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Salt Lake City, UT
Dr. Dean is Adjunct Professor of Medicine, University of Utah, and has received honoraria during the past 5 years from Pfizer, Abbott, Ortho-McNeil, Bristol Myers Squibb, Roche, Glaxo Smith Kline, Bayer, Elan, Chiron, and Merck. Dr. Dean has also served on advisory boards for Roche, Bayer, GlaxoSmithKline, and Bristol-Myers Squibb. Unrestricted grants for research have come to the Deseret Foundation, Salt Lake City, under Dr. Dean’s name from Roche, Pfizer, and Bristol-Myers Squibb.
Correspondence to: Nathan C. Dean, MD, FCCP, Intermountain Health Care, 333 South Ninth East, Salt Lake City, UT 84102; e-mail: slndean{at}ihc.com
Streptococcus pneumoniae is the most common pathogen isolated from patients with community-acquired pneumonia,1 2 and also causes the most deaths.3 Resistance to multiple antibiotics has been rising among pneumococcal isolates over the past 20 years, leading to treatment failures and increased costs.4 5 6 Studies repeatedly have linked antibiotic consumption to antibiotic resistance, with the greatest resistance observed in noninvasive isolates from children. Children may be vectors for resistant pneumococci, given evidence for transmission of strains within families.7 Antibiotics not prescribed for younger children (doxycycline and fluoroquinolones) have been slower to develop resistance than macrolides and ß-lactams used to treat childhood infections.8
In this issue of CHEST (see page 519), Waterer et al report increasing susceptibility to penicillin among noninvasive isolates of S pneumoniae from Memphis, TN, 1996 to 2001. Among children, susceptibility increased from 22 to 44%; in adults, susceptibility increased from 22 to 55%. Importantly, the proportion of isolates with high-level resistance (minimum inhibitory concentration [MIC] 
4 µg/mL, linked with increased mortality in ß-lactam–treated patients9
) decreased among adults from 39.7 to 10.3%. Concurrently, Memphis antimicrobial prescription data from the National Ambulatory Medical Care Survey reported less consumption of ß- lactams. While temporal association cannot prove causality, reductions in antibiotic consumption have often been followed by increased susceptibility.10
11
This report is consistent with the observation that increased pneumococcal susceptibility to penicillin followed decreased antibiotic consumption in Iceland.12
Iceland decreased antibiotic use through professional and public education, as well as discontinuation of government payment for antibiotic prescriptions.
Waterer et al also report that erythromycin susceptibility decreased from 61 to 33% among noninvasive, oxacillin-resistant isolates from adults. Macrolide prescribing was common throughout the study period. Increased macrolide use has been followed by decreased macrolide susceptibility in multiple reports worldwide.13 14 15 The opposite trends in susceptibility for erythromycin vs clindamycin are striking. Active drug efflux apparently was increasing at the same time that ribosomal target site modification resistance was decreasing. The explanation for this discordance is not known.
Levofloxacin susceptibility was unchanged at 97% of isolates between 1996 and 2001 despite a sixfold increase in prescribing. However, Chen et al8
linked increased quinolone prescribing with decreased quinolone susceptibility in Canada. Ho et al16
reported similar findings from Hong Kong. Microbiologically documented clinical failures with levofloxacin have been reported in invasive pneumococcal disease.4
Empiric use of any quinolone should be avoided if a patient has previously received a quinolone within 3 months.4
The Centers for Disease Control and Prevention recommend that quinolones only be used for pneumococcal disease in adults for the following reasons: (1) after failure of another treatment regimen, (2) allergy to alternative agents, or (3) documented infection with a pneumococcus whose MIC is 4 µg/mL.17
When a quinolone is prescribed for pneumococcal disease, the most active agent against this pathogen should be used.18
Treatment failures in invasive pneumococcal disease have been reported for macrolides, less-active fluoroquinolones (levofloxacin, ofloxacin, and ciprofloxacin), and some ß-lactams (cefazolin, cefuroxime, ceftazidime, and ticarcillin).6
There have been no reports of bacteriological failure with penicillins active against resistant strains (high-dose penicillin, ampicillin/amoxicillin, and ceftriaxone or cefotaxime).6
Resistance to penicillin is caused by alterations in the penicillin-binding protein, and can be overcome by using higher doses of more active agents. Less-active cephalosporins have been associated with resistance more than aminopenicillins.19
Pallares et al20
reported effectiveness of ceftriaxone, 1 g/d, or cefotaxime, 1.5 g q8h, in the treatment of invasive pneumococcal disease (26% with MICs > 0.5 µg/mL) in 185 adults. Among 522 episodes of nonmeningeal pneumococcal disease in a region plagued by pneumococcal resistance, no isolate could be found with a MIC to ceftriaxone/cefotaxime 4 µg/mL. These data support ceftriaxone, cefotaxime, or high-dose ampicillin/amoxicillin combined with a macrolide for empiric therapy of moderate-to-severe community-acquired pneumonia.
What must we do to increase pneumococcal susceptibility to antimicrobial drugs? Prescribing the most active antimicrobial agent in optimum doses to treat the pneumococcus is a good start. Dead bugs don’t mutate. In addition, physicians should only prescribe antimicrobials for bacterial disease processes where randomized studies have shown treatment benefit. Studies of acute bronchitis, as well as "lower respiratory tract infection," show no benefit of antibiotic treatment.21 22 Among immunocompetent individuals, bacterial infections of the lower airway, and even mild infections of the lung parenchyma, are self-limited in most cases. The practice of treating purulent sputum in acute bronchitis or purulent nasal discharge in rhinosinusitis must be eliminated.23 24 Similarly, antibiotics should not be prescribed for aspiration pneumonitis,25 or acute exacerbations of chronic bronchitis that do not fulfill the three criteria of Anthonisen et al.26 Public and patient education about appropriate antibiotic use likely decreases demand for antibiotics. Advertising, news stories, health fairs, educational handouts, and physician education have been associated with a 10% compounded yearly reduction in antibiotic use among Intermountain Health Care outpatients since 1999 (Eric Cannon, PharmD; personal communication; February 2003).
Combating the pneumococcus has been termed a hundred years’ war.27 The dispatch of Waterer et al from the Memphis front suggests that we do not have to surrender.
References
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