Treatment Of Bacterial Infections Research Articles

Investigating the hypothermic effects of fluoroquinolone antimicrobials on non-bacterial fever model mice

BackgroundFluoroquinolone (FQ) antimicrobials have antipyretic effects during the treatment of bacterial infections; however, it is not clear whether these are due to their antimicrobial activities or their hypothermic effects. In this study, we investigated the hypothermic effects of FQ antimicrobials (ciprofloxacin [CPFX], gatifloxacin [GFLX], and levofloxacin [LVFX]) on fever by evaluating rectal body temperature changes in a mouse model of non-bacterial fever.MethodsCPFX, GFLX, and LVFX were administered intraperitoneally to non-bacterial fever model mice induced by yeast. Rectal body temperature was measured up to 180 min after administration.ResultsA decrease in rectal body temperature of up to 1.2 °C for CPFX, 3.4 °C for GFLX, and 1.0 °C for LVFX was observed. The decrease in temperature was induced by an increase in the plasma concentration of FQ antimicrobials, suggesting that they are responsible for the temperature reduction. Focusing on glucocorticoids, one thermoregulation mechanism, we investigated the substances responsible for the reduction in rectal body temperature induced by FQ antimicrobials. Aminoglutethimide (an inhibitor of glucocorticoid production) were premedicated, followed by intraperitoneal administration of GFLX in the yeast-induced fever mouse model, resulting in attenuated GFLX-induced hypothermic effects.ConclusionsThese results suggest that certain antipyretic effects of CPFX, GFPX, and LVFX during fever may contribute to their hypothermic effects; certain mechanisms are glucocorticoid-mediated.

Antimicrobial Peptide Delivery Systems as Promising Tools Against Resistant Bacterial Infections

The extensive use of antibiotics during recent years has led to antimicrobial resistance development, a significant threat to global public health. It is estimated that around 1.27 million people died worldwide in 2019 due to infectious diseases caused by antibiotic-resistant microorganisms, according to the WHO. It is estimated that 700,000 people die each year worldwide, which is expected to rise to 10 million by 2050. Therefore, new and efficient antimicrobials against resistant pathogenic bacteria are urgently needed. Antimicrobial peptides (AMPs) present a broad spectrum of antibacterial effects and are considered potential tools for developing novel therapies to combat resistant infections. However, their clinical application is currently limited due to instability, low selectivity, toxicity, and limited bioavailability, resulting in a narrow therapeutic window. Here we describe an overview of the clinical application of AMPs against resistant bacterial infections through nanoformulation. It evaluates metal, polymeric, and lipid AMP delivery systems as promising for the treatment of resistant bacterial infections, offering a potential solution to the aforementioned limitations.

Evaluating omadacycline dosing regimens against drug-resistant pathogens including Staphylococcus aureus, Streptococcus pneumoniae and Haemophilus influenzae in adults: a pharmacokinetic/pharmacodynamic analysis using Monte Carlo simulation.

The objective of this study was to evaluate the efficacy of various dosing regimens of omadacycline against main drug-resistant pathogens in the treatment of acute bacterial skin and skin structure infections (ABSSSI) and community-acquired bacterial pneumonia (CABP). Monte Carlo simulations were conducted using pharmacokinetic parameters and pharmacodynamic data to calculate cumulative fractions of response (CFRs) in terms of drug area under the concentration curve/minimum inhibition concentration targets.CFR ≥ 90% was considered optimal for a dosage regimen. CFR of any approved oral/intravenous regimen with loading-dose was ≥ 90% against methicillin-resistant Staphylococcus aureus (MRSA) for ABSSSI and penicillin-resistant Streptococcus pneumonia, tetracycline-resistant Streptococcus pneumonia, MRSA and β-lactamase positive Haemophilus influenzae for CABP. In conclusion, approved oral/intravenous loading and maintenance doses of omadacycline showed enough efficacy in the treatment of ABSSI and CABP caused by the main drug-resistant pathogens.

Precise Photothermal Treatment of Bacterial Infection Mediated by Charge-Switchable Nanoplatform with Acylsulfonamide Betaine Surface

Precise Photothermal Treatment of Bacterial Infection Mediated by Charge-Switchable Nanoplatform with Acylsulfonamide Betaine Surface

Guanethidine Enhances the Antibacterial Activity of Rifampicin Against Multidrug-Resistant Bacteria

The escalating global threat of antibiotic resistance necessitates innovative strategies, such as the combination of antibiotics with adjuvants. Monotherapy with rifampicin is more likely to induce resistance in pathogens compared to other antibiotics. Herein, we found that the antihypertensive drug guanethidine enhanced the activity of rifampicin against certain clinically resistant Gram-negative bacteria, resulting in a reduction of up to 128-fold in the minimum inhibitory concentration. In infected animal models, this combination has achieved treatment benefits, including increased survival and decreased bacterial burden. The antimicrobial mechanism of guanethidine in synergy with rifampicin involves the disruption of the outer membrane of Gram-negative bacteria, leading to dissipation of the proton motive force. This results in an increase in reactive oxygen species and a reduction in ATP synthesis, severely disturbing energy metabolism and ultimately increasing bacterial mortality. In summary, guanethidine has the potential to become a novel adjuvant for rifampicin, offering a new option for the treatment of clinical Gram-negative bacterial infections.

Exploration of New Drug Candidate Derived from Antioxidants of Korean Native Halophytes: Control of Acinetobacter baumannii with Antipathogenic Activity

The rise of antibiotic-resistant bacteria poses a significant challenge to the treatment of bacterial infections, necessitating the development of novel antibiotics or strategies to preserve the efficacy of existing ones. This study investigates the role of oxidative stress modulation in the pathogenicity of multidrug-resistant (MDR) bacterial strains, aiming to identify potential avenues for new drug design. Specifically, the anti-biofilm effects of crude extracts and fractions from seven halophyte species native to Jeju Island, South Korea, were evaluated against Acinetobacter baumannii ATCC 17978. Notably, the 85% aqueous methanol fraction of Peucedanum japonicum Thunb. (Pj) and the n-hexane fraction of Lysimachia mauritiana Lam. (Lm) demonstrated significant anti-biofilm activity. Further assessments revealed that these fractions also exhibited notable antioxidant and anti-inflammatory properties, with the Pj fraction showing a lifespan extension effect in the Caenorhabditis elegans model. These findings suggest that Pj and Lm hold promise as potential candidates for the development of new therapeutic agents targeting MDR bacteria.

Experience with expanded use of oritavancin in a tertiary hospital: indications, tolerability and outcomes.

Oritavancin is a lipoglycopeptide antibacterial agent used to treat infections caused by Gram-positive organisms. It is FDA-approved for the treatment of acute bacterial skin and soft tissue infections (ABSSIs) but is increasingly being used off-label to treat invasive bacterial infections such as osteomyelitis, prosthetic joint infection and infective endocarditis. This study describes the clinical outcomes and adverse reactions related to oritavancin. This was a retrospective study conducted over a 5 year period at a tertiary care medical centre. Ninety-five adult patients were included in this study and were followed for 1 year after the last dose of oritavancin. The most common indication for oritavancin at our institution was osteomyelitis, followed by ABSSI. Other indications were vertebral infection, hardware-associated infection, bacteraemia and infective endocarditis. Fourteen percent (13/95) of patients developed an adverse reaction to oritavancin during the study period. Cure with no recurrence up to 1 year after the last dose of oritavancin was achieved in 74% (53/71) of patients, and the treatment failure rate was 19% (14/71 patients). Oritavancin is an effective agent that can be used to treat invasive Gram-positive bacterial infections other than ABSSI. Adverse events requiring drug discontinuation were common.

Self-assembly antimicrobial peptide for treatment of multidrug-resistant bacterial infection

The wide-spreading of multidrug resistance poses a significant threat to human and animal health. Although antimicrobial peptides (AMPs) show great potential application, their instability has severely limited their clinical application. Here, self-assembled AMPs composed of multiple modules based on the principle of associating natural marine peptide N6 with ß-sheet-forming peptide were designed. It is noteworthy that one of the designed peptides, FFN could self-assemble into nanoparticles at 35.46 µM and achieve a dynamic transformation from nanoparticles to nanofibers in the presence of bacteria, resulting in a significant increase in stability in trypsin and tissues by 1.72–57.5 times compared to that of N6. Additionally, FFN exhibits a broad spectrum of antibacterial activity against multidrug-resistant (MDR) gram-positive (G+) and gram-negative (G−) bacteria with Minimum inhibitory concentrations (MICs) as low as 2 µM by membrane destruction and complemented by nanofiber capture. In vivo mouse mastitis infection model further confirmed the therapeutic potential and promising biosafety of the self-assembled peptide FFN, which can effectively alleviate mastitis caused by MDR Escherichia coli (E. coli) and Staphylococcus aureus (S. aureus), and eliminate pathogenic bacteria. In conclusion, the design of peptide-based nanomaterials presents a novel approach for the delivery and clinical translation of AMPs, promoting their application in medicine and animal husbandry.Graphical

Synergistic effect of antibiotics, α-linolenic acid and solvent type against Staphylococcus aureus biofilm formation.

A promising approach to the treatment of bacterial infections involves inhibiting the quorum sensing (QS) mechanism to prevent the formation and growth of bacterial biofilm. While antibiotics are used to kill remaining bacteria, QS inhibitors (QSIs) allow for antibiotic doses to be reduced. This study focuses on evaluating the synergy between gentamicin sulphate (GEN), tobramycin (TOB), or azithromycin (AZM) with linolenic acid (LNA) against the formation of an early Staphylococcus aureus biofilm. Minimum biofilm inhibitory concentration (MBIC) was determined using the resazurin reduction assay for all antibiotics and LNA. The reduction of biofilm mass was assessed using the crystal violet (CV) assay. We have also evaluated the effect of dimethyl sulfoxide with TWEEN (DMSO_T) on early biofilm formation. Synergy was determined by metabolic activity assay and fractional biofilm inhibitory concentration (FBIC). DMSO_T at a concentration of 1% enhanced early biofilm formation, but also decreased the doses of antibiotic needed to reduce the biofilm by up to 8 times. Adding LNA at a concentration of 32µg/ml or 64µg/ml allowed up to a 32-fold reduction of antibiotic doses for GEN and TOB and a 4-fold reduction for AZM. LNA's use in combination with various antibiotics could reduce their doses and help fight drug-resistant bacteria in the biofilm.

Intravenous Versus Oral Omadacycline or Linezolid for Acute Bacterial Skin and Skin Infections: A post hoc Analysis of the OASIS Trials.

Appropriate oral antibiotic therapy for the treatment of acute bacterial skin and skin structure infections (ABSSSI) is a challenge, as current oral treatment guidelines do not fully cover the most common skin pathogens. Both linezolid and omadacycline are available as intravenous or bioequivalent oral formulations. This post hoc analysis of the OASIS-1 (ClinicalTrials.gov identifier NCT02378480) and OASIS-2 (ClinicalTrials.gov identifier NCT02877927) phase 3 trials assessed safety and clinical efficacy of intravenous (IV)-start versus oral (PO)-start therapy in patients treated with omadacycline or linezolid for ABSSSI. In OASIS-1, patients were randomized to IV omadacycline or linezolid, with optional switch to oral therapy, while patients in OASIS-2 received oral omadacycline or linezolid. Treatment was provided for 7-14days in both studies. The primary endpoint was an early clinical response (ECR) at 48 to 72h, defined as survival and ≥ 20% reduction in lesion size, without rescue antibacterial therapy. A total of 645 IV-start inpatients and 735 PO-start outpatients were assessed. Median age was 47years for the IV-start group and 44years for the PO-start group. Most patients had solely gram-positive infections (97% in each group; ECR [85.2% IV-start and 85.0% PO-start]), and the incidence of treatment-emergent adverse events (AEs) was similar between the groups. The most frequent AEs observed were nausea (11.2% [IV-start] versus 18.9% [PO-start]) and subcutaneous abscess (5.6% [IV-start] versus 1.9% [PO-start]). Discontinuation due to AEs was infrequent in both groups (2% [IV-start] versus 1.2% [PO-start]). Oral therapy is equally efficacious to IV therapy when omadacycline or linezolid is used to treat ABSSSIs. These data strengthen the evidence for oral omadacycline as a therapeutic option for ABSSSI, particularly for patients who have experienced treatment failure because of the limitations of other therapies. Clinicaltrials.gov, NCT02378480 and NCT02877927.

Factors Affecting the Use of Probiotics during Antibiotic Therapy

Aim: To indicate the importance of the use of probiotics and the factors that influence the use of probiotics during antibiotic therapy. Introduction: Antibiotics are pharmacological agents selectively toxic to bacteria, but non-toxic or acceptably toxic to humans, prescribed and used in the treatment of bacterial infections. The most common gastrointestinal complication during antibiotics use is diarrhea. Probiotics are live microorganisms, bacteria and yeasts, which are used in the therapy of numerous conditions, especially in intestinal diseases. Methods: An anonymous survey of 207 patients from Bosnia and Herzegovina who used antibiotics and probiotics in the period from February 2023 to March 2024. Results: The results indicate that the use of antibiotics is frequent. About a third of the examined patients used the probiotic occasionally or not at all during the duration of the antibiotic therapy. About two thirds of the patients took the probiotic on their own initiative. A large part of the examined patients is familiar with the purpose of using probiotics. The price of probiotics plays a significant role in the application and length of use of probiotics. Discussion: Frequent use of antibiotics can increase the likelihood of gastrointestinal side effects, especially diarrhea. The use of probiotics is often shorter than the duration of antibiotic therapy. It’s use is often occasional, and on patients initiative, mostly because of the price of probiotics. Conclusion: The obtained results indicate that it is important to point out the purpose of the use of probiotics in addition to antibiotics to patients, and that a decrease in the price of probiotics would increase the length of use of probiotics.

Development of bacterial resistance in Germany from 2008 to 2022 - major culprit pathogens, antibacterial drugs, and prescribing practices.

Rising bacterial resistance is a global threat, causing rising financial burdens on healthcare systems and endangering effective treatment of bacterial infections. To ensure the efficacy of antibacterial drugs, it is essential to identify the most dangerous pathogens and vulnerable antibacterial drugs. Previous research by our group suggested irrational outpatient prescribing practices in Germany, supporting a growing bacterial resistance. This study analyses developments and characteristics for the ten most prescribed antibacterial drugs in Germany from 2008 to 2022. Conclusions are based on the development of bacterial resistance levels and an analysis of correlations between pathogens. We identified cefuroxime axetil, sulfamethoxazole-trimethoprim and nitrofurantoin as the most problematic drugs. Particularly problematic pathogens include E. faecalis, E. faecium, K. pneumoniae, and P. mirabilis. Besides increasing bacterial resistance, they are characterised by a high proportion of significant positive correlations, indicating a high potential for mutually reinforcing resistance development. Alarmingly, most of the antibacterial drugs analysed showed a growing resistance to at least one of the analysed pathogens. In most cases, the best treatment option is threatened by increasing bacterial resistance. We also identified several differences between current bacterial resistance data and therapeutic guidelines. In aggregate, our findings support irrational prescribing behaviour and underscore the urgent need for improved prescribing practices to counter rising bacterial resistance in Germany. Moreover, therapeutic guidelines for bacterial infections, the "holy grail" of pharmacotherapy, must be updated more frequently.

First Report on Salvia Sahendica Boiss & Buhs roots biocomponents characterization by GC-MS and HPLC and Antibacterial Potency

Treatment of bacterial infections with antibiotic resistance is complicated. For this reason, new therapeutic methods are needed to control bacterial infections. Therefore, it is necessary to discover new antibiotics from medicinal plants that can destroy drug-resistant bacteria. Essential oils (EO) of some medicinal plants have antimicrobial effects and can be used as antimicrobial agents in the treatment of infections and food industries. The aim of this study was to determine the EO composition and antimicrobial effects of EO and polyphenols profile of Salvia Sahendica roots for the first time. Chemical compounds and antibacterial activity of EOs against Staphylococcus aureus and Bacillus cereus as gram-positive and Escherichia coli and Pseudomonas aeruginosa as gram- negative bacteria were evaluated using microtiter broth dilution method. Studied organs of S. sahendica showed significant diversity in terms of type and percentage of essential oil and polyphenol compounds. Overall, 44, 46, 42, and 45 compounds were identified in the essential oil of leaves, flowers, stems, and roots of this plant, which constituted 99.6, 99.3, 98.2, and 99.4% of total oil composition, respectively. The current study collectively demonstrated inhibitory effects ranged from strong (S. aureus) to low inhibition (P. aeruginosa). According to the HPLC result, the amounts of coumaric acid, chlorogenic acid, and gallic acid compounds in the root are higher than in other plant parts, which indicate that the root can be a suitable source for the production of these valuable polyphenol compounds. Due to the results, it is possible to hope for the application of EO from S. sahendica as natural antibacterial in the pharmaceutical and food industries.

Antibacterial activity of Savory (Satureja hortensis) extract against pure culture strains of

The paper presents the results of a study of the antibacterial activity of supercritical carbon dioxide extract of the aboveground part of Savory (Satureja hortensis) against Escherichia coli, Salmonella spp. and Staphylococcus aureus bacteria.To study the antibacterial properties of Savory extract (Satureja hortensis) against infections caused by Staphylococcus aureus, Escherichia coli and Salmonella spp.In the course of the experiment, Savory extract obtained by supercritical carbon dioxide extraction was studied for antimicrobial activity against these bacteria. The component composition of the extract was determined by chromatography–mass spectrometry. To determine the antibacterial activity, we used the method of dilution in a liquid medium with subsequent measurement of the growth of the suspension culture biomass. The activity of the extract was compared with certified drugs included in the protocols for the treatment of bacterial infections. DMSO and potassium phosphate buffer were used as a negative control.The studies showed that the extract exhibits high antibacterial activity against all the studied bacterial strains and has a direct positive correlation with its concentration. Chromatographic mass‐spectrometry analysis showed that the extract of garden Savory contains 28 substances, the main ones being thymol (30.51 %), gamma‐terpinene (15.27 %), para‐ cymene (14.25 %) and Carvacrol (9.18 %), which both individually and in combination could exhibit antibacterial activity.Supercritical carbon dioxide extract exhibits pronounced antimicrobial activity against reference strains of S. aureus, Escherichia coli and Salmonella spp.

Time-Dependent Electrical Active and Ultrasound-Responsive Calcium Titanate Implant Coating with Immunomodulation, Osteogenesis, and Customized Antibacterial Activity.

Surgical site infection and insufficient osseointegration are notable risks factors associated with oral implant surgery. In this study, the development of a polarized calcium titanate (CT-P) coating for titanium surfaces is proposed as a solution to these problems. The coating generated electrical stimulation (ES) can inhibit pro-inflammatory M1-type macrophage polarization and promote anti-inflammatory M2-type macrophage polarization, resulting in favorable bone immunomodulation. The ES generated by the coating can match the physiological electrical potential that will change during bone repair, thereby promoting osseointegration in vivo. In addition, the system can also achieve on-demand antibacterial activity, mainly depending on the CT-P coating responding to ultrasound (US) irradiation to produce reactive oxygen species (ROS) and remove Staphylococcus aureus (S. aureus) on the surface of the implant. In conclusion, this work provides valuable insights for the development and clinical application of highly efficient electroactive coatings, as well as novel solutions for the selective treatment of bacterial infections in the surgical area.

Mechanism of imipenem-induced mental disorder: A meta-analysis.

Imipenem is a highly effective carbapenem antibiotic, which is widely used in the treatment of many serious bacterial infections. At the same time, it can also cause some adverse reactions, mental abnormalities are the most concerned central nervous system adverse reactions. Different patients respond differently to imipenem, and the effect of imipenem on psychiatric disorders is unclear. Therefore, meta-analysis summarizing the results of multiple previous studies can provide stronger evidence support for clinical guidelines to guide clinical rational use of imipenem to minimize risks. To systematically review the effects of imipenem on mental-health disorders. Method in Cochrane Library, Web of science, PubMed, ProQuest, and China's biomedical literature databases Wanfang, Weipu and China HowNet, the related literatures about the controlled trials of imipenem-induced mental disorders from the establishment of the database to May 2024 were searched; the included literatures were analyzed using RevMan 5.4 software; and the heterogeneity among the studies was also discussed. After reviewing the literature published between 2003 and 2017, seven controlled trials with a total of 550 patients were included, with 273 and 277 patients in the control and experimental groups, respectively. The sample size of the study ranged from a minimum of 30 cases to a maximum of 61 cases. Patients in the experimental group were treated with imipenem while the control group was treated with conventional drugs. Meta-analysis showed that the incidence of mental disorders in the experimental group was higher than that in the control group (odds ratio = 3.66, 95% confidence interval: 1.11-12.11, P = 0.030); however, there was no significant difference in the incidence of adverse reactions between the two groups (odds ratio = 0.05, 95% confidence interval: 0.00 to 0.10, P = 0.060). Funnel diagrams showed that the scattered points of each study were symmetrical and distributed in an inverted funnel shape; therefore, there was no publication bias. Imipenem can cause mental disorders in patients. However, the low quality of the included literature may have affected the final results. Therefore, it is necessary to conduct a high-quality randomized controlled study with multiple samples to further confirm the mechanism of imipenem-induced mental disorders and provide effective guidance for clinical treatment.

Biomimetic Electrodynamic Metal-Organic Framework Nanosponges for Augmented Treatment of Biofilm Infections.

Electrodynamic therapy (EDT) is a promising alternative approach for antibacterial therapy, as reactive oxygen species (ROS) are produced efficiently in response to an electric field without relying on endogenous H2O2 and O2. However, the inherent toxicity of metallic catalysts and numerous bacterial toxins during the therapeutic process still hinder its development. Herein, biomimetic metal-organic (MOF@EV) nanosponges composed of ginger-derived extracellular vesicles (EVs), and electrodynamic metal-organic frameworks (MOFs) are developed for the eradication of bacterial infections and the absorption of toxins. The prolonged circulation time of MOF@EV in vivo facilitates their accumulation at infection sites. More interestingly, MOF@EV can behave as nanosponges and effectively prevent host cells from binding to bacterial toxins, thereby reducing damage to cells. Subsequently, the MOF@EV nanosponges are discovered to work as electro-sensitizers, which is confirmed through both theoretical calculation and experimental verification. As a result, ROS is continuously produced under the electric field to achieve effective EDT-mediated bacterial eradication. Meanwhile, the treatment process of MOF@EV in vivo is visualized in mice infected with luciferase-expressing Staphylococcus aureus (S. aureus), and excellent biofilm eradication capacity and detoxification efficiency are demonstrated in a subcutaneous abscess model. This work provides a promising strategy for the treatment of bacterial infections.

Bioequivalence Analysis of Clindamycin Hydrochloride Capsules in Healthy Chinese Subjects Under Fasted and Fed Conditions.

Clindamycin is a lincosamide antibiotic for the treatment of staphylococcal, streptococcal, and anaerobic bacterial infections. We conducted a single-center, single-dose, 2-preparation, 2-period, 2-sequence, randomized, open-label, 2×2 crossover study to evaluate the pharmacokinetics (PKs) and safety of the test and reference clindamycin hydrochloride capsules in healthy Chinese subjects under both fasted and fed conditions. Forty-eight subjects were enrolled in the study totally, with 24 subjects in each group. All subjects were asked to take a test or reference preparation, under either fasted or fed condition, and their blood samples were collected and assayed by a validated high-performance liquid chromatography-tandem mass spectrometry method. PK parameters including maximum plasma concentration, area under the plasma concentration-time curve from time 0 to the last concentration, and area under the plasma concentration-time curve from time 0 to infinity were estimated with noncompartmental model and analyzed. Results showed that the PK profiles of the 2 preparations were consistent and met the bioequivalence criteria. Food was identified as a factor that had an impact on clindamycin absorption. The safety of clindamycin hydrochloride capsules was satisfactory. This study proved that the 2 clindamycin hydrochloride capsules were bioequivalent in healthy Chinese subjects under both fasted and fed conditions.

Recombinant Lactococcus lactis secreting FliC protein nanobodies for resistance against Salmonella enteritidis invasion in the intestinal tract

Salmonella Enteritidis is a major foodborne pathogen throughout the world and the increase in antibiotic resistance of Salmonella poses a significant threat to public safety. Natural nanobodies exhibit high affinity, thermal stability, ease of production, and notably higher diversity, making them widely applicable for the treatment of viral and bacterial infections. Recombinant expression using Lactococcus lactis leverages both acid resistance and mucosal colonization properties of these bacteria, allowing the effective expression of exogenous proteins for therapeutic effects. In this study, nine specific nanobodies against the flagellar protein FliC were identified and expressed. In vitro experiments demonstrated that FliC-Nb-76 effectively inhibited the motility of S. Enteritidis and inhibited its adhesion to and invasion of HIEC-6, RAW264.7, and chicken intestinal epithelial cells. Additionally, a recombinant L. lactis strain secreting the nanobody, L. lactis-Nb76, was obtained. Animal experiments confirmed that it could significantly reduce the mortality rates of chickens infected with S. Enteritidis, together with alleviating the inflammatory response caused by the pathogen. These results provide a novel strategy for the treatment of antibiotic-resistant S. Enteritidis infection in the intestinal tract.Graphical

Macrolide resistance through uL4 and uL22 ribosomal mutations in Pseudomonas aeruginosa

Macrolides are widely used antibiotics for the treatment of bacterial airway infections. Due to its elevated minimum inhibitory concentration in standardized culture media, Pseudomonas aeruginosa is considered intrinsically resistant and, therefore, antibiotic susceptibility testing against macrolides is not performed. Nevertheless, due to macrolides’ immunomodulatory effect and suppression of virulence factors, they are used for the treatment of persistent P. aeruginosa infections. Here, we demonstrate that macrolides are, instead, effective antibiotics against P. aeruginosa airway infections in an Air-Liquid Interface (ALI) infection model system resembling the human airways. Importantly, macrolide treatment in both people with cystic fibrosis and primary ciliary dyskinesia patients leads to the accumulation of uL4 and uL22 ribosomal protein mutations in P. aeruginosa which causes antibiotic resistance. Consequently, higher concentrations of antibiotics are needed to modulate the macrolide-dependent suppression of virulence. Surprisingly, even in the absence of antibiotics, these mutations also lead to a collateral reduction in growth rate, virulence and pathogenicity in airway ALI infections which are pivotal for the establishment of a persistent infection. Altogether, these results lend further support to the consideration of macrolides as de facto antibiotics against P. aeruginosa and the need for resistance monitoring upon prolonged macrolide treatment.