-
Scientific Reports Jun 2024Hyperthermia induced by phenethylamines, such as 3,4-methylenedioxymethamphetamine (MDMA), can lead to life-threatening complications and death. Activation of the...
Hyperthermia induced by phenethylamines, such as 3,4-methylenedioxymethamphetamine (MDMA), can lead to life-threatening complications and death. Activation of the sympathetic nervous system and subsequent release of norepinephrine and activation of uncoupling proteins have been demonstrated to be the key mediators of phenethylamine-induced hyperthermia (PIH). Recently, the gut microbiome was shown to also play a contributing role in PIH. Here, the hypothesis that bile acids (BAs) produced by the gut microbiome are essential to PIH was tested. Changes in the serum concentrations of unconjugated primary BAs cholic acid (CA) and chenodeoxycholic acid (CDCA) and secondary BA deoxycholic acid (DCA) were measured following MDMA (20 mg/kg, sc) treatment in antibiotic treated and control rats. MDMA-induced a significant hyperthermic response and reduced the serum concentrations of three BAs 60 min post-treatment. Pretreatment with antibiotics (vancomycin, bacitracin and neomycin) in the drinking water for five days resulted in the depletion of BAs and a hypothermic response to MDMA. Gut bacterial communities in the antibiotic-treated group were distinct from the MDMA or saline treatment groups, with decreased microbiome diversity and alteration in taxa. Metagenomic functions inferred using the bioinformatic tool PICRUSt2 on 16S rRNA gene sequences indicated that bacterial genes associated to BA metabolism are less abundant in the antibiotic-MDMA treated group. Overall, these findings suggest that gut bacterial produced BAs might play an important role in MDMA-induced hyperthermia.
Topics: Gastrointestinal Microbiome; N-Methyl-3,4-methylenedioxyamphetamine; Animals; Rats; Male; Hyperthermia; Bile Acids and Salts; Anti-Bacterial Agents; Rats, Sprague-Dawley; RNA, Ribosomal, 16S; Deoxycholic Acid
PubMed: 38914648
DOI: 10.1038/s41598-024-65433-2 -
International Journal of Surgery... Jun 2024To evaluate the safety and efficacy of intra-wound vancomycin powder in reducing surgical site infections (SSIs) after spine surgery.
BACKGROUND
To evaluate the safety and efficacy of intra-wound vancomycin powder in reducing surgical site infections (SSIs) after spine surgery.
DESIGN
A prospective, double-blind, randomized controlled study.
PARTICIPANTS
Patients who underwent posterior lumbar interbody fusion (PLIF) surgery from May 2021 to September 2022.
METHODS
Patients who underwent posterior lumbar interbody fusion (PLIF) surgery between May 2021 and September 2022 were included. Participants were randomized to the vancomycin treatment or control groups using block randomization (block size 4). Except for baseline and surgical data, the plasma levels of white blood cells, C-reactive protein (CRP), erythrocyte sedimentation rate (ESR), aspartate aminotransferase, alanine aminotransferase, and serum vancomycin concentration in the groups were analyzed on postoperative days (PODs) 1, 3, and 5. Vancomycin concentration was measured daily until the drainage tubes were removed. The primary outcomes were the 90-day vancomycin-related adverse reactions and SSI rates. Secondary outcomes were perioperative hematological parameters and vancomycin serum (drain) concentrations.
RESULTS
A total of 156 participants (78 each in each group) were analyzed by an independent researcher. The follow-up rate was 91%. All participants were followed up for at least 90 days. The 90-day SSI rate in the vancomycin group was 1.3% (1/78), comprising one case of superficial infection. The SSI rate in the control group was 10.3% (8/78), comprising seven cases of superficial infection and one case of deep infection. Compared with that in the control group, the SSI rate in the vancomycin group was decreased by 87.5%, with a statistically significant difference (RR=0.125, 95% CI=0.016-0.976). Additionally, the vancomycin group demonstrated a statistically significant decrease in serum ESR on POD 3 (P=0.039) and CRP on POD 5 (P=0.024) compared to the control group. The local plasma concentration of vancomycin remained elevated for at least 4 days postoperatively, while the serum concentration of vancomycin remined low. Vancomycin-associated adverse reactions were not observed.
CONCLUSION
Intra-wound application of vancomycin powder is a safe and effective procedure for reducing the risk of SSI during PLIF surgery.
PubMed: 38913429
DOI: 10.1097/JS9.0000000000001846 -
Intensive Care Medicine Experimental Jun 2024The aim of this experimental study was to elucidate whether different distances between central venous catheter tips can affect drug clearance during continuous renal...
BACKGROUND
The aim of this experimental study was to elucidate whether different distances between central venous catheter tips can affect drug clearance during continuous renal replacement therapy (CRRT). Central venous catheters (CVCs) are widely used in intensive care patients for drug infusion. If a patient receives CRRT, a second central dialysis catheter (CDC) is required. Where to insert CVCs is directed by guidelines, but recommendations regarding how to place multiple catheters are scarce. There are indications that a drug infused in a CVC with the tip close to the tip of the CDC, could be directly aspirated into the dialysis machine, with a risk of increased clearance. However, studies on whether clearance is affected by different CVC and CDC tip positions, when the two catheters are in the same vessel, are few.
METHODS
In this model with 18 piglets, gentamicin (GM) and vancomycin (VM) were infused through a CVC during CRRT. The CVC tip was placed in different positions in relation to the CDC tip from caudal, i.e., proximal to the heart, to cranial, i.e., distal to the heart. Serum and dialysate concentrations were sampled after approximately 30 min of CRRT at four different positions: when the CVC tip was 2 cm caudally (+ 2), at the same level (0), and at 2 (- 2) and 4 (- 4) cm cranially of the tip of the CDC. Clearance was calculated. A mixed linear model was performed, and level of significance was set to p < 0.05.
RESULTS
Clearance of GM had median values at + 2 cm, 0 cm, - 2 cm and - 4 cm of 17.3 (5.2), 18.6 (7.4), 20.0 (16.2) and 26.2 (12.2) ml/min, respectively (p = 0.04). Clearance of VM had median values at + 2 cm, 0 cm, - 2 cm and - 4 cm of 16.2 (4.5), 14.7 (4.9), 19.0 (10.2) and 21.2 (11.4) ml/min, respectively (p = 0.02).
CONCLUSIONS
The distance between CVC and CDC tips can affect drug clearance during CRRT. A cranial versus a caudal tip position of the CVC in relation to the tip of the CDC led to the highest clearance.
PubMed: 38913212
DOI: 10.1186/s40635-024-00635-6 -
Infection and Drug Resistance 2024In this study we aimed to evaluate the postoperative safety of cytoreductive surgery (CRS) combined with hyperthermic intraperitoneal chemotherapy (HIPEC) for the...
Postoperative Bloodstream Infections in Patients with Peritoneal Surface Malignancies Undergoing Cytoreductive Surgery and Hyperthermic Intraperitoneal Chemotherapy: Risk Factors and Pathogen Resistance.
OBJECTIVE
In this study we aimed to evaluate the postoperative safety of cytoreductive surgery (CRS) combined with hyperthermic intraperitoneal chemotherapy (HIPEC) for the treatment of peritoneal surface malignancies (PSM), and analyzed the risk factors and pathogen resistance associated with bloodstream infections.
METHODS
We retrospectively analyzed the incidence of postoperative bloodstream infections in 1500 patients undergoing CRS and HIPEC for PSM. We utilized univariate and multivariate analyses to screen for independent risk factors associated with postoperative bloodstream infections in CRS combined with HIPEC.
RESULTS
Among the 1500 cases of individuals undergoing CRS combined with HIPEC, 207 cases (13.8%) experienced bloodstream infections. A total of 233 strains of pathogens were isolated and cultured, consisting of 151 gram-positive cocci, 52 gram-negative bacilli, and 30 fungi. Coagulase-negative staphylococci (SCN) were the gram-positive cocci (54.94%), while (7.30%) and (5.58%) dominated the Gram-negative bacilli. was the predominant fungus. Staphylococci exhibited high sensitivity to tigecycline, linezolid, vancomycin, and quinupristin/dalfopristin. However, and were resistant to imipenem. Furthermore, five parameters were associated with the development of bloodstream infections: age ( = 0.040), surgical history ( = 0.033), prior tumor treatment ( < 0.001), tumor tissue type ( = 0.034), and completeness of cytoreduction (CC) score ( = 0.004). Among these, age ( = 0.013), prior tumor treatment ( = 0.001), tumor tissue type ( = 0.032), and CC score ( = 0.002) emerged as independent risk factors for postoperative bloodstream infections in patients undergoing CRS combined with HIPEC.
CONCLUSION
Postoperative bloodstream infections in patients with PSM undergoing CRS combined with HIPEC are predominantly attributed to SCN, , and . Notably, Enterobacteriaceae exhibited resistance to carbapenem. Independent risk factors for postoperative infections in PSM include age, prior tumor treatment, tumor tissue type, and completeness of cytoreduction score.
PubMed: 38912220
DOI: 10.2147/IDR.S462639 -
Open Life Sciences 2024, predominantly recognized as an opportunistic pathogen affecting immunocompromised hosts, and , a widespread zoonotic bacterium, infrequently co-infect immunocompetent...
, predominantly recognized as an opportunistic pathogen affecting immunocompromised hosts, and , a widespread zoonotic bacterium, infrequently co-infect immunocompetent adults, thereby posing a distinctive diagnostic challenge. Here, we describe a case involving a 53-year-old male with a history of goat farming, who presented with persistent chest tightness, cough, and notable weight loss, absent fever. Radiological and bronchoscopic assessments showed a right hilar mass, extensive vertebral destruction, and bronchial lesions, deviating from the typical symptoms associated with either pathogen. Laboratory analyses confirmed a co-infection involving and . Initial therapy with levofloxacin and vancomycin proved ineffective; however, a subsequent treatment regimen comprising azithromycin, etimicin, minocycline, and moxifloxacin resulted in substantial clinical improvement. This case accentuates the intricacies involved in diagnosing and managing atypical co-infections in immunocompetent individuals and underscores the importance of careful microbiological testing to inform effective therapeutic strategies.
PubMed: 38911933
DOI: 10.1515/biol-2022-0888 -
RSC Medicinal Chemistry Jun 2024() is one of the most threatening bacteria globally, causing high mortality and morbidity in humans and animals, and is considered a public health threat that requires...
() is one of the most threatening bacteria globally, causing high mortality and morbidity in humans and animals, and is considered a public health threat that requires urgent and aggressive action. Interruption of the human gut microbiome and the development of antibiotic resistance urgently require development and synthesis of effective alternative antibiotics with minimal effects on the normal gut microbial flora. In this study, cyclization of the aminoguanidine head to the thiazole nucleus while maintaining its other pharmacophoric features leads to selective targeting of as shown in the graphical abstract. The most promising compound, 5, was significantly more efficient than vancomycin and metronidazole against six strains of with MIC values as low as 0.030 μg mL. Additionally, compound 5 was superior to vancomycin and metronidazole, showing no inhibition toward nine tested strains of the normal human gut microbiota (>64 μg mL). The high safety profile of compound 5 was also observed with two cell lines HRT-18 and Vero cells.
PubMed: 38911156
DOI: 10.1039/d4md00164h -
Zhongguo Gu Shang = China Journal of... Jun 2024To explore clinical effect of vancomycin calcium sulfate combined with internal fixation on calcaneal beak-like fracture secondary to calcaneal osteomyelitis caused by...
OBJECTIVE
To explore clinical effect of vancomycin calcium sulfate combined with internal fixation on calcaneal beak-like fracture secondary to calcaneal osteomyelitis caused by diabetic foot.
METHODS
From April 2018 to October 2021, a retrospective analysis was performed on 5 patients with calcaneal bone osteomyelitis secondary to diabetic foot, including 2 males and 3 females, aged from 48 to 60 years old;diabetes course ranged from 5 to 13 years;the courses of diabetic foot disease ranged from 18 to 52 days;5 patients were grade Ⅲ according to Wagner classification. All patients were treated with debridement, vancomycin bone cement implantation, negative pressure aspiration at stageⅠ, vancomycin calcium sulfate and internal fixation at stageⅡfor calcaneal beak-like fracture. Surgical incision and fracture healing time were recorded, and the recurrence of osteomyelitis was observed. American Orthopedic Foot Andankle Society (AOFAS) score and exudation at 12 months after operation were evaluated.
RESULTS
Five patients were successfully completed operation without lower extremity vascular occlusion, and were followed up for 16 to 36 months. The wound healing time after internal fixation ranged from 16 to 26 days, and healing time of fractures ranged from 16 to 27 weeks. AOFAS score ranged from 65 to 91 at 12 months after operation, and 2 patients got excellent result, 2 good and 1 fair. Among them, 1 patient with skin ulcer on the back of foot caused by scalding at 5 months after operation (non-complication), was recovered after treatment;the wound leakage complication occurred in 2 patients, and were recovered after dressing change. No osteomyelitis or fracture occurred in all patients.
CONCLUSION
Vancomycin calcium sulfate with internal fixation in treating calcaneal osteomyelitis secondary to calcaneal osteomyelitis caused by diabetic foot could not only control infection, but also promote fracture healing, and obtain good clinical results.
Topics: Humans; Male; Middle Aged; Female; Osteomyelitis; Diabetic Foot; Calcaneus; Retrospective Studies; Fracture Fixation, Internal; Fractures, Bone
PubMed: 38910385
DOI: 10.12200/j.issn.1003-0034.20230327 -
The Knee Jun 2024Periprosthetic joint infections (PJIs) are commonly treated with two-stage revision surgery utilising antibiotic-loaded spacers; however, antibiotic release from spacers...
BACKGROUND
Periprosthetic joint infections (PJIs) are commonly treated with two-stage revision surgery utilising antibiotic-loaded spacers; however, antibiotic release from spacers is limited and usually drops below effective levels a few days after placement. This study compared high-dose and standard-dose vancomycin-loaded spacers in terms of efficacy, safety, and overall treatment duration in a rat periprosthetic joint infection model.
METHODS
Thirty male Wistar albino rats (8-10 weeks old, 300-320 g) were housed individually at standard conditions. A periprosthetic infection model was established in the right knee of the rats using methicillin-resistant Staphylococcus aureus (MRSA) -contaminated Kirschner wires. Two weeks later, the infection was verified, and the Kirschner wires were removed. Rats were randomly divided into three groups (n = 10): standard-dose (SVanc) and high-dose (HVanc) vancomycin groups had 2.5 and 7.5% vancomycin in their spacers, respectively, while the control group had no spacers. All groups received intramuscular (IM) vancomycin and gentamicin for 4 weeks after spacer implantation. Microbiological counts and vancomycin levels in the blood and joint flush samples were measured, and histopathological assessments were conducted on the femur and kidneys.
RESULTS
After spacer implantation, MRSA was eliminated in the HVanc group with 4 weeks of treatment, while the SVanc group required 6 weeks of treatment (P < 0.001). Histopathological findings of the femoral medulla and cortical samples were better in the HVanc group compared with other groups (P = 0.007). Vancomycin levels in serum remained within safe limits in all groups, and kidney damage was not observed.
CONCLUSION
The use of high-dose vancomycin spacers might accelerate the transition period, which in turn reduces the duration of systemic antibiotic use and mitigates the risk of nephrotoxicity. Thus, this method may decrease the medical costs associated with PJI treatment.
PubMed: 38909590
DOI: 10.1016/j.knee.2024.06.004 -
Chinese Medicine Jun 2024Rising resistance to antimicrobials, particularly in the case of methicillin-resistant Staphylococcus aureus (MRSA), represents a formidable global health challenge....
BACKGROUND
Rising resistance to antimicrobials, particularly in the case of methicillin-resistant Staphylococcus aureus (MRSA), represents a formidable global health challenge. Consequently, it is imperative to develop new antimicrobial solutions. This study evaluated 68 Chinese medicinal plants renowned for their historical applications in treating infectious diseases.
METHODS
The antimicrobial efficacy of medicinal plants were evaluated by determining their minimum inhibitory concentration (MIC) against MRSA. Safety profiles were assessed on human colorectal adenocarcinoma (Caco-2) and hepatocellular carcinoma (HepG2) cells. Mechanistic insights were obtained through fluorescence and transmission electron microscopy (FM and TEM). Synergistic effects with vancomycin were investigated using the Fractional Inhibitory Concentration Index (FICI).
RESULTS
Rheum palmatum L., Arctium lappa L. and Paeonia suffructicosaas Andr. have emerged as potential candidates with potent anti-MRSA properties, with an impressive low MIC of 7.8 µg/mL, comparable to the 2 µg/mL MIC of vancomycin served as the antibiotic control. Crucially, these candidates demonstrated significant safety profiles when evaluated on Caco-2 and HepG2 cells. Even at 16 times the MIC, the cell viability ranged from 83.3% to 95.7%, highlighting their potential safety. FM and TEM revealed a diverse array of actions against MRSA, such as disrupting the cell wall and membrane, interference with nucleoids, and inducing morphological alterations resembling pseudo-multicellular structures in MRSA. Additionally, the synergy between vancomycin and these three plant extracts was evident against MRSA (FICI < 0.5). Notably, aqueous extract of R. palmatum at 1/4 MIC significantly reduced the vancomycin MIC from 2 µg/mL to 0.03 µg/mL, making a remarkable 67-fold decrease.
CONCLUSIONS
This study unveil new insights into the mechanistic actions and pleiotropic antibacterial effectiveness of these medicinal plants against resistant bacteria, providing robust evidence for their potential use as standalone or in conjunction with antibiotics, to effectively combat antimicrobial resistance, particularly against MRSA.
PubMed: 38909250
DOI: 10.1186/s13020-024-00960-8 -
Biomaterials Jun 2024Conventional wound approximation devices, including sutures, staples, and glues, are widely used but risk of wound dehiscence, local infection, and scarring can be...
Conventional wound approximation devices, including sutures, staples, and glues, are widely used but risk of wound dehiscence, local infection, and scarring can be exacerbated in these approaches, including in diabetic and obese individuals. This study reports the efficacy and quality of tissue repair upon photothermal sealing of full-thickness incisional skin wounds using silk fibroin-based laser-activated sealants (LASEs) containing copper chloride salt (Cu-LASE) or silver nanoprisms (AgNPr-LASE), which absorb and convert near-infrared (NIR) laser energy to heat. LASE application results in rapid and effective skin sealing in healthy, immunodeficient, as well as diabetic and obese mice. Although lower recovery of epidermal structure and function was seen with AgNPr-LASE sealing, likely because of the hyperthermia induced by laser and presence of this material in the wound space, this approach resulted in higher enhancement in recovery of skin biomechanical strength compared to sutures and Cu-LASEs in diabetic, obese mice. Histological and immunohistochemical analyses revealed that AgNPr-LASEs resulted in significantly lower neutrophil migration to the wound compared to Cu-LASEs and sutures, indicating a more muted inflammatory response. Cu-LASEs resulted in local tissue toxicity likely because of effects of copper ions as manifested in the form of a significant epidermal gap and a 'depletion zone', which was a region devoid of viable cells proximal to the wound. Compared to sutures, LASE-mediated sealing, in later stages of healing, resulted in increased angiogenesis and diminished myofibroblast activation, which can be indicative of lower scarring. AgNPr-LASE loaded with vancomycin, an antibiotic drug, significantly lowered methicillin-resistant Staphylococcus aureus (MRSA) load in a pathogen challenge model in diabetic and obese mice and also reduced post-infection inflammation of tissue compared to antibacterial sutures. Taken together, these attributes indicate that AgNPr-LASE demonstrated a more balanced quality of tissue sealing and repair in diabetic and obese mice and can be used for combating local infections, that can result in poor healing in these individuals.
PubMed: 38908232
DOI: 10.1016/j.biomaterials.2024.122668