What is the treatment for Pseudomonas aeruginosa in sputum?

From the Guidelines

Treatment for Pseudomonas aeruginosa in sputum should prioritize antipseudomonal antibiotics, with combination therapy often recommended for severe infections, and inhaled antibiotics like tobramycin or colistin for suppressive therapy in patients with cystic fibrosis or bronchiectasis. The most recent and highest quality study 1 recommends first-line treatment with antipseudomonal beta-lactams such as piperacillin-tazobactam, ceftazidime, or cefepime, combined with an aminoglycoside like tobramycin or amikacin. For less severe infections, fluoroquinolones like ciprofloxacin may be used. Treatment duration typically ranges from 7-14 days depending on clinical response and infection severity. In patients with chronic Pseudomonas colonization, inhaled antibiotics like tobramycin (300mg nebulized twice daily) or colistin (1-2 million units nebulized twice daily) may be used for suppressive therapy, as recommended by the British Thoracic Society guideline for bronchiectasis in adults 1. It is essential to consider the patient's culture and mycobacterial status, optimize airway clearance, and treat other associated conditions before starting long-term antibiotics. Regular monitoring of sputum culture and sensitivity is necessary to adjust the treatment regimen accordingly. The choice of long-term antibiotic therapy should take into account factors such as tolerance, allergies, and sensitivity, and alternative inhaled/nebulised agents may be considered as international studies are completed. Targeted therapy based on susceptibility testing is crucial for effective treatment, as Pseudomonas is naturally resistant to many antibiotics due to its outer membrane permeability, efflux pumps, and ability to produce beta-lactamases.

Some key points to consider in the treatment of Pseudomonas aeruginosa in sputum include:

• The use of inhaled colistin for patients with bronchiectasis and chronic P. aeruginosa infection, as recommended by the British Thoracic Society guideline 1
• The consideration of azithromycin or erythromycin as an alternative to inhaled antibiotics for patients with bronchiectasis and chronic P. aeruginosa infection, as suggested by the British Thoracic Society guideline 1
• The importance of monitoring for potential major side effects with long-term antibiotics and counseling patients to seek urgent attention if these develop, as recommended by the British Thoracic Society guideline 1
• The need for regular review of patients on long-term antibiotics to assess efficacy, toxicity, and continuing need, as recommended by the British Thoracic Society guideline 1

From the FDA Drug Label

2.2 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 grams every six hours plus an aminoglycoside, [totaling 18.0 grams (16.0 grams piperacillin and 2. 0 grams tazobactam)], administered by intravenous infusion over 30 minutes. The recommended duration of piperacillin and tazobactam for injection treatment for nosocomial pneumonia is 7 to 14 days. Treatment with the aminoglycoside should be continued in patients from whom P. aeruginosa is isolated.

1. 1 Nosocomial Pneumonia Levofloxacin tablets are indicated for the treatment of nosocomial pneumonia due to methicillin-susceptible Staphylococcus aureus, Pseudomonas aeruginosa, Serratia marcescens, Escherichia coli, Klebsiella pneumoniae, Haemophilus influenzae, or Streptococcus pneumoniae. Adjunctive therapy should be used as clinically indicated Where Pseudomonas aeruginosa is a documented or presumptive pathogen, combination therapy with an anti-pseudomonal β-lactam is recommended [see Clinical Studies (14.1)].

Skin and Skin Structure Infections caused by Escherichia coli, Klebsiella pneumoniae, Enterobacter cloacae, Proteus mirabilis, Proteus vulgaris, Providencia stuartii, Morganella morganii, Citrobacter freundii, Pseudomonas aeruginosa, methicillin-susceptible Staphylococcus aureus, methicillin-susceptible Staphylococcus epidermidis, or Streptococcus pyogenes

The treatment for Pseudomonas aeruginosa in sputum may include:

• Piperacillin-tazobactam (IV) at a dosage of 4.5 grams every six hours plus an aminoglycoside 2
• Levofloxacin (PO) as part of the treatment for nosocomial pneumonia, with combination therapy with an anti-pseudomonal β-lactam recommended if P. aeruginosa is a documented or presumptive pathogen 3
• Ciprofloxacin (PO) as part of the treatment for skin and skin structure infections caused by P. aeruginosa 4

From the Research

Treatment Options for Pseudomonas aeruginosa in Sputum

• The treatment of Pseudomonas aeruginosa infections is challenging due to its intrinsic resistance to many antimicrobial agents and the emergence of acquired resistance 5.
• Ceftolozane-tazobactam and ceftazidime-avibactam are recommended as empirical treatment for suspected P. aeruginosa infections, especially in cases with risk factors for multidrug-resistant (MDR) or extensively drug-resistant (XDR) infections 6.
• Cefiderocol, a new cephalosporin, shows promising results against P. aeruginosa, with excellent in vitro activity and good stability to β-lactamases and porin and efflux pumps mutations 5, 7.
• Combination therapy is only recommended in limited scenarios, and extended-infusion of β-lactams may exhibit clinical benefit 7, 8.
• Antimicrobial stewardship is essential to preserve new drugs and prevent future development of resistance 7.

Antibiotic Choices

• Ceftazidime, carbapenems, and piperacillin-tazobactam are commonly used antibiotics for P. aeruginosa infections, but their effectiveness may vary depending on the local epidemiology and resistance patterns 9, 8.
• New combinations of β-lactams/β-lactamase inhibitors, such as cefepime-taniborbactam and cefepime-zidebactam, are being developed and show promising results 5.
• Fosfomycin, an "old" antimicrobial, can be used as a combination strategy in certain cases 5.

Considerations for Treatment

• The choice of antibiotic should be guided by the patient's risk factors, the site of infection, and the available treatment options 6, 7.
• Local institutional use of combination antibiograms can help optimize empirical therapy of infections caused by difficult-to-treat pathogens like P. aeruginosa 8.
• The emergence of MDR/XDR P. aeruginosa necessitates the need for newer agents and highlights the importance of antimicrobial stewardship 6, 7.