New Players in the treatment of Community-Acquired Pneumonia (CAP): Ceftaroline and Corticosteroids by Steven P. LaRosa, M.D.
The treatment of community-acquired pneumonia (CAP) has been
for many years unchanged and boring. We give a macrolide to cover Legionella,
Chlamydophila, and Mycoplasma and Ceftriaxone, a 3rd generation
Cephalosporin, to cover the dreaded Pneumococcus and Haemophilus influenzae. Data from recent clinical trials would
suggest a role for Ceftaroline and corticosteroids.
Ceftaroline
Ceftaroline, a “5th Generation Cephalosporin” has
a similar spectrum of action as the CAP workhouse drug Ceftriaxone but also has
activity against MRSA. There have now been 3 Phase III trials of Ceftaroline
vs. Ceftriaxone in CAP patients with a moderate severity of illness as indicated
by PORT scores III and IV. The primary efficacy variable was clinical response
at days 8-15 in the modified intent to treat population (patients who were
randomized and received some study drug). In a meta-analysis (Antimicrob
Chemother 2016; 71: 862–870), A superior clinical response was observed with
Ceftaroline 600mg IV q 12 hours 784/961 patients (81.5%) compared with Ceftriaxone 1-2gms/day 695/955 (74.7%);
OR 1.66, 95% CI 1.34-2.06, p < 0.001. A statistically significant difference
in treatment effect was also observed in patients with confirmed S. pneumoniae infections with a clinical
response of 73/85 (85.9%) with Ceftaroline and 54/74 (73.0%). The difference in
treatment effects has biologic plausibility. Ceftaroline has greater affinity
for Penicillin Binding Protein 2 (PBP2) than Ceftriaxone. In patients with S.aureus and S. pneumoniae, the MIC was on average 16 fold lower for Ceftaroline
than Ceftriaxone.
Corticosteroids
The
efficacy of corticosteroids has been studied and debated for different
infectious diseases for years. Guyatt and colleagues performed a meta-analysis
of the efficacy of corticosteroids in CAP (Ann Intern Med. 2015; 163:519-528)
in 1974 patients in 12 trials. The use of corticosteroids was associated with a
3% reduction in mortality, a 5% decrease in the need for mechanical ventilation
and a 1% decrease in hospital length of stay. The treatment benefit of
corticosteroids on mortality was confined to the 6 studies of patients with
severe pneumonia; 10% mortality with corticosteroids vs. 22% in the control arm.
A Swiss study (Lancet 2015; 385:1511-1518) was performed in 485 patients with
CAP who were randomized to either prednisone 50mg/day x 7 days or placebo. A total of 50% of patients had severe CAP as
indicated by a PSI class of IV and V. A statistically significant shorter time
to clinical stability of 1.4 days and shorter length of hospitalization by 1
day was observed. Torres and colleagues in a Spanish study ( randomized 120 patients with severe CAP to either methylprednisolone
(MP) 0.5mg/kg every 12 hours X 5 days or placebo. Severe CAP was defined as a
PSI class of V and a CRP level of >150mg/L. A statistically significant
reduction in treatment failure was observed; MP 13%, Placebo 31%, OR 0.34 (0.14-0.87). A
non-significant 5% lower mortality was observed in the methylprednisolone group
Bottom Line
Ceftaroline was not available at the time of the 2007
IDSA/ATS Guidelines of the treatment of CAP and corticosteroid use is mentioned
only in the context of treating concomitant adrenal insufficiency. An update of
these guidelines is currently underway. The available data would indicate that
Ceftaroline should take the place of Ceftriaxone in the treatment of CAP.
Corticosteroids at a dose of methylprednisolone 0.5mg/kg IV q 12 hours x 5 days
should be considered in patients with severe CAP. I personally like to stay
away from scoring systems that are difficult to remember, but there clearly are
phone apps that can determine a PSI class of at least IV. A CURB 65 score of at
least 2 is easy to determine and could be used to determine severe CAP. For
simplicity I would also consider any CAP patient in the ICU with a CRP of at
least 150mg/L.
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