Multidrug-resistant gram-negative organisms: a review of recently approved antibiotics and novel pipeline agents.

Background The discovery of antibiotics several decades ago was a defining moment in history. They were used to treat previously incurable diseases and save many lives. However, the use of antibiotics is not benign. Antibiotic resistance occurs due to the natural evolution of bacteria and gene transfer between bacteria via vertical and horizontal routes, resulting in protective mechanisms that render antibacterial agents ineffective. Aim of the review To list and describe current, novel pipeline antibiotics indicated for multidrug-resistant gram-negative bacteria. This review discusses the limited number of novel pipeline drugs available to combat the rapidly increasing number of multidrug-resistant bacteria and the need for initiatives to research and discover more novel antibiotics. Method A search of MEDLINE/PubMed using the search terms antibacterial pipeline OR antibiotic pipeline including publications between 1 January 2018 through 23 January 2020 resulted in 230 items. The results obtained were narrowed by adding the search term AND multi-drug resistant which resulted in 12 items. Then, ClinicalTrials.gov was searched for phase 2-3 "interventional" trials registered between 1 January 2018 and 23 January 2020 with the status "recruiting" or "completed" function and including World Health Organization-defined priority pathogens in the "condition or disease" field. The search process was then completed by introducing the term antibacterial agents in the "other terms" field. The trials search and selection resulted in 13 items. Relevant English-language studies and those conducted in humans were considered. Those drugs belonging to new antibiotic classes or to antibiotic classes already known but with new chemical structure were defined as "novel antibiotics". Results The studies selected and reviewed were those referring to a novel antibiotics. Thus, from MEDLINE/PubMed, we found only 1 item referred to a novel chemical class (Murepavadin n = 1). From ClinicalTrials.gov a total of 4 citations were identified (Ftortiazinon n = 1, Zoliflodacin n = 1, Gepotidacin n = 1, ETX2514 + sulbactam n = 1). Conclusion The antibiotics annually approved by the Food and Drug Administration (FDA) mostly belong to existing classes of antibiotics and have specific indications, limiting their use in many multidrug-resistant infections. There are limited novel drug classes targeting gram-negative infections in the pipeline. Providers must be vigilant with the use of current antibiotics, especially until research and development (R&D) advancements are made.

[Blood and urine chromium: compared values between chromium exposed workers and common people]. / Cromemia e cromuria: valori a confronto tra soggetti professionalmente esposti al cromo e popolazione generale.

Aim of present study is the valutation and quantification of chromium in blood and urine. We compared 3 groups of persons formed by building workers, in particular masons, because cement contains potassium chromate that is dangerous for health, and by common people: urban population and outside the town population. In fact, exposure to CrVI risk is high for people who live near chromate industries. We maked a medical examination, blood and instrumental tests, chromium measuring in blood (recent exposure indicator) and urine (recent and previous indicator). Then we used statistical methods to estimate obtained values of blood and urine chromium among professional exposed people and common people. At the end we think that preventive measures in working environment reduced exposure to CrVI but environmental exposure (for example road dust from catalytic converter erosion, from brake lining erosion, cement dust and tobacco smoke), in the last years, has increased. So there are no difference between urban population and outside the town population and there are also no difference with professional exposed people for work prevention according to law in force, that let down professional risk using safe limits.

[Observational study on a group of health care workers assigned to antiblastic drugs manipulation in three Sicilian hospitals]. / Studio osservazionale su un gruppo di operatori sanitari addetti alla manipolazione di farmaci antiblastici di tre nosocomi siciliani.

UNLABELLED: Neoplastic disease therapy problems, e.g. antiblastic drugs manipulation, is developing. We suggested correlation assessment between the lasting professional workers' exposition of three city hospital and disease development. We selected 43 exposed workers; we gave a questionnaire regarding the modality of activity; then we examined this sample with a protocol including clinical examination and special tests (blood tests, ECG, audiometry and spirometry). RESULTS: over 55% of the workers reported aspecific complaint related to antiblastic exposure (headache, nausea, vertigo, dermatitis, alopecia, rhino-conjunctivitis, asthenia, parageusia, fauces dryness); we registered, instead, the absence of significant diseases related to antiblastic drugs exposure, because of both environmental and personal prevention, and clinical surveillance co-ordinated by occupational physician.

[Occupational exposure to environmental pollution: observational study about a newspaper-agents group]. / Esposizione professionale ad agenti inquinanti ambientali: studio osservazionale su un gruppo di edicolanti della città di Palermo.

UNLABELLED: Environmental pollution constantly menaces urban people's health. This public-health question has a remarkable interest in occupational medicine, because some professions require operations outdoor for most of the day. Therefore airborne pollutants could be considered occupational risk factors. Our object is health evaluation of a newspaper-agents group of Palermo, in association with pollution level monitored during the 2006. We examined these subjects regarding especially lung, ear, kidney, liver and cardiovascular system, with particular consideration for endothelial structure. RESULTS: high prevalence of carotid artery damage can't exclude a concausal role of airborne pollutants.

[Professional exposure to hardwood dusts in a group of Sicilian joiners]. / Esposizione professionale a polveri di legno duro in un gruppo di falegnami siciliani.

Wood is a system of vegetable tissues chemically formed by biopolymers (90-99%) and phenolic substances, alkaloids, glucosides and saponins (1-10%). There are two botanical groups of wood: hardwood and softwood. Aim of present study was the research of possible work related diseases with professional exposure to hardwood about 25 joiners of Palermo in 2006; in fact wood dust inhalation is very dangerous for workers health because it is cancerogenous for nasal and paranasal sinus (1 IARC). We studied beech and fraxinus dusts (hardwood) and mahogany and teak dusts (exotic hardwood) in the environmental air of joiners during wood cutting and finishing touch. We also analysed exposed workers registry to know joiners duties, exposure values to wood dust, inhalatory exposure, wood type, chemical components, individual protection safety devices, environmental protection means. Then we examined workers medical case and risk histories. At the end we noticed that particle material in environmental air was regular according law reference values (D.Lgs. 66/2000: TLV-TWA 5 mg/m3); but although environmental dust values were normal, we found nasal haemorrhages in 3 workers and vasomotory headache in other 3; we also diagnosed one paranasal sinus polypus and then irritative contact dermatitis in 3 workers. So there is an answer: "can current TLV-TWA be protective and sure? And can it guarantee health of hardwood exposed workers?".

Glucosylation of isatin-3-oxime followed by 2D in situ NMR in plant cells at highest magnetic field without labelling.

The glucosylation of isatin-3-oxime (1) was monitored by in situ 2D 1H-13C inverse correlated gradient assisted NMR spectroscopy in plant cell suspension cultures of Rauvolfia serpentina without labelling. The applied high magnetic field of 800 MHz allowed measurements within 20 min at concentrations of 1 of 5.76 mM. Complete glucosylation of 1 occurs inside the cells within 72 hours. During this time isatin-3-oxime-glucoside (2) accumulates without further metabolism.

[Case study of a population of subjects in Sicily operated for hydatidosis: correlation with profession and living environment]. / Studio casistico di una popolazione di soggetti residenti in Sicilia operati per idatidosi: correlazione con l'attività professionale e con l'ambiente di vita.

The aim of the study was to evaluate significant factors in the spread of echinococcosis in certain areas of Sicily. Data was obtained from operating registers of four surgical departments of the University Hospital of Palermo which covered 104 subjects, 57 women and 47 men, who underwent an operation for echinococcosis cysts in the period January 1996-June 1999. About 15% of these subjects were farmers, slaughterers, shepherds or gardeners and more than 80% lived in rural areas. The study showed that echinococcosis is still widespread in Sicily, at higher rates than the population, physicians and Health and safety Institutes generally believe. The place of origin is of particular importance because in rural areas it is very easy to be contaminated by infected animals or eat vegetables contaminated by parasitic eggs.

[Rickettsia infections in Sicily and mass media: attention not entirely groundless]. / Rickettsiosi in Sicilia e mezzi di comunicazione di massa: attenzione non del tutto immotivata.

The aim of the study was to assess the prevalence of rickettsiosis cases in Sicily with special attention to possible occupational exposure. This research was prompted by the high number of cases reported in the press in the summer of 1999. Epidemiological data for previous years showed that Sicily was always the region where most cases of rickettsiosis occurred; we therefore examined the clinical data of patients admitted to the major infectious diseases hospital department in Palermo in the period 1996-1999. Analysis of the cases showed that an occupational risk existed (among small farmers), but that there was also an environmental risk for subjects living in rural areas due to contact with infected dogs or rural areas activities. It is therefore of fundamental importance to carry out a primary prevention programme against rickettsiosis for everyone exposed to the risk either occupationally or in leisure activities in rural areas.