Is Pneumonia (pneumonia) suitable for step-down therapy with Piperacillin-Tazobactam (Pip-Taz, piperacillin-tazobactam) for discharge?

From the Guidelines

When transitioning a patient with pneumonia from intravenous piperacillin-tazobactam (Pip-Tazo) to oral antibiotics for discharge, amoxicillin-clavulanate is typically the preferred step-down option, as it maintains appropriate coverage against many respiratory pathogens, allowing patients to complete treatment at home, reducing hospitalization costs and risks. The recommended adult dosage is 875mg/125mg twice daily for 5-7 days to complete a total antibiotic course of 5-7 days for community-acquired pneumonia, as per guidelines from the Infectious Diseases Society of America and the American Thoracic Society 1. For patients with penicillin allergies, alternatives include doxycycline (100mg twice daily), a respiratory fluoroquinolone like levofloxacin (750mg daily), or a combination of a macrolide (azithromycin 500mg on day 1, then 250mg daily) with a cephalosporin if the patient can tolerate cephalosporins. Some key points to consider when selecting an oral antibiotic for step-down therapy include:

• The patient's allergy history, particularly to penicillin and other beta-lactam antibiotics
• The suspected or confirmed pathogens involved in the pneumonia
• The patient's renal function, as some oral antibiotics require dose adjustment in renal impairment
• The patient's ability to take oral medications and their overall clinical stability, with at least 24-48 hours of clinical stability (normal vital signs, ability to take oral medications, and normal mental status) before discharge, as recommended by guidelines 1. It's also important to note that the step-down approach is effective because Pip-Tazo provides broad-spectrum coverage against many respiratory pathogens, and the oral options maintain appropriate coverage while allowing patients to complete treatment at home. Some of the key pathogens that Pip-Tazo covers include:
• Streptococcus pneumoniae
• Haemophilus influenzae
• Moraxella catarrhalis
• Enterobacteriaceae, such as Escherichia coli and Klebsiella pneumoniae
• Pseudomonas aeruginosa, in some cases. However, it's crucial to select an oral antibiotic that provides adequate coverage against the suspected or confirmed pathogens involved in the pneumonia, and to consider the patient's individual factors, such as allergy history and renal function, when making this selection.

From the FDA Drug Label

1. 2 Nosocomial Pneumonia Piperacillin and tazobactam for injection is indicated in adults and pediatric patients (2 months of age and older) for the treatment of nosocomial pneumonia (moderate to severe) caused by beta-lactamase producing isolates of Staphylococcus aureus and by piperacillin/tazobactam-susceptible Acinetobacter baumannii, Haemophilus influenzae, Klebsiella pneumoniae, and Pseudomonas aeruginosa (Nosocomial pneumonia caused by P. aeruginosa should be treated in combination with an aminoglycoside) [see Dosage and Administration (2)]. 2.3 Dosage in Adult Patients with Nosocomial Pneumonia Initial presumptive treatment of adult patients with nosocomial pneumonia should start with piperacillin and tazobactam for injection at a dosage of 4. 5 g every six hours plus an aminoglycoside, [totaling 18 g (16 g piperacillin/2 g tazobactam)], administered by intravenous infusion over 30 minutes.

The step-down therapy for nosocomial pneumonia is not explicitly mentioned in the provided drug labels. However, the labels do provide information on the treatment of nosocomial pneumonia with piperacillin and tazobactam for injection.

• The recommended duration of piperacillin and tazobactam for injection treatment for nosocomial pneumonia is 7 to 14 days 2.
• The dosage for adult patients with nosocomial pneumonia is 4.5 g every six hours plus an aminoglycoside 2. Since the labels do not provide direct information on step-down therapy for discharge, a conservative clinical decision would be to consult other reliable sources or clinical guidelines for specific recommendations on step-down therapy for nosocomial pneumonia.

From the Research

Pneumonia Treatment with Piperacillin/Tazobactam

• The use of piperacillin/tazobactam in the treatment of pneumonia has been studied in various clinical trials 3, 4, 5, 6, 7.
• A study published in 2010 compared the efficacy of tazobactam/piperacillin with imipenem/cilastatin in patients with moderate-to-severe aspiration pneumonia, and found that tazobactam/piperacillin was as effective and safe as imipenem/cilastatin 3.
• Another study published in 2020 compared the clinical benefits of piperacillin/tazobactam with ceftriaxone plus clindamycin in the treatment of early, non-ventilator, hospital-acquired pneumonia, and found that piperacillin/tazobactam was more effective than ceftriaxone plus clindamycin 4.
• A study published in 1998 compared the efficacy and safety of piperacillin/tazobactam with co-amoxiclav plus an aminoglycoside in the treatment of severe pneumonia, and found that piperacillin/tazobactam was safe and highly efficacious 5.
• A descriptive cross-sectional study published in 2023 found that piperacillin-tazobactam was the most commonly prescribed empirical treatment for community-acquired pneumonia, but the current empirical antibiotic treatment accuracy was low for Legionella pneumophila, Mycoplasma pneumoniae, and Clamydophila pneumoniae 6.
• A study published in 2013 found that prolonged infusion of piperacillin/tazobactam was more effective than regular infusion in the treatment of hospital-acquired pneumonia, with a higher treatment success rate and lower remedial treatment rate 7.

Step-Down Therapy for Discharge

• The decision to step down therapy for discharge should be based on the patient's clinical response to treatment and the results of microbiological tests 3, 4, 5, 6, 7.
• A study published in 2020 found that clinical failure was more frequent in the ceftriaxone plus clindamycin group than in the piperacillin/tazobactam group, suggesting that piperacillin/tazobactam may be a better option for step-down therapy 4.
• Another study published in 2013 found that prolonged infusion of piperacillin/tazobactam was more effective than regular infusion in the treatment of hospital-acquired pneumonia, and may be a good option for step-down therapy 7.