In an adult with intra‑abdominal infection receiving piperacillin‑tazobactam, who develops a new fever on day 8, what is the appropriate next management?

Management of New Fever on Day 8 of Piperacillin-Tazobactam for Intra-Abdominal Infection

Immediately obtain CT imaging of the abdomen and pelvis with IV contrast to identify persistent or recurrent intra-abdominal infection requiring additional source control, while continuing current antibiotics during the investigation. 1

Diagnostic Workup Priority

Patients with fever beyond 5-7 days of antibiotic treatment warrant diagnostic investigation to determine whether additional surgical intervention is necessary or if antimicrobial treatment has failed. 1

Imaging and Source Control Assessment

• CT of the abdomen is the most accurate method to diagnose ongoing or recurrent intra-abdominal infection and should be performed urgently 1
• Look specifically for:
  • Undrained abscesses or fluid collections 1
  • Anastomotic leaks or bowel perforations 1
  • Organ-space infections 1
  • Signs of persistent peritoneal contamination 1

Alternative Infection Sources to Exclude

Beyond intra-abdominal pathology, systematically evaluate for: 1

• Nosocomial pneumonia (chest imaging, sputum cultures) 1
• Catheter-associated urinary tract infection (urinalysis, urine culture) 1
• C. difficile colitis (stool PCR testing, even without diarrhea) 1
• Venous thrombosis or pulmonary embolism (D-dimer, Doppler ultrasound, CT angiography as indicated) 1
• Surgical site infections (wound examination) 1

Antibiotic Management During Investigation

Continue piperacillin-tazobactam while the diagnostic workup proceeds, particularly if the patient manifests signs of sepsis or organ dysfunction. 1

When to Broaden Antimicrobial Coverage

If imaging confirms persistent or new intra-abdominal infection after 8 days of therapy, broaden to meropenem 1g IV every 8 hours (or every 6 hours by extended infusion for septic shock) to cover healthcare-associated organisms including ESBL-producing pathogens and resistant gram-negatives. 1, 2, 3

The rationale for escalation: 1

• Healthcare-associated infections developing after 5-7 days typically involve more resistant organisms 1
• Piperacillin-tazobactam activity against ESBL producers is controversial 1
• Carbapenems provide broader coverage against multidrug-resistant Enterobacteriaceae 1

When to Stop Antibiotics

If thorough investigation reveals no evidence of persistent infection and the patient has no signs of sepsis, terminate antimicrobial therapy rather than continuing empirically. 1

This prevents: 1

• Selection pressure for resistant pathogens 1
• C. difficile colitis risk 1
• Unnecessary cost and toxicity 1

Surgical Re-Intervention Decision

If CT demonstrates undrained collections, anastomotic dehiscence, or ongoing peritoneal contamination, immediate surgical consultation for repeat source control is mandatory. 1

Adequate source control is the cornerstone of treatment—antibiotics alone cannot cure uncontrolled intra-abdominal sepsis. 1

Critical Pitfalls to Avoid

• Do not empirically escalate antibiotics without imaging confirmation of persistent infection—this drives resistance without improving outcomes 1
• Do not continue antibiotics beyond 7 days if adequate source control was achieved and no persistent infection is identified—prolonged therapy increases resistance and C. difficile risk 1, 3
• Do not delay CT imaging in favor of empiric antibiotic changes—identifying the need for repeat source control is more important than antibiotic selection 1
• Do not overlook extra-abdominal sources, particularly C. difficile colitis which can occur without diarrhea in patients on prolonged antibiotics 1