Glossary: Antimicrobial Resistance (AMR) and Infectious Diseases Terms

Introduction

The Glossary aims to provide accurate and clear definitions of terms used mainly in the context of antimicrobial resistance and infectious diseases.

Disclaimer: While we have strived for accuracy and clarity, we cannot guarantee the copyright status of all included terms in the glossary.

A

1. Absorption:

   The process of a substance getting into the body through the eyes, skin, stomach, intestines, or lungs.

2. Absorption, distribution, metabolism, elimination (ADME):

   The key factors affecting the concentration and distribution of a drug within the body and the time it spends in the body. ADME are the core elements of pharmacokinetics.

3. Acellular vaccine:

   A vaccine containing partial cellular material as opposed to complete cells.

4. Acinetobacter baumannii-calcoaceticus complex (ABC):

   Clinically significant Acinetobacter species, including A. baumannii, A. nosocomialis, A. pittii, A. seifertii, A. lacticae, and the environmental species, A. calcoaceticus collectively designated as members of the Acinetobacter baumannii-calcoaceticus complex.

5. Acquired Immune Deficiency Syndrome (AIDS):

   A medical condition where the body’s immune system cannot function properly and protect the body from disease. As a result, the body is unable to defend itself against infections such as pneumonia. AIDS is caused by the Human Immunodeficiency Virus (HIV), which is spread through direct contact with the blood and bodily fluids of an infected individual.

6. Acquired resistance:

   When a particular microorganism obtains the ability to resist a particular antimicrobial agent to which it was previously susceptible.

7. Active immunity:

   The production of antibodies against a specific disease by the immune system. Active immunity can be acquired by a) contracting the disease, or b) vaccination. It is usually long-lasting, but individuals may remain susceptible to variants of the etiologic agent or a milder presentation of the disease.

8. Active pharmaceutical ingredients (API):

   The biologically active ingredients in a pharmaceutical drug.

9. Active surveillance culture/testing (ASC/AST):

   Testing that is intended to identify the presence or carriage of microorganisms for the purpose of instituting or discontinuing isolation precautions (e.g., nasal swab for methicillin-resistant Staphylococcus aureus, rectal swab for vancomycin-resistant enterococci), or monitoring for eradication of a carrier state. It does not include the identification of microorganisms with cultures or tests performed for diagnosis and treatment purposes (for example, specimens collected from sterile body sites, including blood samples).

10. Acute:

    Short-term, intense (as in a health effect).

11. Acute bacterial skin and skin structure infection (ABSSSI):

    A bacterial infection of the skin with a lesion size area of at least 75 cm². It includes cellulitis, erysipelas, wound infections, and major cutaneous abscesses.

12. Acute exposure:

    Contact with a substance that occurs once or for a short time.

13. Acute toxicity:

    Adverse effects that occur shortly after an exposure, within a few hours to several days.

14. Adjunctive treatment:

    A complementary treatment that is taken in combination with another drug to obtain an additive effect.

15. Adjuvant

    A vaccine component that is distinct from the antigen that enhances the immune response to the antigen.

16. Advanced HIV disease (AHD):

    The World Health Organization defines AHD as a CD4 cell count of less than 200 cells/mm³ or WHO stage 3 or 4 in adults and adolescents. All children younger than 5 years of age with HIV are considered to have AHD.

17. Adverse event:

    An undesirable medical condition that occurs following vaccination. It may be associated with the vaccine or its components or might occur by coincidence.

18. Advisory Committee on Immunization Practices (ACIP):

    A group of medical and public health experts who develop recommendations on the use of vaccines in the U.S. civilian population. The recommendations stand as public health guidance for the safe use of vaccines and related biological products.

19. Allergy (hypersensitivity):

    A condition in which the body has an exaggerated response to a substance such as a food or a drug.

20. Alternative products:

    Strategies or products other than antimicrobials that could be used for either disease prevention or therapy. For example, vaccines, phage therapy, antibodies, and probiotics, as well as improved biosecurity practices and sanitation.

21. AmpC β-lactamases:

    β-lactamase enzymes that are produced by several Enterobacterales and glucose-non-fermenting Gram-negative bacteria. While these enzymes can hydrolyze several β-lactam antibiotics, their primary function is to help with cell wall recycling.

22. Antagonistic pleiotropy:

    The expression of a gene resulting in multiple competing effects, some beneficial while others are detrimental to the organism. Whether or not pleiotropy is antagonistic may depend on the environment. For example, a bacterial gene that enhances glucose utilization efficiency at the expense of the ability to use other energy sources (such as lactose) has positive effects when there is plenty of glucose in the environment. However, it can be lethal if lactose is the only available food source.

23. Antibacterial agent:

    Any substance that kills or inhibits the growth of bacteria.

24. Antibiogram:

    A laboratory resource used to determine the sensitivity of a bacterial strain to different antibiotics. A cumulative antibiogram provides a profile of antibacterial susceptibilities within an institution or aggregation of institutions over a given period to monitor trends in antibacterial resistance and to guide empirical antibacterial therapy selection.

25. Antibiotic resistance:

    The genetically acquired capacity for bacteria to withstand antibiotic treatment.

26. Antimicrobial agent (antimicrobial):

    A general term for drugs, chemicals, or other substances that either kill or slow the growth of microorganisms. Different classes exist that are specific to the class of microorganism, including antibacterial drugs (antibiotics) that are used for treating bacterial infections, antiviral agents that are used for treating viral infections, antifungal agents that treat fungi, and antiparasitic agents that treat parasites.

27. Antimicrobial peptides (AMPs):

    A varied class of naturally occurring molecules that multicellular organisms produce as a first line of defense. These proteins can have broad activity to directly kill bacteria, yeasts, fungi, and cancer cells. AMPs are deployed by insects and plants primarily as an antibiotic to protect against potential pathogenic microorganisms. AMPs are also produced by microorganisms to defend their environmental niche.

28. Antimicrobial residue:

    The parent compounds, metabolites, and impurities of veterinary drugs that persist in edible animal products and the environment. The release of such residues may facilitate the selection and transfer of antibiotic resistance genes within the microbial community.

29. Antimicrobial resistance:

    A microorganism's ability to resist a drug's effects. Antimicrobial-resistant germs are not killed by the drugs that are typically used against them and may continue to grow and multiply. Antimicrobial resistance includes antibacterial, antifungal, antiviral, and antiparasitic resistance.

30. Antimicrobial stewardship:

    Coordinated interventions that are designed to promote, improve, monitor, and evaluate the judicious use of antimicrobials to preserve their future effectiveness and to promote and protect human and animal health. Antimicrobial stewardship encompasses the 5Rs of AMU (antimicrobial use): responsibility, reduction, refinement, replacement, and review.

31. Antimicrobial susceptibility testing (AST):

    Laboratory testing performed on microorganisms (mainly bacteria) to find out if they are susceptible or resistant to one or more antimicrobial agents. Results of AST show whether bacteria are susceptible (can be treated with the drug), intermediate (may be treatable with the drug, but may require adjusted dosage), or resistant (cannot be treated with the drug). AST is also referred to as antibiotic susceptibility testing when tests are being performed on bacteria.

32. Antimicrobial time-out:

    An active reassessment of an antimicrobial prescription 48-72 hours after first administration to allow medical staff to consider laboratory culture and susceptibility testing results and the patient’s response to therapy and current condition.

33. Antimicrobial use (AMU):

    How antimicrobials are used, including treatment goals, treatment of populations versus targeted individuals, duration of use, route of administration, and species treated (i.e., human, plant, or animal).

34. Antiseptic:

    A substance that is applied to living tissue/skin to prevent the growth of disease-causing microorganisms

35. Appropriate use:

    Antimicrobial use (AMU) that maximizes therapeutic impact while minimizing toxicity and the development of resistance.

36. Area under the curve (AUC):

    The area under the curve represents the total drug concentration in blood plasma over a given time. AUC is the concentration and time the concentration of an antibiotic remains above the MIC after any one dose. It is dependent on the bioavailability and clearance of the drug from the body: the higher the bioavailability, the higher the AUC, and vice versa.

37. Aseptically obtained:

    Specimen obtained in a manner to prevent the introduction of organisms from the surrounding tissues.

38. AWaRe (Access, Watch, Reserve):

    The WHO classifies antibiotics into three stewardship groups: Access, Watch, and Reserve. This emphasizes the importance of their optimal uses and potential for antimicrobial resistance. The Access group includes 48 antibiotics that have activity against a wide range of commonly encountered susceptible pathogens while also showing lower resistance potential than antibiotics in the other groups. The Watch group contains 110 antibiotics that have higher resistance potential and includes most of the highest-priority agents among the Critically Important Antimicrobials for Human Medicine and/or antibiotics that are at relatively high risk of selection of bacterial resistance. Antibiotics in the Reserve group are reserved for the treatment of confirmed or suspected infections due to multi-drug-resistant organisms.

B

1. Bacterial strain:

   A sub-group of bacteria of the same species. Different strains are variants of the same bacterial species.

2. Bactericidal agent:

   An antibiotic that kills bacteria.

3. Bacteriostatic agent:

   An antibiotic that inhibits bacterial growth.

4. Bedaquiline, Pretomanid, Linezolid (BPaL) regimen:

   An all-oral combination of Bedaquiline, pretomanid, and linezolid that is administered by direct observation to adults with a diagnosis of extensively drug-resistant or treatment-intolerant or nonresponsive (TI/NR) multidrug-resistant tuberculosis.

5. Benchmarking antimicrobial use (AMU):

   Organizing multiple hospitals into networks to allow for inter-hospital comparison of antimicrobial use or comparison of antimicrobial use by farm or of prescription history by a veterinarian. This is considered a valuable national and farm-level management tool in promoting antimicrobial stewardship and reducing AMU.

6. Best available therapy (BAT) (Standard of care-SOC):

   The most appropriate or best available treatment based on current scientific evidence.

7. Beta (β)-lactamase:

   Bacterial enzymes that hydrolyze and inactivate beta-lactam antibiotics, leading to antibiotic resistance. These enzymes target the 4-atom β-lactam ring found in beta-lactam antibiotics. The Ambler classification most widely used classification system for the β-lactamases, wherein they are grouped into four classes: A-D.

8. Beta (β)-lactamase inhibitor (BLI):

   Drugs that block the activity of certain beta-lactamases and are therefore combined with beta-lactam antibiotics to prevent antimicrobial resistance. Examples of β-lactam-β-lactamase (BLBLI) combinations are: ampicillin-sulbactam, amoxicillin-clavulanic acid, piperacillin-tazobactam, ceftolozane-tazobactam, ceftazidime-avibactam, meropenem-vaborbactam, and imipenem-cilastatin-relebactam.

9. Bill & Melinda Gates Foundation (BMGF):

   Guided by the belief that every life has equal value, the Bill & Melinda Gates Foundation works to help all people lead healthy, productive lives. In developing countries, it focuses on improving people’s health and giving them the chance to lift themselves out of hunger and extreme poverty. In the United States, it seeks to ensure that all people, especially those with the fewest resources, have access to the opportunities they need to succeed in school and life.

10. Bioavailability:

    The fraction (%) of the initial dose of an administered or active drug that reaches the systemic circulation unaltered. Bioavailability is influenced by the physicochemical characteristics of the drug and the physiological factors of the patient.

11. Biomedical Advanced Research and Development Authority (BARDA):

    This U.S. agency provides an integrated, systematic approach to the development of the necessary vaccines, drugs, therapies, and diagnostic tools for public health medical emergencies such as chemical, biological, radiological, and nuclear (CBRN) accidents, incidents, and attacks; pandemic influenza (PI), and emerging infectious diseases (EID).

12. Broad-spectrum antibiotic:

    Antibiotics that work against a wide range of Gram-positive and Gram-negative bacteria.

13. By-product:

    An unintentional or secondary product formed when an intended product or chemical is being formed.

C

1. Carbapenem-resistant Enterobacterales (CRE):

   Members of the Enterobacterales order resistant to at least one carbapenem antibiotic or producing a carbapenemase enzyme.

2. Centers for Disease Control and Prevention (CDC):

   A branch of the U.S. Public Health Service under the Department of Health and Human Services. It is the national public health agency of the United States. The main goal of the CDC is the protection of public health and safety through the control and prevention of disease, injury, and disability in the US and worldwide.

3. Central line-associated bloodstream infection (CLABSI):

   A primary laboratory-confirmed bloodstream infection in a patient with a central line at the time of (or within 48 hours prior to) the onset of symptoms and the infection is not related to an infection from another site.

4. Chemical Abstracts Service (CAS) registry number:

   A unique number assigned to a substance or mixture by the Chemical Abstracts Service (CAS) of the American Chemical Society.

5. Chronic (health) effect:

   A health condition that develops and persists over a long period of time. For example,

6. Clade:

   A group of biological taxa (such as a species) that includes all the descendants of one common ancestor.

7. Clinical breakpoint concentration:

   The concentration of an antibiotic used to define whether an infection by a particular bacterial strain/isolate is likely to be treatable in a patient. Typically, these are defined as susceptible or resistant to an antibiotic. The definition of the term ‘intermediate’ depends on the reference method.

8. Clinical compassionate use (expanded access):

   Providing seriously ill patients with access outside of clinical trials to a new, unapproved drug when other treatment options have been exhausted or none is yet available. Regulatory authorities provide guidance outlining the circumstances when compassionate use can be considered and the procedures that should be followed.

9. Clinical exposure-response (CER) relationship:

   The relationship between plasma/serum drug levels (exposure) and clinical efficacy (response) in patients.

10. Clinically relevant resistance:

    Resistance where the minimum inhibitory concentration (MIC) of a drug is above the recommended breakpoint concentration and so is likely to result in treatment failure.

11. Cmax:

    Peak concentration of a drug in the bloodstream or other part of the body after drug administration. Cmax is a key pharmacokinetic measure and informs dosing schedules. Drug concentrations in the body need to be high enough over a sustained period for the drug to be effective but without causing significant side effects.

12. Collateral sensitivity:

    Antibiotic resistance to one antibiotic that confers increased susceptibility to another antibiotic.

13. Colonization:

    When a new species of bacteria develops a colony (a group of the same bacterial type) in a new location, such as the human gastrointestinal tract. Colonization may or may not cause infection.

14. Colony-forming unit (CFU)

    A unit that is used in microbiology to estimate the number of viable bacteria or fungi in a sample.

15. Combating Antibiotic-Resistant Bacteria Biopharmaceutical Accelerator (CARB-X):

    A global, non-profit partnership funding new antibiotics, vaccines, rapid diagnostics, and other products to prevent, diagnose, and treat life-threatening bacterial infections.

16. Combination therapy:

    Treatment involving more than one drug. One reason for choosing combination therapy is to reduce the chances of a pathogen developing resistance to multiple drugs at the same time.

17. Commensal:

    A microorganism that lives in close contact with a host organism (either human, animal, or plant) without causing disease in the host. Commensals can be beneficial to the host. A microorganism can be a commensal in one host species but can cause disease in a different species. Also, a commensal in one part of the body can cause disease in another part of the body.

18. Community-acquired infection:

    Infection acquired in the community by someone who has not been hospitalized nor had a recent medical procedure.

19. Community-associated methicillin-resistant Staphylococcus aureus (CA-MRSA)

    MRSA infections in people with no history of the following risk factors within the year before the MRSA culture date: a) hospitalization or surgery; b) permanent indwelling catheters or percutaneous medical devices; c) residence in a long-term care facility; d) dialysis; and e) MRSA culture "‹"48 hours after hospital admission.

20. Community-setting:

    Refers to where antimicrobials are used or prescribed outside a hospital or emergency room setting; for instance, a private medical or veterinary clinic, pharmacy, or a public health center.

21. Complicated skin and soft tissue infections (cSSTI):

    Microbial invasion of the layers of the skin and the underlying deeper soft tissue.

22. Complicated urinary tract infection (cUTI):

    Urinary tract infections that occur in association with a structural or functional abnormality of the genitourinary tract, or any urinary tract infection in an adolescent or adult male.

23. Computer-based decision support:

    Support programs to provide real-time recommendations on antimicrobial choice that link national or local antimicrobial formularies to computerized systems.

24. Critically important antimicrobials:

    A classification system described by the World Health Organization (WHO) and the World Organization for Animal Health (OIE) for medical and veterinary antimicrobials, respectively. Two criteria are used to classify antibiotics by their level of importance. For human medical antibiotics, criterion 1 is that the antimicrobial agent is used as the sole therapy or one of few alternatives to treat serious human disease; criterion 2 is that the antimicrobial agent is used to treat diseases caused by either a) organisms that may be transmitted via non-human sources or b) diseases caused by organisms that may acquire resistance genes from non-human sources. For veterinary antimicrobials, criterion 1 is that the importance of the antimicrobial class is widely recognized; criterion 2 is that the antimicrobial agents in this class are widely identified as essential for the treatment of serious animal diseases and few alternatives are available. Both human and veterinary antimicrobial agents are thus classified based on whether they meet their respective criteria, i.e., they are classified as ‘critically important’ if they meet criteria 1 and 2, ‘highly important’ if they meet criteria 1 or 2, and ‘important’ if they meet neither criteria 1 nor 2.

D

1. De-escalation:

   Change from a broad-spectrum antimicrobial to a narrower spectrum drug or change from combination therapy to monotherapy. Antibiotic de-escalation is a key component of antimicrobial stewardship programs.

2. Defined daily dose (DDD):

   Assumed average maintenance dose per day for a drug used for the main indication in its target species.

3. Device days:

   A count of the number of patients with a specific device in a patient care location during a time period.

4. Differential diagnosis:

   The distinguishing of a disease or a condition from others presenting with similar signs and symptoms.

5. Difficult-to-treat resistance (DTR):

   Nonsusceptibility to all first-line antibiotics.

6. Disability-adjusted life-year (DALY):

   A measure of health burden, including both reduction in life expectancy and diminished quality of life. More specifically, the DALY burden for a particular condition is the sum of YLL (years of life lost due to premature mortality) and YLD (years lost to disability). Health interventions seek to avert DALYs, and in doing so, increase the number of years that a person lives in good health. Mathematically, a DALY is represented by the equation: DALY= YLL + YLD, where YLL is calculated as the number of deaths (n) multiplied by the standard of life expectancy at the age of death (L1). YLL measures the reduction in life expectancy; and YLD is the number of new cases of a disease (I), multiplied by a disability weight (DW), multiplied by the average time a person lives with the disease before remission or death (L2). YLD represents the diminished quality of life experienced by an individual with injury or illness.

7. Disease prevention:

   Activities designed to protect patients (or other members of the public or animals) from actual or potential health threats and their harmful consequences.

8. Dose finding:

   Pharmacological, mathematical, and statistical methodologies to characterize exposure-response relationships as a basis for determining the best dosing regimen.

9. Dose optimization:

   The time course of drugs in the body concerning their absorption, distribution, metabolism, and elimination.

10. Dosing regimen:

    The frequency and dose at which a drug is to be administered.

11. Dosing:

    OD- omne in die, once a day; BID- bis in die, twice a day; TID: ter in die, three times a day.

12. Drivers of antimicrobial resistance:

    Increased and continued transmission of antimicrobial resistance mechanisms between microorganisms due to human and animal antimicrobial misuse and overuse.

13. Druglikeness:

    The similarity of the properties between compounds and existing drugs. Druglike compounds are more likely to be transformed into drugs.

E

1. Ecological impact:

   The changes induced by natural or human activity on the ecology and living organisms.

2. Ecology:

   The study of the relationships and interactions between organisms and the environment.

3. Ecosystem:

   A place where living (animals, plants, microorganisms, and other organisms) and non-living (soil, water, rocks) elements form a complex web of interdependency.

4. Effluent:

   Treated/untreated wastewater that leaves a water treatment plant, sewer, or industrial operation.

5. Efflux pump:

   A resistance mechanism that allows bacteria to pump out any antibiotics that penetrate them.

6. Empirical diagnosis/treatment:

   A diagnosis or treatment based on a clinically educated guess in the absence of complete or perfect information. Clinicians use their expertise, intuition, and professional judgment to ‘guess’ whether an infection is present and what is likely to be causing it, and thus the most appropriate treatment.

7. Endpoints for antibacterial trials (microbiologic):

   A clinical trial outcome assessing the proportion of the study population achieving microbiological cure (eradication of the putative pathogen from a repeated culture of the site of infection) following treatment with an antibiotic.

8. Endpoints for antibacterial trials (timing of assessments):

   Antibacterial treatment outcomes are measured at pre-specified intervals from the start of treatment at (a) the end of treatment, and (b) time points thereafter to demonstrate maintenance of clinical/microbiological cure.

9. Enteric bacteria:

   Bacteria that live in the gastrointestinal tracts of humans or animals.

10. Enterobacterales:

    An order of diverse facultatively anaerobic and rod-shaped Gram-negative bacteria. It includes the following families: Enterobacteriaceae, Morganellaceae, Yersiniaceae, Erwiniaceae, and Hafniaceae.

11. Enterobacteriaceae:

    A family of Gram-negative, facultatively anaerobic, glucose-fermenting bacteria commonly found in the gastrointestinal tract of humans and other animals. This family forms part of the Enterobacterales order. Clinically relevant members of the Enterobacteriaceae include Escherichia coli, Salmonella species, Enterobacter species, Shigella species, Klebsiella pneumoniae, and Proteus mirabilis.

12. Epistasis:

    A phenomenon in genetics in which the interaction between genes influences a phenotype. Epistasis describes the effect of combining mutations that influence the same phenotype.

13. Equivocal imaging:

    Findings from medical imaging studies that do not conclusively identify an infection or infectious process. Image findings such as fluid collection visualized in the right lower quadrant vs. abscess visualized in the right lower quadrant require additional conclusive clinical evidence that an infection is present, such as physician documentation of antimicrobial therapy for treating the infection or infectious process.

14. ESKAPE:

    A group of bacteria- Enterococcus faecium, Staphylococcus aureus, Klebsiella pneumoniae, Acinetobacter baumannii, Pseudomonas aeruginosa and Enterobacter species- that are a leading cause of hospital-acquired infections globally. Variations of ESKAPE exist, with ‘E’ standing for Escherichia coli and Enterobacterales.

15. European Medicines Agency (EMA):

    The agency responsible for the scientific evaluation, supervision, and safe monitoring of medicines in the European Union.

16. Extended-spectrum beta-lactamases (ESBLs):

    Enzymes that inactivate most penicillins, cephalosporins, and aztreonam. They do not inactivate non-β-lactam agents such as aminoglycosides and trimethoprim-sulfamethoxazole. However, ESBL-carrying organisms often harbor additional genes or mutations in genes that mediate resistance to a broad range of antibiotics.

17. Extended-spectrum beta-lactamase-producing Enterobacterales (ESBL-E):

    Enterobacterales that contain extended-spectrum beta-lactamases, enzymes that inactivate most penicillins, cephalosporins, and aztreonam. ESBL-E are usually susceptible to carbapenems. While any Gram-negative bacterium can harbor ESBL genes, they are most prevalent in Escherichia coli, Proteus mirabilis, Klebsiella pneumoniae, and Klebsiella oxytoca. Non-susceptibility to ceftriaxone is generally used as a proxy for ESBL production.

18. Extensively drug-resistant (XDR):

    Non-susceptibility to at least one agent in all but one or two antimicrobial categories (i.e., bacterial isolates remain susceptible to drugs from at most two classes of antibiotic).

19. Extralabel:

    Actual use or intended use of a drug in a manner that is not in accordance with the approved labeling. This includes but is not limited to, use in species not listed in the labeling, use for indications (disease or other conditions) not listed in the labeling, use at dosage levels, frequencies, or routes of administration other than those stated in the labeling, and deviation from the labeled withdrawal time based on these different uses.

20. European Medicines Agency (EMA):

    The agency responsible for the scientific evaluation, supervision, and safe monitoring of medicines in the European Union.

F

1. Fastidious bacteria:

   Bacteria that are difficult to grow in the laboratory because they have complex or restricted nutritional and/or environmental requirements.

2. Feed additives:

   Antimicrobials added to animal feed for growth promotion or disease prevention purposes.

3. First choice, restricted, and reserve drugs:

   First choice drugs are classified as antimicrobials that can be prescribed without restriction by any authority. Restricted drugs can be prescribed for a specific indication as defined by a policy or with expert consultation. Reserve drugs can be prescribed only after permission from expert consultation or a national expert committee.

4. Fractional inhibitory concentration (FIC) index:

   The sum of the FICs of each drug when used in combination. The FIC for each drug is determined by dividing each drug’s MIC when used in combination with each drug’s MIC when used alone.

5. Fragment-based drug design (FBDD):

   A drug discovery approach to develop clinical candidates from fragments (small molecules with low molecular weights). FBDD relies on two main approaches: a) target-binding screening of a library of fragments to find hits; and b) hit-to-lead optimization by increasing the molecular weight of the fragments using various approaches (such as fragment growth or fragment merging).

6. Frequency of resistance (FoR):

   Frequency at which detectable mutant cells emerge in a bacterial population in the presence of an antibiotic.

G

1. Generic vs. trade name (non-generic) antibiotics:

   Commercially available antibiotics may be referred to by two different names. The generic name is the common family identification provided by chemists (for example, amoxicillin). The trade name is given by the manufacturer and is often used by healthcare practitioners and pharmacists when prescribing and dispensing the drug. One trade name for amoxicillin is ‘Amoxil’.

2. Global Antibiotic Research & Development Partnership (GARDP):

   A not-for-profit organization that was created by the World Health Organization and the Drugs for Neglected Diseases initiative (DNDi) in 2016. GARDP works with partners to accelerate the development and access of treatments for drug-resistant infections.

3. Gram-positive/negative:

   Characterization of bacteria according to their appearance after Gram staining, reflecting differences in their cell wall structures. Gram-positive bacteria stain dark purple, whereas Gram-negative bacteria stain red.

4. Gram stain:

   A laboratory staining technique used to distinguish between two groups of bacteria, Gram-positive and Gram-negative, based on differences in their cell wall structure.

5. Growth promotion:

   Administration of an antimicrobial, usually as a feed additive, over a period to growing animals that is thought to result in improved physiological performance (i.e., weight gain, feed conversion).

H

1. Half-maximal inhibitory concentration (IC50):

   The concentration of a drug or inhibitor needed to inhibit a biological process or response by 50%.

2. Harmonisation of Technical Requirements for Pharmaceuticals for Human Use (ICH):

   A global body that brings together regulatory authorities and the pharmaceutical industry to discuss scientific and technical aspects of pharmaceutical development, approval, and safety monitoring, and develops good practice guidelines.

3. Heteroresistance:

   The presence of one or several subpopulations that show antibiotic resistance compared with much of the population.

4. Hit:

   A compound or extract identified in an initial screen for antibacterial activity. A hit must be re-tested to confirm its activity.

5. Hollow fiber infection model (HFIM):

   An in vitro closed system that allows bacteria to be cultured continuously and mimics in vivo infections and drug concentration profiles.

6. Hospital-acquired infection/healthcare-associated infection (HAI):

   Infections that occur more than 48 hours after a patient is admitted to a hospital or any healthcare facility and that were not present at the time of admission. Common HAIs include hospital-acquired pneumonia and surgical site infections.

7. Hospital-acquired pneumonia (HAP):

   Pneumonia that occurs more than 48 hours after hospital admission. It is not associated with mechanical ventilation.

8. Host:

   A multicellular organism such as a human colonized by either commensal or pathogenic microorganisms.

9. Host-specificity:

   The restriction to colonizing one, or a defined group, of hosts.

I

1. Inappropriate antimicrobial use:

   When antimicrobials are used unnecessarily or for non-therapeutic reasons, such as over-prescribing or as feed additives in animals.

2. Inappropriate disposal:

   When active antimicrobials are disposed of in such a way that they can potentially contaminate the environment, i.e., share their resistance genes with normal bacteria living in that environment. One example of inappropriate disposal would be flushing antibiotics down a toilet.

3. Infection prevention and control interventions (IPCI):

   Interventions intended to minimize the spread of pathogens (including drug-resistant microbes), decrease the likelihood of infection in healthcare settings, and reduce the overall need for antimicrobials. The WHO has proposed 4 core areas for healthcare facilities, including hand hygiene, environmental cleaning, disinfection and sterilization, and staff education.

4. Infectious Diseases Society of America (IDSA):

   A community of over 12,000 physicians, scientists, and public health experts who specialize in infectious diseases. IDSA’s mission is to improve the health of individuals, communities, and society by promoting excellence in patient care, education, research, public health, and prevention relating to infectious diseases.

5. Innovation:

   Creating new solutions to counteract loss in antimicrobial effectiveness through research and development. For example, developing new and/or improved rapid diagnostic tests or alternatives to antimicrobials, such as probiotics and vaccines.

6. Intra-abdominal infection (IAI):

   A group of infections that occur within the abdominal cavity. Uncomplicated IAIs (uIAI) involve only a single organ and do not extend to the peritoneum, while complicated IAIs (cIAI) involve more than one organ and infection of the peritoneal space.

7. Intrinsic resistance:

   Inherent or innate (not acquired) antimicrobial resistance, which is reflected in all or almost all representatives of a bacterial species.

L

1. Lead compound:

   A promising newly discovered compound with antibacterial properties that has been selected for more intensive testing.

2. Ligand-based drug design (LBDD):

   A drug discovery approach based on knowledge of molecules with biological activity. It is an approach that is independent of any information about the molecular target. LBDD is based on the chemical information of the active and non-active compounds within a tested series to correlate the biological activity with the chemical structure.

3. Limited population pathway for antimicrobial and antifungal drugs (LPAD):

   A US regulatory pathway designed to accelerate the availability of new treatments for serious and life-threatening infections in a limited population of patients with unmet needs.

4. Lipinski’s Rule of 5:

   Rule of thumb to determine if a chemical compound has physicochemical properties that would likely make it an orally active drug in humans.

M

1. Maximum tolerated dose (MTD):

   The highest dose of a medicine or treatment that will produce the desired effect without resulting in unacceptable side effects.

2. Minimum bactericidal concentration (MBC):

   The minimum concentration of an antibacterial agent required to kill a bacterium.

3. Minimum inhibitory concentration (MIC):

   The lowest concentration of an antibiotic that prevents the visible growth of bacteria. Potent antibiotics have low MIC values. As bacteria become less susceptible to an antibiotic, MIC values increase.

4. Minimum selective concentration (MSC):

   The minimum concentration of an antimicrobial agent at which resistant strains have a competitive advantage.

5. Monitoring:

   Periodic health surveillance of the population or individual animal examination. Therapeutic-treatment, control, and prevention of bacterial disease.

6. Monte Carlo simulation (MCS):

   A Monte Carlo simulation is a mathematical technique that simulates the range of possible outcomes for an uncertain event. MCS generates predictions based on an estimated range of values evolving randomly instead of a fixed set of values. In antibacterial drug development, MCS is used to generate data for pharmacokinetic-pharmacodynamic (PK-PD) target attainment analyses to assess antibacterial dosing regimens early on.

7. Morbidity (disease burden):

   Suffering from a medical condition. Morbidity can refer to an individual or a population. A person can have several morbidities simultaneously (i.e., co-morbidities).

8. Mortality:

   Death caused by a specific health event. Mortality is usually expressed as mortality rate: the frequency of occurrence of death in a defined population during a specified interval of time.

9. Multi-drug resistant (MDR) isolate:

   A bacterial isolate that is resistant to at least one antibiotic in three or more drug classes for which susceptibility is generally expected.

10. Multi-drug resistant (MDR) Pseudomonas aeruginosa:

    Isolates of Pseudomonas aeruginosa that are not susceptible to at least one antibiotic in at least three antibiotic classes for which susceptibility is generally expected: penicillins, cephalosporins, fluoroquinolones, aminoglycosides, and carbapenems.

N

1. Narrow-spectrum antibiotic:

   An antibiotic that is active against a select group of bacterial types.

2. Natural products:

   Natural products are small molecules produced by living organisms (plants, invertebrates, microorganisms). They are also called secondary metabolites as they are non-essential to life. However, they play key roles in defence and cell-to-cell communication. Natural products represent a unique chemical space with compounds distributed in a broad diversity of chemical classes.

3. Natural selection:

   A process by which organisms that are better adapted to their environment thrive and multiply, while organisms that are less well adapted to their environment fail to thrive and do not reproduce successfully.

4. Neglected tropical diseases (NTDs):

   A diverse group of 20 conditions that are mainly prevalent in tropical areas, where they affect more than one billion people who live in impoverished communities. They are caused by a variety of pathogens, including bacteria (e.g., leprosy), viruses (e.g., rabies), fungi (e.g., mycetoma), parasites (e.g., lymphatic filariasis), and toxins (e.g., snakebite envenoming).

5. Non-culture-based microbiologic testing:

   Identification of microorganisms using a method of testing other than a culture. Culture-based testing requires inoculation of a specimen into culture media, incubation, and observation for actual growth of microorganisms. Depending on the microorganism identified, culturing can take several days to weeks for a final report. On the other hand, non-culture-based testing methods generally provide faster results, which can assist with early diagnosis and tailoring of antimicrobial therapy.

6. Non-susceptible isolate:

   An isolate that is either resistant or not completely susceptible to one or more antibiotics.

7. Non-susceptibility to ceftriaxone:

   Ceftriaxone minimum inhibitory concentrations (MICs) ≥ 2µg/mL. This is often used as a substitute for ESBL production in bacteria.

8. Nonventilated intensive care unit-acquired pneumonia (NV-ICUAP):

   Pneumonia that occurs more than 48 hours after admission to the intensive care unit.

O

1. Off-target activity:

   The effects that can occur when a drug binds to or interacts with molecules other than those it is meant to. Off-target activity can lead to harmful side effects (e.g., toxicity).

2. Outpatient parenteral antimicrobial therapy (OPAT):

   The administration of parenteral antimicrobial therapy in at least 2 doses on different days without intervening hospitalization.

P

1. Pandrug-resistant (PDR):

   Non-susceptibility to all agents in all antimicrobial categories (i.e., bacterial isolates are not susceptible to any clinically available antimicrobial).

2. Panel:

   A set of antibiotics used to determine if an isolate is resistant to antibiotics and, if so, which ones. The set of antibiotics used differs by the type of bacteria being used.

3. Pathognomonic:

   Distinctively characteristic of a particular disease.

4. Persister:

   Bacterial survival in the presence of antibiotics.

5. Pharmacodynamics:

   Study of the uptake, movement, binding, and interactions of drugs in the body and how they affect drug activity. Broadly speaking, pharmacodynamics considers the properties of a drug that affects target engagement in the body, while pharmacokinetics considers the effect of the body on a drug.

6. Pharmacokinetics (PK):

   Study of the body’s handling and metabolism of drugs in the body, including their absorption, distribution between different tissues, localization within tissues, modification, and excretion (ADME). Broadly speaking, pharmacokinetics considers the effect of the body on a drug, while pharmacodynamics considers the properties of a drug that affect target engagement in the body.

7. Pharmacokinetics-pharmacodynamics (PK/PD):

   Integration of pharmacokinetic and pharmacodynamic data to understand how a drug is likely to be distributed through the body over time and the access it will have to its molecular target. This understanding provides the basis for dosing strategies.

8. Plasma concentration:

   The concentration of an agent in the plasma. Plasma concentrations are used to define major pharmacokinetic (PK) and PK/PD parameters.

9. Plasma protein binding:

   The degree of binding of a drug to plasma proteins. It is a key characteristic of antibiotics since it affects both their pharmacokinetics (PK) and pharmacodynamics (PD).

10. Polypharmacology (Multi-targeting):

    The ability of a drug to alter the activities of multiple targets. Multi-target drugs act on more than one isoenzyme or closely related proteins of the same pathway or bind to different molecules involved in separate processes. Such multi-functional drugs have a direct antibiotic target but also an additional indirect antibacterial activity (for example, permeabilizing or immunomodulatory properties).

11. Predicted resistance pattern:

    The antimicrobial resistance expected based on analysis of an organism’s genome. This analysis identifies resistance genes and mutations.

12. Pro-drug:

    A drug that is administered in an inactive form and is metabolized in the body into a pharmacologically active agent.

13. Pseudomonas aeruginosa with Difficult-to-Treat Resistance (DTR):

    Isolates of Pseudomonas aeruginosa that exhibit non-susceptibility to all the following drugs: piperacillin-tazobactam. Ceftazidime, cefepime, aztreonam, meropenem, imipenem-cilastatin, ciprofloxacin, and levofloxacin.

Q

1. Qualified infectious disease product (QIDP):

   A U.S. initiative scheme designed to promote the development of antibacterial and antifungal drugs to treat serious or life-threatening infections.

2. Quorum sensing:

   A communication mechanism between bacteria that allows specific processes to be controlled. For example, biofilm formation, virulence factor expression, production of secondary metabolites, and stress adaptation mechanisms. Different types of quorum sensing mechanisms are used by Gram-positive and Gram-negative bacteria.

R

1. Relapse:

   Following demonstration of the initial pathogen eradication, subsequent isolation of the pathogen from the original site of infection, with or without clinical deterioration.

2. Reservoir:

   A host organism in which an infectious agent from some other species lives and multiplies typically without damaging the host. A reservoir serves as a source from which transmission of infection and outbreaks of disease can occur.

3. Resistance determinant:

   A catch-all term that includes both resistance genes and resistance mutations that give a microorganism the ability to resist the effects of one or more drugs.

4. Resistance gene:

   A gene that gives microorganisms the ability to resist the effects of one or more drugs. The gene may be naturally present in the microorganism, or it may be transferred from other microorganisms.

5. Resistance mechanisms:

   Resistance to antimicrobials that develop through several genetic mechanisms. The main mechanisms of resistance are inactivation of a drug; reduced uptake of a drug; active efflux of a drug; and, modification of a drug target.

6. Resistance mutation:

   A change in the normal genetic code that gives a microorganism the ability to resist the effects of one or more drugs.

7. Resistance pattern:

   Description of the antibiotic resistance testing results for an isolate.

8. Resistance profile:

   Description of the resistance patterns for all isolates in an investigation.

9. Resistant isolate:

   An isolate that is resistant to one or more antibiotics.

10. R₀ (R naught) (the basic reproduction number/the basic reproductive rate):

    An epidemiologic metric used to describe the contagiousness or transmissibility of infectious agents. Since R₀ is affected by numerous biological, socio-behavioral, and environmental factors that govern pathogen transmission, it is usually estimated using various types of complex mathematical models. R₀ is not a biological constant for a pathogen, a rate over time, or a measure of disease severity. It cannot be modified through vaccination campaigns.

S

1. Secondary bloodstream infection:

   A bloodstream infection that is thought to be seeded from a site-specific infection at another body site.

2. Semi-synthetic antibiotics:

   These are compounds that are chemically derived from natural antibiotics. Semi-synthetic antibiotics have improved pharmaceutical properties compared to their natural parent, making them more suitable for clinical use.

3. Sequelae:

   Pathological conditions resulting from infection, disease, injury, therapy, or other trauma.

4. Serial passage:

   Process of growing microorganisms in a new environment under defined conditions sequentially over time. Such studies are used to examine the evolution of drug resistance or virulence.

5. Site of infection:

   The location within a host organism’s cells where an infection occurs. Infections can be extracellular (outside the cells in body fluids or on mucosal surfaces) or intracellular (within cells).

6. Skin and soft tissue infection (SSTI):

   Microbial invasion of the layers of the skin and underlying soft tissues.

7. Specimen:

   A sample collected for laboratory testing. During outbreak investigations, samples may be collected from the blood, stool, or another location of a human or animal, and from food and the environment.

8. Standardized infection ratio (SIR):

   A summary measure used to track hospital-acquired infections (HAIs) over time. It compares the number of reported HAIs to the number of predicted HAIs, based on baseline data. The SIR adjusts for several factors that may impact the risk of acquiring an HAI.

9. Structure-permeation relationship:

   Correlation between the structure and permeability of compounds into cells or across cell layers.

10. Superinfection (superimposed infection):

    A secondary infection that occurs during an existing infection, or immediately following a previous infection; this is especially so when caused by microorganisms that are resistant or have become resistant to the antibiotics used earlier.

11. Susceptible isolate:

    An isolate that is not resistant to any of the antibiotics tested.

T

1. The German Federal Ministry of Education and Research (Bundesministerium für Bildung und Forschung-BMBF):

   The BMBF promotes international cooperation in education, science, research, and technology with European and non-European states, and within international organizations such as the EU, UNESCO, and the Council of Europe.

2. Therapeutic index:

   The ratio of the blood concentration at which a drug becomes toxic (TD50) and the concentration at which it is effective (ED50).

3. The United States Food and Drug Administration (FDA):

   he FDA’s mission is to protect the public health by ensuring the safety, efficacy, and security of human and veterinary drugs, biological products, and medical devices; and by ensuring the safety of food supply, cosmetics, and products that emit radiation in the USA.

4. Time above MIC (T>MIC):

   Cumulative percentage of 24 hours that the drug concentration exceeds the minimum inhibitory concentration (MIC) at steady-state pharmacokinetic conditions. fT>MIC refers to the unbound fraction of the drug.

5. Tissue concentration:

   The concentration of a drug in a tissue. The pharmacological compartment of the tissue (cells, subcellular organelles, interstitial fluid) is not specified.

6. Tissue penetration:

   The extent to which a drug reaches infected tissue.

7. Toxicity:

   The harmful effects of a drug. Acute toxicity results when the adverse effects of a drug appear in a short period of time (usually less than 24 hours) after administration. The development of adverse effects because of long-term exposure to a drug is referred to as chronic toxicity.

U

1. Usual drug resistance (UDR):

   Usual drug resistance describes isolates that are not fully susceptible wild-type strains but that can nonetheless be readily treated with standard therapies.

V

1. Vancomycin-resistant enterococci (VRE):

   Any of several enterococci (such as Enterococcus faecalis and Enterococcus faecium) that are resistant to vancomycin and other commonly used antibiotics (such as cephalosporins and tetracycline).

2. Ventilator-associated pneumonia (VAP):

   Pneumonia that arises more than 48 hours after mechanical ventilation.

3. Ventilator-hospital acquired pneumonia (vHAP):

   Severe hospital-acquired pneumonia in patients requiring mechanical ventilation.

4. Vital signs:

   Clinical measurements used to assess a patient's essential body functions.

5. Volume of distribution (Vd):

   A pharmacokinetic parameter that relates the total amount of drug in the body to the concentration in the bloodstream.

W

1. World Health Organization:

   The directing and coordinating authority for health within the United Nations system. It is responsible for providing leadership on global health matters, shaping the health research agenda, setting norms and standards, articulating evidence-based policy options, providing technical support to countries and monitoring and assessing health trends.

2. World Health Organization fungal priority pathogens list (WHO FPPL):

   The first global effort to systematically prioritize fungal pathogens, considering their unmet research and development needs and perceived public health importance. The list is divided into three categories: critical, high, and medium priority.

3. World Health Organization priority pathogen list:

   The World Health Organization’s list of twelve groups of antibiotic-resistant bacteria assessed to be of the highest priority for new antibiotic development. It is divided into three categories- critical, high, and medium priority-according to the urgency for new antibiotics.