Successful treatment of listeriosis by using high dose ampicillin in third trimester of pregnancy: a case report

Introduction

Background

Listeria monocytogenes (L. monocytogenes) is the causative agent of listeriosis, a serious food-borne infection and typically occurs sporadically. It has a predilection for pregnant women and their unborn fetuses, newborn infants and immunocompromised individuals (1-3).

Rationale and knowledge gap

Among pregnant women diagnosed with listeriosis, most of them present with asymptomatic or mild flu-like symptoms including fever, nausea, vomiting, myalgias or arthralgia (1,3). L. monocytogenes can cross the fetoplacental barrier and result in fetal loss, premature delivery, and neonatal bacteremia or meningitis. Because of the potentially severe consequences, obstetricians should be vigilant about diagnosis and prevention of listeriosis in pregnant women. Given that no prospective in vivo studies on antibiotic regimens in combating listeriosis, the optimal treatment regimen and its dosage for listeriosis in pregnancy remains unknown. Some prior studies used ampicillin combined with gentamicin in the treatment of listeriosis (4-6). Although in vitro studies suggest a synergistic effect when gentamicin is added to treatment regimen, but the toxicities of gentamicin cannot be neglected. Theoretically, appropriate diagnosis and adequate treatment of maternal listeriosis favor better clinical outcomes for both the mothers and their fetuses, but successful treatment of maternal listeriosis without fetal sequelae has been seldom reported (5,7,8).

Objective

Herein, we report successful treatment of L. monocytogenes with only ampicillin in a pregnant woman at the 31^st week of pregnancy, and the patient gave birth a healthy girl and they both kept long-term health. We present this article in accordance with the CARE reporting checklist (available at https://gpm.amegroups.com/article/view/10.21037/gpm-24-33/rc).

Case presentation

A 33-year-old multiparous woman (gravida 3 and para 1, with a first-trimester pregnancy loss at 25 years of age) was referred to the emergency room because of a 4-day history of cough, white sputum and fever (38.8 ℃) occurring during the 31^st week of pregnancy.

The patient had been receiving routine prenatal care and none of which showed abnormalities. Before this admission, the patient was presented to a local urgent care clinic, and she was diagnosed as respiratory tract infection and cefixime (100 mg bid, orally) was prescribed. However, her fever and cough did not abate, and pain in the lower abdominal developed. Two days later she returned to the emergency department of the local clinic, and empirical treatment with piperacillin/tazobactam (cefixime discontinued) was initiated and the blood was obtained for culture. During the initial hours after admission, the patient’s condition worsened with hypothermia and she was transitioned to West China Second University Hospital to seek further evaluation.

On examination, the body temperature varied from 34.2 to 35 ℃ but the rest physical and obstetrical examination was unremarkable. Laboratory investigations confirmed an increased neutrophils count (77.5%), a raised C reactive protein (182 mg/L) and a raised procalcitonin (0.34 ng/mL). Her coagulation profile was normal. Rubella, cytomegalovirus, parvovirus and Toxoplasma IgM (TORCH) were negative. An antenatal screen for hepatitis B, human immunodeficiency virus (HIV) and Treponema were all negative.

Ultrasonography scan confirmed a single intrauterine pregnancy with an estimated gestation of 31 weeks. On non-stress test (NST), fetal bradycardia (100–105 beats/min) accompanied by minimal baseline variability, and irregular contractions were observed (Figure 1A). But reassuring, NST returned to normal (Figure 1B) shortly after treatment. Cultures of four blood samples taken from the local clinic and this hospital (Figure 2) were all positive for L. monocytogenes. So intravenous antibiotic treatment was switched to ampicillin (2 g/q6h for 14 days) promptly, and within 72 hours, her symptoms substantially improved, and particularly her temperature returned to normal. The NST showed a reactive fetal heart pattern with normal variability and no decelerations (Figure 1B). As ampicillin is generally considered safe and effective during pregnancy, the patient elected to continue the pregnancy and the 2-week course of treatment was uneventful.

Figure 1 Non-stressed test. (A) Fetal heart rate was 100–105 beats/min with minimal baseline variability and irregular contractions. (B) Fetal heart rate speeds up to 130–150 beats/min with normal variability and no decelerations.

Figure 2 Colonies of Listeria monocytogenes on blood agar.

On further questioning, the patient volunteered ingestion of homemade ice-cream 2 days before the onset of her symptoms. This may be correlated with the diagnosis of listeriosis, which had been ultimately proven by blood culture.

At the 39^th week of gestation the patient went into spontaneous labor. She gave birth to a 3,650 g female infant with Apgar scores 10/10/10 at 1, 5, and 10 minutes, respectively. Placenta showed infarcts on the maternal site and mild chorioamnionitis, but no cultures were taken.

From birth to 2 years, the child was healthy with psychomotor development appropriate for her age. Figure 3 summarizes the timeline of this case report.

Figure 3 Timeline of this case report. Rx, recipe; PROM, premature rupture of membranes.

All procedures performed in this study were in accordance with the ethical standards of the institutional and/or national research committee(s) and with the Helsinki Declaration (as revised in 2013). Written informed consent was obtained from the patient for the publication of this case report and accompanying images. A copy of the written consent is available for review by the editorial office of this journal.

Discussion

Key findings

Due to nonspecific symptoms, early diagnosis of listeria in pregnancy is often problematic. Testing is usually by blood culture. Once listeriosis is diagnosed, ampicillin, as a monotherapy option is sufficient for complete sterilization.

Strengths and limitations

There is no doubt that early diagnosis can lead to best maternal-fetal clinical outcomes. However, listeriosis usually presents itself as a non-specific flu-like illness which can easily escape the attention of the physician. Furthermore, the poor availability of diagnostic resources might lead to listeriosis under-reporting (9,10). Thus, a high index of suspicion is required for the diagnosis of maternal listeriosis at any stage of pregnancy, particularly when fetus was complicated. According to in vitro studies, case report, and expert opinion, penicillin-type antibiotics (e.g., ampicillin, penicillin, and amoxicillin) could be used to treat listeriosis because they can block penicillin-binding protein 3 (PBP3) and do penetrate intracellularly (11,12). High doses are generally used to assure adequate penetration of the umbilical cord and placenta. In this case, ampicillin 8 g/day for 2 weeks has been proved to be effective and safety for treatment of listeria during pregnancy. If suspicion for listeria infection is high, cephalosporins should be avoided because they are ineffective against listeria (cephalosporins do not bind to PBP3) (3,13).

The case report also had some limitations. Blood cultures did not take after discontinuation of ampicillin, but the remainder of her pregnancy was unremarkable, which indirectly suggests that ampicillin effectively sterilizes the blood and placenta. In addition, the patient declined serotyping test, thus we cannot identify and differentiate which types of strain caused this listeria infection.

Comparison with similar researches

The incidence of listeriosis in pregnancy is more common compared with the general population (3). L. monocytogenes has placenta-philic characteristics and often causes spontaneous abortion, fetal death and neonatal sepsis. If the infection occurs during the second or third trimester of pregnancy, the case fatality rate is 20–30% (3). Over 80% pregnancies with maternal listeriosis faced adverse fetal outcomes, and only few cases were unaffected with an infant born at term (3,7,8,14). This case report adds to the limited knowledge on the third trimester listeriosis, an infection which is probably more common than previously thought.

Given that listeriosis in pregnancy is serious and difficult to differentiate, diagnosis can only be made by culturing of blood, amniotic, or spinal fluid (1,11). Although delaying, clinicians should start timely antibiotic treatment after obtaining cultures. Compared with ampicillin therapy in this case, prior studies suggested the combination regimens of penicillin-type antibiotics and gentamicin (4-6), but the balance of the synergistic effect and toxicities of gentamicin need to confirm in the future study. In addition, the duration optimal and the dosage of therapy in pregnancy has not been established. In case reports, duration of therapy has varied from 2 weeks to continuous treatment until delivery (4-6). This study suggested that 4 weeks of ampicillin treatment could eradicate L. monocytogenes. Whichever antibiotic is chosen, dosage is critical. This study, like other case reports, recommend 6 g or more per day of ampicillin for treatment during pregnancy because high dosage can maintain adequate intracellular penetration (5,11,13), but this needs to verify in randomized clinical trials.

Implications and actions needed

Listeriosis, a serious food-borne infection caused by consumption of food contaminated with listeria, such as soft cheeses, hot dogs and refrigerated seafood (15). As for our patient, she had an ingestion history of homemade ice-cream, and this might have been associated with her listeria infection. For prevention, it is crucial to educate pregnant women to maintain healthy diet habits (e.g., avoiding directly eating unpasteurized dairy products, cheeses and seafood).

In view of the effective antibiotic treatment and the continuing pregnancy, fetal listeria can be particularly challenging to isolate by placental cultures. However, the placenta infarctions and chorioamnionitis in our patient reflected that maternal infection passed to the fetus through the fetoplacental unit. Although the case report represents only anecdotal information, appropriate treatment of both the mother and the fetus may result in complete recovery.

Conclusions

Listeriosis in pregnancy is serious and difficult to diagnose, and blood cultures should be considered in any pregnant women presenting with fever. Once listeriosis is diagnosed, ampicillin should be initiated promptly to combatting listeria infection.

Acknowledgments

We would like to thank Hong Chang for the English language review of this manuscript.

Funding: None.

Footnote

Reporting Checklist: The authors have completed the CARE reporting checklist. Available at https://gpm.amegroups.com/article/view/10.21037/gpm-24-33/rc

Peer Review File: Available at https://gpm.amegroups.com/article/view/10.21037/gpm-24-33/prf

Conflicts of Interest: All authors have completed the ICMJE uniform disclosure form (available at https://gpm.amegroups.com/article/view/10.21037/gpm-24-33/coif). The authors have no conflicts of interest to declare.

Ethical Statement: The authors are accountable for all aspects of the work in ensuring that questions related to the accuracy or integrity of any part of the work are appropriately investigated and resolved. All procedures performed in this study were in accordance with the ethical standards of the institutional and/or national research committee(s) and with the Helsinki Declaration (as revised in 2013). Written informed consent was obtained from the patient for the publication of this case report and accompanying images. A copy of the written consent is available for review by the editorial office of this journal.

Open Access Statement: This is an Open Access article distributed in accordance with the Creative Commons Attribution-NonCommercial-NoDerivs 4.0 International License (CC BY-NC-ND 4.0), which permits the non-commercial replication and distribution of the article with the strict proviso that no changes or edits are made and the original work is properly cited (including links to both the formal publication through the relevant DOI and the license). See: https://creativecommons.org/licenses/by-nc-nd/4.0/.

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