Salih Turkoglu

Characterization of Class 1 Integrons from Pseudomonas aeruginosa That Contain the blaVIM-2 Carbapenem-Hydrolyzing β-Lactamase Gene and of Two Novel Aminoglycoside Resistance Gene Cassettes

ABSTRACT Two clonally unrelated Pseudomonas aeruginosa clinical strains, RON-1 and RON-2, were isolated in 1997 and 1998 from patients hospitalized in a suburb of Paris, France. Both isolates expressed the class B carbapenem-hydrolyzing β-lactamase VIM-2 previously identified in Marseilles in the French Riviera. In both isolates, theblaVIM-2 cassette was part of a class 1 integron that also encoded aminoglycoside-modifying enzymes. In one case, two novel aminoglycoside resistance gene cassettes,aacA29a and aacA29b, were located at the 5′ and 3′ end of the blaVIM-2 gene cassette, respectively. The aacA29a and aacA29b gene cassettes were fused upstream with a 101-bp part of the 5′ end of theqacE cassette. The deduced amino acid sequence AAC(6′)-29a protein shared 96% identity with AAC(6′)-29b but only 34% identity with the aacA7-encoded AAC(6′)-I1, the closest relative of the AAC(6′)-I family enzymes. These aminoglycoside acetyltransferases had amino acid sequences much shorter (131 amino acids) than the other AAC(6′)-I enzymes (144 to 153 amino acids). They conferred resistance to amikacin, isepamicin, kanamycin, and tobramycin but not to gentamicin, netilmicin, and sisomicin.

The mgrB gene as a key target for acquired resistance to colistin in Klebsiella pneumoniae

OBJECTIVES Alterations in the PhoPQ two-component regulatory system may be associated with colistin resistance in Klebsiella pneumoniae. MgrB is a small transmembrane protein produced upon activation of the PhoPQ signalling system, and acts as a negative regulator on this system. We investigated the role of the MgrB protein as a source of colistin resistance in a series of K. pneumoniae. METHODS Colistin-resistant K. pneumoniae isolates were recovered from hospitalized patients worldwide (France, Turkey, Colombia and South Africa). The mgrB gene was amplified and sequenced. A wild-type mgrB gene was cloned and the corresponding recombinant plasmid was used for complementation assays. Clonal diversity was evaluated by MLST and Diversilab analysis. RESULTS Of 47 colistin-resistant isolates, 12 were identified as having a mutated mgrB gene. Five clonally unrelated isolates had an mgrB gene truncated by an IS5-like IS, while one clone also harboured an insertional inactivation at the exact same position of the mgrB gene, but with ISKpn13. Another clone harboured an insertional inactivation due to ISKpn14 at another location of the mgrB gene. Two clonally related isolates harboured an IS (IS10R) in the promoter region of mgrB. Finally, three clonally unrelated isolates harboured substitutions leading to anticipated stop codon in the MgrB protein. Complementation assays with a wild-type MgrB protein restored full susceptibility to colistin for all colistin-resistant isolates identified with qualitative or quantitative MgrB modifications. CONCLUSION The inactivation or down-regulation of the mgrB gene was shown to be a source of colistin resistance in K. pneumoniae. Interestingly, identical genetic events were identified among clonally unrelated isolates.

Is severe cryptogenic chronic hepatitis similar to autoimmune hepatitis

BACKGROUND/AIMS It has been reported that severe cryptogenic chronic hepatitis may be a subgroup of autoimmune hepatitis. The aims of this study were to investigate the clinical features, liver function tests, human leukocyte antigens and response to immunosuppressive therapy in severe cryptogenic chronic hepatitis, and to compare the findings in such patients with those in patients with autoimmune hepatitis. METHODS History of alcohol and hepatotoxic drug intake, markers of metabolic liver disease, autoantibodies (antinuclear antibody, smooth muscle antibody, antibody to liver/kidney microsome type 1), and viral markers (HBsAg, HBV DNA, anti-HCV, HCV RNA) were negative in all severe cryptogenic chronic hepatitis patients (histological activity index > 9 and alanine aminotransferase level > 2 x normal). Fifteen cryptogenic patients (13 women; mean age, 33 +/- 16 years) and seven autoimmune patients (seven women; mean age, 28 +/- 3.9 years; five type 1; two type 2a) received prednisolone and azathioprine for at least 2 years. RESULTS Cryptogenic chronic hepatitis patients were similar to patients with autoimmune hepatitis with respect to age, sex, clinical presentation, liver function tests and Knodell scores at admission. HLA phenotype frequencies were comparable between cryptogenic and autoimmune groups: BW6 (77% vs. 100%), DR4 (62% vs. 57%), and HLA B8 (15% vs. 43%). The rates of complete and partial remissions achieved during therapy were 87% vs. 57% and 13% vs. 29%, respectively (p > 0.05). CONCLUSIONS The clinical, biochemical and HLA phenotypic features, and the responsiveness to immunosuppressive therapy in severe cryptogenic chronic hepatitis support the idea that it may be an autoimmune liver disease similar to autoimmune hepatitis.

NDM-1-producing Klebsiella pneumoniae, now in Turkey

The emergence of NDM producers among Gram-negative rods is being reported worldwide, with Escherichia coli, Klebsiella pneumoniae, and Acinetobacter baumannii being the main hosts for this resistance trait ([7][1]). Whereas the United Kingdom, India, and Pakistan have been identified as reservoirs

Amantadine Monotherapy of Chronic Hepatitis C Patients Infected with Genotype 1b

We aimed to test the efficacy of amantadine in chronic hepatitis C (CHC) patients infected with genotype b. Twenty patients completed treatment with amantadine HCl, 100 mg b.i.d., for 6 months. Non-sustained biochemical improvement was observed without loss of HCV-RNA. We conclude that amantadine monotherapy is not effective in CHC.We aimed to test the efficacy of amantadine in chronic hepatitis C (CHC) patients infected with genotype 1b. Twenty patients completed treatment with amantadine HCl, 100 mg b.i.d., for 6 months. Non-sustained biochemical improvement was observed without loss of HCV-RNA. We conclude that amantadine monotherapy is not effective in CHC.

KPC-producing Klebsiella pneumoniae, finally targeting Turkey

We report here the first identification of the worldwide spread of Klebsiella pneumoniae carbapenemase-2-producing and carbapenem-resistant K. pneumoniae clone ST258 in Turkey, a country where the distantly-related carbapenemase OXA-48 is known to be endemic. Worryingly, this isolate was also resistant to colistin, now considered to be the last-resort antibiotic for carbapenem-resistant isolates.

High occurrence of cyclosporiasis in Istanbul, Turkey, during a dry and warm summer

We evaluated the incidence of Cyclospora cayetanensis in immunocompetent, diarrheic patients during the summers of 2006-2009 in Istanbul. Stools from 1876 patients were examined using microscopic techniques. Cyclospora oocysts were observed in wet preparations by light and epifluorescence microscopy and in fecal smears that were stained by Kinyouns modified acid-fast stain. Characteristic Cyclospora oocysts were observed in 2 patients in 2006, 17 in 2007, and one in 2009. Samples positive for Cyclospora were further analyzed by a single step polymerase chain reaction (PCR) with Cyclospora-specific primers from the ITS-1 region of the genome.The majority of the Cyclospora positive cases (15) were clustered during about 15 days in June 2007, indicating an unusual incidence of cyclosporiasis in this time period. The climatic characteristics of 2007 could have played a role in this high occurrence rate.

Human herpes virus type 8-associated Kaposi sarcoma in a pediatric liver transplant recipient

Çeltik C, Ünüvar A, Aydoğan A, Gökçe S, Öztürk G, Güllüoğlu M, Yılmaz G, Türkoğlu S, Anak S, Sökücü S, Durmaz Ö. Human herpes virus type 8‐associated Kaposi sarcoma in a pediatric liver transplant recipient.
Pediatr Transplantation 2011: 15: E100–E104.

Acute prostatitis as an uncommon presentation of brucellosis

The present report concerns a 46-year-old man who presented with acute prostatitis due to Brucella melitensis infection. He was first treated with doxycycline and ciprofloxacin, but after 3 months he was admitted again with the same diagnosis. The relapse was probably related to ciprofloxacin use, or the length of treatment not being sufficient. The patient was successfully treated with a combination of doxycycline and rifampin for 3 months. In conclusion, prostatitis due to Brucella, such as spondylitis, meningoencephalitis and endocarditis, should be treated for longer courses.

Serial measurements of serum transaminases in renal transplant recipients with chronic hepatitis C: do they reflect disease severity?

Chronic hepatitis C infection is a common problem in renal allograft recipients. This study was designed to investigate the association of serum aminotransferase levels with liver histology, in renal transplant patients with chronic hepatitis C virus (HCV) infection, in the long term. 
Methods. In this study, 82 HCV‐infected renal allograft recipients, who were followed up with functioning grafts for at least 6 months, were analyzed. Patients were classified according to their transaminase values as persistently normal, intermittently abnormal, or continuously abnormal liver function tests. Serum transaminase levels exceeding at least 1.5 times the upper limit of normal (40 IU) for periods longer than 1 month were taken as abnormal. Patients with abnormal liver function tests owing to HCV unrelated causes (drugs, alcohol, or other toxic substances, other viruses, etc.) were excluded from the study. Forty‐eight of these patients underwent at least one liver biopsy. 
Results. Of the 82 patients, 34 (41.5%) had persistently normal (liver biopsy revealed normal or minimal changes in 77.0%, chronic persistent hepatitis in 15.3%, chronic active hepatitis in 7.7%; no patient had cirrhosis), 29 (35.3%) intermittently abnormal (liver histology was consistent with minimal changes in 50%, chronic persistent hepatitis in 27.8%, chronic active hepatitis in 16.7%, cirrhosis in 5.5%), 19 (23.2%) persistently abnormal (liver biopsy showed minimal changes in 41.1%, chronic persistent hepatitis in 17.6%, chronic active hepatitis in 35.3%, cirrhosis in 5.9%) transaminase values. 
Conclusion. Although continuously or intermittently elevated transaminases do not always indicate morphologically advanced disease, the normal course of serum transaminases is mostly accompanied by normal, or near‐normal, liver histology, in HCV‐infected renal transplant patients. Liver biopsy is not indicated in deciding disease severity in these patients unless clinical findings dictate otherwise.