Discussion:
In a nationally representative sample of pediatric CF hospitalizations,
we found that concomitant CDI is associated with higher mortality,
length of stay, and hospital charges. Furthermore, we observed an
increasing proportion of CF hospitalizations complicated by CDI over
time between 1997 and 2016. Taken together, these data highlight the
need for heightened awareness, early identification, and aggressive
management of CF hospitalizations complicated by CDI.
Prior studies have reported the rare occurrence of CDI in CF, despite
high colonization rates (47% to 50% of CF patients) with C.
difficile . In contrast, our study adds support to the more recent case
reports and small case series describing the severe, life threatening
impact of C. difficile infection in CF patients, creating an
urgent need for interventions to improve hospital outcomes among CF
children with CDI.
Increasing CDI among children with CF could be due to several factors,
including increased survival rates and thus more time at risk for
acquiring nosocomial CDI, exposure to newer antimicrobial agents in the
treatment of CF exacerbations, and the dissemination of a more-virulent
epidemic strain of C difficile , such as North American
pulsed-field gel electrophoresis type 1 (NAP1) . Alternative
explanations include the possibility of more frequent testing and/or
documentation and coding for CDI during inpatient admissions for CF. Our
findings may also be partially explained by greater detection of
asymptomatic carriage of C. difficile . Indeed, patients with CF
and infants less than 1 year of age are the only populations reported in
which C. difficile cytotoxin is frequently recovered from
asymptomatic individuals. Early exposure to C. difficile with
induction of an immunological response that offers protection against
the effects of toxin(s) but not against colonization, epithelial cell
associated factors that prevent the binding of cytotoxin, altered
intestinal environment unfavorable for C difficile to exert its
virulence have been proposed. As such, increasing awareness of C.
difficile emergence overall and testing in hospitalized children may
contribute to the rising trend, which may not necessarily reflect true
infection with C. difficile in the CF population. In addition, in
the late 2000s, the introduction of more sensitive C.
difficile assays, such as nucleic acid amplification tests (NAATs),
could have probably led to potential overdiagnosis of CDI, since this
test detects the gene encoding the toxin rather than the actual toxin.
The relative contribution of each of these factors in the CF population
has not been defined.
Nevertheless, the excess in-hospital mortality in C. difficile -CF
was striking and persisted after multivariate analysis after adjusting
for underlying patient and hospital characteristics. Clinicians caring
for CF patients should be aware of this risk, particularly as CDI may
have an atypical presentation with lack of diarrhea in CF patients.
Given this excess mortality along with longer LOS and higher hospital
charges, improved diagnosis and treatment will be needed to help
mitigate the increased virulence of C. difficile that has been
associated with greater morbidity and/or resistance to standard
treatment in the general population..