a Division of Clinical Pharmacology, Department of Medicine and Therapeutics, Level 4, Robert Kilpatrick Clinical Sciences Building, Leicester Royal Infirmary, PO Box 65, Leicester LE2 7LX; b Clinical Microbiology and Public Health Laboratory, Level 5, Sandringham Building, Leicester Royal Infirmary NHS Trust, Leicester LE5 5WW, UK
Sir,
Al-Eidan et al.1 describe how the implementation of an antimicrobial prescribing protocol reduced antibiotic costs, average inpatient stay and treatment failures when treating lower respiratory tract infections (LRTI) in their hospital. They ascribe the lion's share of these benefits to a scoring system used to stratify severity of infection and a correspondingly graded antibiotic regimen based on oral co-amoxiclav, intravenous cefuroxime and intravenous cefuroxime plus erythromycin for moderate, severe and very severe LRTI, respectively.
An alternative explanation is that their adoption of objective criteria to promote the early conversion of parenteral to oral antimicrobial therapy shortened the period of inpatient antibiotic treatment without reducing clinical efficacy. The average duration of intravenous therapy was reduced by 3.6 days, whereas average inpatient stay was reduced by 4.7 days. A Canadian study of levofloxacin monotherapy used analogous algorithms to guide the switch from intravenous to oral levofloxacin in patients with community-acquired pneumonia (CAP).2 Its results were broadly similar. Al-Eidan et al.1 do not comment on treatment following the switch to oral therapy and postdischarge. It is thus unclear whether the length of antibiotic courses was reduced overall.
The authors' use of a single algorithm to cover both infective exacerbations of chronic obstructive pulmonary disease (COPD) and CAP is questionable. Non-pneumonic LRTI should not be treated in the same way as pneumonia.
The prognostic factors used in Al-Eidan et al.'s1 LRTI severity score have been verified for pneumonic, but not non-pneumonic LRTI. The severity of COPD is better evaluated in terms of pre-admission blood gases and lung function tests or if these are unavailable, the patient's clinical state, history of previous hospital admissions and prior antibiotic treatment. It remains important, therefore, to differentiate the conditions clinically.
Surprisingly, no patients with very severe LRTI were admitted to the medical wards during this study. Although the authors1 state that data were collected on all hospitalized patients, no mention is made of whether patients were referred to their Intensive Care Unit either on admission or thereafter. In addition, no details are given of standard exclusions to usual CAP therapy, such as suspected nosocomial pneumonia, aspiration, suppurative complications (abscess or empyema), immunocompromise or possible underlying malignancy. There are no defined criteria for the success or failure of empirical antibiotic therapy and no indications are given for early specialist referral.
Al-Eidan et al.1 attempt to justify their guidelines in terms of healthcare cost savings. Although cost-effectiveness analysis is an important factor in designating best therapy, treatment efficacy and in particular, attempts to prolong the useful life of antibiotics by retarding the development of future resistance are also important. The main factor behind the increasing use of the newer broader spectrum antibiotics in LRTI has been the emergence and spread of penicillin-tolerant/resistant and multidrug-resistant Streptococcus pneumoniae.3 These bacteria commonly have MICs in vitro that exceed the serum levels seen with usual ß-lactam or macrolide regimens.
Concerns have, however, been exaggerated and there has been a general tendency to over-treatment. Notwithstanding an increase in the prevalence of resistant S. pneumoniae, the anticipated increase in clinically observed treatment failures has failed to occur. This observation, combined with the success of ultrashort iv treatment regimens, has led to the suggestion that the breakpoints established for infections such as meningitis, where tissue penetration is borderline, are not relevant to infections in vascular organs, such as lung, where tissue antibiotic levels may be an order of magnitude greater.4 The promotion of newer antibiotics such as the third generation cephalosporins and fluoroquinolones as therapy for LRTI has been associated with increasing S. pneumoniae resistance rates to these drugs and a growing incidence of several resistant nosocomial infections.5,6 Responsible antibiotic prescribing policies are essential to minimize these dangers. The widespread use of co-amoxiclav and cefuroxime, as in Al-Eidan et al.'s1 guideline, has been associated with an increased incidence of pseudomembranous colitis. Remarkably, no mention is made of this complication and one wonders whether this and other complications are incorporated in their calculations of inpatient stay. A better balance of risks and benefits may well lie with protocols based on higher dose amino-penicillins and macrolides, particularly in the UK where the incidence of resistant S. pneumoniae is still low.
There needs to be a paradigm shift in our view of practice guidelines such that they only achieve widespread adoption if appropriate methods have been used to gather all the relevant evidence, including an estimate of complications such as pseudomembranous colitis. Any recommendations must be based on a concrete assessment of evidence from randomized clinical trials appropriately adapted to the local environment and target setting. Only then can we be assured that they are maximizing benefits for current and future patients.
Notes
* Corresponding author. E-mail: GarfieldDrummond{at}msn.com
J Antimicrob Chemother 2000; 46: 640641
References
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Al-Eidan, F. A., McElnay, J. C., Scott, M. G., Kearney, M. P., Corrigan, J. & McConnell, J. B. (2000). Use of a treatment protocol in the management of community-acquired lower respiratory tract infection. Journal of Antimicrobial Chemotherapy 45, 38794.
2
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Marrie, T. J., Lau, C. Y., Wheeler, S. L., Wong, C. J., Vandervoort, M. K. & Feagan, B. G. (2000). A controlled trial of a critical pathway for treatment of community-acquired pneumonia. Journal of the American Medical Association 283, 74955.
3 . Brown, P. D. & Lerner, S. A. (1998). Community-acquired pneumonia. Lancet 352, 1295302.[ISI][Medline]
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Siegel, R. E. (1999). The significance of serum vs. tissue levels of antibiotics in the treatment of penicillin-resistant Streptococcus pneumoniae and community-acquired pneumonia: are we looking in the wrong place? Chest 116, 5358.
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Chen, D. K., McGeer, A., de Azavedo, J. C. & Low, D. E. (1999). Decreased susceptibility of Streptococcus pneumoniae to fluoroquinolones in Canada. New England Journal of Medicine 341, 2339.
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Struelens, M. J. (1998). The epidemiology of antimicrobial resistance in hospital acquired infections: problems and possible solutions. British Medical Journal 317, 6524.