Broad-spectrum Antimicrobials Research Articles

Conjugated carbon monoxide-releasing moleculeshave broad-spectrum antimicrobial activity.

Aim: To test the antimicrobial effect of carbon monoxide-releasing molecules (CORMs) conjugated with azoles on different microorganisms. Methods & results: We used broth microdilution, checkerboard and cytotoxicity assays, as well asimaging, fluorescenceand bioluminescence experiments to study [Re(CO)3(2,2'-bipyridyl)(Ctz)]+ (also known asReBpyCtz). ReBpyCtz exhibits alow minimum inhibitory concentrationvalue, increases the intracellular formation of reactive oxygen species and causes significant alterations on Staphylococcus aureus's membrane. ReBpyCtz is active against fungi, having a more prolonged fungicidal effect on Candida glabrata than clotrimazole andis selectively active onblood-stage malaria parasites, at a concentration that is not toxicto kidney epithelial cells. Conclusion: Conjugated CORMs have the potential to be active against different types of pathogens, thus constituting a promising class of broad-spectrum antimicrobials.

Transient Coatings from Nanoparticles Achieving Broad-Spectrum and High Antimicrobial Performance.

Cationic and hydrophilic coatings based on casting and drying water dispersions of two different nanoparticles (NPs) onto glass are here described and evaluated for antimicrobial activity. Discoid cationic bilayer fragments (BF) surrounded by carboxy-methylcellulose (CMC) and poly (diallyl dimethyl ammonium) chloride (PDDA) NPs and spherical gramicidin D (Gr) NPs dispersed in water solution were cast onto glass coverslips and dried, forming a coating quantitatively evaluated against Pseudomonas aeruginosa, Staphylococcus aureus and Candida albicans. From plating and colony forming units (CFU) counting, all strains interacting for 1 h with the coatings lost viability from 105 to 106, to zero CFU, at two sets of Gr and PDDA doses: 4.6 and 25 μg, respectively, or, 0.94 and 5 μg, respectively. Combinations produced broad spectrum, antimicrobial coatings; PDDA electrostatically attached to the microbes damaging cell walls, allowing Gr NPs interaction with the cell membrane. This concerted action promoted optimal activity at low Gr and PDDA doses. Further washing and drying of the deposited dried coatings showed that they were washed out so that antimicrobial activity was no longer present on the glass surface. Significant applications in biomedical materials can be foreseen for these transient coatings.

Bacterial etiology of urinary tract infections in patients treated at Kenyan health facilities and their resistance towards commonly used antibiotics.

Evidence-based empirical antibiotic prescribing requires knowledge of local antimicrobial resistance patterns. The spectrum of pathogens and their susceptibility strongly influences guidelines for empirical therapies for urinary tract infections (UTI) management. This study aimed to determine the prevalence of UTI causative bacteria and their corresponding antibiotic resistance profiles in three counties of Kenya. Such data could be used to determine the optimal empirical therapy. In this cross-sectional study, urine samples were collected from patients who presented with symptoms suggestive of UTI in the following healthcare facilities; Kenyatta National Hospital, Kiambu Hospital, Mbagathi, Makueni, Nanyuki, Centre for Microbiology Research, and Mukuru Health Centres. Urine cultures were done on Cystine Lactose Electrolyte Deficient (CLED) to isolate UTI bacterial etiologies, while antibiotic sensitivity testing was done using the Kirby-Bauer disk diffusion using CLSI guidelines and interpretive criteria. A total of 1,027(54%) uropathogens were isolated from the urine samples of 1898 participants. Staphylococcus spp. and Escherichia coli were the main uropathogens at 37.6% and 30.9%, respectively. The percentage resistance to commonly used drugs for the treatment of UTI were as follows: trimethoprim (64%), sulfamethoxazole (57%), nalidixic acid(57%), ciprofloxacin (27%), amoxicillin-clavulanic acid (5%), and nitrofurantoin (9%) and cefixime (9%). Resistance rates to broad-spectrum antimicrobials, such as ceftazidime, gentamicin, and ceftriaxone, were 15%, 14%, and 11%, respectively. Additionally, the proportion of Multidrug-resistant (MDR) bacteria was 66%. High resistance rates toward fluoroquinolones, sulfamethoxazole, and trimethoprim were reported. These antibiotics are commonly used drugs as they are inexpensive and readily available. Based on these findings, more robust standardised surveillance is needed to confirm the patterns observed while recognising the potential impact of sampling biases on observed resistance rates.

Isolation and Characterization of a Weizmannia coagulans Bacteriophage Youna2 and Its Endolysin PlyYouna2.

Weizmannia coagulans (formerly Bacillus coagulans) is Gram-positive, and spore-forming bacteria causing food spoilage, especially in acidic canned food products. To control W. coagulans, we isolated a bacteriophage Youna2 from a sewage sludge sample. Morphological analysis revealed that phage Youna2 belongs to the Siphoviridae family with a non-contractile and flexible tail. Youna2 has 52,903 bp double-stranded DNA containing 61 open reading frames. There are no lysogeny-related genes, suggesting that Youna2 is a virulent phage. plyYouna2, a putative endolysin gene was identified in the genome of Youna2 and predicted to be composed of a N-acetylmuramoyl-L-alanine amidase domain (PF01520) at the N-terminus and unknown function DUF5776 domain (PF19087) at the C-terminus. While phage Youna2 has a narrow host range, infecting only certain strains of W. coagulans, PlyYouna2 exhibited a broad antimicrobial spectrum beyond the Bacillus genus. Interestingly, PlyYouna2 can lyse Gram-negative bacteria such as Escherichia coli, Yersinia enterocolitica, Pseudomonas putida and Cronobacter sakazakii without other additives to destabilize bacterial outer membrane. To the best of our knowledge, Youna2 is the first W. coagulans-infecting phage and we speculate its endolysin PlyYouna2 can provide the basis for the development of a novel biocontrol agent against various foodborne pathogens.

Chlorhexidine Mouthwash in Dentistry

Chlorhexidine is a mouthwash used by dentist and the public for its anti-bacterial properties. It is used in dentistry for many years as an excellent anti-plaque agent to prevent the development of periodontal diseases. Chlorhexidine not only exhibits special property of substantivity, it also possesses a broad antimicrobial spectrum which makes its use in wide variety of oral diseases and conditions. It is often used as an ingredient in various mouth washes designed to reduce plaque and oral disease. It has been shown to have an immediate bactericidal and long-term bacteriostatic effect due to adsorption on the enamel surface covered with the pellicle. It’s used in almost all the fields of dentistry in various forms such as mouth –washes, sprays, gels and restorative materials. The usual dose is 10- 15 ml of undiluted chlorhexidine gluconate oral rinse, swished in the mouth for 30 seconds, and expectorated.

Metabolic syndrome is independently associated with improved overall survival to first-line therapy with immune checkpoint inhibitors in non-small cell lung cancer.

Many co-existing medical conditions may affect the outcome in patients treated with immune checkpoint inhibitors for advanced cancer. There is currently not any information on whether metabolic syndrome (MetS) impacts the clinical outcome in patients treated with immune checkpoint inhibitors (ICIs) for advanced non-small cell line cancer (NSCLC). We carried out a single-center retrospective cohort study to determine the effects of MetS on first-line ICI therapy in patients with NSCLC. One hundred and eighteen consecutive adult patients who received first-line therapy with ICIs and had adequate medical record information for the determination of MetS status and clinical outcomes were included in the study. Twenty-one patients had MetS and 97 did not. There was no significant difference between the two groups in age, gender, smoking history, ECOG performance status, tumor histologic types, pre-therapy use of broad-spectrum antimicrobials, PD-L1 expression, pre-treatment neutrophil:lymphocyte ratio, or proportions of patients who received ICI monotherapy or chemoimmunotherapy. With a median follow-up of 9 months (range 0.5-67), MetS patients enjoyed significantly longer overall survival (HR 0.54, 95% CI: 0.31-0.92) (p = 0.02) but not progression-free survival. The improved outcome was only observed in patients who received ICI monotherapy and not chemoimmunotherapy. MetS predicted for higher probability of survival at 6 months (p = 0.043) and 12 months (p = 0.008). Multivariate analysis indicated that, in addition to the known adverse effects of use of broad-spectrum antimicrobials and the beneficial effects of PD-L1 (Programmed cell death-ligand 1) expression, MetS was independently associated with improved overall survival but not progression-free survival. Our results suggest that MetS is an independent predictor of treatment outcome in patients who received first-line ICI monotherapy for NSCLC.

Association of Time of Day with Delays in Antimicrobial Initiation among Ward Patients with Hospital-Onset Sepsis.

Rationale: Although the mainstay of sepsis treatment is timely initiation of broad-spectrum antimicrobials, treatment delays are common, especially among patients who develop hospital-onset sepsis. The time of day has been associated with suboptimal clinical care in several contexts, but its association with treatment initiation among patients with hospital-onset sepsis is unknown. Objectives: Assess the association of time of day with antimicrobial initiation among ward patients with hospital-onset sepsis. Methods: This retrospective cohort study included ward patients who developed hospital-onset sepsis while admitted to five acute care hospitals in a single health system from July 2017 through December 2019. Hospital-onset sepsis was defined by the Centers for Disease Control and Prevention Adult Sepsis Event criteria. We estimated the association between the hour of day and antimicrobial initiation among patients with hospital-onset sepsis using a discrete-time time-to-event model, accounting for time elapsed from sepsis onset. In a secondary analysis, we fit a quantile regression model to estimate the association between the hour of day of sepsis onset and time to antimicrobial initiation. Results: Among 1,672 patients with hospital-onset sepsis, the probability of antimicrobial initiation at any given hour varied nearly fivefold throughout the day, ranging from 3.0% (95% confidence interval [CI], 1.8-4.1%) at 7 a.m. to 13.9% (95% CI, 11.3-16.5%) at 6 p.m., with nadirs at 7 a.m. and 7 p.m. and progressive decline throughout the night shift (13.4% [95% CI, 10.7-16.0%] at 9 p.m. to 3.2% [95% CI, 2.0-4.0] at 6 a.m.). The standardized predicted median time to antimicrobial initiation was 3.2 hours (interquartile range [IQR], 2.5-3.8 h) for sepsis onset during the day shift (7 a.m.-7 p.m.) and 12.9 hours (IQR, 10.9-14.9 h) during the night shift (7 p.m.-7 a.m.). Conclusions: The probability of antimicrobial initiation among patients with new hospital-onset sepsis declined at shift changes and overnight. Time to antimicrobial initiation for patients with sepsis onset overnight was four times longer than for patients with onset during the day. These findings indicate that time of day is associated with important care processes for ward patients with hospital-onset sepsis. Future work should validate these findings in other settings and elucidate underlying mechanisms to inform quality-enhancing interventions.

Secretory Expression and Application of Antilipopolysaccharide Factor 3 in Chlamydomonas reinhardtii.

Anti-lipopolysaccharide factor is a class of antimicrobial peptides with lipopolysaccharide-binding structural domains, which has a broad antimicrobial spectrum, high antimicrobial activities, and broad application prospects in terms of the aquaculture industry. However, the low yield of natural antimicrobial peptides and their poor expression activity in bacteria and yeast have hindered their exploration and utilization. Therefore, in this study, the extracellular expression system of Chlamydomonas reinhardtii, by fusing the target gene with the signal peptide, was used to express anti-lipopolysaccharide factor 3 (ALFPm3) from Penaeus monodon in order to obtain highly active ALFPm3. Transgenic C. reinhardtii T-JiA2, T-JiA3, T-JiA5, and T-JiA6, were verified using DNA-PCR, RT-PCR, and immunoblot. Additionally, the IBP1-ALFPm3 fusion protein could be detected not only within the cells but also in the culture supernatant. Moreover, the extracellular secretion containing ALFPm3 was collected from algal cultures, and then its bacterial inhibitory activity was analyzed. The results showed that the extracts from T-JiA3 had an inhibition rate of 97% against four common aquaculture pathogenic bacteria, including Vibrio harveyi, Vibrio anguillarum, Vibrio alginolyticus, and Vibrio parahaemolyticus. The highest inhibition rate of 116.18% was observed in the test against V. anguillarum. Finally, the minimum inhibition concentration (MIC) of the extracts from T-JiA3 to V. harveyi, V. anguillarum, V. alginolyticus, and V. parahaemolyticus were 0.11 μg/μL, 0.088 μg/μL, 0.11 μg/μL, and 0.011 μg/μL, respectively. This study supports the foundation of the expression of highly active anti-lipopolysaccharide factors using the extracellular expression system in C. reinhardtii, providing new ideas for the expression of highly active antimicrobial peptides.

Thiazolyl hydrazineylidenyl indolones as unique potential multitargeting broad-spectrum antimicrobial agents

The emergence of pathogenic and drug-resistant microorganisms seriously threatens public safety. This work constructed a unique type of thiazolyl hydrazineylidenyl indolones (THIs) to combat global microbial multidrug-resistance. Bioactive evaluation discovered that some target THIs displayed much superior antimicrobial efficacy than clinical chloromycetin, norfloxacin, cefdinir or fluconazole against the tested strains. Eminently, butyl THI 6c displayed a broad antimicrobial spectrum with low MICs of 0.25–1 μg/mL. The highly active THI 6c not only showed low cytotoxicity and hemolysis, rapidly bactericidal ability, good antibiofilm activity and promising pharmacokinetic properties, but also could significantly impede the development of bacterial resistance. Preliminary exploration of antibacterial mechanism revealed that THI 6c could effectively penetrate the cell membrane of MRSA and embed DNA to form 6c‒DNA supramolecular complex and thus hinder DNA replication. Moreover, THI 6c could reduce cell metabolic activity, which might be attributed to the fact that THI 6c could target the pyruvate kinase of MRSA and interfere with the function of the enzyme. These results provided powerful information for further developing thiazolyl hydrazineylidenyl indolones as new broad-spectrum antimicrobial agents.

Delayed onset ADA-SCID presenting as secondary HLH in a patient with normal newborn screening

Severe combined immunodeficiency (SCID) is a rare genetic syndrome caused by aberrant immune cell development or function and is fatal without early identification and treatment. The Centers for Disease Control estimates the annual incidence of SCID to be one case per 40,000 to 100,000 live births. Newborn screening using T-cell receptor excision circles (TREC) allows for early detection and timely treatment of SCID. Adenosine deaminase (ADA) is a vital enzyme in the purine salvage pathway, and its deficiency results in disruption of T, B and NK cell development, accounting for 10–20% of SCID cases. The timing of ADA-SCID presentation ranges from birth to delayed onset disease. Importantly, without early recognition and treatment, delayed onset ADA-SCID results in accumulation of toxic metabolites causing immune dysfunction, recurrent infections, and subsequent organ damage. Recently, some groups have questioned whether traditional TREC newborn screening adequately identifies ADA-SCID, especially those cases with delayed onset. We present the case of a 2-year-old male with normal newborn screening but a history of recurrent otitis media and respiratory infections who developed multisystem organ failure and septicemia with Escherichia coli, candida, adenovirus and enterovirus despite broad-spectrum antimicrobials. The patient also had features of a hyperinflammatory syndrome with fever, pancytopenia, hypertriglyceridemia, and hyperferritinemia and was treated for hemophagocytic lymphohistiocytosis (HLH) with dexamethasone and plasma exchange followed by anakinra, etoposide, and emapalumab. The patient was maximally supported with mechanical ventilation, extracorporeal membrane oxygenation, and renal replacement therapy but had progressive clinical deterioration and ultimately expired. Autopsy was notable for thymic aplasia and erythrophagocytosis in the bone marrow and lymph nodes. Genetic testing revealed a heterozygous missense pathogenic variant in exon 7 in the ADA gene as well as novel heterozygous intronic variant of unknown significance in the ADA gene. Postmortem data suggests this patient had ADA-SCID with multi-pathogen infections and secondary HLH. This case potentially identifies a novel pathogenic variant in ADA missed by traditional TREC newborn screening and highlights the need to retain a high clinical suspicion of SCID in patients with a history of recurrent infections despite normal TREC screening.

Severe pediatric adenoviral pneumonia combined with invasive pulmonary aspergillosis

BackgroundThis study aimed to analyze the clinical characteristics of severe pediatric adenoviral pneumonia combined with invasive pulmonary aspergillosis.MethodsWe retrospectively analyzed the clinical data of five children clinically diagnosed with severe adenoviral pneumonia combined with invasive pulmonary aspergillosis at Xiamen Children’s Hospital.ResultsThese five children included one boy and four girls, with ages of onset ranging from 8 months and 15 days to 2 years and 2 months. All of them had fever with a mean duration of 11–35 days and cough. Pulmonary imaging was performed, which revealed solid pulmonary opacification in all five children, pleural effusion in two children, and emphysema and multiple small cavity formations in one child. Multiple microbiological tests were performed on the 5 children, and adenovirus was positive in the alveolar lavage fluid for the first time, and aspergillus culture was positive in the second test. On tracheoscopy, the bronchial mucosa was seen to be congested and edematous or pale and eroded; white moss-like material was seen adhering to the tracheal wall or even blocking the airway. The five children were treated with a combination of two or more broad-spectrum antimicrobials, glucocorticoids, and gamma globulins and underwent bronchoscopy. Voriconazole was added in the treatment regimen after the diagnosis of aspergillosis (28–34 days of treatment). Four of the children were discharged in good condition with a mean total length of hospital stay of 17–47 days. The other child leave against medical advice. Follow-up 3–5 months after discharge showed that one child had been cured; two children had developed obliterative bronchiolitis; one child had developed bronchiectasis; and the remaining child who had been discharged spontaneously was not contactable via telephone.ConclusionsImmune disorders and antibiotic and steroid treatments for adenovirus infection are high-risk factors for secondary invasive pulmonary aspergillosis in children. Prolonged fever and cough are the main manifestations, but which lack specificity, and bronchoscopic mucosal-specific injury evaluation and alveolar lavage fluid culture are helpful in the diagnosis of aspergillosis. The long-term prognosis of severe pediatric adenoviral pneumonia combined with invasive pulmonary aspergillosis maybe poor.

Recombinant Antimicrobial Peptide OaBac5mini Alleviates Inflammation in Pullorum Disease Chicks by Modulating TLR4/MyD88/NF-κB Pathway.

Pullorum disease (PD), caused by Salmonella Pullorum (S. Pullorum), is a serious threat to the poultry industry worldwide. Antimicrobial peptides (AMPs) have drawn extensive attention as new-generation antibiotics because of their broad antimicrobial spectrum, low resistance, and low cytotoxicity. AMP OaBac5mini exhibits strong antibacterial activity against Gram-negative bacteria, but its efficacy and anti-inflammatory effects on chicks with PD remain unclear. The aim of this study was to generate recombinant OaBac5mini via the Escherichia coli (E. coli) recombinant expression system and evaluate its antibacterial effect against S. Pullorum in vitro and in vivo. Real-time cellular analysis (RTCA) results showed that recombinant OaBac5mini exhibited no cytotoxicity on IPEC-J2 and RAW 264.7 cells and significantly alleviated the drop in the cell index of S. Pullorum-infected cells (p < 0.0001). In the chick model of PD, recombinant OaBac5mini significantly attenuated the increase in organ indexes (heart, liver, spleen, and kidney) and bacterial loads (liver and spleen) induced by S. Pullorum. Histopathology examination showed that recombinant OaBac5mini ameliorated histopathological changes and inflammation in chicks with PD, including impaired epithelium of duodenal villi, infiltration of pseudoacidophilic granulocytes in the cecum and bursa of Fabricius, congested blood clots and increased macrophages in the liver, and increased lymphoid nodule and B lymphocytes in the spleen. Western blot and quantitative real-time PCR (qRT-PCR) results indicated that recombinant OaBac5mini alleviated inflammation by modulating innate immunity through the TLR4/MyD88/NF-κB pathway and by suppressing the expression of pro-inflammatory cytokines. These results suggested that recombinant OaBac5mini has good potential as a clinical substitute for antibiotics in PD intervention.

Aspergillus niger CJ6 extract with antimicrobial potential promotes in-vitro cytotoxicity and induced apoptosis against MIA PaCa-2 cell line

Nowadays, the increased number of multidrug-resistant strains among pathogens is a severe public health concern and cancer is posing a great threat for humans. These problems should be tackled with the development of novel and broad-spectrum antimicrobials from microbial origin. During the present study, the bioactive secondary metabolites from Aspergillus niger CJ6 were extracted, characterized; their biological properties were evaluated by subjecting them for antimicrobial, antifungal and anticancer activities. The potent isolate Aspergillus niger CJ6 with nucleotide sequence of 959 base pairs showed antagonistic activity against fungal pathogens in dual culture. The chemical profiling of crude ethyl acetate extract indicated the presence of various bioactive molecules belonging to phenolic, hydrocarbons, and phthalate derivative classes. In antimicrobial activity, the crude extract displayed increasing activity with increased concentration; the highest activity observed against Shigella flexneri with 15 ± 1.0, 19 ± 0.5, 20 ± 1.0 and 24 ± 1.0 mm zones of inhibition at 25, 50, 75 and 100 μl concentrations. The MTT assay illustrated deformed cells of MIA PaCa-2 cell line in in-vitro cytotoxic activity; outflow of cell matrix and membrane rupture; the IC50 of 90.78 μg/ml suggested moderate potential of extract to prevent cancer cell growth. The apoptosis/necrosis study by flow cytometer exhibited 8.98 ± 0.85% early and 73 ± 0.7% of late apoptotic population with 3.8 ± 1.1% necrotic cells; only 14.22 ± 0.6% of healthy cells suggested the increased apoptosis inducing capacity of Aspergillus niger CJ6 crude extract. The outcomes of this study persuade further exploration on the identification, purification and development of novel bioactive agents that could help battle fatal diseases in humans.

An increasing threat in intensive care units: evaluation of multi-drug-resistant Myroides spp. infections and risk factors

Myroides spp. are Gram-negative bacilli that are commonly found in soil and water, acting as low-level opportunistic pathogens and causing a variety of infections. To assess the risk factors for multi-drug-resistant myroides infections, association with comorbid illnesses, patient care and susceptibility to antibiotics. This retrospective analytical study was conducted in Istanbul Başakşehir Çam and Sakura City Hospital, and included patients with Myroides spp. isolated in their culture samples. Total hospitalization days, first isolation day and 30-day mortality values of the patients were analysed statistically, and P<0.05 was considered to indicate significance. Myroides spp. were isolated from 437 culture samples from 228 patients. Of these cases, 210 (92.1%) were classified as having asymptomatic bacteriuria, and 18 (7.9%) as having an infection caused by Myroides spp. One hundred and seventy-four (76.3%) patients were followed up in the intensive care unit, and total hospitalization days (median 24.5 days) and first isolation day (median 9.5 days) of infected patients were shorter than those for colonized patients (P=0.023 and 0.030, respectively). No difference was found in 30-day mortality between infected and colonized patients (P=0.312). Myroides infections were seen more frequently in patients who were hospitalized for a long time, used broad-spectrum antimicrobials, underwent invasive procedures, and had co-factors such as diabetes and cerebrovascular disease. In addition, the resistance rates of Myroides odoratus were higher than those of Myroides odoratimimus, and the use of quinolones for the treatment of patients with M.odoratimimus infection led to a higher cure rate.

Candida lipolytica Bloodstream Infection in an Adult Patient with COVID-19 and Alcohol Use Disorder: A Unique Case and a Systematic Review of the Literature.

Candida lipolytica is an uncommon Candida species causing invasive fungemia. This yeast is mainly associated with the colonisation of intravascular catheters, complicated intra-abdominal infections, and infections in the paediatric population. Here, we report a case of C. lipolytica bloodstream infection in a 53-year-old man. He was admitted for an alcohol withdrawal syndrome and mild COVID-19. Among the primary risk factors for candidemia, only the use of broad-spectrum antimicrobials was reported. The empiric treatment was commenced with caspofungin and then targeted with intravenous fluconazole. Infective endocarditis was ruled out using echocardiography, and PET/TC was negative for other deep-seated foci of fungal infection. The patient was discharged after blood culture clearance and clinical healing. To the best of our knowledge, this is the first case of C. lipolytica candidemia in a patient with COVID-19 and alcohol use disorder. We performed a systematic review of bloodstream infections caused by C. lipolytica. Clinicians should be aware of the possibility of C. lipolytica bloodstream infections in patients with alcohol use disorder, especially in a COVID-19 setting.

A Novel Generation of Tailored Antimicrobial Drugs Based on Recombinant Multidomain Proteins.

Antibiotic resistance has exponentially increased during the last years. It is necessary to develop new antimicrobial drugs to prevent and treat infectious diseases caused by multidrug- or extensively-drug resistant (MDR/XDR)-bacteria. Host Defense Peptides (HDPs) have a versatile role, acting as antimicrobial peptides and regulators of several innate immunity functions. The results shown by previous studies using synthetic HDPs are only the tip of the iceberg, since the synergistic potential of HDPs and their production as recombinant proteins are fields practically unexplored. The present study aims to move a step forward through the development of a new generation of tailored antimicrobials, using a rational design of recombinant multidomain proteins based on HDPs. This strategy is based on a two-phase process, starting with the construction of the first generation molecules using single HDPs and further selecting those HDPs with higher bactericidal efficiencies to be combined in the second generation of broad-spectrum antimicrobials. As a proof of concept, we have designed three new antimicrobials, named D5L37βD3, D5L37D5L37 and D5LAL37βD3. After an in-depth exploration, we found D5L37D5L37 to be the most promising one, since it was equally effective against four relevant pathogens in healthcare-associated infections, such as methicillin-susceptible (MSSA) and methicillin-resistant (MRSA) Staphylococcus aureus, methicillin-resistant Staphylococcus epidermidis (MRSE) and MDR Pseudomonas aeruginosa, being MRSA, MRSE and P. aeruginosa MDR strains. The low MIC values and versatile activity against planktonic and biofilm forms reinforce the use of this platform to isolate and produce unlimited HDP combinations as new antimicrobial drugs by effective means.

Subgingival chlorhexidine irrigation for scaling and root planing adjunctive therapy in chronic periodontitis: a systematic review

BACKGROUND Scaling and root planing (SRP) is a conventional treatment for chronic periodontitis; however, it has limitations in treating deep pockets. To enhance its efficacy, chlorhexidine (CHX) is proposed as adjunctive therapy with SRP due to its broad antimicrobial spectrum, low systemic toxic activity in humans, absence of oral microorganism resistance, and lack of teratogenic effects. This study aimed to know the efficacy of the adjunctive therapy of CHX.&#x0D; METHODS A literature search was conducted using various databases including PubMed, LIVIVO, EBSCOhost, and Google Scholar, following the Preferred Reporting Items for Systematic Review and Meta-Analyses guidelines within the last 10 years (2011–2021). Clinical parameters such as plaque index (PI), gingival index (GI), bleeding on probing (BOP), pocket depth (PD), and clinical attachment level (CAL) were recorded. The risk of bias in the selected studies was assessed using Cochrane Collaboration’s Handbook version 5.2.0.&#x0D; RESULTS Of 368 studies, 10 met the inclusion criteria, with 8 of them having a higher quality. Higher reduction of PI, GI, BI, PD, and CAL were observed in SRP with CHX irrigation compared with SRP alone.&#x0D; CONCLUSIONS Overall, adding CHX to SRP appeared to have additional clinical benefits compared with SRP alone in the treatment of chronic periodontitis.

Subgingival chlorhexidine irrigation for scaling and root planing adjunctive therapy in chronic periodontitis: a systematic review

BACKGROUND Scaling and root planing (SRP) is a conventional treatment for chronic periodontitis; however, it has limitations in treating deep pockets. To enhance its efficacy, chlorhexidine (CHX) is proposed as adjunctive therapy with SRP due to its broad antimicrobial spectrum, low systemic toxic activity in humans, absence of oral microorganism resistance, and lack of teratogenic effects. This study aimed to know the efficacy of the adjunctive therapy of CHX.&#x0D; METHODS A literature search was conducted using various databases including PubMed, LIVIVO, EBSCOhost, and Google Scholar, following the Preferred Reporting Items for Systematic Review and Meta-Analyses guidelines within the last 10 years (2011–2021). Clinical parameters such as plaque index (PI), gingival index (GI), bleeding on probing (BOP), pocket depth (PD), and clinical attachment level (CAL) were recorded. The risk of bias in the selected studies was assessed using Cochrane Collaboration’s Handbook version 5.2.0.&#x0D; RESULTS Of 368 studies, 10 met the inclusion criteria, with 8 of them having a higher quality. Higher reduction of PI, GI, BI, PD, and CAL were observed in SRP with CHX irrigation compared with SRP alone.&#x0D; CONCLUSIONS Overall, adding CHX to SRP appeared to have additional clinical benefits compared with SRP alone in the treatment of chronic periodontitis.

Description of Antimicrobial-Resistant Escherichia coli and Their Dissemination Mechanisms on Dairy Farms.

Despite its importance in veterinary medicine, there is little information about antimicrobial resistance (AMR) and its transmission in dairy cattle. The aim of this work is to compare AMR phenotypes and genotypes in resistant Escherichia coli and to determine how the resistance genes spread among the E. coli population on dairy farms in Québec, Canada. From an existing culture collection of E. coli isolated from dairy manure, a convenient selection of the most resistant isolates (a high level of multidrug resistance or resistance to broad-spectrum β-lactams or fluoroquinolones) was analyzed (n = 118). An AMR phenotype profile was obtained for each isolate. Whole genome sequencing was used to determine the presence of resistance genes, point mutations, and mobile genetic elements. In addition, a subset of isolates from 86 farms was taken to investigate the phylogenetic relationship and geographic distribution of the isolates. The average agreement between AMR phenotypes and genotypes was 95%. A third-generation cephalosporin resistance gene (blaCTX-M-15), a resistance gene conferring reduced susceptibility to fluoroquinolones (qnrS1), and an insertion sequence (ISKpn19) were detected in the vicinity of each other on the genome. These genes were harbored in one triplet of clonal isolates from three farms located >100 km apart. Our study reveals the dissemination of resistant E. coli clones between dairy farms. Furthermore, these clones are resistant to broad-spectrum β-lactam and fluoroquinolone antimicrobials.

An Electronic Health Record Intervention to Limit Viral Testing of Cerebrospinal Fluid.

Meningitis and encephalitis are neurologic emergencies that require immediate management and current guidelines recommend empiric treatment with broad-spectrum antimicrobials. Cerebrospinal fluid (CSF) testing algorithms are heterogeneous and largely institution-specific, reflecting a lack of consensus on how to effectively identify CSF pathogens while conserving resources and avoiding false positives. Moreover, many lumbar punctures (LPs) performed in the inpatient setting are done for noninfectious workups, such as evaluation for leptomeningeal metastasis. As such, tailoring CSF testing to clinical context has been a focus of multiple prior reports and several healthcare systems have focused on efforts to limit low-yield diagnostic testing when a positive result is unlikely. To curb ordering viral PCRs when pre-test probability is low, some peer institutions have implemented pleocytosis criteria for virus-specific polymerase chain reaction (PCR) tests from CSF. In this report, we retrospectively analyzed the diagnostic testing of CSF from patients who had an LP while admitted to a single, large academic medical center and found that many cases of Herpes Simplex Virus (HSV) meningoencephalitis were diagnosed by non-neurologists. The rate of positive virus-specific PCR tests was very low, and tests were frequently ordered in duplicate with a multiplexed meningitis/encephalitis PCR panel (M/E panel, BioFire, Salt Lake City, UT). We designed and implemented a systems-level intervention to promote a revised stepwise testing algorithm that minimizes unnecessary tests. This intervention led to a significant reduction in the number of low-yield virus-specific PCR tests ordered without implementing a policy of cancelling virus-specific PCRs.