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Another reason to limit antibiotic use?
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Countless articles and many pages of Infectious Disease News have discussed the reasons and consequences of overuse of antibiotics.
Perhaps chief among the consequences of antibiotic overuse is the development of bacterial resistance, which is well known to occur with frequent antibiotic use. Added cost to the health care system may be another reason, although antibiotics as a class are typically not among the most expensive medications, especially when older antibiotics, available generically, are used. While adverse effects or toxicity should be considered when assessing the use of any drug, again this may not be given extensive thought with many antibiotics, as most antibiotics, in general, are relatively safe and have a wide therapeutic margin. Newly published data, however, suggest that adverse effects from antibiotics may deserve more attention.
Extent of use
When reviewing the published literature on the extent of use of systemic antibiotics in both children and adults, major themes on appropriateness of use and methods to decrease use are found.
Several recently published studies are commonly referred to in this context. The National Ambulatory Medical Care Survey was used in 1992 to assess antibiotic prescribing practices for children given a diagnosis of common cold, upper respiratory tract infection, or bronchitis (Nyquist et al). This study found that antibiotics were prescribed to 44% of children with common colds, 46% with upper respiratory tract infections, and 75% with bronchitis.
Using the National Ambulatory Medical Care Survey and the National Hospital Ambulatory Medical Care Survey in 1995-2003, other researchers sought to evaluate rates of antibiotic prescribing and testing for group A, beta-hemolytic streptococci in children aged 3 to 17 years with sore throat (Linder et al). These researchers found that physicians prescribed antibiotics for 53% of an estimated 7.3 million annual visits for sore throat, exceeding the expected rate of 15% to 36% of group A, beta-hemolytic streptococci presence in children with sore throat. Testing for group A, beta-hemolytic streptococci was performed in 53% of visits and in 51% of visits at which an antibiotic was prescribed. Other surveys have found similar results of extensive antibiotic use.
Data from the National Ambulatory Medical Care Survey in 1998 were used to evaluate antibiotic use for children and adults with respiratory tract infections (Gonzales et al). In this study, antibiotic use greater than the expected rate of bacterial pathogen infection amounted to 22.6 million of all antibiotics prescribed for acute respiratory tract infections. The diagnoses accounting for most of this excess use were upper respiratory tract infection, pharyngitis, and bronchitis.
Guidelines
Clinicians reading this column are likely familiar with the available published guidelines for many of the common infectious illnesses seen in ambulatory pediatric practice. These guidelines can be useful to assist clinicians in the appropriateness of diagnosis and use of antibiotics for these common illnesses. A series of guidelines on the diagnosis and appropriate use of antibiotics for common pediatric infections was published by the American Academy of Pediatrics in Pediatrics in January of 1998 as a supplement. These principles of judicious antibiotic use for common pediatric infections outline important diagnostic criteria and assist in defining the role for appropriate use of antibiotics. Specific guidelines on sinusitis were additionally published in 2001 (Pediatrics. 2001;108:798-808). Guidelines on acute otitis media were published in 2004 (Pediatrics. 2004;113:1451-1465).
These newly published data come from researchers of the CDC who sought to characterize emergency department ED visits from drug-related adverse events from systemic antibiotic use in the United States (Shehab et al).
Data collected in 2004 to 2006 from the National Electronic Injury Surveillance System-Cooperative Adverse Drug Event Surveillance project were used.
This project, sponsored by the CDC, U.S. Consumer Product Safety Commission, and the FDA, is a national stratified probability sample of 63 hospitals. At these institutions every ED visit is reviewed to identify drug-related adverse effects diagnosed by a physician. National estimates of outpatient prescription visits were obtained from the National Ambulatory Medical Care Survey and the National Hospital Ambulatory Medical Care Survey, both of which are national sample surveys. Adults and children were evaluated in this study. During the three-year study period between 2004 and 2006, 6,614 cases were identified, translating to a national estimate of 142,505 ED visits because of a systemic antibiotic-associated adverse effect. This represented 19.3% of all ED visits for a drug-related adverse event. Hospitalization due to the adverse effect occurred in 6.1%. Children accounted for 25.9% of the total ED visits due to antibiotics. The estimated rate of ED visits due to an antibiotic adverse effect was highest in the younger than 1-year age group (15.9 ED visits/10,000 outpatient prescription visits).
Most (78.7%) adverse effects due to antibiotics were classified as allergic. Specific antibiotic classes were evaluated, with penicillins and cephalosporins accounting for nearly one-half of the estimated ED visits. Sulfonamides and clindamycin accounted for the highest rates of ED visits due to adverse effects. Sulfonamides were associated with a significantly higher rate of moderate-severe allergic reactions (defined as anaphylaxis, angioedema, erythema multiforme, exfoliative dermatitis, facial-pharyngeal-genital edema, hypersensitivity vasculitis, red man syndrome, respiratory distress or arrest, serum sickness, or Stevens-Johnson syndrome). Mild allergic reaction rates (defined as dermatitis, drug eruption, erythema, flushing, localized edema, pruritis, rash, rash morbilliform, and urticaria), however, were similar among penicillins, sulfonamides, and clindamycin, but higher than all other antibiotic classes combined. Gastrointestinal adverse effect rates were highest with clindamycin, although this rate was not significantly higher than any other antibiotic class.
It is interesting that the rate of adverse effects due to amoxicillin or penicillin was significantly higher than that attributable to amoxicillin-clavulanate. Data from this study are unique in that they provide useful information from a large national evaluation of drug adverse effects specific to the use of systemic antibiotics. This study assessed antibiotic use and adverse effects in the pediatric and adult populations, and although specific uses and rates by age and antibiotic class are not available, it is noteworthy that over one-quarter (37,000 visits) of all estimated ED visits attributable to antibiotic-associated adverse effects occurred in infants and children 14 years of age and younger.
Conclusions
The decision process involved in the clinical use of antibiotics for common ambulatory infectious diseases is complex, including diagnostic accuracy, parental pressure and desire, perceived need, time available per patient, among many other factors. New data now suggest that the potential for adverse effects from these antibiotics should perhaps be given heightened consideration. While commonly prescribed systemic antibiotics are generally safe to use, adverse effects may be more common and clinically more significant than previously perceived. Although most allergic reactions to antibiotics may not be serious, they can commonly result in visits to an emergency department, as has been shown.
Additionally, it is possible, and perhaps likely, that patients experiencing such allergic reactions are then labeled as “allergic,” thus limiting (probably unnecessarily) the use of good, effective antibiotics in specific patients. Studies have shown than most claiming an allergy to an antibiotic do not harbor antibiotic-specific IgE antibodies. As much of the cause of common respiratory tract infections is virally induced, the potential for harm from antibiotic use (along with the potential for bacterial resistance, cost, etc.) should give clinicians pause when contemplating the prescription of an antibiotic for a patient.
For more information:
- Shehab N, et al. Emergency department visits for antibiotic-associated adverse events. Clin Infect Dis. 2008;47:735-743
- Nyquist AC, et al. Antibiotic prescribing for children with colds, upper respiratory tract infections, and bronchitis. JAMA. 1998;279:875-877
- Linder JA, et al. Antibiotic treatment of children with sore throat. JAMA. 2005;294:2315-2322
- Gonzales R, et al. Excessive antibiotic use for acute respiratory infections in the United States. Clin Infect Dis .2001;33:757-762
Edward Bell, PharmD, is a professor of Pharmacy Practice at Drake University College of Pharmacy, Blank Children's Hospital in Des Moines, Iowa.