Broad-spectrum Antimicrobials Research Articles

Genomic characterization of two community-acquired methicillin-resistant Staphylococcus aureus with novel sequence types in Kenya.

Staphylococcus aureus is a clinically important bacteria with high antimicrobial resistance (AMR) challenge globally. The emergence of methicillin-resistant Staphylococcus aureus (MRSA) clones with unique sequence types have been identified in the community showing evidence that the epidemiology of MRSA globally is changing and requires continual surveillance. We utilized whole genome sequencing to characterize two community acquired-MRSA (CA-MRSA) strains isolated from wound swabs from community-onset infections in two health facilities in Kenya. The two strains belonged to multilocus sequence type (MLST) sequence type (ST) 7460, and ST 7635. The resistance genes detected showed that the novel STs are carriers of clinically relevant resistance genes. Linezolid and mupirocin resistance was observed, yet mupirocin is not commonly used in the country. Mutations within resistance genes were also detected and the pathogenicity toward the human host matched various pathogenic global S. aureus families, e.g., S. aureus subsp. aureus USA300. Multidrug efflux transporters, important in antimicrobial resistance including restriction enzymes type I and type IV were detected. Plasmids identified showed similarities with the plasmids in other clinically significant non-staphylococcal species, such as Pseudomonas aeruginosa, Escherichia coli, Morganella morganii, and Enterococcus faecium. Both STs belong to clonal complex 8 (CC8) which is the most successful MRSA clone in Kenya. Spa type t30 to which ST 7635 belongs has not been reported in the country. The results of this study further highlight the need for epidemiological studies to reveal circulating strains and antimicrobial resistance spread between hospitals and the community. The genomic research highlights resistance to anti-staphylococcal broad-spectrum antimicrobials not used frequently in the country, jeopardizing successful MRSA treatment since most health facilities do not perform genotypic resistance tests for routine patient management. Preliminary insights into unidentified STs of CA-MRSA in Kenya show the need for molecular epidemiological surveillance studies to further understand the diversity of S. aureus in Africa.

Polyhexamethylene biguanide hydrochloride (PHMB)-properties and application of an antiseptic agent. A narrative review.

The prevention and management of ocular surface infections is still one of the great challenges for ophthalmologists. The spread of antimicrobial resistance makes it necessary to use antiseptic substances with a broad antimicrobial spectrum. Polyhexamethylene biguanide hydrochloride (Polyhexanide, PHMB) is a broad-spectrum antiseptic with excellent tolerance and a low-risk profile. Its physicochemical action on the phospholipid membrane and DNA replication or repair mechanism, prevents or impedes the development of resistant bacterial strains. PHMB revealed its effective against numerous organisms like viruses, Gram-negative and Gram-positive bacteria, and fungi. Polyhexanide is commonly used as preservative in commercially available disinfecting solutions for contact lens care and in ophthalmic formulations at different concentrations ranging from 1 µg/ml to 50 µg/ml. The administration of 0.02% (200 µg/ml) PHMB is often the first-line therapy of Acanthamoeba keratitis. However, to date, only one close-out randomized controlled study tested the efficacy of 0.02% PHMB in Acanthamoeba keratitis and a phase III study is still ongoing. This paper reviews the antiseptic agent PHMB, focusing on biochemical mechanisms, safety profile and applications in ophthalmology.

Where Electrostatics Matter: Bacterial Surface Neutralization and Membrane Disruption by Antimicrobial Peptides SAAP-148 and OP-145.

The need for alternative treatment of multi-drug-resistant bacteria led to the increased design of antimicrobial peptides (AMPs). AMPs exhibit a broad antimicrobial spectrum without a distinct preference for a specific species. Thus, their mechanism, disruption of fundamental barrier function by permeabilization of the bacterial cytoplasmic membrane is considered to be rather general and less likely related to antimicrobial resistance. Of all physico-chemical properties of AMPs, their positive charge seems to be crucial for their interaction with negatively charged bacterial membranes. Therefore, we elucidate the role of electrostatic interaction on bacterial surface neutralization and on membrane disruption potential of two potent antimicrobial peptides, namely, OP-145 and SAAP-148. Experiments were performed on Escherichia coli, a Gram-negative bacterium, and Enterococcus hirae, a Gram-positive bacterium, as well as on their model membranes. Zeta potential measurements demonstrated that both peptides neutralized the surface charge of E. coli immediately after their exposure, but not of E. hirae. Second, peptides neutralized all model membranes, but failed to efficiently disrupt model membranes mimicking Gram-negative bacteria. This was further confirmed by flow cytometry showing reduced membrane permeability for SAAP-148 and the lack of OP-145 to permeabilize the E. coli membrane. As neutralization of E. coli surface charges was achieved before the cells were killed, we conclude that electrostatic forces are more important for actions on the surface of Gram-negative bacteria than on their cytoplasmic membranes.

424.3: Trends of Antibiotic Resistance in E. Coli, Klebsiella Spp., Pseudomonas Aeruginosa and Enterococcus Spp. Urinary Tract Infection in Renal Transplant Recipients From Pakistan Over a Decade

Introduction: Antimicrobial resistance is a major public threat worldwide. There has been an emergence of multi-drug resistant (MDR) bacterial infections over the last decade. MDR Klebsiella species have become one of the most common nosocomial pathogens in hospitals. In Pakistan, many studies reported a rising trend of resistance to antimicrobials in clinical isolates of Klebsiella species (spp.), E-coli, Pseudomonas aeruginosa and Enterococcus spp. Solid-organ transplant (SOT) recipients are more prone to infections, particularly with MDR organisms due to immunocompromised status, multiple hospital visits, and increased exposure to antibiotics. There is a paucity of data on antibiotic susceptibility patterns among renal transplant recipients from Pakistan. This study is conducted to find the trends in antimicrobial resistance patterns among common organisms isolated in the urinary tract over a 10-year period in renal transplant recipients. The aim is to guide the physicians regarding decisions over empirical antimicrobial choices. Methods: Sindh Institute of Urology and Transplantation (SIUT) is a 700-bedded tertiary care hospital in Karachi, Pakistan. It has had a comprehensive renal transplantation program with more than 6500 transplantations now. A retrospective computerized data review of urine cultures from renal transplant recipients in 2010 and 2020 was conducted. The trend of E.coli, Klebsiella species (spp.) Pseudomonas aeruginosa and Enterococcus spp. were collected. The resistance pattern of amoxicillin-clavulanic acid, ceftriaxone (ceftazidime for Pseudomonas aeurginosa), piperacillin-tazobactam, ciprofloxacin, amikacin, co-trimoxazole, and imipenem were compared over the 10 years period. Results: A total of 2,088 out of 6,249 (33%) and 2902 out of 8,115 (36%) urine cultures were positive in 2010 and 2020 respectively. The most common organisms isolated and their trend in the last decade is shown in figure 1.Over the decade, E-coli strains become 100% resistant to ciprofloxacin, ceftriaxone resistance has increased to 80%, and imipenem to 11%. In Klebsiella spp. imipenem resistance has increased to 19%. There is no significant change in the resistance pattern among Pseudomonas aeurginosa. Regarding Enterococcus spp. there is a rise in vancomycin resistance over the decade from 13% to 17% (Figure 2).Conclusion: Resistance to broad-spectrum antimicrobials has been increased with a>10% increase in carbapenems resistance over the last 10 years. E-coli has particularly become more resistant over the decade. We are also seeing more vancomycin-resistant enterococcus. The alarming increase in resistance may lead to increased morbidity in renal transplant recipients because we are left with only injectable options. We need a robust stewardship program for judicious use of antimicrobials and better infection control measures to contain increasing resistance.

Structure and functions of Aggregation-Induced Emission-Photosensitizers in anticancer and antimicrobial theranostics.

Photosensitizers with Aggregation-Induced Emission (AIE) can allow the efficient light-mediated generation of Reactive Oxygen Species (ROS) based on their complex molecular structure, while interacting with living cells. They achieve better tissue targeting and allow penetration of different wavelengths of Ultraviolet-Visible-Infrared irradiation. Not surprisingly, they are useful for fluorescence image-guided Photodynamic Therapy (PDT) against cancers of diverse origin. AIE-photosensitizers can also function as broad spectrum antimicrobials, capable of destroying the outer wall of microbes such as bacteria or fungi without the issues of drug resistance, and can also bind to viruses and deactivate them. Often, they exhibit poor solubility and cellular toxicity, which compromise their theranostic efficacy. This could be circumvented by using suitable nanomaterials for improved biological compatibility and cellular targeting. Such dual-function AIE-photosensitizers nanoparticles show unparalleled precision for image-guided detection of tumors as well as generation of ROS for targeted PDT in living systems, even while using low power visible light. In short, the development of AIE-photosensitizer nanoparticles could be a better solution for light-mediated destruction of unwanted eukaryotic cells and selective elimination of prokaryotic pathogens, although, there is a dearth of pre-clinical and clinical data in the literature.

Transepithelial Corneal Cross-linking with Supplemental Oxygen in Keratoconus Treatment - Corneal Stromal Demarcation Line and Safety

Purpose: To evaluate the corneal stromal demarcation line and safety of transepithelial corneal cross-linking (CXL) with supplemental oxygen in progressive keratoconus treatment. Methods: This is a retrospective review of 25 patients with progressive keratoconus who underwent epithelial-on CXL with supplemental oxygen from December 2019 to February 2022. Outcomes measured include corneal stromal demarcation line depth, volume of cornea treated, endothelial cell count, best-corrected visual acuity, keratometric parameters and post-treatment adverse events. Results: 25 eyes of 25 patients were included and mean age was 28.3 years. Mean follow-up period was 11.5 ± 1.39 months. Pre-operatively, mean ± standard deviation (SD) of K1, K2, Kmax and minimal corneal thickness were 45.9D ± 3.79D, 50.2D ± 4.83D, 57.5D ± 6.98D and 482.3um ± 36.8um respectively. There is no significant difference between pre and post-treatment corneal topographic parameters. There was improvement in BCVA post-treatment. The mean post-treatment corneal stromal demarcation line depth was 367.3 ± 89.8um. The volume of treated cornea including the central corneal epithelial thickness was 73.3 ± 4.39%. There was no reduction in endothelial cell count (ECC) post-procedure (pre-treatment mean ECC±SD: 2695.4 ± 224.5 cells/mm2, post-treatment ECC 2730.1 ± 252.0 cells/mm2, p-value = 0.33). Post-treatment corneal haze was mild and seen in 8 patients postoperatively. One patient developed a non-visual axis involving stromal infiltrate that resolved with topical broad-spectrum anti-microbials. Conclusion: Trans-epithelial CXL with supplemental oxygen for keratoconus treatment achieved comparable corneal stromal demarcation line depth comparable to that of conventional epithelial-off corneal cross-linking and had a similar safety profile.

Clinical Approach to Nosocomial Bacterial Sepsis.

Bacterial sepsis and septic shock are associated with a high mortality, and when clinically suspected, clinicians must initiate broad-spectrum antimicrobials within the first hour of diagnosis. Thorough review of prior cultures involving multidrug-resistant (MDR) pathogens along with other likely pathogens should be performed to provide an appropriate broad-spectrum empiric antibiotic coverage. The appropriate antibiotic loading dose followed by individualized modification of maintenance dose should be implemented based on the presence of hepatic or renal dysfunction. Use of procalcitonin is no longer recommended to determine need for initial antibacterial therapy and for de-escalation. Daily reevaluation of appropriateness of treatment is necessary based on the culture results and clinical response. All positive cultures should be carefully screened for possible contamination or colonization, which may not represent the true organism causing the sepsis. Culture negative sepsis accounts for one-half of all cases, and de-escalation of initial antibiotic regimen should be done gradually in these patients with close monitoring.

Antimicrobial use and aetiology of bloodstream infections in critically ill patients during early stages of SARS-CoV-2 pandemic

BackgroundDuring early stages of COVID-19 pandemic, antimicrobials were commonly prescribed.AimTo describe clinical, microbiological and antimicrobial use changes in bloodstream infections (BSI) of ICU patients during the first wave of COVID-19 pandemic compared to pre-COVID-19 era.MethodsObservational cohort study of patients admitted to ICU of Bellvitge University Hospital was conducted during the COVID-19 pandemic (March-June 2020) and before COVID-19 pandemic (March-June 2019). Differences in clinical characteristics, antimicrobial consumption and incidence and aetiology of BSI were measured.FindingsCOVID-19 patients had significantly less comorbidities with obesity the only risk factor that increased in frequency. COVID-19 patients more frequently required invasive supportive care measures, had longer median ICU stay and higher mortality rates. The incidence of BSIs was higher in COVID-19 period (RR 3.2 [95%CI 2.2–4.7]), occurred in patients who showed prolonged median ICU stay (21days) and was associated with high mortality rate (47%). The highest increases in the aetiological agents were observed for AmpC-producing bacteria (RR 11.1 [95%CI 2.6–47.9]) and non-fermenting rods (RR 7.0 [95%CI 1.5–31.4]). The emergence of bacteraemia caused by Gram-negative rods resistant to amoxicillin-clavulanate, which was used as empirical therapy during early stages of the pandemic, led to an escalation towards broader-spectrum antimicrobials such as meropenem and colistin which was also associated with the emergence of resistant isolates.ConclusionsThe epidemiological shift towards resistant phenotypes in critically ill COVID-19 patients was associated with the selective use of antimicrobials. Our study provides evidence of the impact of empirical therapy on the selection of bacteria and their consequences on BSI over the subsequent months.

Hemophagocytic Lymphohistiocytosis in the Setting of Therapy-Induced Acute Myeloid Leukemia: An Autopsy Report

Hemophagocytic lymphohistiocytosis (HLH) is a life-threatening hyper-inflammatory disorder that occurs due to immunologic dysregulation. HLH can be primary (hereditary) or secondary to infections, autoimmune diseases, immune deficiencies, metabolic diseases, drugs, or malignancies. Lymphoid neoplasms mostly accompany malignancy-associated HLH. We present a case of a 12-year-old boy with a history of precursor B lymphoblastic leukemia (B-ALL), who subsequently developed chemotherapy-induced acute myeloid leukemia (t-AML). The patient was admitted for febrile neutropenia and initial laboratory tests revealed hemophagocytic lymphohistiocytosis (HLH). The hospital course was complicated by multiple infections and septic shock. The patient received several broad-spectrum antimicrobials, dexamethasone, as well as a pericardial drain to drain the hemorrhagic pericardial effusion. Despite intervention, the patient expired, and an autopsy was performed. We provide a synopsis of the main autopsy findings.

Revealing the Adverse Effects of Trace Amount Broad‐Spectrum Antimicrobial: a Direct and Sensitive Visualization Method Based on Carbon Nanoprobe

AbstractThe widespread use of broad‐spectrum antimicrobials has accelerated their entry into aquatic environment, which in turn can adversely affect aquatic organisms and humans, especially in the COVID‐19 outbreak and the post‐pandemic era. For early detection and intervention of adverse effects, this study develops a new carbon nanoprobe (CNP) that can reveal the adverse effects of trace amount triclosan (TCS), a commonly used broad‐spectrum antimicrobial (BSA), through a direct visualization method. CNP has excellent fluorescent properties and strong positive charges, which can be applied as fluorescent indicator and trapped in mitochondria by electrostatic attraction. The highly sensitive responsiveness of CNP to mitochondrial membrane potential ensures the visualization method can be used for monitoring the adverse effects of TCS. The trace amount TCS monitoring is achieved according to the decrease of fluorescence signal in mitochondria and the change of mitochondrial morphological structure from lines to dots. Moreover, monitoring TCS level in aquatic organisms of zebrafish is further realized. Compared with the morphological toxicity test, this visualizing strategy reveals the adverse effects in organisms under low‐dose TCS exposure more sensitively. This developed highly sensitive nanoprobe is cruical for direct BSA monitoring and thus prevents the harm of BSA to aquatic organisms and humans.

Impact of the COVID-19 pandemic on hospital antimicrobial consumption in Croatia

The aim of the study was to assess the impact of the COVID-19 pandemic on antimicrobial consumption (AMC) in the hospital sector in Croatia by analysing data reported to the European Surveillance of Antimicrobial Consumption Network (ESAC-Net) between 2016 and 2020. AMC was measured as the number of DDDs/1000 inhabitants/day and as the number of DDDs/100 bed days. To assess trends, linear regression was performed. To assess the impact of the pandemic on AMC, the compound annual growth rate was calculated for the years preceding the pandemic based on which AMC for 2020 was forecasted and compared with the actual consumption. While hospital AMC expressed as DDDs/1000 inhabitants/day between 2019 and 2020 decreased by 17%, when expressed as DDDs/100 bed days, an 8% increase was observed. Hospital consumption of antibacterials for systemic use in the 5 year period did not significantly change when expressed as DDDs/1000 inhabitants/day, while it statistically significantly increased when expressed as DDDs/100 bed days. An increasing trend in consumption of broad-spectrum antimicrobials was found. During the pandemic there was an increase in hospital AMC with a shift towards broad-spectrum antimicrobials requiring further in-depth qualitative analysis based on patient-level data. Contrasting results obtained using different denominators indicate that the metric DDDs/1000 inhabitants/day is not sensitive enough to evaluate hospital AMC. When assessing hospital AMC, the population under surveillance should be relevant for healthcare context. Antimicrobial stewardship remains one of the most important strategies to tackle antimicrobial resistance and antimicrobial surveillance methods must be as sensitive as possible.

Antimicrobial Prescribing Practices at Dermatology Outpatient Departments in Tertiary Care Hospitals: A Multi-Centered, Cross Sectional Study

Background: An antimicrobial is an agent, that kills micro organisims or prevents their growth. The purpose of this study is to evaluate antimicrobial prescribing behaviors in the Dermatology Outpatient Department. Materials and methods: This multi-centered, cross-sectional study was conducted at Dermatology Outpatient Department of three tertiary care hospitals in Chattogram division, Bangladesh during the period October, 2021 to April, 2022. Results: During the study period, 463 prescriptions were obtained. Over half of the participants were female (57%) and between the ages of 21 to 40 years. The majority of patients were diagnosed with eczema (19%), acne (17%) and scabies (15%). Most commonly prescribed antimicrobials was Azithromycin (22%) followed by Permethrin (16%) and Erythromycin (7%). In most cases, antimicrobials were recommended for more than two weeks (60%). Nearly half of the antimicrobials (53 %) were recommended as combination of systemic and topical route. Conclusion: Current study found that dermatologists frequently recommended broad-spectrum antimicrobials for extended periods of time, which may lead to antimicrobial resistance. There is a need for continuing medical education on the appropriate use of antimicrobials, which will result in the effective management of skin diseases. IAHS Medical Journal Vol 5(1), June 2022; 16-21

Impact of hospital environmental cleaning with a potassium peroxymonosulphate-based environmental disinfectant and antimicrobial stewardship on the reduction of hospital-onset Clostridioides difficile infections

A 1% potassium peroxymonosulphate-based environmental disinfectant (PPED) produces sodium hypochlorite when combined with sodium chloride, which functions as a disinfectant. However, little is known about the impact of hospital cleaning with PPED on hospital-onset Clostridioides difficile infection (HO-CDI). To reduce HO-CDI, we promoted antimicrobial stewardship and hospital ward cleaning with PPED: this study was conducted to evaluate their impact. We began a promotion of post-prescription review with feedback for broad-spectrum antimicrobials and hospital ward cleaning with PPED. We reviewed the ratio of HO-CDI, PPED consumption, and days of therapy (DOT) of broad-spectrum antimicrobials between July 2014 and March 2018, dividing this time into the pre-promotion (July 2014 to June 2015) and post-promotion periods (July 2015 to March 2018). Using interrupted time series analysis, an immediate significant change in HO-CDI was observed after intervention (P=0.03), although a downward trend was not observed over this period (P=0.19). Trends in PPED consumption significantly changed over this period (P=0.02). DOT of carbapenems decreased immediately after the intervention began (P<0.01). A Poisson regression analysis showed that PPED consumption and DOT of carbapenems were independent factors affecting HO-CDI (P=0.039 and 0.016, respectively). We revealed that DOT of carbapenems and use of PPED were associated with the HO-CDI ratio and that both interventions reduced the rate of HO-CDI. This is the first report on the impact of hospital ward cleaning with PPED on the reduction of HO-CDI.

Guanylated Hyperbranched Polylysines with High In Vitro and In Vivo Antifungal Activity.

With the rapid growth of fungal infections and the emergence of multi-drug resistant (MDR) fungal strains, new antifungals with novel mechanisms are a pressing need to tackle this emerging health problem. Herein it is reported for the first time that hyperbranched polylysine (HPL) shows antifungal activities against Candida, especially for drug-sensitive and MDR C. albicans strains, and broad-spectrum antibacterial activities against both Gram-negative and Gram-positive bacteria. The high antimicrobial activities are ascribed to the high charge density and compact size of the globular structure of HPL. The in vitro antifungal activities of HPL3 are further enhanced by the modification of amine groups to form guanylated polylysines (HPL3-Gxs). Similar to antimicrobial peptides (AMPs), HPLs and HPL3-Gxs interact with and lyse the membranes of microbes, which mitigates the emergence of drug resistance. HPLs and HPL3-Gxs demonstrate excellent in vivo antimicrobial efficacies against both lethal C. albicans challenge in the invasive candidiasis model and lethal Methicillin resistant Staphylococcus aureus challenge in the peritonitis model, and have potentials as broad-spectrum antimicrobials.

Practice Summary of Antimicrobial Therapy for Commonly Encountered Conditions in the Neonatal Intensive Care Unit: A Canadian Perspective.

Neonates are highly susceptible to infections owing to their immature cellular and humoral immune functions, as well the need for invasive devices. There is a wide practice variation in the choice and duration of antimicrobial treatment, even for relatively common conditions in the NICU, attributed to the lack of evidence-based guidelines. Early decisive treatment with broad-spectrum antimicrobials is the preferred clinical choice for treating sick infants with possible bacterial infection. Prolonged antimicrobial exposure among infants without clear indications has been associated with adverse neonatal outcomes and increased drug resistance. Herein, we review and summarize the best practices from the existing literature regarding antimicrobial use in commonly encountered conditions in neonates.

Evaluation of Piperacillin/Tazobactam Use and Resistance Ppattern in a Teaching Hospital, Northwest Iran

Background: Inappropriate use of broad-spectrum antibiotics has contributed to the emergence of resistant microorganisms, increased treatment costs, morbidity and mortality, drug toxicity, and prolonged hospitalization period. Determining the epidemiology of antibiotic resistance in various hospital wards allows for more precise drug selection in the hospital setting. This study evaluated the use and resistance pattern of a broad-spectrum antibiotic, Piperacillin/tazobactam, in Imam Khomeini, a referral teaching hospital in Urmia, Iran.&#x0D; Methods: All hospitalized patients who were treated with Piperacillin\Tazobactam from January to August 2018 were included. Demographic (age, sex, weight, comorbidities) and clinical data (Indication, dosing, duration of the treatment, susceptibility test, creatinine clearance, need for dose adjustment, clinical outcome, and mortality) of the patients were collected, and the compliance of piperacillin\tazobactam administration and its resistance pattern was assessed according to Lexi-comp- 2019 recommendations.&#x0D; Results: Among 177 patients, 88.7% received piperacillin\tazobactam without any appropriate susceptibility tests. The piperacillin disk was used in only 33.3% of the culture-positive cases in our research, with 70% resistance. Acinetobacter was the most common bacteria found in our culture-positive samples. The average duration of piperacillin\tazobactam treatment was 8.52 ± 5.84 days. Indications in 8.5%, doses in 18.5%, prescription period in 19.7%, and dose intervals in 31.4% of the cases were inappropriate. Piperacillin\tazobactam was mainly administered for pneumonia (34.5%)&#x0D; Conclusion: This study showed an injudicious use of Piperacillin/tazobactam in our hospital, evidenced by the significant number of inappropriate doses, intervals, and treatment duration. Decision-making based on susceptibility tests using appropriate and accurate methods, close monitoring of the patients' clinical status, including creatinine clearance, and antimicrobial stewardship programs may optimize the rational administration of broad-spectrum antimicrobials and avoid the emergence of bacterial resistance.&#x0D;

Burden of bacterial bloodstream infections and recent advances for diagnosis.

Bloodstream infections (BSIs) and subsequent organ dysfunction (sepsis and septic shock) are conditions that rank among the top reasons for human mortality and have a great impact on healthcare systems. Their treatment mainly relies on the administration of broad-spectrum antimicrobials since the standard blood culture-based diagnostic methods remain time-consuming for the pathogen's identification. Consequently, the routine use of these antibiotics may lead to downstream antimicrobial resistance and failure in treatment outcomes. Recently, significant advances have been made in improving several methodologies for the identification of pathogens directly in whole blood especially regarding specificity and time to detection. Nevertheless, for the widespread implementation of these novel methods in healthcare facilities, further improvements are still needed concerning the sensitivity and cost-effectiveness to allow a faster and more appropriate antimicrobial therapy. This review is focused on the problem of BSIs and sepsis addressing several aspects like their origin, challenges, and causative agents. Also, it highlights current and emerging diagnostics technologies, discussing their strengths and weaknesses.

Spatiotemporal Release of Reactive Oxygen Species and NO for Overcoming Biofilm Heterogeneity

AbstractThe heterogeneity in biofilms is a major challenge in biofilm therapies due to different susceptibility of bacteria and extracellular polymeric substances (EPS) to antibacterial agents. Here, we describe a therapeutic strategy that overcame biofilm heterogeneity, where antibacterial agent (NO) and EPS dispersant (reactive oxygen species (ROS)‐inducing Fe3+) were separately loaded in the yolk and shell compartment of a yolk–shell nanoplatform. Compared with traditional combinational chemotherapies which suffer from inconsistent pharmacokinetics profiles, this strategy drew on the pharmacokinetic complementarity of ROS and NO, where ROS with a short diffusion distance and a high redox potential corrupted the EPS, facilitating NO, which has a long diffusion distance and a broad antimicrobial spectrum, to penetrate the biofilm and eliminate the resident bacteria. Additionally, the construction of a three‐dimensional spherical biofilm model is novel and clinically relevant.

Spatiotemporal Release of Reactive Oxygen Species and NO for Overcoming Biofilm Heterogeneity.

The heterogeneity in biofilms is a major challenge in biofilm therapies due to different susceptibility of bacteria and extracellular polymeric substances (EPS) to antibacterial agents. Here, we describe a therapeutic strategy that overcame biofilm heterogeneity, where antibacterial agent (NO) and EPS dispersant (reactive oxygen species (ROS)-inducing Fe3+ ) were separately loaded in the yolk and shell compartment of a yolk-shell nanoplatform. Compared with traditional combinational chemotherapies which suffer from inconsistent pharmacokinetics profiles, this strategy drew on the pharmacokinetic complementarity of ROS and NO, where ROS with a short diffusion distance and a high redox potential corrupted the EPS, facilitating NO, which has a long diffusion distance and a broad antimicrobial spectrum, to penetrate the biofilm and eliminate the resident bacteria. Additionally, the construction of a three-dimensional spherical biofilm model is novel and clinically relevant.

Anti-virulence therapeutic strategies against bacterial infections: recent advances.

The emergence and increasing prevalence of multidrug-resistant pathogens has become a major global healthcare problem. According to the World Health Organization if these trends continue, mortality from infection in 2050 will be higher than that from cancer. Microorganisms have various resistance mechanisms against different classes of antibiotics that emphasize the need for discovery of new antimicrobial compounds to treat bacterial infections. An interesting and new strategy for disarming pathogens is antivirulence therapy by blocking bacterial virulence factors or pathogenicity. Therefore, the use of these new pathoblockers could reduce the administration of broad-spectrum antimicrobials and prevalence of resistant strains. This review provides an overview of the antivirulence strategies published studies between years 2017 and 2021. Most antivirulence strategies focused on adhesins, toxins and bacterial communication. Additionally, targeting two-component systems and ncRNA elements were also examined in some studies. These new strategies have the potential to replace traditional antimicrobial agents and can be used to treat infections, especially infections caused by resistant pathogens, by targeting virulence factors.