Mortality-associated factors of candidemia: a multi-center prospective cohort in Turkey.

Candidemia may present as severe and life-threatening infections and is associated with a high mortality rate. This study aimed to evaluate the risk factors associated with 30-day mortality in patients with candidemia. A multi-center prospective observational study was conducted in seven university hospitals in six provinces in the western part of Turkey. Patient data were collected with a structured form between January 2018 and April 2019. In total, 425 episodes of candidemia were observed during the study period. Two hundred forty-one patients died within 30 days, and the 30-day crude mortality rate was 56.7%. Multivariable analysis found that SOFA score (OR: 1.28, CI: 1.154-1.420, p < 0.001), parenteral nutrition (OR: 3.9, CI: 1.752-8.810, p = 0.001), previous antibacterial treatment (OR: 9.32, CI: 1.634-53.744, p = 0.012), newly developed renal failure after candidemia (OR: 2.7, CI: 1.079-6.761, p = 0.034), and newly developed thrombocytopenia after candidemia (OR: 2.6, CI: 1. 057-6.439, p = 0.038) were significantly associated with 30-day mortality. Central venous catheter removal was the only factor protective against mortality (OR: 0.34, CI:0.147-0.768, p = 0.010) in multivariable analysis. Candidemia mortality is high in patients with high SOFA scores, those receiving TPN therapy, and those who previously received antibacterial therapy. Renal failure and thrombocytopenia developing after candidemia should be followed carefully in patients. Antifungal therapy and removing the central venous catheter are essential in the management of candidemia.

Management of diabetic foot infections in the light of recent literature and new international guidelines.

Introduction: In May 2019 the International Working Group on the Diabetic Foot (IWGDF) launched their quadrennially updated guidelines on the management of diabetic foot infections (DFIs). Concomitantly, the number of new publications regarding DFI increased.Areas covered: The IWGDF committee developed and addressed key questions and produced evidence-based recommendations related to diagnosing and treating DFIs. This narrative review provides an overview of this new guideline and also of other recently published literature in the field of DFIs.Expert opinion: The 2019 IWGDF guidelines provide an authoritative, international, evidence-based approach to diagnosing and treating DFIs. The 27 recommendations are supported by systematic reviews of both diagnosis and interventions. Our review of this guideline, along with other recent publications in the field, allows us to offer state-of-the-art guidance for caring for these difficult infections. As the evidence base for management of DFIs remains suboptimal, we need further research to improve the management of DFIs.

Dynamics of HCV epidemiology in Aydin province of Turkey and the associated factors.

This paper gives an update on the local distributions of HCV genotypes in Aydin province of Turkey, provides a comparison with the previous records, and discusses the potential causal reasons shaping the evolving genotype profiles. Patient files from 2011 to 2016 were retrospectively analyzed, and newly detected cases were documented. Out of 286 patients, male and female ratios were determined to remain nearly the same (~50%). Genotype 1 was still the most common (90.2%), followed by genotype 3 (5.9%), genotype 2 (2.1%), and genotype 4 (1.4%) in frequency. There were international patients (4.50%). One patient had genotyped 2+3 together. Genotypes 4 and 2+3 were detected for the first time, and the patients with genotype 4 were interestingly all male and also domestic individuals. However, these patients traveled or lived abroad in the past due to occupational reasons, thereby likely acquired the infection while abroad. HCV surveillance system is currently inadequate and some infected patients may go undetected in the province. Remapping the regional distribution of HCV genotypes from time-to-time is required for identifying the local dynamics and causes leading to it. This process enhances the clinical preparation and readiness for the better management of the disease.

Virulence genes fliC, toxA and phzS are common among Pseudomonas aeruginosa isolates from diabetic foot infections.

BACKGROUND: Outcomes of antibiotic treatment of diabetic foot infections (DFIs) may depend not only on the antimicrobial susceptibility of the aetiologic agents, but also their ability to produce virulence factors. This study aimed to use polymerase chain reaction (PCR) with specific primers to investigate the presence of virulence genes among isolates of Pseudomonas aeruginosa isolates cultured from specimens from diabetic foot and other infections. METHODS: We examined 63 P. aeruginosa isolates from inpatients at two University Hospitals for the presence of 23 known bacterial virulence genes, including lasI, lasR, lasA, lasB, rhll, rhlR, rhlAB, aprA, fliC, toxA, plcH, plcN, ExoS, ExoT, ExoU, ExoY, phzI, phzII, phzM, phzS, pvdA, pilA and pilB. RESULTS: Seven virulence genes (lasl, lasR, lasB, rhll, rhlR, rhlABand Exo T) were present in each isolate. No isolate expressed or presented aprA gene. We found that fliC (p = .01), toxA (p = .041) and phzS (p < .001) were statistically and significantly more common in diabetic foot isolates, while plcH (p < .001) was significantly more common in other infections. CONCLUSIONS: Among clinical isolates of P. aeruginosa from patients with DFIs, three virulence genes that can play important roles in tissue penetration (fliC), tissue damage and survival under anaerobic condition (phzS) and cell death (toxA) were significantly more common than isolates from other infections. The Multilocus sequence typing (MLST) analysis of diabetic foot isolates failed to point/indicate the existence of a specific clone or was not able to characterize/identify a specific clone/clonal complex group. Development of new agents to inhibit the synthesis of these genes may improve outcomes in DFIs treatment.

Angiographic assessment of atherosclerotic load at the lower extremity in patients with diabetic foot and charcot neuro-arthropathy.

BACKGROUND: The aim of this study was to investigate atherosclerotic load at the lower extremity in patients with diabetic foot and charcot neuro-arthropathy and compare them with patients with diabetic foot without charcot neuro-arthropathy. METHODS: This retrospective study consists of 78 patients with diabetic foot who had lower extremity angiography with antegrade approach. All patients were classified into two groups; neuro ischemic wounds with charcot neuro-arthropathy (30/78) and without charcot neuro-arthropathy (48/78).Atherosclerotic load at the side of diabetic foot was determined by using the Bollinger angiogram scoring method. Comparison of atherosclerotic load between the two groups was performed. RESULTS: The mean of total and infrapopliteal level angiogram scoring of all patients was 33.3 (standard deviation, sd:±17.2) and 29.3 (sd:±15.6), respectively. The mean of total and infrapopliteal level angiogram scoring of neuroischemic wounds with charcot neuro-arthropathy group was 18.1 (sd:±11.6) and 15.7 (sd:±10.4), respectively. The mean of total and infrapopliteal level angiogram scoring of neuroischemic wounds without charcot neuro-arthropathy group was 42.8 (sd:±12.7) and 37.7 (sd:±12.0), respectively. There was a statistically significant difference between the two groups of mean total and infrapopliteal angiogram scoring (p < 0.01). CONCLUSION: This angiographic study confirms that the atherosclerotic load in patients with diabetic foot and chronic charcot neuro-arthropathy is significantly less than in patients with neuroischemic diabetic foot wounds without chronic charcot neuro-arthropathy.

Risk Factors for Infection with Pseudomonas aeruginosa in Diabetic Foot Infections.

BACKGROUND: Selecting empirical therapy for a diabetic foot infection (DFI) requires knowing how likely infection with Pseudomonas aeruginosa is in a particular patient. We designed this study to define the risk factors associated with P aeruginosa in DFI. METHODS: We performed a preplanned microbiological subanalysis of data from a study assessing the effects of treatment with intralesional epidermal growth factor for diabetic foot wounds in patients in Turkey between January 1, 2012, and December 31, 2013. Patients were screened for risk factors, and the data of enrolled individuals were recorded in custom-designed patient data forms. Factors affecting P aeruginosa isolation were evaluated by univariate and multivariate logistic regression analyses, with statistical significance set at P < .05. RESULTS: There were 174 patients enrolled in the main study. Statistical analysis was performed in 90 evaluable patients for whom we had microbiological assessments. Cultures were sterile in 19 patients, and 89 bacterial isolates were found in the other 71. The most frequently isolated bacteria were P aeruginosa (n = 23, 25.8%) and Staphylococcus aureus (n = 12, 13.5%). Previous lower-extremity amputation and a history of using active wound dressings were the only statistically significant independent risk factors for the isolation of P aeruginosa in these DFIs. CONCLUSIONS: This retrospective study provides some information on risk factors for infection with this difficult pathogen in patients with DFI. We need prospective studies in various parts of the world to better define this issue.

The effects of ozone on bacterial growth and thiol-disulphide homeostasis in vascular graft infection caused by MRSA in rats.

PURPOSE:: To investigate the microbiological, inflammatory and oxidant effects of adjuvant ozone administration in experimental rat vascular graft infection model which has not been previously investigated. METHODS:: Forty adult Wistar rats were divided into Sham, Control, Vancomycin, Ozone, Vancomycin+Ozone groups. Grafts were inoculated with Methicillin-resistant Staphylococcus aureus (MRSA) strain and implanted subcutaneously. Rats were treated intraperitoneally with ozone and /or intramuscularly with vancomycin for 10 days. Grafts were evaluated by quantitative bacterial cultures. Blood samples were harvested for determination of thiol-disulphide and cytokine profiles. RESULTS:: There was no significant difference in bacterial counts between Control and Ozone Groups. In the Ozone Group median colony count was significantly higher than the Vancomycin and Vancomycin+Ozone Groups. Total thiol and disulphide levels increased and disulphide/native thiol and disulphide/total thiol ratios decreased in Ozone Group significantly. Albumin levels decreased significantly in Vancomycin and Vancomycin+Ozone Groups compared to the Sham Group. IL-1 and TNF-alpha levels significantly increased in infected rats. Decreased levels of VEGF due to infection reversed by ozone therapy in control and vancomycin groups. CONCLUSIONS:: We didn't observe any benefit of the agent on MRSA elimination in our model. Likewise, effects of ozone on thiol-disulphide homeostasis and inflammatory cytokines were contradictory.

An Assessment of Intralesional Epidermal Growth Factor for Treating Diabetic Foot WoundsThe First Experiences in Turkey.

BACKGROUND: Intralesional epidermal growth factor (EGF) has been available as a medication in Turkey since 2012. We present the results of our experience using intralesional EGF in Turkey for patients with diabetic foot wounds. METHODS: A total of 174 patients from 25 Turkish medical centers were evaluated for this retrospective study. We recorded the data on enrolled individuals on custom-designed patient follow-up forms. Patients received intralesional injections of 75 µg of EGF three times per week and were monitored daily for adverse reactions to treatment. Patients were followed up for varying periods after termination of EGF treatments. RESULTS: Median treatment duration was 4 weeks, and median frequency of EGF administration was 12 doses. Complete response (granulation tissue >75% or wound closure) was observed in 116 patients (66.7%). Wounds closed with only EGF administration in 81 patients (46.6%) and in conjunction with various surgical interventions after EGF administration in 65 patients (37.3%). Overall, 146 of the wounds (83.9%) were closed at the end of therapy. Five patients (2.9%) required major amputation. Adverse effects were reported in 97 patients (55.7%). CONCLUSIONS: In patients with diabetic foot ulcer who received standard care, additional intralesional EGF application after infection control provided high healing rates with low amputation rates.

The effects of ozone on bacterial growth and thiol-disulphide homeostasis in vascular graft infection caused by MRSA in rats

Abstract: Purpose: To investigate the microbiological, inflammatory and oxidant effects of adjuvant ozone administration in experimental rat vascular graft infection model which has not been previously investigated. Methods: Forty adult Wistar rats were divided into Sham, Control, Vancomycin, Ozone, Vancomycin+Ozone groups. Grafts were inoculated with Methicillin-resistant Staphylococcus aureus (MRSA) strain and implanted subcutaneously. Rats were treated intraperitoneally with ozone and /or intramuscularly with vancomycin for 10 days. Grafts were evaluated by quantitative bacterial cultures. Blood samples were harvested for determination of thiol-disulphide and cytokine profiles. Results: There was no significant difference in bacterial counts between Control and Ozone Groups. In the Ozone Group median colony count was significantly higher than the Vancomycin and Vancomycin+Ozone Groups. Total thiol and disulphide levels increased and disulphide/native thiol and disulphide/total thiol ratios decreased in Ozone Group significantly. Albumin levels decreased significantly in Vancomycin and Vancomycin+Ozone Groups compared to the Sham Group. IL-1 and TNF-alpha levels significantly increased in infected rats. Decreased levels of VEGF due to infection reversed by ozone therapy in control and vancomycin groups. Conclusions: We didn't observe any benefit of the agent on MRSA elimination in our model. Likewise, effects of ozone on thiol-disulphide homeostasis and inflammatory cytokines were contradictory.

Effects of vancomycin, daptomycin, and tigecycline on coagulase-negative staphylococcus biofilm and bacterial viability within biofilm: an in vitro biofilm model.

Bacteria may hide in a hydrated polysaccharide matrix known as a biofilm. The structure of the bacterial biofilm renders phagocytosis difficult and increases antibiotic resistance. We hypothesized that repeated doses of antibiotics have an effect on bacteria within the biofilm and that it could inhibit or eradicate biofilm formation. Two clinical biofilm-positive coagulase-negative staphylococcus isolates were evaluated. The effects of antibiotics on preformed and nascent biofilm and on bacterial eradication within the biofilm were determined using different doses of vancomycin, daptomycin, and tigecycline for different durations in an in vitro biofilm model. Vancomycin neither penetrated the biofilm nor had any microbicidal effect on bacteria within the biofilm. Daptomycin had a microbicidal effect on bacteria within the biofilm but had no effect on biofilm inhibition and eradication (independent from dose and treatment time). Tigecycline inhibited and eradicated biofilm formation and had a microbicidal effect on bacteria within the biofilm. In conclusion, (i) biofilm formation appeared to be a major barrier to vancomycin activity, (ii) daptomycin had an antimicrobial effect on the bacteria within the biofilm but not on the biofilm burden, and (iii) tigecycline had effects both on bacteria within the biofilm and on biofilm burden. Thus, both tigecycline and daptomycin might be promising candidates for the treatment of biofilm infections.

Two rare cases of head and neck tuberculosis.

Tuberculosis is an infectious disease, which is the leading cause of mortality and morbidity and is still a serious health concern. The fact that extra pulmonary tuberculosis does not have specific examination and radiographic findings and that clinical findings vary depending on the organ in which it is detected cause diagnostic difficulties. The head and neck region is an uncommon site for tuberculosis and tuberculosis can localise in many different places of the head and neck region. In this article, the authors present a case of nasopharyngeal tuberculosis, which clinically mimics nasopharyngeal carcinoma and rare cutaneous tuberculosis of the pinna. A wide knowledge of head and neck tuberculosis, including the disease in the differential diagnosis and carrying out microbiological examinations are necessary for accurate diagnosis.

Intralesional epidermal growth factor for diabetic foot wounds: the first cases in Turkey.

BACKGROUND: Intralesional recombinant epidermal growth factor (EGF) was produced in the Centre for Genetic Engineering and Biotechnology (CIGB), Cuba, in 1988 and licensed in 2006. Because it may accelerate wound healing, it is a potential new treatment option in patients with a diabetic foot wound (whether infected or not) as an adjunct to standard treatment (i.e. debridement, antibiotics). We conducted the initial evaluation of EGF for diabetic foot wounds in Turkey. METHODS: We enrolled 17 patients who were hospitalized in various medical centers for a foot ulcer and/or infection and for whom below the knee amputation was suggested to all except one. All patients received 75 µg intralesional EGF three times per week on alternate days. RESULTS: The appearance of new granulation tissue on the wound site (≥75%) was observed in 13 patients (76%), and complete wound closure was observed in 3 patients (18%), yielding a 'complete recovery' rate of 94%. The most common side effects were tremor (n=10, 59%) and nausea (n=6, 35%). In only one case,a serious side effect requiring cessation of EGF treatment was noted. That patient experienced severe hypotension at the 16th application session, and treatment was discontinued. At baseline, a total of 21 causative bacteria were isolated from 15 patients, whereascultures were sterile in two patients. The most frequently isolated species was Pseudomonas aeruginosa. CONCLUSION: Thus, this preliminary study suggests that EGF seems to be a potential adjunctive treatment option in patients with limb-threatening diabetic foot wounds.

Does physical therapy and rehabilitation improve outcomes for diabetic foot ulcers?

One of the most common and serious complications of diabetes mellitus is ulceration of the foot. Among persons with diabetes, 12%-25% will present to a healthcare institution for a foot disorder during their lifespan. Despite currently available medical and surgical treatments, these are still the most common diabetes-related cause of hospitalization and of lower extremity amputations. Thus, many adjunctive and complementary treatments have been developed in an attempt to improve outcomes. We herein review the available literature on the effectiveness of several treatments, including superficial and deep heaters, electro-therapy procedures, prophylactic methods, exercise and shoe modifications, on diabetic foot wounds. Overall, although physical therapy modalities seem to be useful in the treatment of diabetic foot wounds, further randomized clinical studies are required.

Hypochlorous Acid: an ideal wound care agent with powerful microbicidal, antibiofilm, and wound healing potency.

INTRODUCTION: Chronic wounds and the infections associated with them are responsible for a considerable escalation in morbidity and the cost of health care. Infection and cellular activation and the relation between cells are 2 critical factors in wound healing. Since chronic wounds offer ideal conditions for infection and biofilm production, good wound care strategies are critical for wound healing. Topical antiseptics in chronic wounds remain in widespread use today. These antiseptics are successful in microbial eradication, but their cytotoxcity is a controversial issue in wound healing. OBJECTIVE: The aim of this study was to investigate the effect of stabilized hypochlorous acid solution (HOCl) on killing rate, biofilm formation, antimicrobial activity within biofilm against frequently isolated microorganisms and migration rate of wounded fibroblasts and keratinocytes. MATERIALS AND METHODS: Minimal bactericidal concentration of stabilized HOCl solution for all standard microorganisms was 1/64 dilution and for clinical isolates it ranged from 1/32 to 1/64 dilutions. RESULTS: All microorganisms were killed within 0 minutes and accurate killing time was 12 seconds. The effective dose for biofilm impairment for standard microorganisms and clinical isolates ranged from 1/32 to 1/16. Microbicidal effects within the biofilm and antibiofilm concentration was the same for each microorganism. CONCLUSION: The stabilized HOCl solution had dose-dependent favorable effects on fibroblast and keratinocyte migration compared to povidone iodine and media alone. These features lead to a stabilized HOCl solution as an ideal wound care agent.

Osteomyelitis or Charcot neuro-osteoarthropathy? Differentiating these disorders in diabetic patients with a foot problem.

Both osteomyelitis and Charcot neuro-osteoarthropathy (CN) are potentially limb-threatening complications of diabetic neuropathy, but they require quite different treatments. Almost all bone infections in the diabetic foot originate from an infected foot ulcer while diabetic osteoarthropathy is a non-infectious process in which peripheral neuropathy plays the critical role. Differentiating between diabetic foot osteomyelitis and CN requires careful evaluation of the patient, including the medical history, physical examination, selected laboratory findings, and imaging studies. Based on available studies, we review the approaches to the diagnostic differentiation of osteomyelitis from CN of the foot in diabetic patients.

The seroprevalence of Crimean-Congo haemorrhagic fever among inhabitants living in the endemic regions of Western Anatolia.

BACKGROUND: In Turkey, Crimean-Congo haemorrhagic fever (CCHF) is seen particularly in the north-eastern part of Anatolia. Aydin was thought to be a non-endemic area, however the first case was reported from Aydin in 2006 and a total of 39 cases were reported between 2006 and 2010. METHODS: Four hundred and twenty-nine volunteers from 3 endemic regions of Aydin were enrolled in this study. We determined the IgG seropositivity against the virus by enzyme-linked immunosorbent assay (ELISA) method. RESULTS: IgG seropositivity in the study group was found to be 19.6% (n = 84). Chi-squared automatic interaction detector (CHAID) analysis was performed and a significant relationship between IgG seropositivity and tick-bite was found. The IgG seropositivity rate was 13% in cases without a history of tick-bite, while it was 41.1% in those with a tick-bite history (p < 0.001). In cases without a history of tick-bite (n = 339), the most important factor related to seropositivity was cattle-dealing. The seropositivity rate was higher in women than in men in the group dealing with cattle without a history of tick-bite (p = 0.013). In cases with a tick-bite history, the most important factor related to IgG seropositivity was age; the rate was 81% in cases younger than 34 y old, while it was 29% in cases older than 34 y. CONCLUSIONS: This study indicates that people suffering from the disease did not ask for any professional healthcare or that the healthcare providers could not diagnose these cases.

Insulin resistance in nodular thyroid disease.

BACKGROUND: Insulin had been shown to have a mitogenic effect on thyroid cell cultures. The aim of this study was to investigate insulin resistance in patients with euthyroid nodular goiter. METHODS: Sixty-three patients with nodular thyroid disease and 83 healthy controls were included in the study. Both the patient and the control group were euthyroid, euglycemic and normotensive. None of the study subjects had risk factors for insulin resistance. All the study subjects were evaluated by serum insulin levels and biochemical parameters and thyroid ultrasound. All subjects with thyroid nodules greater than 1cm (n = 36) were offered to undergo thyroid fine needle aspiration biopsy. RESULTS: The two groups were similar with respect to age, gender, BMI, waist circumference, serum lipid levels, serum fT3, fT4 and TSH levels. But HOMA was found to be significantly higher in the patient group (p: 0.007) and thyroid volume was significantly greater in the patient group (p = 0.03). In the patient group there was a significant correlation between HOMA and nodule volume (p < 0.001) while there was not a significant correlation between HOMA and number of thyroid nodules. Thyroid cancer was diagnosed in 3 of the 36 patients (8.33 %). CONCLUSIONS: Insulin resistance may induce increased thyroid proliferation and nodule volume and nodule formation. Therefore, insulin resistance may be a risk factor for euthyoid nodular goiter.

Mean platelet volume in patients with subclinical hypothyroidism.

Subclinical hypothyroidism (SCH) is frequently encountered in the general population. Since it is generally asymptomatic, these patients are mostly identified through routine screening or evaluation of non-specific symptoms. It has been suggested as a risk factor for cardiovascular disease. On the other hand, mean platelet volume (MPV), which is a determinant of platelet function, is an independent risk factor for cardiovascular disease. The aim of this study was to evaluate MPV values in subclinical hypothyroidic patients when they were subclinical hypothyroidic and became euthyroidic after 12 weeks of levothyroxine replacement therapy. Sixty patients with subclinical hypothyroidism and 78 euthyroid healthy subjects matched for age, gender and body mass index were enrolled in the study. None of the study subject had diabetes, hypertension or dyslipidemia. All the study subjects were evaluated by biochemical and platelet parameters. Subclinical hypothyroidic patients were then reevaluated with the same parameters when they became euthyroid after 12 weeks of levothyroxine treatment. Platelet counts and metabolic parameters, except serum triglyceride and high density lipoprotein cholesterol (HDLC) levels, were similar between the two groups. Serum triglyceride and MPV values were significantly higher (pTG=0.007 and pMPV<0.001) while HDLC levels were lower (pHDLC=0.008) in the subclinical hypothyroidic group. MPV was found to be correlated with only antithyroid peroxidase (anti-TPO) antibody levels (P<0.001). MPV values were decreased after subclinical hypothyroidic patients became eythyroid. However, post-treatment MPV values were still higher (p=0.035) in the patient group than in control group. These results suggest that subjects with SCH are susceptible to increased platelet activation and increased MPV values which contribute to increased risk of cardiovascular complications.