A R T I C L E

Pregnancy Complicated by Listeria

Monocytogenes: A Case Report and Review
of the Literature

abdominal pain and fever to 100.9 F. Maternal tachycardia

Abstract: Listeria Monocytogenes, a small facultative anaerobic, gram positive, of 110 bpm, and fetal tachycardia to 190 bpm were appre-
motile bacillus is a rare, but consequential etiologic agent of food borne illness
which inordinately impacts immunocompromised individuals. The organism ciated on evaluation. The patient stated she had sick contacts
infects many types of animals and contaminates a multitude of foodstuffs such
as milk, chicken, beef and vegetables. This microbe additionally has a distinct
at home; both her children and husband had upper respira-
proclivity to infect the maternal-fetoplacental unit with resultant adverse tory infections. The patient was admitted, assessed for
perinatal outcomes inclusive of spontaneous abortion, preterm delivery,
chorioamnionitis, neonatal meningitis and death. We present a case of Listeriosis Influenza, had a renal ultrasound, chest x-ray, blood/urine
complicating pregnancy with a subsequent comprehensive review of the cultures and initiated on empiric triple antibiotic therapy
literature.
(Ampicillin, Gentamicin, Clindamycin), and Tylenol. An
Keywords: Listeriosis-Pregnancy-Infection-Chorioamnionitis-Maternal fetal
medicine-Obstetrics
initial biophysical profile was noted to be 4/10; however
upon resolution of the patient’s fever, a biophysical profile of
10/10 was noted. Pelvic exam denoted a closed cervix, and
positive bacterial vaginosis. Patient remained hospitalized
for 28 hours and received antenatal steroid therapy during
INTRODUCTION that time along with Flagyl. Laboratory and radiologic
evaluations/cultures were normal and she was discharged

W
e present a case of Listeriosis occurring in the
home. Final diagnosis given was that of a viral syndrome.
third trimester of pregnancy. Listeriosis is a rare
Four days post the second discharge, the patient again
and potentially fatal clinical entity impacting
presented to Labor and Delivery with complaints of
the maternal fetal dyad, but with recognition and timely
vaginal bleeding for one day and lower abdominal pain/
intervention, a successful perinatal outcome may be
tenderness. The fetal heart tracing was noted to be non-
obtained.
reactive by criteria, biophysical was 8/10, patient was
noted to have a low-grade fever of 100.6. The patient was
Case report admitted, diagnosed with likely abruption with cho-
A 28-year-old Hispanic woman @ 28 1/7 weeks gestation rioamnionitis; she had blood and urine cultures sent,
presented for a routine prenatal care visit; her prenatal initiated on empiric triple antibiotic therapy (Ampicillin
course was complicated by chronic hypertension, Quanti- Gentamicin, Clindamycin), magnesium sulfate for neuro-
FERON positive, obesity, history of prior large for gesta- protection, and induction of labor was initiated. A
tional age baby, and iron deficiency anemia. During the Neonatology consult was had with the patient. Twelve
course of her evaluation, fetal tachycardia of 170 beats per hours into the induction process, the patient was noted to
minute (bpm) was auscultated and she was sent to Labor have recurrent decelerations of the fetal heart rate, and was
and Delivery for evaluation. On arrival, initially she was subsequently taken for operative delivery.
noted to have a fetal heart rate of 165 bpm, she had no The patient delivered a viable female infant, Apgar
complaints, she was afebrile, and her physical exam was scores of 5 and 8 at 1 and 5 minutes respectively, umbilical
unremarkable. Laboratory analysis consisting of complete artery blood gas pH of 7.35. Placental abruption with
blood count, urinalysis, basic metabolic panel and bio- micro abscesses were noted [Figure 1] and placental cul-
physical profile were all within normal limits. After pro- tures were taken. Pathological examination of the placenta
longed monitoring for approximately 2 hours, the fetal
heart rate normalized and patient was discharged home
with follow-up to clinic in 1 week.
Eight days later, the patent presented to Labor and De-
livery with complaints of chills, cough, bilateral lower https://doi.org/10.1016/j.jnma.2020.05.002

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 PREGNANCY COMPLICATED BY LISTERIA

Figure 1. Gross examination of placenta infected with Listeria may Figure 3. Pathway of Listeria infection. Ingestion of contaminated food
appear normal; upon careful inspection contain minute yellow-white goes to the intestine >>> disseminated via lymphatic þ hematogenous
macro and micro-abscesses with diffuse areas of necrosis. spread to the spleen, liver, brain and placenta.

revealed acute chorioamnionitis and funisitis [Figure 2].

The placental cultures were positive for Listeria Mono- pulmonary hemorrhage, hypocalcemia, bacteremia, sei-
cytogenes; blood cultures were negative. The mothers’ zures, respiratory distress, and hyperbilirubinemia. Head
post-operative course was unremarkable and she was dis- ultrasound on days 1, 3 and 10 of life revealed bilateral
charged home on post-operative day 5. Prior to discharge, grade 2 germinal matrix hemorrhages. Brain Magnetic
upon extensive review of her dietary history-the patient did Resonance Imaging on day 32 of life, revealed tiny foci of
recall consuming tacos with cheese, and hot dogs hemosiderin deposition noted in the biparietal periven-
approximately 3 weeks prior to her third admission, at a tricular white matter, likely related to prior germinal matrix
family event. hemorrhages. At the age of 4 months the infant is being
The infant’s course, however, was complicated. Post- followed in both the developmental behavioral and pedi-
delivery, the infant was taken to the Neonatal Intensive atric neurology clinics, with development appropriate for
Care Unit (NICU) and intubated due to poor respiratory her corrected gestational age. She does have issues with
effort, low birth weight, and prematurity. The neonate had eye tracking and increased tone in her upper limbs.
blood and cerebral spinal fluid (CSF) cultures. However,
the lumbar puncture was successfully obtained after initi-
ation of Ampicillin and Gentamicin. Blood cultures were DISCUSSION
positive for Listeria, CSF was negative. It should be noted Listeria Monocytogenes is a small facultative anaerobic
that the CSF cell count and chemistries were consistent gram-positive motile bacillus. In clinical samples the or-
with meningitis. The infant was treated with Ampicillin ganism may appear as cocci, diplococci or diphtheroids
and Gentamicin for 21 days, and remained in NICU for a with the result of often misleading laboratory analysis
total of 52 days. During her hospitalization she was clearly identifying the correct pathogen. The organism is
diagnosed with: early onset neonatal sepsis, meningitis, resilientdtolerating high pH, low temperatures, and high
saline concentrations allowing it to proliferate in water,
sewage, manure, animal feed and contaminated refriger-
Figure 2. Histologically- A) Small foci of purulent villitis in which groups of ated foods. There are seven species of Listeria e four of
acutely inflamed villi are surrounded by fibrin and an acute peri-villous
and intervillous inflammatory exudate. B) The abscess is surrounded by a
which directly infect humans. The majority of infections
rim of giant cells and palisaded histiocytes. are primarily due to three serotypes; 1A, 1B and 4B.
Serotype 4B is responsible for the preponderance of out-
breaks of Listeriosis.1 Listeria species have a worldwide
distribution; however human infections occur predomi-
nantly in developed countries. In industrialized nations,
Listeriosis has an incidence of 3e6/million population
yearly2, however as the demographics change, this is likely
to increase. The incidence of the disease has been noted to
vary in different ethnic groups, place of residence and
socioeconomic status, with a higher incidence noted
among Hispanics.3e6

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PREGNANCY COMPLICATED BY LISTERIA

The microbes play a considerable role in zoonoses, considered the gold standard for treating confirmed listeri-
infecting multiple animal types (fish, arthropods, livestock, osis. Whatever antibiotic is chosen, the dosage is critical.
mammals, rodents, amphibians, and birds). In mammals, Many experts recommend 6 g or more per day of Ampicillin
Listeria infection can cause miscarriages and the devel- for treatment during pregnancy; this allows for adequate
opment of “circling disease”da clinical symptom of intracellular penetration as well as maintaining an adequate
basilar meningitis whereby the animal moves continuously dose for traversing the placentaddosage of 2 g every 6e8
in a circle. Listeria can be transmitted animal to animal, via hours is generally given. If a Penicillin allergy exists,
the fecal oral route, animal to human via direct trans- Trimethoprim/Sulfamethoxazole is an alternative. Expert
missiondand additionally humans can be infected by opinion holds for a dose of 200 mge320 mg per day as
consuming infected food products. Vertical transmission optimal therapy. Trimethoprim/Sulfamethoxazole, however
can occur transplacentally to the fetus or via birth through is best avoided in early pregnancy or in patients at risk for
an infected vaginal canal. neural tube defects due to the antifolate activity of the
The vast majority of Listeria infections appear to be trimethoprim component. Optimal therapy in pregnancy
food borne, particularly those occurring in pregnant hasn’t been firmly established; in many case reports duration
women. Foods commonly encountered which are often of therapy has varied from 2 weeks until delivery. For those
contaminated include raw vegetables/milk, fish, poultry, patients diagnosed with meningitis/endocarditis, addition of
processed chicken, beef and soft cheeses. Approximately Gentamicin is recommended. For meningitis, therapy should
15e70% of frankfurters are reported to be contaminated continue for 3 weeks; bacteremic patients without CNS
with Listeria species; Listeria is also noted to be found in involvement may be treated for 2 weeks. Endocarditis and
the stools of healthy adults.7 An infectious dose of brain abscesses require a full 6 weeks of Ampicillin therapy.
104e106 organisms/gram of ingested product causes the
Fetal listeriosis
disease. In immunocompromised individuals, patients that
have diminished gastric acidity or have undergone ulcer Perinatal mortality rates secondary to Listeria infection are
surgery, this dose may be considerably lower, in causing astoundingly high,11, with fetal demise being more com-
infectious sequelae.8 mon than neonatal death.12 Research has readily estab-
lished that placental infection precedes fetal infection in
early onset disease.13 However, it hasn’t been fully eluci-
MATERNAL LISTERIOSIS dated as to why there is a marked increased risk of Listeria
Listeria infection in pregnancy warrants special consider- infection targeting the feto-placental unit in a manner
ation. After the pregnant woman ingests food inoculated different than other tissues. It has been noted that two
with the bacteria, it traverses intestinal cells, translocates to different methodologies exist e direct invasion, or cell to
the mesenteric lymph nodes to reach their primary target cell spread. The microbe produces a number of proteins
organs, the liver and spleen, and then establishes a focus of known as internalins which play a major role in virulence
infection, which in immunocompetent individuals is and cellular invasion into the placenta. Syncytiotropho-
readily cleared. [Figure 3]. The incubation period has been blasts are directly exposed to maternal blood within the
reported to be anywhere from 24 hours to 70 days. In intervillous space. The internalin protein of Listeria exhibit
immunocompromised individuals and pregnant women, a dual pathway of virulence by:
the primary foci may be inadequately cleared. Listeria may
then be released into the bloodstreamdresulting in a 1. Adhering to and altering the membranes on the
febrile bacteremia. Pregnancy poses an increased risk of luminal surface of the intestinal villi offering an
disease, presumably secondary to the physiologic sup- entry point into the blood stream and
pression of cell mediated immunity. 2. Subsequently adhering to trophoblastic epithelium
Maternal infection is often difficult to detect and and invading the trophoblast layer to access the core
generally presents with a mild febrile illness with flu like of the placental villi.14,15
symptoms, myalgias, arthralgias, and nonspecific gastro-
intestinal symptoms. Due to the non-specific nature of the The timing of infection during gestation directly cor-
clinical symptoms, there is often a delay in diagnosis. relates with fetal outcomes. Infections early in gestation
Despite such an impediment in diagnosis, maternal mor- result in spontaneous abortions, whereas those occurring in
tality is rare.9,10 However delay in diagnosis results in the late second/third trimester have up to a 26% incidence
potentially disastrous fetal/neonatal consequences. of IUFD.16 In utero infections can additionally occur via
While Penicillin, Ampicillin and Amoxicillin have all inhalation and ingestion of infected amniotic fluid as well
been utilized in the treatment of the disease, Ampicillin is as by the hematogenous transplacental route. Fetal

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 PREGNANCY COMPLICATED BY LISTERIA

listeriosis can also be associated with the occurrence of Treatment

meconium stained amniotic fluid, fetal heart tracing ab-
There are multiple factors which make treatment for lis-
normalities, chorioamnionitis, preterm labor and increased
teria difficult:
incidence of operative delivery17e19
Neonatal listeriosis 1. The hosts’ susceptibility to infection (immunocom-
promised, pregnant) is correlated with an atypical
The incidence of neonatal listeriosis is noted to be
onset of disease
approximately 8/100,000 live births with a fatality rate
2. Intracellular survival of the microbe and involve-
reported as high as 20%.16,20,21 Infected infants may have
ment of granulomatous tissue preclude successful
pustular lesions of the skin and pharynx, be hypothermic,
therapy
lethargic, and manifest with scattered salmon colored
3. Diagnosis and treatment are often delayed
truncal papules.22
4. Dosing of antibiotic therapy is critical, particularly in
The onset of disease is divided into early (days 1e7) or
pregnancy as sufficient doses are required to cross
late (8e28)21. The early onset neonatal listerial infection is
the placenta
quite similar in presentation to that of Group Beta Strep-
tococcal (GBS) infections characterized by respiratory
The recommended therapeutic agents of choice for
distress, fever, sepsis and meningitis. Early onset infection
diagnosed or suspected Listeria infection in pregnancy
additionally is associated with a high mortality rate,
include Penicillin, Ampicillin and Amoxicillindwith
whereas late onset infection-characterized more commonly
Ampicillin being the drug of choice.23 Combination thera-
with meningitis-is less severe. Listeria is the third leading
pies have been proposed to enhance the activity of penicil-
cause of neonatal bacterial meningitis.23 CNS infections
lin’s against Listeria in an attempt to achieve complete
may mimic viral encephalitis and cause focal brain ab-
killing and decrease mortality. In acute settings, the recom-
scesses. CSF gram stains are usually negative, but pleo-
mended dose is 12 g/day of Ampicillin, while fever is pre-
cytosis is common. Neonates with late onset infections
sent, followed by 14e21 days of 1 g Amoxicillin 3  day.
tend to be term and healthy before delivery, and prior to
the diagnosis of meningitis. Infants with late onset liste-
riosis often have lower mortality rates as compared to early CONCLUSION
onset neonatal infection, 20% vs 60% respectively.23 Listeria infection is a rare pathologic entity which often
Initial therapy with intravenous Ampicillin and an lacks signs and symptoms specific enough to alert the
aminoglycoside is recommended.24 For invasive infections physician as to establishing a rapid diagnosis. This case is
without associated meningitis, treatment for 10e14 days is unique in that it clearly highlights the difficulty in estab-
usually sufficient; with meningitis 14e21 days is recom- lishing a diagnosis of Listeria in pregnancy. The patient did
mended. Diagnostic brain imaging near the end of treat- in fact have a history of ingesting apparently contaminated
ment allows determination of parenchymal involvement of food (cheese, hot dogs, taco meat). In demographics with a
the brain. high concentration of Hispanic pregnant patients its pres-
ence should be high on the differential diagnosis list when
Diagnosis and management during
the presentation of a “febrile gastroenteritis” exists.
pregnancy
Disease prevention is paramount for decreasing the
The diagnosis of Listeria in pregnancy is often problem- incidence of Listeria in pregnancy. The CDC/ACOG
atic, as approximately 30% of women are asymptomatic. If publish and update information regularly concerning
disease is suspected, it is imperative to initiate antibiotic appropriate food preparation/refrigerated storage to pre-
therapy prior to confirmatory studies. The gold standard vent contamination and bacterial growth. When consid-
for diagnosis of maternal fetal listeriosis is via placental ering the high degree of morbidity and mortality of the
cultures. Maternal blood cultures often have low sensi- maternal fetal dyad with this pathologic entity, the incor-
tivity, between 0 and 55%.18,22,25 Diagnostic amniocen- poration of patient education into clinical practice should
tesis may be considered. Alerting the laboratory be a priority for practicing health providers in these set-
technicians to perform targeted amniotic fluid cultures for tings. Early diagnosis and intervention have been corre-
Listeria Monocytogenes is prudent. If the CNS is infected, lated with improved perinatal outcomes, therefore a
gram stain is positive in less than 40% of cases, protein compilation of education, heightened suspicion, interdis-
levels are elevated, and polymorphonuclear leukocytes ciplinary management between the obstetricians/neo-
predominate in 70% of cases.26 Blood cultures are natologists and expeditious initiation of antibiotic therapy
generally positive if CNS involvement occurs. will result in positive perinatal outcomes.

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PREGNANCY COMPLICATED BY LISTERIA

11. McLauchlin, J. (1990). Human listeriosis in Britain 1967-85, A

CONFLICT OF INTEREST
summary of 722 cases. Listeriosis during pregnancy and in the
There is no conflict of interest. newborn. Epidemiol Infect, 104, 181e189.

12. Girard, D., Leclercq, A., Laurent, E., et al. (2014). Pregnancy
Lisa Serventi, M.D., Berenice Curi, M.D.,
Related Listeriosis in France 1984-2011, with a Focus on 606
Rochelle Johns, M.D., Jessica Silva, M.D., Cases from 199-2011. Euro Surveill, 19. pii 20909.
Ronald Bainbridge, M.D., FAAP,
Kecia Gaither, M.D., M.P.H., FACOG* 13. Kaur, S., Malik, S. V., Vaudya, V. M., & Barbuddhe, S. B. (2007).
Listeria Monocytogenes in spontaneous abortion in humans and
email: [email protected]
its detection by multiplex pcr. J Appl Microbiol, 103, 1889e1896.
NYC Healthþ Hospitals/Lincoln
Department of Ob/Gyn 14. Pentecost, M., Otto, G., Theriot, J. A., & Amievea, M. R. (2006).
234 East 149th Street Listeria monocytogenes invades the epithelial junctions at sites
Bronx, 10451, NY of cell extrusion. PLoS Pathog, 2, e3.

15. Lecuit, M., Nelson, D. M., Smith, S. D., et al. (2004). Targeting and
crossing of the human maternofetal barrier by Listeria Mono-
cytogenes:role of internalin interaction with trophoblast E-
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