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In recent years a revolution in hepatitis C virus drug development has taken place from troublesome regimens with pegylated interferon-alfa for 24 to 48 weeks with limited success to all-oral single tablet regimens taken for 12 weeks with very high chances of success. These promising results are not available to everybody. Depending on, for example, geographical factors with limited availability of new compounds, virus factors like hepatitis C virus genotype and host factors like presence of cirrhosis, these favorable outcomes can be compromised. This review discusses the recent clinical trials (from phase 3 registration through real-world application), highlighting the different available regimens and their success rates. [ABSTRACT FROM AUTHOR]

To investigate whether antibiotic treatment of 6 days' duration is non-inferior to treatment for 12 days in patients hospitalized for cellulitis. This multicentre, randomized, double-blind, placebo-controlled, non-inferiority trial enrolled adult patients hospitalized for severe cellulitis who were treated with intravenous flucloxacillin. At day 6 participants with symptom improvement who were afebrile were randomized between an additional 6 days of oral flucloxacillin or placebo in a 1:1 ratio, stratified for diabetes and hospital. The primary outcome was cure by day 14, without relapse by day 28. Secondary outcomes included a modified cure assessment and relapse rate by day 90. Between August 2014 and June 2017, 151 of 248 included participants were randomized. The intention-to-treat population consisted of 76 and 73 participants allocated to 12 and 6 days of antibiotic therapy, respectively (mean age 62 years, 67% males, 24% diabetics); 38/76 (50.0%) and 36/73 (49.3%) were cured in the 12- and 6-day groups respectively (ARR 0.7 percentage points, 95%CI: –15.0 to 16.3). Cure rates were 56/76 (73.7%) and 49/73 (67.1%) with the modified cure assessment (ARR 6.6, 95%CI: –8.0 to 20.8). After initial cure without relapse, day 90 relapse rates were higher in the 6-day group (6% versus 24%, p < 0.05). Given the wide confidence intervals, we can neither confirm nor refute our hypothesis that 6 days of therapy is non-inferior to 12 days of therapy. However, a 6-day course resulted in significantly more frequent relapses by day 90. These findings require confirmation in future studies. [ABSTRACT FROM AUTHOR]

Chronic infection with Coxiella burnetii (chronic Q fever) can cause life-threatening conditions such as endocarditis, infected vascular prostheses, and infected arterial aneurysms. We aimed to assess prognosis of chronic Q fever patients in terms of complications and mortality. A large cohort of chronic Q fever patients was assessed to describe complications, overall mortality and chronic Q fever-related mortality. Chronic Q fever-related mortality was expressed as a case fatality rate (number of chronic Q fever-related deaths/number of chronic Q fever patients). Complications occurred in 166 of 439 (38%) chronic Q fever patients: in 61% of proven (153/249), 15% of probable (11/74), and 2% of possible chronic Q fever patients (2/116). Most frequently observed complications were acute aneurysms (14%), heart failure (13%), and non-cardiac abscesses (10%). Overall mortality was 38% (94/249) for proven chronic Q fever patients (median follow-up 3.6 years) and 22% (16/74) for probable chronic Q fever patients (median follow-up 4.7 years). The case fatality rate was 25% for proven (63/249) chronic Q fever patients and 4% for probable (3/74) chronic Q fever patients. Overall survival was significantly lower in patients with complications, compared to those without complications (p <0.001). In chronic Q fever patients, complications occur frequently and contribute to the mortality rate. Patients with proven chronic Q fever have the highest risk of complications and chronic Q fever-related mortality. Prognosis for patients with possible chronic Q fever is favourable in terms of complications and mortality. [ABSTRACT FROM AUTHOR]

Background HIV-associated neurocognitive disorders (HAND) are frequently occurring comorbidities in HIV-positive patients, diagnosed by means of a neuropsychological assessment (NPA). Due to the magnitude of the HIV-positive population in Sub-Saharan Africa, easy-to-use cognitive screening tools are essential. Methods This was a cross-sectional clinical trial involving 44 HIV-positive patients (on stable cART) and 73 HIV-negative controls completing an NPA, the International HIV Dementia Scale (IHDS), and a culturally appropriate cognitive screening tool, the Montreal Cognitive Assessment–Basic (MoCA-B). HAND were diagnosed by calculating Z -scores using internationally published normative data on NPA, as well as by using data from the HIV-negative group to validate the MoCA-B. Results One hundred and seventeen patients were included (25% male, median age 35 years, median 11 years of education). A moderate correlation was found between the MoCA-B and NPA total Z -score (Pearson’s r = 0.36, p = 0.02). Area under the curve (AUC) values for MoCA-B and IHDS were 0.59 and 0.70, respectively. The prevalence of HAND in HIV-positive patients was 66% when calculating Z -scores using published normative data versus 48% when using the data from the present HIV-negative cohort. Conclusion The MoCA-B appeared not to be a valid screening tool for HAND in this setting. The prevalence of HAND in this setting is high, but appeared overestimated when using published norms. [ABSTRACT FROM AUTHOR]

Summary Background Some studies done in Asian patients have shown that serum levels of hepatitis B virus (HBV) DNA predict the development of cirrhosis. However, it is unclear whether this also applies for non-Asian patients. This study investigated historic and current HBV DNA and quantitative hepatitis B surface antigen (HBsAg) levels as predictors of cirrhosis in non-Asian women with chronic HBV. Methods A retrospective cohort study of non-Asian women with chronic HBV was performed. Among other variables, HBV DNA and quantitative HBsAg levels were measured in stored historic serum samples obtained during pregnancy (period 1990–2004) and current serum samples (period 2011–2012) to determine any association with liver cirrhosis by liver stiffness measurement (LSM). Results One hundred and nineteen asymptomatic, treatment-naïve non-Asian women were included; the median number of years between the historic sample and the current sample was 17 (interquartile range (IQR) 13–20). The median historic log HBV DNA and quantitative log HBsAg levels were 2.5 (IQR 1.9–3.4) IU/ml and 4.2 (IQR 3.6–4.5) IU/ml, respectively. LSM diagnosed 14 patients (12%) with F3–F4 fibrosis, i.e. stiffness >8.1 kPa. No association of cirrhosis was found with historic HBV DNA (relative risk (RR) 0.34, 95% confidence interval (CI) 0.05–2.44) or with the quantitative HBsAg level (HBsAg level >1000 IU/ml, RR 0.35, 95% CI 0.11–1.11). Multivariable analysis identified alcohol consumption (odds ratio (OR) 6.4, 95% CI 1.3–30.1), aspartate aminotransferase >0.5 times the upper limit of normal (OR 15.4, 95% CI 1.9–122.6), and prothrombin time (OR 12.0, 95% CI 1.2–120.4), but not HBV DNA or quantitative HBsAg level, to be independent predictors of the presence of cirrhosis. Conclusions Neither historic nor current HBV DNA or the quantitative HBsAg level is associated with the development of HBV-related cirrhosis in non-Asian women. [ABSTRACT FROM AUTHOR]

Abstract: Hepatitis E virus (HEV) genotype 3 is the most recently characterized hepatotropic virus and is increasingly being recognized as the cause of unexplained liver disease in many western countries. Although asymptomatic in most cases, HEV GT3 may be responsible for a wide range of illnesses, from mild to fulminant acute hepatitis, and also chronic hepatitis in immunocompromised patients. Extrahepatic manifestations have been occasionally described. Anti-HEV antibody detection by immunoassays is hampered by moderate test accuracy particularly in immunocompromised hosts while a WHO international standard for molecular detection of HEV RNA by RT-PCR has recently been introduced. This review describes the basic virology, epidemiology, clinical virology and treatment of HEV GT3 infections in high income countries. [Copyright &y& Elsevier]

Summary: Background: The worldwide increasing resistance to antibiotics has complicated antimicrobial treatment of urinary tract infections (UTIs), especially in Latin America. This study aimed to report the present etiology and antimicrobial susceptibility of UTIs, and the effects of the national guidelines for UTIs introduced in 2003. Methods: Urine samples were collected from 304 patients with a clinical suspicion of UTI at the university hospital and primary health centers of León, Nicaragua. When bacterial growth was reported, antimicrobial susceptibility tests for nine frequently used antibiotics were performed. Results: Ninety-one (29.9%) patients had a positive urine culture. The most frequently isolated microorganisms were Escherichia coli (n =44), Serratia spp (n =11), and Escherichia fergusonii (n =10). High resistance rates were observed in E. coli to ampicillin (61.4%), cefalothin (45.5%), trimethoprim–sulfamethoxazole (38.6%), ciprofloxacin (31.8%), and ceftriaxone (20.5%). Amikacin and nitrofurantoin were the only drugs to which >90% of E. coli were susceptible. E. fergusonii and Serratia spp showed comparable high resistance patterns. Thirteen strains (29.5%) of E. coli were suspected to produce extended-spectrum beta-lactamase (ESBL). Conclusions: Resistance rates in community-acquired UTIs in Nicaragua are increasing. The introduction of therapeutic guidelines with ceftriaxone recommended for upper UTIs and nitrofurantoin for lower UTIs, has led to increasing resistance against both antibiotics. The emergence of ESBL-producing E. coli is worrisome, along with the appearance of Serratia spp in the population. [Copyright &y& Elsevier]

Summary: Background: In order to develop guidelines for the use of antimicrobial agents, it is necessary to obtain detailed information on the prevalence of infectious diseases and antibiotic usage. Methods: A retrospective study was conducted among outpatients with acute infections visiting the emergency department of the University Hospital of León, Nicaragua. Results: Over the course of one month, 2027 patients visited the emergency department. Seven hundred and thirty-two patients (36.1%) had an infection, with a total of 799 acute infections. The majority of patients (55.9%) were children. Respiratory tract infections (43.4%), urogenital infections (29.5%), and diarrhea or gastroenteritis of presumed infectious origin (8.8%) were the most frequent infections. Among respiratory tract infections, the most frequent diagnoses were community-acquired pneumonia (CAP; 31.4%), acute tonsillitis (28.2%), and the common cold (17.6%). CAP was treated with procaine benzylpenicillin in 70.6% of cases, whereas 84.0% of patients with acute tonsillitis were treated with a single dosage of benzathine benzylpenicillin intramuscularly. Among urogenital infections, the most frequent diagnosis was acute uncomplicated urinary tract infection (24.2%). Approximately a quarter of patients with uncomplicated urinary tract infections did not receive treatment according to the local guidelines. Of the patients with acute diarrhea, 27.1% were treated with antibiotics, while only a minority had leukocytes in Wright stain of the feces. Conclusions: In conclusion our study shows that the use of antimicrobial agents is not optimal. Antibiotics were prescribed too often and not according to the local guidelines. This will further exacerbate the resistance problem in Nicaragua. [Copyright &y& Elsevier]

Chronic Q fever is a persistent infection with the intracellular bacterium Coxiella burnetii. Development of chronic Q fever is associated with single nucleotide polymorphisms (SNPs) in genes encoding for pattern recognition receptors, for phagolysosomal pathway components and for matrix metalloproteinases (MMPs). We evaluated the association of SNPs in these innate-immunity and MMP genes with clinical outcomes. SNPs were selected from previous association studies and analysed in a cohort of patients with chronic Q fever. The primary outcome was all-cause mortality; secondary outcomes were therapy failure and chronic Q fever–related complications. Subdistribution hazard ratios (SHR) were calculated. Nineteen SNPs were analysed in 134 patients with proven and 29 with probable chronic Q fever. In multivariable analysis, none of the selected SNPs was associated with all-cause mortality. However, SNP rs3751143 located in P2RX7 appeared to be associated with therapy failure (SHR 2.42; 95% confidence interval, 1.16–5.05; p 0.02), which is in line with other reports, showing that a loss of function of the P2X7 receptor leads to inefficient killing of intracellular organisms. In addition, SNP rs7125062 located in MMP1, involved in the cleavage of extracellular matrix, was associated with fewer chronic Q fever–related complications such as acute aneurysms (SHR 0.49; 95% confidence interval, 0.29–0.83; p 0.008). A polymorphism in P2RX7, known to lead to loss of function of the receptor and inefficient killing of intracellular organisms, and a polymorphism in MMP1 were respectively associated with more therapy failures and fewer complications such as acute aneurysms in patients with chronic Q fever. [ABSTRACT FROM AUTHOR]

Summary: Background: The impact of Candida-colonized catheter tips in patients without candidemia is unclear. Methods: A retrospective study of patients with tip cultures positive for Candida was conducted over an 8-year period, to determine the outcomes in patients with Candida cultured from an intravascular catheter tip in the absence of preceding Candida-positive blood cultures. The primary outcome measure was definite candidemia. Secondary outcomes included possible candidemia and in-hospital mortality. A possible candidemia was defined as clinical signs and symptoms of invasive candidiasis without explanation other than a candidemia, but with negative blood cultures. Results: Sixty-eight cultures from 64 patients were included in the study. Definite candidemia developed in three cases (4%) and possible candidemia developed in five cases (7%). In-hospital mortality was significantly increased in patients with definite or possible candidemia (63% vs. 22%, p =0.028). Risk factors for the development of definite or possible candidemia were catheter time in situ >8 days (odds ratio (OR) 6.0, 95% confidence interval (CI) 1.1–32.9) and abdominal surgery (OR 6.0, 95% CI 1.1–32.4). Conclusions: Intravascular catheter tip colonization in patients without preceding blood cultures with Candida is associated with candidemia in from 4% of patients (definite candidemia) up to 12% of patients (definite and possible candidemia combined). Considering the adverse prognosis associated with delayed treatment of candidemia, preemptive treatment based on catheter tip cultures might outweigh the disadvantages of costs and side effects of antifungal therapy. [ABSTRACT FROM AUTHOR]