scholarly journals Activity of Tedizolid in Methicillin-Resistant Staphylococcus aureus Experimental Foreign Body-Associated Osteomyelitis

2016 ◽  
Vol 60 (11) ◽  
pp. 6568-6572 ◽  
Author(s):  
Kyung-Hwa Park ◽  
Kerryl E. Greenwood-Quaintance ◽  
Jayawant Mandrekar ◽  
Robin Patel
Keyword(s):  
Staphylococcus Aureus ◽  
Foreign Body ◽  
Rat Model ◽  
Peak Plasma ◽  
Peak Plasma Concentration ◽  
Intraperitoneal Administration ◽  
Control Group ◽  
Methicillin Resistant ◽  
Trough Concentrations ◽  
Rifampin Resistance

ABSTRACTWe compared tedizolid alone and tedizolid with rifampin to rifampin and vancomycin plus rifampin in a rat model of methicillin-resistantStaphylococcus aureus(MRSA) foreign body-associated osteomyelitis. The study strain was a prosthetic joint infection-associated isolate. Steady-state pharmacokinetics for intraperitoneal administration of tedizolid, vancomycin, and rifampin were determined in uninfected rats. MRSA was inoculated into the proximal tibia, and a wire was implanted. Four weeks later, the rats were treated intraperitoneally for 21 days with tedizolid (n= 14), tedizolid plus rifampin (n= 11), rifampin (n= 16), or vancomycin plus rifampin (n= 13). Seventeen rats received no treatment. After treatment, quantitative bone cultures were performed. Blood was obtained for determination of drug trough concentrations in the tedizolid and tedizolid plus rifampin groups. The mean peak plasma concentration and mean area under the concentration-time curve from time zero to 24 h for tedizolid were 12 μg/ml and 60 μg · h/ml, respectively. The bacterial loads in all treatment groups were significantly lower than those in the control group; those in the tedizolid- plus rifampin-treated animals were not significantly different from those in the vancomycin- plus rifampin-treated animals. The range of mean plasma trough concentrations in the tedizolid group was 0.44 to 0.73 μg/ml. Although neither tedizolid nor vancomycin resistance was detected in isolates recovered from bones, rifampin resistance was detected in 10 animals (63%) in the rifampin group, 8 animals (73%) in the tedizolid plus rifampin group, and a single animal (8%) in the vancomycin plus rifampin group. Tedizolid alone or tedizolid combined with rifampin was active in a rat model of MRSA foreign body-associated osteomyelitis. The emergence of rifampin resistance was noted in animals receiving tedizolid plus rifampin.

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 Causes and Implications of the Disappearance of Rifampin Resistance in a Rat Model of Methicillin-Resistant Staphylococcus aureus Foreign Body Osteomyelitis

2015 ◽  
Vol 59 (8) ◽  
pp. 4481-4488 ◽  
Author(s):  
Cassandra L. Brinkman ◽  
Harmony L. Tyner ◽  
Suzannah M. Schmidt-Malan ◽  
Jayawant N. Mandrekar ◽  
Robin Patel
Keyword(s):  
Staphylococcus Aureus ◽  
Foreign Body ◽  
Treatment Completion ◽  
Resistant Bacteria ◽  
Methicillin Resistant ◽  
Content Type ◽  
Susceptible Isolate ◽  
Rifampin Resistance

ABSTRACTOrthopedic foreign body-associated infections are often treated with rifampin-based combination antimicrobial therapy. We previously observed that rifampin-resistant and methicillin-resistantStaphylococcus aureus(MRSA) isolates were present 2 days after cessation of rifampin therapy in experimental foreign body osteomyelitis. Unexpectedly, only rifampin-susceptible isolates were detected 14 days after the completion of treatment. We studied two rifampin-resistant isolates recovered 2 days after treatment and one rifampin-susceptible isolate recovered 14 days after treatment. Growing these isolates alonein vitroorin vivodemonstrated no fitness defects; however, in mixed culture, rifampin-susceptible bacteria outcompeted rifampin-resistant bacteria.In vivo, two courses of rifampin treatment (25 mg/kg of body weight every 12 h for 21 days) yielded a greater decrease in bacterial quantity in the bones of treated animals 14 days following treatment than that in animals receiving a single course of treatment (P= 0.0398). In infections established with equal numbers of rifampin-resistant and rifampin-susceptible bacteria, one course of rifampin treatment did not affect bacterial quantities. Rifampin-resistant and rifampin-susceptible isolates were recovered both 2 days and 14 days following treatment completion; however, the proportion of animals with rifampin-resistant isolates was lower at 14 days than that at 2 days following treatment completion (P= 0.024). In untreated animals infected with equal numbers of rifampin-resistant and rifampin-susceptible bacteria for 4 weeks, rifampin-susceptible isolates were exclusively recovered, indicating the outcompetition of rifampin-resistant by rifampin-susceptible isolates. The data presented imply that although there is no apparent fitness defect in rifampin-resistant bacteria when grown alone, they are outcompeted by rifampin-susceptible bacteria when the two are present together. The findings also suggest that selected rifampin resistance may not persist in initially rifampin-susceptible infections following the discontinuation of rifampin.

Pharmacokinetics of Moxifloxacin in A 5/6th Nephrectomized Rat Model

1970 ◽  
Vol 2 (4) ◽  
pp. 748-755
Author(s):  
Hariprasath Kothandam ◽  
Venkatesh Palaniyappan ◽  
Sudheer Babu Idpuganti ◽  
Umamaheswari Muthusamy
Keyword(s):  
Renal Failure ◽  
Rat Model ◽  
Peak Plasma ◽  
Peak Plasma Concentration ◽  
Area Under The Curve ◽  
Laboratory Animals ◽  
Pharmacokinetic Parameters ◽  
Control Group ◽  
Significant Difference ◽  
And Control

Moxifloxacin (MFLX) is a new 8-methoxyfluoroquinolone derivative with a broad spectrum of antibacterial activity. MFLX at doses of 200 and 400 mg was selected to conduct the pharmacokinetic study and the drug was given orally to control and nephrectomized rats. A 5/6th nephrectomized rat model was used in this study. The drug levels in the plasma were determined using a spectrofluorimetric assay. The pharmacokinetic parameters viz. peak plasma concentration (Cmax) and area under the curve (AUC0-8) of the nephrectomized and control rats were compared. The Cmax for both 200 and 400 mg dose of MFLX in nephrectomized rats showed significant difference(P<0.001) from the control group, which reveals the changes in the Cmax of MFLX in renal failure. The AUC0-8 for both 200 and 400 mg dose of MFLX in nephrectomized rats differ significantly (P<0.001) from sham operated control group, which implies the variation in MFLX availability in altered renal function. The AUC0-8 for 400 mg dose of MFLX in nephrectomized rats differ significantly from 200 mg dose of MFLX in nephrectomized group, which reveals that in higher dose, MFLX shows an abrupt increase in the drug availability in renal failure. It is conclude that preclinical drug monitoring of moxifloxacin in laboratory animals can be performed by using 5/6th nephrectomized rat models for determining the dose of MFLX for kidney failured patients. Various pharmacokinetic parameters determined differed in nephrectomised rats when compared to the control.

scholarly journals In VitroEfficacies and Resistance Profiles of Rifampin-Based Combination Regimens for Biofilm-Embedded Methicillin-Resistant Staphylococcus aureus

2013 ◽  
Vol 57 (11) ◽  
pp. 5717-5720 ◽  
Author(s):  
Hung-Jen Tang ◽  
Chi-Chung Chen ◽  
Kuo-Chen Cheng ◽  
Kuan-Ying Wu ◽  
Yi-Chung Lin ◽  
...  
Keyword(s):  
Staphylococcus Aureus ◽  
Fusidic Acid ◽  
Antibacterial Activities ◽  
Methicillin Resistant ◽  
Content Type ◽  
Biofilm Model ◽  
Rifampin Resistance ◽  
Combination Regimens ◽  
Resistant Mutation

ABSTRACTTo compare thein vitroantibacterial efficacies and resistance profiles of rifampin-based combinations against methicillin-resistantStaphylococcus aureus(MRSA) in a biofilm model, the antibacterial activities of vancomycin, teicoplanin, daptomycin, minocycline, linezolid, fusidic acid, fosfomycin, and tigecycline alone or in combination with rifampin against biofilm-embedded MRSA were measured. The rifampin-resistant mutation frequencies were evaluated. Of the rifampin-based combinations, rifampin enhances the antibacterial activities of and even synergizes with fusidic acid, tigecycline, and, to a lesser extent, linezolid, fosfomycin, and minocycline against biofilm-embedded MRSA. Such combinations with weaker rifampin resistance induction activities may provide a therapeutic advantage in MRSA biofilm-related infections.

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.

Recurrent Methicillin-Resistant Staphylococcus Aureus Osteomyelitis: Combination Antibiotic Therapy with Evaluation by Serum Bactericidal Titers

1995 ◽  
Vol 29 (7-8) ◽  
pp. 694-697 ◽  
Author(s):  
Sherrie L Aspinall ◽  
David M Friedland ◽  
Victor L Yu ◽  
John D Rihs ◽  
Robert R Muder
Keyword(s):  
Staphylococcus Aureus ◽  
Back Pain ◽  
Antibiotic Therapy ◽  
Sedimentation Rate ◽  
Methicillin Resistant Staphylococcus Aureus ◽  
Blood Cultures ◽  
Low Back ◽  
Methicillin Resistant ◽  
Trough Concentrations

Objective: To report on a patient with recurrent methicillin-resistant Staphylococcus aureus (MRSA) osteomyelitis and bacteremia successfully treated with combination antibiotic therapy. Case Summary: Two sets of blood cultures from a 55-year-old man with fever, malaise, and low back pain grew MRSA. Radiologic studies of the spine showed bony changes consistent with osteomyelitis. Soon after completing 6 weeks of vancomycin, the patient experienced a recurrence of back pain. Laboratory values included an increase in the sedimentation rate to 53 mm/h and positive blood cultures for MRSA. Vancomycin, gentamicin, and rifampin were administered for 8 weeks. Serum inhibitory and bactericidal titers were more than 1:1024 for both the peak and trough concentrations. Radiologic studies of the spine showed healing osteomyelitis. Two years after completion of antibiotic therapy, the infection has not recurred. Discussion: Antibiotic therapy alone was attempted because the patient was considered a risky surgical candidate. Serum inhibitory and bactericidal titers documented the high in vivo activity of the vancomycin, gentamicin, and rifampin combination. Initiation of vancomycin therapy led to disappearance of the fever and back pain. Cure was documented by sustained normalization of the erythrocyte sedimentation rate and radiologic evidence of healing. Conclusions: Combination antibiotic therapy with vancomycin, rifampin, and low-dose gentamicin (1 mg/kg q12h) may be useful for deep-seated tissue infection caused by MRSA.

scholarly journals Utilizing Pharmacy Records to Assess Antibiotic Prescribing Patterns on the Incidence of Community-Acquired Methicillin-Resistant Staphylococcus aureus Infections in Children

2007 ◽  
Vol 12 (2) ◽  
pp. 91-101
Author(s):  
Peter N. Johnson ◽  
Robert P. Rapp ◽  
Christopher T. Nelson ◽  
J.S. Butler ◽  
Sue Overman ◽  
...  
Keyword(s):  
Staphylococcus Aureus ◽  
Antibiotic Therapy ◽  
Methicillin Resistant Staphylococcus Aureus ◽  
Prescribing Patterns ◽  
Control Group ◽  
Antibiotic Prescribing ◽  
Antibiotic Exposure ◽  
Pharmacy Records ◽  
Methicillin Resistant ◽  
Prior Antibiotic Therapy

OBJECTIVE To assess the effect of prior antibiotic therapy on the incidence of community-acquired methicillin-resistant Staphylococcus aureus (CA-MRSA) infections in children. METHODS This was a concurrent and retrospective review of antibiotic records for children &lt; 18 years of age with documented CA-MRSA infection identified between January 1, 2004, and December 31, 2005. Antibiotic records were compared against a control group. The primary outcome was the incidence of CA-MRSA using linear regression as a function of age and prior antibiotic therapy (i.e., 3 months prior to admission). Secondary objectives included a comparison of antibiotic courses and classes and a description of antibiotic susceptibilities in patients with CA-MRSA RESULTS Data from 26 patients were included. Nine out of 51 patients (18%) with CA-MRSA were included. Another 17 children were enrolled in the control group. The median age was approximately 1.75 years (0.08–14 years) in the CA-MRSA group versus 2.75 years (0.005-15 years) in the control group. A statistical difference was noted in the number of patients with prior antibiotic exposure between the CA-MRSA and control group, 8 (88.9%) versus 6 (35.3%), respectively (P = .01). Antibiotic exposure was found to be a significant independent risk factor (P = .005; 95% CI, 0.167–0.846) for the development of CA-MRSA. The interaction between antibiotic exposure and age &lt; 3 was the most significant predictor of CA-MRSA (P = .019; 95% CI, 0.139–1.40). CONCLUSIONS Prior antibiotic therapy in patients &lt; 3 years of age was associated with a significant risk of developing CA-MRSA. A comprehensive assessment of CA-MRSA patients should include objective methods of measuring prior antibiotic exposure such as pharmacy records.

scholarly journals Virulence of methicillin-resistant Staphylococcus aureus modulated by the YycFG two-component pathway in a rat model of osteomyelitis

2019 ◽  
Vol 14 (1) ◽  
Author(s):  
Shizhou Wu ◽  
Yunjie Liu ◽  
Lei Lei ◽  
Hui Zhang
Keyword(s):  
Staphylococcus Aureus ◽  
Western Blot ◽  
Rat Model ◽  
Biofilm Formation ◽  
Bacterial Biofilm ◽  
Invasive Ability ◽  
Methicillin Resistant ◽  
Two Component ◽  
Mrsa Strains

Abstract Objectives Methicillin-resistant Staphylococcus aureus (MRSA) strains present an urgent medical problem in osteomyelitis cases. Our previous study indicated that the YycFG two-component regulatory pathway is associated with the bacterial biofilm organization of MRSA strains. The aim of this study was to investigate the regulatory roles of ASyycG in the bacterial biofilm formation and the pathogenicity of MRSA strains using an antisense RNA strategy. Methods An ASyycG-overexpressing MRSA clinical isolate was constructed. The bacterial growth was monitored, and the biofilm biomass on bone specimens was examined using scanning electron microscopy and confocal laser scanning microscopy. Furthermore, quantitative RT-PCR (QRT-PCR) analysis was used to measure the expression of yycF/G/H and icaA/D in the MRSA and ASyycG strains. The expression of the YycG protein was quantified by Western blot assays. We validated the role of ASyycG in the invasive ability and pathogenicity of the strains in vivo using histology and peptide nucleic acid fluorescent in situ hybridization. Results The results showed that overexpression of ASyycG lead to a reduction in biofilm formation and exopolysaccharide (EPS) synthesis compared to the control MRSA strains. The ASyycG strains exhibited decreased expression of the yycF/G/H and icaA/D genes. Furthermore, Western blot data showed that the production of the YycG protein was inhibited in the ASyycG strains. In addition, we demonstrated that ASyycG suppressed the invasive ability and pathogenicity of the strain in vivo using an SPF (specific pathogen free) rat model. Conclusion In summary, the overexpression of ASyycG leads to a reduction in biofilm formation and bacterial pathogenicity in vivo, which provides a potential target for the management of MRSA-induced osteomyelitis.

scholarly journals Vancomycin In Vitro Bactericidal Activity and Its Relationship to Efficacy in Clearance of Methicillin-Resistant Staphylococcus aureus Bacteremia

2007 ◽  
Vol 51 (7) ◽  
pp. 2582-2586 ◽  
Author(s):  
Pamela A. Moise ◽  
George Sakoulas ◽  
Alan Forrest ◽  
Jerome J. Schentag
Keyword(s):  
Staphylococcus Aureus ◽  
Median Time ◽  
Bactericidal Activity ◽  
Peak Plasma ◽  
Plasma Concentrations ◽  
Accessory Gene ◽  
Vancomycin Therapy ◽  
Methicillin Resistant ◽  
Vancomycin Mics

ABSTRACT We examined the relationship between the time to clearance of methicillin-resistant Staphylococcus aureus (MRSA) bacteremia while patients were receiving vancomycin therapy and the in vitro bactericidal activity of vancomycin. Vancomycin killing assays were performed with 34 MRSA bloodstream isolates (17 accessory gene regulator group II [agr-II] and 17 non-agr-II isolates) from 34 different patients with MRSA bacteremia for whom clinical and microbiological outcomes data were available. Vancomycin doses were prospectively adjusted to achieve peak plasma concentrations of 28 to 32 μg/ml and trough concentrations of 8 to 12 μg/ml. Bactericidal assays were performed over 24 h with ∼107 to 108 CFU/ml in broth containing 16 μg/ml vancomycin. The median time to clearance of bacteremia was 6.5 days for patients with MRSA isolates demonstrating ≥2.5 reductions in log10 CFU/ml at 24 h and >10.5 days for patients with MRSA isolates demonstrating <2.5 log10 CFU/ml by 24 h (P = 0.025). The median time to clearance was significantly longer with MRSA isolates with vancomycin MICs of 2.0 μg/ml compared to that with MRSA isolates with MICs of ≤1.0 μg/ml (P = 0.019). The bacteremia caused by MRSA isolates with absent or severely reduced delta-hemolysin expression was of a longer duration of bacteremia (10 days and 6.5 days, respectively; P = 0.27) and had a decreased probability of eradication (44% and 78%, respectively; P = 0.086). We conclude that strain-specific microbiological features of MRSA, such as increased vancomycin MICs and decreased killing by vancomycin, appear to be predictive of prolonged MRSA bacteremia while patients are receiving vancomycin therapy. Prolonged bacteremia and decreased delta-hemolysin expression may also be related. Evaluation of these properties may be useful in the consideration of antimicrobial therapies that can be used as alternatives to vancomycin for the treatment of MRSA bacteremia.

scholarly journals 569. Evaluation of a Povidone-Iodine Preparation for Nasal Decolonization of Methicillin-Resistant Staphylococcus aureus

2019 ◽  
Vol 6 (Supplement_2) ◽  
pp. S269-S269
Author(s):  
Hussein Abou Ghaddara ◽  
Jennifer Cadnum ◽  
Y Karen Ng Wong ◽  
Curtis Donskey
Keyword(s):  
Staphylococcus Aureus ◽  
Povidone Iodine ◽  
Perioperative Period ◽  
Control Group ◽  
Single Application ◽  
Methicillin Resistant ◽  
Dosing Intervals ◽  
And Control ◽  
Emergence Of Resistance

Abstract Background Mupirocin is commonly used for nasal decolonization of Staphylococcus aureus, but it has limitations including frequent emergence of resistance and non-adherence due to the need for repeated applications. Povidone-iodine is increasingly used as an alternative for nasal decolonization because it has a low propensity for emergence of resistance and rapid in vitro antibacterial activity. However, limited data are available on the microbiological efficacy of povidone-iodine for suppression of nasal S. aureus. Methods We compared the effectiveness of a single application or 5 days of twice daily application of a commercial 10% povidone-iodine preparation vs. phosphate-buffered saline for a reduction in nasal MRSA in methicillin-resistant S. aureus (MRSA)-colonized patients (9–11 per treatment group). Nasal swabs were collected for quantitative culture of MRSA before and at 1, 6, 12 and 24 hours after the single application or before each dose for the 5-day regimen. Analysis of variance was used to compare MRSA colony counts in povidone iodine vs. control patients. Results The concentrations of MRSA in the nares were similar for povidone-iodine and control group patients prior to treatment. As shown in the figure, the single application of povidone-iodine resulted in a statically significant reduction in nasal MRSA in comparison to controls at 2 and 6 hours after treatment (P10 colonies per swab). Conclusion Our findings suggest that single preoperative applications povidone-iodine could be useful for short-term suppression of S. aureus during the perioperative period. Additional studies are needed to evaluate the efficacy of the povidone-iodine preparation for MRSA decolonization when used at more frequent dosing intervals or in combination with chlorhexidine bathing. Disclosures All authors: No reported disclosures.

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