Global Threat Of Antibiotic Resistance Research Articles

Dual-channel fluorescent sensors based on chitosan-coated Mn-doped ZnS micromaterials to detect ampicillin

The global threat of antibiotic resistance has increased the importance of the detection of antibiotics. Conventional methods to detect antibiotics are time-consuming and require expensive specialized equipment. Here, we present a simple and rapid biosensor for detecting ampicillin, a commonly used antibiotic. Our method is based on the fluorescent properties of chitosan-coated Mn-doped ZnS micromaterials combined with the β-lactamase enzyme. The biosensors exhibited the highest sensitivity in a linear working range of 13.1–72.2 pM with a limit of detection of 8.24 pM in deionized water. In addition, due to the biological specificity of β-lactamase, the proposed sensors have demonstrated high selectivity over penicillin, tetracycline, and glucose through the enhancing and quenching effects at wavelengths of 510 nm and 614 nm, respectively. These proposed sensors also showed promising results when tested in various matrices, including tap water, bottled water, and milk. Our work reports for the first time the cost-effective (Mn:ZnS)Chitosan micromaterial was used for ampicillin detection. The results will facilitate the monitoring of antibiotics in clinical and environmental contexts.

Nosocomial infections: a look at the problem in the context of the global threat of antibiotic resistance (review)

Antibiotic resistance poses a serious threat to public health. The problem of nosocomial infections is inextricably linked with antibiotic resistance. Nosocomial infections in most cases are caused by the formation and spread of hospital strains that are resistant to antibacterial drugs. Nosocomial infections caused by multidrug-resistant microorganisms increase healthcare costs, lengthen hospital stays, and lead to extremely poor patient outcomes. The article systematizes data on the prevalence of nosocomial infections and examines the problem of antibiotic resistance of leading nosocomial pathogens. Approaches to monitoring and management of antibiotic resistance and epidemiological surveillance of nosocomial infections are analyzed. A promising area of research in public health is considered – osocomial infections associated with previous hospitalization.

ApoE Mimetic Peptide COG1410 Kills Mycobacterium smegmatis via Directly Interfering ClpC's ATPase Activity.

Antimicrobial peptides (AMPs) hold promise as alternatives to combat bacterial infections, addressing the urgent global threat of antibiotic resistance. COG1410, a synthetic peptide derived from apolipoprotein E, has exhibited potent antimicrobial properties against various bacterial strains, including Mycobacterium smegmatis. However, our study reveals a previously unknown resistance mechanism developed by M. smegmatis against COG1410 involving ClpC. Upon subjecting M. smegmatis to serial passages in the presence of sub-MIC COG1410, resistance emerged. The comparative genomic analysis identified a point mutation in ClpC (S437P), situated within its middle domain, which led to high resistance to COG1410 without compromising bacterial fitness. Complementation of ClpC in mutant restored bacterial sensitivity. In-depth analyses, including transcriptomic profiling and in vitro assays, uncovered that COG1410 interferes with ClpC at both transcriptional and functional levels. COG1410 not only stimulated the ATPase activity of ClpC but also enhanced the proteolytic activity of Clp protease. SPR analysis confirmed that COG1410 directly binds with ClpC. Surprisingly, the identified S437P mutation did not impact their binding affinity. This study sheds light on a unique resistance mechanism against AMPs in mycobacteria, highlighting the pivotal role of ClpC in this process. Unraveling the interplay between COG1410 and ClpC enriches our understanding of AMP-bacterial interactions, offering potential insights for developing innovative strategies to combat antibiotic resistance.

Rationally designed protein A surface molecularly imprinted magnetic nanoparticles for the capture and detection of Staphylococcus aureus.

Staphylococcus aureus (S. aureus), a commensal organism found on the human skin, is commonly associated with nosocomial infections and exhibits virulence mediated by toxins and resistance to antibiotics. The global threat of antibiotic resistance has necessitated antimicrobial stewardship to improve the safe and appropriate use of antimicrobials; hence, there is an urgent demand for the advanced, cost-effective, and rapid detection of specific bacteria. In this regard, we aimed to selectively detect S. aureus using surface molecularly imprinted magnetic nanoparticles templated with a well-known biomarker protein A, specific to S. aureus. Herein, a highly selective surface molecularly imprinted polymeric thin layer was created on ∼250 nm magnetic nanoparticles (MNPs) through the immobilization of protein A to aldehyde functionalized MNPs, followed by monomer polymerization and template washing. This study employs the rational selection of monomers based on their computationally predicted binding affinity to protein A at multiple surface residues. The resulting MIPs from rationally selected monomer combinations demonstrated an imprinting factor as high as ∼5. Selectivity studies revealed MIPs with four-fold higher binding capacity (BC) to protein A than other non-target proteins, such as lysozyme and serum albumin. In addition, it showed significant binding to S. aureus, whereas negligible binding to other non-specific Gram-negative, i.e. Escherichia coli (E. coli), Pseudomonas aeruginosa (P. aeruginosa), and Gram-positive, i.e. Bacillus subtilis (B. subtilis), bacteria. This MIP was employed for the capture and specific detection of fluorescently labeled S. aureus. Quantitative detection was performed using a conventional plate counting technique in a linear detection range of 101-107 bacterial cells. Remarkably, the MIPs also exhibited approximately 100% cell recovery from milk samples spiked with S. aureus (106 CFU mL-1), underscoring its potential as a robust tool for sensitive and accurate bacterial detection in dairy products. The developed MIP exhibiting high affinity and selective binding to protein A finds its potential applications in the magnetic capture and selective detection of protein A as well as S. aureus infections and contaminations.

Antimicrobial Stewardship in the Hospital Setting: A Narrative Review.

The increasing global threat of antibiotic resistance, which has resulted in countless fatalities due to untreatable infections, underscores the urgent need for a strategic action plan. The acknowledgment that humanity is perilously approaching the "End of the Miracle Drugs" due to the unjustifiable overuse and misuse of antibiotics has prompted a critical reassessment of their usage. In response, numerous relevant medical societies have initiated a concerted effort to combat resistance by implementing antibiotic stewardship programs within healthcare institutions, grounded in evidence-based guidelines and designed to guide antibiotic utilization. Crucial to this initiative is the establishment of multidisciplinary teams within each hospital, led by a dedicated Infectious Diseases physician. This team includes clinical pharmacists, clinical microbiologists, hospital epidemiologists, infection control experts, and specialized nurses who receive intensive training in the field. These teams have evidence-supported strategies aiming to mitigate resistance, such as conducting prospective audits and providing feedback, including the innovative 'Handshake Stewardship' approach, implementing formulary restrictions and preauthorization protocols, disseminating educational materials, promoting antibiotic de-escalation practices, employing rapid diagnostic techniques, and enhancing infection prevention and control measures. While initial outcomes have demonstrated success in reducing resistance rates, ongoing research is imperative to explore novel stewardship interventions.

Therapeutic Potential and Application Prospects of Antimicrobial Peptides in the Era of Global Spread of Antibiotic Resistance

In the era of the growing global threat of antibiotic resistance, antimicrobial peptides (AMPs) are considered as new generation drugs for treatment of various infectious diseases. In this review, AMPs are seen as an alternative to traditional antibiotics, many of which have already lost or are gradually reducing their effectiveness against a number of critically important pathogenic microorganisms. Recent outbreaks of secondary infections during the COVID-19 pandemic have increased the interest in AMPs due to an acute shortage of effective agents against bacterial and fungal infections. The review summarized current data on clinical studies of AMPs, assembled a list of developed drugs based on AMPs at various stages of clinical trials, highlighted the urgency of study of new AMPs, and systematized the most relevant clinical data and application of AMPs.

Spectroscopic, conductivity and voltammetric investigations of interaction of sulfamethoxazole alone and in combination with trimethoprim with self-assembled structures

The demand and urgency of new drug design and discovery is facing new challenges in the wake of spread and persistence of serious global threat of antibiotic resistance. One of the major hurdles in the development of new drugs that are more aqueous soluble and passively diffusible is the paucity of knowledge regarding their physicochemical interactions with biological membranes. Being chemical-mimics of biomembranes, surfactant-based micellar systems present excellent pseudo-membrane models to study biophysical interactions of drugs with biological membranes in vitro. The present research focuses on physicochemical interaction of sulfamethoxazole (SMZ) alone and in combination with trimethoprim (TMP) with cationic surfactant cetyltrimethylammonium bromide (CTAB) and anionic surfactant sodium dodecyl sulfate (SDS). UV–visible spectroscopy, electrical conductivity and cyclic voltammetric techniques were employed to quantitate different drug-surfactant interaction parameters. UV–visible spectroscopic was used to evaluate critical micelle concentration (CMC) of CTAB and SDS in the presence of SMZ, TMP and their binary mixture in aqueous medium (pH 7.0). Differential absorption technique was used to determine partition coefficient (Kc ) and binding constant (Kb ) of SMZ and (SMZ + TMP) mixture with ionic micelles. Thermodynamic parameters of micellization such as and of CTAB and SDS in the presence SMZ and its mixed form with TMP were calculated in deionized water. Further, voltammetric investigations depict the strong binding of SMZ and its TMP mixture with CTAB micelles relative to SDS micelles.

Evolutionary Dynamics between Phages and Bacteria as a Possible Approach for Designing Effective Phage Therapies against Antibiotic-Resistant Bacteria.

With the increasing global threat of antibiotic resistance, there is an urgent need to develop new effective therapies to tackle antibiotic-resistant bacterial infections. Bacteriophage therapy is considered as a possible alternative over antibiotics to treat antibiotic-resistant bacteria. However, bacteria can evolve resistance towards bacteriophages through antiphage defense mechanisms, which is a major limitation of phage therapy. The antiphage mechanisms target the phage life cycle, including adsorption, the injection of DNA, synthesis, the assembly of phage particles, and the release of progeny virions. The non-specific bacterial defense mechanisms include adsorption inhibition, superinfection exclusion, restriction-modification, and abortive infection systems. The antiphage defense mechanism includes a clustered regularly interspaced short palindromic repeats (CRISPR)–CRISPR-associated (Cas) system. At the same time, phages can execute a counterstrategy against antiphage defense mechanisms. However, the antibiotic susceptibility and antibiotic resistance in bacteriophage-resistant bacteria still remain unclear in terms of evolutionary trade-offs and trade-ups between phages and bacteria. Since phage resistance has been a major barrier in phage therapy, the trade-offs can be a possible approach to design effective bacteriophage-mediated intervention strategies. Specifically, the trade-offs between phage resistance and antibiotic resistance can be used as therapeutic models for promoting antibiotic susceptibility and reducing virulence traits, known as bacteriophage steering or evolutionary medicine. Therefore, this review highlights the synergistic application of bacteriophages and antibiotics in association with the pleiotropic trade-offs of bacteriophage resistance.

A one health approach versus Acanthamoeba castellanii, a potential host for Morganella morganii.

Acanthamoeba castellanii, known as the “Trojan horse of the microbial world,” is known to host a variety of microorganisms including viruses, yeasts, protists, and bacteria. Acanthamoeba can act as a vector and may aid in the transmission of various bacterial pathogens to potential hosts and are found in a variety of places, thus impacting the health of humans, animals, and the environment. These are interconnected in a system known as “one health.” With the global threat of antibiotic resistance, bacteria may avoid harsh conditions, antibiotics, and disinfectants by sheltering within Acanthamoeba. In this study, Acanthamoeba castellanii interaction with Morganella morganii, a Gram-negative bacterium was studied. Escherichia coli K1 interaction with Acanthamoeba was carried out as a control. Association, invasion, and survival assays were accomplished. Morganella morganii was found to associate, invade, and survive within Acanthamoeba castellanii. Additionally, Escherichia coli K1 was also found to associate, invade, and survive within the Acanthamoeba at a higher number in comparison to Morganella morganii. For the first time, we have shown that Morganella morganii interact, invade, and survive within Acanthamoeba castellanii, suggesting that Acanthamoeba may be a potential vector in the transmission of Morganella morganii to susceptible hosts. Taking a one health approach to tackle and develop disinfectants to target Acanthamoeba is warranted, as the amoebae may be hosting various microbes such as multiple drug-resistant bacteria and even viruses such as the novel coronavirus.

A Cascaded Droplet Microfluidic Platform Enables High-Throughput Single Cell Antibiotic Susceptibility Testing at Scale.

The global threat of antibiotic resistance underscores critical but unmet needs for rapid antibiotic susceptibility testing (AST) technologies. To this end, droplet microfluidic-based single-cell AST offers promise by achieving unprecedented rapidity, but its potential for clinical use is marred by the capacity of testing one to few antibiotic conditions per device, which falls short from the required scale in clinically relevant scenarios. To lift the scalability constraint in rapid single-cell AST technologies, a new cascaded droplet microfluidic platform that can streamline bacteria/antibiotic mixing, single-cell encapsulation within picoliter droplets, incubation, and detection in a continuous, assembly-line-like workflow is developed. The scalability of the platform is demonstrated by generating 32 groups of ≈10000 droplets with custom antibiotic conditions within a single device, from which a new statistics-based method is used to analyze the single cell data and produce clinically useful antibiograms with minimum inhibitory concentrations in ≈90min for the first antibiotic, plus 2min for each subsequent antibiotic condition. Potential clinical utility of this platform is demonstrated by testing three clinical isolates and eight urine specimens against four frequently used antibiotics, and 100% and 93.8% categorical agreements are achieved compared to laboratory-based results that became available after 48 h.

Farmers' Perceptions of Preventing Antibiotic Resistance on Sheep and Beef Farms: Risk, Responsibility, and Action.

Antibiotic resistance is one of the most serious public health risks facing humanity. The overuse of antibiotics in the treatment of infectious disease have been identified as sources of the global threat of antibiotic resistance. This paper examines how farmers perceive and manage risks associated with overuse of antibiotics. Specifically, the paper examines the role of habitus and risk in determining farmers' decisions to adopt national antibiotic reduction targets set by members of the Responsible Use of Medicines in Agriculture Alliance's Targets Task Force. Semi-structured interviews were conducted with 34 sheep and beef farmers in England and Wales. Farmers presented four scripts which illuminated reasons for limited adoption of the targets. The scripts presented the farmers as “good farmers” facing an emerging threat to their ontological security. Scripts suggested that they engaged in preventative measures but deflected responsibility for reducing antibiotic resistance to veterinarians and poorly run farms. This research provides valuable insights for policy makers and highlight the benefits of including social science research to support effective implementation.

Utilizing Organoid and Air-Liquid Interface Models as a Screening Method in the Development of New Host Defense Peptides.

Host defense peptides (HDPs), also known as antimicrobial peptides, are naturally occurring polypeptides (~12–50 residues) composed of cationic and hydrophobic amino acids that adopt an amphipathic conformation upon folding usually after contact with membranes. HDPs have a variety of biological activities including immunomodulatory, anti-inflammatory, anti-bacterial, and anti-biofilm functions. Although HDPs have the potential to address the global threat of antibiotic resistance and to treat immune and inflammatory disorders, they have yet to achieve this promise. Indeed, there are several challenges associated with bringing peptide-based drug candidates from the lab bench to clinical practice, including identifying appropriate indications, stability, toxicity, and cost. These challenges can be addressed in part by the development of innate defense regulator (IDR) peptides and peptidomimetics, which are synthetic derivatives of HDPs with similar or better efficacy, increased stability, and reduced toxicity and cost of the original HDP. However, one of the largest gaps between basic research and clinical application is the validity and translatability of conventional model systems, such as cell lines and animal models, for screening HDPs and their derivatives as potential drug therapies. Indeed, such translation has often relied on animal models, which have only limited validity. Here we discuss the recent development of human organoids for disease modeling and drug screening, assisted by the use of omics analyses. Organoids, developed from primary cells, cell lines, or human pluripotent stem cells, are three-dimensional, self-organizing structures that closely resemble their corresponding in vivo organs with regards to immune responses, tissue organization, and physiological properties; thus, organoids represent a reliable method for studying efficacy, formulation, toxicity and to some extent drug stability and pharmacodynamics. The use of patient-derived organoids enables the study of patient-specific efficacy, toxicogenomics and drug response predictions. We outline how organoids and omics data analysis can be leveraged to aid in the clinical translation of IDR peptides.

Reducing Antibiotic Use in Ambulatory Care Through Influenza Vaccination.

Improving appropriate antibiotic use is crucial for combating antibiotic resistance and unnecessary adverse drug reactions. Acute respiratory illness (ARI) commonly causes outpatient visits and accounts for ~41% of antibiotics used in the United States. We examined the influence of influenza vaccination on reducing antibiotic prescriptions among outpatients with ARI. We enrolled outpatients aged ≥6 months with ARI from 50-60 US clinics during 5 winters (2013-2018) and tested for influenza with RT-PCR; results were unavailable for clinical decision making and clinical influenza testing was infrequent. We collected antibiotic prescriptions and diagnosis codes for ARI syndromes. We calculated vaccine effectiveness (VE) by comparing vaccination odds among influenza-positive cases with test-negative controls. We estimated ARI visits and antibiotic prescriptions averted by influenza vaccination using estimates of VE, coverage, and prevalence of antibiotic prescriptions and influenza. Among 37 487 ARI outpatients, 9659 (26%) were influenza positive. Overall, 36% of ARI and 26% of influenza-positive patients were prescribed antibiotics. The top 3 prevalent ARI syndromes included: viral upper respiratory tract infection (47%), pharyngitis (18%), and allergy or asthma (11%). Among patients testing positive for influenza, 77% did not receive an ICD-CM diagnostic code for influenza. Overall, VE against influenza-associated ARI was 35% (95% CI, 32-39%). Vaccination prevented 5.6% of all ARI syndromes, ranging from 2.8% (sinusitis) to 11% (clinical influenza). Influenza vaccination averted 1 in 25 (3.8%; 95% CI, 3.6-4.1%) antibiotic prescriptions among ARI outpatients during influenza seasons. Vaccination and accurate influenza diagnosis may curb unnecessary antibiotic use and reduce the global threat of antibiotic resistance.

2062. Improving Antibiotic Prescribing in the Ambulatory Care Setting—Stewardship through Influenza Vaccination, US Flu VE Network 2013–2014 Through 2017–2018

BackgroundImproving antibiotic use is a key strategy to combat antibiotic resistance and improve patient safety. Acute respiratory illness (ARI) is a common cause of outpatient visits and accounts for ~41% of antibiotics used in the United States. We sought to determine the proportion of antibiotic prescriptions (Rx) prescribed among outpatients with ARI that can be potentially averted through influenza vaccination.MethodsFrom 2013–2014 through 2017–2018 influenza seasons, we enrolled patients aged ≥6 months with ARI in the US Influenza Vaccine Effectiveness (VE) Network of >50 outpatient clinics. Antibiotic Rx and diagnosis codes were collected from medical records. Study influenza test results were not available to treating clinicians at most sites, and clinical influenza testing was infrequently performed (a), prevalence of influenza among unvaccinated ARI patients (b), prevalence of antibiotic Rx among unvaccinated influenza-positive ARI patients (c) and prevalence of antibiotic Rx among ARI patients overall (d), we derived estimates of the proportion of ARI antibiotic Rx that can be averted by influenza vaccination [(a × b × c)/d].ResultsAmong 37487 outpatients with ARI, 13,316 (36%) were prescribed an antibiotic and 9,689 (26%) tested positive for influenza. Of those positive, 2,496 (26%) were prescribed an antibiotic. Adjusted VE against influenza-associated ARI was 35% (95% confidence interval (CI), 32 to 39). Among unvaccinated patients with ARI, 30% were influenza-positive and 24% received antibiotics. Based on these estimates, we determined that influenza vaccination may prevent 10.6% of all ARI syndromes and may avert 1 in 14 or 7.3% of antibiotic Rx among ARI patients.ConclusionBy preventing influenza-associated ARI syndromes, influenza vaccination may substantially reduce antibiotic prescribing. Increasing influenza vaccine coverage and improving protection may facilitate national goals to improve antibiotic use and reduce the global threat of antibiotic resistance. Disclosures All authors: No reported disclosures.

Genomic and Metagenomic Approaches for Predictive Surveillance of Emerging Pathogens and Antibiotic Resistance.

Antibiotic-resistant organisms (AROs) are a major concern to public health worldwide. While antibiotics have been naturally produced by environmental bacteria for millions of years, modern widespread use of antibiotics has enriched resistance mechanisms in human-impacted bacterial environments. Antibiotic resistance genes (ARGs) continue to emerge and spread rapidly. To combat the global threat of antibiotic resistance, researchers must develop methods to rapidly characterize AROs and ARGs, monitor their spread across space and time, and identify novel ARGs and resistance pathways. We review how high-throughput sequencing-based methods can be combined with classic culture-based assays to characterize, monitor, and track AROs and ARGs. Then, we evaluate genomic and metagenomic methods for identifying ARGs and biosynthetic pathways for novel antibiotics from genomic data sets. Together, these genomic analyses can improve surveillance and prediction of emerging resistance threats and accelerate the development of new antibiotic therapies to combat resistance.

Global resistance to antimicrobials and their sustainable use in agriculture

Global resistance to antimicrobials and their sustainable use in agriculture

Transposon Insertion Sequencing Elucidates Novel Gene Involvement in Susceptibility and Resistance to Phages T4 and T7 in Escherichia coli O157.

ABSTRACTExperiments using bacteriophage (phage) to infect bacterial strains have helped define some basic genetic concepts in microbiology, but our understanding of the complexity of bacterium-phage interactions is still limited. As the global threat of antibiotic resistance continues to increase, phage therapy has reemerged as an attractive alternative or supplement to treating antibiotic-resistant bacterial infections. Further, the long-used method of phage typing to classify bacterial strains is being replaced by molecular genetic techniques. Thus, there is a growing need for a complete understanding of the precise molecular mechanisms underpinning phage-bacterium interactions to optimize phage therapy for the clinic as well as for retrospectively interpreting phage typing data on the molecular level. In this study, a genomics-based fitness assay (TraDIS) was used to identify all host genes involved in phage susceptibility and resistance for a T4 phage infecting Shiga-toxigenic Escherichia coli O157. The TraDIS results identified both established and previously unidentified genes involved in phage infection, and a subset were confirmed by site-directed mutagenesis and phenotypic testing of 14 T4 and 2 T7 phages. For the first time, the entire sap operon was implicated in phage susceptibility and, conversely, the stringent starvation protein A gene (sspA) was shown to provide phage resistance. Identifying genes involved in phage infection and replication should facilitate the selection of bespoke phage combinations to target specific bacterial pathogens.

World Health Organization's essential medicines list 2017: Addresses the global threat of antibiotic resistance

World Health Organization's essential medicines list 2017: Addresses the global threat of antibiotic resistance

Probiotic capsules and xylitol chewing gum to manage symptoms of pharyngitis: a randomized controlled factorial trial.

Reducing the use of antibiotics for upper respiratory tract infections is needed to limit the global threat of antibiotic resistance. We estimated the effectiveness of probiotics and xylitol for the management of pharyngitis. In this parallel-group factorial randomized controlled trial, participants in primary care (aged 3 years or older) with pharyngitis underwent randomization by nurses who provided sequential intervention packs. Pack contents for 3 kinds of material and advice were previously determined by computer-generated random numbers: no chewing gum, xylitol-based chewing gum (15% xylitol; 5 pieces daily) and sorbitol gum (5 pieces daily). Half of each group were also randomly assigned to receive either probiotic capsules (containing 24 × 109 colony-forming units of lactobacilli and bifidobacteria) or placebo. The primary outcome was mean self-reported severity of sore throat and difficulty swallowing (scale 0-6) in the first 3 days. We used multiple imputation to avoid the assumption that data were missing completely at random. A total of 1009 individuals consented, 934 completed the baseline assessment, and 689 provided complete data for the primary outcome. Probiotics were not effective in reducing the severity of symptoms: mean severity scores 2.75 with no probiotic and 2.78 with probiotic (adjusted difference -0.001, 95% confidence interval [CI] -0.24 to 0.24). Chewing gum was also ineffective: mean severity scores 2.73 without gum, 2.72 with sorbitol gum (adjusted difference 0.07, 95% CI -0.23 to 0.37) and 2.73 with xylitol gum (adjusted difference 0.01, 95% CI -0.29 to 0.30). None of the secondary outcomes differed significantly between groups, and no harms were reported. Neither probiotics nor advice to chew xylitol-based chewing gum was effective for managing pharyngitis. Trial registration: ISRCTN, no. ISRCTN51472596.

The global threat of antibiotic resistance: what can be done?

In addition to treating bacterial infections, antibiotics guard against infections. Antibiotics make surgical operations possible, promote the survival of premature babies, and enable immunosuppression (e.g. cancer chemotherapy). With an ageing and increasingly overweight global population, chronic illnesses treated surgically (e.g. hip replacements) may become very hazardous without effective antibiotics. Due to antibiotic misuse and a lack of successful development of new antibiotics, antibiotic resistance is an increasing global threat. In this overview, I address the problem of the global threat of antibiotic resistance through the following sections: A brief history of antibiotics; What are antibiotics used for?; How does antibiotic resistance develop?; How does antibiotic resistance spread?; Why is resistance an increasing problem?; Why are there no new antibiotics?; How bad is the problem?; and What can we do?