Antibiotic Efficacy in Respiratory Tract Infections - Application of Pharmacokinetic and Pharmacodynamic Principles
Michael R Jacobs, MD Director, Clinical Microbiology, University Hospitals of Cleveland and
Professor of Pathology, Case Western Reserve University
Respiratory infections are the most frequent reason for physician visits, accounting for over 44 million visits in the US in 2003, and the most frequent group of diseases for which antibiotics are prescribed, according to the National Ambulatory Medical Care Survey (NAMCS).1 These infections include pneumonia, which remains among the top 10 causes of death in the US, acute exacerbations of chronic bronchitis (AECB), acute sinusitis, and acute otitis media (AOM). While most respiratory infections are viral in origin, primary and secondary bacterial infections are the reasons why antibiotics are prescribed, as these account for a significant amount of morbidity and mortality. Streptococcus pneumoniae, the most frequently isolated bacterial pathogen in pneumonia, otitis, and sinusitis and the one least likely to resolve untreated, is estimated to cause seven million cases of otitis media, six million cases of sinusitis, 500,000 cases of pneumonia, 60,000 cases of bacteremia, and 2,000 cases of meningitis every year in the US.2–7 In addition, other bacterial pathogens such as Haemophilus influenzae, Moraxella catarrhalis, Staphylococcus aureus, Streptococcus pyogenes, Legionella pneumophila, Chlamydophila (Chlamydia) pneumoniae, and Mycoplasma pneumoniae, among others, all contribute to respiratory infection-associated disease and disability. As most respiratory infections are treated empirically, especially in the out-patient setting, it is important that antibiotics prescribed are active against the most frequent pathogens in the condition being treated.This article addresses the issues associated with optimizing the choice of antibiotics to treat these infections.
Incidence of Respiratory Tract Infections
In the US, 20 million cases of bacterial sinusitis are estimated to occur every year. It is the fifth most common diagnosis for which an antibiotic is prescribed and accounted for 9% of pediatric and 21% of adult antibiotic prescriptions in 2002.3 The most common bacterial species associated with sinusitis in adults are S. pneumoniae (20–43%), H. influenzae (22–35%), other streptococcal species (3–9%), anaerobes (0–9%), M. catarrhalis (2–10%), S. aureus (0–8%), and other species (4%).3 In children, again, S. pneumoniae and H. influenzae predominate, accounting for a combined 40–50%, but other species are more prevalent than in adults, with M. catarrhalis (15–20%) equal in prevalence to H. influenzae.3
It is estimated that there are two to four million cases of pneumonia per year in the US. S. pneumoniae accounts for up to two-thirds of bacteremic pneumonia cases, with non-typeable H. influenzae, M pneumoniae, C. pneumoniae, S. aureus, S. pyogenes, Neisseria meningitidis, M. catarrhalis, Klebsiella pneumoniae and other gram-negative species, L. pneumophila and others accounting for the rest.8,9
Acute otitis media is the most commonly treated bacterial infection in children, accounting for nearly 30 million medical office visits and half of all pediatric antibiotic prescriptions in the US every year.10 It most often occurs between ages six months and three years and usually follows a viral respiratory infection. As in the other respiratory infections, S. pneumoniae (25–50% of cases) and H. influenzae (23–67%) predominate, with M. catarrhalis (12–15%) also commonly isolated.11
Need for Appropriate Treatment of Respiratory Infections
Given the high prevalence of respiratory infections and the high transmissibility and broad spectrum of pathogens, it is important to maintain a healthy armamentarium of antibacterial agents. Part of that maintenance is minimizing the development of drug resistance, a large part of which is achieved by choosing agents appropriate to the infection being treated.Tailoring chemotherapy to a known pathogen with a known susceptibility profile is ideal. Unfortunately, isolating the causative agent before beginning treatment is often difficult or impractical and generally impossible after treatment has begun.8 Using a drug that is not clinically active against the target pathogen has consequences beyond not curing the infection in question. Inappropriately active agents may be partially active against other bacteria in the body while not affecting the infection for which it was prescribed, and may additionally select for resistant bacteria among the normal flora, leading to a potentially more complex infection at a later date. With upwards of 150 million antibiotic prescriptions given in the US every year,12 there are myriad opportunities for under- and over-treatment of bacterial infections and a need to address efficacy and appropriateness of drug and pathogen combinations.
