Content uploaded by Pasquale Pagliano
Author content
All content in this area was uploaded by Pasquale Pagliano on Feb 09, 2020
Content may be subject to copyright.
REVIEW
210
Le Infezioni in Medicina, n. 3, 210-216, 2017
Corresponding author
Pasquale Pagliano
E-mail: ppagliano@libero.it
n INTRODUCTION
Listeria monocytogenes is a Gram-positive intra-
cellular pathogen causing listeriosis, a food
borne infection causing severe and life threaten-
ing diseases. In the industrialized countries, liste-
riosis has an incidence estimated at around three-
six cases per million population per year, if we
consider the most common forms of the infection:
neurolisteriosis, bacteraemia, and maternal-neo-
natal infection. Patients with listeriosis are at
the extremes age of the life or report specic risk
factors such as malignancies, diabetes, cirrhosis,
alcoholism, or other diseases causing a defect of
cellular immunity. Only a few prospective studies
Epidemiology and treatment
of the commonest form of listeriosis:
meningitis and bacteraemia
Pasquale Pagliano1, Ferhat Arslan2, Tiziana Ascione1
1AORN dei Colli, D. Cotugno Hospital, Department of Infectious Diseases, Naples, Italy;
2Department of Infectious Diseases and Clinical Microbiology, Istanbul University Hospital, Istanbul, Turkey
Listeria monocytogenes is a Gram-positive bacillus and
facultative intracellular bacterium whose transmission
occurs mainly through the consumption of contami-
nated food. Listeriosis has an incidence estimated at
around three-six cases per million per year and the
most common forms of the infection are neuroliste-
riosis, bacteraemia, and maternal-neonatal infection.
Those affected by listeriosis are at the extremes age of
the life or report specic risk factors, such as malignan-
cies, causing a defect of cellular immunity.
Patients with L. monocytogenes meningitis present with
signs and symptoms similar to those reported in the
general population with community-acquired bacteri-
al meningitis, but can experience a longer prodromal
phase. Instead, patients with bacteraemia present gen-
erally with a febrile illness without focal symptoms, or
with inuenza-like symptoms and diarrhoea. These
aspecic ndings make the diagnosis difcult in the
population of patients at the highest risk such as cir-
rhotics or those receiving chemotherapy. Mortality rate
is estimated around 20% with a signicant increase
among those reporting a delay in diagnosis and treat-
ment and in those with severe comorbidity.
A number of antibiotics have been demonstrated to be
active against L. monocytogenes, but penicillin, amoxi-
cillin, and ampicillin are those used with the highest
SUMMARY
frequency and suggested by current guidelines and
expert opinions. These antibiotics bind to PBP-3 with
high afnity and are stored in the cytosol when taken
up by cells. Although amoxicillin appears to have a bet-
ter activity than ampicillin on the basis of studies, am-
picillin is currently the drug of choice for the treatment
of listeriosis. Cotrimoxazole could be administered
as an alternative treatment; its use is associated with
a favourable outcome probably due to the favourable
penetration with brain. Quinolones have an excellent
tissue and cell penetration and are rapidly bactericidal,
but their clinical activity is not as high as we can pre-
dict on the basis of experimental model. Linezolid of-
fers a number of advantages in the empiric treatment
of meningitis due to its favourable penetration of CSF
and the absence of bacteriolytic effect on S. pneumoniae
as conrmed by a number of case-series highlighting
its use as rescue therapy of pneumococcal meningitis,
but data are currently limited particularly if we consid-
er neurolisteriosis. Combination therapies have been
proposed to enhance the activity of penicillins against
Listeria in an attempt to achieve complete killing and
decrease mortality. Steroids use is ineffective.
Keywords: Listeria monocytogenes, meningitis, treatment,
immunocompromised, cirrhosis, infection.
211Epidemiology and treatment of listeriosis
investigated the characteristic of patients affect-
ed by listeriosis and current therapeutic guide-
lines are based only on the analysis of case-series,
lacking prospective studies on the treatment. No
improvement has been reported over the past de-
cades in term of prognosis [1-5].
Epidemiology and clinical findings of listeriosis
Listeriosis is a sporadic disease, but outbreaks
can occur after the consumption of contaminat-
ed food (Table 1). L. monocytogenes exists in dif-
ferent conditions due to its ability to survive in
extreme conditions, such as wide pH range, high
salt concentrations and due to the ability to grow
and persist at refrigeration temperatures. All
these conditions can give an advantage in respect
to other more common pathogens transmitted
by contaminated food [6]. An idea of the ability
of Listeria to persist in extreme condition can be
given by the observation that L. monocytogenes can
persist over12 months in the extreme condition of
a milkshake machine causing cases of invasive
disease [7]. Several listeriosis outbreaks occurred
in United States recently, linked to dairy products
and fresh produce [8-10].
On the basis of a recent prospective study consid-
ering over 800 patient with listeriosis observed in
372 centre in France over a 4-year period, it was
estimated that less than 15% of the cases report
maternal-neonatal infections, 50% reports bacte-
raemia, and the remaining are cases of neurolis-
teriosis [5]. Current investigations and guidelines
suggest that L. monocytogenes has to be considered
among the causative agents of invasive infection
and meningitis in all patients at the extremes
ages of the life and in those reporting immuno-
compromission. Evaluating the whole population
of patient with listeriosis enrolled in the MON-
ALISA study, specic risk factors are considered
maternal origin from Maghreb or sub-Saharan
Africa for newborn; instead male sex, diabetes
mellitus, treatment with steroids, and solid can-
cer are the condition reported with the highest
frequency in those with neuroinvasive infection
and bacteraemia. Only 4% of patients with neu-
rolisteriosis were younger than 40 years, reported
no comorbidity, and did not report any infection
before listeriosis [5]. Moreover, less than 5% of the
cases of bacteraemia and neurolisteriosis report-
ed during a 15-year period in a Danish study and
14% of the cases with neurolisteriosis reported in
the multinational retrospective study reported
no specic risk factor. On the basis of cumulative
data reported, we can establish that L. monocyto-
genes has to be strongly considered as the caus-
ative agents of neuroinvasive infection and sepsis
mainly in particular subset of immunocompro-
mised patients [3, 5, 11].
Patients with bacteraemia present generally with
a febrile illness without focal symptoms, or with
inuenza-like symptoms and diarrhoea. These
nonspesic ndings make the diagnosis difcult
in some patients at high risk such as cirrhotics or
those receiving chemotherapy as they can acquire
a wide range of infections with aspecic prodro-
mal symptoms [12-15]. Alteration of conscious-
ness and fever are frequently reported in neurolis-
teriosis cases. Nuchal rigidity can be observed in
about 60% of these cases and the classic triad of
nuchal rigidity, fever and impaired consciousness
status was reported in about 50% of them [16,
17]. No conclusive data are reported regarding
incidence of septic shock that is observed among
1% of the cases reported in the MONALISA pro-
spective study, but appears to be more frequent
on the basis of other retrospective studies consid-
ering patients with bacteraemia or meningitis. L.
monocytogenes is not considered among the com-
mon causes of septic shock [18]. Moreover, focal
neurologic decit or seizure are reported in about
20% of the cases, less frequently than reported in
those with pneumococcal meningitis considering
studies comparing the ndings of pneumococcal
and listerial meningitis (Table 2). Respiratory fail-
ure within 48 hours from admission is reported
less frequently in Listeria meningitis patients [16].
Patients with bacteraemia/meningitis sustained
by L. monocytogenes report a mortality rate exceed-
ing 20%. Lack of administration of an adequate
therapy resulted in the patient’s death within
Table 1 - Food item with the highest risk of contamina-
tion with Listeria monocytogenes.
Sausages
Raw meat, in particular turkey and chicken
Sandwiches
Raw milk and products made from this ingredient
Any meat conserved after having been heated
Soft cheese
Sea food (salmon, mussels)
212 P. Pagliano, et al.
3 days in all the untreated cases reported in the
MONALISA study and any delay of initiation of
an adequate treatment was associated to an in-
crease of the risk of death [5].
Treatment
The intracellular nature of Listeria makes its ef-
fective treatment difcult. Many antibiotics have
been demonstrated to be active in vitro against
Listeria, but most of them have been demonstrat-
ed to be only bacteriostatic in the intracellular en-
vironment. Moreover, the ndings deriving from
studies in vitro do not directly correlate with in
vivo efcacy [19].
An ideal antibiotic active against Listeria must
penetrate within host cell, and must bind tightly
to an intracellular target (Table 3). Ideally, antibi-
otic has to concentrate within host cell creating
depots, ensuring a long-lasting optimal antibi-
otic concentration to avoid that bacteria can sur-
vive when antibiotic concentration becomes low.
Moreover, an antibiotic active against Listeria
must have the ability to bind to penicillin-bind-
ing protein 3 (PBP-3) of Listeria, which causes cell
death [20, 21].
A number of antibiotics have been demonstrated
to be active against L. monocytogenes, penicillin,
amoxicillin, and ampicillin are those used with
the highest frequency and suggested on the basis
of guidelines or expert opinions. These antibiotics,
as expected, bind to PBP-3 with high afnity and
are stored in the cytosol when taken up by cells,
but have been demonstrated to be only slowly
bactericidal in a model of intracellular infection in
vitro. Although amoxicillin appears to have a bet-
ter activity than ampicillin on the basis of in vitro
studies, ampicillin is currently the drug of choice
for the treatment of listeriosis. Current investiga-
tions suggest that the adult dose of ampicillin has
to be over 9g per day and that the treatment has
to be administered for at least 21 days when men-
ingitis has to be treated [22].
Listeriosis is observed with the highest frequency
in immunocompromised whose immune mecha-
nisms can be inadequate to complete the bacterial
killing after antibiotic treatment [23]. On the basis
of pharmacokinetic considerations, encapsula-
tion of antibiotics within liposomes has been pro-
posed because of the favourable effect observed
in a mouse model of meningitis, no similar study
in humans has been reported [24].
Cotrimoxazole could be administered as an alter-
native treatment for listeriosis. However, it was
not as effective as quinolones or ampicillin in an
experimental model of meningitis, raising some
doubt on its efcacy when administered as mono-
Table 3 - Clinical and neurological findings of 131 ageing patients with bacterial meningitis (Adapted from Paglia-
no P. et al [16]).
Streptococcus pneumoniae
(109 cases)
Listeria monocytogenes
(22 cases) P
Extrameningeal infection (%) 72 (66) 1 (5) <0.0001
Respiratory failure within 48 hours from admission (%) 55 (50) 2 (10) <0.001
Fever (%) 96 (88) 22 (100) 0.12
Neck stiffness (%) 86 (79) 15 (68) 0.45
GCS <11 (%) 77 (71) 21 (95) <0.05
Motor decit 9 (8) 1 (5) 0.99
Seizure before admission 9 (8) 2 (9) 0.99
Table 2 - Antibiotics commonly administered to treat
listeriosis.
Antibiotic Daily dosage Number of
administrations
Penicillin G 24 MU 4-6
Ampicillin 9-12 g 4
Amoxicillin 8 g 4
Meropenem 6 g 3
Vancomycin 2 4
Gentamicin 5 mg x kg 3
Rifampin 600-900 mg 1-2
Cotrimoxazole 10-20 mg x kg 2-4
Levooxacin 1000 2
Linezolid 1200 mg 2
213Epidemiology and treatment of listeriosis
therapy. Cotrimoxazole had the same effects on
intracellular and extracellular L. monocytogenes,
probably due to the ability of trimethoprim to
inhibit cell wall synthesis and cell separation. An
advantage in term of survival after cotrimoxazole
administration in respect to the other antibiotic
treatments (excluding ampicillin) was demon-
strated in the French study [5, 25, 26].
Quinolones are valuable drugs in the treatment
of listeriosis as they have an excellent tissue and
cell penetration and are rapidly bactericidal. On
the basis of an intracellular model of listerial in-
fection, it was demonstrated that intracellular
activity of quinolones against L. monocytogenes
is only a fraction of what could be anticipated if
their apparent accumulation in cells is taken into
account. Thus, whereas quinolones show higher
concentrations in cells compared with medium,
they are also characterized by somewhat weaker
activity against intracellularL. monocytogenes [27].
Levooxacin has been proposed as empiric ther-
apy of bacterial meningitis to ensure Listeria cov-
erage, but its use has to be evaluated in larger se-
ries [28]. In using quinolones as empiric therapy
of meningitis, we have to remember that their
administration can increase teichoic acid release
if Streptococcus pneumoniae is the causative agent
boostering host immunity and contributing to
brain damage [29].
Linezolid is an oxazolidinone reporting in vitro
activity against L. monocytogenes. Its elevated CSF
and intracellular concentrations seem adequate
for the treatment of neurolisteriosis, as extrapo-
lated by reliable animal models [30]. When aller-
gy to both penicillin and cotrimoxazole became
of concern, a linezolid-rifampin combination was
successful administered to a patient with brain
abscess sustained by L. monocytogenes without
any hematological toxicity after 107 consecutive
days of treatment [31]. Overall, linezolid offers a
number of advantages in the empiric treatment
of meningitis due to its favourable penetration of
CSF and the absence of bacteriolytic effect on S.
pneumonia, as conrmed by a number of case-se-
ries highlighting its use as rescue therapy of
pneumococcal meningitis, but data are currently
limited if we consider neurolisteriosis. Only 6 cas-
es receiving linezolid are reported in the MON-
ALISA study.
Meropenem, a broad-spectrum antibiotic of the
carbapenem class of beta-lactam agents, displays
a remarkably low minimum inhibitory concen-
tration (even lower than that of ampicillin)
against L. monocytogenes [32]. However clinical
data are not conclusive and failure after treat-
ment was suspected on the basis of case-reports.
A Danish retrospective study highlights that pa-
tients receiving meropenem report a higher mor-
tality, as assessed by multivariate analysis, com-
pared to those receiving aminopenicillins and
benzylpenicillin [11, 33]. The reason for this dif-
ference remains unclear, and we could speculate
that some difference in the intracellular activity
of the drug justies the changes in the cure rate.
Overall, these ndings may be of some concern
in some populations such as cirrhotics that re-
port an increase of the risk of both Listeria and
Escherichia coli meningitis and receive frequently
treatment with carbapenems to cover the risk of
multiresistant E. coli.
Rifampin has demonstrated excellent intracellu-
lar and extracellular bacteriostatic activity that is
not dose dependent against L. monocytogenes in
vitro. Rifampin is capable of excellent penetration
into the CSF and cells. However, recent in vitro
testing using time-kill studies indicated an an-
tagonistic effect when combined with penicillins
or cotrimoxazole. Therefore, rifampin use has to
receive careful evaluation in the treatment of liste-
riosis [34].
Vancomycin shows variable activity against Liste-
ria strains. It is bactericidal within six hours; how-
ever, its use is limited in cases of meningitis due to
its inability to cross the blood-brain barrier reach-
ing therapeutic concentration. L. monocytogenes
meningitis was reported during treatment with
vancomycin in a neutropenic patient receiving
the drug due to staphylococcal infection, demon-
strating that the drug has not sufcient activity
against Listeria, at least in severely immunode-
pressed patients [35].
Combination therapies have been proposed to
enhance the activity of penicillins against Liste-
ria in an attempt to achieve complete killing and
decrease mortality. Addition of gentamicin to
ampicillin reports the best killing rate on the ba-
sis of in vitro studies, but activity of gentamicin
within intracellular bacteria is quite irrelevant
and we have to remember that L. monocytogenes
reports the ability to penetrate rapidly within
host cells [36]. Animal models fail to demonstrate
signicant advantages by this combined therapy
214 P. Pagliano, et al.
administration, but the large MONALISA study
demonstrated that those receiving amoxicillin/
aminoglycoside combination therapy reported a
lower risk of death [5]. However, in reporting the
results of this study, we have to consider that the
effect of this combination therapy was reported
for the whole population of patients including
those with bacteraemia and neurolisteriosis and
no separate analysis was reported.
Other drug combination has been tested against
L. monocytogenes, in a small retrospective series
of 22 cases with Listeria meningitis published
over 20 years ago combination of cotrimoxaz-
ole and ampicillin was the most effective treat-
ment, but the small size of the study cannot
give denitive indication on the most effective
treatment [37].
On the basis of the MONALISA study in the
subset of patients with neurolisteriosis, the ad-
ministration of steroids reported an increase of
the risk of an unfavourable outcome. This nd-
ing was quite surprising as, on the basis of the
randomized study by de Gans, dexamethasone
administration in patients with non-pneumococ-
cal meningitis did not worsen outcome [38]. No
relevant information is reported in the French
study about the dosage of steroids, but we can
suppose that some impairment in immunity en-
hanced by steroids could justify this evidence
[5]. Similar ndings were not reported by other
authors in other case-series analysis suggesting
that steroids administration has no harm or ben-
et in patients with Listeria meningitis [39]. On
the basis of current evidence, it is reasonable to
stop dexamethasone when L. monocytogenes is
identied in patients with meningoencephalitis.
n CONCLUSIONS
On the basis of current evaluations, treatments of
listeriosis remains challenging, mainly because
patients affected are immunocompromised due
to relevant comorbidity or report an impairment
of immunity related to age.
MONALISA study provides a lot of useful in-
formation, conrming the ndings retrieved in
smaller retrospective studies. First of all it under-
lines that L. monocytogenes must be suspected in
immunocompromised host or in those patients
at the extreme age of the life presenting with
bacteraemia or meningitis: in these patients, an
empirical treatment containing a drug active
against Listeria is associate with a reduced mor-
tality. Second, treatment cannot exclude amino-
penicillin, as the other drugs currently proposed
have limited data supporting their use and do
not demonstrate a signicant increase in term of
in vitro activity or cure rate. Patients with inva-
sive listeriosis can receive a combined therapy
considering the administration of ampicillin and
amynoglocosides if blood cultures are positive
or ampicillin and cotrimoxazole if neurolog-
ic involvement is evident. Data supporting the
use of other drugs in combination therapy has
to receive careful evaluation, considering that
the clinical experience is limited and that exper-
imental data itself cannot be conclusive. Among
the drugs proposed for the treatment, we be-
lieve that linezolid could be promising due to
its activity against penicillin-tolerant strains of
S. pneumoniae and due to the efcacy reported
in case-reports, but the small number of cases
treated makes difcult every conclusion. Third,
steroids administration cannot be currently pro-
posed to patients with listeriosis.
Conict of interest
The authors declare no conict of interest
n REFERENCES
[1] Thigpen M.C., Whitney C.G., Messonnier N.E., et al.
Bacterial meningitis in the United States, 1998-2007. N.
Engl. J. Med. 364, 2016-2025, 2011.
[2] Vázquez-Boland J.A., Kuhn M., Berche P., et al. Liste-
ria Pathogenesis and Molecular Virulence Determi-
nants. Clin. Microbiol. Rev. 14, 584-640, 2001.
[3] Pagliano P., Ascione T., Boccia G., De Caro F., Esposi-
to S. Listeria monocytogenes meningitis in the elderly: ep-
idemiological, clinical and therapeutic ndings. Infez.
Med. 24, 105-111, 2016.
[4] de Noodhout C.M., Devleesschauwer B., Angulo
F.J., et al. The globalburdenof listeriosis: a systemat-
icreviewandmeta-analysis. Lancet Infect. Dis. 14, 1073-
1082, 2014.
[5] Charlier C., Perrodeau E., Leclercq A., et al. Clinical
features and prognostic factors of listeriosis: the MON-
ALISA National prospective color study. Lancet Infect.
Dis.17, 519-519, 2017.
[6] Ferreira V., Wiedmann M., Teixeira P., Stasiewicz
M.J. Listeria monocytogenes persistence in food-associat-
ed environments: epidemiology, strain characteristics,
215Epidemiology and treatment of listeriosis
and implications for public health. J. Food Prot. 77, 150-
170, 2014.
[7] Li Z., Pérez-Osorio A., Wang Y., et al. Whole ge-
nome sequencing analyses of Listeria monocytogenes
that persisted in a milkshake machine for a year and
caused illnesses in Washington State. BMC Microbiol-
ogy 17, 134, 2017.
[8] Silk B.J., Date K.A., Jackson K.A., et al. Invasive
listeriosis in the foodborne diseases active surveillance
network (FoodNet), 2004-2009: further targeted pre-
vention needed for higher-risk groups. Clin. Infect. Dis.
54 (Suppl. 5), S396-S404, 2012.
[9] Chen Y., Gonzalez-Escalona N., Hammack T.S., Al-
lard M.W., Strain E.A., Brown E.W. Core genome multi-
locus sequence typing for identication of globally dis-
tributed clonal groups and differentiation of outbreak
strains of Listeria monocytogenes. Appl. Environ. Microbi-
ol. 82, 6258-6272, 2016.
[10] Chen Y., Burall L.S., Luo Y., et al. Listeria monocy-
togenes in stone fruits linked to a multistate outbreak:
enumeration of cells and whole-genome sequencing.
Appl. Environ. Microbiol. 82, 24, 7030-7040, 2016.
[11] Thønnings S., Knudsen J.D., Schønheyder H.C., et
al. Antibiotic treatment and mortality in patients with
Listeria monocytogenes meningitis or bacteraemia. Clin.
Microbiol. Infect. 22, 725-730, 2016.
[12] Pagliano P., Carannante N., Gramiccia M., et al.
Visceral leishmaniasis causes fever and decompensa-
tion in patients with cirrhosis. Gut 56, 893-894, 2007.
[13] Pagliano P., Costantini S., Gradoni L., et al. Dis-
tinguishing visceral leishmaniasis from intolerance to
pegylated interferon-alpha in a thalassemic splenec-
tomized patient treated for chronic hepatitis C. Am. J.
Trop. Med. Hyg. 79, 9-11, 2008.
[14] Arslan F., Meynet E., Sunbul M., et al. The clinical
features, diagnosis, treatment, and prognosis of neuro-
invasive listeriosis: a multinational study. Eur. J. Clin.
Microbiol. Infect. Dis. 34, 1213-1221, 2015.
[15] Ascione T.,Pagliano P., Balato G., Mariconda M.,
Rotondo R., Esposito S. Oral therapy, microbiologi-
cal ndings, and comorbidity inuence the outcome
of prosthetic joint infections undergoing 2-stage ex-
change. J. Arthroplasty 32, 2239-2243, 2017.
[16] Pagliano P., Attanasio V., Rossi M., et al. Listeria
monocytogenes meningitis in the elderly: distinctive
characteristics of the clinical and laboratory presenta-
tion. J. Infect. 71, 134-136, 2015.
[17] Pagliano P., Attanasio V., Rossi M., et al. Pneumo-
coccal meningitis in cirrhotics: distinctive ndings of
presentation and outcome. J. Infect. 65, 577-579, 2012.
[18] Esposito S., De Simone G., Boccia G., De Caro
F.,Pagliano P. Sepsis and septic shock: New denitions,
new diagnostic and therapeutic approaches. J. Glob. An-
timicrob. Resist. 10, 204-212,2017.
[19] Hof H. An update on the medical management of
listeriosis. Expert Opin. Pharmacother. 5, 1727-1735, 2004.
[20] Temple M.E., Nahata M.C. Treatment of losteriosis.
Ann. Pharmacother. 34, 656-661, 2000.
[21] Krawczyk-Balska A., Popowska M., Markiewicz Z.
Re-evaluation of the signicance of penicillin binding
protein 3 in the susceptibility of Listeria monocytogenes
to β-lactam antibiotics. BMC Microbiology 12, 57, 2012.
[22] van de Beek D., Cabellos C., Dzupova O., et al.
ESCMID guideline: diagnosis and treatment of acute
bacterial meningitis Clin. Microbiol. Infect. 22 (Suppl. 3),
S37-S62, 2016.
[23] Pagliano P., Boccia G., De Caro F., Esposito S. Bac-
terial meningitis complicating the course of liver cir-
rhosis. Infection 2017, in press doi: 10.1007/s15010-017-
1039-7.
[24] Bakker-Woudenberg I.A., Lokerse A.F., Roerdink
F.H. Effect of lipid composition on activity of lipo-
some-entrapped ampicillin against intracellular Listeria
monocytogenes. Antimicrob. Agents Chemother. 32, 1560-
1564, 1988.
[25] Michelet C., Leib S.L., Bentue-Ferrer D., Täuber
M.G. Comparative efcacies of antibiotics in a rat mod-
el of meningoencephalitis due to Listeria monocytogenes.
Antimicrob. Agents Chemother. 43, 1651-1656, 1999.
[26] Minkowski P., Staege H., Groscurth P., Schaffner
A. Effects of trimethoprim and co-trimoxazole on the
morphology of Listeria monocytogenes in culture medi-
um and after phagocytosis. J. Antimicrob. Chemother.
48,185-193, 2001.
[27] Van de Velde S., Nguyen H.A., Van Bambeke F.,
et al. Contrasting effects of human THP-1 cell differen-
tiation on levooxacin and moxioxacin intracellular
accumulation and activityagainst Staphylococcus aureus
and Listeria monocytogenes. J. Antimicrob. Chemother. 62,
518-521, 2008.
[28] Viale P., Scudeller L., Pea F., et al. Implementation
of a meningitis care bundle in the emergency room re-
duces mortality associated with acute bacterial menin-
gitis. Ann. Pharmacother. 49, 978-985, 2015.
[29] Pagliano P., Brouwer M.C. Comment: “Implemen-
tation of a meningitis care bundle in the emergency
room reduces mortality associated with acute bacterial
meningitis”. Ann. Pharmacother. 50, 152, 2016.
[30] Callapina M., Kretschmar M.,Dietz A.,Mosbach
C.,Hof H.,Nichterlein T. Systemic and intracerebral in-
fections of mice with Listeria monocytogenes successfully
treated withlinezolid. J. Chemother. 13, 265-269, 2001.
[31] Leiti O., Gross J.W., Tuazon C.U. Treatment of brain
abscess caused by Listeria monocytogenes in a patient
with allergy to penicillin and trimethoprim-sulfame-
thoxazole. Clin. Infect. Dis. 40, 907-908, 2005.
[32] Carryn S., Van Bambeke F., Mingeot-Leclercq
M.P.,TulkensP.M. Activity of beta-lactams (ampicillin,
meropenem), gentamicin, azithromycin and moxiox-
acin against intracellularListeria monocytogenes in a
24 h THP-1 human macrophage model. J. Antimicrob.
Chemother. 51, 1051-1052, 2003.
216 P. Pagliano, et al.
[33] Stepanović S., Lazarević G., Jesić M., Kos R.
Meropenem therapy failure in Listeria monocytogenes
infection. Eur. J. Clin. Microbiol. Infect. Dis. 23, 484-
486.2004.
[34] Chenal-Francisque V., Charlier C., Mehvish S., et
al. Highly rifampin-resistant Listeria monocytogenes iso-
lated from a patient with prosthetic bone infection. An-
timicrob. Agents Chemother. 58, 1829-1830, 2014.
[35] Arsene O., Linassier C., Quentin R., Legras A., Co-
lombat P. Development of listeriosis during vancomy-
cin therapy in a neutropenic patient. Scand. J. Infect. Dis.
28, 415-416, 1996.
[36] Sipahi O.R., Turhan T., Pullukcu H., et al. Moxiox-
acin versusampicillin+gentamicinin the therapy of
experimental Listeriamonocytogenes meningitis. J. Anti-
microb. Chemother. 61, 670-673, 2008.
[37] Merle-Melet M., Dossou-Gbete L., Maurer P., et al.
Is amoxicillin-cotrimoxazole the most appropriate an-
tibiotic regimen for listeria meningoencephalitis? Re-
view of 22 cases and the literature. J. Infect. 33, 79-85,
1996.
[38] de Gans J., van De Beek D. Dexamethasone in
adults with bacterial meningitis. N. Engl. J. Med. 347,
1549-1556, 2002.
[39] BrouwerM.C., van de Beek D., Heckenberg S.G.,
Spanjaard L., de Gans J. Community-acquired Liste-
ria monocytogenes meningitis in adults. Clin. Infect.
Dis.43, 1233-1238, 2006.
