Serda Gulsun

Efficacy and safety of tenofovir disoproxil fumarate in pregnancy for the prevention of vertical transmission of HBV infection

AIM To evaluate the effects of tenofovir disoproxil fumarate (TDF) use during late pregnancy to reduce hepatitis B virus (HBV) transmission in highly viremic mothers. METHODS This retrospective study included 45 pregnant patients with hepatitis B e antigen (+) chronic hepatitis B and HBV DNA levels > 10⁷ copies/mL who received TDF 300 mg/d from week 18 to 27 of gestation (n = 21). Untreated pregnant patients served as controls (n = 24). All infants received 200 IU of hepatitis B immune globulin (HBIG) within 24 h postpartum and 20 μg of recombinant HBV vaccine at 4, 8, and 24 wk. Perinatal transmission rate was determined by hepatitis B surface antigen and HBV DNA results in infants at week 28. RESULTS At week 28, none of the infants of TDF-treated mothers had immunoprophylaxis failure, whereas 2 (8.3 %) of the infants of control mothers had immunoprophylaxis failure (P = 0.022). There were no differences between the groups in terms of adverse events in mothers or congenital deformities, gestational age, height, or weight in infants. At postpartum week 28, significantly more TDF-treated mothers had levels of HBV DNA < 250 copies/mL and normalized alanine aminotransferase compared with controls (62% vs none, P < 0.001; 82% vs 61%, P = 0.012, respectively). CONCLUSION TDF therapy during the second or third trimester reduced perinatal transmission rates of HBV and no adverse events were observed in mothers or infants.

The microbiological diagnosis of tuberculous meningitis: results of Haydarpasa-1 study

We aimed to provide data on the diagnosis of tuberculous meningitis (TBM) in this largest case series ever reported. The Haydarpasa-1 study involved patients with microbiologically confirmed TBM in Albania, Croatia, Denmark, Egypt, France, Hungary, Iraq, Italy, Macedonia, Romania, Serbia, Slovenia, Syria and Turkey between 2000 and 2012. A positive culture, PCR or Ehrlich-Ziehl-Neelsen staining (EZNs) from the cerebrospinal fluid (CSF) was mandatory for inclusion of meningitis patients. A total of 506 TBM patients were included. The sensitivities of the tests were as follows: interferon-γ release assay (Quantiferon TB gold in tube) 90.2%, automated culture systems (ACS) 81.8%, Löwenstein Jensen medium (L-J) 72.7%, adenosine deaminase (ADA) 29.9% and EZNs 27.3%. CSF-ACS was superior to CSF L-J culture and CSF-PCR (p <0.05 for both). Accordingly, CSF L-J culture was superior to CSF-PCR (p <0.05). Combination of L-J and ACS was superior to using these tests alone (p <0.05). There were poor and inverse agreements between EZNs and L-J culture (κ = -0.189); ACS and L-J culture (κ = -0.172) (p <0.05 for both). Fair and inverse agreement was detected for CSF-ADA and CSF-PCR (κ = -0.299, p <0.05). Diagnostic accuracy of TBM was increased when both ACS and L-J cultures were used together. Non-culture tests contributed to TBM diagnosis to a degree. However, due to the delays in the diagnosis with any of the cultures, combined use of non-culture tests appears to contribute early diagnosis. Hence, the diagnostic approach to TBM should be individualized according to the technical capacities of medical institutions particularly in those with poor resources.

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.

Respiratory System Involvement in Brucellosis: The Results of the Kardelen Study

BACKGROUND Pulmonary involvement is a rare complication of brucellosis. We describe the largest series to date, to our knowledge, of patients with pulmonary brucellosis. METHODS This 10-year, retrospective, descriptive study involved 27 centers in Turkey, including all patients with brucellosis with confirmed respiratory system involvement. RESULTS Of 133 patients (67 men), 123 (92.5%) had acute infection (defined as < 2 months), with an overall mean ± SD duration of symptoms of 33.9 ± 8.5 days. The radiologic pattern of pulmonary disease was consolidation/lobar pneumonia in 91 patients (68.4%) and pleural effusion in 41 patients (30.8%), including 30 (22.5%) with both. Moreover, 23 patients (17.3%) had bronchitis (one with coexistent pneumonia), and 10 (7.5%) had nodular lung lesions (one with coexistent pneumonia and effusion). Blood culture results were positive in 56 of 119 patients, and all other cases were serologically confirmed. None of 60 sputum specimens and two of 19 pleural fluid samples (10.5%) yielded positive culture results for brucellosis. Other features of brucellosis, such as osteoarticular complications, were detected in 61 patients (45.9%); 59 (44.4%) had raised liver transaminase levels, and 59 (44.4%) had thrombocytopenia. Fifteen patients (11.3%) required management in an ICU for an average of 3.8 ± 2.2 days. All patients responded to standard combination antimicrobial therapy for brucellosis with no deaths, although treatment regimens required modification in seven patients. CONCLUSIONS Brucellosis with pulmonary involvement is rare but has a good prognosis following treatment with appropriate antibiotics. Many clues in the exposure history, presenting clinical features, and baseline blood tests should alert the clinician to consider brucellosis.

TREATMENT OF CHRONIC DELTA HEPATITIS: A NINE-YEAR RETROSPECTIVE ANALYSIS

Background Chronic delta hepatitis is the most severe form of viral hepatitis, for which interferon administration is the only available treatment. However, the efficacy of interferon treatment is affected by the dose and duration of treatment, and relapse rates are high. Objectives In this study, we sought to evaluate the efficacy of treatment with pegylated interferon and observe the relapse rates of delta hepatitis after treatment. Patients and Methods Forty-six patients with chronic delta hepatitis were retrospectively studied between January 2002 and December 2010. Patients were evaluated for biochemical, virological, and histological responses. They were then followed-up for at least 1 year after discontinuation of the treatment. Results All the 46 patients in the study received PEG-IFN therapy. Of the 46 patients,25 were treated with PEG-IFN for 1 year and 21 were treated for 2 years. Sixteen patients(34.7%) showed a biochemical response, 27 (58.6%) showed a virological response, and 39 (84.7%) showed a histological response. Sustained virological and biochemical responseswere achieved in 41% and 47.8% of the patients, respectively. Sixteen (84.2%) patients of the 19 with high levels of hepatitis delta virus RNA (HDV RNA) (HDV RNAlevel > 1 × 105) and 10 (71.4%) of the 14 patients with high titers of hepatitis B surface antigen(HbsAg) (HbsAg > 102 IU/mL) at the beginning of the treatment showed relapse after treatment. Conclusions We found no significant differences between 1-year and 2-year treatments.However, the relapse rate was lower in the 2-year treatment group. Higher HDV RNA and HbsAg levels before treatment were associated with higher relapse rates. Younger age was a significant factor in predicting response.

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.

Analysis of antimicrobial consumption and cost in a teaching hospital

BACKGROUND The aim of this study is to compare the periods before and after the intervention applied using the ATC/DDD method in order to ascertain the rational use of antibiotics in a newly established hospital. METHOD The appropriateness of the hospitals antibiotic use, consumption rates and the costs were calculated and compared with other hospitals. Based on these data, an intervention has been planned in order to raise the quality of antibiotic use. The periods before and after the intervention were compared. Between 16 May 2011 and 23 May 2012, data were collected from all hospital units by the infectious diseases specialists and a point prevalence survey was conducted. Anatomical therapeutic chemical classification and the defined daily dose (DDD) methodology were used to calculate the antibiotic consumption. RESULTS On two specific days in 2011 and 2012, 194 out of 307 patients (63.2%) and 224 out of 412 patients (54.4%) received antibiotic treatment, respectively. In 2011 and 2012, the percentage of appropriate antibiotic use was 51% and 64.3%, respectively. Both in 2011 and 2012, inappropriate antibiotic use was found to be significantly higher in surgical clinics in comparison to the internal diseases clinics and the ICU. This was caused by the high rates of inappropriate perioperative antimicrobial prophylaxis observed in surgical clinics. During both years, approximately one-third of the antibiotics were prescribed for the purposes of perioperative prophylaxis, while 88.5% and 43.7% of these, respectively, were inappropriate and unnecessary. Cephalosporins, fluoroquinolones, combinations of penicillins (including β-lactamase inhibitors) and carbapenems were the most frequently prescribed antibiotics during the study periods. The mean total antibiotic consumption was 93.6 DDD/100 bed-days and 63.1 DDD/100 bed-days, respectively. The cost of total antibacterial consumption was € 7901.33 for all the patients (€ 40.72 per infected patient) and € 6500.26 (€ 29.01 per infected patient), respectively. CONCLUSION Each hospital should follow and assess their antibiotic use expressed in DDD in order to compare their antibiotic use with national and international hospitals (WHO, 2009 [14]).

Original ResearchChest InfectionsRespiratory System Involvement in Brucellosis: The Results of the Kardelen Study

BACKGROUND Pulmonary involvement is a rare complication of brucellosis. We describe the largest series to date, to our knowledge, of patients with pulmonary brucellosis. METHODS This 10-year, retrospective, descriptive study involved 27 centers in Turkey, including all patients with brucellosis with confirmed respiratory system involvement. RESULTS Of 133 patients (67 men), 123 (92.5%) had acute infection (defined as < 2 months), with an overall mean ± SD duration of symptoms of 33.9 ± 8.5 days. The radiologic pattern of pulmonary disease was consolidation/lobar pneumonia in 91 patients (68.4%) and pleural effusion in 41 patients (30.8%), including 30 (22.5%) with both. Moreover, 23 patients (17.3%) had bronchitis (one with coexistent pneumonia), and 10 (7.5%) had nodular lung lesions (one with coexistent pneumonia and effusion). Blood culture results were positive in 56 of 119 patients, and all other cases were serologically confirmed. None of 60 sputum specimens and two of 19 pleural fluid samples (10.5%) yielded positive culture results for brucellosis. Other features of brucellosis, such as osteoarticular complications, were detected in 61 patients (45.9%); 59 (44.4%) had raised liver transaminase levels, and 59 (44.4%) had thrombocytopenia. Fifteen patients (11.3%) required management in an ICU for an average of 3.8 ± 2.2 days. All patients responded to standard combination antimicrobial therapy for brucellosis with no deaths, although treatment regimens required modification in seven patients. CONCLUSIONS Brucellosis with pulmonary involvement is rare but has a good prognosis following treatment with appropriate antibiotics. Many clues in the exposure history, presenting clinical features, and baseline blood tests should alert the clinician to consider brucellosis.

Assessment of perioperative antimicrobial prophylaxis using ATC/DDD methodology

OBJECTIVES In the light of international experience and guidelines and in order to improve the quality of perioperative antimicrobial prophylaxis (PAP), various hospitals have set up their own multidisciplinary healthcare teams and have evaluated the density of PAP through close supervision and interventions. The aim of the present study was to compare the density, quality, and cost of PAP before and after an intervention implemented at our hospital in order to increase the quality of PAP. METHODS PAP was monitored using a form prepared in line with the international guidelines, which was completed by the infection control nurse under the supervision of the infectious diseases specialist. In order to reduce the frequent errors in our PAP procedures, an intervention was implemented, and the period before this intervention (January-April 2011) was compared with the post-intervention period 1 year later (January-April 2012). The density of PAP was calculated according to the Anatomical Therapeutic Chemical classification/defined daily dose (ATC/DDD) methodology. RESULTS A total of 2398 patients received PAP during this period. The most frequently used antibiotic before and after the intervention was cefazolin. Its use further increased after the intervention (p<0.001). After the intervention, the ratio of the correct timing of the first antibiotic dose increased from 91.7% to 99.0% (p<0.001), while the excessively long administration of PAP was reduced from 77.0% to 44.7% (p<0.001). The ratio of full compliance with the guidelines increased from 15.5% to 40.2% (p<0.001) and the rate of surgical site infections dropped from 18.5% to 12.0%. The density of antibiotic use dropped from 305.7 DDD/100 procedures=3.1 DDD/procedure to 162.1 DDD/100 procedures=1.6 DDD/procedure. CONCLUSION The quality of PAP may be improved through better compliance with healthcare guidelines, close supervision, and training activities. Also, surgical site infections and the cost of PAP may be reduced through more appropriate antibiotic use, thus contributing to the national healthcare budget.

Comparison of brucellar and tuberculous spondylodiscitis patients: results of the multicenter "Backbone-1 Study".

BACKGROUND CONTEXT No direct comparison between brucellar spondylodiscitis (BSD) and tuberculous spondylodiscitis (TSD) exists in the literature. PURPOSE This study aimed to compare directly the clinical features, laboratory and radiological aspects, treatment, and outcome data of patients diagnosed as BSD and TSD. STUDY DESIGN A retrospective, multinational, and multicenter study was used. PATIENT SAMPLE A total of 641 (TSD, 314 and BSD, 327) spondylodiscitis patients from 35 different centers in four countries (Turkey, Egypt, Albania, and Greece) were included. OUTCOME MEASURES The pre- and peri- or post-treatment spinal deformity and neurologic deficit parameters, and mortality were carried out. METHODS Brucellar spondylodiscitis and TSD groups were compared for demographics, clinical, laboratory, radiological, surgical interventions, treatment, and outcome data. The Student t test and Mann-Whitney U test were used for group comparisons. Significance was analyzed as two sided and inferred at 0.05 levels. RESULTS The median baseline laboratory parameters including white blood cell count, C-reactive protein, and erythrocyte sedimentation rate were higher in TSD than BSD (p<.0001). Prevertebral, paravertebral, epidural, and psoas abscess formations along with loss of vertebral corpus height and calcification were significantly more frequent in TSD compared with BSD (p<.01). Surgical interventions and percutaneous sampling or abscess drainage were applied more frequently in TSD (p<.0001). Spinal complications including gibbus deformity, kyphosis, and scoliosis, and the number of spinal neurologic deficits, including loss of sensation, motor weakness, and paralysis were significantly higher in the TSD group (p<.05). Mortality rate was 2.22% (7 patients) in TSD, and it was 0.61% (2 patients) in the BSD group (p=.1). CONCLUSIONS The results of this study show that TSD is a more suppurative disease with abscess formation requiring surgical intervention and characterized with spinal complications. We propose that using a constellation of constitutional symptoms (fever, back pain, and weight loss), pulmonary involvement, high inflammatory markers, and radiological findings will help to differentiate between TSD and BSD at an early stage before microbiological results are available.