The Spectrum of MEFV Gene Mutations and Genotypes in the Middle Northern Region of Turkey.

OBJECTIVE: Familial Mediterranean fever (FMF) is a common, inherited, autosomal recessive inflammatory disease in children. The diagnosis of FMF is based on clinical features and positive family history supported with genetic testing. This study aimed to determine the frequency and distribution of Mediterranean fever (MEFV) gene alterations of a city in Northern Anatolia. MATERIALS AND METHODS: We evaluated MEFV gene mutations in 374 children preliminary diagnosed as FMF by a commercial kit based on real-time polymerase chain reaction technique in a one-year period, and screened 12 mutations. RESULTS: At least one mutation was detected in 213 patients (57%) and 38 genotypes with 11 distinct mutations.A total of 137 (64. 3%) of mutation-positive children were heterozygous, 45 (21. 1%) were compound heterozygous, and 2 (0.9%) were complex heterozygous; and 14 (6.4%) patients were homozygous, 6 (2.8%) were compound homozygous, and 3 (1.4%) were complex homozygous. With a frequency of 50.1%, R202Q was the most common mutation. Also, R202Q/M694V was the most common compound heterozygous genotype. In 43 alleles, R202Q-M694V mutations were found to be in linkage disequilibrium. In our cohort, M694V, E148Q, V726A, and M680I (G/C) were other common mutations; whereas F479L, A744S, K695R, P369S, M694I, and R761H were the rare mutations. None of our patients had M680I (G/A) mutation. CONCLUSION: We determined the most common MEFV alteration prevalence in children of our region for the first time. The high R202Q mutation and linkage disequilibrium (LD) rates were the remarkable results of this study.

Effect of mazEF, higBA and relBE toxin-antitoxin systems on antibiotic resistance in Pseudomonas aeruginosa and Staphylococcus isolates.

Background: A toxin-antitoxin (TA) system is a set of two or more closely linked genes that are encoded as a poison and a corresponding antidote on a protein. In typical bacterial physiology, an antitoxin binds to a toxin and neutralizes it, which prevents the bacterium from killing itself. We aimed to determine whether P.aeruginosa and Staphylococcus isolates have TA genes and to investigate whether there is a relationship between the expression levels of TA genes and resistance to antibiotics. Methods: This study included 92 P. aeruginosa and 148 Staphylococcus isolates. RelBE, higBA genes were investigated in P.aeruginosa by multiplex polymerase chain reaction (PCR). The mazEF gene and the all TA genes expression were detected by real time PCR. Results: RelBE and higBA genes were detected in 100% of P. aeruginosa. It was found that the level of relBE TA gene expression is increased in isolates sensitive to aztreonam compared to resistant isolates (p<0.05). The mazEF gene was detected in 89.1% of Staphylococcus isolates. In terms of MazEF gene expression level there was no significant difference between methicillin-sensitive Staphylococcus aureus (MSSA) and methicillin-resistant S. aureus (MRSA) isolates (p>0.05) whereas there was a significant difference between MSSA and coagulase-negative Staphylococcus (CNS) isolates, MRSA and CNS isolates (p<0.05). The levels of mazEF gene expression were found to be higher in isolates sensitive to gentamicin, ciprofloxacin, levofloxacin, clindamycin, phosphomycine, nitrofurantoin, fusidic acid, cefoxitin compared to resistant isolates (p<0.05). Conclusion: Studies on the prevalence and functionality of TA systems emphasize that it may be possible to have new sensitive regions in bacteria by activating TA systems. The results of this study lead to the idea that resistance to antibiotics can be reduced by increasing TA gene expression levels. But there is need for further studies to support and develop this issue.

Comparison of biofilm formation and efflux pumps in ESBL and carbapenemase producing Klebsiella pneumoniae.

INTRODUCTION: Klebsiella pneumoniae is an opportunistic pathogen that causes a range of diseases. The appearance of extended-spectrum ß-lactamase -and carbapenemase-producing strains, in addition to the biofilm-forming phenotype, is a major problem in the clinical environment. METHODOLOGY: A total of 33 clinical K. pneumoniae isolates were used in this study. Antimicrobial susceptibilities were assessed by a disc diffusion assay. Biofilm formation was determined by a microtiter plate assay, staining with 1% crystal violet and measuring  absorbance after destaining. Moreover, expression of acrA, kdeA, ketM, kpnEF, and kexD efflux associated genes  was measured by qRT-PCR. RESULTS: Isolates displayed high resistance to ß-lactams such as cefazolin, cefuroxime, ceftriaxone, cefepime, piperacillin-tazobactam, imipenem, and meropenem and decreased resistance to gentamicin, amikacin, ciprofloxacin, and levofloxacin. ESBL-producing isolates formed more biofilm than carbapenemase-producing isolates. The mRNA expression levels in KPC isolates for acrA (2-fold), kdeA (2.7-fold), ketM (2.2-fold), and kpnEF (3.4-fold) were significantly increased compared to ESBL-producing isolates. There was no significant difference in kexD expression level. CONCLUSIONS: Under the conditions used here ESBL-producing isolates formed more biofilm than KPC postive isolates; this was associated with virulence determinants which were also transferred by plasmids together with ESBLs enzymes. Moreover, the upregulation of acrA, kdeA, ketM, and kpnEF efflux pumps was seen in carbapenemase-producing isolates demonstrating that high expression of efflux pumps alone could not confer resistance but may act as a physiological determinant such as bacterial pathogenicity and virulence, and cell-to-cell communication for bacteria.

Does the Intestinal Parasite Enterobius vermicularis Cause Acute Appendicitis?

OBJECTIVE: Although intestinal parasitic infections rarely cause acute appendicitis, they are common public health problems in undeveloped and developing countries. Parasitic infections should be kept in mind in patients clinically suspected of having acute appendicitis, and treatment procedures should be adopted according to the etiology. METHODS: Herein we presented the cases of four patients with clinical findings of acute appendicitis. Patients were clinically suspected of having acute appendicitis, and Enterobius vermicularis was detected in the pathological examinations of specimens. Pinworm infections are common parasitic infections that may mimic appendicitis. RESULTS: The pathology of the four cases was noted when the file of 186 patients aged between 4 and 72 years who underwent surgery for acute appendicitis in my hospital was retrospectively reviewed. When the appendectomy specimen was examined histopathologically it was understood that acute appendicitis was caused by Enterobius vermicularis parasite. CONCLUSION: In Enterobius infections, performing systemic therapy for patients and their family members is sufficient. To prevent unnecessary appendectomy, this type of infection should be made to ask in the history and clinical findings of patients.

Examination of the specific clinical symptoms and laboratory findings of Crimean-Congo hemorrhagic fever.

BACKGROUND & OBJECTIVES: Crimean-Congo hemorrhagic fever (CCHF) is a fatal disease, caused by a tick-borne virus (Nairovirus), having a high mortality rate. The study was aimed to evaluate the risk factors, the presenting symptoms and findings of the patients with prediagnosis of CCHF disease, and to compare these variables between the CCHF-positive and CCHF-negative patients. It was also aimed to develop a scoring formula for the diagnosis of CCHF. METHODS: In total, 281 patients who were admitted to the Sabuncuoglu Serafeddin Training and Research Hospital, Amasya, Turkey between 2011 and 2015 and were prediagnosed with CCHF based on the clinical symptoms, laboratory findings and risk factors were included in the study. The definitive laboratory diagnosis of patients with prediagnosis of CCHF was ensured via molecular and serological methods. In addition, a mathematical diagnostic scoring formula was developed for enhancing the laboratory results of CCHF. RESULTS: The ratio of certain clinical symptoms such as fever (p<0.001), headache (p<0.001), widespread body pain (p<0.001), fatigue (p = 0.001), nausea and vomiting (p = 0.013) in CCHF-positive patients were found to be significantly higher compared to the ratio in CCHF-negative patients. In terms of laboratory findings such as presence of leucopenia (p<0.001), creatine kinase (CK) elevation (p<0.001), thrombocytopenia (p<0.001), aspartate aminotransferase/alanine aminotransferase (AST/ALT) elevation (p<0.001), lactate dehydrogenase (LDH) levels (p = 0.002), absence of abnormal findings on chest radiograph (p = 0.042), and the absence of anaemia (p = 0.007), the CCHF-positive patients had higher rates in comparison to CCHF-negative ones. INTERPRETATION & CONCLUSION: It was inferred that certain clinical symptoms and laboratory findings such as fever, headache, widespread body pain, fatigue, leucopenia, nausea, vomiting, high CK levels, thrombocytopenia, AST/ ALT elevation and elevated LDH levels are highly specific and are required to be considered in the definitive diagnosis of CCHF, particularly in regions where this infection is observed as endemic.

[In vitro activity of ceftaroline to MRSA isolates: a multicenter study]. / Seftarolinin MRSA Izolatlarina In Vitro Etkinligi: Çok Merkezli Bir Çalisma.

Methicillin-resistant Staphylococcus aureus (MRSA) is an emerging pathogen that cause severe community- and hospital-acquired infections. Studies continue on searching alternatives due to the limited number of therapeutic options in MRSA infections. Ceftaroline is a wide-spectrum new generation cephalosporin which has been begun to be used in treatment of skin and respiratory tract infections caused by MRSA. The aim of this study was to investigate the in vitro activity of ceftaroline against MRSA strains isolated from various clinical specimens in microbiology laboratories of seven hospitals located at different provinces (Bolu, Samsun, Rize, Tekirdag, Sakarya, Amasya, Osmaniye) of Turkey. A total of 192 MRSA isolates (89 skin/wound/abscess, 38 blood, 36 respiratory tract, 29 urine/sterile body fluids/catheter) were included in the study, and ceftaroline susceptibilities of the strains were detected by broth microdilution method. MIC values of 181 (94.3%) isolates were determined as ≤ 1 µg/ml meaning of susceptible according to the criteria of CLSI, and MIC values of 11 (5.7%) isolates were found as 2 µg/mL indicating intermediate susceptibility. The range of MIC values of the isolates was found between 0.25-2 µg/ml. The rates of intermediate isolates have varied between 0-12.5% from the participating centers. MIC50 and MIC90 values of all the isolates were determined as 0.5 µg/ml and 1 µg/ml, respectively. No significant differences were found between the centers in terms of mean MIC values (p> 0.05). MIC50 and MIC90 values in Samsun and Bolu isolates were found to be the same with the whole group, however, MIC50 and MIC90 were 0.5 µg/ml and 0.5 µg/ml in Amasya isolates and 1 µg/ml and 1 µg/ml in Rize, Tekirdag, Osmaniye and Sakarya isolates, respectively. When evaluating MIC50 and MIC90 values and isolation rates of intermediate strains according to the specimen types, there were no significant differences (p> 0.05). Susceptibility rates to ceftaroline and the distribution profiles of MIC values of the isolates obtained from seven centers of Turkey have been detected similar with the previous American and European reports. With this study, initial data on the activity of ceftaroline against MRSA were obtained from Turkey. These preliminary findings indicate that ceftaroline is effective even on Turkish isolates and can be a suitable treatment in cases requiring wide-spectrum antimicrobiotic use, however further large-scaled studies are needed.