Fungal Wound Infection (Not Colonization) Is Independently Associated With Mortality in Burn Patients

Horvath, Edward E.; Murray, Clinton K.; Vaughan, George M.; Chung, Kevin K.; Hospenthal, Duane R.; Wade, Charles E.; Holcomb, John B.; Wolf, Steven E.; Mason, Arthur D.; Cancio, Leopoldo C.

doi:10.1097/01.sla.0000256914.16754.80

Cited by 129 publications

(128 citation statements)

References 9 publications

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“…Colonization with fungi has become an increasing problem because the introduction of topical antimicrobials and liberal use of broad-spectrum antibiotics. This has resulted in a surge in invasive fungal infection, which has been linked to higher death rates regardless of the extent of the burn, coincident inhalation injury, or patient age [28]. In a recent review of 15 burn units, fungi were isolated at least once from 6.3% of 6,918 patients [29], with positive cultures being obtained most commonly from the wound itself followed by (in order of decreasing frequency) respiratory, urine, and blood specimens.…”

Section: Gram-negative Bacteriamentioning

confidence: 99%

Infection in Burns

Norbury

Herndon

Tanksley

et al. 2016

Surgical Infections

269

158

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Background: Developments in critical care and surgical approaches to treating burn wounds, together with newer antimicrobial treatments, have significantly reduced the morbidity and mortality rates associated with this injury. Methods: Review of the pertinent English-language literature. Results: Several resistant organisms have emerged as the maleficent cause of invasive infection in burn patients, including methicillin-resistant Staphylococcus aureus, vancomycin-resistant Enterococcus, Pseudomonas, Acinetobacter, non-albicans Candida spp., and Aspergillus. Advances in antimicrobial therapies and the release of new classes of antibiotics have certainly added to the armamentarium of therapeutic resources for the clinician. Conclusion: Strict infection control measures, constant wound surveillance with regular sampling of tissues for quantitative culture, and early excision and wound closure remain the principal adjuncts to control of invasive infections in burn patients.

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Section: Gram-negative Bacteriamentioning

confidence: 99%

Infection in Burns

Norbury

Herndon

Tanksley

et al. 2016

Surgical Infections

269

158

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“…1 Thermal destruction of the skin barrier and concomitant depression of local and systemic host cellular and humoral immune responses are the pivotal factors contributing to infectious complications in patients with severe burns. [2][3][4][5][6] Staphylococcus aureus, especially methicillin-resistant S. aureus (MRSA), is a major cause of sepsis in patients who are immunosuppressed by their burns.…”

Section: Introductionmentioning

confidence: 99%

Chloramphenicol encapsulated in poly-ε-caprolactone–pluronic composite: nanoparticles for treatment of MRSA-infected burn wounds

Kalita¹,

Devi²,

Kandimalla³

et al. 2015

IJN

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The emergence of methicillin-resistant Staphylococcus aureus (MRSA) infection has increased precipitously over the past several decades, with far-reaching health care and societal costs. MRSA infections in the context of burn wounds lead to invasive disease that could potentially cause mortality. Chloramphenicol is a well-known broad-spectrum bacteriostatic antibiotic that has been used since 1949, but due to its hydrophobicity, poor penetration in skin, fast degradation, and toxicity, its application has been hindered. Furthermore, it has been demonstrated that old antibiotics such as chloramphenicol remained active against a large number of currently prevalent resistant bacterial isolates due to their low-level use in the past. Recently, the novel nanoparticulate drug-delivery system has been used and reported to be exceptionally useful for topical therapeutics, due to its distinctive physical characteristics such as a high surface-to-volume ratio and minuscule size. It helps to achieve better hydrophilicity, bioavailability, and controlled delivery with enhanced therapeutic index, which has resulted in decreased toxicity levels compared to the crude drug. Here, we report a novel chloramphenicol loaded with poly(ε-caprolactone) (PCL)-pluronic composite nanoparticles (CAM-PCL-P NPs), physicochemical characterizations, and its bioactivity evaluation in a MRSA-infected burn-wound animal model. CAM-PCL-P NPs could encapsulate 98.3% of the drug in the nanoparticles and release 81% of the encapsulated drug over 36 days with a time to 50% drug release of 72 hours (51%). Nanoparticle suspensions maintained the initial properties with respect to size and encapsulation efficiency, even after 6 months of storage at 4°C and 25°C, respectively ( P >0.05). Significant reduction in the level of toxicity was observed for CAM-PCL-P NPs compared with that of free drug as confirmed from hemolytic activity against human blood erythrocytes and cytotoxicity assay against an MCF-7 breast cancer cell line. In vitro antibacterial activities were performed by zone of inhibition, minimum inhibitory concentrations, minimum bacterial concentration, and time-kill assays, which showed that CAM-PCL-P NPs exhibited significantly enhanced anti-MRSA activity against ten clinical isolates of MRSA strains. The augmented activity of CAM-PCL-P NPs was further tested on a MRSA-infected burn-wound animal model and achieved quicker efficacy in MRSA clearance and improved the survival rate compared with free-chloramphenicol treatment. Thus, we propose CAM-PCL-P NPs as a promising novel antimicrobial candidate that may have a good potential for preclinical applications.

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“…Although improvements in supportive care have led to lower mortality rates, infections, especially wound fungal infections, continue to be a life-threatening complication (1,2). Burn patients are a population at a significant risk of opportunistic infections (3), and burn wound infections are caused by fungi in 20 to 25% of the cases (4).…”

mentioning

confidence: 99%

Comparative Population Plasma and Tissue Pharmacokinetics of Micafungin in Critically Ill Patients with Severe Burn Injuries and Patients with Complicated Intra-Abdominal Infection

Garcı́a-de-Lorenzo

Luque

Grau

et al. 2016

Antimicrob Agents Chemother

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g Severely burned patients have altered drug pharmacokinetics (PKs), but it is unclear how different they are from those in other critically ill patient groups. The aim of the present study was to compare the population pharmacokinetics of micafungin in the plasma and burn eschar of severely burned patients with those of micafungin in the plasma and peritoneal fluid of postsurgical critically ill patients with intra-abdominal infection. Fifteen burn patients were compared with 10 patients with intra-abdominal infection; all patients were treated with 100 to 150 mg/day of micafungin. Micafungin concentrations in serial blood, peritoneal fluid, and burn tissue samples were determined and were subjected to a population pharmacokinetic analysis. The probability of target attainment was calculated using area under the concentration-time curve from 0 to 24 h/MIC cutoffs of 285 for Candida parapsilosis and 3,000 for non-parapsilosis Candida spp. by Monte Carlo simulations. Twenty-five patients (18 males; median age, 50 years; age range, 38 to 67 years; median total body surface area burned, 50%; range of total body surface area burned, 35 to 65%) were included. A three-compartment model described the data, and only the rate constant for the drug distribution from the tissue fluid to the central compartment was statistically significantly different between the burn and intra-abdominal infection patients (0.47 ؎ 0.47 versus 0.15 ؎ 0.06 h ؊1 , respectively; P < 0.05). Most patients would achieve plasma PK/pharmacodynamic (PD) targets of 90% for non-parapsilosis Candida spp. and C. parapsilosis with MICs of 0.008 and 0.064 mg/liter, respectively, for doses of 100 mg daily and 150 mg daily. The PKs of micafungin were not significantly different between burn patients and intra-abdominal infection patients. After the first dose, micafungin at 100 mg/day achieved the PK/PD targets in plasma for MIC values of <0.008 mg/liter and <0.064 mg/liter for non-parapsilosis Candida spp. and Candida parapsilosis species, respectively.

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Fungal Wound Infection (Not Colonization) Is Independently Associated With Mortality in Burn Patients

Abstract: FWI accompanies larger burns and is associated with mortality in burn patients, particularly in those with TBS 30% to 60%. This association is independent of burn size, inhalation injury, and age.

Cited by 129 publications

References 9 publications

Infection in Burns

Infection in Burns

Chloramphenicol encapsulated in poly-ε-caprolactone–pluronic composite: nanoparticles for treatment of MRSA-infected burn wounds

Comparative Population Plasma and Tissue Pharmacokinetics of Micafungin in Critically Ill Patients with Severe Burn Injuries and Patients with Complicated Intra-Abdominal Infection

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Fungal Wound Infection (Not Colonization) Is Independently Associated With Mortality in Burn Patients

Abstract: FWI accompanies larger burns and is associated with mortality in burn patients, particularly in those with TBS 30% to 60%. This association is independent of burn size, inhalation injury, and age.

Cited by 129 publications

References 9 publications

Infection in Burns

Infection in Burns

Chloramphenicol encapsulated in poly-&epsilon;-caprolactone&ndash;pluronic composite: nanoparticles for treatment of MRSA-infected burn wounds

Comparative Population Plasma and Tissue Pharmacokinetics of Micafungin in Critically Ill Patients with Severe Burn Injuries and Patients with Complicated Intra-Abdominal Infection

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Chloramphenicol encapsulated in poly-ε-caprolactone–pluronic composite: nanoparticles for treatment of MRSA-infected burn wounds