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Background Antibiotic use is associated with collateral damage to the healthy microbiota. Afabicin is a first-in-class prodrug inhibitor of the FabI enzyme that, when converted to the pharmacologically active agent afabicin desphosphono, demonstrates a staphylococcal-specific spectrum of activity. An expected benefit of highly targeted antibiotics such as afabicin is microbiome preservation. Objectives To compare the effects of oral treatment with afabicin and standard-of-care antibiotics upon the murine gut microbiota, and to assess the effects of oral afabicin treatment on the human gut microbiota. Methods Gut microbiota effects of a 10 day oral course of afabicin treatment were monitored in mice and compared with clindamycin, linezolid and moxifloxacin at human-equivalent dose levels using 16S rDNA sequencing. Further, the gut microbiota of healthy volunteers was longitudinally assessed across 20 days of oral treatment with afabicin 240 mg twice daily. Results Afabicin treatment did not significantly alter gut microbiota diversity (Shannon H index) or richness (rarefied Chao1) in mice. Only limited changes to taxonomic abundances were observed in afabicin-treated animals. In contrast, clindamycin, linezolid and moxifloxacin each caused extensive dysbiosis in the murine model. In humans, afabicin treatment was not associated with alterations in Shannon H or rarefied Chao1 indices, nor relative taxonomic abundances, supporting the findings from the animal model. Conclusions Oral treatment with afabicin is associated with preservation of the gut microbiota in mice and healthy subjects. [ABSTRACT FROM AUTHOR]

Sera from patients with chronic hepatitis C were examined for the presence of GBV-C/HGV RNA by RT-PCR. The amplified products, derived from the 5' non-coding, NS3, and NS5a regions, were detected in 19 (19%) of the 100 HCV RNA-positive samples. Analysis of GBV-C/HGV prevalence rates revealed that dual infections are related to shared parenteral risk factors. Intravenous drug abuse and multiple transfusions were the factors clearly associated with a simultaneous HCV and GBV-C/HGV infection. Apart from this, patients with dual infections had a statistically significant lower mean age compared to those patients infected solely by HCV. Determination of HCV genotypes involved in GBV-C/HGV coinfection by RFLP analysis showed no correlation between the presence of GBV-C/HGV and a distinct HCV genotype. The study demonstrates that, based on the assessment of risk criteria, GBV-C/HGV is transmitted efficiently parenterally and is frequently linked to hepatitis C coinfection, regardless of HCV genotype.

The objective of this study was to characterize the immune response of children after the use of two different vaccine doses and to evaluate whether vaccination benefits children attending day care centers in areas with high anti-HAV seroprevalence. The study was conducted in a day care center with a stable population in São Paulo, Brazil. Two groups of 20 children, all seronegative for hepatitis A antibodies, were assigned randomly to receive three times 0.5 and 1.0 ml of the vaccine, the second and third dose 1 and 6 months after the first dose, respectively. There were 27 children in the control group. All children in both vaccinated groups had protective levels of antibodies in the serum after two inoculations, and serious adverse reactions were not observed. In the eighth month of follow-up, a hepatitis A outbreak occurred in the day care center. Five children in the control group had high titers of IgM class anti-HAV, four with clinical manifestations of acute hepatitis. None of the vaccinated children developed symptoms or signs of hepatitis (P = 0.0125), and the estimate of vaccine efficacy was 100%. Two nonstudy children from the center also had clinical and serological evidence of acute hepatitis A. It is concluded that vaccination represents an important method for prevention of hepatitis A transmission in day care centers. The results of this pilot study justify further testing in larger groups.

The relationship of hepatitis A virus (HAV) isolates associated with an outbreak in Genoa, Italy, in 1993 was examined using direct sequencing of amplicons derived by antigen capture PCR (AC/PCR) from faecal samples of the infected persons. Forty samples recovered from 38 primary and two secondary cases were examined. The latter were household contacts of the primary cases. In addition, faecal material of 2 unrelated persons infected simultaneously with hepatitis A in Genoa were tested. The PCR products derived from the P1/P2 junction of the HAV genome were analysed. A 100% nucleotide identity was detected between the viral isolates originating from the primary as well as the secondary cases. The viral isolates recovered from the faecal samples of the two unrelated cases differed from the virus causing the outbreak as well as from each other. These results indicate that a single HAV strain caused the outbreak. The virus might have been transmitted by ingestion of contaminated food or water since all hepatitis A infected employees of the factory had eaten in the same canteen. Definitions of HAV genotypes are based on numerous genetic comparisons of different strains. The sequence comparison of the investigated isolates with published HAV sequences of the P1/P2 genome region revealed that the virus associated with the outbreak belongs to HAV subgenotype IA, whereas the strains recovered from the viral isolates of the unrelated cases belong to subgenotype IB.