| Literature DB >> 34536087 |
Roland Seifert1, Bastian Schirmer2.
Abstract
The term "antibiotics" is a broadly used misnomer to designate antibacterial drugs. In a recent article, we have proposed to replace, e.g., the term "antibiotics" by "antibacterial drugs", "antibiosis" by "antibacterial therapy", "antibiogram" by "antibacteriogram", and "antibiotic stewardship" by "antibacterial stewardship" (Seifert and Schirmer Trends Microbiol, 2021). In the present article, we show that many traditional terms related to antibiotics are used much more widely in the biomedical literature than the respective scientifically precise terms. This practice should be stopped. Moreover, we provide arguments to end the use of other broadly used terms in the biomedical literature such as "narrow-spectrum antibiotics" and "reserve antibiotics", "chemotherapeutics", and "tuberculostatics". Finally, we provide several examples showing that antibacterial drugs are used for non-antibacterial indications and that some non-antibacterial drugs are used for antibacterial indications now. Thus, the increasing importance of drug repurposing renders it important to drop short designations of drug classes such as "antibiotics". Rather, the term "drug" should be explicitly used, facilitating the inclusion of newly emerging indications such as antipsychotic and anti-inflammatory. This article is part of an effort to implement a new rational nomenclature of drug classes across the entire field of pharmacology.Entities:
Keywords: Antibiogram; Antibiotic stewardship; Antibiotics; Broad-spectrum antibiotics; Chemotherapeutics; Reserve antibiotics
Mesh:
Substances:
Year: 2021 PMID: 34536087 PMCID: PMC8449524 DOI: 10.1007/s00210-021-02144-9
Source DB: PubMed Journal: Naunyn Schmiedebergs Arch Pharmacol ISSN: 0028-1298 Impact factor: 3.195
Definitions of some important pharmacological terms in the field of antibacterial and antipathogenic therapy
| Pharmacological term | Definition |
|---|---|
| Antibacterial drug | A drug that possesses inhibitory effects on bacteria. Bacteriostatic drugs inhibit the growth of bacteria without killing them. Bactericidal drugs kill bacteria |
| Antibacterial resistance | The uncritical use of antibacterial drugs in medicine and agriculture has resulted in ineffectiveness of many antibacterial drugs in important diseases |
| Antibacterial stewardship | This constitutes an interdisciplinary approach of microbiologists, pharmacologists, pharmacists, and clinicians to optimize the use of antibacterial drugs in patient treatment and to avoid development of antibacterial resistance |
| Antibacteriogram | In an antibacteriogram, a pathogenic bacterium is cultured and the minimum inhibitory concentration (MIC) of various antibacterial drugs on bacterial growth is assessed. The antibacteriogram provides a rational basis for selecting the best antibacterial drug for a patient |
| Antimycotic (antifungal) drug | A drug that possesses inhibitory effects on fungi. Mycostatic (fungistatic) drugs inhibit the growth of fungi. Mycocidal (fungicidal) drugs kill fungi |
| Antiparasitic drug | A drug that possesses inhibitory effects on parasites. Parasites include protozoa, worms, and ectoparasites |
| Antipathogenic drug | An umbrella term for drugs including antibacterial drugs, antimycotic drugs, antiparasitic drugs, and antiviral drugs |
| Antiviral drug | A drug that possesses inhibitory effects on viruses. Virtually all antiviral drugs are virustatic; i.e., they interfere with the reproduction of viruses in human cells |
| Bactericidal drug | A drug that kills bacteria. Prototypical bactericidal drugs are penicillins, cephalosporins, fluoroquinolones, and aminoglycosides |
| Bacteriostatic drug | A drug that inhibits the growth of bacteria without killing them. Prototypical bacteriostatic drugs are tetracyclines, macrolides, and lincosamides |
| Chemotherapeutic | Historic umbrella term for antipathogenic drugs (antibacterial drugs) and cytostatic drugs |
| Drug | A drug is a chemical substance with beneficial effects on human health. In contrast, poisons possess detrimental effects on human health |
| Drug repurposing | This procedure describes a strategy of using already approved drugs for new clinical indications beyond the traditional uses. The advantage of drug repurposing is that it is much less expensive than the de novo development of drugs because important parameters such as pharmacokinetics, drug interactions, and adverse effects are already known |
| MIC (minimum inhibitory concentration) | This is the lowest effective concentration of an antibacterial drug at which it shows an inhibitory effect on bacterial growth in an antibacteriogram |
| MRSA (multidrug (methicillin)-resistant | Strains of |
| Mycobactericidal drug | A drug that kills mycobacteria. Isoniazide (INH), rifampicin (RMP), and pyrazinamide (PZA) are prototypical mycobactericidal drugs |
| Mycobacteriostatic drug | A drug that inhibits the growth of mycobacteria without killing them. Ethambutol (EMB) is a prototypical mycobacteriostatic drug |
| Potency | Potency defines the concentration at which a drug exhibits 50% of its maximum effect. Many antipathogenic drugs are enzyme inhibitors. Therefore, the potency of many antipathogenic drugs refers to the inhibitory drug concentration causing 50% of enzyme inhibition (IC50) |
Fig. 1Citation frequency of modern and traditional terms related to antipathogenic drugs. The PubMed search was performed on May 13, 2021, and was confined to titles and abstracts of searchable items. Depicted in the plots are the absolute number of publications per year that use a specific term (red line/left y-axis) and the relative number of these publications normalized to the total number of citable items of the corresponding year (black line/right y-axis). Except for panels a, g, m, and n, both singular and plural forms of the search term have been included
Traditional terms related to antibacterial drugs that should not be used anymore
| Traditional term | Reason why the traditional term should not be used anymore | Reference for use |
|---|---|---|
| Antimicrobial drugs | The term is too broad in the sense that it refers all types of “microbes”. In fact, in medicine, we are interested only in interfering with pathogenic microorganisms. Microorganisms belonging to the microbiome have beneficial effects and should not be adversely affected by antipathogenic drugs. Hence, the term antipathogenic drugs is more precise | (Sokol et al. |
| Non-antimicrobial drugs | This is a classic negative definition of a drug class with no common underlying mechanism. An analogous term is “non-opioid analgesics” encompassing various mechanistically diverse drugs. The term “non-antimicrobial drugs” is defined far too imprecisely because every drug that originally has no antimicrobial effect is included in this class. However, since nowadays several so-called non-antimicrobial drugs are being repurposed for treatment of diseases caused by pathogens, the former term causes only confusion and should be dropped | (Pereira et al. |
| Broad-spectrum antibiotics | There is no generally accepted definition which antibacterial drug is a broad-spectrum antibacterial drug. In fact, the spectrum of pathogenic bacteria covered by a given antibacterial drug varies greatly in terms of time and geographical location. Due to uncritical use the “spectrum” of many antibacterial drugs has become narrower during the past years. The term “broad spectrum” also conveys the false impression to the physician that all or at least most pathogenic bacteria are coved by a broad-spectrum antibacterial drug. But in contrast, this misconception increases the probability that resistances emerge | (Gerber et al. |
| Narrow-spectrum antibiotics | In fact, as the result of the uncritical use of “broad-spectrum” antibacterial drugs, several of these drugs have become “narrow-spectrum” antibacterial drugs. Thus, like the term “broad-spectrum”, the term “narrow-spectrum” is not clearly defined. Dropping these two misleading terms honestly acknowledges the fact that the spectrum of antibacterial drugs changes temporarily and geographically | (Gerber et al. |
| Reserve antibiotics | Originally, the use of reserve antibacterial drugs was restricted to cases in which “broad-spectrum” and “narrow-spectrum” antibacterial drugs did not work anymore. However, the increasing resistance problem has resulted in an expansion of the use of “reserve” antibacterial drugs beyond the originally intended indications into traditional fields of “broad-spectrum” and “narrow-spectrum” antibacterial drugs. Hence, like for the other types of antibacterial drugs, the term “reserve antibacterial drugs” lacks a clear definition. Rather, a given antibacterial drug must be assigned to a specific pathogenic bacterial strain and a clearly defined clinical use | (Robertson et al. |
| Chemotherapeutics (chemotherapeutic agents) | Historic term used to designate antipathogenic drugs or antibacterial drugs. Sometimes, the term “chemotherapeutics” designates only synthetic antibacterial drugs, but often natural (e.g., fungus- or plant-derived) antibacterial drugs are included as well. To complicate matters, the term “chemotherapeutics” also includes classic cytostatic drugs used for the treatment of malignant tumors. In current language, the term “chemotherapy” is almost exclusively used for therapy of malignant tumors, but not for pathogen-caused diseases. The term “chemo” also has a negative connotation, signaling harm, danger and toxic effects. This should be avoided because several antipathogenic drugs are tolerated very well. Moreover, the term “chemotherapeutics” also alludes to the existence of allegedly “good” biotherapeutics, but the term “biotherapeutics” is uncommon in medicine. Instead, the term “biologicals” is broadly used, also suggesting via the prefix “bio” that these drugs have few if any adverse effects | (Nandi et al. |
| Leprostatics | The term “leprostatics” is used as an umbrella term to cover both leprostatic and “leprocidal drugs”. Because it is important to discriminate between the two classes of drugs, the incorrect umbrella term should be dropped. The term “anti-leprosy drugs” is a more appropriate umbrella term. The term “antimycobacterial drugs” also covers anti-tuberculosis drugs | (Caliskan et al. |
| Tuberculostatics | The term “tuberculostatics” is often used as an umbrella term to cover both tuberculostatic and tuberculocidal drugs. Isoniazide, pyrazinamide and rifampicin are prototypical tuberculocidal drugs, while ethambutol is a tuberculostatic drug. Because it is important to discriminate between the two classes of drugs, the incorrect umbrella term should be dropped. The term antimycobacterial drugs also covers anti-leprosy drugs | (Damasceno Junior et al. |
Fig. 2Citation frequency of several traditional terms related to antibacterial drugs that should not be used anymore. The PubMed search was performed on May 13, 2021, and was confined to titles and abstracts of searchable items. Depicted in the plots are the absolute number of publications per year that use a specific term (red line/left y-axis) and the relative number of these publications normalized to the total number of citable items of the corresponding year (black line/right y-axis). Both singular and plural, hyphenated and non-hyphenated forms of the respective search term have been included
Repurposing of antipathogenic drugs for indications beyond pathogen-caused diseases
| Antipathogenic drug or drug class | Traditional indication | New indication | Reference |
|---|---|---|---|
| Chloroquin (antimalarials, disease-modifying antirheumatic drugs, DMARDs) | Malaria | Lupus erythematosus, rheumatoid arthritis | (Rainsford et al. |
| Doxycyclin, minocyclin (tetracyclines, antibiotics) | Bacterial infections, malaria | Schizophrenia, major depressive disorder, neurodegenerative diseases, cancer therapy | (Husain et al. |
| Erythromycin (macrolides, macrolide antibiotics, broad-spectrum antibiotics) | Bacterial infections | Gastric hypomotility | (Jun et al. |
| Fluconazole (triazoles, azole antimycotics, antimycotics) | Fungal infections | Hypoxic pulmonary vasoconstriction | (El-Sherbeni and El-Kadi |
| Ivermectin (antiparasitics, antiparasitic drugs) | Parasitic diseases | Treatment of alcoholism, cancer therapy | (Yardley et al. |
| Ceftriaxone (cephalosporins, antibiotics, β-lactam antibiotics, broad-spectrum antibiotics, broad-spectrum cephalosporins) | Bacterial infections | neurological disorders, drug dependency/withdrawal | (Yimer et al. |
| Rifampicin (ansamycins, tuberculostatics, tuberculocidal drugs, antimycobacterial drugs) | Mycobacterial infections | Neurodegenerative diseases | (Socias et al. |
| Ciclopirox | Fungal infections | Porphyria, ischemic stroke | (Urquiza et al. |
| Metronidazole (nitroimidazoles, antianaerobials, chemotherapeutics) | Bacterial infections | (Simões-Silva et al. | |
| Macrolides (macrolide antibiotics, broad-spectrum antibiotics) | Bacterial infections | Chronic inflammatory diseases (asthma/chronic obstructive lung disease, osteoarthritis, cystic fibrosis), acute respiratory distress syndrome, sepsis, pneumonia | (Zimmermann et al. |
In parentheses, representative names of drug classes (both traditional and mechanistic) are provided
Repurposing for pathogen-caused diseases of drugs not traditionally used for pathogen-caused diseases
| Drug or drug class | Traditional indication | New indication for pathogen-caused disease | Reference |
|---|---|---|---|
| Auranofin (disease-modifying antirheumatic drugs, DMARDs) | Rheumatoid arthritis | Inhibition of biofilm formation | (She et al. |
COX-inhibitors (e.g., diflunisal, piroxicam) | Osteoarthritis, rheumatoid arthritis | Infections with | (Ogundeji et al. |
Dihydropyridines (e.g., nitrendipine) | Hypertension | (González et al. | |
| 5-Fluorouracil (classic cytostatics, pyrimidine analogs) | Various malignant tumor diseases | Bacterial infections | (Soo et al. |
| Metformin (biguanides, oral antidiabetics) | Type-2 diabetes | Malaria, trypanosomiasis, bacterial infections, hepatitis B | (Butts et al. |
| Propranolol (β-adrenergic receptor antagonists, βxAR antagonists) | Migraine prophylaxis, tremor, infantile hemangioma | Hepatitis, | (Ueno et al. |
| Thalidomide (hypnotics) | Sleeplessness in pregnant women | Tuberculous meningitis, leprosy | (Walker et al. |
| Disulfiram | Treatment of alcoholism | (Potula et al. | |
| Tamoxifen (selective estrogen receptor modulators, SERM) | Breast cancer | Cryptococcal infections | (Butts et al. |
| Statins (HMG-CoA reductase inhibitors, e.g., atorvastatin, fluvastatin) | Hypercholesterinemia | Fungal infections | (Macreadie et al. |
| Sertraline (selective serotonin reuptake inhibitors, SSRI) | Major depressive disorder | (Weeks et al. | |
| Lorazepam (benzodiazepines, allosteric GABAA-receptor modulators) | Sedation, anxiety disorders | Fungal infections | (Kathwate et al. |
| Ticagrelor (irreversible P2Y12-receptor antagonists) | Thrombosis prevention and therapy | (Phanchana et al. |
In parentheses, representative names of drug classes (both traditional and mechanistic) are provided