Infectious Diseases II
| (e) | A recent multicenter, randomized, double-blind, comparator controlled trial compared |
|---|
the efficacy and safety of imipenem/relebactam and colistin combined with imipenem/
cilastatin in patients with imipenem-resistant gram-negative bacterial infections (health
care-associated/ventilator-associated pneumonia, complicated intra-abdominal infections,
or complicated UTI). Clinical response rates were higher for imipenem/relebactam
compared to imipenem/colistin.
vi.
Cefiderocol
| (a) | Novel siderophore cephalosporin with a unique mechanism of action that confers activity |
|---|
against a broad spectrum of resistant gram-negative bacteria, including Enterobacterales,
Pseudomonas, Acinetobacter, and Stenotrophomonas. It has no clinically relevant in vitro
activity against most gram-positive bacteria and anaerobes.
| (b) | Cefiderocol is able to chelate ferric ions and use bacterial iron transport systems, which |
|---|
has been called a βTrojan Horseβ strategy and translates to higher concentrations of
susceptible gram-negatives in the periplasmic space.
| (c) | Due to the cephalosporin/catechol structure, it has increased stability against hydrolysis |
|---|
by clinically relevant Ξ²-lactamases, including serine (including KPCs and OXA-48) and
metallo-Ξ²-lactamases. Given the use of the iron transport pathway, cefiderocol does
not require classic Ξ²-lactam porin channels to penetrate the cells, and therefore, retains
activity in the presence of porin channel mutations and remains unaffected by common
efflux pumps present in Enterobacterales.
| (d) | FDA-approved in 2019 for complicated UTIs. |
|---|---|
| (e) | In vitro studies have demonstrated excellent activity of cefiderocol against class A, B, and |
D CRE.
| (f) | A multicenter, randomized, open-label study of cefiderocol compared to best-available |
|---|
therapy for the treatment of severe infections (hospital-acquired pneumonia, ventilator-
associated pneumonia, complicated UTI, bloodstream infection, and sepsis) caused
by carbapenem-resistant gram-negative pathogens. All-cause mortality versus other
antibiotics in critically ill patients was higher in the cefiderocol arm. The cause of higher
mortality was not established.
vii.
Eravacycline
| (a) | Novel fluorocycline of the tetracycline class with a similar structure to tigecycline, |
|---|
escaping many resistance mechanisms seen in other tetracyclines
| (b) | FDA-approved in 2018 for complicated intra-abdominal infections. It was investigated for |
|---|
use with UTIs, but outcomes were not favorable.
| (c) | Demonstrated in vitro activity against most gram-positive and gram-negative pathogens, |
|---|
including CRE and Acinetobacter, and anaerobes. It lacks activity against Pseudomonas.
| (d) | Low oral bioavailability; therefore, only IV formulation is FDA-approved. |
|---|---|
| (e) | Randomized, double-blind, multicenter trial found that eravacycline was noninferior to |
ertapenem for the management of complicated intra-abdominal infections.
viii.
Omadacycline
| (a) | Omadacycline is an aminomethylcycline antibiotic in the tetracycline class escaping many |
|---|
resistance mechanisms seen in other tetracyclines.
| (b) | FDA approved in 2018 for community-acquired bacterial pneumonia and SSIs |
|---|---|
| (c) | Has activity against most gram-positive and gram-negative pathogens, including ESBL- |
producing isolates, Acinetobacter, Stenotrophomonas, anaerobes, and atypicals. It lacks
activity against Pseudomonas.
| (d) | Available as an injectable and oral |
|---|---|
| (e) | Randomized, double-blind, multicenter trial found that eravacycline was noninferior to |
moxifloxacin for the management of community-acquired bacterial pneumonia.