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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 -
The Journal of Antimicrobial... Jun 2024Elizabethkingia spp. are emerging as nosocomial pathogens causing various infections. These pathogens express resistance to a broad range of antibiotics, thus requiring...
BACKGROUND
Elizabethkingia spp. are emerging as nosocomial pathogens causing various infections. These pathogens express resistance to a broad range of antibiotics, thus requiring antimicrobial combinations for coverage. However, possible antagonistic interactions between antibiotics have not been thoroughly explored. This study aimed to evaluate the effectiveness of antimicrobial combinations against Elizabethkingia infections, focusing on their impact on pathogenicity, including biofilm production and cell adhesion.
METHODS
Double-disc diffusion, time-kill, and chequerboard assays were used for evaluating the combination effects of antibiotics against Elizabethkingia spp. We further examined the antagonistic effects of antibiotic combinations on biofilm formation and adherence to A549 human respiratory epithelial cells. Further validation of the antibiotic interactions and their implications was performed using ex vivo hamster precision-cut lung sections (PCLSs) to mimic in vivo conditions.
RESULTS
Antagonistic effects were observed between cefoxitin, imipenem and amoxicillin/clavulanic acid in combination with vancomycin. The antagonism of imipenem toward vancomycin was specific to its effects on the genus Elizabethkingia. Imipenem further hampered the bactericidal effect of vancomycin and impaired its inhibition of biofilm formation and the adhesion of Elizabethkingia meningoseptica ATCC 13253 to human cells. In the ex vivo PCLS model, vancomycin exhibited dose-dependent bactericidal effects; however, the addition of imipenem also reduced the effect of vancomycin.
CONCLUSIONS
Imipenem reduced the bactericidal efficacy of vancomycin against Elizabethkingia spp. and compromised its capacity to inhibit biofilm formation, thereby enhancing bacterial adhesion. Clinicians should be aware of the potential issues with the use of these antibiotic combinations when treating Elizabethkingia infections.
PubMed: 38906827
DOI: 10.1093/jac/dkae210 -
Journal of Microbiology (Seoul, Korea) Jun 2024Alcaligenes faecalis is one of the most important and clinically significant environmental pathogens, increasing in importance due to its isolation from soil and...
Alcaligenes faecalis is one of the most important and clinically significant environmental pathogens, increasing in importance due to its isolation from soil and nosocomial environments. The Gram-negative soil bacterium is associated with skin endocarditis, bacteremia, dysentery, meningitis, endophthalmitis, urinary tract infections, and pneumonia in patients. With emerging antibiotic resistance in A. faecalis, it has become crucial to understand the origin of such resistance genes within this clinically significant environmental and gut bacterium. In this research, we studied the impact of antibiotic overuse in poultry and its effect on developing resistance in A. faecalis. We sampled soil and faecal materials from five poultry farms, performed whole genome sequencing & analysis and identified four strains of A. faecalis. Furthermore, we characterized the genes in the genomic islands of A. faecalis isolates. We found four multidrug-resistant A. faecalis strains that showed resistance against vancomycin (MIC >1000 μg/ml), ceftazidime (50 μg/ml), colistin (50 μg/ml) and ciprofloxacin (50 μg/ml). From whole genome comparative analysis, we found more than 180 resistance genes compared to the reference sequence. Parts of our assembled contigs were found to be similar to different bacteria which included pbp1A and pbp2 imparting resistance to amoxicillin originally a part of Helicobacter and Bordetella pertussis. We also found the Mycobacterial insertion element IS6110 in the genomic islands of all four genomes. This prominent insertion element can be transferred and induce resistance to other bacterial genomes. The results thus are crucial in understanding the transfer of resistance genes in the environment and can help in developing regimes for antibiotic use in the food and poultry industry.
PubMed: 38904697
DOI: 10.1007/s12275-024-00129-w -
Journal of Burn Care & Research :... Jun 2024Vancomycin is a glycopeptide antibiotic that requires close therapeutic monitoring. Prolonged exposure to elevated concentrations increases risk for serious adverse...
A Multicenter, Retrospective Outcome Analysis of Vancomycin Area Under the Curve versus Trough-Based Dosing Strategies in Patients with Burn OR Inhalational Injuries (MONITOR).
Vancomycin is a glycopeptide antibiotic that requires close therapeutic monitoring. Prolonged exposure to elevated concentrations increases risk for serious adverse effects such as nephrotoxicity. However, sub-therapeutic concentrations may lead to bacterial resistance and clinical failure or death. The most recent Infectious Diseases Society of America (IDSA) publication regarding therapeutic monitoring of vancomycin recommends utilizing area under the curve (AUC)-based monitoring to maximize clinical success. Despite the guideline recommendation for AUC-guided dosing, many institutions still use trough-only monitoring in their practices, including those caring for patients with acute burn injuries. Following burn injury, patients are at a higher risk for infections, multi-organ failure, and pharmacokinetic alterations. The primary objective of this multi-center retrospective study is to determine optimal therapeutic monitoring of vancomycin by comparing clinical success between AUC vs. trough-based monitoring in burn patients. MONITOR was a multicenter, retrospective study of patients with thermal or inhalation injury admitted to one of 13 burn centers from 1/1/17 to 8/31/22 who received vancomycin. Demographic and clinical course data, including acute kidney injury (AKI) incidence and clinical success were obtained. Patients were evaluated for clinical success and grouped according to method of monitoring and adjusting doses: AUC vs. trough-based monitoring. Clinical success was a composite definition and lack of meeting any 1 of 5 criteria: 1) persistent infection, 2) relapse, 3) antibiotic failure (clinical worsening), 4) AKI, 5) death. Five-hundred seventeen vancomycin courses were assessed from 485 patients. There was no difference in the rate of clinical success between AUC monitored and the trough-only monitored groups. Incidence of AKI was higher in the trough-only group; however, was not statistically significant after controlling for renal function on admission, past medical history of chronic kidney disease (CKD), and concomitant nephrotoxins.
PubMed: 38900835
DOI: 10.1093/jbcr/irae109