Discussion
The present study was designed to evaluate the efficacy of IV antibiotics compared to non-IV eradication regimens. IV antibiotic treatment is considered to be more effective compared to other routes in pulmonary exacerbation and it is recommended for the patients with moderate to severe pulmonary exacerbation or with no response to oral and/or inhalation antibiotics20. There is a limited data on IV vs oral and/or inhalation antibiotic regimens for the eradication of early P. aeruginosa or MRSA acquisition. The data from our study demonstrated that there is not any statistically significant difference between IV vs non-IV (oral and/or inhalation) antibiotic eradication regimens in terms of eradication at one year of the first isolation of P. aeruginosa and MRSA.
IV treatment often requires hospitalization, might have a negative effect on HRQoL in individuals with CF and costs significantly more than oral/inhalation treatments16; 21. Although a number of studies have been reported the effectiveness of oral, inhalation and IV eradication protocols, there are only a few comparative studies available and the optimal antibiotic regimens for both MRSA and P. aeruginosa are not clear. 12; 15; 22.
A recent RCT on P. aeruginosa eradication compared the efficacy of 14 days IV ceftazidime and tobramycin vs 12 weeks oral ciprofloxacin; both groups were combined with 12 weeks inhaled colistimethate sodium16. In line with our results, IV antibiotics did not achieve sustained eradication ofP. aeruginosa in a greater proportion of patients with CF compared to the oral therapy group. The study also evaluated the cost-effectiveness and found that oral eradication therapy has similar effectiveness for the primary clinical parameters and considerably cheaper compared to IV treatment.
Even though non-parenteral eradication protocols have been more commonly used since they have similar effectiveness with IV treatment and more preferable method in terms of cost effectiveness and patients QoL, insufficient effect of inhaled antibiotics on inflammation is a valid concern. A RCT comparing the systemic antibiotics to inhaled tobramycin alone in terms of reduction in lower airways inflammation suggests that systemic antibiotic treatment has a greater effect on reducing lower airways inflammation, even though systemic and inhaled treatments appeared to have similar effects on reduction of bacterial burden23. These results might cause concerns about the impact of inflammation in lower airways such as increase in bronchiectasis and decrease in pulmonary function. However, studies did not show any difference in FEV1pp change between inhaled with oral antibiotics and only inhaled antibiotic regimens 24; 25.
There are several MRSA eradication protocols evaluated in the literature including very mild regimens such as single or dual oral antibiotics and very aggressive treatments such as dual iv antibiotic treatment over 3 weeks followed by a 6-week period with dual oral antibiotic therapy and inhalation with vancomycin, all in addition to environmental hygienic directives and topical therapies22; 26-31. These studies have been reported successful eradication rates from 41.4% to 84% with the first isolation for MRSA. The successful eradication rate of MRSA in our study cohort was 35.4%. Our eradication rate was lower than other studies and this might be due to the different study end-points. We determined the successful eradication as not having any isolations 12 months after the treatment compared to evaluating at 28-day of the treatment in most of the studies in the literature.
To the best of our knowledge, this is the first study comparing IV and non-IV antibiotics for the eradication of MRSA. Our results indicate that oral antibiotics (TMP/SMX with or without rifampicin) may be as efficient as IV teicoplanin for the eradication treatment.
Determining risk factors influencing acquisition and eradication of MRSA and P. aeruginosa in CF is crucial for prevention and treatment success. To date, studies showed lower socio-economic status, female gender, ΔF508 mutation and pancreatic insufficiency as risk factors forP. aeruginosa 32; 33. Additionally, retrospective cohort studies of individuals with CF in the Cystic Fibrosis Foundation Patient Registry demonstrated that pancreatic insufficiency, CFRD and number of hospitalizations in the preceding year were the most common risk factors for eradication failure of MRSA34; 35. In our study, none of these clinical risk factors were significantly associated with eradication failure both in P. aeruginosa and MRSA groups.
Our study has a number of limitations. Firstly, this is a retrospective design and the generalizability of the results is limited due to being a single-center study. Also, while our sample size is relatively bigger than comparative studies in the literature, most patients were given IV treatment due to the hospital protocol and this limited the numbers of non-IV treatment cohort.
In conclusion, we did not find any difference between IV and non-IV treatments in successful eradication at 1 year for both P. aeruginosa and MRSA. This study, in line with TORPEDO-CF, shows that IV treatment does not add any benefit in the eradication of P. aeruginosa 16. Additionally, eradication rates were not significantly different in the eradication of MRSA and this should be verified by further prospective studies. In light of these results, cost-effectiveness and to decrease the treatment burden due to hospitalization and IV administration of antibiotics, we have increased the use non-parenteral eradication protocols in our CF clinic.