Treatment of Bacteremia with Zosyn (Piperacillin/Tazobactam)
Piperacillin/tazobactam (Zosyn) is an effective and appropriate treatment for bacteremia, particularly when polymicrobial infection or gram-negative pathogens (including Pseudomonas aeruginosa) are suspected, but should be avoided if the causative organism has reduced susceptibility (MIC ≥32 mg/L) due to significantly increased mortality risk. 1
Empiric Use in Bacteremia
Piperacillin/tazobactam provides broad-spectrum coverage against gram-positive, gram-negative aerobic bacteria, and anaerobes, making it suitable for empiric therapy when the source and pathogen are unknown 2
Standard dosing is 3.375 g IV every 6-8 hours (or 4.5 g every 6-8 hours for severe infections), with the piperacillin component dosed at 60-75 mg/kg/dose in pediatric patients 2
Clinical efficacy has been demonstrated in bacteremia with overall cure rates of 67/73 (92%) in evaluable cases, though failures occurred primarily with staphylococcal species 3
When to Use Piperacillin/Tazobactam for Bacteremia
Appropriate scenarios include:
Severe intra-abdominal infections with secondary bacteremia, where it covers mixed aerobic-anaerobic flora 2
Necrotizing skin and soft tissue infections with bacteremia, as part of combination therapy with vancomycin for broad empiric coverage 2
Febrile neutropenia with bacteremia, where piperacillin/tazobactam plus amikacin was significantly more effective than ceftazidime plus amikacin 4, 5
Pseudomonas aeruginosa bacteremia in critically ill patients, combined with either a fluoroquinolone or aminoglycoside to prevent inappropriate initial therapy 2
Community-acquired pneumonia with bacteremia requiring ICU admission, as part of combination therapy 2
Critical Limitations and When NOT to Use
Do not use piperacillin/tazobactam monotherapy if:
The Pseudomonas isolate has MIC ≥32 mg/L (reported as "susceptible" but with reduced susceptibility) - this is associated with 85.7% mortality versus 22.2% with alternative agents (P=0.004) 1
ESBL-producing Enterobacteriaceae are documented or highly suspected in unstable patients - carbapenems are preferred despite some controversy about piperacillin/tazobactam use in stable patients 2
Carbapenem-resistant Enterobacteriaceae (CRE) are suspected - newer agents like meropenem-vaborbactam or ceftazidime-avibactam are preferred 2
AmpC-producing organisms are identified - piperacillin/tazobactam lacks reliable activity 6
Combination Therapy Considerations
For septic shock with bacteremia, combination therapy (piperacillin/tazobactam plus fluoroquinolone or aminoglycoside) should be used initially for patients with mortality risk >25%, then de-escalated within the first few days based on clinical response 2
For Pseudomonas bacteremia, always use combination therapy initially (piperacillin/tazobactam plus ciprofloxacin, levofloxacin, or aminoglycoside) until susceptibilities are known 2
Avoid routine combination therapy for neutropenic bacteremia unless septic shock is present 2
Duration of Therapy
For catheter-related bloodstream infections, remove the catheter and treat for 7-14 days after catheter removal 2
For complicated intra-abdominal infections with bacteremia, 3-5 days after adequate source control is reasonable if clinical improvement occurs 2
Continue therapy until fever resolves for 48-72 hours and signs of systemic illness improve 2
Monitor procalcitonin levels to guide antimicrobial discontinuation in severe infections 2
De-escalation Strategy
Once culture and susceptibility results are available:
Narrow to targeted single-agent therapy if the organism is susceptible and the patient is clinically improving 2
Switch to oral fluoroquinolone (if susceptible) for step-down therapy in stable patients with bacteremia of urinary tract source 2
Discontinue combination therapy within the first few days in response to clinical improvement 2
Common Pitfalls to Avoid
Do not rely solely on "susceptible" reporting - specifically check the MIC value for Pseudomonas, as MIC ≥32 mg/L predicts treatment failure despite being within the susceptible range 1
Do not use as monotherapy for severe septic shock - combination therapy improves outcomes in patients with high mortality risk 2
Do not continue empiric broad-spectrum therapy beyond 5-7 days without reassessing for uncontrolled source or treatment failure 2
Do not forget to add metronidazole if using piperacillin/tazobactam for anaerobic coverage is questionable, though this is rarely necessary as piperacillin/tazobactam has inherent anaerobic activity 2