Patient Considerations in Antimicrobial Selection

® 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, pregnancy or breast-feeding status, organ dysfunction that may affect drug clearance, immunosuppression, compliance, and the severity of illness (see Table 69-2).

Host Factors

Host factors can help to ensure selection of the most appropriate antimicrobial agent. Age is an important factor in antimicrobial selection. With regard to dose and interval, renal and hepatic function varies with age. Populations with diminished renal function include neonates and the elderly. Hepatic function in the neonate is not fully developed, and drugs that are metabolized or eliminated by this route may produce adverse effects. For example, sulfonamides and ceftriaxone may compete with bilirubin for binding sites and may result in hyperbilirubinemia and kernicterus. Gastric acidity also depends on age; the elderly and children younger than 3 years of age tend to be achlorhydric. Drugs that need an acidic environment (e.g., ketoconazole) are not well absorbed, and those whose absorption is enhanced in an alkaline environment will have increased concentrations (e.g., penicillin G).

Disruption of host defenses owing to IV catheters, indwelling Foley catheters, burns, trauma, surgery, and increased gastric pH (secondary to antacids, H2 blockers, and proton pump inhibitors) may place patients at higher risk for infection. Breaks in and entry into the skin provide a route for infection because the natural barrier of the skin is disrupted. Increased gastric pH can allow for bacterial overgrowth and has been associated with an increased risk of pneumonia.18

Recognizing the presumed site of infection and most common pathogens associated with the infectious source should guide antimicrobial choice, dose, and route of administration. For example, community-acquired pneumonia is caused most commonly by S. pneumoniae, E. coli is the primary cause of uncomplicated UTIs, and staphylococci and streptococci are implicated most frequently in skin and skin-structure infections (e.g., cellulitis).

Patients with a history of recent antimicrobial use may have altered normal flora or harbor resistant organisms. If a patient develops a new infection while on therapy, fails therapy, or has received antimicrobials recently, it is prudent to prescribe a different class of antimicrobial because resistance is likely. Previous hospitalization or health care utilization (e.g., residing in a nursing home, hemodialysis, and outpatient antimicrobial therapy) are risk factors for the acquisition of nosocomial pathogens, which are often resistant organisms.

Antimicrobial allergies are some of the most common drug-related allergies reported and have significant potential to cause adverse events. In particular, penicillin-related allergy is common and can be problematic because there is an approximately 4% cross-reactivity with cephalosporins as well as carbapenems.19,20 In general, a patient's medical history should be reviewed to determine the offending ^-lactam and nature of the allergic reaction. In some cases, patients with mild or nonimmunolo-gic reactions may receive a ^-lactam antimicrobial with low cross-reactive potential. However, patients with a history of physical findings consistent with IgE-mediated reactions such as anaphylaxis, urticaria, or bronchospasm should not be administered any type of ^-lactam antimicrobial, including cephalosporins, unless there are no other alternatives. Administration of potentially cross-reactive agents in this situation should occur only under controlled conditions, and some patients may need to undergo desensitization. If the specific medical history relating to a reported allergy cannot be obtained, the patient should be assumed to have had an IgE-mediated reaction and should be managed in a similar manner.

Renal and/or hepatic function should be considered in every patient prior to initiation of antimicrobial therapy. In general, most antimicrobials undergo renal elimination and exhibit decreased clearance with diminished renal function, and dosing ad-

justments are found readily in the literature. In contrast, dosing adjustments for an timicrobials that are not eliminated renally are less well documented. Failure to adjust the antimicrobial dose or interval may result in drug accumulation and an increase in adverse effects.

Concomitant administration of other medications may influence the selection of the antimicrobial, dose, and monitoring. Medications that are commonly associated with drug interactions include, but are not limited to, warfarin, rifampin, phenytoin, digoxin, theophylline, multivalent cations (e.g., calcium, magnesium, and zinc), and sucralfate. Drug interactions between antimicrobials and other medications may occur via the cytochrome P-450 system, protein-binding displacement, and alteration of vitamin K-producing bacteria. Interactions may result in increased concentrations of one or both agents, increasing the risk of adverse effects or additive toxicity. A key consideration in selecting antimicrobial regimens starts with obtaining a good patient medical and drug history, recognizing drug-specific adverse-event characteristics, and anticipating potential problems proactively. If it is necessary to use an antimicrobial with a relatively high incidence of adverse effects, informing patients of the risks and benefits of therapy, as well as what to do if an adverse effect occurs, may improve patient compliance and may facilitate patient safety.

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