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Antibiotic resistance is a major threat to global health. It emerges in multispecies microbial communities under antibiotic exposure. This makes antibiotic spectrum -- a drug's distribution of effects across species -- a potential key parameter in resistance management. However, we currently lack evolutionary theory for resistance dynamics in a multispecies setting. Analysing established community ecology theory, we develop a simple mathematical measure for how one taxon (strain or species) affects another taxon through all direct and indirect interactions in a complex interaction network. Using this, we derive the expected effects of different antibiotic spectra on the abundance of resistant taxa in microbial communities. This furthers our understanding of microbial evolutionary ecology in multispecies communities, and provides a formal theoretical basis for empirical work on optimal antibiotic choice.
Understanding how antibiotics inhibit bacteria can help to reduce antibiotic use and hence avoid antimicrobial resistance - yet few theoretical models exist for bacterial growth inhibition by a clinically relevant antibiotic treatment regimen. In particular, in the clinic, antibiotic treatment is time dependent. Here, we use a recently-developed model to obtain predictions for the dynamical response of a bacterial cell to a time-dependent dose of ribosome-targeting antibiotic. Our results depend strongly on whether the antibiotic shows reversible transport and/or low-affinity ribosome binding ("low-affinity antibiotic") or, in contrast, irreversible transport and/or high affinity ribosome binding ("high-affinity antibiotic"). For low-affinity antibiotics, our model predicts that growth inhibition depends on the duration of the antibiotic pulse, with a transient period of very fast growth following removal of the antibiotic. For high-affinity antibiotics, growth inhibition depends on peak dosage rather than dose duration, and the model predicts a pronounced post-antibiotic effect, due to hysteresis, in which growth can be suppressed for long times after the antibiotic dose has ended
Ribosome-targeting antibiotics, such as chloramphenicol, stall elongating ribosomes during protein synthesis, disrupting mRNA translation. These antibiotic-induced pauses occur stochastically, alter collective ribosome dynamics and transiently block protein production on the affected transcript. Existing models of ribosome traffic often rely on idealized assumptions, such as infinitely long mRNAs and simplified pausing dynamics, overlooking key biological constraints. Here, we develop a Totally Asymmetric Simple Exclusion Process (TASEP) that incorporates stochastic particle pausing, using experimentally determined pausing and unpausing rates to model the effects of ribosome-targeting antibiotics. We introduce a Single-Cluster approximation, which is analytically treatable, tailored to capture the biologically relevant regime of rare and long antibiotic-induced pauses. This biologically constrained model reveals three key insights: (i) the inhibition of antibiotic-induced translation strongly depends on transcript length, with longer transcripts being disproportionately affected; (ii) reducing ribosome initiation rates significantly mitigates antibiotic vulnerability; and (iii) inh
Antimicrobial resistance (AMR) poses a global health threat, reducing the effectiveness of antibiotics and complicating clinical decision-making. To address this challenge, we introduce abx_amr_simulator, a Python-based simulation package designed to model antibiotic prescribing and AMR dynamics within a controlled, reinforcement learning (RL)-compatible environment. The simulator allows users to specify patient populations, antibiotic-specific AMR response curves, and reward functions that balance immedi- ate clinical benefit against long-term resistance management. Key features include a modular design for configuring patient attributes, antibiotic resistance dynamics modeled via a leaky-balloon abstraction, and tools to explore partial observability through noise, bias, and delay in observations. The package is compatible with the Gymnasium RL API, enabling users to train and test RL agents under diverse clinical scenarios. From an ML perspective, the package provides a configurable benchmark environment for sequential decision-making under uncertainty, including partial observability induced by noisy, biased, and delayed observations. By providing a customizable and extensible
This study presents the first large-scale empirical evaluation of quantum machine learning for predicting antibiotic resistance in clinical urine cultures. Antibiotic resistance is amongst the top threats to humanity, and inappropriate antibiotic use is a main driver of resistance. We developed a Quantum Projective Learning (QPL) approach and executed 60 qubit experiments on IBM Eagle and Heron quantum processing units. While QPL did not consistently outperform classical baselines, potentially reflecting current quantum hardware limitations, it did achieve parity or superiority in specific scenarios, notably for the antibiotic nitrofurantoin and selected data splits, revealing that quantum advantage may be data-dependent. Analysis of data complexity measures uncovered a multivariate signature, which comprised Shannon entropy, Fisher Discriminant Ratio, standard deviation of kurtosis, number of low-variance features, and total correlations. The multivariate model accurately (AUC = 0.88, $p$-value = 0.03) distinguished cases wherein QPL executed on quantum hardware would outperform classical models. This signature suggests that quantum kernels excel in feature spaces with high entrop
A survey was conducted from February 2022 to May 2022 on the usage of antibiotics at a poultry farm in different areas of Multan, Punjab Pakistan. A well-organized questionnaire was used for the collection of data. Sixty poultry farms were surveyed randomly in the Multan district. All of these Farms were using antibiotics. Antibiotics are commonly used for the treatment of diseases. Some are used as preventive medicine and a few are used as growth promotors. neomycin, erythromycin, oxytetracycline, streptomycin, and colistin are the broad-spectrum antibiotics that are being used commercially. Enrofloxacin and Furazolidone are the common antibiotics that are being used in Studies these days. The class of Fluoroquinolones is commonly used in poultry farms. Thirty-three patterns of antibiotic usage were observed at poultry farms. multi-drug practices were also observed on various farms. In this study, 25% of antibiotics are prescribed by the veterans while more than 90 % were acquired from the veterinary store. This study provides information about the antibiotics which are commonly being used in the study location district Multan. It is expected that the finding of this survey will b
Timely transition from intravenous (IV) to oral antibiotic therapy shortens hospital stays, reduces catheter-related infections, and lowers healthcare costs, yet one in five patients in England remain on IV antibiotics despite meeting switching criteria. Clinical decision support systems can improve switching rates, but approaches that learn from historical decisions reproduce the delays and inconsistencies of routine practice. We propose using neural processes to model vital sign trajectories probabilistically, predicting switch-readiness by comparing forecasts against clinical guidelines rather than learning from past actions, and ranking patients to prioritise clinical review. The design yields interpretable outputs, adapts to updated guidelines without retraining, and preserves clinical judgement. Validated on MIMIC-IV (US intensive care, 6,333 encounters) and UCLH (a large urban academic UK hospital group, 10,584 encounters), the system selects 2.2-3.2$\times$ more relevant patients than random. Our results demonstrate that forecasting patient physiology offers a principled foundation for decision support in antibiotic stewardship.
There is an urgent need for the development of novel and truly rapid (equal or less than 1 hour) antibiotic susceptibility testing (AST) platforms in order to provide best antimicrobial prescribing practices and to help reduce the increasing global threat of antibiotic resistance. A 785 nm surface enhanced Raman spectroscopy (SERS) based phenotypic methodology is described that results in accurate minimum inhibitory concentration (MIC) determinations for all tested strain-antibiotic pairs. The SERS-AST procedure results in accurate MICs, the key quantitative measure of in vitro drug susceptibility, in 1 hour, including a 30-minute incubation period. The method is effective for both Gram positive and negative species, and for antibiotics with different initial primary targets of antibiotic activity, and for both bactericidal and bacteriostatic antibiotics. The molecular level mechanism of this methodology is described. Bacterial SERS spectra are due to secreted purine nucleotide degradation products (principally adenine, guanine, xanthine and hypoxanthine) resulting from water washing induced bacterial stringent response and the resulting (p)ppGpp alarmone mediates nucleobase format
Comparing future antibiotic resistance levels resulting from different antibiotic treatments is challenging because some patients may survive only under one of the antibiotic treatments. We embed this problem within a semi-competing risks approach to study the causal effect on resistant infection, treated as a non-terminal event time. We argue that existing principal stratification estimands for such problems exclude patients for whom a causal effect is well-defined and is of clinical interest. Therefore, we present a new principal stratum, the infected-or-survivors (ios). The ios is the subpopulation of patients who would have survived or been infected under both antibiotic treatments. This subpopulation is more inclusive than previously defined subpopulations. We target the causal effect among these patients, which we term the feasible-infection causal effect (FICE). We develop large-sample bounds under novel assumptions, and discuss the plausibility of these assumptions in our application. As an alternative, we derive FICE identification using two illness-death models with a bivariate frailty random variable. These two models are connected by a cross-world correlation parameter.
Antibiotic resistance, which is a serious healthcare issue, emerges due to uncontrolled and repeated antibiotic use that causes bacteria to mutate and develop resistance to antibiotics. The Antibiotics Time Machine Problem aims to come up with treatment plans that maximize the probability of reversing these mutations. Motivated by the severity of the problem, we develop a risk-averse approach and formulate a scenario-based mixed-integer linear program with a conditional value-at-risk objective function. We propose a risk-averse scenario batch decomposition algorithm that partitions the scenarios into manageable risk-averse subproblems, enabling the construction of lower and upper bounds. We develop several algorithmic enhancements in the form of stronger no-good cuts and symmetry breaking constraints in addition to scenario regrouping and warm starting. We conduct extensive computational experiments for static and dynamic versions of the problem on a real dataset and demonstrate the effectiveness of our approach. Our results suggest that risk-averse solutions can achieve significantly better worst-case performance compared to risk-neutral solutions with a slight decrease in terms o
Due to the rise in antimicrobial resistance, identifying novel compounds with antibiotic potential is crucial for combatting this global health issue. However, traditional drug development methods are costly and inefficient. Recognizing the pressing need for more effective solutions, researchers have turned to machine learning techniques to streamline the prediction and development of novel antibiotic compounds. While foundation models have shown promise in antibiotic discovery, current mainstream efforts still fall short of fully leveraging the potential of multimodal molecular data. Recent studies suggest that contrastive learning frameworks utilizing multimodal data exhibit excellent performance in representation learning across various domains. Building upon this, we introduce CL-MFAP, an unsupervised contrastive learning (CL)-based multimodal foundation (MF) model specifically tailored for discovering small molecules with potential antibiotic properties (AP) using three types of molecular data. This model employs 1.6 million bioactive molecules with drug-like properties from the ChEMBL dataset to jointly pretrain three encoders: (1) a transformer-based encoder with rotary posi
Antibiotic resistance poses a significant threat in in-patient settings with high mortality. Using MIMIC-III data, we generated Sentence-BERT embeddings from clinical notes and applied Neural Networks and XGBoost to predict antibiotic susceptibility. XGBoost achieved an average F1 score of 0.86, while Neural Networks scored 0.84. This study is among the first to use document embeddings for predicting antibiotic resistance, offering a novel pathway for improving antimicrobial stewardship.
The discovery of novel antibiotics is critical to address the growing antimicrobial resistance (AMR). However, pharmaceutical industries face high costs (over $1 billion), long timelines, and a high failure rate, worsened by the rediscovery of known compounds. We propose an LLM-based pipeline that acts as an alarm system, detecting prior evidence of antibiotic activity to prevent costly rediscoveries. The system integrates organism and chemical literature into a Knowledge Graph (KG), ensuring taxonomic resolution, synonym handling, and multi-level evidence classification. We tested the pipeline on a private list of 73 potential antibiotic-producing organisms, disclosing 12 negative hits for evaluation. The results highlight the effectiveness of the pipeline for evidence reviewing, reducing false negatives, and accelerating decision-making. The KG for negative hits and the user interface for interactive exploration will be made publicly available.
Growth in bacterial populations generally depends on the environment (availability and quality of nutrients, presence of a toxic inhibitor, product inhibition..). Here, we build a model to describe the action of a bacteriostatic antibiotic, assuming that this drug inhibits an essential autocatalytic cycle involved in the cell metabolism. The model recovers known growth laws, can describe various types of antibiotics and confirms the existence of two distinct regimes of growth-dependent susceptibility, previously identified only for ribosome targeting antibiotics. Interestingly, below a certain threshold in terms of antibiotic concentration, a coexistence between two values of the growth rate is possible, which has also been observed experimentally. Interesting extensions of the model include the antagonistic effect of two drugs targeting different autocatalytic cycles or the production of an inhibiting waste.
Antibiotic resistance (AR) is one of the greatest public health challenges worldwide. Processes that allow the reduction of AR predictor of hospital wastewater has become crucial process that contributes to the protection of public health and the environment. The aim of this review article was to compare the effectiveness of various methods for treatment hospital wastewater in eliminating antibiotic-resistant bacteria (ARB) and degrading antibiotic resistance genes (ARGs) and antibiotics. A large number of studies dealing with wastewater treatment suggest that this topic is highly relevant and that new solutions are being developed to limit the spread of AR. Some wastewater treatment techniques have been in use for decades. Despite the negative effects of chlorine compounds, chlorination is still applied to eliminate ARB, ARGs, and drug metabolites. Ultraviolet (UV) radiation and ozonation have long been recognized for their treating properties. In the literature, advanced oxidation processes (AOPs) are increasingly often indicated as the most effective alternative to conventional treatment methods. Various methods for disinfecting hospital wastewater were reviewed and their enviro
The Antibiotic Resistance Microbiology Dataset (ARMD) is a de-identified resource derived from electronic health records (EHR) that facilitates research in antimicrobial resistance (AMR). ARMD encompasses big data from adult patients collected from over 15 years at two academic-affiliated hospitals, focusing on microbiological cultures, antibiotic susceptibilities, and associated clinical and demographic features. Key attributes include organism identification, susceptibility patterns for 55 antibiotics, implied susceptibility rules, and de-identified patient information. This dataset supports studies on antimicrobial stewardship, causal inference, and clinical decision-making. ARMD is designed to be reusable and interoperable, promoting collaboration and innovation in combating AMR. This paper describes the dataset's acquisition, structure, and utility while detailing its de-identification process.
Antibiotic resistance presents a growing global health threat by diminishing the effectiveness of treatments and allowing once-manageable bacterial infections to persist. This study develops and analyzes an optimization-based mathematical model to investigate the impact of varying antibiotic dosages on bacterial resistance, incorporating the role of the immune system. Additionally, to capture the effects of over and underdosing, a floor function is newly introduced into the model as a switch function. The model is examined both analytically and numerically. As part of the analytical solution, the validity of the model through the existence and uniqueness theorem, stability at the equilibrium points, and characteristics of equilibrium points in relation to state variables have been investigated. Numerical simulations, performed using the Runge Kutta 4th order method, reveal that while antibiotics effectively reduce sensitive bacteria, they simultaneously increase resistant strains and suppress immune cell levels. The results also demonstrate that underdosing antibiotics increases the risk of resistance through bacterial mutation, while overdosing weakens the immune system by disrupt
Bacteria develop resistance to antibiotics through various mechanisms, with the specific mechanism depending on the drug-bacteria pair. It remains unclear, however, which resistance mechanism best supports favorable treatment outcomes, specifically in clearing infections and inhibiting further resistance. In this study, we use periodic ordinary differential equation models to simulate different antibiotic treatment protocols for bacterial infections. Using stability analysis and numerical simulations, we investigate how different resistance mechanisms, including plasmid-induced and mutation-induced resistance, affect treatment outcomes. Our findings suggest that antibiotic treatments with fixed dosing schedules are more likely to be effective when resistance arises exclusively through plasmid-mediated transmission. Further, when treatment fails, mutation-driven mechanisms tend to favor the selection of fully resistant bacterial strains. We also investigated the efficacy of different treatment strategies based on these mechanisms, finding that a twice-daily regimen consistently outperforms a once-daily regimen in terms of infection clearance. Additionally, our simulations with short
Antibiotics are the wonder discoveries to combat microbes. For decades, multiple varieties of antibiotics have been used for therapeutic purposes in hospital settings and communities throughout the world. Unfortunately, bacteria have become resistant to commonly prescribed antibiotics. This review aims to explore the development, challenges, and the current state of antibiotic resistance available literature in Malaysia. This review aims to explore the development, challenges, and the current state of antibiotic resistance available literature in Malaysia. This review reiterates the antibiotic resistance among the gram-negative bacteria is increasing and they are becoming resistant to nearly all groups of antibiotics. The antibiotic treatments are minimal and hard to treat in multi-drug resistance bacterial infection, resulting in morbidity and mortality. The prevalence rate of antibiotic resistance from the literature suggests that educating patients and the public is essential to prevent and control the spread of antibiotic resistance. In particular, there is an urgent need for a surveillance system of regular monitoring on the microbiomes, the discovery of novel antibiotics and
Detecting anomalies in irregularly sampled multi-variate time-series is challenging, especially in data-scarce settings. Here we introduce an anomaly detection framework for irregularly sampled time-series that leverages neural jump ordinary differential equations (NJODEs). The method infers conditional mean and variance trajectories in a fully path dependent way and computes anomaly scores. On synthetic data containing jump, drift, diffusion, and noise anomalies, the framework accurately identifies diverse deviations. Applied to infant gut microbiome trajectories, it delineates the magnitude and persistence of antibiotic-induced disruptions: revealing prolonged anomalies after second antibiotic courses, extended duration treatments, and exposures during the second year of life. We further demonstrate the predictive capabilities of the inferred anomaly scores in accurately predicting antibiotic events and outperforming diversity-based baselines. Our approach accommodates unevenly spaced longitudinal observations, adjusts for static and dynamic covariates, and provides a foundation for inferring microbial anomalies induced by perturbations, offering a translational opportunity to op