Why the term “antibiotic” is problematic

Literally, the term “antibiotic” means “directed against life”. However, in reality, antibiotics designate drugs directed against bacteria. But, in fact, antibiotics are still both prescribed by professionals and expected by patients for treatment of non-bacterial diseases, most notably virus-caused diseases such as acute respiratory infections (Dhingra et al. 2020; Ray et al. 2019). The broad use of antibiotics in general medicine against “flu-like” diseases of the upper respiratory tract is a particularly bad example for overprescription of antibiotics (Fleming-Dutra et al. 2016; McDonagh et al. 2018). This misuse of antibiotics is a consequence of numerous interconnected factors, including misconceptions about the indication of antibiotics, intercollegial dynamics, patient expectations, and normative beliefs (Akkerman et al. 2005; Faure et al. 2009; Warreman et al. 2019). It can be hypothesized that the use of the historic misnomer “antibiotic” contributes to each of these factors. Because the socio-cultural/psycho-social research on the determinants of antibiotic resistance development is a quite young discipline, further research is needed to firmly establish such a contribution of imprecise terminology (Donisi et al. 2019). Regardless of the causes of misuse of antibacterial drugs, their inappropriate use has resulted in the emergence of numerous resistant bacterial strains including multi-resistant (or methicillin-resistant) Staphylococcus aureus (MRSA). These bacterial strains cause serious hospital-acquired infections and have led to the closure of whole wards (Curtis et al. 2019; Wu et al. 2019; Oliver et al. 2020; Zhao et al. 2020). Knowledge-based and psycho-social intervention programs targeting prescribers, “consumers”, and pharmacists have proven beneficial in reducing misuse of antibacterial drugs (Altiner et al. 2007; Burstein et al. 2019; Hickman et al. 2003). The use of precise terms in such interventions might help to clearly and unequivocally define the problems and challenges of antibacterial stewardship and prevention of emerging resistances.

Based on this linguistically and medically inacceptable situation, we have recently proposed to replace the term “antibiotics” by the term “antibacterial drugs” (Seifert and Schirmer 2021). This proposed change in nomenclature is actually consistent with the well-established use of the terms “bacteriostatic drugs” and “bactericidal drugs”. Related to this change in nomenclature, the term “antibiosis” should be replaced by “antibacterial therapy”, “antibiogram” by “antibacteriogram”, “antimicrobial” by “antipathogenic drug”, “antibiotic agents” by “antibacterial drugs”, “antibiotic activity” by “antibacterial potency”, and “antibiotic stewardship” by “antibacterial stewardship”. Table 1 provides the definitions of some important pharmacological terms in the field of antibacterial and antipathogenic therapy.

Table 1 Definitions of some important pharmacological terms in the field of antibacterial and antipathogenic therapy
Full size table

Problematic traditional terms are deeply rooted in the biomedical literature

To assess how often traditional terms are used in the biomedical literature, we analyzed scientific articles indexed in PubMed and compared the citation frequency of traditional (imprecise) terms versus that of scientifically precise terms (Fig. 1). It is quite astonishing that the imprecise term “antibiotics” is used 50 times more often than the precise term “antibacterial drug” (compare Fig. 1a versus Fig. 1b). This discrepancy is an indication that convention rather than critical reflection determines the use of this term in scientific literature. However, the imprecise term “antibiosis” and the precise term “antibacterial therapy” (compare Fig. 1c and d) are used with similar frequency which is inconsistent to the comparisons shown in Fig. 1a and b. Thus, as previously discussed for the terms “bactericidal” and “bacteriostatic”, precise terms are not necessarily ignored in the literature. Most strikingly, the imprecise term “antibiogram” (derived from “antibiotic”) is very broadly used in the literature, even with increasing frequency, whereas the precise term “antibacteriogram” was not found in a single PubMed-indexed publication under our search conditions at all (Fig. 1e versus Fig. 1f). In fact, even a non-confined Google search with the term “antibacteriogram” currently yields only ~ 60 hits (search date May 14, 2021).

Fig. 1
figure 1figure 1

Citation 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

Full size image

The diffusely defined term “antimicrobials” is also excessively used in the literature, while the precise term “antipathogenic drugs” is rather uncommon (compare Fig. 1g and h). The historic term “agent”, which is poorly defined pharmacologically, is also deeply rooted in the biomedical literature although the precise term “antibacterial drug” has become more prevalent in recent years (compare Fig. 1i and j).

As stated recently, the term “activity” should be reserved to receptor agonists possessing intrinsic activity and stabilizing a pharmacologically active receptor conformation. Most antibiotic “agents” are actually enzyme inhibitors and not receptor agonists. Nonetheless, the imprecise term “antibiotic activity” is used far more commonly in the literature than the term “antibacterial potency” (compare Fig.1k and l).

As a result of improper and unreflective use of antibacterial drugs and the emergence of bacterial resistances, the biomedical field of antibacterial stewardship was developed to improve the rational use of these drugs in the clinics and fight development of bacterial resistances (Ha et al. 2019). Ironically, these important measures to improve proper use of antibacterial drugs have not yet penetrated scientific language. The imprecise term “antibiotic stewardship” is used more than 100-fold more often than the precise term “antibacterial stewardship” (compare Fig. 1m and n). Taken together, these examples illustrate that imprecise language use in the field of antibacterial therapy is very common in the biomedical literature. This is, however, not a trivial issue because language also strongly influences and shapes thinking and decision processes (Mahon and Kemmerer 2020). In this regard, there is clearly much to be done in the scientific language.

It could be argued that abandoning traditional terms would render literature searches more difficult. We concur that for a transition period, this may be the case, but in the long run, there is no alternative to using the precise term because the dissociation between traditional terminology and actual scientific meaning has become too large over the past seven to eight decades. In the future, the gap between traditional terms and their precision will inevitably further increase. The increased length of the precise terms is a possible downside of our proposed nomenclature, and this may be suspected to complicate communication. But based on the practical experience of the authors using the adapted nomenclature in scientific articles, teaching texts, and lectures, this is rarely the case.

More problematic terms linger in the literature

Table 2 lists several problematic terms in the field of antibacterial therapy that should not be used anymore and provides reasons for avoiding them. Figure 2 illustrates the use of these problematic terms in the biomedical literature. One of the most widely used problematic terms is “broad-spectrum antibiotics”. In fact, with increasing resistance of bacteria against broad-spectrum antibiotics (antibacterial drugs), the term “broad-spectrum antibiotics” is used with increasing frequency (Fig.2b) as if increasing the use of an imprecise term would alleviate the medical problem. Unfortunately, the term “broad-spectrum antibiotics” is not precisely defined. Quite different definitions exist which drugs are included in this definition. In fact, the definition of the term varies greatly with respect to time and geographical location, reflecting the dynamic resistance situation of pathogenic bacteria (Curtis et al. 2019; Wu et al. 2019). The term “narrow-spectrum antibiotics” is similarly poorly defined as the “broad-spectrum antibiotics” but also used with increasing frequency in the biomedical literature. In fact, due to the uncritical use of broad-spectrum antibiotics, several of these drugs have been converted to narrow-spectrum antibiotics meanwhile (Karam et al. 2016; Vivas et al. 2019). Related to the latter two terms, the term “reserve antibiotics” is used in the literature (Fig.2c), but due to their uncritical use, many reserve antibiotics have lost this status now, leaving us empty-handed without therapeutic alternatives (Remschmidt et al. 2017; Richter et al. 2019; Annamalai et al. 2021).

Table 2 Traditional terms related to antibacterial drugs that should not be used anymore
Full size table
Fig. 2
figure 2

Citation 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

Full size image

One of the most widely used terms in the field of antibacterial therapy is “chemotherapeutics”, and its use in the biomedical literature increases (Fig. 1d). Again, the term lacks an unequivocal definition. Historically, the term was initially coined to describe chemically synthesized antibacterial drugs (as opposed to naturally occurring antibiotics). Later, both natural and chemically synthesized antibacterial drugs were included in this category. Subsequently, the chemically synthesized cytostatic drugs with anti-tumor effects were included in this broad category as well. However, nowadays, in the general medical communication and in the media (TV, radio, Internet), the term chemotherapy is almost exclusively used to describe an anti-tumor therapy with cytostatic drugs. Moreover, the syllable “chemo” has a negative connotation of “bad” and “many side effects” (adverse drug reactions, ADR) as opposed to the syllable “bio”, implicating beneficial effects without harmful side effects (Wakiuchi et al. 2019; Ihrig et al. 2020). However, these associations are completely wrong.

Another popular term in the biomedical literature is “tuberculostatics” (Fig. 2e). This term alludes to the fact that these drugs inhibit the growth of Mycobacterium tuberculosis. However, in the biomedical literature, this term is also incorrectly used to include tuberculocidal drugs (Damasceno Junior et al. 2020; García-Caballero et al. 2020). Therefore, the precise terms “tuberculostatic drugs” and “tuberculocidal drugs” should be used. Similar considerations apply to the infrequently used term “leprostatics” including both “leprostatic drugs” and “leprocidal drugs” (Caliskan et al. 2019).

Like the term “chemotherapeutics”, the term “antimicrobial drugs” is not clearly defined, but nevertheless widely used in the literature. In fact, with the advent of drug repurposing, i.e., the use of old drugs for new therapeutic purposes, several traditional antibacterial (antipathogenic) drugs are now used for indications unrelated to bacterial diseases (Table 3). Conversely, many drugs traditionally used for the treatment of diseases unrelated to pathogen-caused diseases are now being repurposed for the treatment of pathogen-caused diseases (Table 4). This development has resulted in the term “non-antimicrobial drugs”. However, this term is a negative definition without a common mechanism of action or chemical structure. Therefore, the term “non-antimicrobial drugs” should not be used anymore, like the “non-opioid analgesics”, also including mechanistically heterogenous classes of drugs with diverse mechanisms of action. The nomenclature problem becomes even more evident considering the traditional and non-traditional designations of drug classes in the context of new indications (Tables 3 and 4).

Table 3 Repurposing of antipathogenic drugs for indications beyond pathogen-caused diseases
Full size table
Table 4 Repurposing for pathogen-caused diseases of drugs not traditionally used for pathogen-caused diseases
Full size table

These few examples highlight that the field of antibacterial (antipathogenic) drug therapy is abound with highly problematic terms that may deteriorate the precision of drug therapy, cause confusion, render literature searches increasingly difficult, and hinder patient communication. The eminent presence of problematic terms in the biomedical literature reflects the fact that authors, journal editors, and peer reviewers alike are not yet sufficiently aware of the issue and/or do not act accordingly.

First simple steps to improve terminology

Many traditional terms in the field of (antibacterial) drug therapy have become highly problematic. Particularly problematic is the use of the common prefix “anti” followed by a brief description of the drug class such as “antibiotics”. A simple immediate solution to the problem is to rigorously avoid all problematic terms, even if they have a long history, and rather use precise terms that do not bear the risk of confusion. As the most important example, instead of using the term “antibiotics”, the term “antibacterial drugs” should be used. The apposition of the simple word “drug” to a given drug class renders the term more precise, because this opens up the possibility that an antibacterial drug also possesses, e.g., antidepressive or antipsychotic effects (example of tetracyclines, Table 3). Conversely, the use of the term “anti-inflammatory drug” also leaves open the possibility that this drug additionally exhibits antibacterial effects (example of diflunisal and piroxicam, Table 4).

The process of abandoning the traditional drug nomenclature, highlighted by the case of antibiotics, will not only be important for pharmacology textbooks, the biomedical literature, and professional communication, but also for physician–patient communication. How should a patient understand that the doctor is prescribing an antibiotic for depression or schizophrenia? As a first step towards solving the problems associated with the use of traditional drug nomenclature in the public, one of the authors of this article has recently published a book in German language for a general audience explaining these problems (Seifert 2021). As the next step, the book will be adapted into English language for an international general audience.

What else needs to be done in the future

How will the revised nomenclature be viewed by international learned societies? Implementation and acceptance of the proposal will require endorsement by international learned societies. First of all, the drug nomenclature proposal will be discussed by the International Union of Basic and Clinical Pharmacology (IUPHAR). Similarly, the proposal must be discussed and approved by the International Union of Microbiological Societies (IUMS).

How will the nomenclature be integrated in textbooks and teaching? A textbook in English language has partially implemented some of the aspects discussed in this article (Seifert 2019). The textbook in German language (Roland Seifert, Basiswissen Pharmakologie (German language), second edition, Springer, 2021) has already fully implemented the proposed new nomenclature. The Federal Institute for Medical and Pharmaceutical Exam Questions (IMPP) in Germany has adopted the new nomenclature as well (https://www.impp.de/pruefungen/allgemein/gegenstandskataloge.html, accessed on May 14, 2021). Hence, the next generation of physicians in Germany will be familiar with the new nomenclature. The modern nomenclature facilitates learning, and students embrace the new nomenclature because of its logic. It will be more challenging for professors and lecturers to switch to the new nomenclature.

How will the nomenclature be implemented in the scientific literature? The traditional nomenclature renders literature searches extremely difficult and biased. The historic scientific track record cannot be changed anymore, but journal editors can gradually implement new nomenclature by amending the instructions for authors. But again, this change will require time because of the large number and heterogeneity of scientific journals.

How will the nomenclature be integrated into daily scientific communication? This issue probably represents the biggest hurdle because all scientists were socialized with the traditional nomenclature without even reflecting its problems.

Summary

Resistance against antibacterial drugs has become a major problem because of uncritical use of these drugs. Drug repurposing in the field of antipathogenic drugs becomes more important. Antipathogenic drugs are used for indications beyond pathogen-caused diseases, and drugs traditionally used in other fields are increasingly used for pathogen-caused diseases. Traditional terminology in the field of antipathogenic drugs is becoming increasingly imprecise. Terms such as “antibiotics”, “antibiogram”, “agent”, and “activity” should be dropped. A precise drug nomenclature based on chemical and mechanistic considerations is proposed. Terms such as “antibacterial drugs”, “antibacteriogram”, “drug”, and “potency” should be used instead of traditional terms. We are convinced that a precise terminology will improve the precision of science, assist reducing drug resistance, and improving antibacterial stewardship. To our knowledge, studies investigating the association between using correct medical terms and correct drug use are missing so far. Further research is needed to provide definitive evidence for this impact of using correct terms.