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KEY POINTS
Because therapeutic delay has been clearly shown to increase mortality, prompt empiric broad-spectrum antimicrobial therapy is crucial in patients with shock and new organ dysfunction thought secondary to infection.
Overuse of antimicrobials in the ICU is common and is associated with multiple adverse drug reactions, superinfections and the development of antimicrobial resistance; antimicrobial therapy should be tailored as soon as possible and courses of therapy should not be prolonged unnecessarily.
Beta-lactams are the most important antibacterial agents used in the ICU; allergic reactions are the most common adverse effects but are frequently misreported so the risks of such reactions must always be weighed against the importance of these agents for severe bacterial infections.
The aminoglycosides are potent agents against gram-negative bacteria but their utility is limited by frequent misdosing due to concerns of nephrotoxicity; extended dosing intervals can be helpful in maximizing efficacy and minimizing toxicity.
The fluoroquinolones have activity against a variety of bacterial infections in the ICU; they are generally well tolerated but are considered second-line agents for a number of severe sepsis syndromes.
Vancomycin, linezolid, and daptomycin are important agents for resistant gram-positive infections in the ICU. Their utility varies by the site of primary infection.
Azithromycin and doxycycline are particularly useful for atypical bacterial infections in the ICU and are generally well tolerated. Metronidazole and clindamycin are useful primarily for coverage of anaerobic infections in the ICU.
Tigecycline and polymyxin B/colistin are used mainly for resistant gram-negative infections in the ICU; use of the former is limited by lack of potency and the latter is limited by high potential for nephrotoxicity.
The three classes of antifungals used in the ICU are the polyenes, the azoles, and the echinocandins. Polyenes are broad spectrum but nephrotoxic; azoles have variable coverage but resistance can be a problem; echinocandins are excellent anticandidal agents and are generally well tolerated.
The nucleoside analogues are the primary agents used to treat herpes viruses in the ICU; their efficacy is variable and they may cause hematologic and renal toxicity.
The neuraminidase inhibitors are important agents that may improve the outcome of influenza virus infections in the ICU.
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The principles used to guide antimicrobial therapy in all patients can be applied to the critically ill patients, with some modification. Patient characteristics including environmental history, immune status, prior antimicrobial exposure, and prior culture results are essential in determining likely organisms and appropriate empiric therapy. In patients who develop infection after hospital admission, knowledge of common local institutional pathogens and their sensitivity patterns is important. Source identification and control are crucial, although imaging tests may be limited by patient instability and organ failure. As discussed further in the Chapter “Pharmacology in Critical Illness,” the efficacy and toxicity of antimicrobial agents can be profoundly affected by the alterations in tissue perfusion, volume of distribution, serum protein levels, and renal and hepatic function that occur in the critically ill patients.
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