Deep Tissue Infection Research Articles

Impact of Deficiencies in Branched-Chain Fatty Acids and Staphyloxanthin in Staphylococcus aureus.

Staphylococcus aureus is a well-known human pathogen with the ability to cause mild superficial skin infections to serious deep-tissue infections, such as osteomyelitis, pneumonia, and infective endocarditis. A key to S. aureus infections and its pathogenicity is its ability to survive in adverse environments, especially at lower temperatures, by regulation of its cell membrane. Branched-chain fatty acids (BCFAs) and staphyloxanthin have been shown to regulate membrane fluidity and staphylococcal virulence. This study was conducted with the hypothesis that the simultaneous lack of BCFAs and staphyloxanthin will have a far greater implication on environmental survival and virulence of S. aureus. Lack of a functional branched-chain α-keto acid dehydrogenase (BKD) enzyme because of a mutation in the lpdA gene led to a decrease in the production of BCFAs, membrane fluidity, slower growth, and poor in vivo survival of S. aureus. A mutation in the crtM gene eliminated the production of staphyloxanthin but it did not affect membrane BCFA levels, fluidity, growth, or in vivo survival. A crtM:lpdA double mutant showed much slower growth and attenuation compared to individual mutants. The results of this study suggest that simultaneous targeting of the BCFA and staphyloxanthin biosynthetic pathways can be a strategy to control S. aureus infections.

Acute Cardiac Events in Patients With Severe Limb Infection.

Recent studies have shown an association between infections, such as influenza, pneumonia, or bacteremia, and acute cardiac events. We studied the association between foot infection and myocardial infarction, arrhythmia, and/or congestive heart failure. We analyzed the records of 318 consecutive episodes of deep soft tissue infection, gangrene, and/or osteomyelitis in 274 patients referred to a vascular surgery service at a tertiary center. We identified 24 acute cardiac events in 21 of 318 (6.6%) episodes of foot infection or foot gangrene. These 24 events included 11 new myocardial infarctions (3.5%), 8 episodes of new onset or worsening congestive heart failure (2.5%), and 5 new arrhythmias (1.6%). Tachycardia and systemic inflammatory response syndrome were associated with acute cardiac events ( P < .05 for each). The 1-year survival of patients with acute cardiac events was 50.4%, significantly lower than the 91.7% 1-year survival of patients without acute cardiac events ( P < .0015). Acute cardiac complications are not uncommon among patients presenting with severe foot infection and are associated with a high 1-year mortality. Primary care physicians, cardiologists, and vascular and orthopedic surgeons must keep a high index of suspicion for the occurrence of an acute cardiac event.

Should antibiotics be administered before arthroscopic knee surgery? A systematic review of the literature.

AIMTo explore the current evidence surrounding the administration of prophylactic antibiotics for arthroscopic knee surgery.METHODSDatabases were searched from inception through May of 2018 for studies examining prophylactic antibiotic use and efficacy in knee arthroscopy. Studies with patient data were further assessed for types of arthroscopic procedures performed, number of patients in the study, use of antibiotics, and outcomes with the intention of performing a pooled analysis. Data pertaining to “deep tissue infection” or “septic arthritis” were included in our analysis. Reported data on superficial infection were not included in our data analysis. For the pooled analysis, a relative risk ratio was calculated and χ2 tests were used to assess for statistical significance between rates of infection amongst the various patient groups. Post hoc power analyses were performed to compute the statistical power obtained from our sample sizes. Number needed to treat analyses were performed for statistically significant differences by dividing 1 by the difference between the infection rates of the antibiotic and no antibiotic groups. An alpha value of 0.05 was used for our analysis. Study heterogeneity was assessed by Cochrane’s Q test as well as calculation of the I2 value.RESULTSA total of 49682 patients who underwent knee arthroscopy for a diverse set of procedures across 19 studies met inclusion critera for pooled analysis. For those not undergoing graft procedures, there were 27 cases of post-operative septic arthritis in 34487 patients (0.08%) who received prophylactic antibiotics and 16 cases in 10911 (0.15%) who received none [risk ratio (RR) = 0.53, 95% confidence interval (CI): 0.29-0.99, P = 0.05]. A sub-group analysis in which bony procedures were excluded was performed which found no significant difference in infection rates between patients that received prophylactic antibiotics and patients that did not (P > 0.05). All anterior cruciate ligament reconstruction studies used prophylactic antibiotics, but two studies investigating the effect of soaking the graft in vancomycin in addition to standard intravenous (IV) prophylaxis were combined for analysis. There were 19 cases in 1095 patients (1.74%) who received IV antibioitics alone and no infections in 2034 patients who received IV antibiotics and had a vancomycin soaked graft (RR = 0.01, 95%CI: 0.001-0.229, P < 0.01).CONCLUSIONProphylactic antibiotics are effective in preventing septic arthritis following simple knee arthroscopy. In procedures involving graft implantation, graft soaking reduces the rate of infection.

Comparison of cemented and uncemented hemiarthroplasty results in the treatment of comminuted displaced proximal humeral fractures

Aim: In this study, we aimed to compare the results of cemented and uncemented hemiarthroplasty results in elderly patients for the treatment of comminuted proximal humerus fractures. Material and Method: Between 2008 and 2014, patients who underwent hemiarthroplasty due to comminuted proximal humerus fracture were retrospectively investigated using the data system of two university hospitals. Patients who were followed for at least 2 years were included. Demographic information of the patients, fracture type, functional results at final follow-up, visual analog scale score and satisfaction status, radiological results, mean follow-up time and complications were noted. Results: A total of 22 patients (12 males, 10 females) (mean age: 76.4 years, range: 67-88)(8 cemented hemiarthroplasty, 14 uncemented hemiarthroplasty) were included. The mean follow-up time was 38 months. Although the mean forward elevation, external rotation and internal rotation were better in patients who underwent uncemented hemiarthroplasty, no significant difference was found between the two groups. The mean visual analog scale score in uncemented hemiarthroplasty group was 0.87 ± 1.12, whereas the mean visual analog scale score in cemented group was 1.28 ± 0.91 and no significant difference was found (p = 0.33). At radiologic evaluation, no significant difference was found. Periprosthetic fracture was seen in 1 patient of both groups. We have seen 1 shoulder stiffness in uncemented group and 1 deep tissue infection in cemented hemiarthroplasty group. Conclusion: The functional and radiological results of our cemented and uncemented HA patients were similar for the treatment of comminuted proximal humerus fractures in at least 2 years follow-up.

29-Year-Old Woman With Fever and Bilateral Lower Extremity Lesions

29-Year-Old Woman With Fever and Bilateral Lower Extremity Lesions

The Role of Circular Frames in the Management of Tibial Fractures.

IntroductionThe purpose of this study is to evaluate the factors that impact the clinical and radiographic outcomes in a patient cohort undergoing external fixation for tibial fractures. We also aim to investigate the use of autograft, allograft, and synthetic bone graft in varying combinations in the setting of tibial bone loss with respect to optimal times to union.MethodsThis was a retrospective study, including 46 patients treated with a circular external fixator for the management of acute tibial fractures. The study was carried out over a 10-year period, between 2007 and 2017, at our institution. The mean follow-up at the time of review was 4.6 years. Primary outcome measures were ‘time to union,’ ‘delayed union’ (> 6 months), ‘infection,’ and ‘duration of external fixation.’ Secondary outcomes included 'length of hospital stay' and functional scores using the 'Short Form-12 (SF-12).' The statistical analysis included both univariate and multivariate analyses to control for confounding variables when assessing predictors of delayed union and infection.ResultsForty-six patients fulfilled the study criteria. Fifteen fractures were classified as open. The mean number of procedures per patient was 3.8 and the mean length of stay per patient was 33 days. The mean time to union was 8.6 months overall. Significant predictors of prolonged time to union were the ‘number of interventions’ (p<0.01) the patient underwent and the ‘bone graft type’ (p<0.01) used. The time to union in the presence of either autograft or allograft was lengthened by the addition of synthetic graft. Five patients developed a deep tissue infection. The use of synthetic bone graft was significantly associated with infection (p<0.05). On subgroup analysis, it was found that the use of synthetic graft in any combination leads to significantly higher rates of deep tissue infection (p<0.05). The mean time to full weight bearing was 10.6 months (s=9.78, 3-36). The majority (57%) were using walking aids and 67% reported that the injury was still affecting their lifestyle.ConclusionTibial fractures with bone loss are a complex group of injuries that often require multiple surgical interventions, prolonged hospital inpatient stay, and suboptimal functional outcomes in many cases. The best times to union are achieved when autograft is used alone without any other combination of bone graft type. The use of synthetic bone graft also significantly increases the rate of deep tissue infection in this cohort. We recommend the use of autograft alone when treating bone defects in tibial fractures with external fixators.

Exoproteome Analysis of Human Pathogenic Dermatophyte Species and Identification of Immunoreactive Proteins.

Increasing incidence of onychomycosis and tinea pedis in humans of industrialized countries together with deep tissue infections are a therapeutic challenge in clinical mycology. For a better understanding of the pathology and immunology of infection, the authors analyze the exoproteomes of three reference strains of the most common clinical dermatophyte species (Trichophyton rubrum, Trichophyton interdigitale, Arthroderma benhamiae) and of Trichophyton strains isolated from affected patients. Extracellular proteins of those in vitro grown strains are separated via 2D High Performance Electrophoresis and identified by mass spectrometry to find proteins with provoked host immune reactivity. More than 80 secreted proteins including virulence factors such as peptidases and other hydrolases are identified. By Western blotting with respective patient sera, up to 31 proteins with significant antigen-antibody reactions are detected in comparison with control sera, for example, peptidases as well as several oxidoreductases. One protein, beta-glucosidase F2SZI9 seems to be a commonly processed antigen in all Trichophyton infections. These first global exoproteome data of three dermatophyte species can be a stepping stone on the way to further study the molecular mechanisms of Trichophyton pathogenicity-associated traits. Possible candidates for potential new diagnostic methods or vaccination have to be validated in further investigations.

Risk Analysis Based on the Timing of Tracheostomy Procedures in Patients with Spinal Cord Injury Requiring Cervical Spine Surgery

To determine the optimal moment to perform tracheostomy in a patient requiring anterior cervical fixation. A retrospective observational study conducted over an 18-year period included 56 patients who had been admitted to the intensive care unit with acute spinal cord injury and underwent tracheostomy and surgical fixation. The sample was divided into 2 groups: at-risk group (31 patients who had undergone tracheostomy before cervical surgery or <4 days after surgery) and not-at-risk group (25 patients who had undergone tracheostomy >4 days after fixation surgery). Descriptive and comparative studies were carried out. Overall trend of the collected data was analyzed using cubic splines (graphic methods). The only infectious complications diagnosed as related to the surgical procedure were infection of the surgical wound in 2 patients in the not-at-risk group (12%) and deep tissue infection in 1 patient in the at-risk group (3.2%). During the study period, we identified a tendency toward performance of early tracheostomies. Our results suggest that the presence of a tracheostomy stoma before or immediately after surgery is associated with a low risk of infection of thecervical surgical wound in instrumented spinal fusion.

A New Technique for The Therapy of Complicated Deep Tissue Infection (with 4 Cases)

AbstractObjectiveThe objective of this study was to discuss the effect of double perfusion cannula accompanied with low negative pressure drainage in the treatment of complexity of abdominopelvic and perineal infections.MethodsThe technology of the double perfusion cannula accompanied with low negative pressure drainage was used to treat complexity of abdominopelvic and perineal infections.ResultsDouble perfusion cannula accompanied with low negative pressure drainage can be applied to the treatment of complexity of abdominopelvic and perineal infections. It has an obvious effect on infection control and reduces recovery time.ConclusionDouble perfusion cannula accompanied with low negative pressure drainage has a good effect on complexity of abdominopelvic and perineal infections; it can be used in wider surgical fields to prevent infections.

Bioluminescence imaging increases in vivo screening efficiency for antifungal activity against device-associated Candida albicans biofilms

Fungal infections are a major problem for a growing number of mostly immunocompromised patients. Candida albicans is an important human fungal pathogen causing mucosal and deep tissue infections, of which the majority are associated with biofilm formation on medical implants. Animal models that are currently in use to test antifungal drugs are limited to ex vivo analyses, requiring host sacrifice that excludes longitudinal monitoring of dynamic processes during biofilm formation in the live host. As a solution, we introduce non-invasive, dynamic imaging and quantification of C. albicans biofilm formation in vivo and subsequent evaluation of treatment efficacy against these biofilms using bioluminescent C. albicans in a catheter-associated mouse model. Bioluminescence imaging (BLI) allowed us to evaluate baseline biofilm load before the start of therapy, which is necessary for correct evaluation and interpretation of antibiofilm efficacy in vivo. Moreover, we demonstrate that this BLI approach monitors the antibiofilm activity of different antifungal agents efficiently in vitro and in vivo. In this study, BLI revealed superior antibiofilm activity for echinocandins compared with amphotericin B and fluconazole. In vitro, anidulafungin showed the highest antibiofilm activity, followed by micafungin and caspofungin. In vivo, caspofungin significantly decreased the biofilm fungal load, as documented by the lower BLI signal and confirmed by CFU counts. In conclusion, this BLI approach increases the power and efficiency of screening and validation of antimycotics both under in vitro and in vivo conditions, thereby refining pre-clinical therapy studies.

Effect of intra-operative glove changing during cesarean section on post-operative complications: a randomized controlled trial.

To compare the rates of wound-related complications among women undergoing a cesarean section when the surgical team used intra-operative glove changing versus usual care. All women undergoing a cesarean section at a single, county hospital were randomized to usual care or intra-operative glove changing prior to abdominal closure. Participants were randomized at the time of decision for cesarean section; surgeons were not blinded to the randomization arm. The primary outcome was any wound-related complication, including wound hematoma, seroma, skin separation of at least 1cm, wound infection, or other incisional abnormality requiring treatment within 8weeks of surgery. To detect a reduction in the primary outcome from 17% in the control group to 9% in the intervention group with 80% power, a total of 554 women (277 per group) were required. Secondary outcomes included other infectious complications including endometritis and other superficial or deep soft tissue infections. From August 2015 to November 2016, 277 women were randomized to usual care and 276 women were randomized to intra-operative glove changing. The two groups were well balanced in terms of demographic data, comorbid conditions and surgical characteristics. Intra-operative glove changing led to a significant decrease in composite wound complications from 13.6% in the control group to 6.4% in the intervention group (p = 0.008). Intra-operative glove changing prior to abdominal closure during cesarean section significantly reduced the incidence of post-operative wound complications.

A Predictive Model Facilitates Early Recognition of Spinal Epidural Abscess in Adults.

IntroductionSpinal epidural abscess (SEA), a highly morbid and potentially lethal deep tissue infection of the central nervous system has more than tripled in incidence over the past decade. Early recognition at the point of initial clinical presentation may prevent irreversible neurologic injury or other serious, adverse outcomes. To facilitate early recognition of SEA, we developed a predictive scoring model.MethodsUsing data from a 10-year, retrospective, case-control study of adults presenting for care at a tertiary-care, regional, academic medical center, we used the Integrated Discrimination Improvement Index (IDI) to identify candidate discriminators and created a multivariable logistic regression model, refined based on p-value significance. We selected a cutpoint that optimized sensitivity and specificity.ResultsThe final multivariable logistic regression model based on five characteristics –patient age, fever and/or rigor, antimicrobial use within 30 days, back/neck pain, and injection drug use – shows excellent discrimination (AUC 0.88 [95% confidence interval {0.84, 0.92}]). We used the model’s β coefficients to develop a scoring system in which a cutpoint of six correctly identifies cases 89% of the time. Bootstrapped validation measures suggest this model will perform well across samples drawn from this population.ConclusionOur predictive scoring model appears to reliably discriminate patients who require emergent spinal imaging upon clinical presentation to rule out SEA and should be used in conjunction with clinical judgment.

Alkynyl-containing phenylthiazoles: Systemically active antibacterial agents effective against methicillin-resistant Staphylococcus aureus (MRSA)

The promising activity of phenylthiazoles against multidrug-resistant bacterial pathogens, in particular MRSA, has been hampered by their limited systemic applicability, due to their rapid metabolism by hepatic microsomal enzymes, resulting in short half-lives. Here, we investigated a series of phenylthiazoles with alkynyl side-chains that were synthesized with the objective of improving stability to hepatic metabolism, extending the utility of phenylthiazoles from topical applications to treatment of a more invasive, systemic MRSA infections. The most promising compounds inhibited the growth of clinically-relevant isolates of MRSA in vitro at concentrations as low as 0.5 μg/mL, and exerted their antibacterial effect by interfering with bacterial cell wall synthesis via inhibition of undecaprenyl diphosphate synthase and undecaprenyl diphosphate phosphatase. We also identified two phenylthiazoles that successfully eradicated MRSA inside infected macrophages. In vivo PK analysis of compound 9 revealed promising stability to hepatic metabolism with a biological half-life of ∼4.5 h. In mice, compound 9 demonstrated comparable potency to vancomycin, and at a lower dose (20 mg/kg versus 50 mg/kg), in reducing the burden of MRSA in a systemic, deep-tissue infection, using the neutropenic mouse thigh-infection model. Compound 9 thus represents a new phenylthiazole lead for the treatment of MRSA infections that warrants further development.

To evaluate the effect of probiotics on the prevalence of oral Candida organisms in denture wearers: An in vivo study

STATEMENT OF PROBLEM: Candida species are the major human fungal pathogens that cause both mucosal and deep-tissue infections. Fungal infections have been successfully treated by systemic antifungal agents for a very long time. The toxicity of available antifungals and resistance to these drugs are a concern; thus, the use of probiotics has emerged as an alternative therapeutic technique for treating Candida infections. PURPOSE: The purpose of this study was to evaluate the effect of probiotics on the prevalence of oral Candida organisms in denture wearers with different age groups. MATERIALS AND METHODS: Sixty completely edentulous denture wearers were divided into three groups: 50–59 years (Group A), 60–69 years (Group B), and 70 years and above (Group C). The sample collected from the denture surface and palatal mucosa pre- and postprobiotic usage were subjected to CHROMagar followed by Germ tube test and then Corn meal agar for identification and counting the number of Candida colonies. The attributed scores were tabulated and submitted for statistical analysis using Kruskal–Wallis ANOVA test, Mann–Whitney U-test, Wilcoxon matched pairs test, and paired t-test. RESULTS: Reduction in the number of Candida colonies was statistically significant in Group A and Group B on the denture surface as compared to that of Group C. However, there was no significant difference observed in all the three groups in the number of Candida colonies on the palatal mucosa. CONCLUSION: The study shows that multispecies probiotic product may represent as an alternative treatment for reduction of Candida infections in the oral cavity of elderly denture wearers.

Breast abscess caused by Staphylococcus aureus in 2 adolescent girls with atopic dermatitis

Atopic dermatitis (AD) is a chronic inflammatory skin disease in children. Patients with AD experience a high rate of colonization of the skin surface by Staphylococcus aureus. Because of a skin barrier defect, there is a potential risk of staphylococcal invasive infection in patients with AD. Here, we present 2 cases of breast abscess caused by S. aureus in 2 adolescent girls with severe AD. Methicillin-sensitive S. aureus was identified from the breast abscess material. They were treated with appropriate antibiotics, however surgical drainage of the abscess was needed in case 1. Identical strains were found from the breast abscess material as well as the lesional and the nonlesional skin of the patients through matrixassisted laser desorption/ionization time-of-flight analysis. We characterized the differential abundance of Firmicutes phylum in patients' skin in microbiota analysis. In particular, S. aureus, a member of Firmicutes, differed significantly between the lesional and the normal-appearing skin. Our cases demonstrate the potential severity of bacterial deep tissue infection in AD and the dysbiosis of skin microbiota may be involved in inflammation in AD.

The role of nonsteroidal anti-inflammatory drugs intramuscular injection in the development and severity of deep soft tissue infection in mice.

The aim of this study was to determine the role of nonsteroidal anti-inflammatory drugs (NSAID) injection on the severity of local infection and the effect on the progression of soft tissue infection (STI).The mouse model of STI with Group A streptococcus (GAS) was developed and treated with diclofenac sodium (DS) intramuscularly. Mice were divided into five groups: administered DS for 48h before GAS (Group 1), GAS-DS and maintained DS for 48h (Group 2), DS for 48h (Group 3), GAS on zero time (Group 4), and control (Group 5). In vitro, a high concentration (40mg/L) of DS inhibited GAS growth, whereas a lower concentration (0.4mg/L) was not effective. Sepsis was observed in animals with DS and GAS inoculation (group 1 and 2). Group 4 had statistically significant higher bacterial load than groups 1 and 2. All groups had a higher inflammation rate than the control group. The median of TNF-alpha and mean IL-6 in the groups 1, 2, and 4 was significantly higher than those in the control group. Even if the animals that were treated with DS injection prior to the GAS inoculation had similar inflammation score, similar cytokine levels and low bacterial load in the tissue, they had a rather high rate of sepsis. In conclusion, DS injection prior to bacterial inoculation might predispose to bacteremia and sepsis.

Negative-Pressure Wound Therapy for Ludwig's Angina: A Case Series.

Summary:Negative-pressure wound therapy (NPWT) is a well-established therapeutic approach for various complex wound classes. There is currently limited information on the use of NPWT for the scope of head and neck wounds. However, NPWT has been used successfully in some cases, including malignancy, infection, and trauma. In West Virginia, the incidence of dental-related infections leading to Ludwig’s Angina is high due to lack of access to dental care. Our case series describes the application of vacuum-based therapy in conjunction with antibiotic therapy for quick, effective closure of deep tissue infections before definitive complex wound repair via graft and flap reconstructions. Over a period of 3 months, 2 patients with submental infections extending to the lateral neck demonstrated clean, efficient wound closure with NPWT for less than 14 days while hospitalized at West Virginia University Medicine. Outpatient follow-up with these patients demonstrated excellent cosmetic outcomes with minimal contracture or hypertrophy of healing tissue. NPWT promotes wound healing through decreased edema, improved perfusion, and increased granulation of tissue based on our findings. Our series encourages the use of NPWT for initial closure of complex wounds secondary to deep neck infections.

The Skin Bacterium Propionibacterium acnes Employs Two Variants of Hyaluronate Lyase with Distinct Properties.

Hyaluronic acid (HA) and other glycosaminoglycans are extracellular matrix components in the human epidermis and dermis. One of the most prevalent skin microorganisms, Propionibacterium acnes, possesses HA-degrading activity, possibly conferred by the enzyme hyaluronate lyase (HYL). In this study, we identified the HYL of P. acnes and investigated the genotypic and phenotypic characteristics. Investigations include the generation of a P. acnes hyl knockout mutant and HYL activity assays to determine the substrate range and formed products. We found that P. acnes employs two distinct variants of HYL. One variant, HYL-IB/II, is highly active, resulting in complete HA degradation; it is present in strains of the phylotypes IB and II. The other variant, HYL-IA, has low activity, resulting in incomplete HA degradation; it is present in type IA strains. Our findings could explain some of the observed differences between P. acnes phylotype IA and IB/II strains. Whereas type IA strains are primarily found on the skin surface and associated with acne vulgaris, type IB/II strains are more often associated with soft and deep tissue infections, which would require elaborate tissue invasion strategies, possibly accomplished by a highly active HYL-IB/II.

Papineau technique combined with vacuum-assisted closure for open tibial fractures: clinical outcomes at five years.

Treatment of open tibial fractures with soft tissue and segmental bone defects is difficult. This study reports our results for treating these injuries with a combination of Papineau open bone grafting and vacuum-assisted wound closure (VAC). The records of 19 patients with open tibial fractures with soft tissue and segmental bone defects treated with bone grafting and VAC from 2004 to 2010 were retrospectively reviewed. Outcomes included: time to complete granulation tissue coverage, wound healing, and bone union; length of hospitalization; frequency of debridement; number of deep tissue infections. Initial surgery was performed within 48 hours of injury. Ten fractures were Orthopaedic Trauma Association classification 41-A3, one was 41-C3, seven were 43-A3, and one was 43-C3. No surgical complications occurred, and the mean length of hospitalization was 11.0±3.0weeks (range, 7-18weeks). The mean follow-up time was 59.35±8.76months. The mean time for complete wound healing was 7.76±1.52weeks (range, 6-11weeks). Bone union was achieved in all patients at a mean of 33.88±8.37weeks (range, 23-53weeks). Only one patient developed a deep tissue infection, which was treated with antibiotics and debridements, and complete bone union wound healing was achieved. Based on Paley grade, five outcomes were excellent, eight were good, and four were fair. The combination of VAC and open bone grafting results in good outcome for patients with open tibial fractures and severe bone and soft-tissue defects.

Management of complicated skin and skin structure infections – a call for infectious disease specialists

There is an increasing insight in the value of infectious disease (ID) specialist service in a variety of severe conditions, including deep tissue infections and septicemia. Messages currently appe...