Key concepts

An inevitable consequence of exposing microbes to antimicrobials is that some organisms will develop resistance to the antimicrobial.

Antimicrobials are different from other classes of pharmaceuticals because they exert their action on bacteria infecting the host as opposed to acting directly on the host.

Two guiding principles to consider when treating patients with antimicrobials are (a) make the diagnosis and (b) do no harm!

Only bacteria that cause disease should be targeted with antimicrobial therapy, and colonizing flora should be left intact whenever possible.

® Bacterial cultures should be obtained prior to antimicrobial therapy in patients with a systemic inflammatory response, risk factors for antimicrobial resistance, or infections where diagnosis or antimicrobial susceptibility is uncertain.

Drug-specific considerations in antimicrobial selection include the spectrum of activity, effects on nontargeted microbial flora, appropriate dose, pharmacokinetic and pharmacodynamic properties, adverse-effect and drug-interaction profile, and cost.

Empirical therapy should be based on patient- and antimicrobial-specific factors such as the anatomic location of the infection, the likely pathogens associated with the presentation, the potential for adverse effects, and the antimicrobial spectrum of activity.

® Key patient-specific considerations in antimicrobial selection include recent previous antimicrobial exposures, identification of the anatomic location of infection through physical examination and diagnostic imaging, history of drug allergies, organ dysfunction that may affect drug clearance, immunosuppression, pregnancy, and compliance.

O Patient education, de-escalation of antimicrobial therapy based on culture results, monitoring for clinical response and adverse effects, and appropriate duration of therapy are important treatment components.

Inadequate diagnosis resulting in poor initial antimicrobial selection, poor source control, or the development of a new infection with a resistant organism are relatively common causes of antimicrobial failure.

The discovery of antimicrobials is among the greatest medical achievements of the 20th century. Prior to the antimicrobial era, patients who contracted common infectious diseases developed significant morbidity or perished. The discovery of penicillin in 1927, followed by the subsequent discovery of other antimicrobials, contributed to a significant decline in infectious disease-related mortality during the next five decades. However, since 1980, infectious diseases related mortality in the United States has begun to increase, in part owing to increases in antimicrobial resistance.

The discovery of virtually every new class of antimicrobials has occurred in response to the development of bacterial resistance and loss of clinical effectiveness to existing antimicrobials. An inevitable consequence of exposing microbes to antimicrobials is that some organisms will develop resistance to the antimicrobial. Today, there are dozens of antimicrobial classes and hundreds of antimicrobials available for clinical use. However, in many cases, differences in mechanisms of action between antimicrobials are minor, and the microbiologic properties of the agents are similar.

A,n,m,croUa,s are Afferent.from o,„er c,asses of ^„caU beca„se .key exert their action on bacteria infecting the host as opposed to acting directly on the host. Because use of an antimicrobial in one patient affects not only that patient but also other patients if they become infected with resistant bacteria, correct selection, use, and monitoring of clinical response are paramount.

There are two guiding principles to consider when treating patients with antimicrobials: (a) make the correct diagnosis and (b) do no harm! Patients with infections frequently present with signs and symptoms that are nonspecific for infection and may be confused with other noninfectious disease. Not only is it important to determine if a disease process is of infectious origin, but it is also important to determine the specific causative pathogen of the infection. Antimicrobials vary in their ability to inhibit or kill different species of bacteria, or their spectrum of activity. Antimicrobials that kill many different species of bacteria are called broad-spectrum antimicrobials, whereas antimicrobials that kill only a few different species of bacteria are called narrow-spectrum antimicrobials. One might argue that treating everybody with very broad antimicrobial coverage will increase the likelihood that a patient will get better without making a definitive diagnosis. However, counter to this argument is the principle of "Do no harm!" Very broad antimicrobial coverage does increase the likelihood of empirically targeting a causative pathogen; unfortunately, the development of secondary infections caused by selection of antimicrobial-resistant nontargeted pathogens is a common problem. In addition, adverse events are thought to complicate up to 10% of all antimicrobial therapy, and for select agents, the adverse-event rates are similar to classical high-risk medications such as warfarin, digoxin, or insulin.1 Therefore, the overall goal of antimicrobial therapy should be to cure the patient's infection; limit harm by minimizing patient risk for adverse effects, including secondary infections; and limit societal risk from antimicrobial-resistant bacteria.

the most common reasons patients seek medical care. Approximately two-thirds of outpatient antimicrobial use is prescribed for respiratory tract infections, and the Centers for Disease Control and Prevention (CDC) estimate that one-third to one-half of all outpatient antimicrobials are used inappropriately to treat nonbacterial processes.3 However, recent trends in prescribing suggest a modest reduction in antimicrobial use for these infections, suggesting an increased recognition of the negative consequences of antimicrobial use. Prescription of antimicrobials in hospitalized patients is also common because up to one-half of all patients receive at least one antimicrobial during hospitalization. In addition, the CDC estimates that almost 2 million nosocomial or hospital-acquired infections and 90,000 related deaths occur annually.5 Generally nosocomial infections tend be associated with more antimicrobial-resistant strains of bacteria. In recent years, there has been a shift in the etiology of some community-acquired infections. Increasingly, infections caused by antimicrobial-resistant pathogens, traditionally nosocomial in origin, are being identified in ambulatory care settings. Reasons for this change include an aging populace, improvement in the management of chronic comorbid conditions including immunosuppressive conditions, and increases in outpatient management of more debilitated patients. The majority of infections caused by antimicrobial-resistant pathogens in the ambulatory care setting have had recent exposure to some aspect of the health care system, therefore are defined as health care-associated infections. The converging bacterial etiologies and increasing resistance in all health care environments emphasize the need to "make the diagnosis."

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