Could chloramphenicol be used against ESKAPE pathogens? A review of in vitro data in the literature from the 21st century

Abstract

The widespread use of antibiotics has been associated with the emergence of antimicrobial resistance among bacteria. ‘ESKAPE’ (Enterococcus faecium, Staphylococcus aureus, Klebsiella pneumoniae, Acintobacter baumannii, Pseudomonas aeruginosa and Enterobacter spp.) pathogens play a major role in the rapidly changing scenario of antimicrobial resistance in the 21st century. Chloramphenicol is a broad spectrum antibiotic that was abandoned in developed countries due to its association with fatal aplastic anemia. However, it is still widely used in the developing world. In light of the emerging problem of multi-drug resistant pathogens, its role should be reassessed. Our paper reviews in vitro data on the activity of chloramphenicol against ESKAPE pathogens. Susceptibility patterns for Gram-positives were good, although less favorable for Gram-negatives. However, in combination with colistin, chloramphenicol was found to have synergistic activity. The risk-benefit related to chloramphenicol toxicity has not been analyzed. Therefore, extra precautions should be taken when prescribing this agent.

Keywords::

• antimicrobials
• chloramphenicol
• combination therapy
• ESKAPE pathogens
• resistance

Authors' contributions

All the authors were actively involved in the collection, analysis and interpretation of the data.

Financial & competing interests disclosure

This study was supported in part by funding from the Ministry of Health (RF 2009–1526402) and Ricerca Corrente IRCCS. Čivljak R received honoraria as a speaker for Pliva, Pfizer, Sanofi Aventis. Giannella M received honoraria as speaker for Pfizer, Novartis, AstraZeneca. Petrosillo N received honoraria as speaker for Pfizer, Astellas, Sanofi Aventis, Wyeth, GlaxoSmithKline, Merck Sharp & Dohme, Novartis, Carefusion, Johnson & Johnson, Janssen Cilag and Bristol-Myers Squibb. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.

No writing assistance was utilized in the production of this manuscript.

Key issues

• Multidrug-resistant (MDR) organisms continue to spread leading to an increase in morbidity and mortality worldwide, especially in healthcare settings.

• ESKAPE pathogens are a subgroup of MDR organisms responsible for most of these threatening infections.

• Chloramphenicol is an old antibiotic with activity against Gram-positives, Gram-negatives and anaerobia. During the last decades, its use has been limited to poor resources countries, due to the advent of less toxic and newer molecules.

• As occurred for other abandoned antimicrobials (i.e., polymyxins, fosfomycin), we hypothesize a role of chloramphenicol as a rediscovered antibiotic, to use in particular situations of limited pharmacological options.

• In vitro analysis of studies published from 2000 until nowadays involving chloramphenicol susceptibility testing against ESKAPE bacteria have shown a good susceptibility pattern for Gram-positives, with mean susceptibility rate of >80% for Enterococcus faecium and 74% for methicillin-resistant Staphylococcus aureus.

• Regarding Gram-negatives, the susceptibility patterns are less favorable with a mean susceptibility rate of 43% for Klebsiella pneumoniae, <20% for Acinetobacter baumannii and 13% for Pseudomonas aeruginosa. Concerning Enterobacter spp. in a limited series of studies, the susceptibility ranges from 20% to >90%.

• Studies reporting drug combinations including chloramphenicol are old; however, interestingly the combination colistin and chloramphenicol was found to have a synergistic activity against Gram-negatives.

• In the next years, performing chloramphenicol susceptibility testing on MDR organisms, especially for Gram-negatives, could be a first key step to better evaluate its wise use in clinical setting waiting for new and effective antibiotics.

Notes