A Potential Effect of Gram-Negative Bacilli Colonization on Periprosthetic Joint Infection.
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ABSTRACT:
SUBMITTER: Ito H
PROVIDER: S-EPMC9490568 | biostudies-literature | 2022 Oct
REPOSITORIES: biostudies-literature
Publications
A Potential Effect of Gram-Negative Bacilli Colonization on Periprosthetic Joint Infection.
Arthroplasty today 20220919
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Project description:The development of new strategic therapies for multidrug-resistant bacteria, like the use of non-antimicrobial approaches and/or drugs repurposed to be used as monotherapies or in combination with clinically relevant antibiotics, has become urgent. A therapeutic alternative for infections by multidrug-resistant Gram-negative bacilli (MDR-GNB) is immune system modulation to improve the infection clearance. We showed that immunocompetent mice pretreated with tamoxifen at 80 mg/kg/d for three days and infected with Acinetobacter baumannii, Pseudomonas aeruginosa, or Escherichia coli in peritoneal sepsis models showed reduced release of the monocyte chemotactic protein-1 (MCP-1) and its signaling pathway interleukin-18 (IL-18), and phosphorylated extracellular signal-regulated kinase 1/2 (ERK1/2). This reduction of MCP-1 induced the reduction of migration of inflammatory monocytes and neutrophils from the bone marrow to the blood. Indeed, pretreatment with tamoxifen in murine peritoneal sepsis models reduced the bacterial load in tissues and blood, and increased mice survival from 0% to 60-100%. Together, these data show that tamoxifen presents therapeutic efficacy against MDR A. baumannii, P. aeruginosa, and E. coli in experimental models of infection and may be a new candidate to be repurposed as a treatment for GNB infections.
| S-EPMC8230278 | biostudies-literature
Project description:The volume of joint replacement surgery has risen steadily in recent years, because the population is aging and increasingly wishes to reserve a high functional status onward into old age. Infection is among the more common complications of joint replacement surgery, arising in 0.2% to 2% of patients, or as many as 9% in special situations such as the implantation of megaprostheses. The associated morbidity and mortality are high. It is thus very important to minimize risk factors for infection and to optimize the relevant diagnostic and therapeutic strategies.This review is based on pertinent publications retrieved by a selective search in PubMed, including current guidelines and expert recommendations.The crucial diagnostic step is joint biopsy for the identification of the pathogenic organism, which succeeds with over 90% sensitivity and specificity. If the prosthesis is firmly anchored in bone, the pathogen is of a type that responds well to treatment, and symptomatic infection has been present only for a short time, then rapidly initiated treatment can save the prosthesis in 35-90% of cases. The pillars of treatment are thorough surgical care (radical débridement) and targeted antibiotic therapy. On the other hand, if the prosthesis is loose or the pathogen is of a poorly treatable type, the infection can generally only be cured by a change of the prosthesis. This can be performed in either one or two procedures, always in conjunction with systemic antibiotic therapy tailored to the specific sensitivity and resistance pattern of the pathogen.The risk of infection of an artificial joint is low, but the overall prevalence of such infections is significant, as the number of implanted joints is steadily rising. Artificial joint infections should be treated by a standardized algorithm oriented toward the recommendations of current guidelines. Many of these recommendations, however, are based only on expert opinion, as informative studies providing high-grade evidence are lacking. Thus, for any particular clinical situation, there may now be multiple therapeutic approaches with apparently comparable efficacy. Randomized trials are urgently needed.
| S-EPMC5471600 | biostudies-other
Project description:Periprosthetic joint infection (PJI), a devastating complication of total joint replacement, is of incompletely understood pathogenesis and may sometimes be challenging to clinically distinguish from other causes of arthroplasty failure. We characterized human gene expression in 93 specimens derived from surfaces of resected arthroplasties, comparing transcriptomes of subjects with infection- versus non-infection-associated arthroplasty failure. Differential gene expression analysis confirmed 28 previously reported potential biomarkers of PJI, including bactericidal/permeability increasing protein (BPI), cathelicidin antimicrobial peptide (CAMP), C-C-motif chemokine ligand 3 (CCL3), 4(CCL4), and C-X-C-motif chemokine ligand 2 (CXCL2), colony stimulating factor 2 receptor beta (CSF2RB), colony stimulating factor 3 (CSF3), alpha-defensin (DEFA4), Fc fragment of IgG receptor 1B (CD64B), intercellular adhesion molecule 1 (ICAM1), interferon gamma (IFNG), interleukin 13 receptor subunit alpha 2 (IL13RA2), interleukin 17D (IL17D), interleukin 1 (IL1A, IL1B, IL1RN), interleukin 2 receptors (IL2RA, IL2RG), interleukin 5 receptor (IL5RA), interleukin 6 (IL6), interleukin 8 (IL8), lipopolysaccharide binding protein (LBP), lipocalin (LCN2), lactate dehydrogenase C (LDHC), lactotransferrin (LTF), matrix metallopeptidase 3 (MMP3), peptidase inhibitor 3 (PI3), and vascular endothelial growth factor A (VEGFA), and identified three novel molecules of potential diagnostic use for detection of PJI, namely C-C-motif chemokine ligand CCL20, coagulation factor VII (F7), and B cell receptor FCRL4. Comparative analysis of infections caused by staphylococci versus bacteria other than staphylococci and Staphylococcus aureus versus Staphylococcus epidermidis showed elevated expression of interleukin 13 (IL13), IL17D, and MMP3 in staphylococcal infections, and of IL1B, IL8, and platelet factor PF4V1 in S. aureus compared to S. epidermidis infections. Pathway analysis of over-represented genes suggested activation of host immune response and cellular maintenance and repair functions in response to invasion of infectious agents. The data presented provides new potential targets for diagnosis of PJI and for differentiation of PJI caused by different infectious agents.
2024-02-19 | GSE255786 | GEO
Project description:BackgroundColonization of the oropharynx with gram-negative bacilli (GNB) is considered a negative prognostic factor in immunocompromised individuals. Hemato-oncologic patients represent a high-risk group due to their immunodeficiencies and associated treatments. This study aimed to determine the rates of oral colonization by GNB, associated factors, and clinical outcomes in patients with hematologic malignancies and solid tumors compared with healthy subjects.MethodsWe conducted a comparative study of hemato-oncologic patients and healthy subjects from August to October 2022. Swabs were taken from the oral cavity; specimens with GNB were identified and tested for antimicrobial susceptibility.ResultsWe included 206 participants (103 hemato-oncologic patients and 103 healthy subjects). Hemato-oncologic patients had higher rates of oral colonization by GNB (34% vs. 17%, P = 0.007) and GNB resistant to third-generation cephalosporins (11.6% vs. 0%, P < 0.001) compared to healthy subjects. Klebsiella spp. was the predominant genus in both groups. The factor associated with oral colonization by GNB was a Charlson index ≥ 3, while ≥ 3 dental visits per year were a protective factor. Regarding colonization by resistant GNB in oncology patients, antibiotic therapy and a Charlson index ≥ 5 were identified as associated factors, while better physical functionality (ECOG ≤ 2) was associated with less colonization. Hemato-oncologic patients colonized with GNB had more 30-day infectious complications (30.5% vs. 2.9%, P = 0.0001) than non-colonized patients.ConclusionOral colonization by GNB and resistant GNB are prevalent in cancer patients, especially those with higher scores on the severity scales. Infectious complications occurred more frequently in colonized patients. There is a knowledge gap about dental hygiene practices in hemato-oncologic patients colonized by GNB. Our results suggest that patients' hygienic-dietary habits, especially frequent dental visits, are a protective factor against colonization.
| S-EPMC10329337 | biostudies-literature
Project description: Not available
| S-EPMC9678642 | biostudies-literature
Project description:BackgroundPeriprosthetic joint infection (PJI) remains one of the most devastating complications following total joint arthroplasty. Appropriate prophylactic antimicrobial administration and antibiotic stewardship are major factors impacting the risk of PJI in total hip arthroplasty (THA). The purpose of our study was to evaluate whether cefazolin administration was superior to noncefazolin antibiotics in prevention of PJI after primary THA.Material and methodsA review of 9910 patients undergoing primary THA from 2013 to 2019 at a single institution was conducted. The primary outcome was PJI within 90 days of surgery. The Musculoskeletal Infection Society definition of PJI was used for this analysis. Groups were those receiving cefazolin + expanded gram-negative antimicrobial prophylaxis (EGNAP) and those receiving an alternative to cefazolin + EGNAP. Chi-square tests were conducted to determine statistical significance. Multivariate logistic regression was performed to eliminate confounders.Results9028 patients received cefazolin + EGNAP, and 882 patients received an alternative to cefazolin + EGNAP. PJI rate using the Musculoskeletal Infection Society criteria was 0.82% (81/9910). PJI rate in the cefazolin + EGNAP group was 0.75% (68/9028). In the group receiving an alternative to cefazolin + EGNAP, the PJI rate was 1.47% (13/882). This difference was statistically significant (P = .023). On multivariate analysis, the odds ratio for developing PJI when an alternative to cefazolin was used was 2.05 (P = .022). When comparing alternatives, there remained a statistically significant increased PJI rate when the alternative used was clindamycin (odds ratio 2.65, P = .007).ConclusionOur data demonstrate that in the presence of EGNAP in THA, there was a higher PJI rate when clindamycin was given as an alternative to cefazolin. The number of THA patients receiving alternatives to cefazolin must be minimized.Level of evidenceIII, Retrospective Cohort Study.
| S-EPMC8943215 | biostudies-literature