The Importance of Carbapenemase-Producing Enterobacterales in African Countries: Evolution and Current Burden

Antimicrobial resistance (AMR) is a worldwide healthcare problem. Multidrug-resistant organisms (MDROs) can spread quickly owing to their resistance mechanisms. Although colonized individuals are crucial for MDRO dissemination, colonizing microbes can lead to symptomatic infections in carriers. Carbapenemase-producing Enterobacterales (CPE) are among the most important MDROs involved in colonizations and infections with severe outcomes. This review aimed to track down the first reports of CPE in Africa, describe their dissemination throughout African countries and summarize the current status of CRE and CPE data, highlighting current knowledge and limitations of reported data. Two database queries were undertaken using Medical Subject Headings (MeSH), employing relevant keywords to identify articles that had as their topics beta-lactamases, carbapenemases and carbapenem resistance pertaining to Africa or African regions and countries. The first information on CPE could be traced back to the mid-2000s, but data for many African countries were established after 2015–2018. Information is presented chronologically for each country. Although no clear conclusions could be drawn for some countries, it was observed that CPE infections and colonizations are present in most African countries and that carbapenem-resistance levels are rising. The most common CPE involved are Klebsiella pneumoniae and Escherichia coli, and the most prevalent carbapenemases are NDM-type and OXA-48-type enzymes. Prophylactic measures, such as screening, are required to combat this phenomenon

Cystic Echinococcosis in the Early 2020s: A Review

Cystic echinococcosis (CE) is a zoonosis caused by metacestodes, the larval stage of Echinococcus granulosus. Although the World Health Organization (WHO) has defined CE as a neglected disease, it is the second most important foodborne parasitic disease, and it remains an important public health issue, considering its zonal endemicity and potential morbidity. The control and prevention of CE is a relevant WHO target, especially from a One Health perspective, as the disease affects not only animals and humans but also the food chain. Since not all countries have a CE surveillance strategy or reporting system and specific management guidelines, recent epidemiological data are relatively scarce, and research concerning the specific geographical distribution of the disease is ongoing. To add new information to the subject, we have analyzed and collected data from national guidelines and several medical databases. Out of the 751 research articles that were originally identified, only 52 were included in the investigation after applying specific inclusion and exclusion criteria. Notable international projects that have provided significant contributions and had a positive impact are presented. The available data were correlated with WHO recommendations on the subject, thus showcasing the measures taken and those that are still needed to properly control the disease’s spread

Effects of Gold Nanoparticles Phytoreduced with Rutin in an Early Rat Model of Diabetic Retinopathy and Cataracts

Diabetic retinopathy (DR) and cataracts (CA) have an early onset in diabetes mellitus (DM) due to the redox imbalance and inflammation triggered by hyperglycaemia. Plant-based therapies are characterised by low tissue bioavailability. The study aimed to investigate the effect of gold nanoparticles phytoreduced with Rutin (AuNPsR), as a possible solution. Insulin, Rutin, and AuNPsR were administered to an early, six-week rat model of DR and CA. Oxidative stress (MDA, CAT, SOD) was assessed in serum and eye homogenates, and inflammatory cytokines (IL-1 beta, IL-6, TNF alpha) were quantified in ocular tissues. Eye fundus of retinal arterioles, transmission electron microscopy (TEM) of lenses, and histopathology of retinas were also performed. DM was linked to constricted retinal arterioles, reduced endogen antioxidants, and eye inflammation. Histologically, retinal wall thickness decreased. TEM showed increased lens opacity and fibre disorganisation. Rutin improved retinal arteriolar diameter, while reducing oxidative stress and inflammation. Retinas were moderately oedematous. Lens structure was preserved on TEM. Insulin restored retinal arteriolar diameter, while increasing MDA, and amplifying TEM lens opacity. The best outcomes were obtained for AuNPsR, as it improved fundus appearance of retinal arterioles, decreased MDA and increased antioxidant capacity. Retinal edema and disorganisation in lens fibres were still present

Optimization of the rapid carbapenem inactivation method for use with AmpC hyperproducers

International audienceOBJECTIVES: Detection of carbapenemase-producing Enterobacterales (CPEs) is sometimes difficult with AmpC-hyperproducing Enterobacterales (AHEs), as they may falsely be classified as CPEs. Here, we present a rapid Carbapenem Inactivation Method (rCIM) optimized for AmpC producers (rCIM-A) that allows rapid and easy discrimination between AHEs and CPEs.METHODS: Enterobacterales (n = 249), including natural AmpC producers, AHEs, CPEs and non-carbapenemase-producing carbapenem-resistant control strains were evaluated, using Carba NP, rCIM and rCIM-A. The rCIM-A differs from the rCIM by the addition of cloxacillin (400 μg/mL) to the initial antibiotic incubation step.RESULTS: The rCIM-A yielded a sensitivity and specificity of 84.26% (95% CI: 76.00%-90.55%) and 99.29% (95% CI: 96.11%-99.98%), respectively, while those of the rCIM were 86.11% (95% CI: 78.13%-92.01%) and 80.85% (95% CI: 73.38%-86.99%), respectively; those of Carba NP were lower at 84.04% (95% CI: 75.05%-90.78%) and 91.37% (95% CI: 85.41%-95.46%), respectively, due to indeterminate results. The rCIM-A was capable of discriminating between AHEs and true CPEs, but still failed to identify OXA-23-producing Proteus mirabilis isolates and remained only partially reliable for identifying IMI-like producers and a few MBL (2 NDM-1, 1 LMB-1, 1 TMB-1 and 1 IMP-13) producers. One chromosomally encoded AmpC variant, MIR-10, gave repeatedly positive results using all three tests and was thus considered a false positive.CONCLUSIONS: Specificity for AHEs greatly improved with the rCIM-A without altering the test performance for the other resistance mechanisms. It may replace the rCIM as a cheap, easy, rapid and accurate CPE detection test

Optimization of the rapid carbapenem inactivation method for use with AmpC hyperproducers-authors’ response

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Phenotypic and genotypic virulence features of staphylococcal strains isolated from difficult-to-treat skin and soft tissue infections.

Chronic infections represent an important burden on the healthcare system and have a significant impact on the patients' quality of life. While Staphylococcus spp. are commensal bacteria, they can become pathogenic, leading to various types of infections. In this study we aimed to characterize the virulence profiles of staphylococcal strains involved in difficult-to-treat skin and soft tissue infections, from both phenotypic and genotypic points of view. Phenotypic ability of the strains to secrete soluble virulence factors was assessed by a culturing dependent assay and their capacity to develop biofilms on inert substrate was screened by an adapted crystal violet microtiter method. We also tested the presence of several virulence genes by PCR. Most of the studied strains were isolated from purulent secretions of acne lesions and frequently secreted two or three soluble virulence factors. Most frequently secreted soluble virulence factors were caseinase (89%), lipase (71%) and lecithinase (67%). Almost half of the strains produced a well-represented biofilm. The molecular characterization showed the presence of the genes cna, hlg, clfA, and clfB. Staphylococcal strains that produce difficult-to-treat skin and soft tissue infections seem to be characterized by an enhanced ability to produce different soluble virulence factors and to develop biofilms in vitro. Further studies need to be developed in other Staphylococcus spp. infections in order to confirm this hypothesis

In Vitro and In Vivo Characterisation of a Mucoadhesive Buccal Film Loaded with Doxycycline Hyclate for Topical Application in Periodontitis

Mucoadhesive films loaded with doxycycline hyclate (Doxy Hyc), consisting of mixtures of hydroxypropylmethyl cellulose (HPMC) E3, K4 and polyacrylic acid (Carbopol 940), were prepared by casting method, aiming to design a formulation intended for application in the oral cavity. The obtained film formulations exhibited a Doxy Hyc content between 7.52 ± 0.42 and 7.83 ± 0.41%, which had adequate mechanical properties for application in the oral cavity and pH values in the tolerance range. The x-ray diffraction studies highlighted the amorphisation of Doxy Hyc in the preparation process and the antibiotic particles present on the surface of the films, identified in the TEM images, which ensured a burst release effect in the first 15 min of the in vitro dissolution studies, after which Doxy Hyc was released by diffusion, the data presenting a good correlation with the Peppas model, n < 0.5. The formulation F1, consisting of HPMC K4 combined with C940 in a ratio of 5:3, the most performing in vitro, was tested in vivo in experimentally-induced periodontitis and demonstrated its effectiveness in improving the clinical parameters and reducing the salivary levels of matrix metalloproteinase-8 (MMP-8). The prepared Doxy Hyc loaded mucoadhesive buccal film could be used as an adjuvant for the local treatment of periodontitis, ensuring prolonged release of the antibiotic after topical application

In Vitro and In Vivo Characterisation of a Mucoadhesive Buccal Film Loaded with Doxycycline Hyclate for Topical Application in Periodontitis

Mucoadhesive films loaded with doxycycline hyclate (Doxy Hyc), consisting of mixtures of hydroxypropylmethyl cellulose (HPMC) E3, K4 and polyacrylic acid (Carbopol 940), were prepared by casting method, aiming to design a formulation intended for application in the oral cavity. The obtained film formulations exhibited a Doxy Hyc content between 7.52 &plusmn; 0.42 and 7.83 &plusmn; 0.41%, which had adequate mechanical properties for application in the oral cavity and pH values in the tolerance range. The x-ray diffraction studies highlighted the amorphisation of Doxy Hyc in the preparation process and the antibiotic particles present on the surface of the films, identified in the TEM images, which ensured a burst release effect in the first 15 min of the in vitro dissolution studies, after which Doxy Hyc was released by diffusion, the data presenting a good correlation with the Peppas model, n &lt; 0.5. The formulation F1, consisting of HPMC K4 combined with C940 in a ratio of 5:3, the most performing in vitro, was tested in vivo in experimentally-induced periodontitis and demonstrated its effectiveness in improving the clinical parameters and reducing the salivary levels of matrix metalloproteinase-8 (MMP-8). The prepared Doxy Hyc loaded mucoadhesive buccal film could be used as an adjuvant for the local treatment of periodontitis, ensuring prolonged release of the antibiotic after topical application

Immunomodulatory Effect of Novel Electrospun Nanofibers Loaded with Doxycycline as an Adjuvant Treatment in Periodontitis

The immunomodulatory effect of a novel biomaterial obtained through electrospinning, based on polylactic acid (PLA) and nano-hydroxyapatite (nano-HAP), loaded with doxycycline (doxy) was evaluated in an animal model. The treatment capabilities as a local non-surgical treatment of periodontitis was investigated on the lower incisors of Wistar rats, after the induction of localized periodontitis using the ligature technique. Following the induction of the disease, the non-surgical treatment of scaling and root planing was applied, in conjunction with the application of the new material. The results of the treatment were evaluated clinically, using the tooth mobility and gingival index scores, as well as histologically. The salivary concentrations of matrix metalloproteinase 8 (MMP-8) and plasmatic concentrations of interleukin 1 (IL-1), interleukin 6 (IL-6) and tumor necrosis factor alpha (TNF-α) were also monitored. Two weeks after the ligature application, the periodontal disease was successfully induced in rats. The application of the novel biomaterial obtained through electrospinning was proven to be more effective in improving the clinical parameters, while decreasing the salivary MMP-8 and plasmatic IL-1 and TNF-α concentrations, compared to the simple scaling and root planing. Thus, the novel electrospun biomaterial could be a strong candidate as an adjuvant to the non-surgical periodontal therapy