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Background Correlation between coronavirus disease 2019 (COVID-19) and superinfections has been investigated, but remains to be fully assessed. This multi-centre study reports the impact of the pandemic on bloodstream infections (BSIs). Methods This study included all patients with BSIs admitted to four Italian hospitals between 1 January and 30 June 2020. Clinical, demographic and microbiologic data were compared with data for patients hospitalized during the same period in 2019. Results Among 26,012 patients admitted between 1 January and 30 June 2020, 1182 had COVID-19. Among the patients with COVID-19, 107 BSIs were observed, with an incidence rate of 8.19 episodes per 1000 patient-days. The incidence of BSI was significantly higher in these patients compared with patients without COVID-19 (2.72/1000 patient-days) and patients admitted in 2019 (2.76/1000 patient-days). In comparison with patients without COVID-19, BSI onset in patients with COVID-19 was delayed during the course of hospitalization (16.0 vs 5 days, respectively). Thirty-day mortality among patients with COVID-19 was 40.2%, which was significantly higher compared with patients without COVID-19 (23.7%). BSIs in patients with COVID-19 were frequently caused by multi-drug-resistant pathogens, which were often centre-dependent. Conclusions BSIs are a common secondary infection in patients with COVID-19, characterized by increased risk during hospitalization and potentially burdened with high mortality.

Summary Background Conflicting results have been published on the impact of contact precautions (CPs) on reduction of transmission of multi-drug-resistant micro-organisms (MDROs) in the endemic setting. Ambiguous definitions coupled with low adherence partly explain these differences. Aim We prospectively monitored the level of adherence to CPs and aimed to relate it to in-hospital transmission of MDROs. Methods Between January 2016 and March 2018, all patients under CPs underwent continuous monitoring of adherence to CPs by routine on-site visits on days 0, 3 and 7 after initiating CPs using a standardized checklist. The protocol included 10 interventions that were routinely checked such as CP sign at the door as well as wearing of gowns and gloves upon entry to the patient room. Patients requiring CPs were defined as colonized or infected with MDROs (meticillin-resistant Staphylococcus aureus (MRSA), non-Escherichia coli extended-spectrum beta lactamase (ESBL) Enterobacterales, vancomycin-resistant enterococci (VRE) and carbapenem-resistant Gram-negative micro-organisms (CRGN)) as well as patients infected with respiratory viruses, norovirus, scabies and hypervirulent strains of Clostridioides difficile. Findings Overall, data from 13,756 CP records from 1378 visits of 812 patients were analysed. Adherence varied between 93% and 100% for each intervention, except for “separate space for contaminated material” with an adherence of 5.3–6.1%. The incidence of in-hospital transmission during the study period was extremely low for MRSA, VRE, non-E.coli ESBL Enterobacterales and CRGN with 0.00–0.064 cases/1000 patient days. Conclusion High adherence coupled with continuous monitoring of CPs correlated with a very low in-hospital transmission rate. These results indicate that CPs are highly effective if routine monitoring of adherence is implemented.

Antimicrobial resistance (AMR) represents a major challenge to global health. This problem is most apparent in healthcare facilities, with a comparatively small number of pathogens being responsible for a substantial burden of hospital acquired infections globally. One of the key pathogens is the Gram-negative coccobacilli, Acinetobacter baumannii. It has been estimated that between 47% and 93% of A. baumannii infections are associated with multi-drug resistance (MDR), which is facilitated through a variety of well documented mechanisms (β-lactamases, efflux pumps, aminoglycoside-modifying enzymes, permeability defects, and target modifications). As our current pool of antimicrobial treatments becomes increasingly less effective, it is vital to identify new targets that can aid in the development novel treatments and strategies. In this we review we outline the key virulence mechanisms in A. baumannii (gene acquisition and adaptation, resistance to stresses, biofilm formation, and host interaction) and discuss their potential as targets for new therapeutics to reduce the impact of infections caused by MDR A. baumannii.

The development of infections still represents a severe problem in orthopedic field. In this work, we developed an anti-microbial and radiopaque calcium phosphate bone cement with a long-lasting inhibitory activity thanks to the addition of gentamicin sulphate-loaded solid lipid microparticles obtained by spray congealing. Cements containing gentamicin both added into cement powder and loaded into microparticles were prepared and characterized and their properties were compared. The results of structural, morphological, mechanical and in vitro characterizations indicate that inclusion of gentamicin into microparticles is a good approach in order to obtain materials able to display a strong inhibition towards the growth of Gram-negative, as well as Gram-positive bacteria and to enhance the viability of osteoblast-like cells. All the compositions have an excellent activity also against clinical isolates, including multi drug resistant phenotypes. In particular, cements containing gentamicin-loaded microparticles display a strong and long-term inhibitory activity. Suitable modification of the liquid/powder ratio provided injectable formulation, whereas addition of BaSO4 produced radiopacity. All the formulations display good injectability and cohesion, and no evidence of demixing.

The emergence and dissemination of multi-drug resistant nosocomial infections has become a major public health menace. These Multi Drug Resistant (MDR) bacteria due to their ability to ‘escape’ the biocidal action of antibiotics, have become increasingly prevalent and are considered a serious problem with very limited treatment options for the infections arising from them. Nanoparticles have the possibility to enter the highly impermeable cell membrane of these MDR bacteria owing to their small size and large surface area. Bio-synthesis of such nanoparticles using phyto-chemical agents, rather than synthesizing them by chemical processes, would result into bioactive compounds binding to the nanoparticles and are found to be more effective as this synthesis route tends to further enhance their antimicrobial activity towards these MDR bacteria.

Summary The homeopathic medicine, Silicea has been used in biological, physico-chemical and clinical studies. In biology, Silicea increase the production of paf-acether by mouse peritoneal macrophages. The high dilutions of Silicea have been studied using nuclear magnetic resonance, with reproducible modifications of water proton relaxation times. It has been used in India for the treatment of tubercular lymphadenitis and could be included in the homeopathic treatment given in addition to the standard care in multi drug resistant pulmonary tuberculosis.

The aminoglycoside (AG) antibiotics have seen a resurgence in their clinical use given the increase in multi drug resistant bacterial infections. Campaigns to generate novel analogs show promise that structural modification can lead to compounds with improved pharmacological properties. The results described herein include a new method to synthesize mono-, di-, and mixed N-alkylated kanosamine sugars and their elaboration into novel glycosides that inhibit bacterial protein synthesis in vitro.

Multi-drug-resistant Gram-negative organisms (MDRGNO) are an emerging global threat, reflected in the increasing incidence of infections in Ireland and elsewhere. The response to this threat has been the development of Infection Prevention and Control (IPC) guidelines. A survey of IPC teams in Ireland was undertaken to assess compliance with national guidelines. To place these survey results in context, IPC guidelines from the Irish Health Protection Surveillance Centre (HPSC) are compared with guidelines from Healthcare Infection Society (HIS), European Society of Clinical Microbiology and Infectious Diseases (ESCMID) and Centre for Disease Control (CDC). Thirty-three percent of hospitals responded across a range of hospital types. The results highlight the variability in implementation of guidelines across Ireland, as well as the variability between guidelines internationally. Respondents are less than 90% compliant with the majority of MDRGNO screening guidelines. Hospitals have variable access to isolation facilities with an average of 29% single rooms available (range 2.6-100%), resulting in some patients with MDRGNO not being isolated. Broad variability in application of guidance on personal protective equipment was demonstrated. This survey gives an insight into the real-life applicability of HPSC guidelines. Survey results are placed in context with a comparison of five MDRGNO IPC guidelines. Although core tenets of IPC are standard across guidelines, research into which practices are efficient in reducing MDRGNO transmission while being cost-effective would be worthwhile.

Diabetes Mellitus (DM) and its associated complications including neuropathy, retinopathy, nephropathy, diabetic wound etc. are major problems all around the globe. Triphala, an ayurvedic formulation consists of fruit powders of Emblica officinalis, Terminalia belerica, and Terminalia chebula. The Triphala nanoparticles (TNp) was formulated, characterized and screened for its antioxidant, anti-diabetic, and antimicrobial potential. TNp was incorporated into medical fabrics and evaluated for its antibacterial potential against E. coli ATCC (25922) and multi drug resistant (MDR) E. coli isolated from diabetic wound. The results suggest that TNp possess antioxidant, antidiabetic and antibacterial activities. In future, TNp incorporated nano biomaterial might be an effective alternate to control diabetes related infection.

There is a growing interest in essential oil-based nanoemulsions, as an alternative antimicrobial compound for controlling multiple drug resistant (MDR) pathogens, such as Acinetobacter baumannii (A. baumannii). In this study, stable nanoemulsion was prepared from Thymus daenensis (T. daenensis) essential oil, and characterized in terms of physical stability, particle size, size distribution and shape, using dynamic light scattering (DLS) and transmission electron microscopy (TEM). Then, the antibacterial activity of the most stable preparation of nanoemulsion and pure oil was investigated, against 10 MDR A. baumannii isolates. In addition, anti-biofilm activity was analysed against selected MDR isolate (The number 40). The most stable nanoemulsion was produced with the particle size of 171.88 ± 1.57 nm, and spherical shape of nanoemulsion particles was confirmed by TEM images. The strong antibacterial activity of T. daenensis nanoemulsion and pure oil was revealed with MIC values of 30–45 μg/mL and 62.5–87.5 μg/mL, respectively. In addition, the nanoemulsion had considerable anti-biofilm activity on sub-lethal dose (56.43% inhibition in 1/2 MIC concentration), after 24 h of incubation. Presented data could help with the development of new therapeutically strategies for bacterial infections.

An endemic multi-drug resistant ST117 E. coli isolate coproducing MCR-1 and 3 ESBL loci was, for the first time, detected from diseased chicken, Liaoning Province, in Northeast China, from 2011 to 2012. Whole-genome sequencing revealed 5 unique plasmids, namely pHXH-1, pHXH-2, pHXH-3, pHXH-4 and pHXH-5). Among them, pHXH1 and pHXH4 encode ESBL, and pHXH-5 mediates MCR-1 colistin resistance. The results indicate that the potentially-national dissemination of MCR-1-positive pathogens with pan-drug resistance proceeds via food chains.

Over the past two decades, we have been confronted with an increase in the frequency and diversity of multi-drug-resistant microorganisms, leading in some cases to serious and life-threatening infections. To compound the problem, during the same timeframe, we have seen a significant decrease in the number of new, FDA-approved antimicrobial agents to treat these infections. In order to understand the gravity of the problem, we need to address the reasons behind the dramatic increase in antimicrobial resistance and the consequences facing us, as well as potential solutions to the problem.

This research was designed to evaluate the AgNPs synthesizing potential of methanol leaf extract of Justicia adhatoda and assessed their potential against multi-drug resistant microbes and in anticancer activity. The results obtained from this study showed that the methanol leaf extract of J. adhatoda has the potential to synthesized AgNPs, and it was initially confirmed by color (brown) change and observed sharp peak at 410 nm under UV-vis analysis. The FTIR analysis confirmed that the presence of functional groups involved in the fabrication of AgNPs. The XRD and EDX analyses confirm the crystalline structure and elemental composition of biofabricated AgNPs. The SEM and TEM analyses confirmed that the synthesized AgNPs were spherical and 5 to 20 nm in size. Furthermore, the synthesized AgNPs have outstanding antimicrobial activities against multi-drug resistant bacteria (S. pyrogens, E. coli, V. cholerae, S. aureus, and K. pneumoniae) and fungi (Penicillium sp., A. niger, C. albicans, Rhizobus sp., and A. flavus). Interestingly, the AgNPs showed remarkable anticancer activity (82.4%) against the cervical cancer cell line (HeLa) at the concentration of 100 µg mL-1 and LD50 value was found as 80 µg mL-1. These results concludes that J. adhatoda has the potential to synthesize AgNPs has remarkable biomedical applications.

We introduce a novel fractional-order model for the coinfection of HIV and tuberculosis (TB), in the presence of multi-drug resistant TB strains (MDR-TB) and treatment for both diseases. We compute the reproduction number of the HIV and TB submodels and of the full model and the local and global stabilities of the disease-free equilibria. Numerical simulations show the different dynamics of the model for variation of biologically relevant parameters, and for the order of the fractional derivative α ∈]0, 1]. The results obtained highlight the importance of treatment for HIV and TB and the role of the MDR-TB strains in the severity of the coinfection. Moreover, the order of the fractional derivative is a significant player in the epidemics theatre.

Background: The aim of this study was to assess the safety and efficacy of colistin use in critically ill neonates. Methods: This was a caseâcontrol study that included newborn infants with proven or suspected nosocomial infections between January 2012 and October 2015, at two centers in Diyarbakir, Turkey. The clinical and laboratory characteristics and outcomes of patients who received colistin therapy were reviewed and compared to patients who were treated with antimicrobial agents other than colistin during the same period. Results: Forty-seven cases who received intravenous colistin (colistin group) and 59 control patients (control group) were included. There were no significant differences between the groups regarding outcomes and nephrotoxicity, including acute renal failure. Colistin therapy was associated with significantly reduced serum magnesium (1.38 ± 0.39 mg/dL vs. 1.96 ± 0.39 mg/dL, pÂ

C. auris is an emerging fungal pathogen with high prevalence of resistance to current antifungal agents. Central nervous system infection with C. auris has been infrequently described. We describe here an adult with nosocomial CSF shunt infection due to multi drug resistant C. auris. Systemic therapy with echinocandin and flucytosine failed. Fortunately, administration of daily intraventricular caspofungin 10 mg for 10 days in conjunction with systemic voriconazole resulted in both clinical and microbiological cure. Keywords: C. auris, CSF shunt, Intraventricular caspofungin

In order to investigate new effective and inexpensive nano-therapeutic approach for P. aeruginosa, staphylococcus aureus and coagulase negative staphylococci (CoNS), the present study reports an eco-friendly process for rapid synthesis of silver nanoparticles (Ag-NPs) using aqueous leaf extract of Corchorus Capsularis (CRCP). Formation of stable Ag-NPs at different time intervals gives mostly spherical particles with diameters ranging from 5 to 45 nm. The resulting Ag-NPs were characterized using Ultraviolet visible (UV–Vis) spectroscopy, Fourier Transform Infrared (FT-IR) spectroscopy, X-Ray Diffraction (XRD) analysis, Transmission Electron Microscopy (TEM) and Energy Dispersive X-ray analysis (EDX). XRD study shows that the particles are crystalline in nature with face centered cubic geometry. TEM studies show the formation of Ag-NPs with average size of 20.52 nm. The antimicrobial activity of the synthesized Ag-NPs was investigated against multi drug resistant (MDR) P. aeruginosa , Staphylococcus aureus and CoNS isolates from post-surgical wound infections. The present study suggests that Ag-NPs synthesized from aqueous leaf extract of CRCP shows significant antibacterial potential against MDR isolates from post-surgical wound infections.

Background Pseudomonas aeruginosa is an emerging threat to public health worldwide due to their rapid development of drug resistance including beta-lactamases. The present study was designed to investigate the incidence of β-lactamases and genotypic pattern of CTX and OXA in the clinical isolate of multidrug resistant P. aeruginosa. Methods In this study a total of 102 MDR P. aeruginosa isolates obtained from Lady Reading Hospital, Peshawar, Pakistan were subjected to extended spectrum beta lactamase (ESBL), metallo beta lactamase (MBL) and plasmid mediated β-lactamase (AmpC) detection using phenotypic and molecular methods. Furthermore, sequencing of CTX and OXA gene was performed. Results Out of 102 MDR P. aeruginosa isolates, 71 (69.6%) were beta lactamase producers. The incidence of ESBL, MBL and AmpC in clinical isolates of P. aeruginosa was found to be 23.94%, 40.84% and 35.21% respectively. Co-production of ESBL and AmpC were also observed in some isolates. There were 14 (19.71%) CTX-M-15 harboring isolates which were ESBL (64.28%), MBL (21.42%) and AmpC (14.28%) producer. Co-production of ESBL/MBL (14.28%), ESBL/AmpC (14.28%) and MBL/AmpC (14.28%) were also observed in the CTX M-15 harboring isolates while 12.28% isolates were not ESBL, MBL or AmpC producer. OXA-10 was detected in 8 (11.26%) isolates which were ESBL (12.5%), MBL (37.5%) and AmpC (12.5%) producer. OXA 10 isolates also exhibit co-production of ESBL/AmpC (12.5%) and MBL/AmpC (12.5%). All CTX-M-15 carried the class A β-lactamase conserved domain while OXA-10 harbored conserved domain of class D β-lactamase. Conclusion The current study for the first time reported and characterized the CTX-M-15 and OXA-10 among MDR P. aeruginosa isolates from Pakistan. Further efforts are needed to understand the molecular mechanism of drug resistance with CTX and OXA harboring P. aeruginosa isolates.

Tuberculosis (TB) is a highly contagious airborne disease with nearly 25% of the world's population infected with it. Challenges such as multi drug resistant TB (MDR-TB), extensive drug resistant TB (XDR-TB) and in rare cases totally drug resistant TB (TDR-TB) emphasizes the critical and urgent need in developing novel TB drugs. Moreover, the prolonged and multi drug treatment regime suffers a major drawback due to high toxicity and vulnerability in TB patients. This calls for intensified research efforts in identifying novel molecular scaffolds which can combat these issues with minimal side effects. In this pursuit, researchers have screened many bio-active molecules among which coumarin have been identified as promising candidates for TB drug discovery and development. Coumarins are naturally occurring compounds known for their low toxicity and varied biological activity. The biological spectrum of coumarin has intrigued medicinal researchers to investigate coumarin scaffolds for their relevance as anti-TB drugs. In this review we focus on the recent developments of coumarin and its critical aspects of structural design required to exhibit anti-tubercular (anti-TB) activity. The information provided will help medicinal chemists to design and identify newer molecular analogs for TB treatment and also broadens the scope of exploring future generation potent yet safer coumarin based anti-TB agents.

We wish to thank members of the Infectious Disease Department and the Pathology Laboratory at King Khaled hospital in the Ministry of the National Guards – Health Affairs Western region for their support of our research. We also wish to acknowledge the Bioscience core laboratory at KAUST for their help with the sequencing operations. We thank Malak Haidar from KAUST Pathogen Genomics Laboratory for the technical help. We also acknowledge help from the team of curators at the Institut Pasteur MLST system (Paris, France) for importing novel alleles, profiles, and/or isolates at http://bigsdb.pasteur.fr.

4H-Chromene-based compounds, for example, CXL017, CXL035, and CXL055, have a unique anticancer potential that they selectively kill multi-drug resistant cancer cells. Reported herein is the extended structure-activity relationship (SAR) study, focusing on the ester functional group at the 4th position and the conformation at the 6th position. Sharp SARs were observed at both positions with respect to cellular cytotoxic potency and selectivity between the parental HL60 and the multi-drug resistant HL60/MX2 cells. These results provide critical guidance for future medicinal optimization.

Photodynamic antimicrobial chemotherapy (PACT) is employed against multi drug resistant Staphylococcus aureus using porphyrins combined with silver nanoparticles to bring about a combined photodynamic effect. We employ Zn-meso-5,10,15,20-tetra(4-pyridyl) (1), Zn-meso-5,10,15,20-tetrathienyl (2), and Zn-meso-5-(4-hydroxyphenyl)- 10,15,20-tris(2-thienyl)(3) porphyrins and their self-assembled conjugates with silver nanoparticles for PACT against Staphylococcus aureus. Complex 3 with nanoparticles was found to perform better resulting in 0% bacterial viability at 60 min.

Antimicrobial nanoemulsions (NEs) are emerging as unique class disinfectant agents for the treatment of MDR pathogens. The ESKAPE pathogens are major causative agents for most of the nosocomial infections, due to drug inactivation, drug binding sites modification and biofilm formation efficiency. The efficacy of NEs and their constituents was determined by MIC, MBC, adherence assay, biofilm studies and in vivo toxicity evaluation with Bombyx mori. The droplet sizes of the nanoemulsions were measured by DLS and the measurement showed monodispersed droplet size distribution (PDI

Thirteen jatrophane diterpenoids (1-10, 13-15), three previously isolated (11, 12, 16) and a known tigliane (17) were isolated from the latex of Euphorbia dendroides. The structures and relative configurations of compounds were elucidated by spectroscopic techniques. The P-glycoprotein (P-gp) inhibiting activities of the representative set of jatrophanes (1-6 and 11-16) have been assessed. Jatrophanes 2 and 5 demonstrated the most powerful inhibition of P-gp, higher than R(+)-verapamil and tariquidar in colorectal multi-drug resistant (MDR) cells (DLD1-TxR). Supplementary material: [http://cherry.chem.bg.ac.rs/handle/123456789/2902]

Multi-drug resistant (MDR) clinical isolates were used to test the bactericidal efficacy of the newly synthesized porous chitosan/silvernanocomposite film. The synthesized composite was characterized by using UV–Vis, FTIR, XRD and HRSEM analysis. The SEM images illustrate the presence of embedded silver nanoparticles (20–50 nm) throughout the films. Moreover, the presence of a small quantity of metal nanoparticles in the composite was enough to significantly enhance inactivation of MDR pathogens as compared with unaltered chitosan.