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This WHO report produced in collaboration withMember States and other partners provides as accuratea picture as is presently possible of the magnitude ofAMR and the current state of surveillance globally.The report focuses on antibacterial resistance (ABR)in common bacterial pathogens. Why? There is amajor gap in knowledge about the magnitude of thisproblem and such information is needed to guideurgent public health actions. ABR is complex andmultidimensional. It involves a range of resistancemechanisms affecting an ever-widening range ofbacteria most of which can cause a wide spectrumof diseases in humans and animals. One important finding of the report which will serveas a baseline to measure future progress is that thereare many gaps in information on pathogens of majorpublic health importance. In addition surveillance ofABR generally is neither coordinated nor harmonized compromising the quality and representativeness ofmany data. Nonetheless the report makes a clear case thatresistance to common bacteria has reached alarminglevels in many parts of the world suggesting thatmany of the available treatment options for commoninfections in some settings are becoming ineffective.Furthermore systematic reviews of the scientificevidence show that ABR has a negative impact onoutcomes for patients and health-care expenditures.Generally surveillance in TB malaria and HIV to detectresistance determine disease burden and monitorpublic health interventions is better established andexperiences from these programmes are describedin the report so that lessons learnt can be appliedto ABR and opportunities for collaboration identified.

Plant antimicrobial peptides (AMPs) are a component of barrier defense system of plants. They have been isolated from roots, seeds, flowers, stems, and leaves of a wide variety of species and have activities towards phytopathogens, as well as against bacteria pathogenic to humans. Thus, plant AMPs are considered as promising antibiotic compounds with important biotechnological applications. Plant AMPs are grouped into several families and share general features such as positive charge, the presence of disulfide bonds (which stabilize the structure), and the mechanism of action targeting outer membrane structures.

Solidago species are often used in traditional medicine as anti-inflammatory, diuretic, wound-healing and antimicrobial agents. Still, the bioactive compounds and biological activities of some species have not been studied. The present work aimed to investigate the polyphenolic profile and the biological properties of Solidago graminifolia L. Salisb., a poorly explored medicinal plant. The hydroalcoholic extracts from aerial parts were evaluated for total phenolic content (TPC), total flavonoid content (TFC) and the polyphenolic compounds were investigated by HPLC-MS. The antioxidant potential in vitro was determined using DPPH and FRAP assays. Antibacterial and antifungal effects were evaluated by dilution assays and MIC, MBC and MFC were calculated. The results showed that Solidago graminifolia aerial parts contain an important amount of total phenolics (192.69 mg GAE/g) and flavonoids (151.41 mg RE/g), with chlorogenic acid and quercitrin as major constituents. The hydroalcoholic extracts showed promising antioxidant and antimicrobial potential, with potent antibacterial activity against Staphylococcus aureus and important antifungal effect against Candida albicans and C. parapsilosis. The obtained results indicated that the aerial parts of Solidago graminifolia could be used as novel resource of phytochemicals in herbal preparations with antioxidant and antimicrobial activities.

Background Antimicrobial peptides are a promising alternative for combating pathogens resistant to conventional antibiotics. Computer-assisted peptide discovery strategies are necessary to automatically assess a significant amount of data by generating models that efficiently classify what an antimicrobial peptide is, before its evaluation in the wet lab. Model’s performance depends on the selection of molecular descriptors for which an efficient and effective approach has recently been proposed. Unfortunately, how to adapt this method to the selection of molecular descriptors for the classification of antimicrobial peptides and the performance it can achieve, have only preliminary been explored. Results We propose an adaptation of this successful feature selection approach for the weighting of molecular descriptors and assess its performance. The evaluation is conducted on six high-quality benchmark datasets that have previously been used for the empirical evaluation of state-of-art antimicrobial prediction tools in an unbiased manner. The results indicate that our approach substantially reduces the number of required molecular descriptors, improving, at the same time, the performance of classification with respect to using all molecular descriptors. Our models also outperform state-of-art prediction tools for the classification of antimicrobial and antibacterial peptides. Conclusions The proposed methodology is an efficient approach for the development of models to classify antimicrobial peptides. Particularly in the generation of models for discrimination against a specific antimicrobial activity, such as antibacterial. One of our future directions is aimed at using the obtained classifier to search for antimicrobial peptides in various transcriptomes.

Microorganisms including actinomycetes, archaea, bacteria, fungi, yeast, and microalgae are an auspicious source of vital bioactive compounds. In this review, the existing research regarding antimicrobial molecules from microorganisms is summarized. The potential antimicrobial compounds from actinomycetes, particularly Streptomyces spp.; archaea; fungi including endophytic, filamentous, and marine-derived fungi, mushroom; and microalgae are briefly described. Furthermore, this review briefly summarizes bacteriocins, halocins, sulfolobicin, etc., that target multiple-drug resistant pathogens and considers next-generation antibiotics. This review highlights the possibility of using microorganisms as an antimicrobial resource for biotechnological, nutraceutical, and pharmaceutical applications. However, more investigations are required to isolate, separate, purify, and characterize these bioactive compounds and transfer these primary drugs into clinically approved antibiotics.

Antimicrobial resistance is a growing global health concern. Antimicrobial stewardship (AMS) curbs resistance rates by encouraging rational antimicrobial use. However, data on antimicrobial stewardship in developing countries is scarce. The objective of this study was to characterize antimicrobial use at the University Teaching Hospital (UTH) in Lusaka, Zambia as a guiding step in the development of an AMS program. This was a cross-sectional, observational study evaluating antimicrobial appropriateness and consumption in non-critically ill adult medicine patients admitted to UTH. Appropriateness was defined as a composite measure based upon daily chart review. Sixty percent (88/146) of all adult patients admitted to the general wards had at least one antimicrobial ordered and were included in this study. The most commonly treated infectious diseases were tuberculosis, pneumonia, and septicemia. Treatment of drug sensitive tuberculosis is standardized in a four-drug combination pill of rifampicin, isoniazid, pyrazinamide and ethambutol, therefore appropriateness of therapy was not further evaluated. The most common antimicrobials ordered were cefotaxime (n = 45), ceftriaxone (n = 28), and metronidazole (n = 14). Overall, 67% of antimicrobial orders were inappropriately prescribed to some extent, largely driven by incorrect dose or frequency in patients with renal dysfunction. Antimicrobial prescribing among hospitalized patients at UTH is common and there is room for optimization of a majority of antimicrobial orders. Availability of certain antimicrobials must be taken into consideration during AMS program development.

Background Meningitis remains a top cause of premature death and loss of disability-adjusted life years in low-income countries. In resource-limited settings, proper laboratory diagnostics are often scarce and knowledge about national and local epidemiology is limited. Misdiagnosis, incorrect treatment and overuse of antibiotics are potential consequences, especially for viral meningitis. Methods A prospective study was conducted over three months in a teaching hospital in Ethiopia with limited laboratory resources. Cerebrospinal fluid (CSF) samples from patients with suspected meningitis were analysed using a multiplex PCR-based system (FilmArray, BioFire), in addition to basic routine testing with microscopy and culture. Clinical data, as well as information on treatment and outcome were collected. Results Two hundred and eighteen patients were included; 117 (54%) neonates (0–29 days), 63 (29%) paediatrics (1 month-15 years) and 38 (17%) adults (≥16 years). Of 218 CSF samples, 21 (10%) were PCR positive; 4% in neonates, 14% in paediatrics and 18% in adults. Virus was detected in 57% of the PCR positive samples, bacteria in 33% and fungi in 10%. All CSF samples that were PCR positive for a bacterial agent had a white cell count ≥75 cells/mm 3 and/or turbid appearance. The majority (90%) of patients received more than one antibiotic for treatment of the meningitis episode. There was no difference in the mean number of different antibiotics received or in the cumulative number of days with antibiotic treatment between patients with a microorganism detected in CSF and those without. Conclusions A rapid molecular diagnostic system was successfully implemented in an Ethiopian setting without previous experience of molecular diagnostics. Viral meningitis was diagnosed for the first time in routine clinical practice in Ethiopia, and viral agents were the most commonly detected microorganisms in CSF. This study illustrates the potential of rapid diagnostic tests for reducing antibiotic usage in suspected meningitis cases. However, the cost of consumables for the molecular diagnostic system used in this study limits its use in low-income countries.

Osteomyelitis is a common occurrence in orthopaedic surgery, which is caused by different bacteria. Treatment of osteomyelitis patients aims to eradicate infection by debridement surgery and local and systemic antibiotic therapy. Local treatment increases success rates and can be performed with different antimicrobial bone graft substitutes. This review is performed to assess the level of evidence of synthetic bone graft substitutes in osteomyelitis treatment. According to the PRISMA statement for reporting systematic reviews, different types of clinical studies concerning treatment of osteomyelitis with bone graft substitutes are included. These studies are assessed on their methodological quality as level of evidence and bias and their clinical outcomes as eradication of infection. In the fifteen included studies, the levels of evidence were weak and in ten out of the fifteen studies there was a moderate to high risk of bias. However, first results of the eradication of infection in these studies showed promising results with their relatively high success rates and low complication rates. Due to the low levels of evidence and high risks of bias of the included studies, these results are inconclusive and no conclusions regarding the performed clinical studies of osteomyelitis treatment with antimicrobial bone graft substitutes can be drawn.

Antimicrobial peptides are small, cationic, amphiphilic peptides of 12-50 amino acids with microbicidal activity against both bacteria and fungi. The eukaryotic antimicrobial peptides may be divided into four distinct groups according to their structural features: cysteine-free alpha-helices, extended cysteine-free alpha-helices with a predominance of one or two amino acids, loop structures with one intramolecular disulfide bond, and beta-sheet structures which are stabilised by two or three intramolecular disulfide bonds. Mammalian defensins are part of the last-mentioned group. The mammalian defensins can be subdivided into three main classes according to their structural differences: the alpha-defensins, beta-defensins and the recently described theta-defensins. Mammalian alpha-defensins are predominantly found in neutrophils and in small intestinal Paneth cells, whereas mammalian beta-defensins have been isolated from both leukocytes and epithelial cells. Recently, two novel human beta-defensins, human beta-defensin-3 (HBD-3), and human beta-defensin-4 (HBD-4) have been discovered. Similar to HBD-1 and HBD-2, HBD-3 has microbicidal activity towards the Gram-negative bacteria (Pseudomonas aeruginosa, Escherichia coli) and the yeasts Candida albicans and Malassezia furfur. In addition, HBD-3 kills Gram-positive bacteria such as Streptococcus pyogenes or Staphylococcus aureus, including multi-resistant S. aureus strains, and even vancomycin-resistant Enterococcus faecium. In contrast to HBD-1 and HBD-2, significant expression of HBD-3 has been demonstrated in non-epithelial tissues, such as leukocytes, heart and skeletal muscle. HBD-4 is expressed in certain epithelia and in neutrophils. Its bactericidal activity against P. aeruginosa is stronger than that of the other known beta-defensins. Here we present an overview of human antimicrobial peptides with some emphasis on their antifungal properties.

To evaluate the long-term outcomes of an antimicrobial stewardship program (ASP) implemented in a hospital with low baseline antibiotic use. Quasi-experimental, interrupted time-series study. Public safety net hospital with 525 beds. Implementation of a formal ASP in July 2008. We conducted a time-series analysis to evaluate the impact of the ASP over a 6.25-year period (July 1, 2008-September 30, 2014) while controlling for trends during a 3-year preintervention period (July 1, 2005-June 30, 2008). The primary outcome measures were total antibacterial and antipseudomonal use in days of therapy (DOT) per 1,000 patient-days (PD). Secondary outcomes included antimicrobial costs and resistance, hospital-onset Clostridium difficile infection, and other patient-centered measures. During the preintervention period, total antibacterial and antipseudomonal use were declining (-9.2 and -5.5 DOT/1,000 PD per quarter, respectively). During the stewardship period, both continued to decline, although at lower rates (-3.7 and -2.2 DOT/1,000 PD, respectively), resulting in a slope change of 5.5 DOT/1,000 PD per quarter for total antibacterial use (P=.10) and 3.3 DOT/1,000 PD per quarter for antipseudomonal use (P=.01). Antibiotic expenditures declined markedly during the stewardship period (-$295.42/1,000 PD per quarter, P=.002). There were variable changes in antimicrobial resistance and few apparent changes in C. difficile infection and other patient-centered outcomes. In a hospital with low baseline antibiotic use, implementation of an ASP was associated with sustained reductions in total antibacterial and antipseudomonal use and declining antibiotic expenditures. Common ASP outcome measures have limitations.