Hospital Pharmacy - February 2018 - 39

Kidd and Walker
Table 1. Antibiotics in Development.
Generic name

Sponsor

Indication

Ceftobiprole

Basilea

Pneumonia

Cefiderocol

Shionogi

UTI, Pneumonia,
Sepsis

Imipenem,
Cilastatin,
Relebactam

Merck & Co

Pneumonia, cIAI,
UTI

Sulopenem

Pfizer

UTI, cIAI

Fusidic acid

Cempra
Pharmaceuticals, Inc
Tetraphase
Pharmaceuticals, Inc

ABSSSI, Prosthetic
joint infections
cIAI, UTI

Omadacycline

Paratek
Pharmaceuticals, Inc

ABSSSI, Hospitalacquired bacterial
pneumonia

Plazomicin

Achaogen, Inc

UTI

Iclaprim

Motif BioSciences, Inc

ABSSSI, hospital
acquired bacterial
pneumonia

Lefamulin

Nabriva Therapeutics
US, Inc

CAP

Eravacycline

Comments
A cephalosporin. Ceftobiprole is available in Europe. The FDA has
requested additional Phase III studies, stating that the clinical data
submitted in support of the application was not reliable. DHHS
through BARDA is providing a grant to support development of
ceftobiprole in the United States.
A cephalosporin. Shionogi announced that in a 452-patient, Phase
III trial, cefiderocol was noninferior to imipenem/cilastatin in the
treatment off Gram-negative urinary tract infections.
An ongoing Phase III trial will compare the safety and efficacy of
imipenem/cilastatin/relebactam with piperacillin/tazobactam. A
second trial imipenem/cilastatin/relebactam will be compared with
colistimethate sodium plus imipenem/cilastatin.
A cephalosporin. A Phase III trial is expected to begin by the end of
2017. According to Pfizer, interim data suggest that sulopenem has
similar safety and efficacy profiles to that of other carbapenems.
A fusidane antibiotic. Cempra announced that fusidic acid was
noninferior to linezolid in a 700-patient, Phase III ABSSSI trial.
A tetracycline. Eravacycline was noninferior to ertapenem for ABSSSI
in a 541-patient, Phase III, trial, but was inferior to levofloxacin in
a Phase III study in complicated UTI. Tetraphase announced that
in a 500-patient, Phase III trial, eravacycline was noninferior to
meropenem in patients with cIAI achieving clinical cure.
A tetracycline. Paratek announced that in a Phase III ABSSSI trial,
omadacycline was noninferior to linezolid. Subgroup analysis of data
from the trial suggested that the dose of omadacycline does not
need adjustment for renal function or obesity. The company also
announced that omadacycline was noninferior to moxifloxacin in a
774-patient CAP trial.
An aminoglycoside. In a 609-patient, Phase II trial, plazomicin was
noninferior to meropenem in the treatment of complicated UTI.
In a 69-patient, Phase III trial, involving patients with carbapenemresistant Enterobacteriaceae bacteremia who were receiving
meropenem or tigecycline, plazomicin had lower mortality and
complications than colestin.
A diaminopyrimidine dihydrofolate reductase inhibitor. Motif Bio
announced that in a Phase III trial, iclaprim was noninferior to
vancomycin in achieving >20% reduction of lesion area at 48-72 h
in 600 patients with ABSSSI.
A pleuromutilin antibiotic. In a 551-patient, Phase III trial, lefamulin
was noninferior to moxifloxacin with or without linezolid in the
treatment of CAP.

Note. Information adapted from the Prescribe Right Pharmaceutical Pipeline Tracker database.7 FDA = Food and Drug Administration;
DHHS = Department of Health and Human Services; BARDA = Biomedical Advanced Research and Development Authority; UTI = urinary tract infection;
cIAI = complicated intra-abdominal infections; ABSSSI = acute bacterial skin and skin structure infections; CAP = community-acquired pneumonia.

New Treatment Options
To stay ahead of drug-resistant bacteria, researchers are
developing new antibiotics (Table 1) and looking for synergistic combinations of older drugs. Beta-lactam antibiotics
such as carbapenem/beta-lactamase inhibitors, new cephalosporins, and carbapenem dehydropeptidase inhibitors are
being tested in an effort to combat the evolution of drugresistant bacteria. Researchers are looking into combination carbapenem/beta-lactamase inhibitors as well as a
triple combination of cilastatin/imipenem/relebactam for

the treatment of multidrug-resistant bacteria. New cephalosporins include ceftobiprole and cefiderocol. Studies have
shown that the drugs listed in Table 1 are noninferior to
current therapies. Phase III trials are currently being conducted that will help determine the safety of cefiderocol
and imipenem/cilastatin/relebactam. New antibiotics also
include a systemic dosage of fusidic acid; new tetracyclines, eravacycline and omadacycline; a new aminoglycoside, plazomicin; a diaminopyrimidine dihydrofolate
reductase inhibitor, iclaprim; and the first pleuromutilin
antibiotic, lefamulin.

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