Is there a terrible issue with bacterial resistance: pro–con

We are observing a major increase in antibiotic resistance of many bacterial species, Klebsiella pneumoniae and Acinetobacter baumannii in particular [1]. This triggers an alarmist response in major journals in the world, the WHO and the CDC [2]. It is clear that the response of the media and governments to ongoing events is not always rational and often leads to overreactions. Hence, very few of the virus or prion alerts in last 30 years have been confirmed, including bioterrorism, avian flu, ‘Mad cow’ disease, severe acute respiratory syndrome, Middle East respiratory syndrome, coronavirus and the globalized threat of Ebola which has been predicted since 1976 [3]. In this context, we must carefully appraise alerts on antibiotic resistance to avoid overreacting. Indeed, in the 1970s, the end of the antibiotic era had already been predicted at the time of the emergence of resistance in Serratia marcescens [4]. It is important to balance correctly the burden of disease, because this impacts drug development, drug agencies’ approval thresholds for new drugs, allocation of research funds and more.

The medical literature draws attention to bacteria becoming resistant but neglects bacteria becoming susceptible. For example Staphylococcus aureus, which is perhaps the biggest bacterial killer in developed countries, is less resistant now than 10 years ago in most of the countries worldwide [5], and in Marseille there is three times less methicillin-resistant S. aureus now as there was 10 years ago [6]. The sum of bacteria that became less resistant and bacteria that became more resistant in the last 15 years in Marseille does not suggest that the problem of resistance has worsened [6]. Susceptibilities to old antibiotics such as trimethoprim-sulfamethoxazole in S. aureus and chloramphenicol or aminoglycosides in Gram-negative bacteria in hospitals is increasing with time in many hospitals. Moreover, community-acquired bacteria such as Streptococcus pyogenes, Streptococcus pneumoniae and Haemophilus influenzae are not more resistant now than they were 20 years ago. There is little evidence that community antibiotic prescribing has played a major role in resistance.

Also a large number of molecules have been abandoned for lack of profitability while retaining full effectiveness and the implementation of a business model that would give new life to old molecules is probably necessary. A systematic evaluation of these molecules alone or in combination can probably answer many of the problems we currently face. For example, in tuberculosis, extensively drug-resistant Mycobacterium tuberculosis strains were defined while omitting those molecules that were most likely to be effective—those used to treat leprosy [7].

This theme issue presents two different views; Mical Paul thinks that there is a real problem of resistance while Didier Raoult thinks the opposite. A study carried out by Jean Marc Rolain [6] defends the position that there are no major problems, but the reviews by Patrice Courvalin [1] and Yehuda Carmeli [8] consider that there is a very big problem and finally Fernando Baquero [9] tries to put this in a much more distant perspective as only his experience allows him to do. Overall, we tried for the first time to balance the information between those who believe that there is a problem of resistance and those who think that ecosystem balance has simply shifted. The point on which everyone agrees is that irrational use of antibiotics in human and veterinary health creates an ecosystem change that will surely promote the multiplication of multiresistant bacteria in the environment and in hospitals.