Infectious Diseases II
| (c) | FDA approved for the treatment of complicated intra-abdominal infection and complex |
|---|
UTIs. However, most clinicians will reserve its coverage for difficult-to-treat pathogens
with minimal coverage options, such as KPC-producing Enterobacterales.
| (d) | An in vitro study that included 120 KPC-producing pathogens showed good activity with |
|---|
ceftazidime/avibactam.
| (e) | A recent multicenter-observational, propensity score-weighted study comparing |
|---|
ceftazidime/avibactam with colistin as the initial treatment for CRE showed significant
improvements in mortality. These findings require confirmation in a randomized
controlled study.
| (f) | Study evaluating compassionate use of ceftazidime/avibactam as a second-line agent |
|---|
compared with a matched cohort of patients with CRE bacteremia treated with a different
agent illustrated significant improvements in mortality (36.5% vs. 55.8%, p=0.005).
| (g) | No major adverse effects were seen with ceftazidime/avibactam in phase II and phase III |
|---|
studies.
| (h) | Currently, the average wholesale price for ceftazidime/avibactam is about $1000 per day |
|---|
with normal dosing. This is similar to meropenem/vaborbactam but considerably more
expensive than other ฮฒ-lactams.
iv.
Meropenem/vaborbactam
| (a) | Vaborbactam, which alone has no antimicrobial activity, is a novel cyclic boronic acid- |
|---|
based ฮฒ-lactamase inhibitor that potentiates the activity of meropenem.
| (b) | Spectrum of activity: Broad gram-negative activity, including multi-drug resistant |
|---|
Enterobacterales, and remains stable in the presence of ESBLs and AmpC ฮฒ-lactamases.
Vaborbactam is a potent inhibitor of class A carbapenemases, including KPC and class
A and C ฮฒ-lactamases. It is not found to expand coverage to carbapenem-resistant
Acinetobacter baumannii, Pseudomonas aeruginosa, or Stenotrophomonas maltophilia.
| (c) | FDA-approved in 2017 for complicated UTIs. However, most clinicians reserve its |
|---|
coverage for difficult-to-treat pathogens with minimal coverage options, such as KPC-
producing Enterobacterales.
| (d) | A recent multicenter, randomized, prospective, open-label, comparative trial evaluated |
|---|
the efficacy of meropenem/vaborbactam to best available therapy (including mono- or
combination therapy with polymyxin B or colistin, carbapenems, aminoglycosides,
tigecycline, or ceftazidime/avibactam) for the management of complicated UTI, healthcare-
associated pneumonia, ventilator-associated pneumonia, bloodstream infections, and
complicated
intra-abdominal
infections.
Meropenem/vaborbactam
demonstrated
improved efficacy and decreased adverse events compared to best available therapy. Of
note, only one patient received ceftazidime/avibactam; therefore, no conclusions can be
drawn regarding comparative efficacy between these two agents.
Imipenem/cilastatin/relebactam
| (a) | Cilastatin is a dehydropeptidase-1 inhibitor that prevents inactivation of imipenem by |
|---|
renal dehydropeptidase-1.
| (b) | Relebactam is a non-ฮฒ-lactam ฮฒ-lactamase inhibitor that is active against class A |
|---|
ฮฒ-lactamases. Compared to avibactam, relebactam has less inhibitory activity against
OXA-48, and neither inhibitor is active against metallo-ฮฒ-lactamases.
| (c) | FDA-approved in 2019 for complicated UTIs, intra-abdominal infections, and health |
|---|
care-associated/ventilator-associated pneumonia. However, most clinicians reserve its
coverage for difficult-to-treat pathogens with minimal coverage options, such as KPC-
producing Enterobacterales.
| (d) | In vitro studies have demonstrated that relebactam, when added to imipenem/cilstatin, |
|---|
restores activity against imipenem nonsusceptible strains that produce KPC.