Wide-spectrum Antibiotics Research Articles

Dealing With Antibiotic Prophylaxis in Lung Transplantation in the Era of Multidrug Resistance: The Milano Algorithm.

Infectious complications significantly impact morbidity and mortality following lung transplantation (LuTx), with over 25% of post-transplant deaths attributed to infections. Antibiotic prophylaxis during the surgical procedure is crucial for reducing early infections, though the current use of wide-spectrum antibiotics, especially in cases of multidrug-resistant organisms (MDROs), is contentious and varies widely across centre. This practice raises concerns about antimicrobial resistance (AMR), particularly in immunosuppressed patients requiring lifelong healthcare access. Syndromic multiplex polymerase chain reaction (mPCR) tests, which detect multiple pathogens simultaneously, have shown promise in quickly identifying pathogens and resistance mechanisms, thus enabling targeted treatments. However, their application in LuTx has been limited.

Synthesis and discovery of simplified pleurotin analogs bearing tricyclic core as novel thioredoxin reductase inhibitors.

Pleurotin (1) is a benzoquinone meroterpenoid known for its wide-spectrum antitumor and antibiotic activities, notably acting as natural inhibitors of the thioredoxin reductase (TrxR). Pleurotin (1) has been chemically synthesized, but only in milligram quantities through at least 13 longest linear steps with 0.8% overall yield due to its complex structure such as fused hexacyclic core with 8 contiguous stereocenters. Therefore, structural simplification strategy is applied to pleurotin natural products for their structure-activity relationship (SAR) study and further therapeutics development. Herein, we judiciously designed pleurotin analogs of tricyclic A/D/E ring core, retaining the putative pharmacophore of para-quinone moiety D and its supportive A and E rings. Thus 16 simplified analogs of pleurotin bearing tricyclic A/D/E core were readily synthesized in only 2 to 6 steps with up to 50% overall yield from commercially available materials. Significantly, the best analog 14f with benzonitrile substituent exhibited more potent TrxR inhibitory activity with an IC50 of 3.5μM than the positive control micheliolide (IC50=6.23μM). Furthermore, the mechanism study revealed that compound 14f could induce apoptosis of tumor cells by inducing ROS generation and inhibiting TrxR activities. Our study for the first time showed that the tricyclic A/D/E ring scaffold from the natural product pleurotin (1) with proper substitution can maintain or even improve the TrxR inhibitory and antiproliferative activities, with high synthetic accessibility, affording natural product-derived lead compounds for the further development of TrxR inhibitors as anti-tumor therapeutics.

Unraveling the Narrative of Orbital Cellulitis as a Sequelae to Trauma

Abstract Orbital cellulitis is often seen as a serious complication of acute rhinosinusitis. Facial trauma is one of the possible causes of orbital cellulitis. A middle-aged man, a mason by occupation, presented to ENT OPD following a facial trauma. He presented with a laceration over the right zygomatic region with right-sided periorbital swelling and redness. Wide-spectrum antibiotics were initiated for the patient. Pus was drained daily, and surgical debridement of the wound followed by sterile dressing of the wound cavity was done regularly until the pus discharge totally stopped. The patient was taken for secondary suturing and was discharged after that. However, the patient lost to follow-up. Facial trauma is a cause of orbital cellulitis. Orbital cellulitis is an emergency condition and requires urgent medical attention. Adequate antibiotic therapy is of utmost importance to treat the condition. Surgical care is advisable if the medical line of management fails.

Characterization and treatment protocol of injuries inflicted to humans by synurbic European wild boars (Sus scrofa).

Wild boar (Sus scrofa) has spread and colonized urban areas. The closer contact with humans can lead to wild boar-inflicted injuries. The objectives of this study are: 1) to systematically review the literature on wild boar-inflicted injuries; 2) to describe our wild boar-inflicted wound management protocol; and 3) to analyse the features, outcomes and complications of our case series. First, a systematic search of the literature was performed using the PubMed (MEDLINE) electronic database. Then, our evidence-based wild boar-inflicted wound management protocol was described. Finally, a retrospective case series study including all the patients with wild boar-inflicted injuries attended in our Emergency Department (2020-2022) was analysed. Fourteen studies (twelve case reports and two case series) were selected for the literature review. Our case series included 34 patients: 50.0% of them presented superficial wounds and 38.2% penetrating wounds. Most of the wounds occurred in the lower limbs (71.9%). Following our protocol, 30.0% of the wounds were primarily closed, the 70.0% of the patients received antibiotics (92.3% in penetrating injuries) and the 26.7% received an antitetanic vaccine. Only one patient (2.9%) presented a complication. This study reports the first specific wild boar inflicted-wound management protocol, which led to a low complication rate. Open wounds affecting the lower limbs were the most common lesions. Care should be taken with penetrating tusk injuries. Wide-spectrum antibiotic and antitetanic treatments are recommended. Decisions on wound management should be taken case-by-case, while antirabies vaccination depends on the local status of the disease.

Electroactive self-standing polyester membranes prepared using magnetite/poly(3,4-ethylenedioxythiophene) core-shell particles

In this work hybrid magnetite (Fe3O4)/poly(3,4-ethylenedioxythiophene) (PEDOT) core-shell particles are used to produce electro-responsive self-standing polycaprolactone (PCL) membranes with many potential applications. For this purpose, Fe3O4/PEDOT core-shell particles with different magnetite contents are prepared by combining chemical precipitation and emulsion polymerization. After chemical, morphological and physical characterization, the electrochemical response of the hybrid particles is analyzed and compared with that of PEDOT nanoparticles. In all cases, Fe3O4/PEDOT core-shell particles are more electroactive than PEDOT particles, with the electrochemical response of the former increasing with the content of magnetite. Composite membranes were prepared by spin-coating a mixture of polycaprolactone (PCL) and Fe3O4/PEDOT particles. The resulting Fe3O4/PEDOT-PCL membranes, which maintained the magnetic behavior, were transformed into electro-responsive by incorporating a PEDOT surface layer through anodic polymerization, which was possible thanks to the role of Fe3O4/PEDOT particles as polymerization nuclei. One of the potential applications of self-supported electro-responsive Fe3O4/PEDOT-PCL/PEDOT membranes was illustrated through a proof-of-concept. Specifically, a wide-spectrum antibiotic, chloramphenicol, was loaded into the membranes during the anodic polymerization step promoted by the hybrid Fe3O4/PEDOT particles and, subsequently, completely released by electrical stimulation. Overall, Fe3O4/PEDOT core-shell particles allowed us to obtain self-standing membranes with electric and magnetic properties, as promising candidates for many technological applications.

Is It Safe to Treat Stable Patients with Bacteremic Urinary Tract Infections with High-Resistant-Rate Antibiotics?

In most areas of the world, urine bacteria have high resistance rates to third-generation cephalosporins, and it is unclear if it is safe to treat stable patients with bacteremic urinary tract infections (UTI) with those antibiotics. There are recommendations that empiric therapy for a suspected UTI should include only antibiotics with resistance rates less than 10%. In this historical observational single center study, we selected 180 stable internal medicine patients hospitalized between January 2019 and December 2021, with identical bacteria isolated from blood and urine cultures. Charts were reviewed to determine if deaths and readmissions up to 30 days after discharge were due to bacterial resistance to initial antibiotic therapy (BRIAT). The patient's median age was 82 years (1st-3rd quartiles, 73-87 years). A total of 54.4% were female. There were 125 patients treated with ceftriaxone. A total of 38 (30.3%) had BRIAT. Four patients died, but none were because of a delay in appropriate treatment. The median days of hospitalization for all patients was 7 days, and 9 days versus 6 days in those with and without BRIAT. There were no re-hospitalizations for a UTI in patients with BRIAT. We conclude that, despite high resistance rates, empiric ceftriaxone in stable hospitalized patients with a bacteremic UTI is safe. There was no urosepsis-related mortality during the hospitalization or on follow-up. The treatment of all patients with wider-spectrum antibiotics might have decreased the median hospital stay by only one day. The potential effect would be even lower if all patients with a suspected systemic UTI were treated with wide-spectrum antibiotics, because some patients do not have an infection of the urinary tract. A reassessment of the recommendation that empiric therapy for a suspected systemic urinary tract infection should include only wider-spectrum antibiotics is warranted.

Epidemiology and Management Paradigm of Head and Neck Infections, Including COVID-19 Pandemic Period: A 10-Year Retrospective Study in a Maxillofacial Center of Cluj-Napoca.

Background. The management of odontogenic infections varies across the globe. To shed light on the subject, this study delves into the practices of the Oral and Maxillofacial Department at Cluj-Napoca County Hospital. Material and Methods. This comprehensive retrospective analysis of 10 years of clinical experience covered a range of factors, including demographics, clinical and investigations factors, medical and surgical treatment approaches, and follow-up. Additionally, the study examined the change in trends over the course of the COVID-19 pandemic. Results. While head and neck infection occurrence had a decreasing trend before the COVID-19 pandemic, during the pandemic era the number of patients almost doubled. The infections were prevalent in the submandibular space, teeth being the prevalent cause. Young adults are prone to suffer from odontogenic infections. High levels of C reactive protein, ASA II-IV risk, and hepatic dysfunction indicated a longer time of hospitalization. The majority of antibiograms were negative, and the positive ones indicated Streptococcus and Staphylococcus species as prevalent pathogens. Extra- or intraoral surgical drainage and wide-spectrum antibiotics proved to be the workhorse for odontogenic infections. Conclusion. This study advances our understanding of oral and maxillofacial surgery and offers actionable strategies for improving patient outcomes in similar healthcare institutions worldwide.

Molecularly imprinted nylon membrane with high hydrophilicity and antifouling properties for efficient separation of sulfonamides

Sulfonamides (SAs) represent a type of wide-spectrum antibiotics, effective in preventing and treating bacterial infections. Nevertheless, excessive SAs usage poses risks to human health and environmental safety. In this investigation, we developed a novel molecular imprinted membrane (MIPs@UiO-66@Nylon) characterized by hydrophilicity and antifouling properties. UiO-66-NH2 was grown in situ on nylon membrane to augment the specific surface area and enhance the adsorption capabilities. Tannic acid (TA), an eco-friendly compound, was incorporated to increase adsorption sites on the nylon membrane. Molecular imprinting was introduced to enhance membrane selectivity, enabling specific separation of SAs. The resulting MIPs@UiO-66@Nylon demonstrated high hydrophilicity, indicated by a hydrophilic angle of 33.7°. Furthermore, the imprinting factors (IF) ranged from 2.34 to 2.98, facilitating effective SAs separation. The recovery rate ranged between 83.2% and 98.4%, with a standard deviation (RSD) of 0.4% to 2.3%. Following ten cycles of adsorption and desorption, the adsorption loss remained below 4.65%. This innovation in MIPs@UiO-66@Nylon offers a promising avenue for SAs detection, with potential applications in human health and environmental preservation.

Probing the pH Sensitivity of OprM: Insights into Metastable States and Semi-Open Conformation.

Efflux pumps are specialized transport proteins that play a key role in the bacterial defense against a wide spectrum of antibiotics. Hence, understanding the biophysical mechanism associated with this complex system of drug expulsion becomes crucial. This work deals with some vital aspects of the outer membrane factor (OMF) of MexAB-OprM. After being passed through MexB and MexA, efflux substrates have to go through OprM for their final judgment. Thus, it is very important to understand the periplasmic pore opening mechanism and the associated biophysical changes during this process. Our study captures a detailed analysis of the pore opening mechanism involving OprM. With powerful molecular dynamics (MD) techniques such as well-tempered metadynamics, the presence of metastable states in between open and closed states was confirmed. Also, upon mutating R376, the energy barrier for the conversion of the close to open conformation decreases, indicating an important role played by the residue. Further, constant pH MD was performed to capture the effect of pH in both conformations. OprM exhibits distinct conformational states at pH values greater than 5.5 and lower than 5.5, suggesting its pH-responsive characteristics. Overall, our study elucidates a crucial undertaking toward discovering potential inhibitors for MexAB-OprM efflux pumps.

Emphysematous pyelonephritis and sepsis in a diabetic female patient caused by extended-spectrum beta-lactamase-producing Escherichia coli – case report

Emphysematous pyelonephritis (EPN) is a rare, severe, spontaneous gas-forming infection of renal parenchyma and its surrounding areas. EPN was detected in diabetic patients. A 49-year-old female with type I diabetes mellitus presented with severe thrombocytopenia, acute kidney injury (AKI) and was in need of haemodialysis treatment. She had impaired liver function tests, with active urine sediment, indicating severe upper urinary tract infection with suspected sepsis. The contrast enhanced CT scan of the abdomen showed multiple areas of air density in renal parenchyma and perirenal regions, suggestive of left-side EPN. The blood and urine cultures reported growth of extended-spectrum beta-lactamase (ESBL) producing Escherichia coli. The final diagnosis of emphysematous pyelonephritis complicated with severe sepsis and AKI was established. The patient was managed conservatively with wide-spectrum antibiotics, fluid resuscitation, consistent blood sugar control, and haemodialysis treatment. Percutaneous drainage techniques (PCD) and nephrectomy were postponed because of the initial clinical response to the antibiotics treatment. However, the patient experienced sudden clinical deterioration and died only a few hours after the established diagnosis. An autopsy was not performed upon the patient’s family’s request. EPN should be highly suspected in poorly controlled diabetic patients with urinary tract infection and should be promptly recognized and aggressively treated. The patients with multiple risk factors had high mortality, even with timely diagnosis and combined (conservative and surgical) treatment.

Comparing the Therapeutic Potency of Camel Milk and Whey Protein Against Toxicity-Induced by Levofloxacin in Male Albino Rats.

<b>Background and Objective:</b> Levofloxacin (LFX) is a wide-spectrum antibiotic that is used to treat many types of infections. Camel milk (CM) and camel whey protein (CWP) are natural antioxidants that work as dietary supplements that enhance immune defenses. The goal of this study was to estimate the therapeutic efficacy of camel whey protein and camel milk, in addition to the toxic effects of the antibiotic levofloxacin. <b>Materials and Methods:</b> As 42 male albino rats were divided as follows: G1: Control, G2: CM orally for 15 days, G3: CWP orally for 15 days, G4: LFX orally for 10 days, G5: LFX for 10 days and followed with CM daily for 15 days and G6: LFX for 10 days followed by CWP orally for 15 days. At the end of the study blood sera from all groups were collected for estimation of serum total protein, albumin, globulins and glucose. Sections of the liver and kidney were separated for estimation of GSH, CAT, GSH-PX. All data were statistically analyzed using analysis of variance. <b>Results:</b> The LFX treatment induced a decrease in serum levels of proteinogram, glucose, hepatic and renal values of oxidative stress and raising values of serum kidney and liver functions, hepatic and renal MDA. The treatment of LFX-treated rats with CWP led to a more increase in serum proteinogram, glucose, hepatic and renal (GSH, CAT, GSH-PX) a decline in serum values of (urea, ALAT, ASAT, ALP, BIL, T.P, D. BIL, Ind. BIL creatinine), hepatic and renal MDA than the treatment with CWP did. <b>Conclusion:</b> The use of CWP after LFX-treatment showed greater therapeutic potency than the use of CM.

A non-antibiotic-disrupted gut microbiome is associated with clinical responses to CD19-CAR-T cell cancer immunotherapy.

Increasing evidence suggests that the gut microbiome may modulate the efficacy of cancer immunotherapy. In a B cell lymphoma patient cohort from five centers in Germany and the United States (Germany, n = 66; United States, n = 106; total, n = 172), we demonstrate that wide-spectrum antibiotics treatment ('high-risk antibiotics') prior to CD19-targeted chimeric antigen receptor (CAR)-T cell therapy is associated with adverse outcomes, but this effect is likely to be confounded by an increased pretreatment tumor burden and systemic inflammation in patients pretreated with high-risk antibiotics. To resolve this confounding effect and gain insights into antibiotics-masked microbiome signals impacting CAR-T efficacy, we focused on the high-risk antibiotics non-exposed patient population. Indeed, in these patients, significant correlations were noted between pre-CAR-T infusion Bifidobacterium longum and microbiome-encoded peptidoglycan biosynthesis, and CAR-T treatment-associated 6-month survival or lymphoma progression. Furthermore, predictive pre-CAR-T treatment microbiome-based machine learning algorithms trained on the high-risk antibiotics non-exposed German cohort and validated by the respective US cohort robustly segregated long-term responders from non-responders. Bacteroides, Ruminococcus, Eubacterium and Akkermansia were most important in determining CAR-T responsiveness, with Akkermansia also being associated with pre-infusion peripheral T cell levels in these patients. Collectively, we identify conserved microbiome features across clinical and geographical variations, which may enable cross-cohort microbiome-based predictions of outcomes in CAR-T cell immunotherapy.

Effects of Cold Atmospheric Plasma on Infectious Diabetic Wound Healing in Rat Models

Objectives: Patients with diabetes often suffer from chronic wounds which can occur due to the impairment of wound healing in these patients. Scientists have been trying to address this issue by using wide spectrum of antibiotics and drugs. However, overusing antibiotics in recent years has led to antibiotic resistant crisis; therefore, there is an urgent need to develop new approaches in order for controlling microbial infections in diabetic patients. This study aimed to determine if cold plasma was effective in wound healing in the infectious diabetic conditions. Material and Methods: In this experimental study, 40 adult male rats with diabetes infected with Staphylococcus aureus were included. The animals were randomly divided into two groups of 20 rats and four sub-groups (i.e., day 3rd, day 7th, day 14th, and day 21st). The rats in the treatment group were exposed to helium plasma irradiated for 3 minutes per day for 21 days. Wound healing in the samples was evaluated using five healing indexes including epithelium formation, Inflammatory cells, new vascularization, fibroblast, and collagen formation. Results: A significant difference (P<0.05) was found between the indexes in the plasma radiation group compared to the control group. The results showed that the speed of wound healing in the group treated with cold helium gas plasma was higher than that in the control group. Collagen formation was always completed faster in the helium plasma group, indicating the positive effects of helium plasma on infected diabetic wounds. Conclusions: Helium plasma was remarkable effective in healing wound and controlling infections in diabetic rats.

Ce-MBGs Loaded with Gentamicin: Characterization and In Vitro Evaluation.

Mesoporous Bioactive Glasses (MBGs) are biomaterials widely used in tissue engineering, particularly for hard tissue regeneration. One of the most frequent postoperative complications following a biomaterial surgical implant is a bacterial infection, which usually requires treatment by the systemic administration of drugs (e.g., antibiotics). In order to develop biomaterials with antibiotic properties, we investigated cerium-doped MBGs (Ce-MBGs) as in situ-controlled drug delivery systems (DDSs) of gentamicin (Gen), a wide spectrum antibiotic commonly employed against bacteria responsible of postoperative infections. Here we report the optimization of Gen loading on MBGs and the evaluation of the antibacterial properties and of retention of bioactivity and antioxidant properties of the resulting materials. The Gen loading (up to 7%) was found to be independent from cerium content, and the optimized Gen-loaded Ce-MBGs retain significant bioactivity and antioxidant properties. The antibacterial efficacy was verified up to 10 days of controlled release. These properties make Gen-loaded Ce-MBGs interesting candidates for simultaneous hard tissue regeneration and in situ antibiotic release.

Tuberculosis with isolated atelectasis: a case report

Introduction Tuberculosis is a significant health issue in developing countries, with the World Health Organization reporting over 10 million cases worldwide in 2014. While methods exist for rapid investigation of Mycobacterium tuberculosis, radiological imaging may lead to an earlier suspicion, such as presence of cavitation. In this case report, a patient with only radiological finding being atelectasis will be presented. Case Presentation An 18 years old female patient with no specific medical background history had been evaluated at an outpatient clinic with complaints of cough and exertional dyspnea. After a fluoroquinolone treatment for 7 days given for a pericardiac density in chest radiography, patient was admitted due to limited clinical response. A chest tomography was performed while the patient was under wide spectrum antibiotics and atelectasis in right lower lobe was observed. Repeated Acid-Fast Bacilli smears and sputum samples were found negative and bronchoscopy sampling did not show any findings of obstruction. Mycobacterium tuberculosis complex DNA was later detected in the lavage samples for which antituberculosis treatment was initiated with a regimen of isoniazid 5 mg/kg, pyrazinamide 25 mg/kg, ethambutol 15 mg/kg, and rifampin 10mg/kg. Discussion The diagnosis of tuberculosis, in this case, was probably masked during the AFB smear testing due to a treatment regimen of fluoroquinolone. The general radiological definition of tuberculosis primarily consists of older studies, with the expected presentation being a combination of cavitation and infiltration. Normal lung imaging results had also been described for tuberculosis regarding chest radiography, and studies have reported the presence of atelectasis in patients with tuberculosis, as seen in tomography case series; however, the isolation of atelectasis had not been specified in the studies. Conclusion Pulmonary tuberculosis may present itself with a myriad of radiological findings. This presentation often complicates the diagnostic process; however, differential diagnosis can be achieved via a combination of clinical symptoms and rapid culture sampling.

Degradation of tetracyclines by peracetic acid and UV/peracetic acid: Reactive species and theoretical computations

As an environment-friendly oxidant and disinfectant, peracetic acid (PAA) and PAA based-advanced oxidation processes (AOPs) for the treatment of emerging micropollutants have raised increasing interest, owing to their ease of activation and less generation of harmful disinfection byproducts. Tetracyclines (TCs) antibiotics as a group of wide-spectrum antibiotics are frequently detected in sewage effluents, while the knowledge of PAA-based advanced oxidation reactions to remove the substrates is quite limited. In this work, we systematically investigated the kinetics and underlying transformation mechanisms of three TCs including tetracycline (TTC), oxytetracycline (OTC), and chlortetracycline (CTC) in the UV-activated PAA oxidation process. The results indicated that three TCs can be efficiently decayed by UV/PAA. The pseudo-first-order reaction rate constants (kobs) of TCs followed the order: kCTC (0.453 min−1) ≫ kTTC (0.164 min−1) > kOTC (0.158 min−1). Quenching experiments showed that the removal of CTC was mainly ascribed to the direct oxidation of PAA, while TTC and OTC were more susceptible to free radicals. The kobs values of the three TCs by PAA oxidation presented a fairly well correlation to the global nucleophilicity and the activation energies of the TC molecules, highlighting the structure-specific reactions of TCs to PAA. Based on product identification and theoretical calculation, N-demethylation and hydroxylation were proposed as the main pathways for TCs degradation by PAA non-radical oxidation. The combination of PAA and UV irradiation can further improve the degradation efficiency of TCs and contribute to reducing the diffusion and transmission of resistance genes in the environment.

Changes in Medication Prescribing Due to COVID-19 in Dental Practice in Croatia-National Study.

The 2019 coronavirus pandemic (COVID-19) has affected clinical practice and, consequently, drug prescribing in dental practice. We investigated how the pandemic affected the prescribing behavior of dentists in Croatia. Data on prescribing practices for this study were provided by the Croatian Health Insurance Institute. The analysis included the number of prescriptions, costs, and the number of packages prescribed. The World Health Organization's defined daily dose per 1000 inhabitants (DID) per day was used as an objective utilization comparison. During the first pandemic year, prescribing practice changed the most. Wide-spectrum antibiotics, analgesics, and antiseptics showed the highest trend in change. A statistically significant change in prescribing practices during the pandemic period was noted for amoxicillin with clavulanic acid, ibuprofen, and ketoprofen which showed an increase in trend, while cephalexin and diclofenac showed a statistically significant decrease. The highest increase in trend was recorded for azithromycin, at +39.3%. The COVID-19 pandemic has been associated with a marked increase in medication utilization, especially in the first year of the pandemic. The increase in wide-spectrum antibiotic classes needs to be addressed and regulated so that patients accept that antibiotics are not a substitute for dental treatment and dentists always start treatment with narrow-spectrum antibiotics regardless of specific times, as is the case with the pandemic.

Tobramycin Nanoantibiotics and Their Advantages: A Minireview.

Nowadays, antimicrobial resistance (AMR) represents a challenge for antibiotic therapy, mostly involving Gram-negative bacteria. Among the strategies activated to overcome AMR, the repurposing of already available antimicrobial molecules by encapsulating them in drug delivery systems, such as nanoparticles (NPs) and also engineered NPs, seems to be promising. Tobramycin is a powerful and effective aminoglycoside, approved for complicated infections and reinfections and indicated mainly against Gram-negative bacteria, such as Pseudomonas aeruginosa, Escherichia coli, Proteus, Klebsiella, Enterobacter, Serratia, Providencia, and Citrobacter species. However, the drug presents several side effects, mostly due to dose frequency, and for this reason, it is a good candidate for nanomedicine formulation. This review paper is focused on what has been conducted in the last 20 years for the development of Tobramycin nanosized delivery systems (nanoantibiotics), with critical discussion and comparison. Tobramycin was selected as the antimicrobial drug because it is a wide-spectrum antibiotic that is effective against both Gram-positive and Gram-negative aerobic bacteria, and it is characterized by a fast bactericidal effect, even against multidrug-resistant microorganisms (MDR).

Outpatient Antibiotic Use and Costs in Adults: A Nationwide Register-Based Study in Finland 2008-2019.

The objective of this study was to describe the prevalence of outpatient use and costs for systemic antibacterials by age and sex among adults in Finland from 2008-2019. Data from the Finnish statistical database Kelasto, containing information concerning all reimbursed medicines for 18+-year-olds during 2008-2019, were analyzed. In addition to the decreased (26%) use of systemic antibiotics, decreased use was observed in all antibiotic categories, notably including several wide-spectrum antibiotics. The use of quinolones decreased by 49% and of tetracyclines by 39%. The 10 most frequently used antibiotics covered 89% of all adult antibiotic prescriptions. Antibiotic use also decreased in every age group during the study period. Although the overall yearly costs of outpatient antibiotics during the 10-year study period decreased from EUR 36.4 million to EUR 30.7 million, the cost per prescription increased slightly. In conclusion, according to the findings of this study, concerning adults and the results of our previous study concerning children and adolescents (2008-2016), there has been a decreasing trend of outpatient antibacterial use among the whole Finnish outpatient population over the duration of nearly one decade. However, during the same time period, there has been a specific increasing trend for the Gram-negative AMR threat regarding E. coli resistance. Therefore, based on our important findings in Finland, methods other than the restriction of antibiotic use, such as new anti-infective innovations, including antibacterials, are needed as soon as possible to tackle this major global health threat-a silent pandemic.

Dual pH- and electro-responsive antibiotic-loaded polymeric platforms for effective bacterial detection and elimination

We describe a multi-tasking flexible system that is able to release a wide spectrum antibiotic (levofloxacin, LVX) under electrostimulation and act as a pH sensor for detecting bacterial infections. Combining anodic polymerization with plasma polymerization processes we engineered dual pH- and electro-responsive polymeric systems. Particularly, the manufactured devices consisted on a layer of poly(hydroxymethyl-3,4-ethylenedioxythiophene) (PHEDOT) loaded with the LVX antibiotic and coated with a plasma polymer layer of poly(acrylic acid) (PAA). The PHEDOT acted as conductive and electro-responsive agent, while the PAA provided pH responsiveness, changing from a compact globular conformation in acid environments to an expanded open coil conformation in alkaline environments. The assembly between the PHEDOT layer and the PAA coating affected the electrochemical response of the former, becoming dependent on the pH detected by the latter. The conformational change experienced by the PAA layer as a function of the pH and the redox properties of PHEDOT were leveraged for the electrochemical detection of bacteria growth and for regulating the release of the LVX antibiotic, respectively. The effectiveness of the system as a stimulus-responsive antibiotic carrier and pH sensor was also investigated on strains of Escherichia coli and Streptococcus salivarius.