Bacterial diversity and inflammatory response at first-time visit in younger and older individuals with diabetic foot infection (DFI).

AIM: Infection of a diabetic foot ulcer (DFU) is common. More than the half of DFUs become infected and 15-20% of them necessitate amputation in course of treatment. Diabetic foot infection (DFI) is therefore the major cause for non-traumatic lower limb amputation in Germany. Prompt and effective treatment of DFI is mandatory to safe limbs and lives. We investigated if there are relevant differences in evoked inflammatory response between different species and age-separated groups. We further investigated if there is an impact of ulcer localization on bacterial diversity. METHODS: For a 12-month period, we investigated 353 individuals with infected DFU, their laboratory results and bacterial diversity at first-time visit in a Diabetic Foot Care Center in Southern Germany. RESULTS: The ulcer microbiota was dominated by gram-positive species, primary Staphylococcus aureus. The gram-negative sector was mainly formed by Pseudomonas aeruginosa and Enterobacteriaceae (Proteus spp., Enterobacter spp., Escherichia coli and Klebsiella spp.). With increase in age, P. aeruginosa and S. aureus became more frequent, while Streptococci decreased. Ischemic and/or deep wounds were more likely to bear gram-negative species. Inflammatory response did not differ between gram-positive and gram-negative species, while Streptococci and Proteus spp. induced the highest serum inflammation reaction in their category. Streptococci, Enterobacter spp. and E. coli were more frequent in summer, while Enterococci spp., coagulase-negative Staphylococci and P. aeruginosa were more prevalent in winter half-year. DFIs of the forefoot and plantar side are mostly caused by gram-positive species, while Enterobacteriaceae were most frequent in plantar ulcerations. CONCLUSION: Gram-positive species dominate bacterial spectrum in DFI. With increase in age, S. aureus, Streptococci and Pseudomonas aeruginosa became more frequent. The inflammatory response did not differ significantly between different species, but gram-negative species were slightly but not significant more frequent in ischemic wounds. Climatic distinction like summer or winter half-year as well as foot ulcer localization seems to influence bacterial diversity in DFUs.

New markers for sepsis caused by Pseudomonas aeruginosa during burn infection.

INTRODUCTION: Sepsis is a leading cause of mortality in burn patients. One of the major causes of sepsis in burn patients is Pseudomonas aeruginosa. We hypothesized that during dissemination from infected burn wounds and subsequent sepsis, P. aeruginosa affects the metabolome of the blood resulting in changes to specific metabolites that would serve as biomarkers for early diagnosis of sepsis caused by P. aeruginosa. OBJECTIVES: To identify specific biomarkers in the blood after sepsis caused by P. aeruginosa infection of burns. METHODS: Gas chromatography with time-of-flight mass spectrometry was used to compare the serum metabolome of mice that were thermally injured and infected with P. aeruginosa (B-I) to that of mice that were neither injured nor infected, mice that were injured but not infected, and mice that were infected but not injured. RESULTS: Serum levels of 19 metabolites were significantly increased in the B-I group compared to controls while levels of eight metabolites were significantly decreased. Thymidine, thymine, uridine, and uracil (related to pyrimidine metabolism), malate and succinate (a possible sign of imbalance in the tricarboxylic acid cycle), 5-oxoproline (related to glutamine and glutathione metabolism), and trans-4-hydroxyproline (a major component of the protein collagen) were increased. Products of amino acid metabolism were significantly decreased in the B-I group, including methionine, tyrosine, indole-3-acetate, and indole-3-propionate. CONCLUSION: In all, 26 metabolites were identified, including a unique combination of five metabolites (trans-4-hydroxyproline, 5-oxoproline, glycerol-3-galactoside, indole-3-acetate, and indole-3-propionate) that could serve as a set of biomarkers for early diagnosis of sepsis caused by P. aeruginosa in burn patients.

Diagnostic accuracy of serum inflammatory markers in late fracture-related infection: a systematic review and meta-analysis.

AIMS: To assess the diagnostic value of C-reactive protein (CRP), leucocyte count (LC), and erythrocyte sedimentation rate (ESR) in late fracture-related infection (FRI). MATERIALS AND METHODS: PubMed, Embase, and Cochrane databases were searched focusing on the diagnostic value of CRP, LC, and ESR in late FRI. Sensitivity and specificity combinations were extracted for each marker. Average estimates were obtained using bivariate mixed effects models. RESULTS: A total of 8284 articles were identified but only six were suitable for inclusion. Sensitivity of CRP ranged from 60.0% to 100.0% and specificity from 34.3% to 85.7% in all publications considered. Five articles were pooled for meta-analysis, showing a sensitivity and specificity of 77.0% and 67.9%, respectively. For LC, this was 22.9% to 72.6%, and 73.5% to 85.7%, respectively, in five articles. Four articles were pooled for meta-analysis, resulting in a 51.7% sensitivity and 67.1% specificity. For ESR, sensitivity and specificity ranged from 37.1% to 100.0% and 59.0% to 85.0%, respectively, in five articles. Three articles were pooled in meta-analysis, showing a 45.1% sensitivity and 79.3% specificity. Four articles analyzed the value of combined inflammatory markers, reporting an increased diagnostic accuracy. These results could not be pooled due to heterogeneity. CONCLUSION: The serum inflammatory markers CRP, LC, and ESR are insufficiently accurate to diagnose late FRI, but they may be used as a suggestive sign in its diagnosis.

Modalities and accuracy of diagnosis of external ventricular drainage-related infections: a prospective multicentre observational cohort study.

BACKGROUND: Device infection is a major complication of placement external ventricular drains (EVD). Diagnostic features are often masked by underlying disease or cerebrospinal fluid (CSF) contamination by blood. We aim to assess which diagnostic modalities are applied for EVD-related infection (ERI) diagnosis and evaluate their accuracy. METHODS: This observational prospective study included 187 adult patients with an EVD. Modalities of clinical diagnosis of ERI diagnosed by treating physicians on clinical grounds and blood and CSF analysis (clinically diagnosed ERI (CD-ERI)) were assessed prospectively. Additionally, the diagnostic accuracy of clinical and laboratory parameters for the diagnosis of culture proven ERI (CP-ERI) was evaluated, using data of the study patients and including a retrospective cohort of 39 patients with CP-ERI. RESULTS: Thirty-one CD-ERIs were diagnosed in the prospective cohort. Most physicians used CSF analysis to establish the diagnosis. ROC analysis revealed an AUC of 0.575 (p = 0.0047) for the number of positive SIRS criteria and AUC of 0.5420 (p = 0.11) for the number of pathological neurological signs for diagnosis of CP-ERI. Diagnostic accuracy of laboratory values was AUC 0.596 (p = 0.0006) for serum white blood cell count (WBCC), AUC 0.550 (p = 0.2489) for serum C-reactive protein, AUC 0.644 (p < 0.0001) for CSF WBCC and AUC 0.690 for CSF WBC/red blood cell count ratio (both p < 0.0001). Neither a temporal trend in potential predictors of CP-ERI nor a correlation between clinical diagnosis and proven CSF infection was found. CONCLUSIONS: Clinicians base their diagnosis of ERI mostly on CSF analysis and occurrence of fever, leading to over-diagnosis. The accuracy of the clinical diagnosis is low. Commonly used clinical and laboratory diagnostic criteria have a low sensitivity and specificity for ERI.

Perioperative hemoglobin A1c as a predictor of deep infection following single-level lumbar decompression in patients with diabetes.

BACKGROUND CONTEXT: Although multiple studies have cited that diabetes mellitus as a risk factor decreased functional outcomes, increased infectious complications, and overall increased reoperation rate following degenerative lumbar spinal surgery, few have investigated how perioperative glycemic control influences such complications. PURPOSE: The primary goal of the present study was to use a national database to evaluate the association of perioperative glycemic control as demonstrated by hemoglobin A1c (HbA1c) levels in patients with diabetes undergoing primary, single-level decompression without concomitant fusion with the incidence of deep postoperative infection requiring operative irrigation and debridement. Our secondary objective was to calculate a threshold level of HbA1c above which the risk of postoperative infection after lumbar decompression increases significantly in patients with diabetes. STUDY DESIGN/SETTING: This is a retrospective case control database study, with Level III evidence. PATIENT SAMPLE: This study comprised private-payer patients with diabetes mellitus undergoing single-level lumbar decompression with an HbA1c laboratory value recorded in the database within 3 months of surgery. OUTCOME MEASURES: The outcome examined in this study was deep infection following primary, single-level lumbar decompression requiring surgical intervention. Postoperative infection within 1 year of the index primary, single-level lumbar decompression was assessed using Current Procedural Terminology (CPT) procedure codes and the International Classification of Diseases, 9th Revision (ICD-9) diagnostic codes. METHODS: The Humana private-payer dataset from the PearlDiver database was used for this study. The database was queried for patients with diabetes mellitus undergoing primary, single-level lumbar decompression surgery using CPT codes. Patients with a diagnosis of diabetes mellitus who had an HbA1c level drawn within 3 months before or after their surgical date were then selected to form the study group using the ICD-9 diagnostic codes. Patients were then divided into groups based on their HbA1c level by increments of 0.5 mg/dL. The incidence of deep infection requiring operative intervention within 1 year for each HbA1c group was then identified using CPT and ICD-9 codes. A receiver operating characteristic (ROC) and area under the curve (AUC) analysis was performed to determine an optimal threshold value of the HbA1c above which the risk of postoperativeinfection was significantly increased. The threshold value was tested using a multivariable binomial logistic regression analysis. RESULTS: A total of 5,194 patients who underwent primary, single-level lumbar decompression with diabetes and a perioperative HbA1c recorded within 3 months of surgery were included in the study. The rate of infection ranged from a low of 0.5% up to 3.5% for patients with an HbA1c level >11.0 mg/dL (p=.012). The inflection point of the ROC curve corresponded to an HbA1c level above 7.5 mg/dL (p=.01, AUC=0.71, specificity=70%, sensitivity=53%). After controlling for patient demographics and medical comorbidities, patients with an HbA1c level of 7.5 mg/dL or above had a significantly higher risk for deep infection compared with patients below this threshold (odds ratio: 2.9, 95% confidence interval: 1.8-4.9, p<.0001). CONCLUSIONS: The risk of deep postoperative infection requiring surgical intervention following single-level lumbar decompression in patients with diabetes mellitus increases as the perioperative HbA1c increases. The ROC and multivariable regression analyses determined that a perioperative HbA1c above 7.5 mg/dL could serve as a threshold for a significantly increased risk of deep postoperative infection following lumbar decompression.

The role of procalcitonin as a marker of diabetic foot ulcer infection.

Foot ulcers are frequent in diabetic patients and are responsible for 85% of amputations, especially in the presence of infection. The diagnosis of diabetic foot ulcer infection is essentially based on clinical evaluation, but laboratory parameters such as erythrocyte sedimentation rate (ESR), white blood count (WBC), C-reactive protein (CRP) and, more recently, procalcitonin (PCT) could aid the diagnosis, especially when clinical signs are misleading. Fifteen diabetic patients with infected foot ulcers were admitted to our department and were compared with an additional group of patients with non-infected diabetic foot ulcers (NIDFUs). Blood samples were collected from all patients in order to evaluate laboratory markers. In the current study, the diagnostic accuracy of PCT serum levels was evaluated in comparison with other inflammatory markers such as CRP, ESR and WBC as an indicator to make the distinction between infected diabetic foot ulcers (IDFUs) and NIDFUs. CRP, WBC, ESR and especially PCT measurements represent effective biomarkers in the diagnosis of foot infections in diabetic patients particularly when clinical signs are misleading.

Blood oxidative stress (BLOS) is a secondary host defense system responding normally to anaerobic wound infection and inadvertently to dietary ultra-exogenous sulfide formation (USF).

Blood oxidative stress (BLOS) is the presence of white blood cells and platelets that are generating high levels of reactive oxygen species (ROS). A mathematical model links the level of BLOS or BLOS# and plasma sulfide concentration. An increase in the BLOS# reduces the plasma sulfide concentration. The reported maximum plasma sulfide concentration for defined health conditions were used to calculate the minimum BLOS#. Elevated BLOS generates high plasma concentration of ROS, which triggers multiple responses in the body that protect the host. First, insulin production by the pancreas is inhibited, which results in elevated blood glucose levels. This results in advanced glycation end products (AGE), which thicken the blood vessel wall. Elevated blood glucose levels also increases urination, which reduces the availability of substrates for infectious bacteria. Second, one or more signaling molecules are stimulated to produce vascular hypertrophy resulting in hypertension. Third, the initial stage of atherosclerosis thickens the blood vessel wall while also protecting the inner surface of the blood vessels from localized infection. The first three mechanisms provide added protection against pathogen migration through the blood vessel wall and reduce the cross-sectional area of blood vessels, which increases the retention time (RT) for improved ROS inactivation of pathogens. Fourth, genes expressed in the liver, which are associated with drug oxidation and uptake transport, are inhibited. This inhibition protects the host from any toxins produced by an anaerobic infection. Elevated BLOS also reduces plasma sulfide concentration, which inhibits wound healing and extends aerobic conditions of the wound. The normal induction of BLOS offers a short-term, cascade of several primary mechanisms for secondary defense against anaerobic infection of a wound. Normal induction of BLOS is due to ultra-exogenous sulfide formation (USF) generated by a local anaerobic infection of a wound in the natural environment. The presence of BLOS without infection is indicative of inadvertent dietary induction. Long-term dietary BLOS results in many severe inflammatory diseases and cancers that are common in an ageing population. Glands were identified as more susceptible to cancers caused by long-term dietary BLOS. Variable BLOS levels in patients of clinical trials may also be reducing effectiveness of experimental drugs and causing drug toxicity. If BLOS is confirmed as a secondary defense against infection that is inadvertently triggered by diet, then a large number of common health problems may be treated and managed by apheresis and dietary changes.

Serum Neopterin and Procalcitonin Levels in Relationship with Pediatric Burn Wound Infections.

Infection and septic complications in burn patients can be monitored by procalcitonin (PCT) and neopterin plasma values. The aim of the study was to investigate serum neopterin and PCT levels with WBC (white blood cell) and CRP (C-reactive protein) levels in patient group (PG) and healthy control group (HCG) and to investigate the relationship of these markers with burn wound infections (BWI). As the PG, 23 patients between 0-12 ages and up to 30% Total Body Surface Area (TBSA) burned and 15 HCG were included. PCT, neopterin, WBC, and CRP results on the first, the seventh, the fourteenth and the 21st day have been compared. During the follow-up period, 11 patients with BWI and 12 patients without BWI were classified as infected and non-infected patients, respectively. PCT and neopterin levels were detected higher in patients with BWI but no significant difference were present. Also, PCT and neopterin levels within the first 24 hours following the burn were detected higher in PG than HCG. CRP and WBC levels were detected high due to burn trauma. PCT and neopterin levels were increased in patients with BWI. PCT levels were increased during the pre-infectious period, while neopterin levels increased during the post-infectious period.

Do Wound Cultures Give Information About the Microbiology of Blood Cultures in Severe Burn Patients?

BACKGROUND: Blood stream infection (BSI) and the subsequent development of sepsis are among the most common infection complications occurring in severe burn patients. This study was designed to evaluate the relationship between the burn wound flora and BSI pathogens. METHODS: Documentation of all bacterial and fungal wound and blood isolates from severe burn patients hospitalized in the burn unit and intensive care unit was obtained from medical records retrieved retrospectively from a computerized, hospital-wide database over a 13-year period. All data were recorded in relation to the Ryan score. RESULTS: Of 195 severe burn patients, 88 had at least 1 BSI episode. Transmission of the same pathogen from wound to blood was documented in 30% of the patients, with a rising BSI frequency as the Ryan score increased. There were a total of 263 bacteremic episodes in 88 study patients, 44% of blood isolates were documented previously in wound cultures, and transmission of the same pathogen from wound to blood was noted in 65% of bacteremic patients. CONCLUSIONS: When there is clinical suspicion of sepsis, appropriate empirical systemic antibiotic therapy should be broad spectrum and should rely on the susceptibility of the organisms from recent cultures of the burn wound surface, until the blood cultures results are completed.

[SOFT TISSUE REPAIR UNDER CONDITIONS OF EXPERIMENTAL SEPTIC WOUND.]

The effectiveness of a new complex preparation based on starch containing active copper (0.05 - 0.07 mass %) and silver 0.03 - 0.05 mass %) nanoparticles was studied in animals with experimental fill-flap septic wounds. Localized application of complex preparation (0.3 g per animal) by uniform layer on 5th, 7th, and 9th day upon wound induction led to significant reduction in wound surface (according to planimetric analysis) at all control periods, in contrast to reference group. There was statistically significant (p < 0.001) decrease in malondialdehyde (by 23%) and increase of serum enzymatic antioxidant ceruloplazmin activity (by 20.5%) in rat blood serum compared to the corresponding indexes in animals before therapy. These results are indicative of the suppression of peroxidation processes and stimulation of antioxidant system. The complex preparation exhibited positive influence on soft tissue repair processes, lipid peroxidation processes, and activity of the antioxidant system.

Lower limb orthopaedic surgery results in changes to coagulation and non-specific inflammatory biomarkers, including selective clinical outcome measures.

BACKGROUND: With an aging society and raised expectations, joint replacement surgery is likely to increase significantly in the future. The development of postoperative complications following joint replacement surgery (for example, infection, systemic inflammatory response syndrome and deep vein thrombosis) is also likely to increase. Despite considerable progress in orthopaedic surgery, comparing a range of biological markers with the ultimate aim of monitoring or predicting postoperative complications has not yet been extensively researched. The aim of this clinical pilot study was to test the hypothesis that lower limb orthopaedic surgery results in changes to coagulation, non-specific markers of inflammation (primary objective) and selective clinical outcome measures (secondary objective). METHODS: Test subjects were scheduled for elective total hip replacement (THR) or total knee replacement (TKR) orthopaedic surgery due to osteoarthritis (n = 10). Platelet counts and D-dimer concentrations were measured to assess any changes to coagulation function. C-reactive protein (CRP) and erythrocyte sedimentation rate (ESR) were measured as markers of non-specific inflammation. Patients were monitored regularly to assess for any signs of postoperative complications, including blood transfusions, oedema (knee swelling), wound infection, pain and fever. RESULTS: THR and TKR orthopaedic surgery resulted in similar changes of coagulation and non-specific inflammatory biomarkers, suggestive of increased coagulation and inflammatory reactions postoperatively. Specifically, THR and TKR surgery resulted in an increase in platelet (P = 0.013, THR) and D-dimer (P = 0.009, TKR) concentrations. Evidence of increased inflammation was demonstrated by an increase in CRP and ESR (P ≤ 0.05, THR and TKR). Four patients received blood transfusions (two THR and two TKR patients), with maximal oedema, pain and aural temperatures peaking between days 1 and 3 postoperatively, for both THR and TKR surgery. None of the patients developed postoperative infections. CONCLUSIONS: The most noticeable changes in biological markers occur during days 1 to 3 postoperatively for both THR and TKR surgery, and these may have an effect on such postoperative clinical outcomes as oedema, pyrexia and pain. This study may assist in understanding the postoperative course following lower limb orthopaedic surgery, and may help clinicians in planning postoperative management and patient care.

Worse limb prognosis for indirect versus direct endovascular revascularization only in patients with critical limb ischemia complicated with wound infection and diabetes mellitus.

OBJECTIVES: To investigate factors in patients with critical limb ischemia (CLI) and isolated infrapopliteal lesions that adversely affect outcomes of endovascular therapy (EVT) with or without angiosome-oriented revascularization. METHODS: This was a retrospective multicenter study. We used a database of 718 consecutive CLI patients (70 ± 11 years, 75% diabetics, 68% on hemodialysis, 24% Rutherford class 6) with ischemic tissue loss due to isolated infrapopliteal lesions undergoing primary EVT. Primary outcome was MALE (major adverse limb event). Association between indirect EVT (recanalization of a non-angiosome-based artery) and outcome was assessed by Cox proportional hazard regression model. RESULTS: C-reactive protein (CRP) level was >3 mg/dL in 32% of cases. Indirect EVT (in 307 CLI patients, 43%), was associated with MALE (p = .04, hazard ratio [95% confidence interval] 1.25 [1.01, 1.55]), and interacted with CRP >3 mg/dL (p < .004) but not with other baseline characteristics. Indirect EVT with CRP >3 mg/dL had higher MALE risk (HR 2.08), and interacted with diabetes mellitus (DM) presence. Indirect EVT with CRP >3 mg/dL and DM had higher MALE risk (HR 2.17). CONCLUSION: Limb prognosis was equivalent for direct and indirect endovascular revascularization except in the presence of both diabetes and wound infection, when indirect revascularization has a poorer outcome.

Single-nucleotide polymorphisms in the Toll-like receptor pathway increase susceptibility to infections in severely injured trauma patients.

BACKGROUND: Sepsis and subsequent multiple-organ failure are the predominant causes of late mortality in trauma patients. Susceptibility and response to infection is, in part, heritable. Single-nucleotide polymorphisms (SNPs) in Toll-like receptor (TLR) and cluster of differentiation 14 (CD14) genes of innate immunity may play a key role. The aim of this study was to assess if SNPs in TLR/CD14 predisposed trauma patients to infection. METHODS: A prospective cohort of trauma patients (age 18-80 years; injury severity score [ISS] ≥ 16) admitted to a Level I trauma center between January 2008 and April 2011 was genotyped for SNPs in TLR2 (T-16934A and R753Q), TLR4 (D299G and T399I), TLR9 (T-1486C and T-1237C), and CD14 (C-159T) using high-resolution melting analysis. Association of genotype with prevalence of positive culture findings (gram positive, gram negative, fungi), systemic inflammatory response syndrome (SIRS), sepsis, septic shock, and mortality was tested with χ(2) and logistic regression analysis. RESULTS: Genotyping was performed for 219 patients, of whom 51% developed positive culture findings in sputum, wounds, blood, or urine. SIRS developed in 64%, sepsis in 36%, and septic shock in 17%. The TLR2 T-16934A TA genotype increased the risk of a gram-positive infection (odds ratio, 2.816; 95% confidence interval, 1.249-6.348; p = 0.013) and SIRS (odds ratio, 2.386; 95% confidence interval, 1.011-5.632; p = 0.047). Trends were noted for TLR9 and CD14 SNPs but did not reach statistical significance. Sepsis and septic shock were unrelated to any of the SNPs studied. CONCLUSION: Aberrant functioning of the TLR/CD14 pathway of innate immunity changes the risk of infectious complications in severely injured trauma patients. Of the seven SNPs studied, the TLR2 T-16934A increased the risk, the TLR9 T-1486C SNPs may decrease the risk, and TLR4 variation seemed unrelated to outcome. Early genotyping may prove to be helpful in the future in identifying polytraumatized patients at risk for infectious outcome. LEVEL OF EVIDENCE: Prognostic and epidemiologic study, level II.

[Soluble form of trigger receptor expressed on myeloid cells-1 as a marker of burn wound mixed infection].

AIM: Detection ofearly non-bacteriological markers ofburn wound mixed microbial infection. MATERIALS AND METHODS: The level of soluble form of trigger receptor expressed on myeloid cells-1 (sTREM-1) and cytokines in blood sera of 60 burn patients on days 3 - 6 and 10 - 17 after the burn was studied by solid phase enzyme immunoassay. RESULTS: At the early periods of burn disease the level ofsTREM- 1 in sera may be a non-bacteriological marker of burn wound mixed infection: at days 3 - 6 after the injury - higher than 298.8 pg/ml, at days 10 - 17 after the burn - higher than 294.2 pg/ml. CONCLUSION: Level of sTREM-1 in blood sera of patients with severe thermic injury could be proposed as an additional laboratory marker of burn wound mixed microbial infection.

Acute glucose elevation is highly predictive of infection and outcome in critically injured trauma patients.

OBJECTIVE(S): To evaluate whether acute glucose elevation (AGE) is predictive of infection and outcome in critically injured trauma patients during the first 14 days of ICU admission. METHODS: A prospective study was conducted on 2200 patients admitted to the ICU over a 2 1/2 year period. The diagnosis of infection was made via a multidisciplinary fashion utilizing CDC criteria. After early glucose stabilization occurred (no significant change for 48 hours after admission) monitoring for AGE was performed utilizing a computational and graded algorithmic model. Iatrogenic causes of AGE were excluded. Stepwise regression models were performed controlling for age, gender, mechanism of injury, diabetes, injury severity, and APACHE 2 score. ROC curves were used to evaluate the positive predictive value of the test. RESULTS: Seventy-seven percent of the patients in the cohort were males, and were admitted for blunt injuries (n = 1870 or 85%). The mean age, Injury Severity Score, and APACHE score were 44 ± 20 years, 29 ± 13, and 13 ± 7, respectively. The mean admission serum glucose value was 141 ± 36 mg/dL (range, 64-418 mg/dL). A total of 616 (28%) patients were diagnosed with an infection during the first 14 days of admission. AGE had a 91% positive predictive value for infection diagnosis. In addition, AGE was associated with a significant increase in ventilator, ICU, and hospital days as well as mortality even when adjusted for age, injury severity, APACHE score, and diabetes (P < 0.001). CONCLUSIONS: AGE is a highly accurate predictor of infection and should stimulate clinicians to identify a new source of infection.

Current techniques to detect foot infection in the diabetic patient.

Diabetic foot infections can be a challenge to diagnose, especially when osteomyelitis is in question. Evaluation of infection should involve a thorough examination of the extremity for clinical signs of infection along with appropriate laboratory and imaging studies. Laboratory markers of inflammation such as peripheral leukocyte count, erythrocyte sedimentation rate, C-reactive protein, and procalcitonin may provide useful information when diagnosing soft tissue and bone infection. However, laboratory markers alone should not be used to diagnose a diabetic foot infection as they are non-specific in nature. Imaging studies may also provide valuable clues regarding the presence of infection. Plain radiographs are a good initial screening tool as they are both inexpensive and easily accessible. However, their sensitivity in diagnosing osteomyelitis is poor. Thus, more advanced imaging such as radionuclide imaging and magnetic resonance imaging are warranted when osteomyelitis is suspected. Magnetic resonance imaging is presently considered the gold standard in diagnosing osteomyelitis, despite its wide variation in reported sensitivity and specificity. However, the significant cost of magnetic resonance imaging prevents its use as a screening tool. Collection of reliable microbiologic data is critical in making a diagnosis as well as for treatment of infection, especially when osteomyelitis is concerned. Deep swabs and transcutaneous bone biopsy are considered the ideal methods of obtaining the necessary information. Finally, monitoring treatment should also be performed with an eye towards both laboratory data and the clinical exam.

Photodynamic inactivation of Escherichia coli and Streptococcus mitis by cationic zinc(II) phthalocyanines in media with blood derivatives.

The photodynamic inactivation (PDI) of Escherichia coli and Streptococcus mitis sensitized by cationic phthalocyanines was studied in different media containing blood derivatives. First, the activity of zinc(II) tetramethyltetrapyridino[3,4-b:3',4'-g:3'',4''-l:3''',4'''-q]porphyrazinium (ZnAPc4+), zinc(II) 2,9,16,23-tetrakis[4-(N-methylpyridyloxy)]phthalocyanine (ZnPPc4+) and zinc(II) 2,9,16,23-tetrakis[2-(N,N,N-trimethylamino)ethoxy]phthalocyanine (ZnEPc4+) were compared to photoinactivate these bacteria in saline solutions. After visible light irradiation, a higher photoinactivation of E. coli cells was found for ZnPPc4+, while ZnEPc4+ was the more effective sensitizer to eradicate S. mitis cells. In the presence of human red blood (HRB) cells, two aspects were analyzed: the photohemolysis induced by these cationic phthalocyanines and the PDI of bacteria in medium containing erythrocytes. The highest photohemolytic damage was produced by ZnPPc4+, which can be avoided using azida ion as photoprotective quencher. In both bacteria, the photoinactivation is possible in presence of HRB cells. Mainly, ZnEPc4+ is effective to photoinactivate S. mitis with a low hemolysis of erythrocytes. However, inactivation of E. coli by ZnPPc4+ decreases in medium with HRB cells, further when azide ion is added to avoid hemolysis. The presence of plasma considerable reduces the photocytotoxic effect, which mainly affects the eradication of E. coli. However, the PDI of S. mitis by ZnEPc4+ is even possible in presence of blood derivatives.

Perioperative blood transfusion in combat casualties: a pilot study.

BACKGROUND: In recent studies, blood transfusion has been shown to increase the rate of wound healing disturbances in orthopedic patients. Furthermore, our group has determined a correlation between delayed wound healing and elevations in inflammatory mediators in combat casualties. Therefore, we sought to determine the effect of blood transfusion on wound healing and inflammatory mediator release in combat casualties. METHODS: Prospective data were collected on 20 severely injured combat casualties sustaining extremity wounds. Patients were admitted to the National Naval Medical Center during a 13-month period from January 2007 to January 2008. Data variables included age, gender, Glasgow coma score (GCS), mechanism of injury, and transfusion history. Injury severity was assessed using the Injury Severity Score (ISS). Serum was collected initially and before each surgical wound debridement and analyzed using a panel of 21 cytokines and chemokines. The association between blood transfusion and wound healing, incidence of perioperative infection, intensive care unit (ICU) admission rate, and ICU and hospital length of stay was assessed. Differences were considered significant when p < 0.05. RESULTS: The study cohort had a mean age of 22 +/- 1, a mean ISS of 15.8 +/- 2.6, and a mean GCS 13.9 +/- 0.6; all were men and suffered penetrating injuries (90% improvised explosive device [IED] and 10% gunshot wound [GSW]). The cohort was divided into two groups. Patients receiving 4 units of blood initially (group 2, n = 9). There was no significant difference in age, ISS, GCS, or mortality between the two groups. However, group 2 patients had significant impairment in wound healing rate (54% vs. 9%, p < 0.05), higher ICU admission rate (78% vs. 9%, p < 0.01), perioperative infection rate (89% vs. 27%, p < 0.01), and a longer hospital length of stay (49.9 +/- 12.8 vs. 23.8 +/- 2.9, p < 0.05) compared with group 1 patients. In addition, there was a significant correlation between the initial mean serum cytokine/chemokine level of interleukin (IL)-10, IL-8, interferon inducible protein (IP)-10, IL-6, and IL-12p40 and the number of units of blood transfused (p < 0.05). CONCLUSION: Allogeneic blood transfusions in combat casualties were associated with impaired wound healing, increased perioperative infection rate, and resource utilization. In addition, the extent of blood transfusion was associated with significant differences in inflammatory chemokine and cytokine release.

The association between blood alcohol level and infectious complications among burn patients.

Approximately 50% of fatal and 15% of nonfatal burn-injured patients have detectable blood alcohol content (BAC) at the time of admission, and it is hypothesized that alcohol exacerbates burn-related immunosuppression. The purpose of this study was to evaluate the association between BAC and infectious complications in burn patients. The study population consisted of 1161 burn patients admitted to a large academic burn center between January 1998 and June 2007. Patients were categorized into no BAC (0.0 g/100 ml), low/moderate BAC (>0.0 and <0.1 g/100 ml) and high BAC (> or =0.1 g/100 ml) groups based on BAC at time of admission. Risk ratios (RRs) and 95% confidence intervals (CIs) were calculated for associations between pneumonia, sepsis, urinary tract infection, line infection, and wound infection and BAC, adjusted for total burn surface area and inhalation injury. Relative to no BAC patients, both low/moderate and high BAC patients had nonsignificantly increased risk for most infectious complications. High BAC patients were at significantly increased risk for any infectious complication (RR 2.06, CI 1.25-3.41) and pneumonia (RR 2.06, CI 1.04-4.09) and a nonsignificantly increased risk of urinary tract infection (RR 2.12, CI 0.0.94-4.78). Results suggest that preinjury alcohol consumption places patients at an increased risk for infectious complications, most notably pneumonia. Further studies examining the relationship between alcohol and pneumonia among burn patients will help elucidate the reason for the increased risk observed in the current study and suggest ways to prevent infection for this particular subgroup of burn patients.