Semiclosure wound therapy plus negative pressure wound therapy for an older patient with grade 4 diabetic foot with concomitant vascular occlusion: A case report.

RATIONALE: Grade 4 diabetic foot (DF) is a severe infection that causes bone destruction, osteomyelitis, and osteoarticular damage, which, in turn, can lead to serious dry or wet gangrene, or amputation. DF is extremely difficult to treat. PATIENT CONCERNS: A 71-year-old female patient with long-term diabetes complicated with uremia, who undergoes regular hemodialysis 2 to 3 times per week, was admitted with grade 4 DF with Pseudomonas aeruginosa infection, and concomitant vascular occlusion of the lower extremities. The patient had a concurrent nutrition and electrolyte disorder. DIAGNOSES: The patient was diagnosed with type 2 diabetes, grade 4 DF, postamputation of the 2nd toe, vascular occlusion of the lower extremities, atherosclerosis, uremia, hypoproteinemia, and electrolyte disturbances. INTERVENTIONS: Treatment with antibiotics and comprehensive measures aimed at improving nutrition and microcirculation, controlling blood glucose, as well as balancing electrolytes were performed to ameliorate the general conditions. Nibbled debridement was used to remove devitalized tissues each time to maintain as much vital cells as possible. Open therapy was used for necrotic tissues, and dressings therapy was used simultaneously for the infected lesion. This combined treatment, involving open therapy with dressing, is referred to as "semiclosure wound therapy." Negative pressure wound therapy (NPWT) was used after a fistula formed. OUTCOMES: During the treatment procedure, the gangrene 3rd toe was spontaneously shed; the necrotic 1st toe was removed by surgery. The wound gradually healed after 3 months of open therapy combined with dressing. High location amputation was avoided. LESSONS: Semiclosure, which constitutes open therapy combined with the use of dressings, plus NPWT can preserve vital skin cells in the wound and control the aggravation of the infection. It is an effective and novel measure that prevents DF amputation in old patient and promotes wound union.

Clinical and microbiological profile of diabetic foot ulcer patients in a tertiary care hospital.

AIM: To evaluate the clinical and microbiological profile of diabetic foot ulcer patients admitted to a tertiary care hospital. METHODOLOGY: This study recruited 120 diabetic foot ulcer patients of all grade. Their medical records were evaluated retrospectively. RESULTS: We found that median age of patient was 60(52, 67.75) years. 68.3% of patients were males. Median duration of diabetes mellitus was 15(10, 20) years. Mean HbA1C and fasting glucose was 10.3±2.3 and 167.6±52.42 respectively. Neuropathy (35%) and peripheral vascular disease (23.3%) was major micro vascular and macro vascular complication associated. Different locations of ulcers were toe (23.3%), sole (20%), dorsum (18.3%), shin (16.6%), heel (13.3%), and ankle (8.3%). Bacterial infection was seen in 81.66% patients out of which 23.3% had poly microbial infection. CONCLUSION: Diabetic foot ulcer patient had poor blood glucose control with elevated HbA1C and fasting blood glucose level. Neuropathy and peripheral vascular disease, hypertension were major complications. Staphylococcus aureus, Pseudomonas aeruginosa were common infecting bacteria.

Use of Self-Expanding Covered Stents as Bailout Treatment of Spontaneous Rupture of the Femoral Artery Caused by Staphylococcus aureus Infection.

Spontaneous rupture of femoropopliteal arteries caused by infection requires treatment in the urgent setting. The present article reports on the performance of self-expanding covered stents in 3 patients who experienced acute rupture of the femoral artery caused by Staphylococcus aureus infection. After a mean follow-up of 16.4 months, the bailout placement of self-expanding covered devices showed sustained patency and sufficient exclusion of the rupture site. A surgical conversion and bypass reconstruction was not necessary. Long-term follow-up and inclusion of more patients are needed to provide more evidence about the utility of this approach.

Diabetic foot ulcer--A review on pathophysiology, classification and microbial etiology.

As the prevalence of diabetes is increasing globally, secondary complications associated to this endocrinal disorder are also ascending. Diabetic foot ulcers are potentially modifying complications. Disruption of harmony in glucose homeostasis causes hyperglycemic status, results in activation of certain metabolic pathways which in their abnormal state subsequently leads to development of vascular insufficiency, nerve damages headed by ulceration in lower extremity due to plantar pressures and foot deformity. Insult to foot caused by trauma at the affected site goes unnoticeable to patient due to loss of sensation. Among the above mention causes, resistance to infection is also considered as chief modulator of pathophysiological image of diabetic foot lesions. Healing as well as non-healing nature of ulcer relies upon the wound microbial communities and the extent of their pathogenicity. A validated classification system of foot ulcer is primarily necessary for clinicians in management of diabetic foot problems. Another aspect which needs management is proper identification of causative pathogen causing infection. The way of approaches presently employed in the diagnosis for treatment of foot ulcer colonized by different microbes is conventional techniques. Conventional diagnostic methods are widely acceptable since decades. But in recent years newly invented molecular techniques are exploring the use of 16S ribosomal regions specific to prokaryotes in bacterial identification and quantification. Molecular techniques would be a better choice if engaged, in finding the specific species harboring the wound.

Emergency endovascular treatment of early spontaneous nonaneurysmal popliteal artery rupture in a patient with Salmonella bacteremia.

Rupture of a nonaneurysmal popliteal artery and subsequent pseudoaneurysm formation is an exceedingly rare event after bacteremia caused by Salmonella spp. Only a few cases have been reported in the literature. Moreover, spontaneous popliteal artery rupture resulting from this pathology, to our knowledge, has not been reported. We describe an early spontaneous rupture of the popliteal artery complicated by acute compartment syndrome in a 67-year-old man who had recently experienced fever, chills, and diarrheal syndrome and had sustained episodes of bacteremia infection, with isolation of S enteritidis. Immediate endovascular sealing of the bleeding site was achieved with a covered stent, and his recovery was uneventful. The long-term durability of endovascular repair in this type of pathology remains to be determined, however.

Arterial reconstruction with cryopreserved human allografts in the setting of infection: A single-center experience with midterm follow-up.

OBJECTIVES: Vascular reconstruction in the setting of primary arterial or prosthetic graft infection is associated with significant morbidity and mortality. Cryopreserved human allografts (CHA) may serve as acceptable alternatives when autogenous or extra-anatomic/in situ prosthetic reconstructions are not possible. METHODS: Between February 1999 and June 2008, 57 CHAs were placed in 52 patients (average age, 65 years) for abdominal aortic (n = 18) or iliofemoral/femoral-popliteal arterial or prosthetic infections (n = 39). Indications for arterial reconstruction included infected implanted prosthetic material (n = 39), mycotic pseudoaneurysms (n = 14), or intra-abdominal bacterial contamination or wound infection (n = 4). Wide local debridement and culture was followed by allograft interposition, bypass, or extra-anatomic reconstruction. Over a similar time period, 53 non-CHA extra-anatomical prosthetic or in situ autogenous tissue reconstructions were performed in 53 patients (average age, 65 years) for abdominal aortic (n = 18) or iliofemoral and femoral-popliteal (n = 35) prosthetic graft infections. Indications for arterial replacement in all cases included infected implanted prosthetic material. RESULTS: Thirty-day mortality for all CHA and non-CHA reconstructions was 5.2% and 7.5%, respectively. The 1-year procedure-related mortality for all CHA and non-CHA procedures was 7.0% and 13.2%, respectively. In the CHA cohort, 5 patients required re-exploration for hemorrhage or anastomotic disruption. In midterm CHA follow-up (20 months), there was 1 graft thrombosis, 2 graft stenoses, 1 recurrent ilioenteric fistula, and 1 non-related amputation. The remainder of the CHA reconstructions remained patent without evidence of aneurysmal change or reinfection. CONCLUSION: In the setting of infection, cryopreserved human allograft arterial reconstruction is a viable alternative to traditional methods of vascular reconstruction in patients without available autogenous conduit and when expedient reconstruction is required. In midterm follow-up, cryopreserved allografts appear to be resistant to subsequent reinfection, thrombosis, or aneurysmal dilatation. However, larger patient populations and longer follow-up are needed to determine if arterial reconstruction with CHA is the safest and most durable method of treatment for arterial infections.

Anti-chlamydial antibiotic therapy for symptom improvement in peripheral artery disease: prospective evaluation of rifalazil effect on vascular symptoms of intermittent claudication and other endpoints in Chlamydia pneumoniae seropositive patients (PROVIDENCE-1).

BACKGROUND: A potentially strong association exists between Chlamydia pneumoniae and atherosclerosis, but the clinical benefits of antibiotic therapy have not been demonstrated. Preliminary studies of antibiotic therapy in peripheral artery disease have shown a decreased need for revascularization and improved walking ability. The objective of this phase-III trial was to assess the effect of a potent anti-Chlamydial agent, rifalazil, on peak walking time in patients with symptomatic peripheral artery disease. METHODS AND RESULTS: Patients with intermittent claudication secondary to peripheral artery disease who were seropositive for C pneumoniae were randomized to 25 mg rifalazil once weekly for 8 weeks or matching placebo. Two hundred ninety-seven patients were enrolled from 3 countries and were followed up for 1 year. The mean+/-SD ankle brachial index at baseline was 0.63+/-0.16. The primary end point, change from baseline in log peak walking time on a graded treadmill, was assessed 180 days after randomization. Secondary end points included changes in claudication onset time and quality of life, assessed with the Walking Impairment Questionnaire and the Short Form Medical Outcomes 36. No benefit of rifalazil therapy was found in the primary or any secondary end point among this cohort of patients with peripheral artery disease. The group treated with rifalazil improved their peak walking times by 23% (95% confidence interval, 15 to 31) from baseline to day 180, whereas the placebo group improved by 18% (95% confidence interval, 11 to 26; P=0.38). Peak walking time, claudication onset time, Walking Impairment Questionnaire, and Short Form Medical Outcomes 36 showed no treatment-by-time interaction during the 360-day study period. Thirty-two adjudicated cardiovascular events occurred, 16 in each treatment group. CONCLUSIONS: Rifalazil did not improve exercise performance or quality of life in patients with intermittent claudication. No safety concerns were identified. Given the very small effect size, it is unlikely that larger studies would demonstrate a symptomatic benefit of this therapy in peripheral artery disease.

Chronic Helicobacter pylori infection is associated with peripheral arterial disease.

It is reported that Helicobacter pylori infection is associated with coronary atherosclerosis both epidemiologically and pathogenetically, but no conclusions have yet been reached. Therefore, we investigated the relationship between H. pylori infection and peripheral arterial disease (PAD). Sixty-nine patients with PAD attending Harasanshin General Hospital (Fukuoka, Japan) were compared with 143 controls (age-matched asymptomatic outpatients with hyperlipidemia). H. pylori infection was diagnosed by the detection of IgG antibodies, the (13)C-urea breath test, and histological examination. Multiple logistic regression analysis was used to assess the data. The 69 PAD patients and 143 controls were aged from 50 to 92 years. According to the Fontaine classification, 43/69 PAD patients (62.3%) were grade I, 25 (36.2%) were grade II, and 1 (0.14%) was grade III. The prevalence of H. pylori infection was higher in the PAD patients than in the controls (79.7% versus 44.8%; P < 0.01). Stepwise logistic regression analysis revealed that H. pylori infection and hypertension had a significant influence on the occurrence of PAD. Our results suggest that chronic H. pylori infection may be one of the risk factors for PAD.

Laboratory diagnosis of bone, joint, soft-tissue, and skin infections.

The diagnosis of infections of bones, joints, skin, and soft-tissues requires the combined use of a number of laboratory and pathology tests. The diagnosis of most infections requires microbiological cultures, both for isolation and for identification of causative organisms, as well as for antimicrobial susceptibility testing. Chemical analysis of joint fluids and histopathologic examination of infected tissues are often necessary to distinguish infections from other causes of inflammation, as well as to provide information as to the type of infection before the results of cultures are available. At this time, the use of molecular amplification tests is of limited value in the diagnosis of these infections, their value primarily being as adjunct tests for the diagnosis of rare or unusual infections.

Markers of Chlamydia pneumoniae and human cytomegalovirus infection in patients with chronic peripheral vascular disease and their relation to inflammation, endothelial dysfunction and changes in lipid metabolism.

Our aim was to detect markers of Chlamydia pneumoniae (CPN) and human cytomegalovirus (HCMV) infection in patients with peripheral vascular occlusive disease and to follow markers of inflammation, endothelial dysfunction and lipid metabolism alteration in patients with active infection. CPN genome was detected in 9 (47.4 %) patients by at least one PCR method. Serological markers of acute CPN infection were found in 5 (26.3 %) subjects; each of them showed also positivity in at least one of the PCR methods. HCMV DNA were detected in 2 (10.5 %) patients; HCMV-specific antibodies were detected in 14 (73.7 %) subjects, however only in IgG subclass. Subjects with HCMV PCR positivity thus showed no serological markers of active HCMV infection. Laboratory findings of acute CPN infection were associated with increased plasma levels of Lp(a), triacylglycerols, atherogenic index of plasma and E-selectin (p < 0.05). No significant differences were found in the other markers, including plasma levels of total cholesterol, ferritin, homocysteine, oxidized LDL, IL-6, IL-8, IL-18, TNF-alpha, soluble forms of VCAM-1 and ICAM-1, von Willebrand factor, C-reactive protein, and plasma nitrites & nitrates. Frequent presence of chlamydial DNA in atheromatous plaques from patients with peripheral vascular disease was confirmed. HCMV DNA was detected only sporadically and with positivity in anamnestic anti-HCMV antibodies (IgG) only, indicating a rare presence of latent virus rather than active replication. Patients with laboratory markers of acute CPN infection exhibited more pronounced alterations in lipid metabolism and endothelial dysfunction.

Periodontitis may increase the risk of peripheral arterial disease.

OBJECTIVES: The aim of this case control study was to evaluate whether periodontitis was associated with peripheral arterial disease (PAD). SUBJECTS AND METHODS: Twenty-five patients diagnosed with aorto-iliac and/or femoro-popliteal occlusive disease and thirty-two generally healthy control subjects were enrolled in this study. Polymerase chain reaction (PCR) was used to identify Porphyromonas gingivalis, Treponema denticola, Actinobacillus actinomycetemcomitans, Prevotella intermedia, Cytomegalovirus (CMV), Chlamydia pneumoniae, and Helicobacter pylori in tissue specimens taken from the anastomotic site of distal bypasses. Periodontal status was evaluated; serum IgG titres against the four listed bacteria were measured. RESULTS: Periodontopathic bacteria were detected in 13/25 (52%) atherosclerotic specimens. CMV or C. pneumoniae was detected in 1/25 (4%) specimens; H. pylori was not detected from any of these specimens. Fontaine grade III or IV patients showed higher detection frequency of P. gingivalis than Fontaine grade II patients (57.1% vs 22.2%, P=0.09). After adjusting for age, gender, diabetes and smoking, periodontitis increased 5-fold the risk of having PAD (OR 5.45). There were preliminary indications that periodontitis was associated with increased serum IL-6 and TNF-alpha concentrations. CONCLUSIONS: This study suggests that periodontitis may be associated with an increased risk of PAD. This association could result from the increased concentration of serum inflammatory cytokines in those with periodontitis.

[Role of chronic infection and heat shock proteins in peripheral arterial disease]. / Rola przewleklego zakazenia i bialek HSP 60/65 w miazdzycy zarostowej.

The activation of the immunologic system plays an immportant role in the initiation of atherogenesis, as shown in numerous studies. However the role of infectious agents in this process still remains controversial. The aim of this study was to investigate the involvement of heat shock protein as a link between infection and peripheral arterial disease. 31 patients suffering from lower limb ischemia were enrolled in the study. Patients were divided into 2 groups. Group I - patients with peripheral arterial disease, group II patients with diabetic macroangiopathy. The control group consisted of 11 healthy volunteers. Blood samples were taken from each participant in order to determine serum concentrations of anti Chlamydia pneumoniae, CMV and HSP 60/65 antibodies. Statistic analysis showed anti-C. pneumoniae IgG (p< 0.025) and anti-CMV IgG (p<0.0157) antibodies were significantly more frequent in both study groups in comparison with healthy controls. Antibodie levels were also found significantly higher than in controls. Mean concentration of anti-C. pneumoniae IgG in the study group was 69.67574 vs. 18.59722 [AU/ml] in the control group (p<0.01). Analogical anti CMV IgG levels in the study group were 337.6516 vs 121.3778 [AU/ml] in controls (p<0.025). Similar changes in antibody concentration were noticed for the C. pneumoniae IgA index. 0.835258 vs. 0.176333 (p< 0.005). Antibodies against HSP 60/65 were present in significantly higher titre (p<0.005). No significant differences in antibody levels were detected beteween groups I and II. The positive correlation between anti-C. pneumoniae Ig A (r=0.3910; p<0.03) and anti HSP 60/65 antibodies titre, as well as anti-C. pneumoniae Ig G (r= 0.7151; p<0.00009) and anti HSP 60/65 speaks for the heat shock protein involvement in atherosclerotic plaque development.

Rifalazil and other benzoxazinorifamycins in the treatment of chlamydia-based persistent infections.

Rifalazil is a benzoxazinorifamycin which inhibits bacterial DNA-dependent RNA polymerase. The benzoxazine ring endows benzoxazinorifamycins with unique physical and chemical characteristics which favor the use of rifalazil and derivatives in treating diseases caused by the obligate intracellular pathogens of the genus chlamydia. Minimal inhibitory concentrations of benzoxazinorifamycins against chlamydia are in the pg/mL range. These compounds have potential as monotherapeutic agents to treat chlamydia-associated disease because they retain activity against chlamydia strains resistant to currently approved rifamycins such as rifampin. A pivotal clinical trial with rifalazil has been initiated for the treatment of peripheral arterial disease. The rationale for this innovative use of rifalazil, including the association of C. pneumoniae in atherosclerotic plaque formation, as well as rifalazil's potency and efficacy against chlamydia in both preclinical and clinical studies, is discussed. Other benzoxazino derivatives may have utility as stand-alone topical antibacterials or combination antibacterials to treat serious Gram-positive infections. None of the benzoxazinorifamycins examined to date induce the cytochrome P450 3A4 enzyme. This is in contrast to currently approved rifamycins which are strong inducers of P450 enzymes, resulting in drug-drug interactions that limit the clinical utility of this drug class.

Chronic peripheral arteriopathy is associated with seropositivity to Chlamydia pneumoniae.

The study was carried out to clarify the correlation between Chlamydia pneumoniae infection and peripheral arterial disease (PAD). The level of specific antibodies of the 133 consecutive patients suffering from PAD at 2nd stage of Leriche's classification were compared with 60 healthy controls by using a commercial Micro-IF Test. A higher incidence of serological evidence of C. pneumoniae infection was found in the patients (106/133) than in controls (6/60). These results are in agreement with other findings that measured the infection in atheromasic plaques. A strong cause-effect relationship between bacterial infection and peripheral arterial disease was not found, but the raised seropositivity level could be considered as a target for medical therapy of PAD.

Inflammation and Chlamydia pneumoniae infection correlate with the severity of peripheral arterial disease.

BACKGROUND: Our aim was to investigate the association of inflammation and Chlamydia pneumoniae infection with the presence and severity of peripheral arterial disease. METHODS: Twenty-eight patients whose initial claudication distance (ICD) in the traditional constant-load treadmill test was <200 m, underwent femoral endarterectomy as part of their interventional treatment (group A). Group B consisted of 23 patients whose ICD was >200 m and were put on medication and a daily exercise program. The control group consisted of 30 non-vascular patients of the Ophthalmology Department (group C). We measured the levels of C-reactive protein, fibrinogen, vascular cell adhesion molecule-1 and tumor necrosis factor-alpha, and the titers of IgA and IgG antibodies against C. pneumoniae in the serum of all the patients. Finally, the atheromas and vein segments of group A patients, were immunohistochemically (IHC) examined for the presence of C. pneumoniae. RESULTS: Peripheral arterial disease (PAD) patients, had significantly higher CRP (p=0.026) and anti-Cp IgA levels (p=0.001) when compared to control subjects, after a multiple linear regression analysis. The odds ratio for the prevalence of femoral atherosclerosis was 3.16 for IgA seropositive patients (CI 1.15-8.67). When comparing group A and group B patients, CRP (p=0.003) and IgA (p=0.011), were significantly correlated with severe PAD. Group A patients with positive immunohistochemical examination of the plaque, had higher anti-Cp IgA levels (p=0.023) and TNF-alpha values (p=0.031), compared to the IHC negative patients. C. pneumoniae was detected in 50% of the femoral atheromas, but in only 3.6% of the veins. CONCLUSION: This study supports the hypothesis that inflammation (CRP) and chronic C. pneumoniae infection (IgA seropositivity), have an important role in lower limb atherosclerosis and correlate with the severity of the disease.

Secondary prevention of atherosclerosis through chlamydia pneumoniae eradication (SPACE Trial): a randomised clinical trial in patients with peripheral arterial disease.

BACKGROUND: Sero-epidemiological and experimental studies suggest that Chlamydia pneumoniae infections play an important role in the development of atherosclerosis. Clinical trials have shown contradictory results regarding the efficacy of antibiotics to prevent atherosclerosis-related complications in patients with coronary artery disease. Our aim was to study the effect of a short course of azithromycin on the incidence of cardiovascular events and peripheral vascular function in patients with stable peripheral arterial disease (PAD). PATIENTS AND METHODS: Five hundred and nine PAD-patients were randomised to receive either a 3-day course of azithromycin (500 mg daily) or placebo, with 2 years of follow-up. C. pneumoniae serology was determined at baseline. Clinical endpoints were death, coronary events (myocardial infarction, unstable angina, and/or coronary revascularization procedures), cerebral events (stroke, TIA, and/or carotid endarterectomy) and peripheral arterial complications (increased PAD-symptoms with decreased ankle-brachial index (ABPI, 0.1-point decrease after 12 months), and/or peripheral revascularization procedures). RESULTS: Five hundred and nine patients (160 women) with an atherosclerotic risk factor profile were randomised, 257 patients to azithromycin and 252 to placebo. Four hundred and forty nine patients (88%) had intermittent claudication and 60 (12%) had critical limb ischemia. By 24-month follow up, 182 patients (36%) developed 252 complications (45 deaths, 34 coronary events, 34 cerebral events and 139 peripheral arterial complications). C. pneumoniae IgA-titres were associated with the development of cardiovascular events. Nevertheless, the number of complications (131 in the azithromycin group vs. 121 in the placebo group) and the number of patients that developed complications (98 (38%) in the azithromycin vs. 84 (33%) in the placebo group) was comparable in both treatment groups. Life table analysis showed no effect of azithromycin on survival or ABPI. CONCLUSION: A short-term course of azithromycin offers no benefits for survival or ankle pressure in PAD-patients.