Treatment of ventilator-associated pneumonia (VAP) caused by Acinetobacter: results of prospective and multicenter ID-IRI study.

Ventilator-associated pneumonia (VAP) due to Acinetobacter spp. is one of the most common infections in the intensive care unit. Hence, we performed this prospective-observational multicenter study, and described the course and outcome of the disease. This study was performed in 24 centers between January 06, 2014, and December 02, 2016. The patients were evaluated at time of pneumonia diagnosis, when culture results were available, and at 72 h, at the 7th day, and finally at the 28th day of follow-up. Patients with coexistent infections were excluded and only those with a first VAP episode were enrolled. Logistic regression analysis was performed. A total of 177 patients were included; empiric antimicrobial therapy was appropriate (when the patient received at least one antibiotic that the infecting strain was ultimately shown to be susceptible) in only 69 (39%) patients. During the 28-day period, antibiotics were modified for side effects in 27 (15.2%) patients and renal dose adjustment was made in 38 (21.5%). Ultimately, 89 (50.3%) patients died. Predictors of mortality were creatinine level (OR, 1.84 (95% CI 1.279-2.657); p = 0.001), fever (OR, 0.663 (95% CI 0.454-0.967); p = 0.033), malignancy (OR, 7.095 (95% CI 2.142-23.500); p = 0.001), congestive heart failure (OR, 2.341 (95% CI 1.046-5.239); p = 0.038), appropriate empiric antimicrobial treatment (OR, 0.445 (95% CI 0.216-0.914); p = 0.027), and surgery in the last month (OR, 0.137 (95% CI 0.037-0.499); p = 0.003). Appropriate empiric antimicrobial treatment in VAP due to Acinetobacter spp. was associated with survival while renal injury and comorbid conditions increased mortality. Hence, early diagnosis and appropriate antibiotic therapy remain crucial to improve outcomes.

The risk factors of colistin methanesulfonate associated nephrotoxicity.

PURPOSE: The risk factors of colistin methanesulfonate (CMS) associated nephrotoxicity are important. Our study attempts look into the prevalence of CMS-associated nephrotoxicity in Intensive Care Units (ICUs), and related risk factors. MATERIALS AND METHODS: The study was conducted between September 2010 and April 2012 on 55 patients who underwent CMS treatment. Nephrotoxicity risk was defined based on the Risk Injury Failure Loss End-stage kidney disease criteria. RESULTS: Fifty-five patients included in the study. A total of 22 (40%) patients developed nephrotoxicity. The correlation was detected between nephrotoxicity and patients over 65 with a high Acute Physiologic Assessment and Chronic Health Evaluation (APACHE) II score. APACHE II score was revealed an independent risk factor for nephrotoxicity. CONCLUSION: Advanced age and a high APACHE II score are significant risk factors in the development of nephrotoxicity at ICUs following CMS use. Patient selection and close monitoring are critical when starting CMS treatment.

Hepatitis B, Hepatitis C and human immunodeficiency virus prevalences among first time blood donors in Istanbul, Turkey, 2004-2011.

OBJECTIVE: This study aims to determine the yearly change rates of the HBsAg, anti-HCV and anti-HIV test results and their positivity rates obtained from the 68,393 donors who applied and donated blood for the first time at the Blood Center of the hospital. MATERIALS AND METHODS: Using the ELISA method, screening tests were applied to the blood samples obtained from blood donors, and the HBsAg, anti-HCV and anti-HIV positivity rates were calculated at the end of year eight. However, HBsAg and anti-HCV positivities showed a decreased tendency of positivity in years. RESULTS: A total of 68,393 donations were received within eight years. Seroprevalences for anti-HIV, HBsAg and anti-HCV tests were, respectively 0.01%, 1.54% and 0.38%. HBsAg and anti-HCV positivities showed a decreased tendency of positivity in years.

Impact of the initiation time of colistin treatment for Acinetobacter infections.

This study aimed to address the relationship between the timing of colistin therapy and the outcome, defined as all-cause mortality in the intensive care unit (ICU). A retrospective study was undertaken in a 16-bed ICU of a 750-bed tertiary care hospital. A total of 46 patients who had been administered intravenous colistin treatment for colistin-susceptible-only Acinetobacter infections were included in the study. Colistin treatment was initiated in 26 (56.5 %) patients within 24 h of the diagnosis (early administration of colistin), whereas the rest of the patients had obtained delayed treatment (delayed administration of colistin). Of the 46 patients, 21 (45.6 %) died. With univariate analysis, age, age greater than 65 years, APACHE II score more than 20 at baseline, and delayed administration of colistin were found to be significant (p < 0.05). Logistic regression analysis revealed a significant association between delayed administration of colistin [adjusted odds ratio (OR), 5.06; confidence interval (CI), 1.18-21.67], and adverse outcome. Other variables included in the final model were underlying disease (OR, 2.81; CI, 1.15-6.84) and APACHE II score at baseline >20 (OR, 3.81; CI, 0.77-18.75). This study found that delayed administration of colistin and underlying disease were independently associated with adverse outcome.

Occupation-Related Injuries Among Healthcare Workers: Incidence, Risk Groups, and the Effect of Training.

Background and objective Occupation-related injuries (ORIs) are undesirable and harmful situations among healthcare workers (HCWs) and may have serious consequences. In this study, we aimed to identify and analyze ORI incidences, risk groups, and the outcomes of a training program to prevent them. Materials and methods Between January 2011 and December 2019, HCWs who applied for infection prevention and control (IPC) due to ORIs (percutaneous needlestick and sharp-object injury or contact with blood or body fluids) were included in the study. Their characteristic features, vaccine histories, injury types, viral serologies, and administered prophylaxis were recorded. After 2014, a periodic ORI training program was started. We used joinpoint regression analysis to compare the ORI incidences before and after the education program. Results During the nine-year study period, 965 ORIs were registered. The mean age of HCWs was 39.3 ± 8.4 years, and 67.9% of them were female. The total injury incidence for all professions was 34.1 (95% CI: 33.1-37.5) per 1,000 HCWs. The injury incidences were significantly higher in nurses compared to other HCWs (p<0.01). Most of the injuries occurred in the ward setting (37%). HCWs were injured most commonly while administering treatment (36.7%). The trend analysis for the incidence of injuries showed no significant change throughout the study period. The trend in personal protective equipment (PPE) use showed a significant increase (annual percentage change: 1.7, p<0.01). Conclusions The major finding of this study with respect to its implication on the healthcare system is that nurses are an important risk group for ORIs. Although the ORI incidence did not change during the study period, a significantly increased use of appropriate PPE following a systematic training program implementation was observed.

Adrenomedullin reduces antioxidant defense system and enhances kidney tissue damage in cadmium and lead exposed rats.

Adrenomedullin (AdM) is synthesized and secreted by a number of cells and tissue. AdM is a potent vasodilator but it is also considered a neuromodulator, an angiogenic factor, and a hormone regulator. AdM possess antiapoptotic, antioxidant, and antimicrobial properties. Heavy metals such as cadmium and lead are found widely in the environment and they have important biological functions. Lead (Pb) and cadmium (Cd) can accumulate in the lungs, liver, bone, and kidneys and cause serious organ damage. In the present study, we investigated the effect of AdM, Pb + AdM, and Cd + AdM treatments on superoxide dismutase (SOD), catalase (CAT), and glutathione peroxidase (GSH-Px) activities as well as the level of malondialdehyde (MDA) in the kidney. Heavy metal accumulation was determined in kidney with and without AdM infusion and kidney damage was evaluated by light and electron microscopy. Increased heavy metal accumulation was observed in the heavy metal and AdM treated groups. SOD, CAT, GSH-Px activities, and MDA levels were significantly different in the treatment groups when compared with the control group. Tubular degeneration, necrosis, cell swelling, mononuclear cell infiltration, and degenerated organelles were observed in the kidney following treatment. Therefore, AdM infusion has no beneficial and/or compensatory role in cadmium and lead toxicity in the kidney. We conclude that heavy metal accumulation in the kidney in conjunction with AdM infusion is cytotoxic despite the known beneficial effects of adrenomedullin.

Development and validation of a modified quick SOFA scale for risk assessment in sepsis syndrome.

Sepsis is a severe clinical syndrome owing to its high mortality. Quick Sequential Organ Failure Assessment (qSOFA) score has been proposed for the prediction of fatal outcomes in sepsis syndrome in emergency departments. Due to the low predictive performance of the qSOFA score, we propose a modification to the score by adding age. We conducted a multicenter, retrospective cohort study among regional referral centers from various regions of the country. Participants recruited data of patients admitted to emergency departments and obtained a diagnosis of sepsis syndrome. Crude in-hospital mortality was the primary endpoint. A generalized mixed-effects model with random intercepts produced estimates for adverse outcomes. Model-based recursive partitioning demonstrated the effects and thresholds of significant covariates. Scores were internally validated. The H measure compared performances of scores. A total of 580 patients from 22 centers were included for further analysis. Stages of sepsis, age, time to antibiotics, and administration of carbapenem for empirical treatment were entered the final model. Among these, severe sepsis (OR, 4.40; CIs, 2.35-8.21), septic shock (OR, 8.78; CIs, 4.37-17.66), age (OR, 1.03; CIs, 1.02-1.05) and time to antibiotics (OR, 1.05; CIs, 1.01-1.10) were significantly associated with fatal outcomes. A decision tree demonstrated the thresholds for age. We modified the quick Sequential Organ Failure Assessment (mod-qSOFA) score by adding age (> 50 years old = one point) and compared this to the conventional score. H-measures for qSOFA and mod-qSOFA were found to be 0.11 and 0.14, respectively, whereas AUCs of both scores were 0.64. We propose the use of the modified qSOFA score for early risk assessment among sepsis patients for improved triage and management of this fatal syndrome.

Adrenomedullin fails to reduce cadmium-induced oxidative damage in rat liver.

Recent studies have demonstrated that chronic cadmium administration induces oxidative stress. In the present study, we investigated the possible therapeutic effect of adrenomedullin, a potent antioxidant, in cadmium-induced morphological, ultrastructural and biochemical alterations. Two groups of rats were exposed to 100 ppm of CdCl(2) in drinking water for four weeks. One of these groups received 3000 ng/kg body weight of adrenomedullin (AdM) intraperitoneally during the last week. Hepatic oxidative stress markers were evaluated by changes in the amount of lipid peroxides and changes in the antioxidant enzyme activities, superoxide dismutase (SOD) and glutathione peroxidase (GPx) and glutathione reductase (GSH) levels. Hepatic damage score was significantly higher in Cd-administered rats than those of controls (p<0.005). Cd-induced ultrastructural changes in hepatocytes included focal parenchymal cell necrosis, dilatation of rough endoplasmic reticulum, proliferation of lysosomes and mitochondrial degeneration. Hepatic damage was accompanied by significant increase in tissue MDA level (p<0.05) and significant decrease in tissue GSH level (p<0.05), and SOD and GPx activities (p>0.05, p>0.005, respectively). Adrenomedullin failed to restore the light and electron microscopic, and biochemical changes. We conclude that although we administered a high dose of adrenomedullin, it failed to reduce cadmium-induced hepatic damage probably because of the irreversibility of Cd-induced hepatic injury.

Risk factors, characteristics, and outcomes of candidemia in an adult intensive care unit in Turkey.

Thirty-six patients with candidemia and 37 control patients were included consecutively to determine the characteristics of candidemia episodes. The patients with candidemia had higher mortality with higher Sequential Organ Failure Assessment scores and frequency of use of a central venous catheter, total parenteral nutrition, and broad-spectrum antibiotics; chronic renal failure with replacement therapy; and longer stay in an intensive care unit. Candida albicans was the predominant species followed by Candida glabrata, Candida tropicalis, and Candida parapsilosis. All isolates of C glabrata were itraconazole-resistant.

Protective role of caffeic acid phenethyl ester in the liver of rats exposed to cold stress.

Cold exposure can induce a form of environmental stress. Cold stress (CS) alters homeostasis, results in the creation of reactive oxygen species and leads to alterations in the antioxidant defense system. The caffeic acid phenethyl ester (CAPE), an active component of propolis, has an antioxidant capacity. We investigated the effect of CS on oxidative stress and antioxidant defense system and the possible protective effect of CAPE in rat liver tissue. Twenty-four female Wistar Albino rats were divided into four groups: Control, CAPE-treated, CS, and CAPE-treated CS (CS + CAPE) group. Catalase (CAT), glutathione peroxidase (GSH-Px), superoxide dismutase (SOD) activities and total glutathione (GSH) and malondialdehyde (MDA) levels were measured. In addition, histological changes in liver tissue were examined by light microscopy. SOD, CAT and GSH-Px activities and total GSH level were significantly declined in the CS group. In the CS + CAPE group, the activities of these three enzymes and GSH level significantly raised with regard to the CS group. MDA levels increased in the CS group and decreased in the CS + CAPE group. The tissues of the CS group showed some histopathological changes such as necrosis, hepatocyte degeneration, sinusoidal dilatation, hemorrhage and vascular congestion and dilatation. In the CS + CAPE group, the histopathological evidence of hepatic damage was markedly reduced. Histological parameters were consistent with biochemical parameters. In this study, CS increased oxidative stress in liver tissue. CAPE regulated antioxidant enzymes, inhibited lipid peroxidation and reduced hepatic damage.

Evaluation of epidemiological characteristics and risk factors affecting mortality in patients with candidemia.

BACKGROUND/AIM: The aim of this study was to determine epidemiologic characters of patients with candidemia and to evaluate risk factors that can affect mortality rates among these patients. MATERIALS AND METHODS: Patients admitted to the Istanbul Medeniyet University Göztepe Training Hospital between 2009 and 2011 who had a positive blood culture for Candida spp. during hospitalization were studied retrospectively for demographic characteristics and risk factors. Statistical comparisons were estimated with the Stata 12 package. Independent variables associated with mortality were estimated by Cox regression analyses. RESULTS: A total of 89 patients were identified with a positive blood culture. Of the isolates, 72% (64/89) were C. albicans and 10% (9/89) were non-albicans Candida, while 18% (16/89) were unidentified. C. parapsilosis was the most frequently isolated species among non-albicans Candida. The crude mortality rate among candidemia cases was 30% (27/89). By univariate analysis, being in the ICU and age (≥50 or ≥60) were found to be statistically significant, whereas by multivariate analysis only age of ≥50 years was independently more associated with mortality (OR, 2.7; CI, 1.05-6.73). CONCLUSION: Candidemia is associated with high mortality rates. Patients older than 50 years are found to be at considerable risk in terms of adverse outcomes.

The resistance rates of urinary tract infections: Our data from year 2010.

OBJECTIVE: More than 95% of all urinary tract infections are caused by a single bacterium. Although E. coli is the most common bacterium causing community-acquired infections, Klebsiella spp., enteric gram-negative bacteria and S. saprophyticus have been also identified. This study evaluated the microorganisms isolated from the urine cultures of patients admitted to our outpatient clinics in 2010 and assessed E. coli resistance and the frequency of extended-spectrum beta lactamase (ESBL)-producing bacteria. MATERIAL AND METHODS: In total, 7145 urine cultures were obtained from patients admitted to all clinics between 1 January 2010 and 31 December 2010. The double-disk synergy test was used to identify the presence of ESBL producers. RESULTS: The most frequently isolated microorganisms were E. coli (60.6%), Enterococcus spp. (10.3%), Klebsiella spp. (7.3%), Pseudomonas spp. (4.8%), and Streptococcus spp. (3.3%). E. coli strains were more resistant to ciprofloxacin (45.12%), trimethoprim-sulfamethoxazole (44.8%) and amoxicillin-clavulanate (31.6%), but they were less likely to be resistant to meropenem (0%), imipenem (0.2%), and amikacin (0.7%). The frequency of ESBL-producing E. coli strains was 14%. CONCLUSION: The choice of antibiotic treatment influences the overall success of treatment and the development of resistance, and it is also closely related to the cost of the treatment. As a result, there is a need to review the current treatment protocols. As resistance rates show regional differences, it is necessary to regularly examine regional resistance rates to determine the appropriate empiric antibiotic treatment and reduce costs.

The rate of device-associated nosocomial infections in a medical surgical intensive care unit of a training and research hospital in Turkey: one-year outcomes.

In the present study, we aimed to assess the rate and effect of device-associated nosocomial infections (DANIs), as well as the rate of antibiotic resistance, in the medical-surgical intensive care unit (ICU) of a research and training hospital in Turkey, and to compare our results with those reported by the National Nosocomial Infections Surveillance (NNIS) system and International Nosocomial Infection Control Consortium (INICC). A total of 509 patients were followed up within a 1-year period from 1 November 2007 to 1 November 2008. The total patient days were 4,087, the number of DANIs was 181. The ventilator-associated pneumonia rate in 1,000 ventilator days was 27.1, the rate of central venous catheter (CVC)-associated blood circulation infections in 1,000 CVC days was 11.8, and the rate of urinary catheter-associated urinary tract infections in 1,000 urinary catheter days was 9.6. The most frequently isolated microorganisms were Pseudomonas aeruginosa and Acinetobacter spp. Of the infections caused by Staphylococcus aureus, 81.2% were due to methicillin-resistant strains. Of the Enterobacteriaceae isolates, 53.5% were found to be resistant to ceftriaxone, while 29% of the P. aeruginosa isolates were found to be resistant to ciprofloxacin. The rates of use of devices such as ventilators, CVCs, and urinary catheters were 0.87, 0.93, and 0.98, respectively, which are higher than the rates reported by NNIS and INICC. On the other hand, the present DANI rate was higher than that reported by NNIS, but close to that reported by INICC. We conclude that the indications for and duration of device use should be reviewed.

Circulating adrenomedullin levels in ankylosing spondylitis and Familial Mediterranean Fever.

INTRODUCTION: Adrenomedullin (AM) is a 52-amino acid peptide with vasorelaxant properties. Apart from its roles on vascular tonus, AM can also contribute to inflammatory events. Plasma AM levels were elevated in connective tissue diseases and vasculitic disorders. Ankylosing spondylitis (AS) is a chronic inflammatory disease of the spine initiating in the sacroiliac joints. Familial Mediterranean Fever (FMF) is a hereditary disorder characterized by self-limiting acute attacks of fever and the presence of sustained subclinical inflammation in the attack-free periods. In this study, we investigated plasma AM levels in patients with AS and patients with FMF. METHODS: Twenty AS patients with active disease manifestations (mean age: 41.6+/-10.9 years, female/male: 7/13), 28 FMF patients with acute attack (mean age: 27.4+/-10.7 years, female/male: 17/11), and 26 healthy controls (mean age: 39.9+/-5.5 years, female/male: 16/10) were enrolled in this study. AM levels were also measured in 11 FMF patients 2 months after the cessation of their attacks. AM levels of those 11 patients during their FMF attacks and attack-free periods were also compared. RESULTS: Median plasma AM levels were 23.86 (17.24-40.09) pmol/mL, 27.33 (17.24-38.52) pmol/mL, and 26.11 (17.05-37.42) pmol/mL in AS patients, FMF patients with acute attack, and healthy controls, respectively (p>0.05). AM levels were also similar in the attack-free periods of FMF patients [26.35 (24.35-34.14) pmol/mL]. There was no correlation between plasma AM levels and C-reactive protein, or between plasma AM levels and erythrocyte sedimentation rate. CONCLUSIONS: AM does not seem to have any role in the pathogenesis of AS and FMF. Previous reports of elevated levels of AM in connective tissue disorders and vasculitic diseases are probably disease specific, and AM does not seem to be a common component of inflammatory rheumatic disorders.

The effect of adrenomedullin on rats exposed to lead.

Adrenomedullin (AdM) was originally discovered as a vasorelaxant peptide. The antioxidative properties of AdM have been reported recently. Through its antioxidative effect, adrenomedullin can protect organs from damage induced by stressors. Lead, commonly detected in air, soil, water and food, is a major source of oxidative stress. The effect of AdM in the liver of rats exposed to lead was investigated. Twenty-four female Wistar rats were divided into four groups: a control group (C), adrenomedullin group (AdM), lead (Pb) group and lead + adrenomedullin (Pb + AdM) group. In the Pb-treated groups, the animals were exposed to lead in drinking water containing 250 ppm PbCl2 for 4 weeks. In the AdM-treated group, the animals received an i.p. injection of AdM (3000 ng kg(-1) body weight) in the third week of lead treatment for 1 week. The activities of catalase (CAT), glutathione peroxidase (GSH-Px) and superoxide dismutase (SOD) and the level of malondialdehyde (MDA) were determined in the liver of rats. Histological changes in the liver were examined by light and electron microscopy as well. The MDA levels were increased significantly in the Pb-treated groups, but in the Pb + AdM group the MDA levels were decreased significantly when compared with the Pb group. AdM reduced hepatic damage in the Pb + AdM group, but the difference in the total histopathological scores between the Pb and Pb + AdM groups was not significant. When the results are taken together, it can be concluded that AdM may have protective or compensating effects in lead toxicity.

Influence of misoprostol (PGE1) on amniotic fluid and maternal serum adrenomedullin levels.

OBJECTIVE: The purpose of this study was to determine the levels of adrenomedullin (AdM) in amniotic fluid (AF) and maternal serum of misoprostol (PGE1)-induced pregnant women. MATERIALS AND METHODS: A total of 40 women were included in the study: 20 were in active labor and were delivered vaginally and a further 20 were not in labor and misoprostol induction was performed. Women who were undergoing labor induction received 50 microg of misoprostol, which was placed in the posterior fornix of the vagina every 4 hrs until the onset of labor. In each patient, maternal plasma and AF samples were collected. Samples of AF were collected by transvaginal route at the time of rupture of the membranes. The labor was at the same stage in both the groups during the sample collection. In all pregnant subjects, maternal blood samples were drawn from the cubital vein at the time of AF sampling. Amniotic fluid and serum AdM concentration was measured by using reverse-phase high-performance liquid chromatography. RESULTS: Misoprostol-induced pregnant women showed significantly higher AdM concentrations than control pregnant women in AF (79.48 +/- 6.14 pmol/ml versus 21.28 +/- 0.90 pmol/ml, P = 0.000) and maternal serum (88.20 +/- 4.34 pmol/ml versus 29.78 +/- 4.51 pmol/ml, P = 0.000). There was no significant difference between maternal serum and AF-AdM concentrations in misoprostol and control subjects. CONCLUSION: Increased serum and AF-AdM concentrations may be necessary to initiate cervical ripening in misoprostol-induced pregnant women.