scholarly journals 1070. In vitro Activity of PLG0206 Against Isolates Commonly Found in Periprosthetic Joint Infections (PJI)

2021 ◽  
Vol 8 (Supplement_1) ◽  
pp. S627-S628
Author(s):  
David Huang ◽  
Jonathan Steckbeck ◽  
Chris Pillar ◽  
Bev Murray ◽  
David Huganfel ◽  
...  
Keyword(s):  
Culture Collection ◽  
Multi Drug Resistance ◽  
Broth Microdilution ◽  
Coagulase Negative Staphylococci ◽  
Cationic Antimicrobial Peptide ◽  
Gram Negative ◽  
Joint Infections ◽  
Prosthetic Joint ◽  
Prosthetic Joint Infections

Abstract Background PLG0206 is a novel engineered cationic antimicrobial peptide being evaluated for treatment of prosthetic joint infections. In this study, the activity of PLG0206 was evaluated by broth microdilution against 104 isolates of Staphylococcus epidermidis, 53 other coagulase-negative staphylococci (CoNS), 3 S. aureus, and 66 Gram-negative isolates consisting of Enterobacterales, Pseudomonas aeruginosa, and Acinetobacter baumannii. Methods Imipenem, levofloxacin, tigecycline, linezolid, vancomycin, oxacillin, ceftazidime, colistin, and amikacin were tested as comparators. Testing was conducted in accordance with guidelines from the Clinical and Laboratory Standards Institute (CLSI; M7 and M100). Test organisms consisted of reference strains from the American Type Culture Collection, the Centers for Disease Control Antibiotic Reference Bank and clinical isolates from the Micromyx repository. The media employed for testing in the broth microdilution MIC assay for all organisms were cation-adjusted Mueller Hinton Broth and for PLG0206 only included RPMI-1640 medium supplemented with 0.002% P-80. Results Activity of PLG0206 in RPMI against CoNS, S. aureus, and resistant Gram-negative* pathogens are shown in Table. Activity of PLG0206 in RPMI against CoNS, S. aureus and resistant Gram-negative* pathogens Activity of PLG0206 in RPMI against CoNS, S. aureus and resistant Gram-negative* pathogens Conclusion PLG0206 was found to have potent antimicrobial activity when evaluated in RPMI against S. epidermidis, CoNS non-epidermidis, S. aureus, Enterobacterales, P. aeruginosa, and A. baumannii, including isolates with multi-drug resistance. Disclosures David Huang, MD, PhD, Peptilogics (Employee) Jonathan Steckbeck, PhD, Peptilogics (Employee) Chris Pillar, PhD, Micromyx (Employee) Bev Murray, BS, Micromyx (Employee) David Huganfel, BS, Micromyx (Employee) Dean Shinabanger, PhD, Micromyx (Employee)

scholarly journals Antimicrobial Activity of Dalbavancin and Comparator Agents Tested against Gram-Positive Clinical Isolates Causing Bone and Joint Infections in United States (US) Medical Centers (2011–2016)

2017 ◽  
Vol 4 (suppl_1) ◽  
pp. S373-S373
Author(s):  
Helio S Sader ◽  
Rodrigo E Mendes ◽  
Robert K Flamm ◽  
Michael A Pfaller
Keyword(s):  
Active Agent ◽  
Coagulase Negative Staphylococci ◽  
Gram Positive ◽  
Joint Infections ◽  
Bone And Joint Infections ◽  
Prosthetic Joint ◽  
Prosthetic Joint Infections ◽  
Viridans Group Streptococci ◽  
Research Grant

Abstract Background Bone and joint infections (BJI) comprise a series of disorders, including septic arthritis, osteomyelitis, and prosthetic joint infections. We evaluated the activity of dalbavancin (DALBA) against pathogens isolated from BJI in US hospitals. Methods A total of 744 organisms collected from 55 hospitals in 2011–2016 were evaluated, including 463 S. aureus, 88 coagulase-negative staphylococci (CoNS), 104 β-haemolytic streptococci (BHS), 60 E. faecalis, and 29 viridans group streptococci (VGS). Bacteria were identified by standard algorithms and MALDI-TOF-MS. Susceptibility testing was performed by CLSI methods (M07-A10); interpretation of MIC results used CLSI (2017) and EUCAST (2017) criteria. Results S. aureus (62.2%) was the most common pathogen associated with BJI, followed by BHS (14.0%) and CoNS (11.8%). All S. aureus (41.5% methicillin-resistant [MRSA]) isolates were susceptible (S) to DALBA, linezolid (LNZ), teicoplanin (TEI) and vancomycin (VAN), while daptomycin (DAPTO) and clindamycin (CLI) showed susceptibility rates of 99.8% and 87.7% (CLSI), respectively. DALBA MIC results (MIC50/90, ≤0.03/0.06 μg/mL) were ≥8-fold lower compared with DAPTO (MIC50/90, 0.25/0.5 μg/mL) against all S. aureus. Among CoNS, (61.4% MRSA), DALBA (MIC50/90, ≤0.03/0.06 μg/mL) was the most potent agent, followed by DAPTO (MIC50/90, 0.25/0.5 μg/mL), LNZ (MIC50/90, 0.5/1 μg/mL), and VAN (MIC50/90, 1/2 μg/mL). DALBA inhibited all E. faecalis isolates at ≤0.25 μg/mL (FDA S breakpoint), except for 3 VAN-resistant (VanA) isolates. High susceptibility rates for ampicillin (98.3%; CLSI), DAPTO (100.0%), LNZ (100.0%), TEI (93.3%) and VAN (93.3%) were obtained against E. faecalis. DALBA, DAPTO, LNZ, ceftriaxone, penicillin, and VAN were active against all BHS (100.0%S), while DALBA (MIC50/90, ≤0.03/0.06 μg/mL; 100.0%S) was the most active agent against VGS, inhibiting all isolates at ≤0.06 μg/mL. Ceftriaxone, LNZ, DAPTO, and VAN were also active against VGS (93.1 – 100.0%S; CLSI), whereas CLI (82.8%S) had marginal activity. Conclusion DALBA demonstrated potent in vitro activity against common gram-positive isolates causing BJI (2011–2016) and appears to be a viable candidate for treating BJI/osteomyelitis caused by gram-positive cocci. Disclosures H. S. Sader, Allergan: Research Contractor, Research grant; R. E. Mendes, Allergan: Research Contractor, Research grant; R. K. Flamm, Allergan: Research Contractor, Research grant; M. A. Pfaller, Allergan: Research Contractor, Research grant

scholarly journals Intraoperative Bacterial Contamination and Activity of Different Antimicrobial Prophylaxis Regimens in Primary Knee and Hip Replacement

Antibiotics ◽  
2020 ◽  
Vol 10 (1) ◽  
pp. 18
Author(s):  
Alba Rivera ◽  
Alba Sánchez ◽  
Sonia Luque ◽  
Isabel Mur ◽  
Lluís Puig ◽  
...  
Keyword(s):  
Hip Replacement ◽  
Bacterial Contamination ◽  
Antimicrobial Prophylaxis ◽  
Coagulase Negative Staphylococci ◽  
Joint Infections ◽  
Prosthetic Joint ◽  
Prosthetic Joint Infections ◽  
Total Knee ◽  
Surgical Antimicrobial Prophylaxis ◽  
Almost All

Surgical antimicrobial prophylaxis (SAP) is important for the prevention of prosthetic joint infections (PJIs) and must be effective against the microorganisms most likely to contaminate the surgical site. Our aim was to compare different SAP regimens (cefazolin, cefuroxime, or vancomycin, alone or combined with gentamicin) in patients undergoing total knee (TKA) and hip (THA) arthroplasty. In this preclinical exploratory analysis, we analyzed the results of intraoperative sample cultures, the ratio of plasma antibiotic levels to the minimum inhibitory concentrations (MICs) for bacteria isolated at the surgical wound and ATCC strains, and serum bactericidal titers (SBT) against the same microorganisms. A total of 132 surgical procedures (68 TKA, 64 THA) in 128 patients were included. Cultures were positive in 57 (43.2%) procedures (mostly for coagulase-negative staphylococci and Cutibacterium spp.); the rate was lower in the group of patients receiving combination SAP (adjusted OR 0.475, CI95% 0.229–0.987). The SAP regimens evaluated achieved plasma levels above the MICs in almost all of intraoperative isolates (93/94, 98.9%) and showed bactericidal activity against all of them (SBT range 1:8–1:1024), although SBTs were higher in patients receiving cefazolin and gentamicin-containing regimens. The potential clinical relevance of these findings in the prevention of PJIs remains to be determined.

scholarly journals Rifampin Combination Therapy for Nonmycobacterial Infections

2010 ◽  
Vol 23 (1) ◽  
pp. 14-34 ◽  
Author(s):  
Graeme N. Forrest ◽  
Kimberly Tamura
Keyword(s):  
Combination Therapy ◽  
Prosthetic Heart Valve ◽  
Case Series ◽  
Source Control ◽  
Retrospective Case ◽  
Coagulase Negative Staphylococci ◽  
Joint Infections ◽  
Prosthetic Joint Infections

SUMMARY The increasing emergence of antimicrobial-resistant organisms, especially methicillin-resistant Staphylococcus aureus (MRSA), has resulted in the increased use of rifampin combination therapy. The data supporting rifampin combination therapy in nonmycobacterial infections are limited by a lack of significantly controlled clinical studies. Therefore, its current use is based upon in vitro or in vivo data or retrospective case series, all with major limitations. A prominent observation from this review is that rifampin combination therapy appears to have improved treatment outcomes in cases in which there is a low organism burden, such as biofilm infections, but is less effective when effective surgery to obtain source control is not performed. The clinical data support rifampin combination therapy for the treatment of prosthetic joint infections due to methicillin-sensitive S. aureus (MSSA) after extensive debridement and for the treatment of prosthetic heart valve infections due to coagulase-negative staphylococci. Importantly, rifampin-vancomycin combination therapy has not shown any benefit over vancomycin monotherapy against MRSA infections either clinically or experimentally. Rifampin combination therapy with daptomycin, fusidic acid, and linezolid needs further exploration for these severe MRSA infections. Lastly, an assessment of the risk-benefits is needed before the addition of rifampin to other antimicrobials is considered to avoid drug interactions or other drug toxicities.

scholarly journals Gram‐Negative Prosthetic Joint Infections: Risk Factors and Outcome of Treatment

2009 ◽  
Vol 49 (7) ◽  
pp. 1036-1043 ◽  
Author(s):  
Pang‐Hsin Hsieh ◽  
Mel S. Lee ◽  
Kuo‐Yao Hsu ◽  
Yu‐Han Chang ◽  
Hsin‐Nung Shih ◽  
...  
Keyword(s):  
Risk Factors ◽  
Gram Negative ◽  
Joint Infections ◽  
Prosthetic Joint ◽  
Prosthetic Joint Infections

Prosthetic Joint Infections Due to Coagulase-Negative Staphylococci

2015 ◽  
Vol 3 (1) ◽  
Author(s):  
Morad Mohamad ◽  
Luca Deabate ◽  
Wilson Belaieff ◽  
Cindy Bouvet ◽  
Mathieu Zingg ◽  
...  
Keyword(s):  
Coagulase Negative Staphylococci ◽  
Joint Infections ◽  
Prosthetic Joint ◽  
Prosthetic Joint Infections

scholarly journals Multidrug-Resistant Gram-Negative bacilli Prosthetic Joint Infection: A Worrisome Scenario

2017 ◽  
Vol 4 (suppl_1) ◽  
pp. S97-S97
Author(s):  
Taiana Ribeiro ◽  
Giselle Klautau ◽  
Mauro Salles ◽  
Keyword(s):  
Joint Infection ◽  
Multidrug Resistant ◽  
Adult Patients ◽  
Tissue Cultures ◽  
Knee Prostheses ◽  
Coagulase Negative Staphylococci ◽  
Gram Negative ◽  
Prosthetic Joint ◽  
Prosthetic Joint Infections ◽  
Fluid Culture

Abstract Background The spectrum of the microbial etiology of prosthetic joint infections (PJIs) is changing, with a higher occurrence of Gram-negative bacilli (GNB) nowadays. In Latine America, GNB infections are usually caused by strains that produce multiple resistance mechanisms, making antimicrobial treatment increasingly difficult, especially for these biofilm-associated infections. We aimed to demonstrate the higher frequency of PJIs caused by GNB. Methods We performed a retrospective observational study with adult patients with a diagnosis of knee and hip PJIs. Patients included were submitted to an exchange of total hip and knee prostheses between September 2010 and December 2016, in two brazilian hospitals. It was included only patients with microbial diagnosis performed using either sonication fluid cultures of retrieved implant and conventional tissue cultures of periprosthetic tissues. The Infectious Disease Society of America (IDSA) definition was used to establish the diagnosis of PJIs. Multidrug-resistant (MDR) organisms were defined as acquired resistance to at least one agent in three or more antimicrobial categories. Results Were included 130 adult patients with a median age of 65.5 years, in which 60% were female. Infected hip arthroplasty was more frequent than knee infections (69% vs. 31%) and 61% were classified as late infection according to Zimmerli’s classification. One hundred twenty-three microorganisms were isolated on the tissue and sonication fluid culture. Despite the Coagulase-negative Staphylococci was the predominant microorganism (35%), Gram-negative bacilli had an expressive frequency of 30% of positivity on culture. Amongst them, 23% showed resistance to carbapenens and 38% were MDR-bacteria. The predominant microorganism was Pseudomonas spp., followed by Enterobacter spp., Acinetobacter spp., Escherichia coli, Stenotrophomonas maltophilia and Klebsiella pneumoniae, Proteus spp. and Serratia marcescens. There was no statistical difference on the resistance profile of the GNB isolated on tissue and sonicate fluid culture. Conclusion We have shown an alarming high frequency of MDR-Gram-negative bacilli PJIs in two Brazilian centers, performing microbial diagnosis using sonication and tissue cultures. Disclosures All authors: No reported disclosures.

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