What are the recommendations for microbiological diagnosis and empirical antibiotic therapy in sepsis?

Microbiological Diagnosis and Empirical Antibiotic Therapy in Sepsis

Appropriate microbiological cultures, including at least two sets of blood cultures (aerobic and anaerobic), must be obtained before starting antimicrobial therapy in patients with suspected sepsis or septic shock, provided this does not cause a significant delay (>45 minutes) in antibiotic administration. 1

Microbiological Diagnosis

Blood Culture Collection

• Obtain at least two sets of blood cultures (both aerobic and anaerobic bottles) before initiating antimicrobial therapy 1
• Draw one set percutaneously and one through each vascular access device, unless the device was recently (<48 hours) inserted 1
• Blood cultures should be collected without delaying antibiotic administration beyond one hour from sepsis recognition 1
• Blood culture positivity is significantly reduced when samples are collected after antibiotic administration (50.6% before antibiotics vs. 27.7% during antibiotics) 2

Additional Diagnostic Tests

• Sample fluid or tissue from the suspected site of infection whenever possible and clinically justifiable 1
• Examine sampled fluid or tissue by Gram stain, culture, and antibiotic susceptibility testing 1
• Consider 1,3-β-D-glucan assay, mannan, and anti-mannan antibody assays when invasive candidiasis is in the differential diagnosis 1
• Perform prompt imaging studies to confirm potential sources of infection 1
• Multiplex PCR can serve as an adjunct to conventional blood culture, potentially identifying additional pathogens that blood cultures might miss 3

Empirical Antibiotic Therapy

Timing and Initial Selection

• Administer IV antimicrobials as soon as possible and within one hour of recognizing sepsis or septic shock 1, 4
• Use broad-spectrum therapy with one or more antimicrobials active against all likely pathogens (bacterial, fungal, or viral) 1
• Select antibiotics that penetrate adequately into the presumed source of infection 1, 4

Combination Therapy Recommendations

• For septic shock, use empiric combination therapy (at least two antibiotics from different classes) targeting the most likely bacterial pathogens 1, 4
• For respiratory failure with septic shock, use a combination of a broad-spectrum beta-lactam and either an aminoglycoside or fluoroquinolone when Pseudomonas aeruginosa is suspected 1, 4
• For septic shock from Streptococcus pneumoniae bacteremia, use a combination of a beta-lactam and a macrolide 1, 4
• For neutropenic patients with sepsis, use combination empirical therapy 1, 4

Antibiotic Duration and De-escalation

• Limit empiric combination therapy to no more than 3-5 days 1, 5
• Reassess antimicrobial regimen daily for potential de-escalation 1
• Narrow therapy once pathogen identification and sensitivities are established and/or adequate clinical improvement is noted 1
• Typical treatment duration is 7-10 days; longer courses may be necessary for patients with slow clinical response, undrainable infection sites, Staphylococcus aureus bacteremia, or certain fungal and viral infections 1, 5

Optimization Strategies

• Optimize antibiotic dosing based on pharmacokinetic/pharmacodynamic principles and specific drug properties 1, 4
• Consider loading doses regardless of organ dysfunction 6
• Consider extended or continuous infusion of beta-lactams to achieve therapeutic levels 6
• Use low procalcitonin levels or similar biomarkers to guide discontinuation of empiric antibiotics in patients initially suspected of sepsis but with no subsequent evidence of infection 1, 7

Source Control

• Drain or debride the source of infection whenever possible 1
• Remove any foreign body or device that may potentially be the source of infection 1
• Implement source control measures as soon as basic resuscitation measures and empiric anti-infective therapy have been instituted 1

Common Pitfalls and Caveats

• Delaying blood cultures until after antibiotic administration significantly reduces pathogen detection (both Gram-positive and Gram-negative) 2
• Failure to obtain adequate samples from the suspected site of infection can lead to incomplete microbiological diagnosis 1
• Continuing broad-spectrum antibiotics for too long promotes antimicrobial resistance 6, 7
• Not reassessing the need for antibiotics daily can lead to unnecessary prolonged therapy 1
• Inadequate source control can result in persistent infection despite appropriate antibiotic therapy 1, 5