Anaesth Crit Care Pain Med 34 (2015) 133–134
Editorial
Bacterial resistance, the medical challenge of the next 20 years
One of the greatest advances in medicine in the last century was the discovery of antibiotics. Indeed, the genius of Sir Alexander Fleming was the almost simultaneous description of the in vitro bactericidal activity of penicillin on Staphylococcus aureus in 1930 and then the resistance of Staphylococcus to penicillin by secretion of penicillinase. Since that time, the bacterial world has always been one step ahead of the medical world. Thus all pharmacochemistry breakthroughs, allowing prescription of new antibiotics efficient against resistant bacteria, are followed by the appearance of new mechanisms of resistance, which are more or less transferable and epidemic. In fact, the bacterial world is a living world that is simply trying to survive in the environment in which it finds itself. To this end, it boasts two major assets. The first is DNA with strong mutagenic capacity that is able to modify and acquire information of resistance. The second is its strong capacity to spread resistance to daughter bacteria due to its ability to multiply extremely fast. For instance, a colony of Escherichia coli multiplies every 20 minutes, allowing fast genomic adaptation to selection pressure generated by the environment. Furthermore, man lives in equilibrium with the saprophytic bacterial flora of the skin and digestive system leading to coexistence of different bacterial species. These are always balanced with environmental flora. Thus, hospitals with a population of vulnerable patients at high risk of infection are responsible for important antibiotic prescription leading to selection of environmental bacterial flora potentially resistant to prescribed antibiotics. This resistant bacterial flora is able to colonize the gut of our patients. Transfer of information, especially between enterobacteria in the digestive flora via exchange of DNA segments of plasmid or integrating types, increases the risk of spreading resistance in the bacterial world. The message arising from this ‘‘bacterial physiology’’ is that high quality antibiotic prescription is absolutely necessary to reduce the risk of bacterial resistance. Targeted prescription enables eradication of the infection being treated while minimally impacting environmental flora. This is possible since bacterial resistance is low in North European countries where antibiotic prescription has always been specialized. Conversely, countries with very liberal policies regarding prescription of anti-infectives have seen a constant rise in antibiotic resistance. Thus, the epidemiology of bacterial resistance
is constantly evolving worldwide. The current global distribution of enterobacteria, which are carriers of extended-spectrum betalactamase and now carbapenemase, is a major concern [1–3]. This is even more so since resistance to all beta-lactams is often associated with cross-resistance to other antibiotics. This raises the specter of total resistance, sending us back a hundred years, to a time when dying from bacterial infection was commonplace. Pseudomonas aeruginosa is a Gram-negative bacillus of the environment, which is champion of accumulated resistance mechanisms [4]. It is readily present in hospitals, especially in ICUs and may be responsible for infections that are particularly difficult to treat because of its multi-resistance. It is in this context that the Amiens team proposes a new therapeutic solution combining two beta-lactams with synergistic effect [5]. Indeed, when hyper-secretion of cephalosporinase is the predominant resistance mechanism, the inhibitory effect of astreonam on cephalosporinase restores all or part of the activity of cefepime. This latter is the most stable cephalosporin for cephalosporinases. Thus, despite nil or reduced in vitro activity in each of the two antibiotics, this association may counteract the AmpC resistance mechanism. This very specific therapeutic choice proposed by the Amiens team warrants further discussion by a multidisciplinary team involving anesthesiologists, microbiologists and infectious disease physicians. It may well be a rescue solution for when all else fails. The findings of this pilot study require confirmation by a prospective study, which would enable genotypic investigation of the pyocyanic strains involved. Nonetheless, physicians treating multi-resistant infections to P. aeruginosa should be informed of this therapeutic option in their search for appropriate treatment strategy.
References [1] Woerther PL, Burdet C, Chachaty E, Andremont A. Trends in human fecal carriage of extended-spectrum b-lactamases in the community: toward the globalization of CTX-M. Clin Microbiol Rev 2013;26:744–58. [2] Hawkey PM, Jones AM. The changing epidemiology of resistance. J Antimicrob Chemother 2009;64:i3–10. [3] Rogers BA, Aminzadeh Z, Hayashi Y, Paterson DL. Country-to-country transfer of patients and the risk of multi-resistant bacterial infection. Clin Infect Dis 2011;53:49–56.
http://dx.doi.org/10.1016/j.accpm.2015.03.002 2352-5568/ß 2015 Socie´te´ franc¸aise d’anesthe´sie et de re´animation (Sfar). Published by Elsevier Masson SAS. All rights reserved.
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Editorial / Anaesth Crit Care Pain Med 34 (2015) 133–134
[4] Hocquet D, Ple´siat P, Dehecq B, Mariotte P, Talon D, Bertrand X. Nationwide investigation of extended-spectrum beta-lactamases, metallo-beta-lactamases, and extended-spectrum oxacillinases produced by ceftazidime-resistant Pseudomonas aeruginosa strains in France. Antimicrob Agents Chemother 2010;54: 3512–5. [5] Dupont H, Marciniak S, Zogheib E, Mammeric H, Friggeri A, Ammenouche N, et al. Use of aztreonam in association with cefepime for the treatment of nosocomial infections due to multidrug resistant strains of Pseudomonas aeruginosa to b-lactams in ICU patients: a pilot study. Anaesth Crit Care Pain Med 2015.
Pr Benoıˆt Veber Anesthesiology – Critical Care, Mobil Medical Emergency Unit, Rouen University Hospital, 1, rue de Germont, 76031 Rouen, France E-mail address: [email protected] (B. Veber) Available online 1 June 2015
Editorial
Bacterial resistance, the medical challenge of the next 20 years
One of the greatest advances in medicine in the last century was the discovery of antibiotics. Indeed, the genius of Sir Alexander Fleming was the almost simultaneous description of the in vitro bactericidal activity of penicillin on Staphylococcus aureus in 1930 and then the resistance of Staphylococcus to penicillin by secretion of penicillinase. Since that time, the bacterial world has always been one step ahead of the medical world. Thus all pharmacochemistry breakthroughs, allowing prescription of new antibiotics efficient against resistant bacteria, are followed by the appearance of new mechanisms of resistance, which are more or less transferable and epidemic. In fact, the bacterial world is a living world that is simply trying to survive in the environment in which it finds itself. To this end, it boasts two major assets. The first is DNA with strong mutagenic capacity that is able to modify and acquire information of resistance. The second is its strong capacity to spread resistance to daughter bacteria due to its ability to multiply extremely fast. For instance, a colony of Escherichia coli multiplies every 20 minutes, allowing fast genomic adaptation to selection pressure generated by the environment. Furthermore, man lives in equilibrium with the saprophytic bacterial flora of the skin and digestive system leading to coexistence of different bacterial species. These are always balanced with environmental flora. Thus, hospitals with a population of vulnerable patients at high risk of infection are responsible for important antibiotic prescription leading to selection of environmental bacterial flora potentially resistant to prescribed antibiotics. This resistant bacterial flora is able to colonize the gut of our patients. Transfer of information, especially between enterobacteria in the digestive flora via exchange of DNA segments of plasmid or integrating types, increases the risk of spreading resistance in the bacterial world. The message arising from this ‘‘bacterial physiology’’ is that high quality antibiotic prescription is absolutely necessary to reduce the risk of bacterial resistance. Targeted prescription enables eradication of the infection being treated while minimally impacting environmental flora. This is possible since bacterial resistance is low in North European countries where antibiotic prescription has always been specialized. Conversely, countries with very liberal policies regarding prescription of anti-infectives have seen a constant rise in antibiotic resistance. Thus, the epidemiology of bacterial resistance
is constantly evolving worldwide. The current global distribution of enterobacteria, which are carriers of extended-spectrum betalactamase and now carbapenemase, is a major concern [1–3]. This is even more so since resistance to all beta-lactams is often associated with cross-resistance to other antibiotics. This raises the specter of total resistance, sending us back a hundred years, to a time when dying from bacterial infection was commonplace. Pseudomonas aeruginosa is a Gram-negative bacillus of the environment, which is champion of accumulated resistance mechanisms [4]. It is readily present in hospitals, especially in ICUs and may be responsible for infections that are particularly difficult to treat because of its multi-resistance. It is in this context that the Amiens team proposes a new therapeutic solution combining two beta-lactams with synergistic effect [5]. Indeed, when hyper-secretion of cephalosporinase is the predominant resistance mechanism, the inhibitory effect of astreonam on cephalosporinase restores all or part of the activity of cefepime. This latter is the most stable cephalosporin for cephalosporinases. Thus, despite nil or reduced in vitro activity in each of the two antibiotics, this association may counteract the AmpC resistance mechanism. This very specific therapeutic choice proposed by the Amiens team warrants further discussion by a multidisciplinary team involving anesthesiologists, microbiologists and infectious disease physicians. It may well be a rescue solution for when all else fails. The findings of this pilot study require confirmation by a prospective study, which would enable genotypic investigation of the pyocyanic strains involved. Nonetheless, physicians treating multi-resistant infections to P. aeruginosa should be informed of this therapeutic option in their search for appropriate treatment strategy.
References [1] Woerther PL, Burdet C, Chachaty E, Andremont A. Trends in human fecal carriage of extended-spectrum b-lactamases in the community: toward the globalization of CTX-M. Clin Microbiol Rev 2013;26:744–58. [2] Hawkey PM, Jones AM. The changing epidemiology of resistance. J Antimicrob Chemother 2009;64:i3–10. [3] Rogers BA, Aminzadeh Z, Hayashi Y, Paterson DL. Country-to-country transfer of patients and the risk of multi-resistant bacterial infection. Clin Infect Dis 2011;53:49–56.
http://dx.doi.org/10.1016/j.accpm.2015.03.002 2352-5568/ß 2015 Socie´te´ franc¸aise d’anesthe´sie et de re´animation (Sfar). Published by Elsevier Masson SAS. All rights reserved.
134
Editorial / Anaesth Crit Care Pain Med 34 (2015) 133–134
[4] Hocquet D, Ple´siat P, Dehecq B, Mariotte P, Talon D, Bertrand X. Nationwide investigation of extended-spectrum beta-lactamases, metallo-beta-lactamases, and extended-spectrum oxacillinases produced by ceftazidime-resistant Pseudomonas aeruginosa strains in France. Antimicrob Agents Chemother 2010;54: 3512–5. [5] Dupont H, Marciniak S, Zogheib E, Mammeric H, Friggeri A, Ammenouche N, et al. Use of aztreonam in association with cefepime for the treatment of nosocomial infections due to multidrug resistant strains of Pseudomonas aeruginosa to b-lactams in ICU patients: a pilot study. Anaesth Crit Care Pain Med 2015.
Pr Benoıˆt Veber Anesthesiology – Critical Care, Mobil Medical Emergency Unit, Rouen University Hospital, 1, rue de Germont, 76031 Rouen, France E-mail address: [email protected] (B. Veber) Available online 1 June 2015
