Multi-drug resistant Gram-negative bacteria: antibiotic-resistance and new treatment strategies

In this editorial, we treat the multi-drug-resistance of microorganisms such as Klebsiella pneumonia (Kp) and Acinetobacter baumanii and the issues concerning the management of these infections. Diseases caused by carbapenemase-resistant Kp (CR-Kp) represent an emerging threat worldwide due to high mortality rate and limited therapeutic options. Consequently innovative therapies have been suggested for their treatment. Colistin- based combinations are considered the milestone of the therapy for CR-Kp. They include meropenem+colistin, meropenem +colistin+tigecycline, the double carbapenem+colistin, tigecycline+colistin, colistin+gentamicin and even colistin +vancomycin. However, colistin use might be limited by its potential nephrotoxicity and resistance. Other antibiotic combinations concern the tigecycline with gentamicin, fosfomycin with aminoglycoside and ertapenem with meropenem. Thus, the double carbapenem-regimen might be considered as a suitable therapy in those subjects in whom previous antimicrobial combinations failed. New antibiotics such as ceftazidime-avibactam effective on CR-Kp and ceftolozane-tazobactam active against XDR (Extensively Drug Resistant) Pseudomonas aeruginosa are now being used in many countries. The mortality results to be lower in patients treated with antibiotic combinations than in those who underwent monotherapy. Efforts should be made by the clinicians in order to limit the widespread of these resistant microorganisms all over the world. Encouraging new solutions as bacteriophage therapy or biocides currently does not seem the right choice

Antibiotic susceptibility, heteroresistance, and updated treatment strategies in helicobacter pylori infection

In this review, we discuss the problem of antibiotic resistance, heteroresistance, the utility of cultures and antibiotic susceptibility tests in Helicobacter pylori (Hp) eradication, as well as the updated treatment strategies for this infection. The prevalence of antibiotic resistance is increasing all over the world, especially for metronidazole and clarithromycin, because of their heavy use in some geographical areas. Heteroresistance (simultaneous presence of both susceptible and resistant strains in different sites of a single stomach) is another important issue, as an isolate could be mistakenly considered susceptible if a single biopsy is used for antimicrobial tests. We also examined literature data regarding eradication success rates of culture-guided and empiric therapies. The empiric therapy and the one based on susceptibility testing, in Hp eradication, may depend on several factors such as concomitant diseases, the number of previous antibiotic treatments, differences in bacterial virulence in individuals with positive or negative cultures, together with local antibiotic resistance patterns in real-world settings. Updated treatment strategies in Hp infection presented in the guidelines of the Toronto Consensus Group (2016) are reported. These suggest to prolong eradication therapy up to 14 days, replacing the old triple therapy with a quadruple therapy based on proton pump inhibitor (PPI), bismuth, metronidazole, and tetracycline for most of the patients, or as an alternative quadruple therapy without bismuth, based on the use of PPI, amoxicillin, metronidazole, and clarithromycin. The new drug vonoprazan, a first-in-class potassium-competitive acid blocker recently approved in Japan, is also considered to be a promising solution for Hp eradication, even for clarithromycin-resistant strains. Furthermore, there is growing interest in finding new therapeutic strategies, such as the development of vaccines or the use of natural resources, including probiotics, plants, or nutraceuticals.In this review, we discuss the problem of antibiotic resistance, heteroresistance, the utility of cultures and antibiotic susceptibility tests in Helicobacter pylori (Hp) eradication, as well as the updated treatment strategies for this infection. The prevalence of antibiotic resistance is increasing all over the world, especially for metronidazole and clarithromycin, because of their heavy use in some geographical areas. Heteroresistance (simultaneous presence of both susceptible and resistant strains in different sites of a single stomach) is another important issue, as an isolate could be mistakenly considered susceptible if a single biopsy is used for antimicrobial tests. We also examined literature data regarding eradication success rates of culture-guided and empiric therapies. The empiric therapy and the one based on susceptibility testing, in Hp eradication, may depend on several factors such as concomitant diseases, the number of previous antibiotic treatments, differences in bacterial virulence in individuals with positive or negative cultures, together with local antibiotic resistance patterns in real-world settings. Updated treatment strategies in Hp infection presented in the guidelines of the Toronto Consensus Group (2016) are reported. These suggest to prolong eradication therapy up to 14 days, replacing the old triple therapy with a quadruple therapy based on proton pump inhibitor (PPI), bismuth, metronidazole, and tetracycline for most of the patients, or as an alternative quadruple therapy without bismuth, based on the use of PPI, amoxicillin, metronidazole, and clarithromycin. The new drug vonoprazan, a first-in-class potassium-competitive acid blocker recently approved in Japan, is also considered to be a promising solution for Hp eradication, even for clarithromycin-resistant strains. Furthermore, there is growing interest in finding new therapeutic strategies, such as the development of vaccines or the use of natural resources, including probiotics, plants, or nutraceuticals

Light propagation in nonuniform plasmonic subwavelength waveguide arrays

International audienceWe study light propagation in nanoscale periodic structures composed of dielectric and metal in the visible range. We demonstrate that diffraction curves of nonuniform waveguide arrays can be tailored by varying the geometric and dielectric features of the waveguides. The results obtained from a proper formulation of Coupled Mode Theory for non uniform arrays are validated through numerical solution of Maxwell equations in frequency domain

In-vitro evaluation of different antimicrobial combinations with and without colistin against carbapenem-resistant acinetobacter baumannii

Carbapenem-resistant Acinetobacter baumannii (CR-Ab) infections are associated with high morbidity and mortality. The aim of the study was to evaluate the in-vitro activity of different antimicrobial combinations (with and without colistin, COL) against clinical isolates of CR-Ab collected from patients with CR-Ab infection, including unconventional combinations such as COL + VANcomycin (VAN) and COL + rifampin (RIF). CR-Ab strains were collected from hospitalized patients at Sapienza University of Rome. Antimicrobial susceptibility patterns were determined throughout MIC50/90s whereas the synergistic activity was evaluated by qualitative (i.e., checkerboard) and quantitative (i.e., killing studies) methods. All the strains were found oxacillinase (OXA) producers and tigecycline (TIG) sensitive whereas 2 strains were resistant to COL. Application of the checkerboard method indicated complete synergism in COL combinations at different extension: 21.4%, 57.1%, 42.8%, 35.7% for COL + meropenem (MEM), COL + RIF, COL + VAN and COL + TIG, respectively, with the non-conventional combinations COL + VAN and COL + RIF exhibiting the highest rate of synergism. Regarding COL-free combination, complete synergism was observed in 35.7% of the strains for MEM + TIG. Killing studies showed that the combinations COL + MEM, COL + TIG and MEM + TIG were bactericidal and synergistic against both colistin-sensitive and low colistin-resistant strains whereas only the combinations COL + VAN and COL + RIF showed an early and durable bactericidal activity against all the tested strains, with absence of growth at 24 h. This study demonstrated that COL-based combinations lead to a high level of synergic and bactericidal activity, especially COL + VAN and COL + RIF, even in the presence of high level of COL resistance

Chemical and antimicrobial analyses of Sideritis romana L. subsp. purpurea (Tal. ex Benth.) Heywood, an endemic of the Western Balkan

A comprehensive study on essential oil and different solvent extracts of Sideritis romana L. subsp. purpurea (Tal. ex Benth.) Heywood (Lamiaceae) from Montenegro is reported. The gas chromatography-mass spectrometry analysis of the essential oil revealed a total of 43 components with bicyclogermacrene (23.8%), germacrene D (8%), (E)-caryophyllene (7.9%) and spathulenol (5.5%) as the major ones. Sesquiterpenoid group was found to be the most dominant one (64.8%), with 19.9% of the oxygenated forms. In the crude methanol extract of the investigated plant, obtained by Sohhlet exraction, the total phenol content was 14.7 ± 0.4 mg of GA/g, the total flavonoids were 0.29 ± 0.03% expressed as hyperoside percentage, whereas the total tannins content was 0.22 ± 0.04% expressed as pyrogallol percentage. For the antimicrobial activity determination, the following microorganisms have been used: methicillin-susceptible Staphylococcus aureus (MSSA (American Type Culture Collection (ATCC) 29213)) and methicillin-resistant S. aureus (MRSA (clinical strain)), Escherichia coli (ATCC 25922), carbapenem-susceptible Klebsiella pneumoniae (clinical strain), carbapenem-resistant K. pneumoniae (clinical strain) and Candida albicans (ATCC 14053). The essential oil showed high potency against MSSA and MRSA, both at high (~5 × 10 5 CFU/mL) and low (~5 × 10 3 CFU/mL) inoculum. With respect to MSSA, the minimal inhibitory concentration (MIC) value was 0.307 mg/mL, with bactericidal activity obtained at 0.615 mg/mL, while, in the case of MRSA, the MIC and minimal bactericidal concentration (MBC) values were 0.076 and 0.153 mg/mL, respectively. Regarding anti-Candida albicans activity, the MIC value was 2.46 mg/mL without reaching fungicidal activity. In addition to the observed essential oil efficacy, different solvent extracts were analyzed for their antimicrobial activity. Similarly to the essential oil, thehighest efficacy was observed against both MSSA and MRSA strains, at high and low inoculums, in the case of the 1,2-dichloroethane and methanol extracts. A potent fungicidal activity has been also found for the n-hexane and 1,2-dichloroethane extracts. It can be concluded that Sideritis romana L. subsp. purpurea (Tal. ex Benth.) Heywood provides a wide range of application in different fields such as phytochemistry, pharmacology, toxicology or pharmacognosy

High potency of melaleuca alternifolia essential oil against multi-drug resistant gram-negative bacteria and methicillin-resistant staphylococcus aureus

Purpose: Herein, an extended investigation of Tea tree oil (TTO) against a number of multi-drug resistant (MDR) microorganisms in liquid and vapor phases is reported. Methods: The activity of TTO was tested against methicillin-sensitive Staphylococcus aureus (MSSA), Escherichia coli, and clinical strains of methicillin-resistant S. aureus (MRSA), extended-spectrum beta lactamases producer carbapenem-sensitive Klebsiella pneumoniae (ESBL-CS-Kp), carbapenem-resistant K. pneumoniae (CR-Kp), Acinetobacter baumannii (CR-Ab), and Pseudomonas aeruginosa (CR-Pa). Minimal inhibitory/bactericidal concentrations (MIC/MBCs) and synergistic activity between TTO and different antimicrobials were determined. In the vapor assay (VP), TTO-impregnated discs were placed on the lid of a petri dish and incubated for 24 h at 37°C. Results: TTO showed a potent bactericidal activity against all the tested microorganisms. TTO in combination with each reference antimicrobial showed a high level of synergism at sub-inhibitory concentrations, particularly with oxacillin (OXA) against MRSA. The VP assay showed high activity of TTO against CR-Ab. Conclusion: Evaluation of in-vitro activity clearly indicated TTO as a potential effective antimicrobial treatment either alone or in association with known drugs against MDR. Therefore, TTO could represent the basis for a possible role in non-conventional regimens against S. aureus and Gram-negative MDR. TTO in VP might represent a promising option for local therapy of pneumonia caused by CR-Ab

Anesthetic management in awake craniotomy

Resection of brain tumors may cause neurological sequelae, according to the site and size of the brain tissue removed. Awake craniotomy has been proposed as a surgical approach to satisfy criteria of radical surgery while minimizing eloquent brain damage.The most critical aspect of awake craniotomy is to maintain adequate patient comfort, analgesia, immobility and cooperation during a long surgical operation, ensuring in the meanwhile the safety, control and maintenance of vital functions. Apart from pharmacological, surgical, technical knowledge and skillfulness, the ability to maintain close psycho-emotionalcontact and support with the patient throughout the operation is a fundamental task that the anesthesiologist has to pursue for the operation to be successfully managed. This review summarizes the current opinion on anesthetic management of patients undergoing awake craniotomy

Near to short wave infrared light generation through AlGaAs-on-insulator nanoantennas

AlGaAs-on-insulator (AlGaAs-OI) has recently emerged as a novel promising platform for nonlinear optics at the nanoscale. Among the most remarkable outcomes, second harmonic generation (SHG) in the visible/near infrared spectral region has been demonstrated in AlGaAs-OI nanoantennas (NA). In order to extend the nonlinear frequency generation towards the short wave infrared window, in this work we propose and demonstrate via numerical simulations difference frequency generation (DFG) in AlGaAs-OI NAs. The NA geometry is finely adjusted in order to obtain simultaneous optical resonances at the pump, signal and idler wavelengths, which results in an efficient DFG with conversion efficiencies up to 0.01%. Our investigation includes the study of the robustness against random variations of the NA geometry that may occur at fabrication stage. Overall, these outcomes identify a new potential and yet unexplored application of AlGaAs-OI NAs as compact devices for the generation and control of the radiation pattern in the near to short infrared spectral region

Severe bloodstream infection due to KPC-producer e coli in a renal transplant recipient treated with the double-carbapenem regimen and analysis of in vitro synergy testing a case report

Transplant recipients are at high risk of infections caused by multidrug resistant microorganisms. Due to the limited thera- peutic options, innovative antimicrobial combinations against carbape- nem-resistant Enterobacteriaceae causing severe infections are necessary. A 61-year-old woman with a history of congenital solitary kidney underwent renal transplantation. The postoperative course was compli- cated by nosocomial pneumonia due to Stenotrophomonas maltophilia and pan-sensitive Escherichia coli, successfully treated with antimicrobial therapy. On postoperative day 22, diagnosis of surgical site infection and nosocomial pneumonia with concomitant bacteremia due to a Kle- bisella pneumoniae carbapenemase-producer E coli was made. The patient was treated with the double-carbapenem regimen (high dose of merope- nem plus ertapenem) and a potent synergistic and bactericidal activity of this un-conventional therapeutic strategy was observed in vitro. Despite a microbiological response with prompt negativity of blood cultures, the patient faced a worse outcome because of severe hemorrhagic shock. The double-carbapenem regimen might be considered as a rescue therapy in those subjects, including transplant recipients, in whom previous antimicrobial combinations failed or when colistin use might be discouraged. Performing in vitro synergy testing should be strongly encouraged in cases of infections caused by pan-drug resistant strains, especially in high-risk patients