Old drugs for new bugs

BMJ 2003; 326 doi: http://dx.doi.org/10.1136/bmj.326.7383.235 (Published 01 February 2003) Cite this as: BMJ 2003;326:235

Anecdotes suggest that some bacteria have lost their resistance to older antibiotics

  1. Silvio Pitlik (spitlik{at}clalit.org.il)
  1. Department of Medicine and Infectious Diseases, Rabin Medical Center, 49100 Petah Tiqva, Israel

    Recent reports have lent support to the potential use of previous generation antibacterial drugs to treat infections caused by new resistant bacteria. The Morbidity and Mortality Weekly Report recently described two isolates from the United States of vancomycin resistant Staphylococcus aureus with a minimum inhibitory concentration≥32 μg/ml, both of which were found to be sensitive in vitro to co-trimoxazole as well as to other older antimicrobials. 1 2 Co-trimoxazole was successfully used to treat one of these patients.1 Unpublished data from our institution and elsewhere3 show that in the last 15 years isolates of methicillin resistant S aureus (MRSA) have progressively, and by now almost universally, become susceptible to co-trimoxazole. Preliminary data indicate that this drug can be used as an alternative to vancomycin to treat infections due to MRSA4 and include a case report about co-trimoxazole being used successfully to treat a patient with endocarditis that failed to respond to linezolid.5

    Chloramphenicol, a drug introduced 50 years ago and essentially abandoned in the past three decades, has been reintroduced recently to treat severe infections caused by vancomycin resistant enterococci.6 A report from India describes the re-emergence of susceptibility to chloramphenicol in Salmonella typhi isolates that are increasingly resistant to quinolones and β lactams.7 The authors suggest reintroducing this drug to treat typhoid fever.

    In a recent report from France, Stein and Raoult used colistin, an old and rarely used antibiotic, to treat bone infections caused by a strain of Pseudomonas aeruginosa with resistance to all other antibiotics tested.8 The same drug has been used to treat infections caused by multiresistant strains of Acinetobacter baumannii.9 Sulbactam, a drug introduced in the early 1980s, is increasingly being used for the same purpose.10 As an alternative to third generation cephalosporins and vancomycin, high doses of penicillin are being proposed to treat pneumococcal infections caused by strains with intermediate levels of penicillin resistance (minimum inhibitory concentration 4–8 μg/ml).11

    Despite extensive research the pace of development of antibacterial drugs has not kept up with the increase in bacterial resistance. As more and more organisms develop resistance, concern is growing that we may be approaching the end of the antibiotic era. The intensive use and excessive abuse of antibiotics have resulted in the selection of bacteria that are resistant to many and sometimes all antibiotics. For unclear reasons, these multiresistant organisms either retain or regain susceptibility to certain antimicrobials.

    Measures to counter the threat of rapidly escalating antimicrobial resistance include surveillance of susceptibility to and consumption of antibiotics, rational use of antibiotics, better compliance with measures to control infection, and increasing development and use of vaccines.

    Are we reverting to the pre-antibiotic era or advancing into the post-antibiotic era? One of the crucial questions is whether the above mentioned examples will remain anecdotal or whether a real chance exists for the strategic use of forgotten drugs on a large enough scale to affect clinical management.

    The recovery of sensitivity to specific antimicrobials by pathogenic bacteria is a complex issue. Two important factors determine rates of resistant bacteria in a specific community—the “human” factor, which is the amount of antimicrobials used, and the “biological” factor, which is the burden that the resistance encoding genes impose on the fitness of the bacteria.12

    The impact of either the discontinuation or the reintroduction of a specific drug on the rate of resistance will differ for various microorganisms. In addition to the information obtained from mathematical models of population dynamics,12 continuous surveillance of in vitro susceptibility will inform us about the effect of reintroducing older drugs. In some instances, resistance could rapidly re-emerge owing to the presence of low rates of resistant genes in a population that once was predominantly resistant. In the future, older antimicrobials will be relied on more and more, either as isolated “no other choice” options or as part of a programmed policy of antibiotic cycling.


    • Competing interests None declared.


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