Oral as good as IV antibiotics for ridding P aeruginosa in cystic fibrosis

Intravenous (IV) antibiotics are no better than oral antibiotics when it comes to eradicating Pseudomonas (P.) aeruginosa in children and adults with cystic fibrosis, yet are more costly than the latter, reveals the TORPEDO-CF study.

“IV treatment often entails hospital admission, requires IV access (which might be traumatic), and carries the risk of side effects, including nephrotoxicity and ototoxicity with aminoglycosides such as tobramycin,” explained the researchers.

While guidelines recommend starting antibiotic regimens early to eradicate P. aeruginosa in cystic fibrosis to prevent progression to chronic infection, there is currently no evidence favouring any one regimen over the other. Also, guidelines differ according to regions, with UK experts recommending an inhaled antibiotic combined with a systemic one; while those from US and Europe favouring inhaled single agent (tobramycin). 

“Our trial has shown that there is no advantage in choosing IV treatment as first-line treatment,” said the researchers.

“Because there were no important clinical benefits to the use of IV over oral therapy, the large difference in cost suggests that oral therapy should usually be recommended for eradication of early infection with P. aeruginosa in cystic fibrosis,” they continued.

In the multicentre, parallel-group, open-label trial, 286 patients (15 adults, the rest were patients below 18 years) were randomized 1:1 to receive IV ceftazidime and tobramycin for 14 days or oral ciprofloxacin for 12 weeks, both in addition to 12 weeks of inhaled colistimethate sodium. [Lancet Respir Med 2020;8:975-986]

More patients in the oral arm achieved the primary outcome than the IV arm (52 percent vs 44 percent), defined as P aeruginosa eradication at 3 months, which was sustained to 15 months. Nonetheless, the difference between groups did not reach statistical significance (relative risk [RR], 0.84; p=0.18).

On the other hand, IV antibiotics led to fewer hospital admission than oral antibiotic during the 12 months of follow-up after P aeruginosa eradication (31 percent vs 45 percent; RR, 0.69; p=0.02).  

“However, this confers no advantage as IV eradication usually requires admission whereas oral treatment does not,” the researchers pointed out.  

Also, the difference in hospitalization during the follow-up period might have been due to reluctance of patients who already had been admitted earlier for IV eradication to undergo another hospitalization.

“Our study found that traditional oral antibiotics are just as effective as IV antibiotics, which means that cystic fibrosis patients who have a new P. aeruginosa can be treated at home and saved the inconvenience of having to be admitted to hospital for treatment,” said lead author Dr Simon Langton Hewer from University Hospitals Bristol, UK.

“The results of the study provide evidence to guide practice in cystic fibrosis centres and will help to reduce unnecessary hospital admissions,” he said.

Moreover, oral antibiotic was considerably cheaper than IV antibiotics, by £5,939 per patient.

The rates of serious adverse events were similar between both treatment groups, at 8 percent each.

“If the findings of this trial are implemented in routine clinical practice, most patients will receive oral eradication treatment as an outpatient and many hospital admissions will be avoided, which in turn will reduce both treatment burden and healthcare costs,” said Hewer.