What is the appropriate antimicrobial therapy for suspected or confirmed bacterial infections, considering host-pathogen interactions?

From the Guidelines

The appropriate antimicrobial therapy for suspected or confirmed bacterial infections, considering host-pathogen interactions, should be guided by the most recent and highest quality evidence, which recommends a targeted approach based on the likely pathogen, infection site, and host factors. Initial empiric therapy should cover the most probable pathogens while awaiting culture results. For community-acquired intra-abdominal infections of mild-to-moderate severity, the use of ticarcillin-clavulanate, cefoxitin, ertapenem, moxifloxacin, or tigecycline as single-agent therapy or combinations of metronidazole with cefazolin, cefuroxime, ceftriaxone, cefotaxime, levofloxacin, or ciprofloxacin are preferable to regimens with substantial anti-Pseudomonal activity 1.

Key Considerations

• The choice of antimicrobial therapy should be based on the likely pathogens involved, with consideration of local resistance patterns 1.
• Host factors, including age, pregnancy status, renal/hepatic function, and immunocompromise, require dosage adjustments and should be taken into account when selecting antimicrobial therapy.
• Antimicrobial stewardship principles should guide therapy, including appropriate duration (typically 5-7 days for most infections), route of administration (switching from IV to oral when clinically improved), and consideration of local resistance patterns.

Pathogen-Directed Therapy

• For Streptococcus infections, penicillin 2–4 MU q 4–6 h IV or clindamycin 600–900 mg / kg every 8 h IV may be used, with vancomycin, linezolid, daptomycin, or quinupristin–dalfopristin as alternatives for patients with severe penicillin hypersensitivity 1.
• For Staphylococcus aureus infections, nafcillin 1–2 g every 4 h IV, oxacillin 1–2 g every 4 h IV, cefazolin 1 g every 8 h IV, or vancomycin 30 mg / kg / day in two divided doses IV may be used, with clindamycin 600–900 mg / kg every 8 h IV as an alternative 1.
• For Clostridium infections, clindamycin 600–900 mg / kg every 8 h IV or penicillin 2–4 MU every 4–6 h IV may be used 1.

Culture and Susceptibility Testing

• Routine aerobic and anaerobic cultures from lower-risk patients with community-acquired infection are considered optional, but may be of value in detecting epidemiological changes in the resistance patterns of pathogens associated with community-acquired intra-abdominal infection and in guiding follow-up oral therapy 1.
• For higher-risk patients, cultures from the site of infection should be routinely obtained, particularly in patients with prior antibiotic exposure, who are more likely to harbor resistant pathogens 1.

From the FDA Drug Label

To reduce the development of drug-resistant bacteria and maintain the effectiveness of cefazolin for injection and other antibacterial drugs, cefazolin for injection should be used only to treat or prevent infections that are proven or strongly suspected to be caused by susceptible bacteria When culture and susceptibility information are available, they should be considered in selecting or modifying antibacterial therapy. In the absence of such data, local epidemiology and susceptibility patterns may contribute to the empiric selection of therapy. To reduce the development of drug-resistant bacteria and maintain the effectiveness of cephalexin capsules, cephalexin for oral suspension, cephalexin tablets, and other antibacterial drugs, cephalexin capsules, cephalexin for oral suspension, and cephalexin tablets should be used only to treat or prevent infections that are proven or strongly suspected to be caused by susceptible bacteria When culture and susceptibility information are available, they should be considered in selecting or modifying antibacterial therapy. In the absence of such data, local epidemiology and susceptibility patterns may contribute to the empiric selection of therapy. To reduce the development of drug-resistant bacteria and maintain the effectiveness of Vancomycin Hydrochloride for Injection, USP and other antibacterial drugs, Vancomycin Hydrochloride for Injection, USP should be used only to treat or prevent infections that are proven or strongly suspected to be caused by susceptible bacteria When culture and susceptibility information are available, they should be considered in selecting or modifying antibacterial therapy. In the absence of such data, local epidemiology and susceptibility patterns may contribute to the empiric selection of therapy.

The appropriate antimicrobial therapy for suspected or confirmed bacterial infections, considering host-pathogen interactions, is to use antimicrobial drugs such as cefazolin 2, cephalexin 3, or vancomycin 4 only to treat or prevent infections that are proven or strongly suspected to be caused by susceptible bacteria.

• Key considerations include:
  • Using culture and susceptibility information to select or modify antibacterial therapy
  • Considering local epidemiology and susceptibility patterns when culture and susceptibility information are not available
  • Discontinuing prophylactic administration of antimicrobial drugs within a 24-hour period after the surgical procedure, or continuing for 3 to 5 days in certain cases
• Main goals are to:
  • Reduce the development of drug-resistant bacteria
  • Maintain the effectiveness of antimicrobial drugs
  • Select appropriate therapy based on susceptibility information or local epidemiology and susceptibility patterns.

From the Research

Host-Pathogen Interactions and Antimicrobial Therapy

• The choice of antimicrobial therapy for suspected or confirmed bacterial infections depends on various factors, including the severity of the infection, the source of the infection, and the patient's individual characteristics 5, 6.
• Rapid initiation of antibiotic treatment is crucial in patients with severe infections such as septic shock and bacterial meningitis, but may not be as important for other infectious syndromes 5.
• For patients presenting with suspected bacterial infections, withholding antibiotic therapy until diagnostic results are available and a diagnosis has been established (e.g. by 4-8 hours) seems acceptable in most cases unless septic shock or bacterial meningitis are suspected 5.

Empirical Antimicrobial Therapy

• Empirical antimicrobial therapy is often used in patients admitted to Intensive Care Units (ICUs), but the microbiological confirmation of the infection can influence the duration of treatment 7.
• The use of broad-spectrum antibiotics can lead to the development of antibiotic-resistant bacteria, and therefore, it is essential to use narrow-spectrum antibiotics whenever possible 8, 6.
• The choice of empirical antimicrobial therapy should be based on the patient's individual characteristics, the suspected source of the infection, and the local epidemiology of antibiotic-resistant bacteria 6.

Specific Antimicrobial Agents

• Cefazolin has been shown to be effective as empiric therapy in hemodialysis-related infections, with achievable blood concentrations that are above the minimum inhibitory concentration breakpoint for susceptible organisms 9.
• Ceftaroline fosamil is a new cephalosporin that has been authorized for the treatment of community-acquired pneumonia and serious infections of the skin and soft tissues, but its use should be reserved for cases where other antibiotics are not effective or are contraindicated 8.
• Vancomycin is a broad-spectrum antibiotic that should be reserved for confirmed resistant organisms, due to the increasing incidence of vancomycin-resistant bacteria 9.

Considerations for Antimicrobial Therapy

• The use of antimicrobial agents should be guided by the principles of antimicrobial stewardship, which includes obtaining an accurate diagnosis of infection, understanding the difference between empiric and definitive therapy, and identifying opportunities to switch to narrow-spectrum, cost-effective oral agents for the shortest duration necessary 6.
• The adverse effects of antimicrobial agents on the host should be considered, including the risk of developing antibiotic-resistant bacteria, and the potential for haematological and renal adverse effects 8, 6.