IV Antibiotics May Be No Better Than Inhaled Ones for P. aeruginosa

Patricia Inácio, PhD avatar

by Patricia Inácio, PhD |

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In children with cystic fibrosis (CF) and a first or new-onset Pseudomonas aeruginosa infection, antibiotics given intravenously are not more effective at eliminating the bacteria than inhaled antibiotics given alone or as combination therapy, a Turkish study suggests. 

Intravenous (IV) treatment was also associated with more pulmonary exacerbations and poorer lung function after one year, the researchers reported, although children treated intravenously may also have had more advanced disease.

The study,“Effectiveness of Different Eradication Treatment Protocols for New-Onset Pseudomonas aeruginosa in Children with Cystic Fibrosis,” was published in the journal Pediatric Pulmonology.

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Chronic lung infection with P. aeruginosa is linked with poor outcomes in CF patients, and early identification and treatment of these bacterial infections are considered crucial in preventing an established and damaging chronic infection.

Antibiotics administered at early stages, when the bacteria have a non-mucoid form — meaning they still lack the sticky and thick biofilms that make them resistant to treatment — are more likely to effectively clear an infection.

U.S., U.K., and European guidelines favor the use of inhaled antibiotics as a first-line approach for eradicating P. aeruginosa infection at early stages. IV antibiotics are recommended for a sudden worsening of symptoms, called pulmonary exacerbations.

Researchers at Hacettepe University conducted a retrospective, observational study to “evaluate the effectiveness of different eradication strategies against the first P. aeruginosa isolation in order to determine the optimal management and prognosis of these children.”

They reviewed clinical data covering 399 children with CF who were followed at their center from 2015 to 2019. This included children with a first positive infection for P. aeruginosa or a new infection after at least one year of no infection, but not those deemed chronically infected with the bacteria.

A second bacterial isolate from a child, confirming an infection, was considered an “episode.”

A total of 140 episodes were analyzed, involving 80 girls and 60 boys with a mean age of about 7 at first or new-onset infection. In the majority of cases, the infection was identified from throat swabs instead of sputum samples.

At the start of the analysis (baseline), mucoid P. aeruginosa — associated with lung function decline — was detected in 27 (19.3%) episodes. Importantly, in 14 (10%) cases, the bacteria isolates were resistant to at least one antibiotic.

Another species of bacteria often found in the lungs of children with CF, called Staphylococcus aureus, was identified along with P. aeruginosa in 84 cases.

A total of 69 children (49%) showed symptoms (cough, shortness of breath, sputum, fever) when infected with P. aeruginosa. Pancreatic insufficiency, which occurs when the pancreas doesn’t make enough digestive enzymes and is common in CF, was seen in 133 children.

The median time to starting antibiotic therapy was eight days after an infection was diagnosed.

Three different antibiotic approaches were given as treatment, with children grouped by approach used. One group had received a combination of  two IV antibiotics for 14 days, another was treated with inhaled tobramycin twice daily for 28 days, and the final group had inhaled tobramycin for 28 days plus oral ciprofloxacin for 14 days.

Of these 140 episodes analyzed, 53 were treated with IV antibiotics, and 87 with tobramycin alone (62 episodes) or in combination with ciprofloxacin (25 episodes). The most common IV antibiotic combination was ceftazidime and amikacin.

Successful eradication — defined as a respiratory sample negative for infection one to two weeks after ending treatment, and at least three negative tests over the following 12 months — was achieved in 85 of the 140 episodes, corresponding to a 60.7% success rate.

Eradication was seen to be more successful with inhaled tobramycin plus oral ciprofloxacin, with a success rate of 72%. Inhaled tobramycin alone had a 59.7% success rate, and IV therapy a 56.6% rate.

However, no significant differences in successful eradication were evident between the three treatment groups.

“14 days of intravenous treatment with antipseudomonal agents was not superior to inhaled tobramycin for 28 days with/without oral ciprofloxacin,” the investigators wrote. “Adding oral ciprofloxacin does not provide additional benefit.”

Children treated with IV antibiotics were significantly younger at first infection (mean age, 5.95) compared with those given inhaled tobramycin alone (mean age, 7.46) or combined with ciprofloxacin (mean age, 8.92).

The mean number of pulmonary exacerbations one year later was significantly higher in the IV group (1.88) than the other two groups (1.18 and 0.08, respectively). In agreement with these findings, lung function one year later was also poorer in children given IV treatment, the researchers reported.

Children’s age, sex, initial (baseline) lung function, concomitant infections, time to the start of antibiotic treatment or antibiotic resistance of P. aeruginosa were not found to affect treatment success.

Rather, a child’s initial respiratory symptoms “were the most significant predictor negatively affecting the success of treatment,” the team wrote.

“Our study did not identify an advantage of intravenous treatment compared to inhalation therapy for the eradication of P aeruginosa,” the researchers concluded.

However, they noted these findings are limited by the lack of a control group. Children in the IV group also had significantly more respiratory symptoms at the study’s start than those in the other two groups, suggesting “intravenous treatment may have been administered to the children with more advanced disease.”