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The clinical impact is still being debated -- An update on antibiotic resistance in community-acquired pneumonia.

Article Excerpt
Byline: Sarah Augustine, MD and Louis B. Rice, MD

Abstract: Over the past 2 decades, the bacterial species that cause community-acquired pneumonia have remained relatively constant, but their susceptibilities to antimicrobial agents have changed considerably. In particular, important changes in the susceptibility of Streptococcus pneumoniae and Staphylococcus aureus are influencing prescribing practices. Resistance to beta-lactam and macrolide antibiotics has been associated with a shift toward the use of fluoroquinolones, despite insufficient evidence that such resistance affects clinical outcomes. In a rare reversal of resistance trends, the widespread use of the 7-valent conjugate pneumococcal vaccine has dramatically reduced rates of invasive and resistant pneumococcal infections. The rapid dissemination of methicillin-resistant S aureus (MRSA) in the community, along with case reports of severe and necrotizing pneumonia caused by these strains, has increased concern that coverage for MRSA should be added to empirical regimens. (J Respir Dis. 2007;28(11):489-499) key words: Antibiotic resistance, MRSA, Community-acquired pneumonia, DRSP

Respiratory infections continue to be major causes of morbidity and mortality. Community-acquired respiratory infections account for approximately 100 million office visits and 3 million emergency department (ED) visits annually, with the diagnosis of community-acquired pneumonia (CAP) accounting for a third of these visits.1,2

Hospitalization is required in about 20% of cases of community-acquired respiratory infections at a cost approaching $8 billion a year.2 CAP is associated with 50,000 deaths per year in the United States, ranking it as the leading cause of infection-related death and the sixth most common cause of death overall.3,4

Several recent studies have demonstrated the importance of adequate empirical antimicrobial therapy and improved outcomes in both hospital-acquired pneumonia and CAP.5,6 While bacteria remain the most common causes identified in CAP, in 50% of cases, no causal pathogen is found despite aggressive testing.

The inability to promptly identify causative agents combined with the importance of early effective therapy forces providers to institute broad-spectrum empirical coverage of a range of potential pathogens when the clinical diagnosis of CAP is established. Emerging resistance in common respiratory pathogens complicates therapeutic choices, requiring that practitioners know the local prevalence of resistance and understand the impact that resistance mechanisms have on the clinical efficacy of different classes of antimicrobial agents.

In this article, we will focus on the impact of emerging antimicrobial resistance in Streptococcus pneumoniae and Staphylococcus aureus on therapeutic choices for the treatment of CAP. Other bacterial pathogens, while important to consider when determining therapeutic regimens, have not undergone the dynamic susceptibility changes observed in S pneumoniae and S aureus.

Understanding antimicrobial resistance

It is estimated that 20% of all antibiotic prescriptions for adults in the United States are written for upper respiratory tract infections, half of which are likely to be nonbacterial in origin. As a result, enormous selective pressure is placed on the bacteria that constitute normal colonizing flora, leading to emergence of resistance in previously susceptible flora and promoting colonization by resistant pathogenic clones. The profound impact of this selective pressure is recognized by the most recent guidelines for the treatment of CAP put forth by the Infectious Diseases Society of America (IDSA) and the American Thoracic Society (ATS), which place great emphasis on previous antimicrobial therapy in determining appropriate therapeutic regimens.7

Defining the level of susceptibility of a bacterial strain to a given antibiotic is a relatively straightforward process involving in vitro testing using broth or agar media to grow the bacteria. However, translating this level of susceptibility to a designation of clinical sensitivity or resistance is a more nuanced process and is performed chiefly by advisory and regulatory agencies. In the United States, these functions are performed by the Clinical Laboratory Standards Institute (CLSI) and the FDA.8 In making these translations, the advisory and regulatory groups rely heavily on the principles of pharmacokinetics and pharmocodynamics.9-12

Pharmacokinetics takes into account absorption, distribution, metabolism, and elimination properties of a given drug and uses measures such as the area under the serum concentration versus time curve (AUC), the maximum plasma concentration, and the amount of time the effective drug concentrations persist. Pharmacodynamics takes into account the relationship between the achievable drug concentration at the site of infection and the antimicrobial activity of the drug as reflected by the minimal inhibitory concentration (MIC).8,12 An MIC that might indicate resistance in the cerebrospinal fluid (where drug concentrations are difficult to achieve) could fall within the sensitive range in the urinary tract (where many antimicrobial agents are concentrated).11,12

When used for recommending therapeutic dosing regimens, pharmacodynamic analyses also con-sider the antimicrobial killing kinetics of a...