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PRINCIPLES OF ANTIMICROBIAL THERAPY

The discovery and rapid development of targeted antimicrobial agents, beginning in the 1930s, are among the most important scientific developments of 20th-century medicine. These drugs have forever changed the practice of medicine, and antimicrobials remain one of medicine’s most effective and widely used interventions. However, choosing an appropriate antimicrobial can be a complex and difficult task. Optimal antimicrobial use requires appreciation of the complicated interactions between host, organism, and drug. This decision-making process, summarized in Table 39–1, begins with an accurate working diagnosis, based on the patient’s clinical history, physical examination, exposure history, and initial laboratory tests. From this foundation, the clinician must consider the most likely organism(s) and that organism’s likely pattern of antimicrobial susceptibility. This information is considered in the context of numerous patient-specific factors, including age, immune status, relevant comorbidities, site of infection, prior antimicrobial exposure, and microbiology of the patient’s prior infections. Different exposures, based on environment, travel, diet, animal contact, or ill close contacts, may suggest a greater likelihood of certain organisms. The pace and severity of the illness are also important. A severe, rapidly progressive illness should be treated initially with broad-spectrum antimicrobials until a specific etiologic diagnosis is made. A mildly ill ambulatory patient should receive treatment with narrow-spectrum antimicrobials, per national guidelines when available. However, decisions of when not to use antimicrobials are equally important, as unnecessary or additional drugs and longer durations may harm patients. A patient unlikely to have an infection, or with an infection unlikely to benefit from antimicrobials (eg, viral respiratory infection), should be spared the added risk of an adverse reaction.

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Table 39–1. Steps in decision-making for use of antimicrobial agents.
Step Action Example
1 Determine presumptive diagnosis Septic arthritis and osteomyelitis
2 Consider age, preexisting condition, antimicrobial penetration Previously healthy 2-year-old child, bone and joint penetration desired
3 Consider common organisms (for age and site of infection) Staphylococcus aureus, Kingella kingae
4 Consider organism susceptibility Penicillin- or ampicillin-resistant; frequency of MRSA in community
5 Obtain proper cultures and gram stains if clinically possible. Particularly important if the organism or susceptibilities are unpredictable Blood cultures, joint fluid, bone biopsy
6 Initiate empiric therapy based on above considerations, and guidelines if they exist Cefazolin, add vancomycin to cefazolin if seriously ill or MRSA prevalent
7 Modify therapy based on culture results and patient response S aureus isolated. Choose cefazolin or vancomycin based on susceptibility
8 Follow clinical response, consider laboratory responses Interval physical examination, inflammatory markers
9 Change to oral therapy Cephalexin if cefazolin susceptible, anti-MRSA drug if needed based on susceptibility (eg, clindamycin, trimethoprim/sulfamethoxazole, linezolid). Change when afebrile, clinically improving, falling inflammatory markers, able to tolerate oral medications
10 Stop therapy Clinically improved or well-treated minimal duration based on standard of care/guidelines

MRSA, methicillin-resistant Staphylococcus aureus.

Once an appropriate initial antimicrobial is chosen, the clinician must consider ...

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