Empirical metronidazole for patients with severe bacterial infection: protocol for a systematic review.

INTRODUCTION: Anaerobic bacteria are believed to be common pathogens in severe infections. Yet, they are difficult to culture and consequently often unrecognised in clinical infections. Metronidazole is often used empirically for potential anaerobic infections, as the resistance to metronidazole is low. However, disadvantages of metronidazole use exist, including drug interactions, side effects and economical expenses. Currently, the balance between the benefits and harms of empirical metronidazole for severe bacterial infections is unknown. We aim to assess patient-important benefits and harms of empirical metronidazole vs. placebo or no treatment in adult patients with severe bacterial infection of any origin in a systematic review of randomised clinical trials with meta-analysis and trial sequential analysis. METHODS AND ANALYSIS: This protocol provides details on the planned systematic review, which will be prepared according to the Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA) statement, the Cochrane Handbook, and the Grading of Recommendations, Assessment, Development and Evaluation (GRADE) criteria. The primary outcome is all-cause mortality. Secondary outcomes include adverse events, secondary infections, use of life support, antibiotic resistance and hospital length of stay. We will conduct conventional meta-analyses, including predefined subgroup- and sensitivity analyses. Additionally, we will assess the risk of random errors by trial sequential analysis. ETHICS AND DISSEMINATION: Ethical approval is not needed, as the outlined review exclusively will include previously published data. We aim to publish in an international, peer-reviewed journal.

Untargeted antifungal therapy in adult patients with complicated intra-abdominal infection: a systematic review.

BACKGROUND: Systematic reviews comparing untargeted antifungal treatment with placebo or no treatment in critically ill patients have provided conflicting results. We aimed to assess patient-important benefits and harms of untargeted antifungal therapy vs. placebo or no treatment in adult patients with complicated intra-abdominal infection. METHODS: We conducted a systematic review with meta-analysis and trial sequential analysis of randomised clinical trials assessing untargeted antifungal therapy compared to placebo or no treatment in adults with complicated intra-abdominal infection. We used the Cochrane and GRADE methodologies and exclusively assessed patient-important outcomes. Two independent authors screened trials for eligibility, extracted data and assessed risk of bias. We performed conventional meta-analyses, including sensitivity and subgroup analyses, and trial sequential analysis to assess the risk of random errors and to estimate trial sequential analysis adjusted confidence intervals. RESULTS: We included six trials (1,067 patients) in the review, and four trials reported data on the predefined outcome measures and were included in the meta-analysis. Three of the four trials had high risk of bias. We observed no statistically significant difference in mortality (relative risk 0.58, 95% confidence interval 0.24-1.39) or in any of the other patient-important outcomes between untargeted antifungal treatment and placebo or no treatment (low/very low quality of evidence). Trial sequential analysis demonstrated lack of data and high risk of random errors. CONCLUSIONS: The quantity and quality of evidence supporting untargeted antifungal treatment in adult patients with complicated intra-abdominal infection are low to very low with no firm evidence for benefit or harm.

Tissue-specific and developmental regulation of cotton gene FbL2A. Demonstration of promoter activity in transgenic plants.

A gene (FbL2A) that is preferentially expressed in cotton (Gossypium barbadense L. cv Sea Island) fiber was isolated and characterized. Genomic and cDNA analyses suggest multiple FbL2A genes in cotton. The gene is developmentally regulated and is activated during late primary and early secondary wall synthesis stages. FbL2A encodes a polypeptide of 43.4 kD and a predicted isoelectric point of 5.97. The nucleotide-derived protein is highly hydrophilic except for a hydrophobic N terminus and has a compositional bias for glutamic acid (26.3 mol%) and lysine (18.9 mol%). Sixty-two percent of the putative protein is composed of repeat motifs. A 55-amino-acid peptide region is repeated four times in a concatenate fashion within the protein. The function of the protein in the fiber cells is not known. A 2.3-kb DNA fragment 5' from the FbL2A gene is shown to direct expression of heterologous proteins in transgenic cotton in a fiber-specific and developmentally regulated fashion. The FbL2A promoter was used to express in transgenic cotton genes encoding acetoacetyl-coenzyme A reductase and polyhydroxyalkanoic acid synthase, which are involved in the synthesis of the thermoplastic polymer polyhydroxybutyric acid. Transgenic plants containing both enzymes produced polyhydroxybutyric acid in fiber. Thus, the FbL2A promoter is useful in genetic engineering schemes to modify cotton fiber.

Cotton (Gossypium hirsutum L.) pollen-specific polygalacturonase mRNA: tissue and temporal specificity of its promoter in transgenic tobacco.

A gene (G9) expressed during late microsporogenesis in cotton (Gossypium hirsutum L.) was isolated. Sequence analysis of the cDNA (1.3 kb) as well as the gene (2.6 kb) revealed an open reading frame of 1233 bases encoding a protein of 43.9 kDa. The coding region of the gene is interrupted by three introns. Northern analysis of the RNA from developing anthers showed that the transcripts appear 12 days before anthesis and that the maximal concentration of RNA occurs in pollen on the day of anthesis. This pattern of gene expression suggests functions in post-anthesis events. Sequence comparisons with other known plant genes indicated that G9 is homologous to polygalacturonases. The G9 promoter conferred tissue and temporal specificity of beta-glucuronidase (GUS) expression in transgenic tobacco plants. Thus, the G9 promoter can be used to drive gene expression in homologous as well as heterologous plants in a tissue-specific manner.