Efficacy of Nano-Encapsulated Daptomycin in an Experimental Methicillin-Resistant Staphylococcus aureus (MRSA) Bone and Joint Infection Model

2021 ◽  
Author(s):  
Cedric Jacqueline ◽  
Jocelyne Caillon ◽  
Olivier Meyer ◽  
Eric Dailly ◽  
Carl Simonsson ◽  
...  
Keyword(s):  
Staphylococcus Aureus ◽  
Antibiotic Treatment ◽  
Methicillin Resistant Staphylococcus Aureus ◽  
Systemic Treatment ◽  
Joint Infection ◽  
Local Administration ◽  
Infection Model ◽  
Systemic Antibiotic ◽  
Bone Infections ◽  
Local Antibiotic

S. aureus bone infections remain a therapeutic challenge, leading to long and expensive hospitalizations. Systemic antibiotic treatments are inconsistently effective due to insufficient penetration into the infectious site. In an osteomyelitis model, the single local administration of nanoparticle-encapsulated daptomycin allows sterilization of the infectious sites after 4 and 14 days of treatment, while daily systemic treatment of daptomycin for 4 days was not effective. These results demonstrate the great interest of this local antibiotic treatment.

COMMUNITY ACQUIRED METHICILLIN RESISTANT STAPHYLOCOCCUS AUREUS HAND INFECTIONS: A SOUTH PACIFIC PERSPECTIVE — CHARACTERISTICS AND IMPLICATIONS FOR ANTIBIOTIC COVERAGE

Hand Surgery ◽  
2012 ◽  
Vol 17 (03) ◽  
pp. 317-324 ◽  
Author(s):  
Derek Buchanan ◽  
Wolfgang Heiss-Dunlop ◽  
Jon A. Mathy
Keyword(s):  
Staphylococcus Aureus ◽  
Antibiotic Treatment ◽  
Methicillin Resistant Staphylococcus Aureus ◽  
The United States ◽  
Control Group ◽  
Methicillin Resistant ◽  
Empiric Treatment ◽  
Sensitivity Data ◽  
Culture Positive ◽  
Antibiotic Coverage

Purpose: Community acquired methicillin resistant Staphylococcus aureus (CA-MRSA) infections are reported to be increasing worldwide. In the United States when rates exceed 15% empiric treatment is suggested. The aim of our study was to determine local rates and treatment of CA-MRSA within our region. Methods: Nine hundred and forty-two patients were admitted to our service during a six-year period with culture-positive hand infections identified from operative cultures at the time of surgery. Results: Sixty-six (7.0%) patients had CA-MRSA positive cultures identified. Thirty-two (48.5%) patients were noted to have remained on antibiotic treatment that did not reflect their MRSA positive status after cultures returned. Despite this, re-admission and re-operation rates were low and comparable to our non-MRSA control group. Conclusions: Within our CA-MRSA group, current rates do not support automatic empiric treatment for CA-MRSA. Based on sensitivity data, co-trimoxazole and intravenous vancomycin are appropriate and effective antibiotic treatment within our region. Our data supports the importance of drainage of pyogenic infections in helping to resolve complicated hand infections.

scholarly journals Antimicrobial Activity against Intraosteoblastic Staphylococcus aureus

2015 ◽  
Vol 59 (4) ◽  
pp. 2029-2036 ◽  
Author(s):  
Florent Valour ◽  
Sophie Trouillet-Assant ◽  
Natacha Riffard ◽  
Jason Tasse ◽  
Sacha Flammier ◽  
...  
Keyword(s):  
Staphylococcus Aureus ◽  
Ex Vivo ◽  
Joint Infection ◽  
Treatment Strategies ◽  
Bactericidal Effect ◽  
Infection Model ◽  
Content Type ◽  
Intracellular Activity ◽  
Mg63 Cells ◽  
Choice Of Treatment

ABSTRACTAlthoughStaphylococcus aureuspersistence in osteoblasts, partly as small-colony variants (SCVs), can contribute to bone and joint infection (BJI) relapses, the intracellular activity of antimicrobials is not currently considered in the choice of treatment strategies for BJI. Here, antistaphylococcal antimicrobials were evaluated for their intraosteoblastic activity and their impact on the intracellular emergence of SCVs in anex vivoosteoblast infection model. Osteoblastic MG63 cells were infected for 2 h with HG001S. aureus. After killing the remaining extracellular bacteria with lysostaphin, infected cells were incubated for 24 h with antimicrobials at the intraosseous concentrations reached with standard therapeutic doses. Intracellular bacteria and SCVs were then quantified by plating cell lysates. A bactericidal effect was observed with fosfomycin, linezolid, tigecycline, oxacillin, rifampin, ofloxacin, and clindamycin, with reductions in the intracellular inocula of −2.5, −3.1, −3.9, −4.2, −4.9, −4.9, and −5.2 log10CFU/100,000 cells, respectively (P< 10−4). Conversely, a bacteriostatic effect was observed with ceftaroline and teicoplanin, whereas vancomycin and daptomycin had no significant impact on intracellular bacterial growth. Ofloxacin, daptomycin, and vancomycin significantly limited intracellular SCV emergence. Overall, ofloxacin was the only molecule to combine an excellent intracellular activity while limiting the emergence of SCVs. These data provide a basis for refining the choice of antibiotics to prioritise in the management of BJI, justifying the combination of a fluoroquinolone for its intracellular activity with an anti-biofilm molecule, such as rifampin.

scholarly journals Comparison of Methicillin-Resistant Staphylococcus aureus Isolates from Cellulitis and from Osteomyelitis in a Taiwan Hospital, 2016–2018

2019 ◽  
Vol 8 (6) ◽  
pp. 816 ◽  
Author(s):  
Kuo-Ti Peng ◽  
Tsung-Yu Huang ◽  
Yao-Chang Chiang ◽  
Yu-Yi Hsu ◽  
Fang-Yi Chuang ◽  
...  
Keyword(s):  
Staphylococcus Aureus ◽  
Antibiotic Resistance ◽  
Methicillin Resistant Staphylococcus Aureus ◽  
Joint Infection ◽  
Sccmec Type ◽  
Multidrug Resistant ◽  
Chang Gung Memorial Hospital ◽  
Methicillin Resistant ◽  
Mrsa Strains ◽  
Resistance Rates

Methicillin-resistant Staphylococcus aureus (MRSA) causes superficial infections such as cellulitis or invasive infections such as osteomyelitis; however, differences in MRSA isolates from cellulitis (CL-MRSA) and from osteomyelitis (OM-MRSA) at the same local area remain largely unknown. A total of 221 MRSA isolates including 106 CL-MRSA strains and 115 OM-MRSA strains were collected at Chang-Gung Memorial Hospital in Taiwan between 2016 and 2018, and their genotypic and phenotypic characteristics were compared. We found that OM-MRSA isolates significantly exhibited higher rates of resistance to multiple antibiotics than CL-MRSA isolates. Genotypically, OM-MRSA isolates had higher proportions of the SCCmec type III, the sequence type ST239, and the spa type t037 than CL-MRSA isolates. Besides the multidrug-resistant lineage ST239-t037-SCCmecIII more prevalent in OM-MRSA, higher antibiotic resistance rates were also observed in several other prevalent lineages in OM-MRSA as compared to the same lineages in CL-MRSA. Furthermore, when prosthetic joint infection (PJI) associated and non-PJI-associated MRSA strains in osteomyelitis were compared, no significant differences were observed in antibiotic resistance rates between the two groups, albeit more diverse genotypes were found in non-PJI-associated MRSA. Our findings therefore suggest that deep infections may allow MRSA to evade antibiotic attack and facilitate the convergent evolution and selection of multidrug-resistant lineages.

scholarly journals 204. Antagonistic Effect of Colistin on Vancomycin Activity Against Methicillin-Resistant Staphylococcus aureus in in vitro and in vivo Studies

2019 ◽  
Vol 6 (Supplement_2) ◽  
pp. S120-S121
Author(s):  
Sungim Choi ◽  
Taeeun Kim ◽  
Seongman Bae ◽  
Eunmi Yang ◽  
Su-Jin Park ◽  
...  
Keyword(s):  
Staphylococcus Aureus ◽  
Methicillin Resistant Staphylococcus Aureus ◽  
Antagonistic Effect ◽  
In Vivo Studies ◽  
Infection Model ◽  
Methicillin Resistant ◽  
Checkerboard Assay ◽  
Mrsa Strains ◽  
Time Kill

Abstract Background There is a concern that the vancomycin MIC of methicillin-resistant Staphylococcus aureus (MRSA) could be increased by concomitant colistin administered against multidrug-resistant gram-negative pathogen. Methods We confirmed the molecular genotypes of MRSA blood isolates collected in a tertiary hospital in Seoul, South Korea, and selected representative strains from the community-associated MRSA strains (CA-MRSA, ST72-SCCmec IV) and hospital-acquired MRSA strains (HA-MRSA, ST5-SCCmec II). USA CA-MRSA (USA300, ST8-SCCmec IV) and MRSA standard strain (ATCC 43300, ST39-SCCmec II) were also used for comparison with representative. We identified changes of the vancomycin MIC in MRSA by colistin exposure in a checkerboard assay and performed a time-kill assay to evaluate the combined effect of vancomycin and colistin on MRSA. In addition, we administered vancomycin, colistin, and combination of two antibiotics, respectively, to a neutropenic murine thigh infection model to evaluate the in vivo antagonistic effect of colistin on vancomycin treatment. Results In the checkerboard assay, all 4 MRSA strains showed a tendency for the vancomycin MIC to increase along with increasing concentrations of colistin. However, the time-kill assay showed the antagonism of vancomycin and colistin only against ST5-MRSA, when vancomycin concentration was 2 times the vancomycin MIC (Figure 1). No antagonism was observed in other strains. In the murine thigh infection model of ST5-MRSA, vancomycin monotherapy showed a significant log CFU reduction compared with a combination of vancomycin and colistin at 24 hours, demonstrating the antagonistic effect of vancomycin and colistin combination (Figure 2). Conclusion This study showed that exposure of colistin to certain MRSA strains may reduce the susceptibility to vancomycin. Combination therapy with vancomycin and colistin for MDR pathogens infections might result in treatment failure for concurrent MRSA infection. Disclosures All authors: No reported disclosures.

scholarly journals Enhancement in Site-Specific Delivery of Carvacrol against Methicillin Resistant Staphylococcus aureus Induced Skin Infections Using Enzyme Responsive Nanoparticles: A Proof of Concept Study

Pharmaceutics ◽  
2019 ◽  
Vol 11 (11) ◽  
pp. 606 ◽  
Author(s):  
Maria Mir ◽  
Naveed Ahmed ◽  
Andi Dian Permana ◽  
Aoife Maria Rodgers ◽  
Ryan F. Donnelly ◽  
...  
Keyword(s):  
Staphylococcus Aureus ◽  
Methicillin Resistant Staphylococcus Aureus ◽  
Ex Vivo ◽  
Infection Model ◽  
Skin Infections ◽  
Site Specific ◽  
Methicillin Resistant ◽  
Hydrogel Matrix ◽  
Skin Retention

Methicillin resistant Staphylococcus aureus (MRSA) induced skin infections have become a challenging problem due to the escalating antibiotic resistance. Carvacrol (CAR) has been reported to be effective against MRSA. However, due to its characteristics, CAR exhibits low skin retention. In this study, CAR was formulated into site-specific nanoparticle (NPs) delivery system using poly(ε-caprolactone) (PCL), following incorporation into a hydrogel matrix to facilitate dermal delivery. The release study exhibited significantly higher release of CAR from PCL NPs in the presence of bacterial lipase, highlighting its potential for differential delivery. Moreover, encapsulation of CAR in PCL NPs resulted in a two-fold increase in its anti-MRSA activity. Dermatokinetic studies revealed that the NPs loaded hydrogel was able to enhance skin retention of CAR after 24 h (83.29 ± 3.15%), compared to free CAR-loaded hydrogel (0.85 ± 0.14%). Importantly, this novel approach exhibited effective antimicrobial activity in an ex-vivo skin infection model. Hence, these findings have proven the concept that the loading of CAR into a responsive NPs system can lead to sustained antimicrobial effect at the desired site, and may provide a novel effective approach for treatment of MRSA induced skin infections. However, further studies must be conducted to investigate in-vivo efficacy of the developed system in an appropriate infection model.

scholarly journals Novel Use of Rifabutin and Rifapentine to Treat Methicillin-Resistant Staphylococcus aureus in a Rat Model of Foreign Body Osteomyelitis

2020 ◽  
Vol 222 (9) ◽  
pp. 1498-1504
Author(s):  
Melissa J Karau ◽  
Suzannah M Schmidt-Malan ◽  
Mariana Albano ◽  
Jayawant N Mandrekar ◽  
Christina G Rivera ◽  
...  
Keyword(s):  
Staphylococcus Aureus ◽  
Foreign Body ◽  
Rat Model ◽  
Methicillin Resistant Staphylococcus Aureus ◽  
Joint Infection ◽  
Kirschner Wire ◽  
Methicillin Resistant ◽  
Joint Infections ◽  
Single Animal ◽  
K Wires

Abstract Background Owing to patient intolerance or drug interactions, alternative agents to rifampin are needed for management of staphylococcal periprosthetic joint infection. In the current study, we evaluated rifabutin, rifapentine and rifampin, with and without vancomycin, in a rat model of foreign body osteomyelitis. Methods Proximal tibiae were inoculated with methicillin-resistant Staphylococcus aureus (MRSA) and a Kirschner wire (K-wire) implanted in each. After 4 weeks of infection, rifampin, rifabutin, or rifapentine were administered, alone or with vancomycin. Tibiae and K-wires were cultured, and medians were reported as log10 colony-forming units (CFUs) per gram of bone or log10 CFUs per K-wire, respectively. Results Rifampin, rifabutin or rifapentine administered with vancomycin yielded less MRSA from bones (0.10, 3.02, and 0.10 log10 CFUs/g, respectively) than did no treatment (4.36 log10 CFUs/g) or vancomycin alone (4.64 log10 CFUs/g) (both P ≤ .02). The K-wires of animals receiving no treatment or vancomycin monotherapy recovered medians of 1.76 and 2.91 log10 CFUs/g per K-wire, respectively. In contrast, rifampin, rifabutin and rifapentine administered with vancomycin yielded medians of 0.1 log10 CFUs per K-wire, respectively. Rifampin resistance was detected in a single animal in the rifampin monotherapy group. Conclusions Rifabutin or rifapentine with vancomycin were as active as rifampin with vancomycin against MRSA in rat foreign body osteomyelitis, suggesting that rifabutin and/or rifapentine may be alternatives to rifampin in the clinical management of staphylococcal periprosthetic joint infections.

scholarly journals Role of Phenol-Soluble Modulins in Formation of Staphylococcus aureus Biofilms in Synovial Fluid

2015 ◽  
Vol 83 (7) ◽  
pp. 2966-2975 ◽  
Author(s):  
Sana S. Dastgheyb ◽  
Amer E. Villaruz ◽  
Katherine Y. Le ◽  
Vee Y. Tan ◽  
Anthony C. Duong ◽  
...  
Keyword(s):  
Staphylococcus Aureus ◽  
Synovial Fluid ◽  
Antibiotic Treatment ◽  
Joint Infection ◽  
Regulatory System ◽  
Surface Proteins ◽  
Host Matrix ◽  
Content Type ◽  
Prosthetic Joint ◽  
Prosthetic Joint Infections

Staphylococcus aureusis a leading cause of prosthetic joint infections, which, as we recently showed, proceed with the involvement of biofilm-like clusters that cause recalcitrance to antibiotic treatment. Here we analyzed why these clusters grow extraordinarily large, reaching macroscopically visible extensions (>1 mm). We found that while specificS. aureussurface proteins are a prerequisite for agglomeration in synovial fluid, low activity of the Agr regulatory system and subsequent low production of the phenol-soluble modulin (PSM) surfactant peptides cause agglomerates to grow to exceptional dimensions. Our results indicate that PSMs function by disrupting interactions of biofilm matrix molecules, such as the polysaccharide intercellular adhesin (PIA), with the bacterial cell surface. Together, our findings support a two-step model of staphylococcal prosthetic joint infection: As we previously reported, interaction ofS. aureussurface proteins with host matrix proteins such as fibrin initiates agglomeration; our present results show that, thereafter, the bacterial agglomerates grow to extremely large sizes owing to the lack of PSM expression under the specific conditions present in joints. Our findings provide a mechanistic explanation for the reported extreme resistance of joint infection to antibiotic treatment, lend support to the notions that Agr functionality and PSM production play a major role in defining different forms ofS. aureusinfection, and have important implications for antistaphylococcal therapeutic strategies.

Local antibiotic treatment of soft tissue and bone infections of the foot

1990 ◽  
Vol 80 (7) ◽  
pp. 345-353 ◽  
Author(s):  
DE Stabile ◽  
AM Jacobs
Keyword(s):  
Soft Tissue ◽  
Bone Cement ◽  
Success Rate ◽  
Polymethyl Methacrylate ◽  
Antibiotic Treatment ◽  
Soft Tissue Infection ◽  
Definitive Diagnosis ◽  
Histologic Examination ◽  
Bone Infections ◽  
Local Antibiotic

Twenty-seven pedal soft tissue and bone infections in 26 patients were treated with surgical necrectomy of infected tissues and implantation of antibiotic-loaded polymethyl methacrylate bone cement beads on chains. The definitive diagnosis of the infected tissues was obtained by culture and histologic examination in all of the cases. A wide variety of foot infections was successfully treated in this manner. The success rate without recurrence of osteomyelitis or soft tissue infection was 95% in this study at an average of 16 months after surgery.

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