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EDITORIALS: Silvio Pitlik Old drugs for new bugs BMJ 2003; 326: 235-236 [Full text]

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This is to be expected

Onisillos Sekkides   (31 January 2003)

Preserving the usefulness of older antimicrobials

maria theresa yates   (4 February 2003)

Old Drugs are more effective

F Kate Gould   (6 February 2003)

This is to be expected 31 January 2003
Onisillos Sekkides, Medical Writer/Editor TW10 6UA Send response to journal: Re: This is to be expected	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
Preserving the usefulness of older antimicrobials 4 February 2003
maria theresa yates, medical microbiologist perth, western australia Send response to journal: Re: Preserving the usefulness of older antimicrobials	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susceptibility or resistance against the so-called older antimicrobial agents, regardless of whether the agent has been superceded in clinical practice.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
Old Drugs are more effective 6 February 2003
F Kate Gould, Consultant Microbiologist Freeman Hospital Newcastle upon Tyne UK NE7 7DN Send response to journal: Re: 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