Principles of Therapy

GENERAL PRINCIPLES

• Infections are caused by bacteria, viruses, fungi, or parasites and can involve any organ system.

• Rising antimicrobial resistance is an urgent problem.

• Infectious disease consultation reduces mortality and can aid with diagnosis and management of complicated infectious diseases and monitoring of antimicrobial therapy.¹

DIAGNOSIS

• History and physical examination are critical, particularly for diagnostic dilemmas such as fever of unknown origin (FUO). Eliciting exposures, sexual history, travel history, and recreational activities informs and helps broaden the differential diagnosis.

• Aerobic, anaerobic, fungal, or acid-fast bacilli (AFB) microbiologic cultures should be performed on patient specimens as indicated. The microbiology laboratory should be consulted if fastidious organisms with special growth requirements are suspected to ensure appropriate transport and processing of cultures.

• Gram stain, fungal stain, or AFB stain from potentially infected patient specimens can facilitate rapid presumptive diagnosis and guide empiric antibiotic selection.

• Rapid diagnostic testing (e.g., polymerase chain reaction [PCR]) can provide early identification of an infectious etiologic agent and/or presence of antibiotic resistance genes (e.g., mecA gene).

• Antimicrobial susceptibility testing of cultures facilitates selection of antimicrobial agents.

TREATMENT

• Choice of initial antimicrobial therapy

๎ Overuse of antimicrobials has led to the emergence of antimicrobial-resistant organisms, some with few treatment options. Therefore, the first question to ask is, “Does an infection exist that needs to be treated?”

๎ Empiric antimicrobial therapy should be directed against the most likely infecting organism(s).

๎ Knowing antimicrobial susceptibility patterns is essential in selecting empiric therapy. Antibiograms provide important insight into trends in local antimicrobial resistance.

๎ Drug allergies, previous microbiologic cultures, and prior antimicrobial exposure help guide antimicrobial selection.

๎ De-escalate to an antimicrobial regimen with the narrowest spectrum of activity once the infectious

etiologic agent is identified and susceptibility data are available.

• Timing for the initiation of antimicrobial therapy

๎ In acute clinical scenarios, empiric therapy should begin immediately, ideally after appropriate microbiologic cultures have been obtained. Emergent therapy is indicated in patients with sepsis, meningitis, or rapidly progressive necrotizing infections, and in those with febrile neutropenia or asplenia.

๎ In clinically stable patients, empiric antimicrobials can be withheld pending further evaluation, allowing for more targeted therapy.

• Antimicrobial route and dosing administration

๎ Patients with serious infections should receive IV antimicrobial agents. Oral therapy is acceptable in less urgent circumstances if adequate drug concentrations can be achieved at the site of infection.

๎ Renal and hepatic function should guide antimicrobial dosing regimens. Some antimicrobials require serum drug monitoring and dosing weight.

๎ Always assess for drug-drug interactions before starting treatment to avoid adverse events and ensure effectiveness of therapy.

• Assessment of outcomes on antimicrobial therapy

๎ If there is concern for potential treatment failure, ask the following questions:

■ Is the isolated organism the etiologic agent? Is there a superinfection?

■ Has an appropriate antimicrobial regimen been selected? Is there treatment adherence?

■ Are adequate concentrations of the antimicrobial achieved at the site of infection?

■ Has adequate source control been accomplished?

• Duration of therapy

๎ Use the shortest duration of therapy for the infection identified.

๎ Treatment of acute uncomplicated infections should be continued until the patient is afebrile and clinically well, usually for a minimum of 72 hours.

๎ Some infections (e.g., endocarditis, septic arthritis, osteomyelitis) require prolonged therapy.

SPECIAL CONSIDERATIONS

• Immunosuppression

๎ In patients living with HIV/AIDS, solid organ or hematopoietic stem cell transplant (HSCT) recipients, patients undergoing chemotherapy, and patients receiving glucocorticoids or other immune-modulating agents, consider opportunistic infections. Neutropenic patients require broader empiric antimicrobial therapy.

• Pregnancy or postpartum

๎ There are no Class A antimicrobials. Penicillins and cephalosporins (Class B) are frequently used. Tetracyclines and fluoroquinolones are contraindicated. Sulfonamides and aminoglycosides should not be used if alternative agents are available.

๎ Many antimicrobials are excreted in breast milk and should be used with caution in breast-feeding women.