalently bound to the polymer gel. They were used to coat the surface of the internal pores of biocomposite bone implants based on bovine cancellous bone used in orthopedics. The chemical structure of the polymer was studied using C NMR spectroscopy and matrix-assisted laser desorption ionization-time of flight (MALDI-TOF) mass spectrometry. The stiffness of the gels was evaluated by the values of the accumulation modulus ' = 170-270 kPa and the loss modulus ″ = 3.7-4.2 kPa determined on a rheometer. Their values are close to those typical for materials used to replace soft tissue in plastic surgery. The minimum inhibitory concentration of the gels against depends on the antibiotic content in the polymer. It equals 2.5 mg/L for vancomycin we used and 100 mg/L for a polymer containing 50% by weight of covalently bound antibiotic. The cytotoxic concentration measured with cell culture exceeds 1200 mg/L in 24 h exposure. The release dynamics of drugs not covalently bound to dextran from the depot gel were studied using fluorescein as a model. The release time is independent of the gel density and lasts up to 6 days for a 2 mm thick layer. Both the gel and the bone implants impregnated with it maintained consistently high antibacterial activity throughout the experiment, up to its completion after 168 h, with the local concentration of the released antibiotic at the site of bacterial attack exceeding the therapeutic level by 200 times.
PubMed: 38922325
DOI: 10.1021/acs.biomac.4c00268