Two drugs with paradoxical effects on liver regeneration through antiangiogenesis and antifibrosis: Losartan and Spironolactone: a pharmacologic dilemma on hepatocyte proliferation.

BACKGROUND: There is a strong relationship between liver regeneration and angiogenesis and fibrosis. It is known that Spironolactone, an aldosterone antagonist, acting on rennin-aldosterone axis, and Losartan, an angiotensin II type I antagonist, have both antifibrotic and antiangiogenic effects. Theoretically, the end result of these mechanisms with contradictory influences on liver regeneration is not known well. In this study, we aimed to reveal the effects on liver regeneration of administration of Spironolactone and Losartan, having contradicting effects on regeneration through antiangiogenesis and antifibrosis. MATERIALS AND METHODS: A total of 72 Wistar albino rats were divided into control, Spironolactone, and Losartan groups and subdivided to conduct examinations on days 1, 3, 5, and 7. The specimens were treated with proliferating cell nuclear antigen to evaluate the characteristics of liver regeneration; with phosphorylated Smad2 (phospho-Smad2), serum transforming growth factor beta (TGF-B) 1, and tissue TGF-B1 to evaluate the termination of regeneration and with vascular endothelial growth factor receptor 2, Flk-1/KDR, to evaluate angiogenesis. RESULTS: The proliferating cell nuclear antigen-labeling index was found to be significantly higher in Spironolactone and Losartan groups than in the control group on days 1, 3, and 5 (P = 0.031, 0.0023, and 0.032, respectively). Vascular endothelial growth factor receptor 2, Flk-1/KDR, expression was significantly lower in Spironolactone and Losartan groups than in the control group on days 3, 5, and 7 (P = 0.032, 0.0024, and 0.007, respectively). Phospho-Smad2 was significantly lower on days 1, 3, and 5 in Spironolactone and Losartan groups than in the control group (P = 0.011, 0.0020, and 0.05, respectively). Tissue TGF-B1 levels were significantly lower in Spironolactone and Losartan groups than in the control group only on day 3 (P = 0039). Serum TGF-B1 levels in Losartan groups were significantly different from those of control and Spironolactone groups only on day 1 (P < 0.05). CONCLUSIONS: Liver regeneration, expected to decrease on day 3, was prolonged and increased even on day 5 despite antiangiogenic effects of Losartan and Spironolactone, which in fact inhibit fibrosis through phospho-Smad2 and increase regeneration. In addition, serum and tissue TGF-B1 levels are not sensitive enough to show active TGF-B1 for the evaluation of regeneration.

[Evaluation of the ChromID ESBL agar for the detection of ESBL-positive Enterobacteriaceae and vancomycin-resistant enterococcus isolates from urine cultures]. / GSBL Pozitif Enterobacteriaceae ve Vankomisine Dirençli Enterokoklarin Idrar Kültürlerinden Erken Tespitinde ChromID ESBL Agarin Degerlendirilmesi.

Extended-spectrum beta-lactamase (ESBL)-producing Enterobacteriaceae strains are frequent causative agents both in community-acquired infections and in nosocomial infections. The newly developed ChromID ESBL agar (bioMerieux, Marcy I'Etoile, France) is a chromogenic medium that helps rapid identification of ESBL-positive Enterobacteriaceae species from the clinical samples. The aim of this study was to evaluate the performance of ChromID ESBL agar in the rapid identification of ESBL-positive pathogens from the urine samples of the patients with urinary tract infections. A total of 672 urine samples (437 outpatients, 235 inpatients) were included in the study. All of the samples were inoculated simultaneously to 5% sheep blood agar, McConkey agar and ChromID ESBL agar media, and evaluated after incubation at 37°C for 18-24 hours. Gram-negative pathogens were tested for ESBL both by the standard combined double-disk diffusion (CDD) method using ceftazidime and cefotaxime disks and by doubledisk synergy (DDS) test. Among 672 urine cultures, 199 yielded microbial growth in routine media (sheep blood agar and/or McConkey agar), whereas 57 yielded bacterial growth in ChromID ESBL agar. When CDD method was accepted as the reference method according to Clinical and Laboratory Standards Institute (CLSI) recommendations, the sensitivity, specificity, positive and negative predictive values for ChromID ESBL agar for the detection of ESBL-positive bacteria in urinary tract infections were estimated as 97%, 92.9%, 89.1%, and 98.1%, respectively. Additionally, we also discovered that Chrom ID ESBL agar could detect vancomycin-resistant enterococci (VRE) as well as ESBL-positive bacteria, in our study. In order to investigate this observation we inoculated a total of 203 stock strains of Enterococcus spp. (118 vancomycin-sensitive, 85 vancomycin-resistant) to this medium. None of the vancomycinsensitive Enterococcus spp. did grow in ChromID ESBL medium, while 83 of the 85 resistant isolates (97.6%) did grow in the medium. As a result, it was concluded that ChromID ESBL agar medium was advantageous since it led to the growth of VRE and ESBL-positive Enterobacteriaceae isolates in different colors and helped in early identification of these two problematic bacteria. We thought that especially early detection of VRE will accelerate the establishment of necessary measures to prevent the nosocomial spread of this microorganism.

[Neurological involvement in brucellosis; clinical classification, treatment and results]. / Brusellozda sinir sistemi tutulumu; klinik siniflama, tedavi ve sonuçlar.

The aim of this retrospective study was to describe and to categorize different clinical pictures of patients with neurobrucellosis in our clinic, and present demographical and laboratory data about the patients. Hospital records of 430 patients with brucellosis between 2003 and 2009, were retrospectively reviewed. Out of 430 patients, 19 (4.4%) had neurobrucellosis. These patients were classified into four groups: Meningitis group (n= 14, 13 cases of subacute/chronic meningitis, one case of acute meningitis), encephalomyelitis group (n= 3, one case of meningoencephalomyelitis, one case of cerebellar abscess and one case of transverse myelitis), polyradicular group (n= 1, Miller-Fisher Syndrome), and others (n= 1, one case of intradural abscess). Ten patients (52.6%) were female, and the mean age of the patients was 48.8 years. About 47.4% of the patients had fever, 26% of the patients had neck stiffness and 5% of the patients were in an unconscious state. Out of 19 patients, 18 underwent lumbar puncture and they had positive brucella antibody test in cerebrospinal fluid (CSF) by standard tube agglutination method. Brucella spp. Were grown in four patient's blood culture and one patient's CSF culture. There were cranial nerve involvement in five cases, the most frequent being the sixth cranial nerve. Out of 19 patients, three recovered with sequela (paraparesis, hearing loss, dementia and sphincter disfunction) and 16 patients recovered completely. Although neurobrucellosis is most frequently presented as subacute/chronic meningitis, it may be associated with different clinical pictures. The classical triad of meningitis (fever, neck stiffness, unconsciousness) is rarely seen in brucellosis-related meningitis. Brucellosis should be kept in mind in patients with unexplained neurological findings particularly in areas where brucellosis is endemic. In addition, a current classification of neurobrucellosis, related to involved location of nervous system, clinical picture and pathogenesis, is needed.

[The performance of two different chromogenic media for the diagnosis of extended spectrum beta-lactamase producing strains]. / Genislemis spektrumlu beta-laktamaz ureten suslarin tanisinda iki farkli kromojenik agarin performansi.

The aim of this study was to evaluate the performances of 2 different chromogenic media for the detection of extended spectrum beta-lactamase (ESBL) producing Escherichia coli and Klebsiella spp. isolated from different clinical samples of patients who were admitted to Baskent University Faculty of Medicine, Adana Application and Research Hospital between September to November 2007. A total of 365 strains [251 were ESBL positive and 114 were negative by double disc synergy (DDS) test] of which 255 were E. coli and 110 were Klebsiella spp. were included to the study. All the isolates have been inoculated onto Drigalski agar (prepared following the formula described by Stürenburg et al.) and chromID ESBL agar (bioMérieux, France) and the production of ESBL were evaluated at 4th and 24th hours for Drigalski agar, and at 24th hours for chromID ESBL agar. The strains which yielded contradictory results by DDS test and chromogenic media, were tested for the presence of TEM, SHV and CTX-M genes by polymerase chain reaction (PCR). The number of ESBL positive strains on Drigalski agar at 4th and 24th hours were 238 and 235, respectively, while chromID ESBL agar detected 259 ESBL positive strains at 24th hours. All (100%) of the 159 ESBL positive E. coli strains by DDS test were also found positive on chromID ESBL agar, and 150 (94.3%) were found positive on Drigalski agar. These rates were detected as 100% (92/92) and 92.3% (85/92) for Klebsiella spp. isolates. Eight of the strains (2 E. coli, 6 Klebsiella spp.) which yielded negative results by DDS test but positive on chromlD ESBL agar, harboured SHV (n = 1), CTX-M (n = 6) and TEM + CTX-M (n = 1) genes detected by PCR. As a result, the consistency of the results obtained by Drigalski agar at 4th and 24th hours has indicated that this medium may provide advantages in rapid diagnosis of ESBL producing bacteria in routine laboratories. The data obtained for chromogenic media seemed to be favourable for the rapid diagnosis of ESBL production, however comparative studies with the use of standard reference methods are needed in order to determine diagnostic sensitivity and specificity of these media.

[Retrospective evaluation of 15 cases with psoas abscesses]. / Psoas apsesi olan 15 hastanin retrospektif olarak degerlendirilmesi.

Psoas abscesses are suppurative collections within the fascia surrounding the psoas and iliacus muscles. In this retrospective study it was aimed to evaluate the demographic characteristics, clinical and laboratory findings and treatment outcomes of 15 psoas abscess cases admitted to Baskent University Hospital, Ankara, Turkey during June 2003-January 2008 period. The mean age of the patients was 55.8 years (range 18 to 70 years) with a female to male ratio of 5/10. Thirteen of the cases (86.5%) were admitted with the complaints of fever and back pain. Thirteen of the cases were diagnosed by abdominal computerized tomography while the other two by abdominal ultrasonography. One of the 15 patients was considered as primary psoas abscess, while the remaining 14 as secondary psoas abscess. The most common accompanying disease was diabetes mellitus (66.6%). Fourteen patients with secondary psoas abscess had vertebral osteomyelitis which was due to tuberculosis in five cases, to urinary tract infection in five cases, to pneumoniae in two cases, to surgical infection in one case and to brucellosis in one case. The cultivation of the abscess material from the 14 secondary psoas abscess cases revealed growth of bacteria in 11 of them (5 Mycobacterium tuberculosis, 1 Escherichia coli, 1 methicillin-sensitive Staphylococcus aureus, 1 methicilin-resistant S. aureus, 1 Acinetobacter baumannii, 1 Brucella melitensis, 1 Serratia marcescens). The biochemical parameters of the cases (mean leukocyte counts: 14.500 cell/mm3; mean erythrocyte sedimentation rates: 78 mm/hour; mean C-reactive protein levels: 108 mg/dl) were also high. Thirteen patients underwent percutaneous drainage and received appropriate antibiotic treatment and the other two patients were treated with open surgical debridement. The duration of antimicrobial treatment was one year for M. tuberculosis cases and about 4-6 weeks in the others. One of the cases died due to complicating meningitis and sepsis. It is remarkable that in our series none of the psoas abscess cases were secondary to the diseases of the digestive tract unlike the series indicated in the literature. The isolation of M. tuberculosis as the causative agent in 5 (33.3%) cases emphasizes the fact that tuberculosis is still an important public health problem in Turkey.

[Retrospective evaluation of the cases with Candida famata fungemia in a burn unit]. / Yanik ünitesinde Candida famata fungemisi gelisen olgularin retrospektif olarak degerlendirilmesi.

The prevalence of fungemia due to non-albicans Candida species is increasing currently. However, there is no reported case of fungemia due to Candida famata in a burn unit. This retrospective study was aimed to evaluate the clinical and laboratory characteristics and outcomes of seven burn patients with fungemia due to C. famata. The study included a total of 410 burn patients followed-up during January 2003-January 2006. Six of the patients (85.7%) were males and one was female (14.3%), with a mean age of 22.2 years. Mean total body surface area of the burns was 39.2% (24%-64%), flame being the most frequent cause of the burns (n= 4), followed by hot water (n= 2) and electroshock (n= 1). Six of the cases had central venous catheter and in 5 of these catheter-associated bacteremia had developed before the establishment of candidemia. Pseudomonas aeruginosa (n= 5) was the most frequent cause of bacteremia; Escherichia coil being isolated from a patient with urinary tract infection and methicillin-resistant Staphylococcus aureus from a patient with wound infection. All patients had received treatment with systemic antibiotics prior to the development of the C. famata episode. C. famata was detected from the blood cultures of the patients, however, the wound swabs were negative in terms of C. famata growth. The isolates were defined according to their negative germ tube test and their carbohydrate assimilation profile in API 20 C AUX (BioMerieux, France). Since the environmental cultures yielded negative results for C. famata, the infections were thought to be derived from cross contamination. Once a positive blood culture for C. famata was obtained, the catheter was removed, and treatment with liposomal amphotericin-B was implemented. Presence of a central venous catheter and prior antibiotic therapy seem to be the predisposing factors in the development of fungemia due to C. famata. Thus, when fungemia due to C. famata is established, central venous catheter should be removed and amphotericin-B therapy should be implemented promptly.

Brucellosis in cases of end-stage renal disease.

BACKGROUND: Patients with brucellosis frequently present with joint and bone pain. However, brucellosis may be overlooked in patients with end-stage renal disease (ESRD) who undergo dialysis since amyloidosis due to renal osteodystrophy and beta-2 microglobulinaemia may cause bone pain as well. Only four cases of end-stage renal failure accompanied by brucellosis have been reported in the literature. We evaluated clinical and laboratory characteristics and organ involvement of seven brucellosis patients with end-stage renal failure and compared them with brucellosis cases without any renal diseases. METHODS: This is a prospective study and involved 158 patients diagnosed with brucellosis. All the patients were divided into two groups: brucellosis patients with ESRD (Group 1) and brucellosis patients without any renal disease (Group 2). RESULTS: Group 1 included 7 patients (5 males and 2 females with the mean age 52.1 +/- 14 years) and Group 2 included 151 patients (62 males and 89 females with the mean age 45.4 +/- 16 years). Out of seven patients in Group 1, one had neurobrucellosis, one had paravertebral abscess, one had epidural abscess and one had peripheral arthritis. In addition, one patient in Group 1 with accompanying sickle cell anaemia presented with pain crisis and was diagnosed with brucellosis on admission. Serological tests were negative for brucellosis, but Brucella melitensis was isolated in blood cultures in another patient with accompanying continuous ambulatory peritoneal dialysis. Group 1 more frequently had joint pain and malaise. B. melitensis was isolated in blood cultures in blood taken in the absence of fever in half of the cases in Group 1 positive for B. melitensis in blood cultures on admission. CONCLUSION: B. melitensis can be isolated in blood cultures even in the absence of high fever. In fact, in the present study, B. melitensis was isolated in most of the cases without high fever. For this reason, blood cultures should be performed in cases of end-stage renal diseases suspected of having brucellosis although fever is not present. In addition, brucellosis can present various clinical forms in endemic areas, mimics several diseases and can be characterized with severe complications.

[Short communication: Investigation of in vitro antibiotic susceptibility of Brucella melitensis]. / Kisa bildiri: Brucella melitensis'in in vitro antibiyotik duyarliliginin arastirilmasi.

The aim of this study was to investigate the in vitro susceptibilities of Brucella melitensis clinical isolates against antibiotics used in conventional treatment regimens and additionally against quinolones. A total of 65 B. melitensis strains isolated from blood and bone marrow specimens of patients who were admitted to an university hospital localized in a region endemic for brucellosis. Minimum inhibitory concentration values (MIC50 and MIC90) of trimethoprim-sulphamethoxazole (TMP-SMX), rifampin, doxycycline, ciprofloxacin, ofloxacin, sparfloxacin and levofloxacin for B. melitensis isolates have been detected by using E-test (AB Biodisk, Sweden). In our study the most effective antimicrobial agent was found to be TMP-SMX (MIC90 = 0.023 mg/L) followed by doxycycline (MIC90 = 0.032 mg/L). With regard to fluoroquinolones, the most active antibiotic was sparfloxacin (MIC90 = 0.064mg/L), followed by levofloxacin and ciprofloxacin (MIC90 = 0.125 mg/L), and ofloxacin (MIC90 = 0.50 mg/L). Rifampin exhibited the highest MIC90 value (1.5 mg/L), and eight isolates yielded intermediate resistance to rifampin. There was no serious resistance problem for TMP-SMX and doxycycline in our study, however, enough care should be taken for the use of rifampin which is frequently used for the treatment of tuberculosis and brucellosis which are endemic in our country. As a result, the antimicrobial susceptibilities of Brucella species should be determined periodically to avoid the possible development of resistance problems in the future.

[Prevalence of inducible clindamycin resistance in Staphylococcus aureus strains isolated from clinical samples]. / Klinik örneklerden izole edilen Staphylococcus aureus suslarinda indüklenebilir klindamisin direnç prevalansi.

Empirical treatment options for staphylococcal infections have become limited, as the prevalence of methicillin-resistant Staphylococcus aureus (MRSA) strains have increased. Clindamycin has been a useful option for treating skin and soft-tissue infections caused by MRSA. However, expression of inducible macrolide-lincosamide-streptogramin B resistance (MLS(B)i) to clindamycin could limit the effectiveness of this drug. The purpose of this study was to investigate the prevalence of inducible clindamycin resistance (MLS(B)i) in S. aureus strains isolated from clinical samples (wound, abscess, blood, sterile body fluids, upper respiratory tract samples, catheter). We prospectively collected sequential non-duplicated S. aureus isolates exhibiting erythromycin resistance and clindamycin susceptibility, as determined by disk diffusion method from September 2005 to August 2007 in Baskent University Adana Research and Practice Center. Testing for MLS(B)i was accomplished by the disk-diffusion induction test (D test). A total of 892 S. aureus isolates were collected during the study period. Of these, 226 were detected as erythromycin resistant-clindamycin susceptible by disk diffusion method. The prevalence of inducible clindamycin resistance in all S. aureus isolates and erythromycin resistant-clindamycin susceptible isolates were found as 19.4% (173/892) and 76.5% (173/226), respectively. Accurate susceptibility data are important for appropriate clindamycin therapy. Since inducible clindamycin resistance is not detected by standard susceptibility tests, application of D-test on a routine basis will be helpful to detect this resistance and to help effective use of clindamycin in staphylococcal infections.

[Four years of monitoring of antibiotic sensitivity rates of Pseudomonas aeruginosa and Acinetobacter baumannii strains isolated from patients in intensive care unit and inpatient clinics]. / Yogun bakim ve servis hastalarindan izole edilen Pseudomonas aeruginosa ve Acinetobacter baumannii izolatlarinin antibiyotik duyarlilik oranlarinin dört yillik izlemi.

Pseudomonas aeruginosa and Acinetobacter baumannii which are usually multiply antibiotic resistant, are the most important agents causing infections in intensive care units (ICUs). The aim of this study was to determine the antibiotic sensitivity patterns of P. aeruginosa and A.baumannii that cause infections in ICUs and hospital service units and to follow the variation in resistance between the years of 2003 to 2006. P. aeruginosa (n:1071) and A.baumannii (n:587) strains were isolated from blood, urine, wound, sterile body fluid, sputum and tracheal aspirate cultures of patients who were diagnosed to have infections in ICUs and hospital service units. Conventional methods were used for the identification of the bacteria, and antibiotic sensitivies of the isolates were investigated by disk diffusion method. The most effective antibiotics in 2003 were piperacillin-tazobactam (84%), ciprofloxacin (79%), imipenem (77.5%), and meropenem (69%) for P. aeruginosa strains isolated from ICUs. Decreasing sensitivities to imipenem (51%), meropenem (45%), cefepime (51%), piperacillin (38.5%), ciprofloxacin (72%), cefoperazone/sulbactam (44%) and piperacillin/tazobactam (67%) for P. aeruginosa were found statistically significant in 2006 (p < 0.05). The most effective antibiotics were meropenem (98%) imipenem (94%) and ampicillin/sulbactam (72%) for A.baumannii strains isolated from ICUs in 2003. Decreasing sensitivities to imipenem (60.5%), meropenem (69%), cefepime (24%), ciprofloxacin (14%), gentamicin (13%), and amikacin (19%) for A.baumannii were statistically significant in 2006 (p < 0.05). Our data have indicated that P. aeruginosa and A.baumannii strains isolated in ICUs at our hospital showed multi-drug resistance in 2006, with significant increases since 2003 against certain antimicrobial agents. In conclusion there is an urgent need for effective strategies to control the use of antibiotics in our hospital.

[Comparative evaluation of 113 cases with severe and mild forms of extrapulmonary tuberculosis]. / Ciddi ve hafif seyirli 113 akciger disi tüberküloz olgusunun karsilastirmali olarak degerlendirilmesi.

Tuberculosis, one of the oldest diseases of human beings, has still high mortality rates. In this prospective study, 113 HIV seronegative patients with extrapulmonary tuberculosis (EPT) who were admitted to our department between January 2001 and July 2006 have been evaluated and cases with severe or mild forms of EPT have been compared with respect to epidemiological and clinical features, laboratory results and treatment outcomes. The age range of the patients were 16-78 years old (mean age: 46.3 +/- 16.9 years), and 64 of them (56.6%) were female. Severe and mild forms of EPT were diagnosed in 49 (43.3%) and 64 (56.6%) of the patients, respectively. The most frequently involved organ was detected as lymph nodes (43.3%), followed by pleura and vertebrate involvements with the rates of 12.4%. There was an underlying disease in 35 (30.9%) of the patients (diabetes mellitus in 15%; chronic renal dysfunction in 11.5%; malignancy in 4.4%), history of passed tuberculosis infection in 13 (11.5%) and history of contact with a tuberculosis patient in 25 (22.1%). In direct microscopic examination, samples from 19 (16.8) patients were found positive for acid-fast bacilli, and samples cultivated in Lowenstein-Jensen media yielded mycobacterial growth in 25 (22.1%) patients. The diagnosis have been made histopathologically in 89 (78.7%) of the cases. In comparison of the patients with severe and mild forms of EPT, the severe form were detected more frequently in males (p= 0.01), the positivity rates of culture and acid-fast staining were higher in patients with severe form (p= 0.0004 and p= 0.001, respectively). The mortality rate was also found higher in patients with severe form (p= 0.046). The cases who were diagnosed as EPT have been treated by three or four antituberculosis drugs. Izoniazid (300 mg/day, 6-12 months), rifampicin (600 mg/day, 6-12 months), ethambutol (1500 mg/day, 2-4 months), pyrazinamide (2000 mg/day, 2-4 months) and streptomycin (1 g/day, 45-60 days) were used for the therapy. Side effects due to the therapy were observed in 13.3% of the cases (most frequently; gastrointestinal intolerance in 53.3% and hepatitis in 40%), however, there was no necessity to quit the therapy. Surgical treatment has been applied in 14 (12.4%) of the patients. As a result, the investigation of epidemiological and clinical characteristics of extrapulmonary tuberculosis on the large series of cases may be essential for early diagnosis and treatment in endemic countries such as Turkey.

Performance of MRSA ID chromogenic medium for detection of methicillin-resistant Staphylococcus aureus directly from blood cultures and clinical specimens.

MRSA ID was evaluated to see its performance in identifying methicillin-resistant Staphylococcus aureus (MRSA) directly from blood culture bottles (n = 837), wound swabs (n = 112), and abscesses (n = 18). Each positive blood culture and clinical specimen was directly inoculated on MRSA ID and the culture media routinely used. The sensitivity of MRSA ID was 97.8% after 24 h and 100% after 48 h for blood cultures, and 88.9% after 24 h and 100% after 48 h for wound samples. The specificity was 99.7% after 24 h and 99.6% after 48 h for blood cultures, and 100% after 24 and 48 h for wound samples. Four strains with green colonies indicating MRSA on MRSA ID were identified as methicillin-susceptible S. aureus (MSSA) by conventional methods. Three of these MSSA strains showed negative results with the mecA polymerase chain reaction, and 1 strain harbored the mecA gene. Using MRSA ID with primary culture media should decrease the time (18-24 h) to report a positive result compared with conventional methods.

[Brucellosis: retrospective evaluation of the clinical, laboratory and epidemiological features of 151 cases]. / Bruselloz: 151 olgunun klinik, laboratuvar ve epidemiyolojik özelliklerinin retrospektif degerlendirilmesi.

The aim of this study was to retrospectively evaluate the clinical and laboratory characteristics, complications and treatment oucomes of 151 brucellosis cases (age range: 15-79 years; 89 female), who were followed in our clinic between the period of January 2003-July 2005. Of them, 66.2% were diagnosed as acute, 23.8% as subacute and 9.9% as chronic brucellosis. Risk factors were detected as consumption of unpasteurized milk and diary products (80%), stock-breeding (14%) and risky profession such as veterinary, laboratory technician and butcher (3.3%). Most common complaints were arthralgia (87.4%), malaise (86%), fever (79.5%), sweating (78%), and waist pain (71%). In view of laboratory findings, increased erytrocyte sedimentation rate was detected in 61.6%, C-reactive protein positivity in 60%, lymphomonocytosis in 44.4% and anemia in 51.7% of them. Blood cultures were performed from 125 of the patients, and 64 (51.2%) of them yielded Brucella spp. The other specimens in which bacterial growth were detected in one of each, were bone marrow, sternoclavicular joint, psoas abscess, urine and pleural fluid. Standard tube agglutination (STA) test was found negative in 1.3% of patients who were culture positive, while it was positive at 1/160 titer in 20.5%, at 1/320 in 14%, at 1/640 in 14.6% and > or = 1/1280 in 49.7 percent. The most common complication was found as musculo-skeletal system involvement (30 spondylodiscitis, 15 sacroileitis, five peripheric arthritis, one tendinitis) with a rate of 33.7 percent. Other complications were nervous system involvement in 6% (two acute and seven chronic meningitis), genitourinary involvement in 5.3% (five epididymo-orchitis, two prostatitis, one with Brucella positive urine culture), peritonitis in 0.6% and skin involvement in 0.6 percent. Seven different therapy protocols were applied to the patients according to complications and case specialty, however doxycycline+rifampicin combination during six weeks was the most preferred one. Relapse and unresponsiveness to the therapy were detected in 8% and 2% of the cases, respectively. Gastrointestinal intolerance was found as the most common side effect. In conclusion, since brucellosis which is endemic in Turkey, displays diagnostic difficulties due to the various clinical presentations and leads to labor loss due to serious complications, it should be considered in the differential diagnosis of numerous diseases.

[In vitro resistance rates of Streptococcus pneumoniae and Haemophilus influenzae clinical isolates to the antibiotics used in therapy]. / Streptococcus pneumoniae ve Haemophilus influenzae klinik izolatlarinin tedavide kullanilan antibiyotiklere karsi in vitro direnç oranlari.

Streptococcus pneumoniae and Haemophilus influenzae which cause infections with high morbidity and mortality all over the world, are also the most important bacterial pathogens of community-acquired pneumoniae. In recent years S. pneumoniae is becoming increasingly resistant to a variety of antibiotics. The aim of this study was to detect the in vitro resistance rates of S. pneumoniae and H. influenzae strains isolated from different clinical samples to the antibiotics which are used in the therapy of infections due to these pathogens. Between the period of January 2005 to May 2006, 77 S. pneumoniae (44 sputum, 20 blood, 8 bronchoalveolar lavage, 4 pleural fluids and 1 tracheal aspirate isolate) and 31 H. influenzae (30 sputum and 1 bronchoalveolar lavage isolate) strains isolated from patients who were admitted to Baskent University Hospital, Research and Practice Center of Adana (located in southern Turkey), were included to the study. The antibiotic susceptibility tests were performed by disc diffusion method according to CLSI (Clinical and Laboratory Standards Institute; M100-S13) guidelines. The MIC values of S. pneumoniae which gave an inhibition zone diameter of > or =19 mm in with disc diffusion test, were detected by E-test (AB Biodisk, Sweden). Intermediate and high resistance rates of pneumococci to penicilin were found as 38.9% (30/77) and 10.4% (8/77), respectively, with a total resistance rate of 49.4%. Trimethoprim-sulphamethoxazole (TMP/SMX), erithromycin, tetracyclin, clindamycin and chloramphenicol were the other antibiotics which followed penicillin with the resistance rates of 42.8%, 37.6%, 31.1%, 23.3% and 10.3%, respectively. Amongst H. influenzae strains, one (3.2%) was found to be a beta-lactamase producer and it was resistant to both ampicillin and azitromycin. Eight (25.8%) of H. influenzae isolates were resistant to TMP/SMX, and two (6.4%) were resistant to chloramphenicol. As a result, the high penicilin and erithromycin resistance rates of S. pneumoniae clinical isolates in our hospital emphasize that the empirical use of these antibiotics should be limited and well-controlled in our region.

[Evaluation of diagnostic value of Brucellacapt test in brucellosis]. / Brusellozun tanisinda Brucellacapt testinin degerinin aratirilmasi.

Although standard tube agglutination (STA) test is the most preferred method for the serodiagnosis of brucellosis, it may yield false negative results because of its incompetence in detecting the blocking (non-agglutinating) antibodies. Blocking antibodies can be detected by Coombs' test (anti-human globulin test), which is generally not performed in laboratories routinely since it is a time consuming and laborious method. Recently more practical Brucellacapt (immunocapture-agglutination) test is being used for the detection of total antibodies without any interference of the presence of blocking ones. The aim of this study was the evaluation of the value of Brucellacapt test in the serodiagnosis of brucellosis. Twenty-five brusellosis patients whose blood cultures yielded Brucella melitensis growth, and 31 healthy subjects as controls, were included to the study. Serum samples obtained from all of the 56 subjects have been searched by STA, Coombs' and Brucellacapt methods, and threshold titre was accepted as 1/160. As a result, 40% (10/25) of culture positive patients were found positive (> or =1/160) by STA, whereas 92% (23/25) were positive (> or =1/160) by both Coombs' and Brucellacapt tests. No positivity was detected in the control group by any one of those three tests. The agreement between Coombs and Brucellacapt methods was found as 100%, while the sensitivity and specificity of Brucellacapt test were estimated as 92% (23/25) and 100% (31/31), respectively, when the culture was accepted as reference method. Although our data have pointed out the high performance of Brucellacapt test in brusellosis serodiagnosis, confirmation with further data carried on extensive and comprehensive study groups, are needed.

Incubation at room temperature may be an independent factor that induces chlamydospore production in Candida dubliniensis.

Production of chlamydospores is one of the phenotypic features used to differentiate Candida albicans and Candida dubliniensis. C. albicans produces few chlamydospores on only cornmeal/rice-Tween agar at room temperature, whereas C. dubliniensis produces abundant chlamydospores at this temperature both on cornmeal agar and some other commonly used media. We tried to determine whether the room temperature is the main factor that induces chlamydospore production of C. dubliniensis, regardless of the medium used. For this purpose, 100 C. albicans and 24 C. dubliniensis isolates were tested for chlamydospore production at room temperature and at 37 degrees C on some routinely used media, including eosin-methylene blue agar (EMB), nutrient agar (NA), nutrient broth (NB), and also on an investigational medium, phenol red agar (PR). At 37 degrees C, none of the isolates produced chlamydospores on any of the tested media. At 26 degrees C, all C. dubliniensis isolates produced abundant chlamydospores and pseudohyphae after 24-48 h on all tested media. At this incubation temperature, all C. albicans isolates failed to produce chlamydospores and pseudohyphae on EMB, NA, and NB, whereas 2 of the C. albicans isolates produced a few chlamydospores on PR. We also observed that all C. dubliniensis isolates tested on EMB and PR produced rough colonies with a hyphal fringe around the colonies, whereas none of the C. albicans isolates showed this property. In conclusion, incubation at 26 degrees C may play the key role for production of abundant chlamydospores and pseudohyphae by C. dubliniensis. Comprehensive molecular studies are needed to clarify the genetic basis of this observation. Using EMB and PR may be an inexpensive, a time-saving, and a simple way of presumptive identification of C. dubliniensis based on chlamydospore formation and colony morphology.

[Mycobacterium tuberculosis virulence factors and its immune evasion mechanisms]. / Mycobacterium tuberculosis'in virulans faktörleri ve immün yanittan kaçis mekanizmalari.

One-third of the world population is infected with Mycobacterium tuberculosis. When tuberculosis develops, the disease localization, severity, and outcome are highly variable between different individuals. The various manifestations of infection with M. tuberculosis reflect the balance between the bacilli and host defense mechanisms, in which the quality of host defense determines the outcome. Recent studies have identified several mycobacterial cell wall components that may be involved in the key steps of pathogenicity. M. tuberculosis is successful as a pathogen because of its ability to persist in an immunocompetent host. This bacterium lives within the macrophages. Hosts infected with M. tuberculosis mount a strong immune response. This response is usually sufficient to prevent progression to active disease. The strong immune response can control, but not eliminate the bacilli, indicating that M. tuberculosis has evolved mechanisms to modulate or avoid detection by the host immune response. Recent advances have improved our understanding of how M. tuberculosis evades two major antimicrobial mechanisms of macrophages; phagolysosome fusion and the production of toxic reactive nitrogen intermediates (RNI). In this review, the recent evidence of M. tuberculosis evasion from phagolysosome fusion and RNI toxicity, as well as prevention of the recognition of infected macrophages by CD4+ T lymphocytes by inhibiting MHC class II presentation, were discussed.

Molecular methods for detection of invasive fungal infections and mycobacteria and their clinical significance in hematopoietic stem cell transplantation.

Infection remains an important source of morbidity and mortality in patients who undergo hematopoietic stem cell transplantation (HSCT). In the immune reconstitution period after transplantation, HSCT recipients are most likely to have bacterial or fungal infections. Invasive fungal infections (IFIs) and mycobacterial infections (MBIs) are among the complications of HSCT, with high morbidity and mortality rates. Early diagnosis of both is crucial in order to manipulate the disease and to avoid fulminant outcomes. This chapter reviews the current knowledge on the molecular diagnosis of IFIs and MBIs in HSCT recipients, describing two different polymerase chain reaction (PCR)-based methods, one commercial (qPCR, Roche) and one in-house IS6110-based protocol.

The African variant of BKV in a Turkish renal transplant patient.

In renal transplant recipients, BK polyomavirus (BKV) is linked to nephropathy. BK virus genotypes have a strong geographic component. This paper presents the African variant of BKV in a Turkish renal transplant patient, which is a rare cause of infection in the Northern Hemisphere and, to our knowledge, the first case from Turkey.

In vitro activity of fosfomycin in combination with imipenem, meropenem, colistin and tigecycline against OXA 48-positive Klebsiella pneumoniae strains.

Carbapenem resistance due to OXA-48 enzymes in Klebsiella pneumoniae is increasing particularly in the Middle Eastern and European regions. Treatment options are limited. The aim of this study was to evaluate the in vitro synergistic activity of fosfomycin in combination with imipenem, meropenem, colistin and tigecycline against OXA-48 producing K. pneumoniae strains. Twelve carbapenem-resistant OXA-48 producing K. pneumoniae isolates were enrolled in this study. Synergistic activity of fosfomycin combined with imipenem, meropenem, colistin, and tigecycline was assessed by chequerboard method. The combination of fosfomycin was synergistic with imipenem, meropenem and tigecycline with the ratios of 42%, 33%, and 33%, respectively. Whilst the combination of fosfomycin with colistin was fully antagonistic against all of the strains, there was no statistically significant difference between the in vitro synergistic activities of fosfomycin in combination with imipenem, meropenem and tigecycline combinations (P > 0.05). Fosfomycin in combination with other agents can be preferred against multidrug resistant K. pneumoniae strains.