A preterm male infant was born at 25 weeks and 4 days of gestation with a birth weight of 750 g to a 34-year-old mother via Cesarean section due to suspected intra-amniotic infection in the setting of complete placenta previa. His mother attended frequent prenatal appointments at a U.S. military treatment facility in Okinawa, Japan due to a history of chronic hypertension and body mass index >30, in addition to complete placenta previa complicating this pregnancy. Her obstetrical history was notable for 3 prior spontaneous abortions. She was followed throughout pregnancy with noninvasive fetal monitoring but did not require any additional medical procedures or medications aside from prenatal vitamins. She began experiencing fevers 3 weeks before delivery, with a maximum temperature of 38 °C at home. One week later, she underwent an outpatient evaluation for infection that revealed elevated inflammatory markers, including a C-reactive protein level of 86 mg/L (819 nmol/L) and erythrocyte sedimentation rate of 71 mm/h. Blood and urine cultures were negative with no focal signs of infection on examination, and she did not receive any antimicrobial therapy at that time. Routine prenatal infectious screening laboratories were also negative. Of note, the mother swam in the Pacific Ocean during the second trimester of pregnancy but denied any contact with fresh bodies of water or hot tubs. She also had no known sick contacts.
She presented to labor and delivery the following week with contractions but was afebrile with intact membranes and reassuring fetal status on continuous heart rate monitoring, and was discharged home after receiving a 2-dose course of betamethasone to accelerate fetal lung maturity. Group B Streptococcus recto-vaginal screening culture obtained at that time was negative. She returned to the hospital the following day after developing continuous yellow-brown vaginal discharge with confirmed preterm, premature rupture of membranes prompting initiation of empiric perinatal latency antibiotics with ampicillin and azithromycin. Fetal tachycardia ensued with subsequent maternal leukocytosis, fever to 38.1 °C, and fundal tenderness 20 hours after membranes ruptured. Due to concern for an evolving intra-amniotic infection, antibiotics were transitioned to ampicillin, gentamicin and clindamycin. She underwent an urgent Cesarean delivery, during which purulent fluid was noted upon entry into the uterus. Placental pathology was consistent with stage 3-severe chorioamnionitis with disrupted placental disc and chorionic plate vasculitis (Fig. 1).
A viable male infant was delivered and demonstrated poor respiratory effort at birth, requiring intubation and surfactant administration with APGARs of 5 and 7 at 1 and 5 minutes, respectively. Arterial blood culture was drawn on admission to the neonatal intensive care unit (NICU), and empiric antibiotics were initiated with intravenous ampicillin (50 mg/kg/dose every 12 hours) and gentamicin (5 mg/kg/dose every 48 hours). Initial laboratory evaluation was notable for mild thrombocytopenia, with platelet level eventually decreasing to 101 × 109/L by 12 hours of life. He also demonstrated hypotension requiring dopamine infusion as well as worsening respiratory failure requiring transition from conventional to high-frequency jet ventilation. At 18 hours of life, his initial blood culture grew Gram-negative rods. Ampicillin dosing was increased to 100 mg/kg every 8 hours for empiric meningitis coverage and, due to the infant’s clinical and hemodynamic instability, a lumbar puncture was not performed. White blood cell count at birth was 7.9 × 109 cells/L, rising to 26.9 × 109 cells/L by the sixth day of life with a normal differential. Peak C-reactive protein level on day of life 3 was elevated to 56 mg/L (533 mmol/L). Blood culture speciation revealed Serratia marcescens, which was eventually proven to be susceptible to gentamicin, meropenem, amikacin, tobramycin, ciprofloxacin, levofloxacin, and trimethoprim-sulfamethoxazole (Fig. 2). Cultures of the placenta also grew the same S. marcescens. Repeat blood cultures on days 2 and 3 of life grew this organism, and meropenem therapy was added with 2 subsequent negative blood cultures 24 hours apart. Gentamicin was discontinued after 48 hours of negative blood cultures while meropenem was continued for 14 days to cover for sepsis and the possibility of meningitis, as no cerebrospinal fluid culture was able to be obtained.
Serial head ultrasounds obtained on days 3, 7, 10, and then weekly for the first month of life were normal with no evidence of intraventricular hemorrhage or brain abscess. NICU course was complicated by severe respiratory failure and subsequent bronchopulmonary dysplasia requiring prolonged intubation. The infant subsequently developed sepsis and pneumonia at 5 weeks of life, due to a new infection with Klebsiella pneumoniae, which resolved after a 10-day course of ceftazidime, after which he was successfully extubated. He was discharged home on oxygen therapy at 42 weeks postmenstrual age with gastrostomy tube feedings. He is now 13 months old and no longer requiring oxygen support or gastrostomy tube, taking all feeds by mouth, and meeting expected neurodevelopmental milestones for corrected age.
S. marcescens is a ubiquitous environmental pathogen commonly found in water, soil, animals and plants, and has become an increasingly important nosocomial pathogen in the NICU.1 It is a common cause of neonatal sepsis with mortality rates reported as high as 44%.1–9 Other serious infections resulting from S. marcescens include pneumonia, meningitis, urinary tract infection, conjunctivitis and endophthalmitis.8,10–12S. marcescens is difficult to eradicate and can become endemic within the NICU environment. Infants admitted to the NICU are at high risk of colonization with S. marcescens via the gut or ventilator apparatus, leading to clinical infection or horizontal transmission.13–16 Infants at greatest risk for infection include those with a history of maternal chorioamnionitis, gestational age ≤32 weeks, or very low birth weight (<1500 g). Other clinical risk factors include prior surgical history, the presence of an indwelling central venous catheter, and the requirement for mechanical ventilation.8,9,15,17 Cases of S. marcescens infection within the NICU may occur sporadically or as large-scale outbreaks.2,5,6,9 Although a primary source is not always known, hand-to-hand spread via health care workers remains the most common mode of transmission between patients. Additionally, environmental sources such as contaminated ventilator tubing, water spray from high-frequency ventilators, parenteral nutrition, laryngoscope blades, baby shampoo and 1% chloroxylenol soap have all been identified during outbreaks of S. marcescens.6,10,14,17–20
In contrast to the well-described nosocomial spread of S. marcescens in the preterm population, our patient’s infection was acquired via vertical transmission in the setting of chorioamnionitis. Chorioamnionitis is most commonly caused by an ascending infection from the maternal lower genital tract, but S. marcescens is not a normal component of the vaginal flora.21,22 Both gross and histologic evaluations are essential to placental pathology when chorioamnionitis or intra-amniotic infection are suspected. As compared with a chronic immune-mediated inflammatory response during pregnancy and the histologic evidence of mononuclear cell infiltrates, bacterial infections typically present histologically as a local inflammatory process with acute neutrophilic infiltration.23 In chorioamnionitis, these infiltrates will include the chorionic plate, placental membrane amnion and/or the fetal membranes. In the case presented, all 3 of the aforementioned criteria were present (Fig. 1), in addition to notable amnionic necrosis.
To assess for previously published cases of vertical transmission of S. marcescens in the setting of maternal chorioamnionitis and preterm delivery, we conducted a literature search utilizing MeSH indexing with the headings [chorioamnionitis], [Serratia], and [infant, newborn] limited to “humans” with a publication date range between 1950 and 2020, which yielded only 1 article. We found no published reports of confirmed S. marcescens chorioamnionitis in conjunction with preterm delivery and positive neonatal cultures. In the single case report identifying a viable infant, the maternal infection was confirmed with positive placental, uterine cavity and surgical wound cultures, but the infant was not infected and had an uncomplicated NICU course.24 Removal of the MeSH heading [infant, newborn] as well as manual inspection of cited references revealed 4 additional relevant cases of confirmed S. marcescens chorioamnionitis; however, all resulted in pre-viable spontaneous abortions.22,25–27 Two of these cases occurred in previously healthy women without any obvious source for S. marcescens infection.22,24–27
Interestingly, each of the aforementioned cases occurred in proximity to a coastline [ie, Japan, Israel, Singapore, Portugal and North Carolina (United States)]. To our knowledge, this finding of pathogenic S. marcescens infections amongst pregnant women in coastal areas has not previously been highlighted and is worth noting. Although S. marcescens is most commonly associated with freshwater contamination, strains have also been isolated from saltwater sources in coastal regions.28,29 We postulate that maternal S. marcescens infection in our case may have occurred following saltwater exposure, as no other risk factors could be elucidated.
In preterm neonates, chorioamnionitis and early-onset sepsis create a cascade of systemic inflammation during a critical developmental window. This systemic inflammatory response has been implicated in the adverse sequelae of early-onset sepsis in premature infants.21,30 Sepsis is an independent risk factor for the development of bronchopulmonary dysplasia and the need for supplemental oxygen upon discharge from the NICU.30,31 We suspect that our patient’s severe bronchopulmonary dysplasia with home oxygen requirement in the setting of adequate antenatal maternal steroids was likely the result of sustained inflammation and alveolar injury secondary to S. marcescens sepsis. The preterm brain is also particularly vulnerable to inflammatory insults and oxidative stress, most notably in the developing white matter.30 Although our patient had no evidence of hemorrhage or cystic periventricular leukomalacia on serial head ultrasounds, he unfortunately did not undergo term-corrected brain MRI to evaluate for subtler white matter injury. His normal developmental progress thus far is reassuring, as evidenced by meeting expected developmental milestones by 1 year of age, but he will require ongoing neurodevelopmental follow-up to assess for potential long-term neurologic sequelae.
In summary, chorioamnionitis is a common occurrence during pregnancy, which can lead to premature rupture of membranes, preterm labor and preterm delivery. However, when coupled with certain uncommon pathogens, such as S. marcescens, the results can be devastating and may lead to spontaneous abortion or neonatal sepsis with associated sequelae of systemic inflammation. Mindfulness of these rare pathogens in the setting of viable preterm delivery and early assessment of placental pathology is important for prompt and optimal antimicrobial treatment for both mother and infant, and implementation of strict isolation procedures to avoid a regional outbreak.
The authors graciously thank the patient’s family for the privilege to care for their son and share their story for the purpose of educating medical professionals.
1. Cristina ML, Sartini M, Sp#agnolo AM. Serratia marcescens
infections in neonatal intensive care units (NICUs). Int J Environ Res Public Health. 2019; 16:E610.
2. Voelz A, Müller A, Gillen J, et al. Outbreaks of Serratia marcescens
in neonatal and pediatric intensive care units: clinical aspects, risk factors and management. Int J Hyg Environ Health. 2010; 213:79–87.
3. Åttman E, Korhonen P, Tammela O, et al. A Serratia marcescens
outbreak in a neonatal intensive care unit was successfully managed by rapid hospital hygiene interventions and screening. Acta Paediatr. 2018; 107:425–429.
4. Karkey A, Joshi N, Chalise S, et al. Outbreaks of Serratia marcescens
and Serratia rubidaea
bacteremia in a central Kathmandu hospital following the 2015 earthquakes. Trans R Soc Trop Med Hyg. 2018; 112:467–472.
5. Redondo-Bravo L, Gutiérrez-González E, San Juan-Sanz I, et al. Serratia marcescens
outbreak in a neonatology unit of a Spanish tertiary hospital: risk factors and control measures. Am J Infect Control. 2019; 47:271–279.
6. Arslan U, Erayman I, Kirdar S, et al. Serratia marcescens sepsis
outbreak in a neonatal intensive care unit. Pediatr Int. 2010; 52:208–212.
7. Mahlen SD. Serratia infections: from military experiments to current practice. Clin Microbiol Rev. 2011; 24:755–791.
8. Bizzarro MJ, Dembry LM, Baltimore RS, et al. Case-control analysis of endemic Serratia marcescens
bacteremia in a neonatal intensive care unit. Arch Dis Child Fetal Neonatal Ed. 2007; 92:F120–F126.
9. Al Jarousha AM, El Qouqa IA, El Jadba AH, et al. An outbreak of Serratia marcescens
septicaemia in neonatal intensive care unit in Gaza City, Palestine. J Hosp Infect. 2008; 70:119–126.
10. Madani TA, Alsaedi S, James L, et al. Serratia marcescens
-contaminated baby shampoo causing an outbreak among newborns at King Abdulaziz University Hospital, Jeddah, Saudi Arabia. J Hosp Infect. 2011; 78:16–19.
11. Morillo Á, González V, Aguayo J, et al. A six-month Serratia marcescens
outbreak in a neonatal intensive care unit. Enferm Infecc Microbiol Clin. 2016; 34:645–651.
12. Sindal MD, Nakhwa CP. Metastatic Serratia
endophthalmitis associated with extravasation injury in a preterm neonate. Oman J Ophthalmol. 2015; 8:114–116.
13. Hurrell E, Kucerova E, Loughlin M, et al. Neonatal enteral feeding tubes as loci for colonisation by members of the Enterobacteriaceae
. BMC Infect Dis. 2009; 9:146.
14. Macdonald TM, Langley JM, Mailman T, et al. Serratia marcescens
outbreak in a neonatal intensive care unit related to the exit port of an oscillator. Pediatr Crit Care Med. 2011; 12:e282–e286.
15. Moles L, Gómez M, Moroder E, et al. Serratia marcescens
colonization in preterm neonates during their neonatal intensive care unit stay. Antimicrob Resist Infect Control. 2019; 8:135.
16. Carl MA, Ndao IM, Springman AC, et al. Sepsis
from the gut: the enteric habitat of bacteria that cause late-onset neonatal bloodstream infections. Clin Infect Dis. 2014; 58:1211–1218.
17. Archibald LK, Corl A, Shah B, et al. Serratia marcescens
outbreak associated with extrinsic contamination of 1% chlorxylenol soap. Infect Control Hosp Epidemiol. 1997; 18:704–709.
18. Dramowski A, Aucamp M, Bekker A, et al. Infectious disease exposures and outbreaks at a South African neonatal unit with review of neonatal outbreak epidemiology in Africa. Int J Infect Dis. 2017; 57:79–85.
19. Allan J, Cunniffe JG, Edwards C, et al. Nebulizer decontamination. J Hosp Infect. 2005; 59:72–74.
20. Buffet-Bataillon S, Rabier V, Bétrémieux P, et al. Outbreak of Serratia marcescens
in a neonatal intensive care unit: contaminated unmedicated liquid soap and risk factors. J Hosp Infect. 2009; 72:17–22.
21. Kim CJ, Romero R, Chaemsaithong P, et al. Acute chorioamnionitis and funisitis: definition, pathologic features, and clinical significance. Am J Obstet Gynecol. 2015; 213(4 suppl):S29–S52.
22. Prosser BJ, Horton J. A rare case of Serratia sepsis
and spontaneous abortion. N Engl J Med. 2003; 348:668–669.
23. Gersell DJ. Chronic villitis, chronic chorioamnionitis, and maternal floor infarction. Semin Diagn Pathol. 1993; 10:251–266.
24. Erenberg M, Yagel Y, Press F, et al. Chorioamnionitis caused by Serratia marcescens
in a healthy pregnant woman with preterm premature rupture of membranes: a rare case report and review of the literature. Eur J Obstet Gynecol Reprod Biol. 2017; 211:227–230.
25. Shimizu S, Kojima H, Yoshida C, et al. Chorioamnionitis caused by Serratia marcescens
in a non-immunocompromised host. J Clin Pathol. 2003; 56:871–872.
26. Chai LY, Rauff M, Ong JS, et al. Serratia
septicaemia in pregnancy: further evidence of altered immune response to severe bacterial infection in pregnancy. J Infect. 2011; 63:480–481.
27. Vale-Fernandes E, Moucho M, Brandão O, et al. Late miscarriage caused by Serratia marcescens
: a rare but dire disease in pregnancy. BMJ Case Rep. 2015; 2015:bcr2015210586.
28. Sutherland KP, Shaban S, Joyner JL, et al. Human pathogen shown to cause disease in the threatened eklhorn coral Acropora palmata
. PLoS One. 2011; 6:e23468.
29. Patel K, Patel S, Parekh V, et al. Isolation and characterization of salt tolerant phosphate solubilizing Serratia marcescens
isolated from coastal area. J Pure Appl Microbiol. 2016; 10:2401–2408.
30. Humberg A, Fortmann I, Siller B, et al.; German Neonatal Network, German Center for Lung Research and Priming Immunity at the beginning of life (PRIMAL) Consortium. Preterm birth and sustained inflammation: consequences for the neonate. Semin Immunopathol. 2020; 42:451–468.
31. Jensen EA, Schmidt B. Epidemiology of bronchopulmonary dysplasia. Birth Defects Res A Clin Mol Teratol. 2014; 100:145–157.