Associations between TLRs 2 and 4, and ß-lactam antibiotics in COPD patients complicated with pulmonary infections.

INTRODUCTION: Chronic obstructive pulmonary disease (COPD) is the third leading cause of death in the world. We aimed to investigate the associations between toll-like receptors 2 and 4 (TLR-2 and TLR-4) and ß-lactam antibiotics in COPD patients complicated with pulmonary infections. METHODOLOGY: A total of 156 COPD patients complicated with pulmonary infections were included. Their blood gas, airway resistance, health status, expression levels of TLR-2 and TLR-4, and pulmonary function were analyzed after treatment with ß-lactam antibiotics. RESULTS: Blood gas indices oxygen saturation, partial pressure of oxygen, and partial pressure of carbon dioxide at one day before treatment, on the fifteenth day of treatment, and on the first day after the end of treatment showed significant differences (p < 0.01). Significant differences were also detected in airway resistance indices (p < 0.01). The differences in the mRNA expression levels of TLR-2 and TLR-4 were significant (p < 0.05). Downward trends were observed in the clinical pulmonary infection score and acute physiology and chronic health evaluation II score, which indicated alleviation of the disease. Pulmonary function indices recorded vital capacity (VC)/predicted VC (%), recorded forced vital capacity at 1 s (FEV1)/predicted FEV1 (%), and residual volume/total lung capacity were significantly different (p < 0.05). CONCLUSIONS: ß-Lactam antibiotics had obvious therapeutic effects on COPD patients complicated with pulmonary infections, probably by suppressing or attenuating TLR-2- and TLR-4-mediated inflammatory responses. It is necessary to comprehensively evaluate and choose appropriate antibiotics, aiming for maximum relief of the pain to help patients recover quickly.

Use of the DMAIC Lean Six Sigma quality improvement framework to improve beta-lactam antibiotic adequacy in the critically ill.

Beta-lactam antibiotics are widely used in the intensive care unit due to their favorable effectiveness and safety profiles. Beta-lactams given to patients with sepsis must be delivered as soon as possible after infection recognition (early), treat the suspected organism (appropriate), and be administered at a dose that eradicates the infection (adequate). Early and appropriate antibiotic delivery occurs in >90% of patients, but less than half of patients with sepsis achieve adequate antibiotic exposure. This project aimed to address this quality gap and improve beta-lactam adequacy using the Define, Measure, Analyze, Improve, and Control Lean Six Sigma quality improvement framework. A multidisciplinary steering committee was formed, which completed a stakeholder analysis to define the gap in practice. An Ishikawa cause and effect (Fishbone) diagram was used to identify the root causes and an impact/effort grid facilitated prioritization of interventions. An intervention that included bundled education with the use of therapeutic drug monitoring (TDM; i.e. drug-level testing) was projected to have the highest impact relative to the amount of effort and selected to address beta-lactam inadequacy in the critically ill. The education and TDM intervention were deployed through a Plan, Do, Study, Act cycle. In the 3 months after "go-live," 54 episodes of beta-lactam TDM occurred in 41 unique intensive care unit patients. The primary quality metric of beta-lactam adequacy was achieved in 94% of individuals after the intervention. Ninety-four percent of clinicians gauged the education provided as sufficient. The primary counterbalance of antimicrobial days of therapy, a core antimicrobial stewardship metric, was unchanged over time (favorable result; P = .73). Application of the Define, Measure, Analyze, Improve, and Control Lean Six Sigma quality improvement framework effectively improved beta-lactam adequacy in critically ill patients. The approach taken in this quality improvement project is widely generalizable to other drugs, drug classes, or settings to increase the adequacy of drug exposure.

Extended-Infusion ß-Lactam Therapy, Mortality, and Subsequent Antibiotic Resistance Among Hospitalized Adults With Gram-Negative Bloodstream Infections.

Importance: Current evidence is conflicting for associations of extended-infusion ß-lactam (EI-BL) therapy with clinical outcomes. Objective: To investigate the association of EI-BL therapy with survival, adverse events, and emergence of antibiotic resistance in adults with gram-negative bloodstream infections (GN-BSI). Design, Setting, and Participants: This cohort study of consecutive adults with GN-BSI admitted to 24 United States hospitals between January 1, 2019, and December 31, 2019, receiving EI-BL were compared with adults with GN-BSI receiving the same agents as intermittent infusion ß-lactam (II-BL; ≤1-hour infusions). Statistical analysis was performed from January to October 2023. Exposures: EI-BL (ie, ≥3-hour infusion). Main Outcomes and Measures: EI-BL and II-BL groups underwent 1:3 nearest-neighbor propensity score matching (PSM) without replacement. Multivariable regression was applied to the PSM cohort to investigate outcomes, all censored at day 90. The primary outcome was mortality; secondary outcomes included antibiotic adverse events and emergence of resistance (≥4-fold increase in the minimum inhibitory concentration of the ß-lactam used to treat the index GN-BSI). Results: Among the 4861 patients included, 2547 (52.4%) were male; and the median (IQR) age was 67 (55-77) years. There were 352 patients in the EI-BL 1:3 PSM group, and 1056 patients in the II-BL 1:3 PSM group. Among 1408 PSM patients, 373 (26.5%) died by day 90. The odds of mortality were lower in the EI-BL group (adjusted odds ratio [aOR], 0.71 [95% CI, 0.52-0.97]). In a stratified analysis, a survival benefit was only identified in patients with severe illness or elevated minimum inhibitory concentrations (ie, in the intermediate range for the antibiotic administered). There were increased odds of catheter complications (aOR, 3.14 [95% CI, 1.66-5.96]) and antibiotic discontinuation because of adverse events (eg, acute kidney injury, cytopenias, seizures) in the EI-BL group (aOR, 3.66 [95% CI, 1.68-7.95]). Emergence of resistance was similar in the EI-BL and II-BL groups at 2.9% vs 7.2%, respectively (P = .35). Conclusions and Relevance: In this cohort study of patients with GN-BSI, EI-BL therapy was associated with reduced mortality for patients with severe illness or those infected with nonsusceptible organisms; potential advantages in other groups remain unclear and need to be balanced with potential adverse events. The subsequent emergence of resistance warrants investigation in a larger cohort.

Case Commentary: Dual ß-lactam as part of regimen to treat Mycobacterium abscessus lung disease.

Individuals with compromised lung function and immunity are susceptible to developing chronic Mycobacterium abscessus infection. Current treatment recommendations typically involve using one ß-lactam antibiotic in combination with non-ß-lactam antibiotics. However, a recent case study (B. Becken, K. M. Dousa, J. L. Johnson, S. M. Holland, and R. A. Bonomo, Antimicrob Agents Chemother 68:e00319-24, 2024, https://doi.org/10.1128/aac.00319-24) demonstrated successful treatment of chronic M. abscessus lung disease in a child using two ß-lactam antibiotics simultaneously. This commentary reviews the emerging evidence and outstanding questions regarding dual ß-lactam therapy for M. abscessus infections.

Genomic investigation and clinical correlates of the in vitro ß-lactam: NaHCO3 responsiveness phenotype among methicillin-resistant Staphylococcus aureus isolates from a randomized clinical trial.

NaHCO3 responsiveness is a novel phenotype where some methicillin-resistant Staphylococcus aureus (MRSA) isolates exhibit significantly lower minimal inhibitory concentrations (MIC) to oxacillin and/or cefazolin in the presence of NaHCO3. NaHCO3 responsiveness correlated with treatment response to ß-lactams in an endocarditis animal model. We investigated whether treatment of NaHCO3-responsive strains with ß-lactams was associated with faster clearance of bacteremia. The CAMERA2 trial (Combination Antibiotics for Methicillin-Resistant Staphylococcus aureus) randomly assigned participants with MRSA bloodstream infections to standard therapy, or to standard therapy plus an anti-staphylococcal ß-lactam (combination therapy). For 117 CAMERA2 MRSA isolates, we determined by broth microdilution the MIC of cefazolin and oxacillin, with and without 44 mM of NaHCO3. Isolates exhibiting ≥4-fold decrease in the MIC to cefazolin or oxacillin in the presence of NaHCO3 were considered "NaHCO3-responsive" to that agent. We compared the rate of persistent bacteremia among participants who had infections caused by NaHCO3-responsive and non-responsive strains, and that were assigned to combination treatment with a ß-lactam. Thirty-one percent (36/117) and 25% (21/85) of MRSA isolates were NaHCO3-responsive to cefazolin and oxacillin, respectively. The NaHCO3-responsive phenotype was significantly associated with sequence type 93, SCCmec type IVa, and mecA alleles with substitutions in positions -7 and -38 in the regulatory region. Among participants treated with a ß-lactam, there was no association between the NaHCO3-responsive phenotype and persistent bacteremia (cefazolin, P = 0.82; oxacillin, P = 0.81). In patients from a randomized clinical trial with MRSA bloodstream infection, isolates with an in vitro ß-lactam-NaHCO3-responsive phenotype were associated with distinctive genetic signatures, but not with a shorter duration of bacteremia among those treated with a ß-lactam.

Optimal use of ß-lactams in neonates: machine learning-based clinical decision support system.

BACKGROUND: Accurate prediction of the optimal dose for ß-lactam antibiotics in neonatal sepsis is challenging. We aimed to evaluate whether a reliable clinical decision support system (CDSS) based on machine learning (ML) can assist clinicians in making optimal dose selections. METHODS: Five ß-lactam antibiotics (amoxicillin, ceftazidime, cefotaxime, meropenem and latamoxef), commonly used to treat neonatal sepsis, were selected. The CDSS was constructed by incorporating the drug, patient, dosage, pharmacodynamic, and microbiological factors. The CatBoost ML algorithm was used to build the CDSS. Real-world studies were used to evaluate the CDSS performance. Virtual trials were used to compare the CDSS-optimized doses with guideline-recommended doses. FINDINGS: For a specific drug, by entering the patient characteristics and pharmacodynamic (PD) target (50%/70%/100% fraction of time that the free drug concentration is above the minimal inhibitory concentration [fT > MIC]), the CDSS can determine whether the planned dosing regimen will achieve the PD target and suggest an optimal dose. The prediction accuracy of all five drugs was >80.0% in the real-world validation. Compared with the PopPK model, the overall accuracy, precision, recall, and F1-Score improved by 10.7%, 22.1%, 64.2%, and 43.1%, respectively. Using the CDSS-optimized doses, the average probability of target concentration attainment increased by 58.2% compared to the guideline-recommended doses. INTERPRETATION: An ML-based CDSS was successfully constructed to assist clinicians in selecting optimal ß-lactam antibiotic doses. FUNDING: This work was supported by the National Natural Science Foundation of China; Distinguished Young and Middle-aged Scholar of Shandong University; National Key Research and Development Program of China.

Oral quinolones versus intravenous ß-lactam for the treatment of acute focal bacterial nephritis: a retrospective cohort study.

BACKGROUND: Evidence regarding the best antibiotic regimen and the route of administration to treat acute focal bacterial nephritis (AFBN) is scarce. The aim of the present study was to compare the effectiveness of intravenous (IV) ß-lactam antibiotics versus oral quinolones. METHODS: This is a retrospective single centre study of patients diagnosed with AFBN between January 2017 and December 2018 in Hospital Universitari Vall d'Hebron, Barcelona (Spain). Patients were identified from the diagnostic codifications database. Patients treated with oral quinolones were compared with those treated with IV ß-lactam antibiotics. Therapeutic failure was defined as death, relapse, or evolution to abscess within the first 30 days. RESULTS: A total of 264 patients fulfilled the inclusion criteria. Of those, 103 patients (39%) received oral ciprofloxacin, and 70 (26.5%) IV ß-lactam. The most common isolated microorganism was Escherichia coli (149, 73.8%) followed by Klebsiella pneumoniae (26, 12.9%). Mean duration of treatment was 21.3 days (SD 7.9). There were no statistical differences regarding therapeutic failure between oral quinolones and IV ß-lactam treatment (6.6% vs. 8.7%, p = 0.6). Out of the 66 patients treated with intravenous antibiotics, 4 (6.1%) experienced an episode of phlebitis and 1 patient (1.5%) an episode of catheter-related bacteraemia. CONCLUSIONS: When susceptible, treatment of AFBN with oral quinolones is as effective as IV ß-lactam treatment with fewer adverse events.

In Enterobacterales bacteremia, antipseudomonal ß-lactam de-escalation was noninferior to continuation for clinical cure at 3 to 5 d.

SOURCE CITATION: López-Cortés LE, Delgado-Valverde M, Moreno-Mellado E, et al; SIMPLIFY study group. Efficacy and safety of a structured de-escalation from antipseudomonal ß-lactams in bloodstream infections due to Enterobacterales (SIMPLIFY): an open-label, multicentre, randomised trial. Lancet Infect Dis. 2024;24:375-385. 38215770.

Dual ß-lactam for treatment of pulmonary Mycobacterium abscessus in a child.

Treatment of Mycobacterium abscessus infection presents significant challenges, exacerbated by the emergence of macrolide-resistant strains that necessitate the use of multiple antimicrobials in combination and carry the potential for significant toxic effects. Select dual beta-lactam combinations, with or without beta-lactamase inhibitors, have been shown to be highly active in vitro. Herein, we describe a 6-year-old child with underlying mild bilateral lower lobe cylindrical bronchiectatic lung disease who developed pulmonary Mycobacterium abscessus infection and was treated with a multi-drug regimen including two ß-lactam antibiotics, achieving both early clinical and microbiological cure. This case highlights the potential benefit of dual ß-lactam therapy for the treatment of drug-resistant Mycobacterium abscessus infection.

Long-Term Outcomes Associated With ß-Lactam Allergies.

Importance: ß-lactam (BL) allergies are the most common drug allergy worldwide, but most are reported in error. BL allergies are also well-established risk factors for adverse drug events and antibiotic-resistant infections during inpatient health care encounters, but the understanding of the long-term outcomes of patients with BL allergies remains limited. Objective: To evaluate the long-term clinical outcomes of patients with BL allergies. Design, Setting, and Participants: This longitudinal retrospective cohort study was conducted at a single regional health care system in western Pennsylvania. Electronic health records were analyzed for patients who had an index encounter with a diagnosis of sepsis, pneumonia, or urinary tract infection between 2007 and 2008. Patients were followed-up until death or the end of 2018. Data analysis was performed from January 2022 to January 2024. Exposure: The presence of any BL class antibiotic in the allergy section of a patient's electronic health record, evaluated at the earliest occurring observed health care encounter. Main Outcomes and Measures: The primary outcome was all-cause mortality, derived from the Social Security Death Index. Secondary outcomes were defined using laboratory and microbiology results and included infection with methicillin-resistant Staphylococcus aureus (MRSA), Clostridium difficile, or vancomycin-resistant Enterococcus (VRE) and severity and occurrence of acute kidney injury (AKI). Generalized estimating equations with a patient-level panel variable and time exposure offset were used to evaluate the odds of occurrence of each outcome between allergy groups. Results: A total of 20 092 patients (mean [SD] age, 62.9 [19.7] years; 12 231 female [60.9%]), of whom 4211 (21.0%) had BL documented allergy and 15 881 (79.0%) did not, met the inclusion criteria. A total of 3513 patients (17.5%) were Black, 15 358 (76.4%) were White, and 1221 (6.0%) were another race. Using generalized estimating equations, documented BL allergies were not significantly associated with the odds of mortality (odds ratio [OR], 1.02; 95% CI, 0.96-1.09). BL allergies were associated with increased odds of MRSA infection (OR, 1.44; 95% CI, 1.36-1.53), VRE infection (OR, 1.18; 95% CI, 1.05-1.32), and the pooled rate of the 3 evaluated antibiotic-resistant infections (OR, 1.33; 95% CI, 1.30-1.36) but were not associated with C difficile infection (OR, 1.04; 95% CI, 0.94-1.16), stage 2 and 3 AKI (OR, 1.02; 95% CI, 0.96-1.10), or stage 3 AKI (OR, 1.06; 95% CI, 0.98-1.14). Conclusions and Relevance: Documented BL allergies were not associated with the long-term odds of mortality but were associated with antibiotic-resistant infections. Health systems should emphasize accurate allergy documentation and reduce unnecessary BL avoidance.

Change in Tissue Microbiome and Related Human Beta Defensin Levels Induced by Antibiotic Use in Bladder Carcinoma.

It is now generally accepted that the success of antitumor therapy can be impaired by concurrent antibiotic therapy, the presence of certain bacteria, and elevated defensin levels around the tumor tissue. The aim of our current investigation was to identify the underlying changes in microbiome and defensin levels in the tumor tissue induced by different antibiotics, as well as the duration of this modification. The microbiome of the tumor tissues was significantly different from that of healthy volunteers. Comparing only the tumor samples, no significant difference was confirmed between the untreated group and the group treated with antibiotics more than 3 months earlier. However, antibiotic treatment within 3 months of analysis resulted in a significantly modified microbiome composition. Irrespective of whether Fosfomycin, Fluoroquinolone or Beta-lactam treatment was used, the abundance of Bacteroides decreased, and Staphylococcus abundance increased. Large amounts of the genus Acinetobacter were observed in the Fluoroquinolone-treated group. Regardless of the antibiotic treatment, hBD1 expression of the tumor cells consistently doubled. The increase in hBD2 and hBD3 expression was the highest in the Beta-lactam treated group. Apparently, antibiotic treatment within 3 months of sample analysis induced microbiome changes and defensin expression levels, depending on the identity of the applied antibiotic.

Unitary Tract Infection Treatment: When to Use What Agents including Beta-lactam Combination Agents.

In this study, the authors review antibiotic treatment options for both acute uncomplicated and complicated urinary tract infection (UTI). In addition, they also review regimens used in the setting of drug-resistant pathogens including vancomycin resistant Enterococcus, extended spectrum beta-lactamase (ESBL) producing Enterobacterals, carbapenem-resistant Enterobacterals and carbapenem-resistant Pseudomonas, which are encountered with increasing frequency.

Effectiveness of novel ß-lactams for Pseudomonas aeruginosa infection: A systematic review and meta-analysis.

BACKGROUND: Novel ß-lactams have in vitro activity against Pseudomonas aeruginosa (PA), but their clinical performances and the selection criteria for practical use are still not clear. We aimed to evaluate the efficacy of novel ß-lactams for PA infection in various sites and to compare the efficacy of each agent. METHODS: We searched PubMed, Embase, Cochrane Library, and Web of Science for randomized controlled trials that used novel ß-lactams to treat PA infection. The primary outcomes were clinical cure and favorable microbiological response. Subgroup analyses were performed based on drug type, drug resistance of pathogens, and site of infection. Network meta-analysis was carried out within a Bayesian framework. RESULTS: In all studies combined (16 randomized controlled trials), novel ß-lactams indicated comparable performance to other treatment regimens in both outcome measures (relative risk = 1.04; 95% confidence interval 0.94-1.15; P = .43) (relative risk = 0.97; 95% confidence interval 0.81-1.17; P = .76). Subgroup analyses showed that the efficacy of ceftolozane-tazobactam (TOL-TAZ), ceftazidime-avibactam (CAZ-AVI), imipenem-cilastatin-relebactam, and cefiderocol had no apparent differences compared to control groups among different infection sites, drug types and drug resistance of PA. In network meta-analysis, the results showed no statistically significant differences between TOL-TAZ, CAZ-AVI, and cefiderocol. CONCLUSIONS: TOL-TAZ, CAZ-AVI, imipenem-cilastatin-relebactam, and cefiderocol are not inferior to other agents in the treatment of PA infection. Their efficacy is also comparable between TOL-TAZ, CAZ-AVI, and cefiderocol.

What are the optimal pharmacokinetic/pharmacodynamic targets for ß-lactamase inhibitors? A systematic review.

BACKGROUND: Pharmacokinetic/pharmacodynamic (PK/PD) indices are widely used for the selection of optimum antibiotic doses. For ß-lactam antibiotics, fT>MIC, best relates antibiotic exposure to efficacy and is widely used to guide the dosing of ß-lactam/ß-lactamase inhibitor (BLI) combinations, often without considering any PK/PD exposure requirements for BLIs. OBJECTIVES: This systematic review aimed to describe the PK/PD exposure requirements of BLIs for optimal microbiological efficacy when used in combination with ß-lactam antibiotics. METHODS: Literature was searched online through PubMed, Embase, Web of Science, Scopus and Cochrane Library databases up to 5 June 2023. Studies that report the PK/PD index and threshold concentration of BLIs approved for clinical use were included. Narrative data synthesis was carried out to assimilate the available evidence. RESULTS: Twenty-three studies were included. The PK/PD index that described the efficacy of BLIs was fT>CT for tazobactam, avibactam and clavulanic acid and fAUC0-24/MIC for relebactam and vaborbactam. The optimal magnitude of the PK/PD index is variable for each BLI based on the companion ß-lactam antibiotics, type of bacteria and ß-lactamase enzyme gene transcription levels. CONCLUSIONS: The PK/PD index that describes the efficacy of BLIs and the exposure measure required for their efficacy is variable among inhibitors; as a result, it is difficult to make clear inference on what the optimum index is. Further PK/PD profiling of BLI, using preclinical infection models that simulate the anticipated mode(s) of clinical use, is warranted to streamline the exposure targets for use in the optimization of dosing regimens.

Carbapenem or new ß-lactam-ß-lactamase inhibitors? An Italian survey supported by SITA, SIMIT and SIAARTI to identify the factors affecting empiric antimicrobial therapy choice in real-life clinical practice.

While a tailored antibiotic treatment plan is often straightforward, what we often observe in daily clinical practice is a highly variable approach when defining empirical therapy. Specifically, a debate exists on preference to spare the new ß-lactams and ß-lactamase inhibitors (BL-BLIs) or to apply a carbapenem-sparing strategy first. To investigate, we designed a web survey aimed at investigating the variables considered relevant to empirically choosing one antibiotic over the other. Submitted to Italian infectious diseases and intensive care physicians through the support of Società Italiana di Malattie Infettive e Tropicali (SIMIT), Società Italiana di Terapia Antinfettiva (SITA) and Società Italiana Anestesia, Analgesia, Rianimazione e Terapia Intensiva (SIAARTI). We found that demographic characteristics were irrelevant when deciding for empirical therapy. Clinical and anamnestic data were most meaningful. Significantly considered were underlying comorbidities and previous exposure to antimicrobial treatments. History of third-generation cephalosporin-resistant, carbapenem-resistant and/or metallo-ß-lactamase-producing Enterobacterales rectal colonisation and/or infection were considered the most relevant by most physicians. Unexpectedly, clinicians considered less the source of infection. These results prompt the need of straightforward methods to retrieve medical histories and the magnitude of rectal colonisation data, often not routinely obtained.

Dual ß-lactam therapy to improve treatment outcome in Mycobacterium abscessus disease.

BACKGROUND: Antibiotic treatment of Mycobacterium abscessus disease is toxic and poorly effective and lacks a firm evidence base. Dual ß-lactam and ß-lactam/ß-lactamase inhibitor combinations may be interesting leads to improve treatment outcomes. OBJECTIVES: To summarize the current preclinical studies on dual ß-lactam and ß-lactam/ß-lactamase inhibitor combinations against M. abscessus. SOURCES: We performed a literature search using the National Center for Biotechnology Information's PubMed interface with additional snowball sampling. CONTENT: Select combinations of ß-lactam antibiotics, as well as ß-lactam/ß-lactamase inhibitor combinations show promising in vitro activity and synergy against M. abscessus. ß-Lactam antibiotics differ in their ability to reach and interfere with their targets and their resistance to the M. abscessus ß-lactamase. The synergy is typically observed for combinations of ß-lactam antibiotics or a ß-lactam antibiotic with a ß-lactamase inhibitor. No additional killing capacity was demonstrated in three-drug combinations of synergistic ß-lactam antibiotics and a ß-lactamase inhibitor. The efficacy of select dual ß-lactam antibiotics and ß-lactam/ß-lactamase inhibitor combinations is retained in intracellular infection assays and mouse models, but no combination has a complete preclinical portfolio. IMPLICATIONS: Future clinical strategies should entail either dual ß-lactam or ß-lactam/ß-lactamase inhibitor combinations. Imipenem-ceftaroline and an all-oral tebipenem-avibactam combination are promising leads but still require a complete preclinical portfolio, target product profiles as well as clinical trial confirmation.

Synergistic Augmentation of Beta-Lactams: Exploring Quinoline-Derived Amphipathic Small Molecules as Antimicrobial Potentiators against Methicillin-Resistant Staphylococcus aureus.

The escalation of bacterial resistance against existing therapeutic antimicrobials has reached a critical peak, leading to the rapid emergence of multidrug-resistant strains. Stringent pathways in novel drug discovery hinder our progress in this survival race. A promising approach to combat emerging antibiotic resistance involves enhancing conventional ineffective antimicrobials using low-toxicity small molecule adjuvants. Recent research interest lies in weak membrane-perturbing agents with unique cyclic hydrophobic components, addressing a significant gap in antimicrobial drug exploration. Our study demonstrates that quinoline-based amphipathic small molecules, SG-B-52 and SG-B-22, significantly reduce MICs of selected beta-lactam antibiotics (ampicillin and amoxicillin) against lethal methicillin-resistant Staphylococcus aureus (MRSA). Mechanistically, membrane perturbation, depolarization, and ROS generation drive cellular lysis and death. These molecules display minimal in vitro and in vivo toxicity, showcased through hemolysis assays, cell cytotoxicity analysis, and studies on albino Wistar rats. SG-B-52 exhibits impressive biofilm-clearing abilities against MRSA biofilms, proposing a strategy to enhance beta-lactam antibiosis and encouraging the development of potent antimicrobial potentiators.