Iftihar Koksal

ABT-450, Ritonavir, Ombitasvir, and Dasabuvir Achieves 97% and 100% Sustained Virologic Response With or Without Ribavirin in Treatment-Experienced Patients With HCV Genotype 1b Infection

BACKGROUND & AIMS The interferon-free regimen of ABT-450 (a protease inhibitor), ritonavir, ombitasvir (an NS5A inhibitor), dasabuvir (a non-nucleoside polymerase inhibitor), and ribavirin has shown efficacy in patients with hepatitis C virus (HCV) genotype 1b infection-the most prevalent subgenotype worldwide. We evaluated whether ribavirin is necessary for ABT-450, ritonavir, ombitasvir, and dasabuvir to produce high rates of sustained virologic response (SVR) in these patients. METHODS We performed a multicenter, open-label, phase 3 trial of 179 patients with HCV genotype 1b infection, without cirrhosis, previously treated with peginterferon and ribavirin. Patients were assigned randomly (1:1) to groups given ABT-450, ritonavir, ombitasvir, and dasabuvir, with ribavirin (group 1) or without (group 2) for 12 weeks. The primary end point was SVR 12 weeks after treatment (SVR12). We assessed the noninferiority of this regimen to the rate of response reported (64%) for a similar population treated with telaprevir, peginterferon, and ribavirin. RESULTS Groups 1 and 2 each had high rates of SVR12, which were noninferior to the reported rate of response to the combination of telaprevir, peginterferon, and ribavirin (group 1: 96.6%; 95% confidence interval, 92.8%-100%; and group 2: 100%; 95% confidence interval, 95.9%-100%). The rate of response in group 2 was noninferior to that of group 1. No virologic failure occurred during the study. Two patients (1.1%) discontinued the study owing to adverse events, both in group 1. The most common adverse events in groups 1 and 2 were fatigue (31.9% vs 15.8%) and headache (24.2% vs 23.2%), respectively. Decreases in hemoglobin level to less than the lower limit of normal were more frequent in group 1 (42.0% vs 5.5% in group 2; P < .001), although only 2 patients had hemoglobin levels less than 10 g/dL. CONCLUSIONS The interferon-free regimen of ABT-450, ritonavir, ombitasvir, and dasabuvir, with or without ribavirin, produces a high rate of SVR12 in treatment-experienced patients with HCV genotype 1b infection. Both regimens are well tolerated, as shown by the low rate of discontinuations and generally mild adverse events. ClinicalTrials.gov number: NCT01674725.

Crimean-Congo hemorrhagic fever in Turkey.

Nineteen cases of suspected Crimean-Congo hemorrhagic fever reported from Turkey.

Risk Factors of Catheter-Related Bloodstream Infections in Parenteral Nutrition Catheterization

BACKGROUND Intravascular catheters are integral to the practice of modern medicine. Potential risk factors for catheter-related bloodstream infection (CRBSI) include underlying disease, method of catheter insertion, and duration and purpose of catheterization. The administration of parenteral nutrition (PN) through intravascular catheters increases CRBSI risks. The purpose of this study was to evaluate the risk factors of CRBSI in patients with PN administration. METHODS This study was conducted at the Karadeniz Technical University Hospital between October 2003 and November 2004. All the patients to whom PN was administered through intravascular catheters were prospectively monitored for the presence of CRBSI and risk factors. RESULTS During the study period, 111 intravascular catheters through which PN was administered were monitored for a total of 1646 catheter-days. CRBSI was determined in 31 cases, a CRBSI rate of 18.8 per 1,000 catheter-days. When risk factors affecting CRBSI were investigated using logistic regression, an increase in APACHE II score (OR, 1.10; 95% CI, 1.01-1.21; p = .012), prolongation of catheterization (OR, 1.08; 95% CI, 1.02-1.14; p = .004), catheterization in emergent conditions (OR, 5.45; 95% CI, 1.20-24.82; p = .016), and poor patient hygiene (OR, 4.38; 95% CI, 1.39-13.78; p = .019) were all determined to be independent risk factors. Proper implementation of hand hygiene and maximal barrier precautions during the insertion of catheters reduced CRBSI levels (OR, 0.28; 95% CI, 0.09-0.88; p = .003 and OR, 0.26; 95% CI, 0.08-0.93; p = .017, respectively). CONCLUSIONS It was concluded that the duration of catheterization should be shortened; that the intravascular catheter, which is inserted in urgent situations, should be removed as soon as possible; and that maximal sterile barrier precautions should be taken and due attention should be paid to hand hygiene.

The efficacy of ribavirin in the treatment of Crimean-Congo hemorrhagic fever in Eastern Black Sea region in Turkey

BACKGROUND The efficiency of ribavirin for treatment of Crimean-Congo hemorrhagic fever (CCHF) is unknown. In the literature, prospective randomized studies investigating the efficacy of ribavirin are not found. OBJECTIVES To investigate the efficacy of ribavirin in treatment of patients with CCHF. STUDY DESIGN In this prospective randomized cohort study 136 cases were included between June 2004 and August 2007. The diagnosis was confirmed in the CCHF reference laboratory of Refik Saydam National Hygiene Central Institute of the Turkish Ministry of Health. Patients either received ribavirin plus supportive treatment (Group A) (n=64) or only supportive treatment (Group B) (n=72). For the evaluation of efficacy of ribavirin, various parameters were compared between Group A and Group B. RESULTS As well as the similarity of demographic features between the two groups, there were no statistical differences in incubation time; hospitalization time; patients requiring platelet replacement therapy; the time taken for platelet levels to return to normal levels and mortality. In Group B, the rate of tick contact was higher (p=0.03). In Group A, leukocyte levels took longer to return to the normal levels (p=0.02). CONCLUSION In our study, there was no positive effect determined on clinical or laboratory parameters in CCHF patients treated with ribavirin, also it was observed that leukocyte levels took longer to return to normal (p=0.02) and, while not statistically significant, the longer period of hospitalization (p=0.09) needed was observed as a negative effect. Because of these reasons, it is thought that the use of ribavirin makes no significant contribution to the prognosis of the CCHF disease.

The diagnostic and prognostic significance of soluble urokinase plasminogen activator receptor in systemic inflammatory response syndrome.

OBJECTIVES This study was intended to investigate the value of suPAR, C-reactive protein (CRP) and procalcitonin (PCT) in the determination and prognosis of systemic inflammatory response syndrome (SIRS) patients. METHODS The study was performed among patients with at least two SIRS criteria. PCT, CRP and suPAR were analyzed from the blood specimens taken. RESULTS Eighty-five patients were enrolled in the SIRS group (44 bacteremia, 20 urinary tract infection, 12 pneumonia and 9 non-infection), and 53 individuals in the control group. A significant correlation was determined between suPAR, PCT and CRP values in both groups (P<0.0001). A suPAR cutoff value of 2.8ng/mL was associated with an NPV of 87% and PPV of 91%, with 92% sensitivity and 85% specificity. A relatively high suPAR level that might predict fatality was also determined in fatal cases (P=0.001). CONCLUSION suPAR possesses high sensitivity and specificity levels in terms of differential diagnosis, and high suPAR levels can predict fatality.

Case Management and Supportive Treatment for Patients with Crimean-Congo Hemorrhagic Fever

Crimean-Congo hemorrhagic fever (CCHF) is a tick-borne infection which has been increasing in Turkey and European countries since the year 2000. The disease is particularly endemic in the Middle East and in some African countries. It is also seen in European countries as a travel infection. Patients with confirmed diagnosis are usually hospitalized for monitoring, while patients with good overall condition may be monitored on an outpatient basis. Hospitals that manage CCHF should have easy access to a blood bank, and tertiary care hospitals must have a well-equipped intensive care unit. Strict blood and body fluid control precautions should be started on admission to limit CCHF exposure. The follow-up period for each patient is determined based on individual clinical status and laboratory values. Since there is no specific antiviral treatment for CCHF, supportive treatment is essential. This review highlights some of the major features of case monitoring and supportive treatment in CCHF.

The effectiveness of routine laboratory findings in determining disease severity in patients with Crimean-Congo hemorrhagic fever: Severity prediction criteria

BACKGROUND Crimean-Congo hemorrhagic fever (CCHF) is a potentially fatal disease caused by a tick-borne virus from the Bunyaviridae family. OBJECTIVES To determine the predictive criteria for severity among patients with CCHF based on clinical and laboratory findings. STUDY DESIGN This retrospective study was conducted on patients with CCHF and hospitalized between June 2004 and August 2008 at Karadeniz Technical University, Turkey. Demographic characteristics, clinical findings and laboratory tests on admission of all patients with CCHF were investigated. RESULTS A total of 152 patients with confirmed CCHF were investigated. Sixty-three (41.4%) of these patients were in the severe group. Laboratory findings using the ROC curve method and optimum diagnostic cut-off points for specific laboratory parameters in the severe group were; PLT: 90,000, Hb: 13.5 g/dL, PT: 13.1s, aPTT: 34 s, INR: 1, AST: 117U/L, ALT: 71U/L, AST/ALT: 1.62, LDH: 508 U/L, CK: 267 U/L and CRP: 0.59 mg/dL. At multivariable analysis, the risk for a severe clinical course in CCHF patients increased 2.59 and 3.93 times in the presence of platelet count and Hb below cut-off values, whereas the same risk increased 2.95, 2.92 and 3.47 times when the results for INR, AST and CRP, respectively, were above the predetermined cut-off values. CONCLUSIONS A number of laboratory findings that can easily be measured at routine examination of patients hospitalized with a suspicion of CCHF are valuable and sensitive predictors. These parameters will contribute considerably to the design, practice and management of supportive treatment, blood and blood products replacement and intensive care services.

Comparative activity of carbapenem testing: the COMPACT study

OBJECTIVES Doripenem is a new carbapenem recently introduced into Europe. The COMParative Activity of Carbapenem Testing (COMPACT) study compared the susceptibility of common Gram-negative bacilli causing serious infections in hospitalized patients with doripenem, imipenem and meropenem. METHODS Gram-negative isolates (4498 total: 2171 Pseudomonas species; 1910 Enterobacteriaceae; and 417 other Gram-negative bacilli) were collected from 80 centres in 16 countries in Europe, the Middle East and Africa during 2008-09. The MICs of doripenem, imipenem and meropenem were determined using Etest methodology and broth microdilution. Susceptibility was interpreted according to CLSI, EUCAST and FDA breakpoints. RESULTS The MIC(90)s of doripenem, imipenem and meropenem for all isolates were 8, ≥64 and 32 mg/L, respectively. Doripenem had the lowest MIC(90) for Pseudomonas species at 16 mg/L, with imipenem and meropenem values of ≥64 mg/L. Enterobacteriaceae were highly susceptible to all three carbapenems, with MIC(90)s of doripenem, imipenem and meropenem of 0.06, 0.5 and 0.12 mg/L, respectively. Other Gram-negative isolates, predominantly Acinetobacter baumannii, were resistant to all three carbapenems (MIC(90) ≥64 mg/L). Susceptibility to doripenem was observed in 14.9% of isolates resistant to imipenem and/or meropenem. CONCLUSIONS Doripenem showed excellent activity against Gram-negative isolates; generally it was more active than imipenem and at least as good as meropenem. Against Pseudomonas species, doripenem was more active than both imipenem and meropenem, with doripenem susceptibility observed for some imipenem- and/or meropenem-resistant isolates.

Impact of a multidimensional infection control approach on central line-associated bloodstream infections rates in adult intensive care units of 8 cities of Turkey: findings of the International Nosocomial Infection Control Consortium (INICC)

BackgroundCentral line-associated bloodstream infections (CLABs) have long been associated with excess lengths of stay, increased hospital costs and mortality attributable to them. Different studies from developed countries have shown that practice bundles reduce the incidence of CLAB in intensive care units. However, the impact of the bundle strategy has not been systematically analyzed in the adult intensive care unit (ICU) setting in developing countries, such as Turkey. The aim of this study is to analyze the impact of the International Nosocomial Infection Control Consortium (INICC) multidimensional infection control approach to reduce the rates of CLAB in 13 ICUs of 13 INICC member hospitals from 8 cities of Turkey.MethodsWe conducted active, prospective surveillance before-after study to determine CLAB rates in a cohort of 4,017 adults hospitalized in ICUs. We applied the definitions of the CDC/NHSN and INICC surveillance methods. The study was divided into baseline and intervention periods. During baseline, active outcome surveillance of CLAB rates was performed. During intervention, the INICC multidimensional approach for CLAB reduction was implemented and included the following measures: 1- bundle of infection control interventions, 2- education, 3- outcome surveillance, 4- process surveillance, 5- feedback of CLAB rates, and 6- performance feedback on infection control practices. CLAB rates obtained in baseline were compared with CLAB rates obtained during intervention.ResultsDuring baseline, 3,129 central line (CL) days were recorded, and during intervention, we recorded 23,463 CL-days. We used random effects Poisson regression to account for clustering of CLAB rates within hospital across time periods. The baseline CLAB rate was 22.7 per 1000 CL days, which was decreased during the intervention period to 12.0 CLABs per 1000 CL days (IRR 0.613; 95% CI 0.43 – 0.87; P 0.007). This amounted to a 39% reduction in the incidence rate of CLAB.ConclusionsThe implementation of multidimensional infection control approach was associated with a significant reduction in the CLAB rates in adult ICUs of Turkey, and thus should be widely implemented.

The diagnostic and prognostic significance of soluble urokinase plasminogen activator receptor in Crimean-Congo hemorrhagic fever

BACKGROUND Crimean-Congo hemorrhagic fever (CCHF) is a potentially fatal disease caused by a tick-borne virus from the Bunyaviridae family. It has recently been reported that soluble urokinase-type plasminogen activator receptor (suPAR), secreted from endothelial cells and the mononuclear phagocyte system, one of the main targets of the CCHF virus, is a potential biomarker for several bacterial and viral infection diseases. OBJECTIVES This study was intended to determine the diagnostic and prognostic significance of suPAR levels in CCHF. STUDY DESIGN This retrospective study was conducted between June 2006 and August 2009 using plasma from patients monitored with a diagnosis of CCHF and from healthy blood donors. Levels of plasma suPAR were determined using an enzyme-linked immunosorbent assay (ELISA) kit according to the manufacturers instructions. RESULTS One hundred CCHF patients were enrolled in the study. The control group was made up of 53 healthy blood donors. suPAR values of 6.2 ± 4.2 were determined in the CCHF patients and of 2.3 ± 0.6 in the control group (p<0.0001). A suPAR level optimum diagnostic cut-off point of 3.06 ng/mL was determined, with an area underneath the ROC (AUROC) curve of 0.94 (95% CI: 0.89-0.97), sensitivity of 87% (95% CI: 79-93%), specificity of 92% (95% CI: 82-98%), PPV of 95% and NPV of 79%. Five of the patients died. suPAR was 18.4 ± 9.1 in the patients that died and 5.6 ± 2.6 in the survivors (p=0.034). In terms of mortality, suPAR level had an optimum diagnostic cut-off point of 10.6 ng/mL, AUROC of 0.97 (95% CI: 0.94-0.99), sensitivity of 100% (95% CI: 48-100%), specificity of 96% (95% CI: 90-99%), PPV of 50% and NPV of 100%. CONCLUSIONS Plasma suPAR level, a new biomarker, is a test that can be used in the differential diagnosis and monitoring of CCHF in patients admitted to hospital with suspected infection. The test is at the same time important in being a possible predictor of mortality.