Electrical monitoring of infection biomarkers in chronic wounds using nanochannels.

Chronic wounds represent an important healthcare challenge in developed countries, being wound infection a serious complication with significant impact on patients' life conditions. However, there is a lack of methods allowing an early diagnosis of infection and a right decision making for a correct treatment. In this context, we propose a novel methodology for the electrical monitoring of infection biomarkers in chronic wound exudates, using nanoporous alumina membranes. Lysozyme, an enzyme produced by the human immune system indicating wound infection, is selected as a model compound to prove the concept. Peptidoglycan, a component of the bacterial layer and the native substrate of lysozyme, is immobilized on the inner walls of the nanochannels, blocking them both sterically and electrostatically. The steric blocking is dependent on the pore size (20-100 nm) and the peptidoglycan concentration, whereas the electrostatic blocking depends on the pH. The proposed analytical method is based on the electrical monitoring of the steric/electrostatic nanochannels unblocking upon the specific degradation of peptidoglycan by lysozyme, allowing to detect the infection biomarker at 280 ng/mL levels, which are below those expected in wounds. The low protein adsorption rate and thus outstanding filtering properties of the nanoporous alumina membranes allowed us to discriminate wound exudates from patients with both sterile and infected ulcers without any sample pre-treatment usually indispensable in most diagnostic devices for analysis of physiological fluids. Although size and charge effects in nanochannels have been previously approached for biosensing purposes, as far as we know, the use of nanoporous membranes for monitoring enzymatic cleavage processes, leading to analytical systems for the specific detection of the enzymes has not been deeply explored so far. Compared with previously reported methods, our methodology presents the advantages of no need of neither bioreceptors (antibodies or aptamers) nor competitive assays, low matrix effects and quantitative and rapid analysis at the point-of-care, being also of potential application for the determination of other protease biomarkers.

Resistance patterns and clinical outcomes of Klebsiella pneumoniae and invasive Klebsiella variicola in trauma patients.

Recent reclassification of the Klebsiella genus to include Klebsiella variicola, and its association with bacteremia and mortality, has raised concerns. We examined Klebsiella spp. infections among battlefield trauma patients, including occurrence of invasive K. variicola disease. Klebsiella isolates collected from 51 wounded military personnel (2009-2014) through the Trauma Infectious Disease Outcomes Study were examined using polymerase chain reaction (PCR) and pulsed-field gel electrophoresis. K. variicola isolates were evaluated for hypermucoviscosity phenotype by the string test. Patients were severely injured, largely from blast injuries, and all received antibiotics prior to Klebsiella isolation. Multidrug-resistant Klebsiella isolates were identified in 23 (45%) patients; however, there were no significant differences when patients with and without multidrug-resistant Klebsiella were compared. A total of 237 isolates initially identified as K. pneumoniae were analyzed, with 141 clinical isolates associated with infections (remaining were colonizing isolates collected through surveillance groin swabs). Using PCR sequencing, 221 (93%) isolates were confirmed as K. pneumoniae, 10 (4%) were K. variicola, and 6 (3%) were K. quasipneumoniae. Five K. variicola isolates were associated with infections. Compared to K. pneumoniae, infecting K. variicola isolates were more likely to be from blood (4/5 versus 24/134, p = 0.04), and less likely to be multidrug-resistant (0/5 versus 99/134, p<0.01). No K. variicola isolates demonstrated the hypermucoviscosity phenotype. Although K. variicola isolates were frequently isolated from bloodstream infections, they were less likely to be multidrug-resistant. Further work is needed to facilitate diagnosis of K. variicola and clarify its clinical significance in larger prospective studies.

Wound Infections from Taiwan Cobra (Naja atra) Bites: Determining Bacteriology, Antibiotic Susceptibility, and the Use of Antibiotics-A Cobra BITE Study.

Wound necrosis and secondary infection are common complications after Naja atra bites. Clinical tools to evaluate the infection risk after Taiwan cobra bites are lacking. In this Cobra BITE study, we investigated the prevalence of wound infection, bacteriology, and corresponding antibiotic usage in patients presenting with Taiwan cobra snakebites. Patients with wound infection lacking tissue necrosis were included in developing Cobra BITE score utilizing univariate and multiple logistic regression, as patients with wound necrosis require antibiotics for infection treatment. 8,295,497 emergency department visits occurred in the span of this study, with 195 of those patients being diagnosed as having cobra bites. Of these patients, 23 had wound necrosis, and 30 had wound infection, resulting in a wound infection rate of 27.2% (53/195). Enterococcus faecalis and Morganella morganii were the main bacteria identified in the culture report regardless of whether patients' wounds had necrosis. As per our Cobra BITE score, the three factors predicting secondary wound infection after cobra bites are hospital admission, a white blood cell count (in 103/µL) × by neu-trophil-lymphocyte ratio value of ≥114.23, and the use of antivenin medication. The area under the receiver operating characteristic curve for the Cobra BITE score system was 0.88; ideal sensitivity and specificity were 0.89 and 0.76. This scoring system enables the assessment of wound infections after N. atra bites, and it could be modified and improved in the future for other Naja spp. bites.

Is Reconstruction of Unstable Midfoot Charcot Neuroarthropathy Cost Effective from a US Payer's Perspective?

BACKGROUND: Charcot neuroarthropathy is a morbid and expensive complication of diabetes that can lead to lower extremity amputation. Current treatment of unstable midfoot deformity includes lifetime limb bracing, primary transtibial amputation, or surgical reconstruction of the deformity. In the absence of a widely adopted treatment algorithm, the decision to pursue more costly attempts at reconstruction in the United States continues to be driven by surgeon preference. QUESTIONS/PURPOSES: To examine the cost effectiveness (defined by lifetime costs, quality-adjusted life-years [QALYs] and incremental cost-effectiveness ratio [ICER]) of surgical reconstruction and its alternatives (primary transtibial amputation and lifetime bracing) for adults with diabetes and unstable midfoot Charcot neuroarthropathy using previously published cost data. METHODS: A Markov model was used to compare Charcot reconstruction and its alternatives in three progressively worsening clinical scenarios: no foot ulcer, uncomplicated (or uninfected) ulcer, and infected ulcer. Our base case scenario was a 50-year-old adult with diabetes and unstable midfoot deformity. Patients were placed into health states based on their disease stage. Transitions between health states occurred annually using probabilities estimated from the evidence obtained after systematic review. The time horizon was 50 cycles. Data regarding costs were obtained from a systematic review. Costs were converted to 2019 USD using the Consumer Price Index. The primary outcomes included the long-term costs and QALYs, which were combined to form ICERs. Willingness-to-pay was set at USD 100,000/QALY. Multiple sensitivity analyses and probabilistic analyses were performed to measure model uncertainty. RESULTS: The most effective strategy for patients without foot ulcers was Charcot reconstruction, which resulted in an additional 1.63 QALYs gained and an ICER of USD 14,340 per QALY gained compared with lifetime bracing. Reconstruction was also the most effective strategy for patients with uninfected foot ulcers, resulting in an additional 1.04 QALYs gained, and an ICER of USD 26,220 per QALY gained compared with bracing. On the other hand, bracing was cost effective in all scenarios and was the only cost-effective strategy for patents with infected foot ulcers; it resulted in 6.32 QALYs gained and an ICER of USD 15,010 per QALY gained compared with transtibial amputation. As unstable midfoot Charcot neuroarthropathy progressed to deep infection, reconstruction lost its value (ICER USD 193,240 per QALY gained) compared with bracing. This was driven by the increasing costs associated with staged surgeries, combined with a higher frequency of complications and shorter patient life expectancies in the infected ulcer cohort. The findings in the no ulcer and uncomplicated ulcer cohorts were both unchanged after multiple sensitivity analyses; however, threshold effects were identified in the infected ulcer cohort during the sensitivity analysis. When the cost of surgery dropped below USD 40,000 or the frequency of postoperative complications dropped below 50%, surgical reconstruction became cost effective. CONCLUSIONS: Surgeons aiming to offer both clinically effective and cost-effective care would do well to discuss surgical reconstruction early with patients who have unstable midfoot Charcot neuroarthropathy, and they should favor lifetime bracing only after deep infection develops. Future clinical studies should focus on methods of minimizing surgical complications and/or reducing operative costs in patients with infected foot ulcers. LEVEL OF EVIDENCE: Level II, economic and decision analysis.

The value of 18 F-FDG PET/CT in diagnosing and localising deep sternal wound infection to guide surgical debridement.

Deep sternal wound infection (DSWI) is a severe complication in patients after open heart surgery (OHS). But there is a lack of appropriate imaging tool to detect the infection sites, which may lead to incomplete debridement. The present study aims to investigate the value of 18 F-fluorodeoxyglucose positron emission tomography/computed tomography (18 F-FDG PET/CT) in comparison with CT scan in diagnosing and localising DSWI. A total of 102 patients with DSWI after OHS were retrospectively collected from January 2012 to December 2017 in our hospital. All the patients had surgical debridements for DSWI with pretreatment imaging of either 18 F-FDG PET/CT or CT scan. The sensitivity, specificity, and accuracy of localising infection sites were compared between PET/CT and CT groups, with surgical, microbiological, and histopathological findings as the gold standard. The length of hospital stays and the rate of recurrence were also compared. Ten patients in the PET/CT group had a follow-up PET/CT scan after debridement, and the correlations between the changes of PET/CT findings and surgical outcomes were analysed. 18 F-FDG PET/CT is more accurate than CT in diagnosing and localising DSWI after OHS, which leads to a more successful surgical debridement with a lower rate of recurrence and a shorter length of hospital stay. In addition, follow-up PET/CT after debridement could evaluate the treatment effect.

Smart wound dressing based on κ-carrageenan/locust bean gum/cranberry extract for monitoring bacterial infections.

A smart wound dressing based on carrageenan (κC), locust bean gum (LBG), and cranberry extract (CB) for monitoring bacterial wound infections was developed and characterized using UV-vis spectroscopy, FT-IR, and SEM. The mechanical, swelling, cytotoxic and pH sensor properties were also investigated. UV-vis spectra demonstrated that the obtained κC:LBG:CB hydrogel film exhibited a visible change of colors as it was immersed in PBS solution pH 5.0, 7.3 and 9.0. The spectra of FT-IR suggested that chemical interactions had occurred between κC and CB extract. The obtained κC:LBG:CB hydrogel film exhibited adequate mechanical properties and a swelling behavior dependent on pH. Cytotoxicity tests indicated that κC:LBG:CB hydrogel film had dose-dependent cytotoxicity against NIH 3T3 fibroblast cells. The in vitro studies using Staphylococcus aureus and Pseudomonas aeruginosa demonstrated that the color changes of the κC:LBG:CB hydrogel film could be observed by naked eyes, confirming the potential use of the obtained hydrogel film as a visual system for monitoring bacterial wound infections.

Distribution of Microbes and Drug Susceptibility in Patients with Diabetic Foot Infections in Southwest China.

OBJECTIVE: To investigate the microbial distribution and drug susceptibility among diabetic foot ulcers (DFUs) with different Wagner grades and between acute and chronic DFUs. Methods. We enrolled 428 DFU patients who were hospitalized and treated in the Southwest Hospital. We collected deep ulcer secretion for microbial culture and drug susceptibility tests and analyzed the results. We reexamined 67 patients with poor anti-infection efficacy and analyzed microbial species. Results: The 354 positive samples included 201 cases (56.8%) of single-pathogen infections and 153 cases (43.2%) of multiple-pathogen infections before antibiotic therapy. A total of 555 strains were cultivated, including 205 (36.9%) strains of gram-positive organisms (GPOs), 283 (51.0%) gram-negative bacilli (GNB), and 67 (12.1%) fungal strains. In terms of distribution, patients with different Wagner grades had different bacterial composition ratios (P < 0.01). Patients with Wagner grades 3-5 mainly had GNB. The specimens from chronic ulcer wounds were primarily GNB (54.2%), whereas fungi accounted for 14.4% of the infections; the distribution was significantly different from that of acute ulcers (P < 0.01). The susceptibility tests showed that the Staphylococcus genus was more susceptible to vancomycin, linezolid, and tigecycline. Tobramycin was the most effective drug (97%) for the treatment of Escherichia coli, followed by ertapenem (96.4%), imipenem (93.5%), and cefotetan (90%). Most of the remaining GNB were susceptible to antibiotics such as carbapenems, aminoglycosides, fluoroquinolones, ceftazidime, cefepime, and piperacillin-tazobactam (>63.2%). After antibiotic therapy, the positive rate of microbial culture was 52.2%, and the proportion of GNB and fungi increased to 68.9% and 20%. CONCLUSION: The distribution and types of bacteria in diabetic foot infection (DFI) patients varied with the different Wagner classification grades, courses of the ulcers, and antibiotic therapy. Multidrug resistance were increased, and the clinical treatment of DFIs should select the most suitable antibiotics based on the pathogen culture and drug susceptibility test results.

Pharmacist-driven antimicrobial optimization in the emergency department.

PURPOSE: A pharmacist-driven antimicrobial optimization service in the non-trauma emergency department (ED) of an 864-bed non-profit tertiary care teaching hospital was reviewed to assess its value. Local antimicrobial resistance patterns of urine, wound, stool, and blood cultures were also studied to determine whether or not empiric prescribing practices should be modified. METHODS: A retrospective electronic chart review was performed for ED patients with positive cultures during two different three-month periods. During Period 1, ED nursing management performed positive culture follow-up. During Period 2, ED clinical pharmacists performed this role. The primary objective was to determine the value of the pharmacist-driven antimicrobial optimization service as measured by the number of clinical interventions made when indicated. The secondary objective was to examine resistance patterns of urine and wound isolates in order to determine if empiric prescribing patterns in the ED should be modified. RESULTS: During Period 1, there were 499 patient visits with subsequent positive cultures. Of those, 76 patients (15%) were discharged home. Nursing management intervened on 21 of 42 (50%) positive cultures that required an intervention; in Period 2, there were 473 patient visits with subsequent positive cultures, and 64 (14%) were discharged home. Pharmacists intervened on 24 of 30 (80%) cultures where an intervention was indicated resulting in a 30% increase in interventions for inappropriate therapy (p = 0.01). A review of the secondary objective revealed a 38% fluoroquinolone resistance rate of E. coli, the most frequently isolated urinary organism. CONCLUSION: Pharmacist-driven antimicrobial stewardship program resulted in a 30% absolute increase in interventions for inappropriate therapy as compared to the nursing-driven model. This stewardship program has further demonstrated the value of ED pharmacists. Pharmacist interventions should help to ensure that infections are resolved through modification of antimicrobial therapies for patients with bug-drug mismatches. The fluoroquinolone resistance rate indicates a need to consider alternative therapies for uncomplicated urinary tract infections. Nitrofurantoin remains with good coverage against E. coli and Enterococcus species but should be used in uncomplicated patients with normal renal function.

Antimicrobial activity of Nigella sativa L. seed oil against multi-drug resistant Staphylococcus aureus isolated from diabetic wounds.

Microbial resistance to existing antibiotics has led to an increase in the use of medicinal plants that show beneficial effects for various infectious diseases. The study evaluates the susceptibility of multidrug resistant Staphylococcus aureus to Nigella sativa oil. Staphylococcus aureus was isolated from 34 diabetic patient's wounds attending the Renaissance hospital, Nsukka, Southeast Nigeria. The isolates were characterized and identified using standard microbiological techniques. Isolates were cultured and a comparative In vitro antibiotic susceptibility test was carried out using the disk diffusion method. Of the 34 samples collected, 19(56%) showed multidrug resistance to the commonly used antibiotics. Nigella sativa oil was then studied for antibacterial activity against these multidrug resistant isolates of Staphylococcus aureus in varying concentration by well diffusion method. The oil showed pronounced dose dependent antibacterial activity against the isolates. Out of 19 isolates, 8(42%) were sensitive to undiluted oil sample; 4(21%) of these showed sensitivity at 200 mg/ml, 400 mg/ml and 800 mg/ml respectively. Eleven (58%) of the isolates were completely resistant to all the oil concentrations. The present study, reports the isolation of multi-drug resistant S. aureus from diabetic wounds and that more than half of isolates were susceptible to different concentrations N. sativa oil.

[The infected diabetic foot: diagnosis and management]. / Pied diabétique infecté: du diagnostic a la prise en charge.

Foot infections are a frequent and potentially harmful complication of diabetes mellitus. In one skin ulceration out of two, further evolution towards infection occurs and often leads to amputation increasing morbidity and health care costs. Skin disruptions, favored by the sensorimotor neuropathy and vascular disease, constitute the initial factors leading to this complication. To ensure effective care, these cases must be managed by a multidisciplinary team in a specialized center. All caretakers involved with patients suffering from diabetes mellitus must be capable of preventing and recognizing diabetic foot infections, as well as informing the patients about this complication and its management.

Managing infection: a holistic approach.

All wound infection presents risks for the patient, but the risks are multiplied in the presence of a comorbidity such as diabetes, when they can potentially be fatal. Where diabetic foot ulcer (DFU) infection is concerned, early recognition is crucial. Prompt treatment, comprising wound cleansing, debridement of devitalised tissue and use of antimicrobial dressings, can stop locally infected ulcers from deteriorating further.

Pseudomonas aeruginosa burn wound infection in a dedicated paediatric burns unit.

BACKGROUND: Pseudomonas aeruginosa infection is a major cause of morbidity in burns patients. There is a paucity of publications dealing with this infection in the paediatric population. We describe the incidence, microbiology and impact of P. aeruginosa infection in a dedicated paediatric burns unit. METHODS: A retrospective review of patients with clinically significant P. aeruginosa infection between April 2007 and January 2010 in the burns unit at Red Cross War Memorial Children's Hospital in Cape Town, South Africa, was performed. RESULTS: During the 36-month study period, 2 632 patients were admitted. Of 2 791 bacteriology samples sent for microscopy, culture and sensitivity, 406 (14.5%) were positive for P. aeruginosa. Thirty-four patients had clinically significant P. aeruginosa wound infection, giving an incidence of 1.3%. Three patients had loss of Biobrane or allografts, and 23 cases of skin graft loss occurred in 18 patients. An average of 12 dressing days was needed to obtain negative swabs. All isolates were sensitive to chlorhexidine, whereas 92.5% were resistant to povidone-iodine. Piperacillin-tazobactam was the systemic antimicrobial to which there was most resistance (36.1%), and tobramycin had least resistance (3.3%). CONCLUSIONS: The incidence of clinically significant burn wound infection is low in our unit, yet the morbidity due to debridement and re-grafting is significant. We observed very high resistance to topical povidone-iodine. Resistance to systemic antimicrobials is lower than that reported from other burns units.

A rare case of Meleney’s Ulcer after partial chemical matricectomy

Antecedentes. La úlcera de Meleney es una infección poco frecuente, pero potencialmente grave que ocurre a menudo en el postoperatorio. Este tipo de úlcera no ha sido anteriormente descrita en el pie tras la realización de una matricectomía parcial con fenol. Caso Clínico. Una paciente fue intervenida mediante fenolización parcial de la matriz ungueal medial del dedo gordo del pie, y transcurridos 2 meses tuvo una recidiva de la deformidad ungueal que causó las úlceras de Meleney. Resultados. Las úlceras se mantuvieron sin cicatrizar aún pautando un régimen de tratamiento con antibióticos, por lo que se requirió de una nueva intervención quirúrgica para eliminar completamente la infección. Conclusión. Este caso presenta una úlcera de Meleney destacando una presentación inicial aparentemente benigna de la fascitis necrotizante en el hallux tras la realización de una matricectomía química parcial mediante abordaje quirúrgico utilizando fenol(AU)

Background. Meleney’s ulcer is a rare, but potentially deadly infection that often occurs in post-surgical sites. This type of ulcer has not previously been reported in the toenail after phenol matricectomy. Patient Case. A female patient underwent partial phenolization of the medial nail matrix of the hallux, but after 2 months had a recurrent spicula that caused Meleney’s ulcers. Results. The ulcers remained after treatment with antibiotics, and further surgery was required to fully clear the infection. Conclusion. This case and review of Meleney’s ulcer highlights the deceptively benign initial presentation of necrotizing fasciitis at the hallux after partial chemical matricectomy surgery using a phenol-based approach(AU)

A simple and effective approach for the treatment of diabetic foot ulcers with different Wagner grades.

Diabetic foot infections are the major cause of morbidity. Infection is the common sequel of diabetic foot ulceration that leads to delayed wound healing. These infections are difficult to control. If not addressed well in time, they may lead to amputation of foot. An attempt has been made to develop simple and effective treatment modality by using citric acid as a sole antimicrobial agent to control diabetic foot infections not responding to conventional treatment. Hundred and fifteen cases of diabetic foot ulcers of different Wagner grades infected with a variety of bacteria were investigated for culture and susceptibility, and susceptibility to citric acid. Citric acid gel was applied to ulcer to determine its efficacy in the management of diabetic foot ulcers with different Wagner grades. Citric acid gel was found effective in the control of foot infections; especially in Wagner grades I and II, the success rate was found to be more than 94%. In Wagner grade III also, it was found effective in complete healing of ulcers without deep osteomyelitis. Citric acid treatment is effective in the control of diabetic foot infections and in successful management of diabetic foot ulcers with Wagner grades I and II, and even with Wagner grade III, without deep osteomyelitis.

Identifying and treating wound infection.

The presence of infection is a major causative factor for delayed or nonhealing wounds. Indiscriminate and routine wound cultures are not recommended, but after the clinical diagnosis of infection is made, culture is recommended to identify the causative organisms and guide antibiotic therapy. The purpose of this article is to discuss how to identify and confirm wound infection and the use of topical and systemic antibiotic agents to treat wound infection.

Ulcer infection by ESbetaL-producing Proteus mirabilis: a case report.

In this article, a case of decubitus ulcer infection caused by an extended-spectrum beta-lactamase-producing Proteus mirabilis strain, successfully treated with oral amoxicillin-clavulanate (1-month therapy) is described. This article focuses on diffusion and clinical effect of extended-spectrum beta-lactamases-producing Proteus mirabilis on treatment of gram negative lower extremity infections.

Emergency management of difficult wounds: part II.

Difficult wounds constitute a significant amount of the morbidity and mortality emergency physicians face on a daily basis. There are specific traumatic and atraumatic wounds that are difficult to manage and have a high risk of complications. Emergency physicians must be able to identify these high-risk wounds and patients and take steps to mitigate further morbidity and mortality.

Diabetic foot ulcers in Cameroon: can microflora prevalence inform probabilistic antibiotic treatment?

OBJECTIVE: To determine the clinical features, regularly associated microorganisms and their susceptibility to antibiotics, and the clinical outcomes of foot ulcers in patients with diabetes at the Yaoundé Central Hospital, Cameroon. METHOD: A retrospective analysis of routinely collected hospital data, and data validation by survey of clinical notes was conducted from November 1999 to October 2002 for adult diabetic patients with foot ulcers. Clinical data were recorded for each patient, followed by a record of microbiological investigations where available. RESULTS: Of 503 patients with diabetes admitted during the study period, 54 (10.7%) had foot ulcers. Male subject represented 66.7% of this population. The mean age of the study population was 59.66 +/- 1.52 years. The foot ulcer led to the diagnosis of diabetes in six patients in whom the condition was previously unidentified. Of the 54 patients with foot ulcers, nine (16.7%) were selected for surgery and the remaining 45 were managed conservatively. Microbiological investigations were available for 21 patients. Proteus mirabilis was the most frequent microorganism yielded, and was regularly associated with Staphylococcus aureus. All the microorganisms isolated showed high sensitivity to second-generation quinolone antibiotics and were regularly sensitive to aminoglycoside antibiotics. Nine (16.7%) patients died and seven (13%) were discharged at their own request. CONCLUSION: The mortality rate among our diabetic patients with foot ulcers is high and the combination of second-generation quinolone and aminoglycoside antibiotics can be proposed as a probabilistic antibiotic approach to treating foot infection.