Old drugs for new bugs
BMJ 2003; 326 doi: https://doi.org/10.1136/bmj.326.7383.235 (Published 01 February 2003) Cite this as: BMJ 2003;326:235All rapid responses
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Older antimicrobials may retain a role in the management of
infections in some clinical settings but new practices may be required for
this to be feasibly implemented.
In microbiology laboratories, isolates are frequently tested for
susceptibility or resistance against the so-called older antimicrobial
agents, regardless of whether the agent has been superceded in clinical
practice.
The susceptibility pattern can sometimes be a useful adjunct to
biochemical reactions for genus or local strain identification. For
example, the most common strains of MRSA encountered in Western Australia
are generally susceptible to Co-trimoxazole & Doxycycline. In vitro
resistance to older antimicobial agents can also be a reliable surrogate
marker for likely in vivo resistance to some newer agents eg Erythromycin
resistance predicts resistance to other macrolides such as Roxithromycin.
Moreover, many laboratories may act pro-actively in the reporting of
resistance & use commentary to qualify its clinical relevance eg high
dose penicillin or amoxycillin is recommended in respiratory tract
infections with "less susceptible" Pneumococci. The aim of this type of
pro-active commentary by the laboratory, is to guide, educate &
support the use of the older antimicrobial in that specific setting.
However, if we are coming into an era where older antimicrobials may have
a "re-birth" of clinical relevance, it may be timely to consider how it
may be possible to optimise & prolong their efficacy this time around,
rather than fall into the same traps which led to their demise &
displacement by newer agents in the first place.
This may require some reassessment as to whether such older agents can be
used singly or whether combinations may be more logical to deter
resistance selection, whether dose size & timing could be improved
over older formulations, whether interactions & adverse effects need
to be carefully reviewed & validated.
Clinical & community demand for the use of older agents may be
necessary if they are to realistically compete with the plethora of new
antimicrobials that persuasively promise to kill anything &
everything.
Laboratories are likely to play a key role in the promotion of their use
& may need to ensure that standardised susceptibility testing,
reporting & resistance surveillance of the older antimicrobial agents
is maintained or re-activated.
Competing interests:
None declared
Competing interests: No competing interests
The reappearence of sensitivity to particular antimicrobials is not a
new phenomenom and from an evolutionary perspective it was expected to
happen, once the selection pressure (i.e. the antimicrobial) was removed.
This phenomenon has been actively brought about in Sweden, where a
national programme of rationalising antimicrobial prescribing brought
about a drop in resistance levels.
Competing interests:
None declared
Competing interests: No competing interests
Old Drugs are more effective
I read with interest the editorial by Silvio Pitlik (1) in the
current issue of the BMJ suggesting that older drugs such as co-
trimoxazole and chloramphenicol have found a new role in the management of
multiply antibiotic-resistant bacteria.
They should, however, also be considered for the treatment of infections
caused by bacteria still sensitive to 'conventional' antibiotics.
Glycopeptides (vancomycin and teicoplanin) are large molecules with poor
diffusing capacity and relatively high MICs for Staphylococci (2) and
clinical trials have demonstrated poor outcomes especially when compared
with beta-lactam antibiotics. (3,4,5)
Other antibiotics such as clindamycin, minocycline and fosfomycin have
been reported to be effective for MRSA, even for difficult infections such
as endocarditis. (6,7,8)
We currently use chloramphenicol, either alone or in combination with
other agents as first line therapy for serious MRSA infections, and have
been encouraged by the results.
Obviously, properly conducted clinical trials are required to assess
effectiveness of any therapy, but funding for large multi-centre trials
using older, patent expired agents would be difficult to obtain unless
driven by national agencies such as NICE or the MRC.
1. Pitlik S. Old drugs for new bugs BMJ 2003 326:236-7
2. Ziglam HM, Finch GC. Limitations of presently available glycopeptides
in the treatment of Gram-positive infection CMI 2001 7 (suppl 4) 53-65
3.Cosgrove SE,Sakoulas G, Perencevich EN, Schwaber J, Karchmer AW,Carmeli
Y. Comparison of mortality associated with methicillin-resistant and
methicillin susceptible Staphylococcus aureus bacteraemia: A meta-analysis
CID 2003 36:53-9
4. Gonzalez C, Rubio M, Romero-Vivas J, Gonzalez M, Picazo JJ. Bacteremic
pneumonia due to Staphylococcus aureus: A comparison of disease caused by
methicillin-resistant and methicillin-susceptible organisms. CID 1999
29:1171-7
5. Calain P, Krause K-H, Vaudaux p, Auckenthaler R, Lew D, Waldvogel F,
Hirschel B. Early termination of a prospective, randomised trial comparing
teicoplanin and flucloxacillin for treating severe staphylococcal
infections. J. Infect.Dis 1987 155;2 187-91
6.Lawlor MT, Sullivan MC, Levitz RE, Quintilani R, Nightingale C.
Treatment of prosthetic valve endocarditis due to methicilin-resistant
Staphylococcus aureus with mincycline J Infect Dis 1990 161:812-4
7. Frank Al, Marchinak JF, Mangat D, Tjhio JT, Kelkar S, Schrekenberger
PC,Quinn JP. Clindamycin treatment of methicillin-resistant Staphylococcus
aureus infections in children Paediatr Infect Dis J 2002 21: 530-4
8. Kono K, Takeda S, Tatara I Arakawa K. Combined therapy with arbekacin
and fosfomycin for methicillin-resistant Staphylococcus aureus Infections.
Japanese J of Antibioitics 1994 47:6 798-803
Competing interests:
None declared
Competing interests: No competing interests