Clinical Infectious Diseases
CORRESPONDENCE
Noncarbapenem ß-Lactams
for the Treatment of Extended-
Spectrum ß-Lactamase
Infections: What Are the
Remaining Drugs Outside the
United States?
To the Editor—We have read with
great interest the outstanding review
by Tamma et  al concerning noncarbap-
enem β-lactam alternatives in case of
extended-spectrum β-lactamase (ESBL)
infections [1]. Authors should be con-
gratulated for their exhaustive review of
the literature. Indeed, in an era of carbap-
enem-sparing regimen, solid data regard-
ing carbapenem alternatives are greatly
appreciated, including the ones regarding
antibiotics of last resort [2]. Nevertheless,
as highlighted by the authors, the review
is limited to antibiotics available in the
United States. We believe it would be
insightful to add data regarding the other
noncarbapenem β-lactam alternatives to
support their availability in the United
States.
For instance in France, following
the benfluorex scandal [3] the French
National Agency for Medicines and
Health Products Safety introduced new
alternatives to nitrofurantoin with the
revival of mecillinam in 2013. Mecillinam
is a β-lactam with data limited to lower
urinary tract infections (UTIs) that
reveal different success rates on ESBL-
producing bacteria depending on doses
(56% with 200 mg thrice daily and 80%
mainly 400 mg thrice daily) [4, 5]. The
same apply to temocillin which is avail-
able since 1985 in Belgium [6] and shares
recent data in the United Kingdom con-
cerning ESBL infections promoting its
utilization [7]. Furthermore, resistance to
these 2 drugs is deemed to be low, includ-
ing against ESBL isolates [8].
Moreover, amoxicillin-clavulanate has
showed interesting in vitro data against
ESBL isolates, particularly because it is
not affected by the so called “inoculum
316 • CID 2018:66 (15 January) •  CORRESPONDENCE
effect” [9] emphasized by the authors
concerning cefepime and piperacillin-ta-
zobactam [1]. Yet, results are showing
encouraging outcomes in the treatment
of ESBL-associated mild UTIs [10, 11]
when minimum inhibitory concentra-
tions have been explored.
The price of antibiotics could be
another factor to be taken into account
for the choice of the carbapenem-spar-
ing molecule, especially because prices
vary widely between countries. For
example, in the university hospitals of
Paris, France, the daily price for amox-
icillin-clavulanate (1 g thrice daily) is
about €3, while piperacillin-tazobactam
(4 g thrice daily) costs €4.70 and temo-
cillin (1 g twice daily) costs €88.80. In
comparison, new drugs such as ceftazi-
dime-avibactam cost €501 (2 g/0.5 g
thrice daily) and €174.50 (1 g/0.5 g thrice
daily) for ceftolozane-tazobactam.
Overall, we believe our data comple-
ment the authors’ review and might be
helpful to promote carbapenem-spar-
ing policies. This might be of particular
interest considering that under real-life
conditions, patient may be infected by
an ESBL-producing bacteria expressing
another resistance mechanism.
Note
Potential conflicts of interest.  Both authors:
No reported conflicts of interest. Both authors
have submitted the ICMJE Form for Disclosure
of Potential Conflicts of Interest. Conflicts that
the editors consider relevant to the content of the
manuscript have been disclosed.
Benjamin Davido and Aurélien Dinh
Maladies Infectieuses, Hôpital Raymond-Poincaré,
Assistance Publique–Hôpitaux de Paris, Garches, France
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Correspondence: B.  Davido, Raymond Poincaré Teaching
Hospital, Infectious Diseases, 104 Bd Raymond Poincaré,
Garches, 92380 France (benjamin.davido@gmail.com).
Clinical Infectious Diseases®  2018;66(2):316
© The Author(s) 2017. Published by Oxford University Press for
the Infectious Diseases Society of America. All rights reserved.
For permissions, e-mail: journals.permissions@oup.com.
DOI: 10.1093/cid/cix803