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.