Omadacycline in the treatment of scrub typhus: Three case reports.

BACKGROUND: Scrub typhus is a naturally occurring acute infectious disease that is primarily transmitted through the bites of chiggers or larval mites infected by Orientia tsutsugamushi (O. tsutsugamushi). Omadacycline, a novel tetracycline, exhibits potent antibacterial efficacy against both typical bacteria and atypical pathogens. However, omadacycline application in the treatment of scrub typhus remains limited. CASE SUMMARY: In the present work, we report several cases of scrub typhus, with the main clinical symptoms being fever, the formation of eschars or ulcers, local or systemic lymphadenopathy, headache, myalgia and rash. Blood samples were collected before omadacycline was administered, and O. tsutsugamushi infection was confirmed through targeted next-generation sequencing (tNGS). After two days of treatment, the patients' symptoms, including fever, were alleviated, with no adverse drug reactions. CONCLUSION: tNGS is an effective method for diagnosing scrub typhus. Omadacycline can be considered an alternative option for antiinfective therapy in patients with O. tsutsugamushi infections.

Skin Necrosis after Total Knee Arthroplasty Treated with Eschar Preservation and Prophylactic Antibiotic Measures: A Case Report.

Introduction: Skin necrosis following total knee arthroplasty (TKA) represents a rare, but serious complication that can lead to deep infection. In the setting of a lateral release performed during TKA, the incised retinaculum unveils a potential pathway to the joint should the superficial skin and tissue be compromised. Thus, the conventional treatment of debridement in this setting may risk infection to the joint, whereas eschar preservation may serve as a biological protective barrier to prevent infection. Case Report: We present a patient with end-stage tricompartmental knee osteoarthritis who underwent a TKA with a concomitant lateral release. The patient developed necrosis in two distinct areas measuring 14 cm × 2 cm along the length of the primary TKA incision, and 7 cm × 4 cm laterally. The patient was treated with eschar preservation, oral doxycycline, an antimicrobial silver dressing, and allowed to heal by secondary intention. The patient's skin necrosis healed fully at 12-week post-operatively, and they have had a successful TKA outcome at 5 years. Conclusion: Eschar preservation, oral doxycycline, an antimicrobial silver dressing, and allowing the wound to heal by secondary intention may represent a viable, less invasive treatment for skin necrosis following TKA with lateral release.

Bromelain-Based Enzymatic Debridement Versus Standard of Care in Deep Burn Injuries: A Systematic Review and Meta-Analysis.

Deep burn injuries necessitate effective debridement to promote healing and reduce complications. Traditional surgical debridement is the standard of care; however, it can lead to significant tissue loss, excessive bleeding and delayed healing. Bromelain-based enzymatic debridement offers a potential less invasive alternative that aims to selectively remove necrotic tissue while preserving viable ones. Therefore, this systematic review and meta-analysis comprehensively compares bromelain debridement versus standard care in the management of partial and full-thickness burns. Cochrane Library, Embase, and Medline were searched until May 30th, 2024 for studies comparing bromelain debridement versus standard care. R version 4.4.0 was used to pooled risk ratio and mean difference in a random-effects model. We included seven studies, comprising 484 participants, of whom 238 (49%) were treated with enzymatic debridement. Bromelain significantly reduced time to eschar removal (MD - 7.60 days 95% CI [-9.76, -5.44]; I² = 70%) in comparison with standard care. Additionally, bromelain group presented a significant reduction in the risk of surgical excision (RR 0.17; 95% CI [0.06, 0.47]; I² = 79%) and need for autografts (RR 0.40; 95% CI [0.18, 0.93]; I² = 76%) in comparison with standard group. No differences were found in behalf of time to wound closure (MD -7.64; 95% CI [-18.46]-[3.18]; I2 = 86%), nor in Modified Vancouver Scar Scale (MD -0.36; 95% CI [-0.96]-[0.23]; I2 = 0%). Bromelain-based enzymatic debridement may accelerate eschar removal and reduce the need for surgical excision and autografts, without adversely affecting wound closure time or long-term scar quality.

Corticosteroid-loaded chitosan-based in-situ forming gel combined with microneedle technology for improvement of burn eschar wound healing.

Burn is one of the most common skin injuries and accounts for 300,000 deaths annually. Debridement and antibiotic therapy are major burn treatments, however, as debridement is not always possible and many drugs have poor penetration into necrotic tissue, permeation enhancement is acquired. Another challenge is the short duration of topically applied drugs. This study aims to address both problems by combining in-situ forming gels and microneedles. A chitosan-based in-situ forming gel of hydrocortisone was applied to human burn eschar using microneedles. The formulation was optimized using Design-Expert software. Formulation characterization was done in terms of gelling time and temperature, thermal analysis, release phenomenon, rheology, texture analysis, and stability. Finally, animal studies on mice burn wound treatment were conducted. Results showed that optimized formulation controlled the drug release, and wherever microneedle was used, drug permeation and flux increased (P-value < 0.05). In all ex-vivo and in-vivo stages, gel plus microneedle (length of 1.5 mm and application mode of 2) produced the best results concerning increased flux and faster recovery of burn eschar. In conclusion, the in-situ forming gel with appropriate texture, quality, and stability in combination with microneedle can be a good candidate for the controlled release of drugs in third-degree burn eschars.

Debridement efficacy of serine protease and formulated cream by In Vitro assessment against artificial wound eschar.

Chronic wounds typically comprise of necrotic tissue and dried secretions, often culminating in the formation of a thick and tough layer of dead skin known as eschar. Removal of eschar is imperative to facilitate wound healing. Conventional approach for eschar removal involves surgical excision and grafting, which can be traumatic and frequently leads to viable tissue damage. There has been growing interest in the use of enzymatic agents for a gentler approach to debridement, utilizing proteolytic enzymes. In this study, a purified intracellular recombinant serine protease from Bacillus sp. (SPB) and its cream formulation were employed to evaluate their ability to degrade artificial wound eschar; composed of collagen, fibrin, and elastin. Degradation was assessed based on percentage weight reduction of eschar biomass, analysis via sodium dodecyl sulphate-polyacrylamide gel electrophoresis (SDS-PAGE), and scanning electron microscopy (SEM). Both SPB and its cream formulation were able to degrade up to 50 % artificial wound eschar, with the SPB cream maintaining its degradation efficiency for up to 24 hours. Additionally, the SPB-based cream demonstrated the ability to hydrolyze proteinaceous components of eschars individually (fibrin and collagen) as determined through qualitative assessment. These findings suggest that SPB holds promise for the debridement of wound eschar.

Eschar Formation Following Coma Bullae: A Case Report.

Coma blisters, or coma bullae, are lesions often seen in the setting of impaired consciousness. Most commonly associated with drug-induced comas, coma bullae have been repeatedly linked to central nervous system (CNS) depressing agents, such as opiates. These lesions are believed to develop due to a complex multifactorial process involving external pressure on the skin, which leads to hypoxia and eventual death of eccrine sweat glands. In addition, the vasoactive and inflammatory properties of CNS depressing agents may play a role in this process. Come bullae usually develop on pressure points 48-72 hours after the onset of impaired consciousness and are self-limiting. We present the case of a 68-year-old male who was brought to the emergency department after being found unresponsive on the street. The urine drug screen was positive for cocaine and fentanyl. The initial examination showed several large, non-tender bullae on his scalp that continued to expand over two days. He subsequently developed similar lesions on his thighs, right shoulder, and knuckles. Dermatology was consulted and clinically diagnosed the patient with coma bullae, likely attributed to his altered consciousness and opiate use. Notably, more violaceous bullae were found on the bilateral lower extremities, with dermatology suspecting additional vasculitic features related to concurrent opiate and cocaine use. Skin biopsy and aspiration were deferred to avoid the risk of infection, and the patient was discharged per dermatology's recommendations for no immediate intervention. He continued to follow with wound care for the next six months, with most of the bullae healing. However, eschars developed over the scalp and left lower extremity, requiring debridement by general surgery. This case report underscores a unique manifestation of coma bullae. Unlike typical presentations localized to pressure-dependent areas and appearing after two to three days of unconsciousness, our patient exhibited blisters in atypical sites with associated vasculitic features. Moreover, the development of eschars over time may be linked to ongoing vasoactive drug use, reperfusion injury, and social determinants of health. This case highlights the complex and multifactorial nature of coma bullae, emphasizing the challenges in wound care and management despite their expected self-resolution.

Masqueraders Around Disaster: Clinical Features of Scrub Typhus in Fukushima, Japan.

Background: Scrub typhus (ST) is endemic in Fukushima, with the largest number of cases reported in Japan from 2009 to 2010. Although ST is highly treatable, its atypical clinical presentation impedes diagnosis, causing delays in treatment. Methods: We review the clinical features of ST in adults from 2008 to 2017 at Ohta Nishinouchi General Hospital in Fukushima, Japan. Results: Fifty-five cases (serotype Karp 24, Irie/Kawasaki 21, Hirano/Kuroki 10) of ST were confirmed via serology based on elevated immunoglobulin (Ig)M and IgG and polymerase chain reaction positivity of eschar samples. The mean age was 69 years, and 64% were female. The case fatality rate was 1.8% (1/55). Approximately 70% of cases (38/55) were not diagnosed as ST upon the initial clinic visit. Inappropriate use of antibiotics was identified in 22% of cases (12/55). In terms of atypical clinical features, 1 or more of the manifestations, fever, rash, and eschar, was absent in 31% of cases (17/55). Approximately 11% of cases presented without eschar (6/55; Karp 1, Irie/Kawasaki 1, Hirano/Kuroki 4). Moreover, severe complications were observed with shock and disseminated intravascular coagulation in 7% of cases (4/55), Thus, while 53% of cases presented with the typical triad (29/55), unusual complications and atypical features occurred in 40% (22/55). Conclusions: Diagnosis of ST becomes clinically challenging in the absence of typical features. In Fukushima, an endemic area of ST, an atypical presentation involving multisystem disease is common.

Scrub Typhus Presenting as Bilateral Sixth Nerve Palsy.

Scrub typhus, a tropical rickettsial infection, can have various neurological manifestations. Here, we present the case of an otherwise healthy 19-year-old female who presented to the emergency department with fever, headache, and diplopia. On examination, she was found to have bilateral sixth nerve palsy and bilateral papilledema. Initial unenhanced CT of the brain and CT venogram were unremarkable. The cerebrospinal fluid study was normal. Later, bloodwork revealed high titers of Orientia tsutsugamushi antibody. A thorough physical examination revealed no evidence of any eschar. She was treated with doxycycline and had significant clinical improvement with partial recovery of bilateral lateral rectus function. We want to highlight the importance of maintaining a high index of suspicion for atypical neurological presentations of scrub typhus.

Assessing the Effect of Enzymatic Debridement on the Scar Quality in Partial-Thickness Burns to Deep Dermal Burns of the Hand: A Long-Term Evaluation.

Background and Objectives: Burn surgery on the hands is a difficult procedure due to the complex anatomy and fragility of the area. Enzymatic debridement has been shown to effectively remove burn eschar while minimizing damage to the surrounding tissue and has therefore become a standard procedure in many burn centers worldwide over the past decade. However, surprisingly, our recent literature review showed limited valid data on the long-term scarring after the enzymatic debridement of the hands. Therefore, we decided to present our study on this topic to fill this gap. Materials and Methods: This study analyzed partial-thickness to deep dermal burns on the hands that had undergone enzymatic debridement at least 12 months prior. Objective measures, like flexibility, trans-epidermal water loss, erythema, pigmentation, and microcirculation, were recorded and compared intraindividually to the uninjured skin in the same area of the other hand to assess the regenerative potential of the skin after EDNX. The subjective scar quality was evaluated using the patient and observer scar assessment scale (POSAS), the Vancouver Scar Scale (VSS), and the "Disabilities of the Arm, Shoulder, and Hand" (DASH) questionnaire and compared interindividually to a control group of 15 patients who had received traditional surgical debridement for hand burns of the same depth. Results: Between January 2014 and December 2015, 31 hand burns in 28 male and 3 female patients were treated with enzymatic debridement. After 12 months, the treated wounds showed no significant differences compared to the untreated skin in terms of flexibility, trans-epidermal water loss, pigmentation, and skin surface. However, the treated wounds still exhibited significantly increased blood circulation and erythema compared to the untreated areas. In comparison to the control group who received traditional surgical debridement, scarring was rated as significantly superior. Conclusions: In summary, it can be concluded that the objective skin quality following enzymatic debridement is comparable to that of healthy skin after 12 months and subjectively fares better than that after tangential excision. This confirms the superiority of enzymatic debridement in the treatment of deep dermal burns of the hand and solidifies its position as the gold standard.

Early Enzymatic Burn Debridement: Results of the DETECT Multicenter Randomized Controlled Trial.

Since 1970 surgeons have managed deep burns by surgical debridement and autografting. We tested the hypothesis that enzymatic debridement with NexoBrid would remove the eschar reducing surgery and achieve comparable long-term outcomes as standard of care (SOC). In this Phase 3 trial, we randomly assigned adults with deep burns (covering 3-30% of total body surface area [TBSA]) to NexoBrid, surgical or nonsurgical SOC, or placebo Gel Vehicle (GV) in a 3:3:1 ratio. The primary endpoint was complete eschar removal (ER) at the end of the debridement phase. Secondary outcomes were need for surgery, time to complete ER, and blood loss. Safety endpoints included wound closure and 12 and 24-months cosmesis on the Modified Vancouver Scar Scale. Patients were randomized to NexoBrid (n = 75), SOC (n = 75), and GV (n = 25). Complete ER was higher in the NexoBrid versus the GV group (93% vs 4%; P < .001). Surgical excision was lower in the NexoBrid vs the SOC group (4% vs 72%; P < .001). Median time to ER was 1.0 and 3.8 days for the NexoBrid and SOC respectively (P < .001). ER blood loss was lower in the NexoBrid than the SOC group (14 ± 512 mL vs 814 ± 1020 mL, respectively; P < .0001). MVSS scores at 12 and 24 months were noninferior in the NexoBrid versus SOC groups (3.7 ± 2.1 vs 5.0 ± 3.1 for the 12 months and 3.04 ± 2.2 vs 3.30 ± 2.76 for the 24 months). NexoBrid resulted in early complete ER in >90% of burn patients, reduced surgery and blood loss. NexoBrid was safe and well tolerated without deleterious effects on wound closure and scarring.