Rapid Responses to:
|
|
Rapid Responses: Rapid Responses published:
-
![[Read Rapid Response]](/icons/misc/sectionDOWN.gif)
Darwin, Lamarck, or Intelligent Design ?
- L Sam Lewis (2 August 2007)
-
Re: Effect of antibiotic prescribing
- David Mitchell (3 September 2007)
-
Formulary Restriction to curb antibiotic resistance
- S Kapoor (4 September 2007)
-
Leave Primary care alone
- Andrew C Barnes (5 September 2007)
-
Re: Effect of antibiotic prescribing
- David Mitchell (6 September 2007)
|
|
|||
|
L Sam Lewis, GP Surgery, Newport, Pembrokeshire, SA42 0TJ
Send response to journal:
|
We already know that "UK general practitioners are strongly encouraged to reduce antibiotic prescribing to minimise the risk of antibiotic resistance" Chung et al. now add that "Prescribing amoxicillin to a child in general practice doubles the risk of recovering a lactamase encoding resistance element from that child's throat two weeks later" What ? Bacteria have the ability to suddenly trot out resistance exactly when it is needed ?? How intelligent is that ! Chung et al agree that "Although a strong correlation between antibiotic prescribing and resistance might seem inevitable from a Darwinian perspective, the relation is complex.4 Actual resistance levels will depend on the pattern of antibiotic use, the specific interaction between bacterium and drug, the potential for transmission, and the stage the country is at in the evolution of resistance." But all they have shown is that Amoxicillin kills the sensitive bacteria. Two weeks later the FREQUENCY of sensitive bacteria remaining in the population is much reduced. Any resistant bacteria now dominate. If the bacterial population is sampled, cultured, and 4 and 2 specific individuals replated ( as Chung et al. did ) you will not be surprised to find that resistant bacteria are much more likely to be found. In no sense has it been shown that Amoxicillin prescribing causes resistance. In particular their Lamarckian Conclusion that "Amoxicillin prescribed in primary care is .. sufficient to sustain a high level of antibiotic resistance in the population " is unjustified. They have simply demonstrated that Amoxicillin works. Competing interests: None declared |
|||
|
|
|||
|
David Mitchell, Microbiologist Trinity College, Dublin
Send response to journal:
|
From this paper and the others cited by it antibiotic resistance is clearly a complex issue in need of further work. The incidence of ampicillin resistance in this group seems a little on the high side. The UK data usually put this resistance rate at ~20% but given that small children are frequent users of antibiotics this figure looks reasonable. If we assume that the H influenenza is the causative organism for the clinical condition being treated then given the data here it seems highly likely that there would have been a high rate of clinical failure. Curiously the clinical failures rates are not given here. If H influenza was not the causative organism in these cases then what we are seeing is a bystander effect. This happens whenever we use antibiotics to treat an infection: resistant but non pathogenic organims are selected and this effect cannot be avoided. If this mobile element is in fact responsible for the resistance we would not expect resistance to non beta lactam antibiotics to increase. This would seem to have been a useful control here to strenghten the argument that this element is indeed responsible but one that has either not been done or reported. The statement that these elements are carried with minimal metabolic cost is not supported by the data. While it looks like it maybe a reasonable presumption, it may or may not in fact be correct. This is relatively simple to test: a comparison of the growth curves with and without the resistance element under various conditions is within the capability of most microbiology departments. While I am inclined to agree with the suggestions of the paper given what is known about antibiotic resistance in the community any recommendations based on these sugestions will - in my view - need considerable additional work as there are many other factors invovled here - particularly the use of antibiotics in vetinary paratice. Competing interests: None declared |
|||
|
|
|||
|
S Kapoor, M.D. University of Illinois at Chicago, Chicago, IL
Send response to journal:
|
The article by Chung et al is highly interesting and suggests that the short term effect of amoxicillin is transitory in the individual child but sufficient to sustain a high level of antibiotic resistance in the population. (1) The unnecessary over prescription of antibiotics such as amoxicillin is one of the primary reasons for this trend. In fact studies suggest that in more than 50% of cases antibiotic use is absolutely unnecessary. One method to overcome this overuse of antibiotics is to enforce formulary restriction of antibiotics. Formulary restriction has been shown to effectively reduce resistance rates in the past. (2) Other beneficial effects of formulary restriction include reduced expenditure on medications as well as reduced rates of antibiotic related side effects such Clostridium difficile associated diarrhea. (3) Automatic pharmacy referrals to infectious disease specialists for prior approval in cases where the indication is not exactly clear can further strengthen the system. (4) Another alternative is antibiotic cycling. This would involve rotating amoxicillin with another antibiotic such as a cephalosporin to decrease the development of resistance. (5) Clearly a multidimensional approach involving all these strategies is necessary to overcome the growing epidemic of antibiotic resistance. 1. Chung A, Perera R, Brueggemann AB, Elamin AE, Harnden A, Mayon- White R, et al. Effect of antibiotic prescribing on antibiotic resistance in individual children in primary care: prospective cohort study. BMJ 2007; Sep 1;335(7617):429. 2. Bassetti M, Di Biagio A, Rebesco B, Amalfitano ME, Topal J, Bassetti D. The effect of formulary restriction in the use of antibiotics in an Italian hospital. Eur J Clin Pharmacol 2001; Sep;57(6-7):529-34. 3. Climo MW, Israel DS, Wong ES, Williams D, Coudron P, Markowitz SM. Hospital-wide restriction of clindamycin: effect on the incidence of Clostridium difficile-associated diarrhea and cost. Ann Intern Med 1998; Jun 15;128(12 Pt 1):989-95. 4. White AC,Jr, Atmar RL, Wilson J, Cate TR, Stager CE, Greenberg SB. Effects of requiring prior authorization for selected antimicrobials: expenditures, susceptibilities, and clinical outcomes. Clin Infect Dis 1997; Aug;25(2):230-9. 5. Pujol M, Gudiol F. Evidence for antibiotic cycling in control of resistance. Curr Opin Infect Dis 2001; Dec;14(6):711-5. Competing interests: None declared |
|||
|
|
|||
|
Andrew C Barnes, Civilian Medical Practitioner British Forces Germany
Send response to journal:
|
The paper from Chung et al represents a very narrow view of the bigger picture. I do not believe that primary care needs to singled out as the main culprit in emerging antibiotic resistance. Our patients are generally healthy and well. Use of antibiotics in the chronically ill, sedentary and immunocompromised patient is logically much more likely to encourage resistance. Everybody knows that MRSA is sourced from hospitals. I had the privilege of working as a flying doctor in the author’s home country, and was witness to the frequent use of parenteral third generation cephalosporins as a substitute for inadequate hygiene in indigenous communities. For over fifty years, antibiotics were administered in large quantities to animals as a food supplement to encourage growth, and they still are in developing countries. Farm animals account for roughly one third of antibiotic usage. Our juniors are obsessed about not prescribing antibiotics, following on from articles such as this one. Proponents of Evidence Based Madness neglect clinical acumen and experience, and my viewpoint is that the pendulum has swung too far. As a junior, I lost a baby to overwhelming streptococcal sepsis, which I am sure I would spot now. Doctors bury, rather than advertise, their mistakes. So, I am still not going to feel guilty about prescribing amoxicillin on the hunch of a secondary infection, any more than I will when the vet does the same for my domestic cat. Competing interests: None declared |
|||
|
|
|||
|
David Mitchell, Microbiologist Trinity College
Send response to journal:
|
Dr Barnes in a post above this one makes an excellent point. The relative contributions of the community, hospitals and vetinary practice and possibly others to the problem of antibiotic resistance is simply not known. He may be (or may not) be incorrect to assert that hospitals are the source of MRSA. This particular resistance gene appears to have been transfered from a coagulase negative staph (S. sceuri) at some point in the past. I dont think the date has been settled yet but it is likely to preceed the introduction of methacillin by a considerable margin. It presently seems likely that this transfer occurred before hospitals (and possibly even humans) existed. What has happened since is that selection pressure has been applied to Staph aureus and that MRSA has been selected for. It seems likely that the hospitals were the source of most of this selection pressure and that it has spread outside these places since. The central question is where control of the selection pressure is best applied secondary to acceptable medical practice. It is obvious that if we stopped useding beta lactams for a century of so MRSA would probably fall under the radar again. This is unlikely to be acceptable to the population at large. Similarly if we stopped using antibiotics in food the selection pressure would be reduced considerably. Think of VRE for an example of where this usage has caused problems outside its original remit. However given the genuine growth enhancing effects of antibiotics in many animals raised for food this use is unlikely to cease in the immediate future. At the moment we have virtually no idea of the relative contributions of any of the major sectors of antibiotic use to the problem of resistance. It seems sensible (to me anyway) to attempt to gather some usable data on this area before proposing potentially major changes to current practice. Competing interests: None declared |
|||