Spread of carbapenem-resistant international clones of Acinetobacter baumannii in Turkey and Azerbaijan: a collaborative study.

Epidemic clones of Acinetobacter baumannii, described as European clones I, II, and III, are associated with hospital epidemics throughout the world. We aimed to determine the molecular characteristics and genetic diversity between European clones I, II, and III from Turkey and Azerbaijan. In this study, a total of 112 bloodstream isolates of carbapenem-resistant Acinetobacter spp. were collected from 11 hospitals across Turkey and Azerbaijan. The identification of Acinetobacter spp. using conventional and sensitivity tests was performed by standard criteria. Multiplex polymerase chain reaction (PCR) was used to detect OXA carbapenemase-encoding genes (bla OXA-23-like, bla OXA-24-like, bla OXA-51-like, and bla OXA-58-like). Pulsed-field gel electrophoresis (PFGE) typing was used to investigate genetic diversity. The bla OXA-51-like gene was present in all 112 isolates, 75 (67 %) carried bla OXA-23-like, 7 (6.2 %) carried bla OXA-58-like genes, and 5 (4.5 %) carried bla OXA-24-like genes. With a 90 % similarity cut-off value, 15 clones and eight unique isolates were identified. The largest clone was cluster D, with six subtypes. Isolates from clusters D and I were widely spread in seven different geographical regions throughout Turkey. However, F cluster was found in the northern and eastern regions of Turkey. EU clone I was grouped within J cluster with three isolates found in Antalya, Istanbul, and Erzurum. EU clone II was grouped in the U cluster with 15 isolates and found in Kayseri and Diyarbakir. The bla OXA-24-like gene in carbapenemases was identified rarely in Turkey and has been reported for the first time from Azerbaijan. Furthermore, this is the first multicenter study in Turkey and Azerbaijan to identify several major clusters belonging to European clones I and II of A. baumannii.

The clinical features, diagnosis, treatment, and prognosis of neuroinvasive listeriosis: a multinational study.

The aim of this study was to determine the independent risk factors, morbidity, and mortality of central nervous system (CNS) infections caused by Listeria monocytogenes. We retrospectively evaluated 100 episodes of neuroinvasive listeriosis in a multinational study in 21 tertiary care hospitals of Turkey, France, and Italy from 1990 to 2014. The mean age of the patients was 57 years (range, 19-92 years), and 64% were males. The all-cause immunosuppression rate was 54 % (54/100). Forty-nine (49 %) patients were referred to a hospital because of the classical triad of symptoms (fever, nuchal rigidity, and altered level of consciousness). Rhombencephalitis was detected radiologically in 9 (9 %) cases. Twenty-seven (64 %) of the patients who had cranial magnetic resonance imaging (MRI) performed had findings of meningeal and parenchymal involvement. The mean delay in the initiation of specific treatment was 6.8 ± 7 days. Empiric treatment was appropriate in 52 (52 %) patients. The mortality rate was 25 %, while neurologic sequelae occurred in 13 % of the patients. In the multivariate analysis, delay in treatment [odds ratio (OR), 1.07 [95 % confidence interval (CI), 1.01-1.16]] and seizures (OR, 3.41 [95 % CI, 1.05-11.09]) were significantly associated with mortality. Independent risk factors for neurologic sequelae were delay in treatment (OR, 1.07 [95 % CI, 1.006-1.367]) and presence of bacteremia (OR, 45.2 [95 % CI, 2.73-748.1]). Delay in the initiation of treatment of neuroinvasive listeriosis was a poor risk factor for unfavorable outcomes. Bacteremia was one of the independent risk factors for morbidity, while the presence of seizures predicted worse prognosis. Moreover, the addition of aminoglycosides to ampicillin monotherapy did not improve patients' prognosis.

Comparison of colistin-carbapenem, colistin-sulbactam, and colistin plus other antibacterial agents for the treatment of extremely drug-resistant Acinetobacter baumannii bloodstream infections.

The purpose of this investigation was to compare the efficacy of colistin-based therapies in extremely drug-resistant Acinetobacter spp. bloodstream infections (XDR-ABSI). A retrospective study was conducted in 27 tertiary-care centers from January 2009 to August 2012. The primary end-point was 14-day survival, and the secondary end-points were clinical and microbiological outcomes. Thirty-six and 214 patients [102 (47.7%): colistin-carbapenem (CC), 69 (32.2%): colistin-sulbactam (CS), and 43 (20.1%: tigecycline): colistin with other agent (CO)] received colistin monotherapy and colistin-based combinations, respectively. Rates of complete response/cure and 14-day survival were relatively higher, and microbiological eradication was significantly higher in the combination group. Also, the in-hospital mortality rate was significantly lower in the combination group. No significant difference was found in the clinical (p = 0.97) and microbiological (p = 0.92) outcomes and 14-day survival rates (p = 0.79) between the three combination groups. Neither the timing of initial effective treatment nor the presence of any concomitant infection was significant between the three groups (p > 0.05) and also for 14-day survival (p > 0.05). Higher Pitt bacteremia score (PBS), Acute Physiology and Chronic Health Evaluation II (APACHE II) score, Charlson comorbidity index (CCI), and prolonged hospital and intensive care unit (ICU) stay before XDR-ABSI were significant risk factors for 14-day mortality (p = 0.02, p = 0.0001, p = 0.0001, p = 0.02, and p = 0.01, respectively). In the multivariable analysis, PBS, age, and duration of ICU stay were independent risk factors for 14-day mortality (p < 0.0001, p < 0.0001, and p = 0.001, respectively). Colistin-based combination therapy resulted in significantly higher microbiological eradication rates, relatively higher cure and 14-day survival rates, and lower in-hospital mortality compared to colistin monotherapy. CC, CS, and CO combinations for XDR-ABSI did not reveal significant differences with respect to 14-day survival and clinical or microbiological outcome before and after propensity score matching (PSM). PBS, age, and length of ICU stay were independent risk factors for 14-day mortality.

Liver involvement in patients with brucellosis: results of the Marmara study.

Brucellosis is a zoonotic disease that primarily affects the reticuloendothelial system. But, the extent of liver damage in due course of the disease is unclear. This study included 325 brucellosis patients with significant hepatobiliary involvement identified with microbiological analyses from 30 centers between 2000 and 2013. The patients with ≥5 times of the upper limit of normal for aminotransferases, total bilirubin level ≥2 mg/dl or local liver lesions were enrolled. Clinical hepatitis was detected in 284 patients (87.3 %) and cholestasis was detected in 215 (66.1 %) patients. Fatigue (91 %), fever (86 %), sweating (83 %), arthralgia (79 %), and lack of appetite (79 %) were the major symptoms. Laboratory tests showed anemia in 169 (52 %), thrombocytopenia in 117 (36 %), leukopenia in 81 (25 %), pancytopenia in 42 (13 %), and leukocytosis in 20 (6 %) patients. The most commonly used antibiotic combinations were doxycycline plus an aminoglycoside (n = 73), doxycycline plus rifampicin (n = 71), doxycycline plus rifampicin and an aminoglycoside (n = 27). The duration of ALT normalization differed significantly in three treatment groups (p < 0.001). The use of doxycycline and an aminoglycoside in clinical hepatitis showed better results compared to doxycycline and rifampicin or rifampicin, aminoglycoside, doxycycline regimens (p < 0.05). However, the length of hospital stay did not differ significantly between these three combinations (p > 0.05). During the follow-up, treatment failure occurred in four patients (1 %) and relapse was seen in three patients (0.9 %). Mortality was not observed. Hepatobiliary involvement in brucellosis has a benign course with suitable antibiotics and the use of doxycycline and an aminoglycoside regimen seems a better strategy in select patients.

Attitude towards seeking psychological help regarding psychiatric symptoms and stigma in patients with fibromyalgia.

OBJECTIVE: The current study aimed to examine the psychiatric symptoms that can be seen in fibromyalgia (FM) patients, their attitudes toward seeking psychological help, and their concerns about stigma. Besides, it was investigated whether the stigma concerns that they may experience about receiving psychiatric treatment constitute an obstacle for patients to receive psychiatric treatment. SUBJECTS AND METHODS: This cross-sectional descriptive study was conducted between February and July 2020. Various seeking help were measured with Attitude Towards Seeking Psychological Help Scale-Short Form (ATSPPH-SF), Self-Stigma in the Process of Seeking Psychological Help Scale (SSPSPHS), Intention to Seek Psychological Help Inventory (ISPHI), and Social Stigma Due to Seeking Psychological Help Scale (SSDSPHS). FM symptoms of patients were measured with The Symptom Screening Questionnaire, Revised 90 Items (SCL-90-R). Quality-of-life parameters were measured with Fibromyalgia Impact Questionnaire (FIQ). RESULTS: Fibromyalgia patients had higher somatization (p=0.001), psychotism (p=0.045) and phobic anxiety (p=0.015) scores than controls. The ATSPPH-SF (p=0.002) and SSPSPHS (p=0.043) scale scores of the FM patients were higher than the controls. There was a significant positive correlation between FIQ and SSPSPHS (r=0.288, p=0.043) and SCL-90 overall (r=0.602, p<0.001) and all subscales scores. Patients with high active psychotic symptom levels had higher FM exposure scale scores and SCL-90 overall scores than those with low active psychotic symptom levels (p<0.001). CONCLUSIONS: The findings of this study showed that fibromyalgia patients have more somatization symptoms than healthy individuals, and as psychiatric symptoms increase in these individuals, their level of being affected by FM increases.

Comparison of immunological, histological and oxidative effects of felbamate and levetiracetam in traumatic brain injury.

OBJECTIVE: We aimed to compare immunological, histological and oxidative effects of antiepileptic agents; felbamate and levetiracetam on head trauma in rats. MATERIALS AND METHODS: In this study, 32 Sprague-Dawley genus male rats were used. A closed head trauma mechanism was constituted in order to perform head trauma in rats. Rats were divided into 4 groups, and each group had 8 rats. Following head trauma, Group 1 (Control); normal saline was administered, Group 2; levetiracetam 50 mg/kg was administered, Group 3; felbamate 100 mg/kg was administered, and Group 4; levetiracetam 50 mg/kg and felbamate 100 mg/kg were administered with a combination. Injections were administered intraperitoneally once a day for 20 days. The rats were decapitated at the end of the 20th day. Blood and tissue samples were collected and analyzed for biochemical, immunohistochemical and histological parameters. RESULTS: Serum cytokine levels in Group 2, 3 and 4 were lower when compared to the control group. In Group 4, in which combined therapy was performed, cytokine levels were found to be the lowest. In Groups 2 and 3, a significant decrease in vascular congestion, mononuclear cell infiltration, hemorrhage, and neural degeneration was noticed in the pia mater. In Group 2, a decrease in vascular congestion and Purkinje cell degeneration was obtained in the cerebellum. However, the best outcomes were determined in Group 4. CONCLUSIONS: We determined that levetiracetam and felbamate alone are useful with respect to immunological, oxidative and histological alterations. However, their utility is better when used in a combination.

The resazurin microplate method for rapid detection of vancomycin resistance in enterococci.

Vancomycin-resistant enterococci (VRE) are a serious challenge for physicians because of the limited treatment options for infections caused by this organism. Prevention of VRE transmission in hospitals requires early detection of infected or colonized patients. Therefore rapid and correct detection of vancomycin resistance is essential. In this study, we use the resazurin microplate method (RMM), which is a modification of the NCCLS and BSAC broth microdilution methods to rapidly determine the susceptibilities of clinical enterococci isolates to vancomycin. The alteration in the RMM was relevant to the final bacterial count. In this method, inoculum that was 10-fold higher than standard methods was used. A total of 80 enterococci, including 11 VRE isolates and 6 vancomycin intermediate isolates, were screened with this modified colorimetric broth microdilution method. After 4 h of incubation 30 microl of 0.01% resazurin solution were added to each well and the plates were reincubated for color change for 5-10 min. The MICs were obtained at the 4th h. The results were in exact agreement with the NCCLS and the BSAC microdilution methods. Absolute and essential agreements were 100% and there were no minor, major or very major errors. In conclusion, this modified colorimetric broth microdilution method can be used as a reliable, easy, cheap and rapid method for early detection of VRE. Moreover, this method has the potential of being used to test the susceptibilities of different bacteria to other antibiotics.

The course of spinal tuberculosis (Pott disease): results of the multinational, multicentre Backbone-2 study.

We aimed to describe clinical, laboratory, diagnostic and therapeutic features of spinal tuberculosis (ST), also known as Pott disease. A total of 314 patients with ST from 35 centres in Turkey, Egypt, Albania and Greece were included. Median duration from initial symptoms to the time of diagnosis was 78 days. The most common complications presented before diagnosis were abscesses (69%), neurologic deficits (40%), spinal instability (21%) and spinal deformity (16%). Lumbar (56%), thoracic (49%) and thoracolumbar (13%) vertebrae were the most commonly involved sites of infection. Although 51% of the patients had multiple levels of vertebral involvement, 8% had noncontiguous involvement of multiple vertebral bodies. The causative agent was identified in 41% of cases. Histopathologic examination was performed in 200 patients (64%), and 74% were consistent with tuberculosis. Medical treatment alone was implemented in 103 patients (33%), while 211 patients (67%) underwent diagnostic and/or therapeutic surgical intervention. Ten percent of the patients required more than one surgical intervention. Mortality occurred in 7 patients (2%), and 77 (25%) developed sequelae. The distribution of the posttreatment sequelae were as follows: 11% kyphosis, 6% Gibbus deformity, 5% scoliosis, 5% paraparesis, 5% paraplegia and 4% loss of sensation. Older age, presence of neurologic deficit and spinal deformity were predictors of unfavourable outcome. ST results in significant morbidity as a result of its insidious course and delayed diagnosis because of diagnostic and therapeutic challenges. ST should be considered in the differential diagnosis of patients with vertebral osteomyelitis, especially in tuberculosis-endemic regions. Early establishment of definitive aetiologic diagnosis and appropriate treatment are of paramount importance to prevent development of sequelae.

Evaluation of tularaemia courses: a multicentre study from Turkey.

In this multicentre study, which is the largest case series ever reported, we aimed to describe the features of tularaemia to provide detailed information. We retrospectively included 1034 patients from 41 medical centres. Before the definite diagnosis of tularaemia, tonsillitis (n = 653, 63%) and/or pharyngitis (n = 146, 14%) were the most frequent preliminary diagnoses. The most frequent clinical presentations were oropharyngeal (n = 832, 85.3%), glandular (n = 136, 13.1%) and oculoglandular (n = 105, 10.1%) forms. In 987 patients (95.5%), the lymph nodes were reported to be enlarged, most frequently at the cervical chain jugular (n = 599, 58%), submandibular (n = 401, 39%), and periauricular (n = 55, 5%). Ultrasound imaging showed hyperechoic and hypoechoic patterns (59% and 25%, respectively). Granulomatous inflammation was the most frequent histological finding (56%). The patients were previously given antibiotics for 1176 episodes, mostly with ß-lactam/ß-lactamase inhibitors (n = 793, 76%). Antituberculosis medications were provided in seven (2%) cases. The patients were given rational antibiotics for tularaemia after the start of symptoms, with a mean of 26.8 ± 37.5 days. Treatment failure was considered to have occurred in 495 patients (48%). The most frequent reasons for failure were the production of suppuration in the lymph nodes after the start of treatment (n = 426, 86.1%), the formation of new lymphadenomegalies under treatment (n = 146, 29.5%), and persisting complaints despite 2 weeks of treatment (n = 77, 15.6%). Fine-needle aspiration was performed in 521 patients (50%) as the most frequent drainage method. In conclusion, tularaemia is a long-lasting but curable disease in this part of the world. However, the treatment strategy still needs optimization.

Genitourinary brucellosis: results of a multicentric study.

This study reviewed the clinical, laboratory, therapeutic and prognostic data on genitourinary involvement of brucellosis in this largest case series reported. This multicentre study pooled adult patients with genitourinary brucellar involvement from 34 centres treated between 2000 and 2013. Diagnosis of the disease was established by conventional methods. Overall 390 patients with genitourinary brucellosis (352 male, 90.2%) were pooled. In male patients, the most frequent involved site was the scrotal area (n=327, 83.8%), as epididymo-orchitis (n=204, 58%), orchitis (n=112, 31.8%) and epididymitis (n=11, 3.1%). In female patients, pyelonephritis (n=33/38, 86.8%) was significantly higher than in male patients (n=11/352, 3.1%; p<0.0001). The mean blood leukocyte count was 7530±3115/mm3. Routine laboratory analysis revealed mild to moderate increases for erythrocyte sedimentation rate (ESR) and C-reactive protein (CRP). The mean treatment duration and length of hospital stay were significantly higher when there were additional brucellar foci (p<0.05). Surgical operations including orchiectomy and abscess drainage were performed in nine (2.3%) patients. Therapeutic failure was detected in six (1.5%), relapse occurred in four (1%), and persistent infertility related to brucellosis occurred in one patient. A localized scrotal infection in men or pyelonephritis in women in the absence of leucocytosis and with mild to moderate increases in inflammatory markers should signal the possibility of brucellar genitourinary disease.

When organ donation from living donors serves as the main source of organ procurement: a critical examination of the ethical and legal challenges to Turkey's recent efforts to overcome organ shortage.

Despite the fact that Turkey has implemented a number of legislative and regulatory efforts to increase cadaveric donations, live donors still serve as the main source of organ procurement in this country. To address this problem, Turkey's regulatory authorities have sought to increase the number of brain death declarations. A new regulation issued in 2012 repeats the criteria for brain death that were first issued in 1993. This paper argues that these efforts are far from adequate owing to a number of complicated, ethical, and legal challenges that must be addressed to increase cadaveric organ donations. After examining these factors, which are completely neglected in current policies, we conclude that Turkey needs a realistic ethically justifiable organ procurement policy that must be supported by a framework of patient rights to implement the concept of patient autonomy and respect for human dignity in health care services as the primary goal.

Laboratory-acquired brucellosis in Turkey.

BACKGROUND: Laboratory healthcare workers (HCWs) are at risk of laboratory-acquired brucellosis (LAB). AIM: To describe the risk factors of LAB among HCWs. METHODS: A multicentre survey study was conducted by face-to-face interview in 38 hospitals from 17 provinces of Turkey. A structured survey was administered to the HCWs, working in infectious diseases clinics and microbiology departments, who were at risk of brucella infection. FINDINGS: The survey response rate was 100%. Of the 667 laboratory workers, 38 (5.8%) had a history of LAB. In multivariate analysis, factors independently associated with an increased risk of LAB included working with the brucella bacteria (odds ratio: 5.12; 95% confidence interval: 2.28-11.52; P < 0.001) and male gender (2.14; 1.02-4.45; P = 0.042). Using a biosafety cabinet level 2 (0.13; 0.03-0.60; P = 0.009), full adherence to glove use (0.27; 0.11-0.65; P = 0.004) and longer duration of professional life (0.86; 0.80-0.92; P < 0.001) were found to be protective. CONCLUSIONS: Working with the brucella bacteria, being male, a lack of compliance with personal protective equipment and biosafety cabinets were the independent risk factors for the development of LAB in our series. Increased adherence to personal protective equipment and use of biosafety cabinets should be priority targets to prevent LAB.

The effect of allopurinol on the liver ultrastructure, reduced glutathione and lipid peroxide levels during liver ischemia in guinea pigs.

1. The preventive effect of allopurinol on reduced glutathione and lipid peroxide levels of the liver and the accompanying ultrastructural changes during liver ischemia was investigated in guinea pigs. 2. Liver glutathione levels decreased significantly while lipid peroxide levels increased slightly in the ischemic group. 3. Allopurinol administered before ischemia resulted in a reverse significant increase in liver glutathione levels and a significant decrease in lipid peroxide levels indicating a protective effect upon cell membrane during ischemia. 4. On the other hand, electron microscopic changes in the liver associated with ischemia could not be altered by allopurinol.

Halothane hepatotoxicity and hepatic free radical metabolism in guinea pigs; the effects of vitamin E.

PURPOSE: The aim of this study was to investigate the relation between halothane hepatotoxicity and hepatic free radical metabolism and to establish a possible protective role of vitamin E against halothane hepatotoxicity. METHODS: Twenty-eight guinea pigs were used in the experiments. Halothane (1.5% v/v) in oxygen (100%) was given to the animals for 90 min over three days. Livers from animals were then taken and prepared for the assays. In the enzymatic study, superoxide dismutase (SOD), glutathione peroxidase (GSH-Px) and catalase (CAT) activities were measured. As a peroxidation index, the malondialdehyde (MDA) concentration was determined. Also, electron spin resonance (ESR) analysis and electron microscopy (EM) were performed. RESULTS: Superoxide dismutase (1168.3 +/- 78.2 U.mg-1) and glutathione peroxidase (14.9 +/- 6.2 mIU.mg-1) activities were decreased, but catalase activity (1260.0 +/- 250.6 IU.mg-1) and malondialdehyde concentration (11.5 +/- 1.8 ppb) were increased in liver tissues exposed to halothane compared with control values (1382.2 +/- 91.8 U.mg-1 for SOD, 27.8 +/- 5.2 mIU.mg-1 for GSH-Px, 840.2 +/- 252.4 IU.mg-1 for CAT and 10.0 +/- 1.0 ppb for MDA). Electron spin resonance analysis revealed a peak of CF3CHCl. radical in the exposed tissue. Electron microscopy indicated ultrastructural changes in the hepatic cells of both halothane groups with and without vitamin E treatment. CONCLUSION: Halothane causes impairment in the hepatic antioxidant defense system and accelerates peroxidation reactions. As a result, some ultrastructural changes in hepatic tissues occur due to halothane treatment. Although vitamin E prevents peroxidative damage, it does not ameliorate ultrastructural changes caused by halothane treatment. This shows that halothane toxicity results not only from impaired hepatic antioxidant defense system but also from other, unknown causes.

Impaired antioxidant defence in guinea pig heart tissues treated with halothane.

PURPOSE: To investigate the effects of halothane and halothane plus vitamin E treatment on myocardial free radical metabolism in guinea pigs. METHODS: Four groups of seven animals were studied: control, halothane, halothane plus vitamin E and vitamin E groups. In the halothane group, halothane 1.5% in oxygen was given for 90 min over three days. In the halothane plus vitamin E group, 300 mg.kg-1.day-1 vitamin E im was started three days before the first halothane treatment and continued for three days. Following sacrifice, the hearts were assayed for superoxide dismutase (SOD), glutathione peroxidase (GSH-Px) and catalase (CAT) and malondialdehyde (MDA) level was determined. Electron spin resonance (ESR) analysis and electron microscopy (EM) were also performed. RESULTS: In the halothane group, SOD activities and MDA concentrations were increased compared with control and GSH-Px and CAT activities were decreased. In the halothane plus vitamin E group, there were no differences in enzyme activity compared with halothane alone but the MDA level was decreased. In the vitamin E group, enzyme activities were increased compared with control. Mainly the CF3CHCl radical was identified by ESR analysis in heart tissues exposed to halothane and the concentration of this radical was reduced by vitamin E. Electron microscopy showed cytoplasmic vacuolisation and dilation in sarcoplasmic reticulum in the heart tissues exposed to halothane: both were prevented by vitamin E. CONCLUSION: Although halothane causes impairment in enzymatic antioxidant defence potential, due to lowered GSH-Px and CAT activity, and accelerates peroxidative reactions in the tissues affected, no subcellular damage occurred. Vitamin E may protect tissues against free radical attack by scavenging toxic free radicals formed in heart tissue during halothane anaesthesia.