Bloodstream Infections Notes

Learning Objectives

• Identify organisms in a blood culture as true pathogens versus contaminants, guiding appropriate treatment decisions.

• Understand the criteria for diagnosing a catheter-related bloodstream infection (CRBSI), differentiating it from other BSIs.

• Describe antibiotic lock therapy, including its application, benefits, and limitations in managing CRBSIs.

• Optimize the management of Staphylococcus aureus bacteremias (SAB):

  • Select appropriate antibiotics based on susceptibility testing, distinguishing between MSSA and MRSA.

  • Monitor vancomycin levels to achieve an AUC/MIC target of 400-600, ensuring optimal efficacy and minimizing toxicity.

  • Determine the appropriate duration of therapy, typically 14 days for uncomplicated SAB and 4-6 weeks for complicated cases, considering factors like metastatic infection and persistent bacteremia.

  • Conduct a thorough patient work-up, including echocardiograms, to rule out metastatic sites of infection such as infective endocarditis.

• Determine the clinical scenarios where oral antibiotics are appropriate for treating Gram-negative bloodstream infections, considering factors like source control, antibiotic susceptibility, and patient stability.

• Identify patients with uncomplicated bloodstream infections who are candidates for shorter durations of therapy (7 days), balancing efficacy with minimizing antibiotic exposure.

Outline

• Intravascular catheter-related bloodstream infections (BSI):

  • Diagnosis: Use blood cultures from peripheral and catheter sites and culture the catheter tip upon removal.

  • Catheter management: Remove catheters in cases of S. aureus, Pseudomonas, or Candida infections.

  • Lock therapy: Instill high-concentration antibiotics into the catheter lumen to eradicate residual bacteria.

• Staphylococcus aureus bloodstream infection (SAB):

  • Workup for deep-seated infections: Perform echocardiograms and examine any prosthetic materials for infection.

  • Antibiotic selection: Use Beta-lactams (e.g., nafcillin/oxacillin or cefazolin) for MSSA, and vancomycin or daptomycin for MRSA.

  • Duration of therapy: Treat for 14 days in uncomplicated cases, and 4-6 weeks for complicated cases.

• Gram-negative bacteria bloodstream infection:

  • Intravenous (IV) vs. oral antibiotics: Consider oral options for uncomplicated cases with susceptible organisms, ensuring source control and clinical improvement.

  • Duration of therapy: Treat for 7-14 days, shortening to 7 days for uncomplicated cases with prompt clinical response.

Diagnosis of Bloodstream Infections

• Blood cultures are crucial for diagnosing bloodstream infections in patients with systemic signs of infection.

• Collect blood cultures before starting antibiotic therapy to maximize diagnostic accuracy.

• Obtain two sets of blood cultures from separate venipuncture sites to improve sensitivity.

• If a central catheter is in place, collect samples from both the central catheter and a peripheral site to differentiate between CRBSI and other BSIs.

• Differentiate between contaminants and true pathogens by considering factors like clinical context, number of positive cultures, and growth patterns.

Culture Processing Workflow

1. Blood is collected for culture (t=0).

2. Samples are plated for sub-culturing (t=12h).

3. Gram stain is performed to identify the pathogen group (t=24-36h).

4. Pathogen identification is conducted using traditional methods or rapid diagnostic tests like MALDI-TOF.

5. Susceptibility testing is performed to determine pathogen resistance (t=48-72h).

Common Pathogens by Site of Infection

• Oral site: Gram-positive bacteria (Streptococcus spp.), Candida spp.

• Respiratory site (ventilator and lungs): Gram-negative bacteria (Pseudomonas spp., Acinetobacter spp., Enterobacteriaceae), Gram-positive bacteria (Staphylococcus spp.), Fungi (Candida spp., Aspergillus spp.).

• Burn wound site: Gram-negative bacteria (Pseudomonas spp.), Gram-positive bacteria (Staphylococcus spp.), Fungi (Candida spp., Aspergillus spp.).

• Lower reproductive tract: Gram-negative bacteria, Gram-positive bacteria, Fungi (Candida spp., Cryptococcus neoformans).

• Cutaneous site and vascular catheters: Gram-positive and Gram-negative bacteria (Staphylococcus spp.), Candida spp.

• Intra-abdominal site: Gram-negative bacteria (Enterobacteriaceae), Gram-positive bacteria (Enterococcus spp.), Candida spp.

• Urinary site with catheters: Gram-negative bacteria (Pseudomonas spp. and Enterobacteriaceae), Gram-positive bacteria, Candida spp.

Potential Blood Culture Contaminants

• Possible contaminants:

  • Coagulase-negative Staphylococci (Staph epidermidis).

  • Micrococcus spp.

  • Bacillus spp.

  • Corynebacterium spp.

• Treat as a true pathogen:

  • Gram-negative organisms.

  • Fungal organisms.

  • Staphylococcus aureus.

Management Principles of Bloodstream Infections

• Initiate effective empiric antibiotic therapy promptly to reduce morbidity and mortality.

• Base empiric therapy on:

  • Risk factors for drug-resistant organisms (past cultures, healthcare exposure, immune status, local/institutional antibiogram).

  • The most likely source of infection.

  • Culture Gram-stain results.

• Identify the source of infection through clinical assessment and imaging studies.

• Confirm clearance of bacteremia (especially for Gram-positive organisms) with follow-up blood cultures.

• Select targeted/definitive antibiotic therapy based on culture and susceptibility results, considering factors like antibiotic allergies and patient-specific pharmacokinetics.

• Determine the appropriate duration of treatment, considering the pathogen, source, and patient-specific factors.

Intravascular Catheter-Related Bloodstream Infections

• Central Venous Catheters:

  • Terminate near the heart, providing central access for various treatments and monitoring.

  • Peripherally inserted central catheter (PICC): A central line placed in a vein in the arm, offering a less invasive option for central access.

  • Used to administer fluids, blood products, parenteral nutrition, and medications.

  • Used to perform hemodialysis in patients with renal failure.

  • Used to monitor hemodynamic status, especially in the ICU, by measuring central venous pressure.

Microbiology of Catheter-Related Infections

• Coagulase-negative Staphylococci spp. (CoNS).

• Staphylococcus aureus.

• Candida spp.

• Enteric Gram-negative bacilli (Pseudomonas aeruginosa).

Diagnosis of Catheter-Related Infections

• Obtain blood cultures from both the catheter and a peripheral site to compare growth patterns.

• If the catheter is removed, culture the catheter tip to identify colonizing organisms.

• Definitive diagnosis requires:

  • The same organism growing from both a peripheral blood culture and a catheter tip culture, or

  • The same organism growing from a peripheral culture and catheter culture, meeting the criteria for differential time to positivity (i.e., earlier growth in the catheter culture).

Management of Catheter-Related Infections

• Select definitive antibiotic therapy based on culture results, considering antibiotic resistance patterns.

• Catheter removal is recommended for:

  • Staphylococcus aureus.

  • Pseudomonas aeruginosa.

  • Fungi (Candida spp.).

  • Mycobacteria.

Duration of Therapy for Catheter-Related Infections

• Generally 7 to 14 days.

• Exception: Coagulase-negative Staphylococcus spp. AND the line is removed: a duration of 5 to 7 days is recommended.

• Longer durations (4 to 6 weeks) are necessary in cases of:

  • Persistently positive cultures >72 hours after catheter removal, indicating deep-seated infection.

  • Infective endocarditis (or other metastatic infection), requiring prolonged treatment to eradicate the infection.

  • Suppurative thrombophlebitis, necessitating extended antibiotic therapy to resolve the venous inflammation and infection.

Catheter Salvage

• Consider when catheter removal is not feasible or desirable.

• Systemic antibiotics targeting the causative pathogen.

• Antibiotic lock therapy:

  • High concentration of antibiotics is instilled into the lumen of the catheter.

  • Dwells within the lumen when not in use, providing sustained antimicrobial activity.

  • Used for the same duration as systemic antibiotic therapy, supplementing systemic treatment.

  • A variety of antibiotics can be utilized, tailored to the specific pathogen and resistance profile.

Staphylococcus Aureus Bacteremias (SAB)

• Checklist to Success:

  • Optimal antibiotic therapy, guided by susceptibility testing.

  • Identify and manage the source of bacteremia, such as catheter removal or abscess drainage.

  • Rule out metastatic sites of infections through clinical examination and imaging studies.

  • Determine optimal duration of therapy based on disease severity and response to treatment.

  • Infectious disease consultation to optimize management strategies.

Optimal Antibiotic Therapy for SAB

• Methicillin-susceptible Staphylococcus aureus (MSSA):

  • Anti-staphylococcal beta-lactams (nafcillin/oxacillin or cefazolin) are preferred over glycopeptides (vancomycin) due to their superior efficacy.

  • Beta-lactams have more rapid bactericidal activity compared to vancomycin.

  • Cefazolin is often preferred due to its lower toxicity profile.

• Methicillin-resistant Staphylococcus aureus (MRSA):

  • Drugs of choice: vancomycin or daptomycin, both with bactericidal activity against MRSA.

  • Alternatives: ceftaroline, oritavancin/dalbavancin (limited supporting data and should be reserved for specific situations).

Vancomycin Dosing and Monitoring

• Recommend dosing to target an AUC/MIC of 400-600 to optimize efficacy and minimize the risk of nephrotoxicity.

• Recommend a weight-based loading dose, especially in critically ill patients or those with renal dysfunction, to rapidly achieve therapeutic levels.

Bacteremia Source Identification and Management

• Common sources: central venous catheters, skin and soft tissue infections, surgical site infections, and hardware infections.

• Remove the source if able (e.g., remove intravascular catheters, surgical intervention to drain abscesses or debride infected tissue).

• Confirm clearance with follow-up blood cultures; persistent bacteremia could indicate an uncontrolled source.

Metastatic Sites of Infection

• Staphylococcus aureus commonly causes metastatic infections, spreading from the primary site to distant locations.

• Pay special attention to areas with prosthetic material, as these are prone to Staph. aureus colonization and biofilm formation.

• Echocardiograms should be done in all patients to rule out infective endocarditis (IE):

  • Transthoracic echocardiogram (TTE) vs. transesophageal echocardiogram (TEE), with TEE being more sensitive for detecting vegetations, especially in patients with prosthetic valves.

Optimal Duration of Therapy for SAB

• Uncomplicated SAB (14 days of therapy):

  • IE is excluded based on clinical and echocardiographic findings.

  • No prosthetic material is present.

  • Confirmed clearance of bacteremia by day 4 of appropriate antibiotic therapy.

  • Defervesces within 72 hours of initiating effective antibiotic treatment.

  • No evidence of metastatic infection.

• All other cases: at least 4 to 6 weeks of IV antibiotics; the duration is usually driven by the source of infection and/or metastatic sites of infection.

Infectious Disease Consultation

• Improved outcomes have been shown in patients with SAB managed in consultation with an infectious disease specialist.

  • Better adherence to quality measures, such as appropriate antibiotic selection and source control.

  • Reduced in-hospital mortality due to optimized management strategies.

  • Shorter time to discharge, resulting in cost savings and improved patient satisfaction.

Gram-Negative Bacteremias

• Pathogens:

  • Aerobes:

  • Enterobacteriaceae: Escherichia coli, Klebsiella spp., Proteus spp., Serratia spp., Morganella spp., Enterobacter spp., Citrobacter spp.

  • Non-fermenting Gram-negative rods: Pseudomonas aeruginosa, Stenotrophomonas maltophilia, Acinetobacter spp.

  • Anaerobes: Bacteroides spp., Prevotella spp., Fusobacterium spp.

Source of Gram-Negative Infections

• Urinary tract (post-procedural), often associated with catheterization or urinary instrumentation.

• Intra-abdominal (community-acquired, post-surgical), including appendicitis, diverticulitis, and surgical site infections.

• Intravascular catheters, serving as a portal of entry for Gram-negative bacteria.

• Complicated skin and soft tissue infections, such as necrotizing fasciitis and deep abscesses.

• Intravenous drug use, increasing the risk of bloodstream infections from both Gram-positive and Gram-negative organisms.

Management of Gram-Negative Bacteremia

• Effective empiric antibiotic therapy is crucial; mortality significantly increases with increased time to effective antibiotic therapy.

• Risk factor assessment to guide appropriate empiric antibiotic selection, considering factors like recent antibiotic use, healthcare exposure, and immune status.

• Focus on rapid diagnostic tests to identify resistant pathogens earlier, enabling timely de-escalation of antibiotic therapy.

Classification of Gram-Negative Bacteremia

• Uncomplicated gram-negative bacteremia:

  • Adequate source control, such as catheter removal or drainage of abscesses.

  • Source is identified as urinary, intra-abdominal, catheter-related, pneumonia, or SSTI.

  • Not immunocompromised, indicating better host defenses.

  • Clinical improvement in 72 hours (defervescence, hemodynamic stability), suggesting a favorable response to treatment.

Oral Antibiotics for Gram-Negative Bacteremia

• Increasing evidence supports oral antibiotics as definitive therapy for select patients with Gram-negative bacteremia.

• Highly bioavailable antibiotics with optimized dosing:

  • Fluoroquinolones: ciprofloxacin 750mg q 12h, levofloxacin 750mg q 12h, offering broad-spectrum coverage.

  • Sulfamethoxazole/trimethoprim: 5mg/kg q 12h, useful for susceptible organisms.

  • Amoxicillin: 1000mg q 8 hours, effective for certain Gram-negative infections.

  • Amoxicillin/clavulanic acid: 875-1000mg q 8 hours, providing broader coverage including beta-lactamase producers.

  • Cephalexin: 1000mg q 6 hours, suitable for some uncomplicated infections.

Duration of Therapy for Gram-Negative Bacteremia

• Only guideline recommendation is 7 to 14 days (intravascular catheter-related bloodstream infection guideline).

• Recent data suggest 7 days of therapy is appropriate for uncomplicated gram-negative bloodstream infections, balancing efficacy and minimizing antibiotic exposure.

Checklist to Success

• Optimal antibiotic therapy, tailored to the specific pathogen and resistance profile.

• Identify and manage the source of bacteremia through appropriate interventions.

• Rule out metastatic sites of infections with clinical and radiological assessments.

• Determine optimal duration of therapy based on disease severity and response to treatment.

• Infectious disease consultation to optimize management strategies and improve patient outcomes.