Systemic Antimicrobial Therapy in Osteomyelitis

Fraimow, Henry

doi:10.1055/s-0029-1214161

Cited by 121 publications

(92 citation statements)

References 56 publications

(108 reference statements)

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“…[28][29][30] Concerns exist over the routine use of systemic antibiotics due to their marginal effectiveness, poor tissue penetration, and propensity for antibiotic resistance. [31][32][33][34] A great deal of current research and numerous treatments focus on localized antimicrobial therapies, however, these topical antibiotics and antiseptics typically require multiple applications and may delay wound healing. 28,29 Therefore, the need exists for a topical antibiotic therapy that supports sustained antimicrobial activity, prevents infection, and facilitates timely healing.…”

Section: Introductionmentioning

confidence: 99%

Ciprofloxacin-Loaded Keratin Hydrogels PreventPseudomonas aeruginosaInfection and Support Healing in a Porcine Full-Thickness Excisional Wound

Roy

Tomblyn

Burmeister

et al. 2015

Advances in Wound Care

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Objective: Cutaneous wound infection can lead to impaired healing, multiple surgical procedures, and increased hospitalization time. We tested the effectiveness of keratin-based hydrogels (termed ''keratose'') loaded with ciprofloxacin to inhibit infection and support healing when topically administered to porcine excision wounds infected with Pseudomonas aeruginosa. Approach: Using a porcine excisional wound model, 10 mm full-thickness wounds were inoculated with 10 6 colony-forming units of P. aeruginosa and treated on days 1 and 3 postinoculation with ciprofloxacin-loaded keratose hydrogels. Bacteria enumeration and wound healing were assessed on days 3, 7, and 11 postinjury. Results: Ciprofloxacin-loaded keratose hydrogels reduced the amount of P. aeruginosa in the wound bed by 99.9% compared with untreated wounds on days 3, 7, and 11 postinjury. Ciprofloxacin-loaded keratose hydrogels displayed decreased wound contraction and reepithelialization at day 7 postinjury. By day 11, wounds treated with ciprofloxacin-keratose hydrogels contained collagen-rich granulation tissue and myofibroblasts. Wounds treated with ciprofloxacin-loaded keratose hydrogels exhibited a transient increase in macrophages in the wound bed at day 7 postinjury that subsided by day 11. Innovation: Current therapies for wound infection include systemic antibiotics, which could lead to antibiotic resistance, and topical antimicrobial treatments, which require multiple applications and can delay healing. Here, we show that ciprofloxacin-loaded keratose hydrogels inhibit cutaneous wound infection without interfering with key aspects of the healing process including granulation tissue deposition and remodeling. Conclusions: Ciprofloxacin-loaded keratose hydrogels have the potential to serve as a point-of-injury antibiotic therapy that prevents infection and supports healing following cutaneous injury.

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Section: Introductionmentioning

confidence: 99%

Ciprofloxacin-Loaded Keratin Hydrogels PreventPseudomonas aeruginosaInfection and Support Healing in a Porcine Full-Thickness Excisional Wound

Roy

Tomblyn

Burmeister

et al. 2015

Advances in Wound Care

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“…Should this become a significant problem, linezolid or daptomycin may be effective alternatives for treatment of S. aureus biofilm infection. 114 Rifampin has the capacity to kill metabolically dormant sessile bacteria, making it highly useful for musculoskeletal infections of which a biofilm is the focus. 115 Furthermore, it exhibits high bioavailability and has very few known side-effects.…”

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confidence: 99%

Staphylococcus aureusbiofilms

et al. 2011

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“…Treatment regimens extend for 4 to 6 weeks, with durations as long as 8 weeks recommended for treatment of infection due to methicillin-resistant S. aureus (MRSA) (2). Commonly used therapies include cefazolin, oxacillin, or vancomycin for coverage of Gram-positive pathogens and cephalosporins, carbapenems, and the ␤-lactamase inhibitor agents for treatment of Gram-negative pathogens (2,3). No other therapies in recent times have received FDA approval.…”

mentioning

confidence: 99%

Extended-Duration Dosing and Distribution of Dalbavancin into Bone and Articular Tissue

Dunne¹,

Puttagunta²,

Sprenger³

et al. 2015

Antimicrob Agents Chemother

171

137

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Dalbavancin is an intravenous lipoglycopeptide with activity against Gram-positive pathogens and an MIC 90 for Staphylococcus aureus of 0.06 g/ml. With a terminal half-life of >14 days, dosing regimens with infrequent parenteral administration become available to treat infectious diseases such as osteomyelitis and endocarditis that otherwise require daily dosing for many weeks. In order to support a rationale for these novel regimens, the pharmacokinetics over an extended dosing interval and the distribution of dalbavancin into bone and articular tissue were studied in two phase I trials and pharmacokinetic modeling was performed. Intravenous administration of 1,000 mg of dalbavancin on day 1 followed by 500 mg weekly for seven additional weeks was well tolerated and did not demonstrate evidence of drug accumulation. In a separate study, dalbavancin concentrations in cortical bone 12 h after infusion of a single 1,000-mg intravenous infusion were 6.3 g/g and 2 weeks later were 4.1 g/g. A twodose, once-weekly regimen that would provide tissue exposure over the dalbavancin MIC for Staphylococcus aureus for 8 weeks, maximizing the initial exposure to treatment while minimizing the frequency of intravenous therapy, is proposed. Osteomyelitis is an infection of the bone associated with either hematogenous dissemination or direct inoculation as a consequence of trauma or infection from contiguous tissues. Its presentation may be either acute or chronic. The most common pathogen responsible for acute infection in adults is Staphylococcus aureus, with Pseudomonas aeruginosa, Serratia marcescens, and Escherichia coli also involved in traumatic infections and chronic presentations. Infection in children occurs less frequently and is predominantly a result of bacteremia with S. aureus and infection in the growth plate (1). Treatment regimens extend for 4 to 6 weeks, with durations as long as 8 weeks recommended for treatment of infection due to methicillin-resistant S. aureus (MRSA) (2). Commonly used therapies include cefazolin, oxacillin, or vancomycin for coverage of Gram-positive pathogens and cephalosporins, carbapenems, and the ␤-lactamase inhibitor agents for treatment of Gram-negative pathogens (2,3). No other therapies in recent times have received FDA approval.Because the incidence of MRSA in the community in the United States is as high as 40% (4), empirical treatment of osteomyelitis now requires consideration of antimicrobial coverage of this organism, typically with vancomycin. Vancomycin has been demonstrated to be active in animal models of osteomyelitis (5). Concentrations in bone from 2.7 to 9.3 g/ml have been documented (6, 7), exceeding the vancomycin MIC 90 for S. aureus of 1 g/ml (8). Because of the wide variety of underlying etiologies and comorbidities associated with osteomyelitis, it is difficult to generalize the rates of clinical success from clinical trials, but one study documented a clinical response in 10/15 patients after continuous intravenous (i.v.) infusion of vancomycin (9). Long-term d...

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Systemic Antimicrobial Therapy in Osteomyelitis

Cited by 121 publications

References 56 publications

Ciprofloxacin-Loaded Keratin Hydrogels PreventPseudomonas aeruginosaInfection and Support Healing in a Porcine Full-Thickness Excisional Wound

Ciprofloxacin-Loaded Keratin Hydrogels PreventPseudomonas aeruginosaInfection and Support Healing in a Porcine Full-Thickness Excisional Wound

Staphylococcus aureusbiofilms

Extended-Duration Dosing and Distribution of Dalbavancin into Bone and Articular Tissue

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