Xanthoepocin, a photolabile antibiotic of Penicillium ochrochloron CBS 123823 with high activity against multiresistant gram-positive bacteria

Background With the steady increase of antibiotic resistance, several strategies have been proposed in the scientific community to overcome the crisis. One of many successful strategies is the re-evaluation of known compounds, which have been early discarded out of the pipeline, with state-of-the-art know-how. Xanthoepocin, a polyketide widespread among the genus Penicillium with an interesting bioactivity spectrum against gram-positive bacteria, is such a discarded antibiotic. The purpose of this work was to (i) isolate larger quantities of this metabolite and chemically re-evaluate it with modern technology, (ii) to explore which factors lead to xanthoepocin biosynthesis in P. ochrochloron, and (iii) to test if it is beside its known activity against methicillin-resistant Staphylococcus aureus (MRSA), also active against linezolid and vancomycin-resistant Enterococcus faecium (LVRE)—a very problematic resistant bacterium which is currently on the rise. Results In this work, we developed several new protocols to isolate, extract, and quantify xanthoepocin out of bioreactor batch and petri dish-grown mycelium of P. ochrochloron. The (photo)chemical re-evaluation with state-of-the-art techniques revealed that xanthoepocin is a photolabile molecule, which produces singlet oxygen under blue light irradiation. The intracellular xanthoepocin content, which was highest under ammonium-limited conditions, varied considerably with the applied irradiation conditions in petri dish and bioreactor batch cultures. Using light-protecting measures, we achieved MIC values against gram-positive bacteria, including methicillin-resistant Staphylococcus aureus (MRSA), which were up to 5 times lower than previously published. In addition, xanthoepocin was highly active against a clinical isolate of linezolid and vancomycin-resistant Enterococcus faecium (LVRE). Conclusions This interdisciplinary work underlines that the re-evaluation of known compounds with state-of-the-art techniques is an important strategy in the combat against multiresistant bacteria and that light is a crucial factor on many levels that needs to receive more attention. With appropriate light protecting measures in the susceptibility tests, xanthoepocin proved to be a powerful antibiotic against MRSA and LVRE. Exploring the light response of other polyketides may be pivotal for re-introducing previously discarded metabolites into the antibiotic pipeline and to identify photosensitizers which might be used for (antimicrobial) photodynamic therapies.

Therapeutic Potential of Injectable Nano-Mupirocin Liposomes for Infections Involving Multidrug-Resistant Bacteria

Antibiotic resistance is a global health threat. There are a few antibiotics under development, and even fewer with new modes of action and no cross-resistance to established antibiotics. Accordingly, reformulation of old antibiotics to overcome resistance is attractive. Nano-mupirocin is a PEGylated nano-liposomal formulation of mupirocin, potentially enabling parenteral use in deep infections, as previously demonstrated in several animal models. Here, we describe extensive in vitro profiling of mupirocin and Nano-mupirocin and correlate the resulting MIC data with the pharmacokinetic profiles seen for Nano-mupirocin in a rat model. Nano-mupirocin showed no cross-resistance with other antibiotics and retained full activity against vancomycin-, daptomycin-, linezolid- and methicillin- resistant Staphylococcus aureus, against vancomycin-resistant Enterococcus faecium, and cephalosporin-resistant Neisseria gonorrhoeae. Following Nano-mupirocin injection to rats, plasma levels greatly exceeded relevant MICs for >24 h, and a biodistribution study in mice showed that mupirocin concentrations in vaginal secretions greatly exceeded the MIC90 for N. gonorrhoeae (0.03 µg/mL) for >24 h. In summary, Nano-mupirocin has excellent potential for treatment of several infection types involving multiresistant bacteria. It has the concomitant benefits from utilizing an established antibiotic and liposomes of the same size and lipid composition as Doxil®, an anticancer drug product now used for the treatment of over 700,000 patients globally.

Increased Use of Antibiotics in the Intensive Care Unit During Coronavirus Disease (COVID-19) Pandemic in a Brazilian Hospital

Background: Microbial drug resistance is one of the biggest public health problems. Antibiotic consumption is an essential factor for the emergence and spread of multiresistant bacteria. Therefore, we aimed to analyze the antibiotics consumption in the Intensive Care Unit (ICU), identifying trends in the antibiotics use profile and microbiological isolates throughout the COVID-19 pandemic.Methods: We performed this retrospective observational study in intensive care units of a Brazilian tertiary hospital from January 2019 to December 2020. The primary outcome was antimicrobial consumption in the ICU, measured by defined daily doses (DDDs) per 100 bed-days. As a secondary outcome, bacterial infections (microbiological isolates) were calculated in the same fashion. Outcomes trends were analyzed using Joinpoint regression models, considering constant variance (homoscedasticity) and first-order autocorrelation assumptions. A monthly percent change (MPC) was estimated for each analyzed segment.Results: Seven thousand and nine hundred fifty-three patients had data available on prescribed and received medications and were included in the analyses. Overall, the use of antibiotics increased over time in the ICU. The reserve group (World Health Organization Classification) had an increasing trend (MPC = 7.24) from February to April 2020. The azithromycin consumption (J01FA) increased rapidly, with a MPC of 5.21 from January to April 2020. Polymyxin B showed a relevant increase from March to June 2020 (MPC = 6.93). The peak of the antibiotic consumption of Reserve group did not overlap with the peak of the pathogenic agents they are intended to treat.Conclusion: Overall antimicrobial consumption in ICU has increased in the context of the COVID-19 pandemic. The peaks in the antimicrobial’s use were not associated with the rise of the pathogenic agents they intended to treat, indicating an empirical use, which is especially concerning in the context of treating multidrug-resistant (MDR) infections. This fact may contribute to the depletion of the therapeutic arsenal for MDR treatment.

Molecular epidemiology of methicillin resistant Staphylococcus species in healthcare workers of a blood bank in the Brazilian Amazon

Background Healthcare workers are susceptible to colonization by multiresistant bacteria, which can increase the risk of outbreaks. Methods Samples were collected from the nasopharynx, hands, and lab coats of healthcare workers. The phenotypic identification was carried out using a VITEK®2 rapid test system. PCR tests for the mecA gene and the sequencing of the amplicons were performed. Staphylococcus epidermidis and Staphylococcus aureus phylogenies were reconstructed using the Bayesian inference. Results A total of 225 healthcare workers participated in this study. Of these, 21.3% were male and 78.7% female. S. epidermidis and S.aureus showed high levels of resistance to penicillin, ampicillin, erythromycin, tetracycline and cefoxitin. The prevalence of methicillin resistant S. aureus was 3.16% and methicillin resistant S. epidermidis was 100%. Multilocus sequence typing identified 23 new S. epidermidis sequence types, and one new allele and sequence type for S. aureus. The frequency of methicillin-resistant S. epidermidis in nursing and hemotherapy technicians as a percentage of the total number of healthcare workers was 5.8–3.1%, while the frequency of methicillin resistant S. aureus in hemotherapy technicians and biomedics, as a percentage of the total number of healthcare workers was 4.2–8.9%%. Conclusions The healthcare workers at the city’s blood bank, even when taking the necessary care with their hands, body and clothes, harbour methicillin-resistant S. aureus and S. epidermidis sequence types, which, as a potential source of multidrug resistant bacteria, can contribute to nosocomial infections among hematological patients.

Utilização do extrato de Nim (Azadirachta indica) e própolis em microrganismos isolados de cães (Canis familiares) com otite

RESUMO A otite canina é uma enfermidade relevante na prática veterinária; desse modo, reveste-se de grande importância o conhecimento do(s) agente(s) associado(s) e seus perfis de susceptibilidade, no intuito de se estabelecer um tratamento direcionado e eficaz e prevenir a disseminação de bactérias multirresistentes (OLIVEIRA et al., 2005). Foram coletadas 29 amostras, través de “swabs” estéreis, de secreções otológicas provenientes de cães de raça, gênero, idade distintas que apresentavam sinais clínicos de otite, no Hospital Veterinário da UFERSA e nas Clínicas do Município de Mossoró- RN no período de agosto 2009 até junho 2010. Isolados e devidamente identificados, os microrganismos foram sujeitos a antibiogramas com antibióticos convencionais e os meios alternativos (extrato Nim e própolis) aqui avaliados, através da técnica de difusão em Ágar pelo disco de papel. Considerando a escassez de dados referentes à otite canina à tratamento provenientes de recursos naturais na região Nordeste do País, este trabalho apresenta resultados da pesquisa por meios alternativos ao tratamento da otite com extrato de Nim (Azadirachta indica) e própolis. ABSTRACT Use of the extract of Nim (Azadirachta indica) and propolis in isolated microrganims from dogs (Canis familiares) with otitis: The canine otitis is a important disease in the practical veterinary medicine; in this manner, the knowledge of the agent(s) and its profiles of susceptibility, in the intention of establishing a directed and efficient treatment and preventing the dissemination of multiresistant bacteria). 29 samples with sterile swabs had been collected, proceeding from dogs of race, generus, age that presented clinical signals of otitis, in the Hospital Veterinarian of the UFERSA and in the clinics of the City of Mossoró- RN in the period of August 2009 until June 2010. Isolated and identified, the microorganisms had been made the antibiogramas with conventional antibiotics and the alternative ways (Nim extract and propolis) here evaluated, through the technique of diffusion in Agar for the paper record. Considering the scarcity of referring data to the canine otitis to the treatment proceeding from natural resources in the Northeast region of the Country, this date present the resulted research for alternative ways to the treatment of the otitis with extract of Nim (Azadirachta indica) and propolis.

Antibacterial effect of titanium dioxide with or without silver as additive on staphylococcus aureus from clinical samples

Antibiotic resistance has now become a perpetual global problem due to the emergence and reemergence of old and new multiresistant bacteria that there is a constant need of newer drugs to combat this phenomenon. Nanoparticles are now considered for their antibacterial effect and those such as Titanium dioxide have a good mechanical properties and biocompatibility, especially being non toxic to human skin and cost effective. This study was done to show the antibacterial effect of Titanium dioxide with and without Silver as addendum on Staphylococcus aureus strains from clinical samples. Staphylococcus aureus isolated from various clinical samples was inoculated onto peptone water and further inoculated onto glass slides coated with TiO2 annealed at 200C, 400C and onto TiO2 with 0.1%, 0.3%, 0.6% and 0.8% silver as additive at 1 hour intervals each. The growth was observed after 18 hours of incubation. The highest antibacterial effect was observed within 2 hours of treatment with 0.8% Ag on TiO2 nanoparticles, while it took longer with the other concentrations of silver. With TiO2 and 0.1% Ag, it took at least 7 hours of treatment for complete antibacterial effect though within the first hour itself the effect was observed. Though TiO2 nanoparticles in pure form have significant antibacterial effect, there is a considerable increase in its antibacterial effect when silver is added as an additive, with higher concentrations of Ag having more effect.

Combination Therapy as a Strategy to control Infections caused by Multiresistant Bacteria. Current Review

: Antimicrobial resistance (AMR) is one of the main challenges of today's medicine because it has become a global problem that affects the treatment of multiple infections and impacts public health. This resistance is caused because the bacteria have generated selective pressure promoting mechanisms to evade the action of conventional drugs, which are also associated with adverse effects. Infections caused by these multi-resistant bacteria potentially reduce the possibility of effective therapy; this situation increases morbidity and mortality and treatment costs. To establish combined therapy as a strategy for the control of infections caused by multi-resistant bacteria. A bibliographic search was carried out between 2015 and 2020 in databases such as PubMed, Scopus and Science Direct. The exhaustive review of the articles allowed a critical analysis of the information. They have identified the mechanisms for obtaining drugs with antimicrobial potential, their biological activity and the possible effect of their combination against multidrug-resistant bacteria as an alternative for infectious disease control and as a response to reduce the use of antibiotics. Combined therapy is presented as an innovative therapeutic alternative, which uses non-antibiotic substances that can be obtained by three routes: the repositioning of drugs, synthetic substances and natural products. In this way, important elements are provided to guide researches who seek to reduce antimicrobial resistance.

Indigenous multiresistant bacteria of Cupriavidus pauculus IrC4 isolated from Indonesia as a heavy metal bioremediation agent

Irawati W, Winoto SE, Kusumawati L, Pinontoan R. 2021. Indigenous multiresistant bacteria of Cupriavidus pauculus IrC4 isolated from Indonesia as a heavy metal bioremediation agent. Biodiversitas 22: 3349-3355. Heavy metal pollution is a serious environmental problem because it endangers humans, animals, and plants. Bioremediation of heavy metals using bacteria is an effective method to remove heavy metals. Cupriavidus pauculus IrC4 is an indigenous multi-resistant bacteria isolated from Indonesia. This study aims to determine the growth of this strain in a medium containing cadmium, mercury, lead, copper, and its ability to accumulate heavy metal. Bacterial resistance was observed by cultivating bacteria on a Luria Bertani medium containing various concentrations of heavy metals. Heavy metal accumulation was measured using atomic absorption spectrophotometer. The study showed that this strain could grow in a solid medium containing 5 mM cadmium, 13 mM lead, and 4 mM mercury, also in 0.5 mM of the heavy metal mixture. A high concentration of heavy metals resulted in lag phase elongation and logarithmic growth phase inhibition. C. pauculus IrC4 could accumulate copper, lead, and cadmium and lead up to 371.42 mg, 254.4 mg, 5.8 mg heavy metals per gram of dry weight of cells, respectively. In conclusion, this strain is a promising bacterium for use as a heavy metal bioremediation agent.