What is the treatment for Carbapenem-Resistant Organism (CRO) Pseudomonas aeruginosa infection?

From the Guidelines

Treatment for carbapenem-resistant organism (CRO) Pseudomonas aeruginosa typically requires combination antibiotic therapy due to limited treatment options, with ceftolozane-tazobactam being a suggested option if active in vitro 1.

Recommended Approach

The recommended approach is to use two or more active agents, often including ceftolozane-tazobactam (Zerbaxa) 3g IV every 8 hours as the backbone therapy.

• These can be combined with agents like colistin (loading dose of 5mg/kg IV, then 2.5mg/kg IV every 12 hours) 1,
• polymyxin B (1.5-2.5mg/kg/day IV divided every 12 hours),
• or high-dose extended-infusion meropenem (2g IV over 3 hours every 8 hours) despite resistance.
• Aminoglycosides like amikacin (15-20mg/kg IV daily) may be added based on susceptibility testing.

Treatment Duration and Adjustments

Treatment duration typically ranges from 7-14 days depending on infection site and clinical response.

• Dosage adjustments are necessary for patients with renal impairment.
• Source control through drainage of abscesses or removal of infected devices is crucial when applicable.

Rationale

This aggressive combination approach is necessary because CRO Pseudomonas has developed resistance mechanisms against most standard antibiotics, and using multiple agents with different mechanisms of action helps overcome resistance and prevent further resistance development during treatment 1.

• However, there is no evidence to recommend for or against the use of combination therapy with the new BLBLI (ceftazidime-avibactam and ceftolozane-tazobactam) or cefiderocol for CRPA infections 1.
• When treating severe infections caused by CRPA with polymyxins, aminoglycosides, or fosfomycin, treatment with two in vitro active drugs is suggested 1.
• In patients with non-severe infections or low-risk CRPA infections, under the consideration of antibiotic stewardship, monotherapy chosen from among the drugs active in vitro, on an individual basis and according to the source of infection, is considered good clinical practice 1.

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)].

Treatment for CRO pseudomonas (specifically Pseudomonas aeruginosa) can be achieved with piperacillin and tazobactam for injection, in combination with an aminoglycoside for nosocomial pneumonia, as stated in the drug label 2.

• The recommended dosage for adult patients with nosocomial pneumonia is 4.5 g every six hours plus an aminoglycoside.
• Treatment with the aminoglycoside should be continued in patients from whom P. aeruginosa is isolated.

From the Research

Treatment Options for CRO Pseudomonas

• Ceftazidime-avibactam (CZA) and ceftolozane-tazobactam (C/T) are potential treatment options for extensively drug-resistant Pseudomonas aeruginosa (XDR-PA) infections, with susceptibility rates of 71.5% and 77.5%, respectively 3.
• CZA has shown good in vitro activity against P. aeruginosa and has demonstrated similar clinical and microbiological outcomes to comparators in patients with complicated infections 4.
• A retrospective cohort study found that CZA was effective in treating MDR/XDR P. aeruginosa infections, with a clinical cure rate of 54.1% by day 14 5.
• A multicentre, retrospective, observational study compared the effectiveness of C/T and CZA for treatment of invasive MDR P. aeruginosa infections and found that C/T resulted in higher rates of clinical success, particularly for patients with pneumonia 6.

Key Considerations

• The choice of treatment should be guided by factors such as the epidemiology of the infection, patient risk factors, and the site of infection 7.
• Combination therapy may be considered in certain scenarios, such as when the infection is caused by a MDR or XDR strain 3, 5.
• The development of resistance to CZA and C/T is a concern, and treatment-emergent resistance was common in one study 6.

Infection-Specific Treatment

• For lower respiratory tract infections, C/T may be a preferred option due to its higher clinical success rate compared to CZA 6.
• For bacteraemia, the choice between C/T and CZA may depend on individual patient factors, as there was no significant difference in clinical success rates between the two treatments in one study 6.