Multidrug-resistant Organisms in Military Wounds from Iraq and Afghanistan

Calhoun, Jason H.; Murray, Clinton K.; Manring, M. M.

doi:10.1007/s11999-008-0212-9

Cited by 161 publications

(142 citation statements)

References 54 publications

(68 reference statements)

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“…Orthopaedic infections are difficult to manage because of the formation of bacterial biofilms on implant surfaces [18], the inflammatory osteolysis that causes osseointegration failures and loosening of infected implants [27], and antibiotic resistance [9,23,29,31,33,41,45]. HDPs are promising new agents [6,14,15,19] that, owing to their unique immunomodulatory mechanisms of action, are less likely to induce bacterial resistance than are conventional antibiotics [14,15].…”

Section: Discussionmentioning

confidence: 99%

“…Antibiotic resistance and the relative lack of new therapies in development further complicate treatment of orthopaedic implant infections, which are often associated with implant loosening, loss of fracture fixation, and fracture nonunion [31,33,41]. Additionally, increased incidence of methicillin-resistant S aureus infections is a major concern in both civilian and military orthopaedics [9,29,31,45], because therapies for methicillin-resistant S aureus infections are limited.…”

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

Immunomodulatory Peptide IDR-1018 Decreases Implant Infection and Preserves Osseointegration

Choe

Narayanan

Gandhi

et al. 2015

Clinical Orthopaedics &Amp; Related Research

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Background Innate defense regulator peptide-1018 (IDR-1018) is a 12-amino acid, synthetic, immunomodulatory host defense peptide that can reduce soft tissue infections and is less likely to induce bacterial resistance than conventional antibiotics. However, IDRs have not been tested on orthopaedic infections and the immunomodulatory effects of IDR-1018 have only been characterized in response to lipopolysacharide, which is exclusively produced by Gram-negative bacteria. Questions/purposes We sought (1) to more fully characterize the immunomodulatory effects of IDR-1018, especially in response to Staphylococcus aureus; and (2) to determine whether IDR-1018 decreases S aureus infection of orthopaedic implants in mice and thereby protects the implants from failure to osseointegrate. Methods In vitro effects of IDR-1018 on S aureus were assessed by determining minimum inhibitory concentrations in bacterial broth without and with supplementation of physiologic ion levels. In vitro effects of IDR-1018 on macrophages were determined by measuring production of monocyte chemoattractant protein-1 (MCP-1) and proinflammatory cytokines by enzyme-linked immunosorbent assay. In vivo effects of IDR-1018 were determined in a murine model of S aureus implant infection by quantitating bacterial burden, macrophage recruitment, MCP-1, proinflammatory cytokines, and osseointegration in nine mice per group on Day 1 postimplantation and 20 mice per group on Day 15 postimplantation. Results IDR-1018 demonstrated antimicrobial activity by directly killing S aureus even in the presence of physiologic ion levels, increasing recruitment of macrophages to the site of infections by 40% (p = 0.036) and accelerating S aureus clearance in vivo (p = 0.008) with a 2.6-fold decrease in bacterial bioburden on Day 7 postimplantation.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Immunomodulatory Peptide IDR-1018 Decreases Implant Infection and Preserves Osseointegration

Choe

Narayanan

Gandhi

et al. 2015

Clinical Orthopaedics &Amp; Related Research

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“…Sepsis led to 15.51% and 37.7% deaths in Syrian Civil War and Philippines, respectively (25). MDR bacteria were found in evacuated military personnel from Afghanistan and Iraq (26)(27)(28)(29).…”

Section: Evolution Of Antimicrobial Resistancementioning

confidence: 99%

Emerging Antimicrobial Resistance and Evolving Healthcare: Dangerous Crossroads for the Community and the Military

Khan¹,

Gupta

Sen

et al. 2017

J Arch Mil Med

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Modern diagnostic and therapeutic procedures including advanced surgeries, organ transplants, and immunotherapy are pillared by antimicrobial therapy. Parallel to the rising incidence of infectious diseases, the menace of antimicrobial resistance (AMR) emerged worldwide. Developing countries are facing the brunt in epidemic proportions due to huge population, substandard housing, overcrowding, rapid unplanned urbanization, deterioration in water and waste management systems, strained public health infrastructure, and limited resource allocation to healthcare. Simultaneously, AMR has adversely affected the outcome of military injuries. The rising problem of AMR is discouraging the development of newer antimicrobials by the pharmaceutical industry. There has been a considerable impetus towards concept development; however, the magnitude of the problem overshadows the progress made towards the control of AMR worldwide. There is a dire need to identify this threat, develop concerted multipronged strategy, develop infrastructure, foster expertise, and take coordinated and urgent steps to tackle the serious public health challenge. An intensified commitment needs to be taken up on a war footing at individual, local, national, regional, and international levels. This article discusses the overall concept for developing countries.

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“…[2][3][4][5] Screening performed over a period of [2003][2004][2005][2006][2007][2008][2009] revealed that an increasing number of isolates could be classified as multidrug-resistant (MDR), additionally complicating the care and treatment of infected patients. 1,6,7 Attempts have been made to prevent infection by administering antimicrobials in the field, but this has only lead to limited success. 8 Thus, there is a clear need for alternative approaches to prevent infections or treat existing infections.…”

Section: Introductionmentioning

confidence: 99%

In vitro characterization of multivalent adhesion molecule 7-based inhibition of multidrug-resistant bacteria isolated from wounded military personnel

et al. 2012

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Treatment of wounded military personnel at military medical centers is often complicated by colonization and infection of wounds with pathogenic bacteria. These include nosocomially transmitted, often multidrug-resistant pathogens such as Acinetobacter baumannii-calcoaceticus complex, Pseudomonas aeruginosa and extended spectrum b-lactamaseproducing Escherichia coli and Klebsiella pneumoniae. We analyzed the efficacy of multivalent adhesion molecule (MAM) 7-based anti-adhesion treatment of host cells against aforementioned pathogens in a tissue culture infection model. Herein, we observed that a correlation between two important hallmarks of virulence, attachment and cytotoxicity, could serve as a useful predictor for the success of MAM7-based inhibition against bacterial infections. Initially, we characterized 20 patient isolates (five from each pathogen mentioned above) in terms of genotypic diversity, antimicrobial susceptibility and important hallmarks of pathogenicity (biofilm formation, attachment to and cytotoxicity toward cultured host cells). All isolates displayed a high degree of genotypic diversity, which was also reflected by large strain-to-strain variability in terms of biofilm formation, attachment and cytotoxicity within each group of pathogen. Using non-pathogenic bacteria expressing MAM7 or latex beads coated with recombinant MAM7 for anti-adhesion treatment, we showed a decrease in cytotoxicity, indicating that MAM7 has potential as a prophylactic agent to attenuate infection by multidrug-resistant bacterial pathogens.

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Multidrug-resistant Organisms in Military Wounds from Iraq and Afghanistan

Cited by 161 publications

References 54 publications

Immunomodulatory Peptide IDR-1018 Decreases Implant Infection and Preserves Osseointegration

Immunomodulatory Peptide IDR-1018 Decreases Implant Infection and Preserves Osseointegration

Emerging Antimicrobial Resistance and Evolving Healthcare: Dangerous Crossroads for the Community and the Military

In vitro characterization of multivalent adhesion molecule 7-based inhibition of multidrug-resistant bacteria isolated from wounded military personnel

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