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Aurr. NZ J Obster Gynaecol 1996: 36: 3: 286

Perinatal Infection with Lister& Monocytogenes Simon Craig’, MB BS, Michael Permezei”, MD, MRCP, MRCOG, FRACOG, Lex Doyle”, MD, FRACP,

Lindsay Mildenhal14, FRACP and Suzanne Garlands, FRCPA, FACVen Royal Women’s Hospital, Melbourne and

*Department of Obstetrics and Gynaecology, University of Melbourne

Summary: Listeria monocytogenes has been increasingly recognized as a cause of intrauterine sepsis with associated perinatal wastage. The condition is mostly acquired through dietary intake and appropriate advice should be given to all pregnant women. The most common presentations in pregnancy include premature labour, an influenza-like illness and reduced fetal movements.

In this report, we present a series of 24 cases of perinatal listeria infection presenting to either our obstetric or neonatal units and confirmed by the microbiology department of the hospital. In particular, we wish to highlight 3 cases in which antenatal diagnosis and aggressive therapy was associated with a successful outcome. Amongst the remaining 21 cases in which an antenatal diagnosis was not made, there were 5 perinatal deaths and 1 mid-trimester loss at 18 weeks.

Clinicians must maintain a high index of suspicion for listeria. particularly in gravid patients who present with fever in the setting of a persistent ‘flu-like’ illness and premature labour. Once suspected, appropriate specimens for listeria culture should include blood, cervical swabs and midstream urine. Empirical antibiotic therapy with amoxicillin should be instituted while waiting for culture results in patients with possible Listeria monocytogenes sepsis.

Listeria monocytogenes is a small Gram-positive bacillus. It is recognized as a pathogen of immuno- suppressed or debilitated patients, pregnant women

1. Obstetric Registrar. 2. Senior Lecturer, Obstetrics and Gynaecology. 3. Associate Professor, Neonatal Paediatrics. 4. Research Fellow, Neonatal Paediatrics. 5. Head of Microbiology and Infectious Disease, Women’s and

Address for correspondence: Dr Simon Craig, Royal Women’s Hospital, Carlton, Victoria 3053.

Children’s Health Care Network.

and the fetus. In pregnancy, listeriosis may be difficult to diagnose as it may present in a variety of forms, particularly as an influenza-like febrile illness or with flank pain leading to confusion with pyelonephritis. Intrauterine infection may result in abortion, stillbirth or preterm delivery. depending on gestational age. Neonatal sepsis may present overwhelmingly as pneumonia, septicaemia or meningitis. The aim of this study was to review a consecutive series of perinatal listeria cases from a large tertiary referral centre, to identify common features leading to early diagnosis and successful treatment.

SIMON CRAIG ET AL 287

MATERIALS AND METHODS The study population included all cases of perinatal

listeriosis during the period 1983-1994 at the Royal Women's Hospital (RWH) in Melbourne. Mother- infant pairs were seen during their hospital stay and details were collected prospectively. In all cases Listeria monocytogenes was microbiologically proven. The organism was identified (from maternal and neonatal blood cultures, genital swabs, neonatal gastric aspirate/surface swabs, cerebrospinal fluid) as a short motile Gram-positive rod. The listeria bacilli exhibited tumbling motility at 20-25"C. and were catalase and Voges-Proskauer positive.

RESULTS The clinical details of patients with listeriosis are

summarized in tables 1 and 2. In the 12 year period ( 1983- 1994) of the study, there were 88,469 deliveries at the RWH. Of the 24 cases of perinatal listeriosis, 17 had antenatal care and delivery in the hospital while the other 7 were transferred to the hospital for postnataheonatal care after delivery elsewhere. One of these women was cared for antenatally at RWH, but delivered at a general hospital whilst an inpatient with an exacerbation of her Crohn disease. The remaining 6 patients had antenatal care and delivery at level 1 or level 2 hospitals followed by transfer of the newborn to RWH because of neonatal sequelae.

The incidence of perinatal listeriosis amongst women having antenatal care at the hospital was therefore 1 per 5,000 (18 in 88,469). The women ranged in age from 18-39 years and parity varied from 0-3. Only one patient was significantly immuno- compromized (Case 1) as she had long standing Crohn disease and was being treated with high dose steroids throughout the pregnancy.

Premature labour was the commonest presenting symptom occurring in 16 of 24 (66%) women. Other presenting symptoms included an influenza-like illness in 8 women (33%), decreased fetal movements in 4 (17%) and backache or loin pain in 4 others (17%).

Labour commenced spontaneously in all patients except Case 17 (see case report) and Case 22 where labour was induced after a fetal death in utem following an initial episode of preterm labour settling without therapy.

Gestational age at delivery ranged from 18-41 weeks with a mean of 31.5 weeks and preterm delivery occurred in 19 of 24 patients (79%). Caes- arean section was the mode of delivery in 5 women (21%). In each case the indication was fetal distress on cardiotocographic tracing. Meconium-staining of the liquor amnii was present in 12 of 23 (52%) cases. Of the I2 patients with meconium-staining of the liquor, 8 were preterm.

The perinatal mortality rate was 22% (5 of 23) and the other pregnancy in the series of 24 cases ended in an 18-week miscarriage. Stillbirths occurred at 22, 24 and 29 weeks and the 2 neonatal deaths on day 3 and day 23 after delivery at 29 and 27 weeks' gestation respectively.

There was no significant maternal morbidity. One woman (Case 22) developed headaches, neck stiffness and had a rigor postpaftum. The possibility of listeria meningitis was considered, but lumbar puncture examination was normal and symptoms settled with antibiotic treatment. All other women recovered rapidly after delivery. Four women had intrapmum antibiotic therapy and 10 women received antibiotics after delivery.

ILLUSTRATIVE CASE REPORTS (tables I and 2) Case 7

A 21-year-old gravida 2 para 0 with a past history of 1 first trimester termination of pregnancy was well until 39 weeks' gestation when she presented with decreased fetal movements for 3 days. She was admit- ted and a cardiotocograph was reactive. Although she had one raised temperature recording of 37.5OC on the ward, she was allowed to go home. She represented 3 days later after 24 hours of fever, rigors, backache and nausea. Her temperature was 38.4"C and there was right loin tenderness and a provisional diagnosis of acute pyelonephritis was made. She was commenced on intravenous amoxycillin (1 g 6 hrly) which was changed to oral amoxycillin after 24 hours. Temper- ature and symptoms settled after 12 hours of intravenous therapy. Mid-stream urine culture was negative and she was discharged home on oral amoxycillin. Blood cultures subsequently grew Listeriu monocytogenes, which was sensitive to penicillin and amoxycillin. A further 3 days later, the patient presented in early labour. Cervical swabs were taken and labour was augmented with an amniotomy and Syntocinon infusion. The amniotic fluid was clear. The patient was afebrile in labour and amoxycillin was administered intravenously.

The cardiotocograph tracing was normal throughout labour and the patient progressed to a normal delivery of a male infant, birth-weight 3,820 g, and with Apgar scores of 4 and 9 at t and 5 minutes respectively. Both mother and baby were well after delivery. The infant did not require admission to the special care nursery. The cervical swabs, placental swabs and surface swabs of the baby were all negative for listeria. Histology of the placenta showed multiple sterile miliary abscesses consistent with listeria infection.

Case 9 A 26-year-old gravida 2 para 0 with a past history

of 1 early termination of pregnancy presented at 35+

288 AUST. AND N.2. JOURNAL OF OBSTETRICS AND GYNAECOL~GY

Table 1. CIinical Presentation of Patients With Listeria Monocyfogenes Infection

Case Gestation at Symptoms Maximum temp. Amniotic fluid Mode delivery no. delivery in labour

(weeks) 1 28 Backache 1 day - ? Spontaneous vaginal delivery 2 30 Backache 2 days 31.5 Clear NVD 3 37 Flu-like 2 weeks 37.6 Meconium Forceps delivery 4 22 Abdominal pain 1 day Afebrile ? Assisted breech delivery 5 35 Nil 38.0 Meconium Forceps 6 29 Decreased FM 4 days Afebrile Clear NVD 7* 41 Loin pain, decrease FM Afebrile Clear NVD 8 38 Nil Afebrile Meconium Emergency LUSCS 9* 37 Flu-like 2 weeks Afebrile Clear NVD

10 34 Flu-like 3 weeks Afebrile Meconium NVD

12 33 Decreased FM 2 days Afebrile Clear NVD 13 33 Nil Afebrile Meconium NVD 14 18 Flu-like 1 week 39.0 Pink Spontaneous aboltion 15 35 Abdominal pain 2 weeks 31.7 Meconium NVD 16 24 Nausea, diarrhoea 3 days 39.6 Clear Assisted breech delivery 17* 36 Rigors. headaches Afebrile Clear/clear TI-forceps, T2-breech extraction 18 29 Dysuria, decreased FM 38.0 Meconium Emergency LUSCS 19 34 Decreased FM 2 days 38.0 Meconium NVD 20 29 Night sweats, malaise 39.5 Meconium Emergency LUSCS

22 29 Flu-like 5 days 37.1 Meconium NVD 23 31 Back pain 1 week 31.9 Meconium Emergency LUSCS 24 24 Febrile illness at 20 weeks 37.1 Blood stained (both twins) TI-forceps. T2-assisted breech *=Indicates antepartum treatment - see case reports; LUSCS=lower uterine segment Caesarean section: NVD=normal vaginal delivery: FM=fetal movement; T=twin

11 27 Flu-like 1 week - Blood-stained Assisted breech delivery

21 38 Nil - Meconium Emergency LUSCS

Table 2. Clinical Outcome of Patients with Lisle& Monocytugenes Infection Case lntrapartum Birth-weight Apgar Neonatal progresdprincipal diagnosis Listeria isolate/microbiology no. antibiotics (g) score

1 - 1,012 ? 12 wks NICU/SCN/HMD Neonatal SS/GA/ETT swab 2 3 4 5 6 7* + 8 9' +

10 11 - 12 -

13 - 14 + 15 16 - 17* -

18 + 19 + 20 +

21 - 22 - 23 - 24 -

- - - - -

-

-

-

1,744 3,448

620 2.300 1,320 3,820 3,210 2,839 2.470 1.040 2,005

2,400 160

2,760 725

2,130 (1) 1,820 (II)

1,456 2,380 1,441

3,000 1,515 2,800 69511)

685 (11)

9 2

Stillborn 6 6 9 9 10 8 5 I

6

5 Stillborn 1 0 & 9

8 8 8

4 Stillborn

5 7 & 7

-

9 wks NICUtSCNlmeningitis 5 wks NICUISCNlmeningitis, pneumonia Stillborn Transfer interstate NICU/pneumonia NICU 3 days-NNDheningitis. pneumonia No problems 7 days SCN/pneumonia 2 days SCNItransient tachypnoea 4 weeks MCU/SCN/pneumonia 23 days NICU-NNDheningitis 4 days NICU-transfer level 2 SCN/

3 weeks NICU/SCN/pneumonia Spontaneous abortion 9 weeks NICU/SCN/pneumonia FDIU No problems with both twins not infected

pneumonia

Neonatal SS Neonatal BC/GA/SS Autopsy-listeria all organs Neonatal stool culture Neon.BC/SS. Listeria all tissues at autopsy Maternal BC 0 39 weeks Neonatal SSIGA. Vaginal swah Maternal BC 0 35+ weeks Neonatal BC/GA/SS. Vaginal swah Neon.BC/SSIGAElT swab. Vaginal swah Neonatal BC/GA/SS. Vaginal swah

Neonatal GA/SS Placental swab Neonatal SSIGA. Placental swah Neonatal SS. Placental swab Maternal BC @ 30 weeks

6 weeks NICU/SCN/pneumonia. pustular rash 2 weeks SCN/pneumonia 4 weeks MCU/SCN-transfer level 2

4 days SCN/transient tachypnoea FDIU 20 days NICU/SCN/pneumonia TI-124 days &T2-132 days

Neonatal BCISSIGA Neonatal BUSS. Amniotic fluid. Placental swah Maternal BClPlaccntal swah. Neonatal SS/GA

Neonatal SS/GA Mater.BC.Autopsy-listeria all tissues and placenta Maternal BC/HVS. Neonatal BC/GA/SS Maternal BC

SCNMMD

NICU/SCNMMD *=indicates antepartum treatment; NICU=neonatal intensive care unit: SCN=special care nursery; ElT=endouacheal tube: FDIU=fetal death in utero: HMD=hyaline membrane disease: BC=blood cultures: SS=surface swabs: GA=gastric aspirate HVS=high vaginal swab NND=neonatal death

SIMON CRAIG ET AL 289

weeks' gestation with a 1 -day history of an influenza- like illness involving headaches, myalgia and lethargy. The temperature on admission was 38°C and the presence of loin tenderness led to the diagnosis of pyelonephritis.

Blood cultures and mid-stream urine cultures were obtained and intravenous amoxycillin (1 g 6 hrly) was commenced. An antenatal cardiotocograph was reac- tive. The patient's temperature settled over the next 24 hours. Urine culture was negative, but the blood cultures grew Listeria monocytogenes after 48 hours incubation. Gentamicin was then added to the amoxycillin therapy and this regimen was continued for the next 6 days. At that time, spontaneous rupture of the membranes occurred. The amniotic fluid was clear and labour soon followed. The patient pro- gressed fairly quickly to a normal delivery of a live male infant, birth-weight 2,839 g, with Apgar scores of 8 and I 0 at 1 and 5 minutes. There was no elevation of the maternal temperature in labour and the postpartum course was uneventful. The infant was admitted to the special care nursery and treated for a further 2 days with parented amoxycillin and gentamicin. No neonatal problems were detected. Neonatal blood cultures, cerebrospinal fluid cultures, surface swabs and gastric aspirate were all negative for Listeriu rnonocytogenes.

Case I7 A 32-year-old gravida 2 para 0 with a twin

pregnancy presented at 30 weeks with a 2 day history of headache, fever and rigors. The pregnancy had been uncomplicated apart from some spotting at 10 and 12 weeks' gestation.

On admission there were no localizing symptoms. Temperature was 38.9"C and there was n o uterine tenderness. Cardiotocography was normal for both twins. Blood cultures and mid-stream urine were obtained and the patient commenced on intravenous amoxycillin (1 g 8 hrly). The maternal temperature settled to normal within 24 hours on this regimen. Blood cultures subsequently grew Listeria monocytogenes; urine was sterile. A vaginal swab was obtained following the blood culture result and also failed to grow listeria (after 2 days of antibiotic therapy). The patient was treated for 6 days with intravenous amoxycillin and subsequently oral amoxycillin for 10 days. There was no recurrence of fever or illness.

Labour was induced at 36 weeks' gestation for preeclampsia (mild). She was afebrile throughout labour and had a forceps delivery of twin 1, birth- weight 2,130 g with Apgar scores of 9 and 10 at 1 and 5 minutes respectively. Twin 2 was delivered by breech extraction, birth-weight 1,820 g with Apgar scores of 4 and 9. Both mother and babies were well postdelivery.

Surface swabs of the babes, repeat vaginal swabs and placental swabs were all negative for listeria. Placental histology was unremarkable.

DISCUSSION Lisleria monocytogenes is a well recognized

pathogen of the pregnant woman and the fetus. Infection is commonly sporadic, but epidemics have occurred in relation to food-borne carriage of listeria. There may also be a seasonal basis with peaks in late summer (1). Foods particularly at risk for listeria carriage are soft cheeses, cook-chill foods, unpasteurized milk and prepacked salads (2). In contrast to many other food-borne pathogens, listeria thrives at refrigeration temperatures of 4 degrees Celcius.

Maternal manifestations of disease are varied, with the most common being an influenza-like picture. Flank pain can mimic pyelonephritis. Premature labour or decreased movements may be the first presentation (3).

The incidence of perinatal listeriosis in this study was only 1 per 5,000, which is similar to that previously reported (4). However, listeriosis is almost certainly an underdiagnosed condition. Once suspected, swabs for culture should be taken from the cervix, vagina, blood and amniotic fluid. Given the difficulty in diagnosis and the virulence of listeria, transabdominal amniocentesis should be considered in patients at premature gestations who have unexplained fever or premature labour in whom chorioamnionitis is a potential diagnosis (5). Assessment of the amniotic fluid could lead to early treatment and delivery if required.

The presence of meconium macroscopically and Gram positive rods with tumbling motility microscopically in the amniotic fluid should alert the clinician to likely listerial infection (6). In our series, 12 of 23 patients exhibited meconium-staining of the liquor which correlates with other studies showing that intraamniotic infection with listeria is strongly associated with meconium-staining of the amniotic fluid despite the often premature gestation (7). It has been suggested that fetal ingestion of infected liquor causes an enteritis and subsequent meconium passage (8).

In 1976, Hume presented a case of successful treatment of maternal listeria sepsis at 19 weeks' gestation with subsequent delivery at term of an unaffected infant (9). Recent case reports have confirmed that diagnosis and aggressive treatment of listeria in the gravid patient may lead to a successful outcome for the neonate (10,ll). This series of patients also includes 3 cases in whom antepartum diagnosis and treatment resulted in excellent outcomes for both mother and baby.

290 AUST. AND N.Z. JOURNAL OF OBSTETRICS AND GYNAECOLOGY

These 3 cases included 1 patient with a multiple pregnancy. To our knowledge, this is the first reported case of successfui antepartum treatment of listerial sepsis in a patient with a multiple pregnancy. Listeria rnonocytogenes infection has been previously reported in a multiple pregnancy and may represent a further risk factor for Iisteriosis (12.13). Two of the 24 cases in our series were multiple pregnancies. If women with multiple pregnancy are at an increased risk of listeriosis, it is proposed that this may be due to relatively greater immunosuppression or alternatively, an increased consumption of ‘at risk’ foods (13).

Zervoudakis and Cederqvist reported a 29% mortality rate of infants born to mothers treated for listeria during pregnancy compared to 71% mortality if Iisteria was first diagnosed after birth (14). The overall perinatal mortality in our series was lower than this at 22%, despite only 4 patients being treated with intrapartum antibiotics. However, there was a perinatal mortality of 3 1% in patients not treated with antepartum or intrapartum antibiotics. Recommended antibiotic therapy for listeriosis involves treatment with a combination of ampicillin or penicillin plus gentamicin which are synergistic in their actions (15). Other antibiotic regimens used successfully in pregnancy have been based on erythromycin and more recently vancomycin (16).

Tocolysis was attempted in 4 patients, but was unsuccessful in all. This corresponds with the findings of Romero et al that patients with intraamniotic infection are more likely to fail tocolysis (8).

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