Is piperacillin-tazobactam (Pip-Tazo) with ciprofloxacin effective as empiric therapy for sepsis caused by a negative Gram bacillus in a patient already receiving doxycycline?

From the Guidelines

For sepsis due to gram-negative bacilli, piperacillin-tazobactam (Pip-tazo) plus ciprofloxacin is generally an appropriate empiric therapy combination, as recommended by the Surviving Sepsis Campaign guidelines 1. This regimen provides broad coverage against most gram-negative pathogens, including Pseudomonas aeruginosa. Since the patient is already on doxycycline, this can be continued as it adds coverage for atypical organisms and some gram-positive bacteria. A typical dosing regimen would be piperacillin-tazobactam 4.5g IV every 6-8 hours (adjusted for renal function) and ciprofloxacin 400mg IV every 8-12 hours. Some key points to consider when selecting empiric antimicrobial therapy include:

• The anatomic site of infection and typical pathogen profile
• Prevalent pathogens within the community, hospital, and even hospital ward
• The resistance patterns of those prevalent pathogens
• The presence of specific immune defects, such as neutropenia or poorly controlled HIV infection
• Age and patient comorbidities, including chronic illness and chronic organ dysfunction Once culture and sensitivity results are available, therapy should be de-escalated to target the specific pathogen, as recommended by the guidelines 1. The combination works well because piperacillin is a broad-spectrum penicillin that inhibits cell wall synthesis, tazobactam prevents beta-lactamase degradation of piperacillin, and ciprofloxacin inhibits DNA gyrase, providing a different mechanism of action. This dual-mechanism approach reduces the risk of treatment failure due to resistance. Monitor renal function, as both medications require dose adjustment in renal impairment, and watch for superinfections, particularly Clostridioides difficile. It's also important to note that the guidelines recommend daily assessment for de-escalation of antimicrobial therapy in patients with sepsis and septic shock 1. In terms of duration of therapy, the guidelines suggest that 7-10 days is typically adequate for most serious infections associated with sepsis and septic shock, but longer courses may be necessary in certain cases, such as slow clinical response or undrainable foci of infection 1.

From the FDA Drug Label

Piperacillin and tazobactam has been shown to be active against most isolates of the following microorganisms, both in vitro and in clinical infections: Aerobic bacteria Gram-negative bacteria Acinetobacter baumannii Escherichia coli Haemophilus influenzae (excluding beta-lactamase negative, ampicillin-resistant isolates) Klebsiella pneumoniae Pseudomonas aeruginosa (given in combination with an aminoglycoside to which the isolate is susceptible)

Piperacillin-tazobactam (pip-tazo) is a good empiric therapy option for sepsis caused by negative gram bacillus, including Acinetobacter baumannii, Escherichia coli, Klebsiella pneumoniae, and Pseudomonas aeruginosa. However, since the patient is already on doxycycline, the addition of cipro (ciprofloxacin) to pip-tazo should be considered with caution due to potential drug interactions and the lack of direct information in the provided drug label regarding this specific combination. The use of pip-tazo with cipro may be considered in certain clinical scenarios, but it is essential to evaluate the patient's specific situation and consider potential interactions or contraindications before making a decision 2.

From the Research

Empiric Therapy for Sepsis due to Gram-Negative Bacillus

• The use of empiric combination antibiotic therapy, such as piperacillin-tazobactam (pip-tazo) with ciprofloxacin, is a viable option for treating sepsis due to Gram-negative bacillus 3, 4.
• Pip-tazo is a broad-spectrum antibiotic that covers most Gram-positive and Gram-negative aerobic bacteria and anaerobic bacteria, including many pathogens producing beta-lactamases 5.
• The addition of an aminoglycoside, such as ciprofloxacin, to pip-tazo can increase the appropriate initial therapy for patients with severe sepsis and septic shock 4.

Considerations for Patients Already on Doxycycline

• For patients already on doxycycline, the use of pip-tazo with ciprofloxacin may be considered, taking into account the potential for increased risk of adverse events, such as gastrointestinal symptoms and skin reactions 5.
• The decision to use combination therapy should be based on the patient's individual factors, predicted infecting organism(s), and local microbial resistance patterns 6, 7.

Recommendations for Empiric Antibiotic Therapy

• Empiric antibiotic therapy should be initiated as soon as possible, and within one hour, for patients with sepsis or septic shock 6, 7.
• The initial antibiotic regimen should have activity against typical Gram-positive and Gram-negative causative micro-organisms, and should be based on local and national resistance data 3, 6.
• Antimicrobial agent therapy should be de-escalated as soon as possible, and biomarkers such as procalcitonin can provide decision support for antibiotic use 7.