Case Report: Gestational Melioidosis through Perinatal Transmission

CASE REPORT

Melioidosis is an infectious disease caused by Burkholderia pseudomallei, a gram-negative, saprophytic soil bacterium.¹ Reports of cases of melioidosis during pregnancy, including cases of vertical transmission, are scarce in the literature. Here, we report a case of gestational melioidosis that was vertically transmitted to a patient in Colombia.

A 21-year-old woman from a rural area of Valledupar, a city on the Colombian Caribbean coast, who was 27 weeks pregnant presented with high fever that lasted more than 24 hours and uterine activity. On admission, the patient had normal blood pressure (110/70 mmHg) with no signs of respiratory distress but was feverish (39°C); her fetus had a normal fetal heart rate of 145 bpm. Vaginal examination revealed that the posterior cervix was soft, with 10-cm dilatation and bulging integral membranes. During delivery, there was evidence of clear amniotic fluid; a moderately preterm baby was delivered at 29.6-week gestational age according to the Ballard scale. The Apgar scores were 4, 7, and 8 out of 10 at 1, 5, and 10 minutes, respectively; the newborn was flaccid and hypotonic without respiratory effort and required vigorous stimulation and 1 minute of positive pressure ventilation.

The mother was administered antibiotic therapy with ampicillin–sulbactam 3 g intravenous dosing (IV) every 6 hours, and obstetric curettage was performed. The admission laboratory test results were as follows: leukocytes, 28,000 cells/mm³; hemoglobin, 9.5 g/dL; platelets, 446,000 cells/mL; creatinine, 0.6 mg/dL; and blood urea nitrogen 6.4 mg/dL. A chest X-ray did not show alveolar infiltrates (Figure 1A), and blood cultures (2/2) were positive for B. pseudomallei. Meropenem 1 gm IV every 8 hours was initiated along with trimethoprim sulfamethoxazole 320/1,600 mg IV every 8 hours for 14 days. The clinical evolution was adequate. After 19 days, the patient was discharged, and outpatient treatment continued with trimethoprim–sulfamethoxazole 160/800 mg every 8 hours for 6 months.

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(A) Normal chest X-ray. (B) Normal chest X-ray. (C) Anteroposterior chest X-ray showing atelectasis at the apex of the right lung; the minor fissure is displaced upward and medially.

Citation: The American Journal of Tropical Medicine and Hygiene 103, 5; 10.4269/ajtmh.20-0223

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The newborn was transferred to the neonatal intensive care unit where he presented with signs of respiratory distress, requiring orotracheal intubation and the use of exogenous pulmonary surfactant (Figure 1B). Because of his perinatal medical history, treatment was initiated with ampicillin 98 mg IV every 12 hours (200 mg/kg/day) plus amikacin 14.7 mg IV every 48 hours (15 mg/kg/dose/48 hours). Blood and endotracheal aspirate samples were collected and cultured, with negative results on the fifth day. On the sixth day of life, the programmed extubation protocol with continuous positive airway pressure was performed; however, a few hours later, the neonate suffered an apnea episode with hemodynamic repercussions that required advanced cardiac resuscitation and orotracheal reintubation. New endotracheal aspirate and blood samples were obtained. A new X-ray of the thorax showed right apical atelectasis and right basal alveolar infiltrates (Figure 1C). Given the maternal positive blood culture, it was decided to initiate ceftazidime 44 mg IV every 12 hours (88 mg/kg/day). Blood culture reports from day 6 were positive for azole-susceptible Candida albicans, whereas endotracheal aspirate culture was positive for B. pseudomallei; thus, caspofungin 2.7 mg IV every 24 hours (25 mg/m²/day) was added. However, clinical efficacy was low. Extubation was challenging, hemodynamics were labile, fungemia persisted, and B. pseudomallei was detected in endotracheal aspirate culture at 12 days; thus, it was decided to remove the epicutaneous cava catheter and initiate meropenem 39 mg IV every 8 hours (40 mg/kg/8 hours). For the management of fungemia, caspofungin was initially administered for 15 days and then fluconazole was administered for 14 days. Treatment with meropenem was administered for 10 days, and then amoxicillin–clavulanate was administered for 3 months. The clinical course of the newborn was consistent with extreme prematurity complicated by sepsis. Respiratory support until 36 weeks of corrected pregnancy, multiple blood transfusions, and prolonged parenteral nutritional support were required. The newborn was discharged on 64th day of life. At the 8-month follow-up examination, there was no disease recurrence in either the mother or the child.

The two isolated strains were identified as B. pseudomallei by a VITEK Compact 2 (BioMérieux, Marcy I’Etoile, France) and MicroScan WalkAway (Beckman Coulter, Brea, CA) system. Minimum inhibitory concentration (MIC) testing was performed using the MicroScan WalkAway system. According to published cutoff points for B. pseudomallei, the isolates were susceptible to trimethoprim/sulfamethoxazole (MIC < 2/38 μg/mL), meropenem (MIC < 1 μg/mL), and ceftazidime (MIC 4 μg/mL). Whole-genome sequencing confirmed both isolates as B. pseudomallei (StrainSeeker v.1.5, Tartu, Estonia) ST1748, a newly designated sequence type (ST). The detection of acquired antibiotic resistance genes revealed the presence of the β-lactamase OXA-57 in both genomes; no other genes were detected. In addition, we explored the presence of genes encoding virulence factors. Both genomes harbored the same genes, including those encoding secretion systems types III, IV, and VI; capsular polysaccharides; and flagellar machinery. Finally, the comparison of both genomes revealed a nucleotide similarity of 100%. Only four single nucleotide polymorphisms and 10 indels were found, confirming close genetic relatedness between the two isolates.

DISCUSSION

Melioidosis is an emerging and life-threatening disease caused by B. pseudomallei. It requires prolonged antibiotic treatment and is characterized by a wide range of clinical presentations. Colombia has reported the second highest number of cases in South America following Brazil.^1,2 Melioidosis cases have been described in residents of the Colombian Caribbean coast³; however, there are no previous reports of gestational melioidosis. Although the first case of neonatal melioidosis in the Americas was described in the United States in 1971,⁴ there is no previous evidence of perinatal transmission in the Americas.

Pregnancy is not a risk factor for the development of melioidosis. The clinical presentation of gestational infection is not different from that in nonpregnant women.^5,6 Placental infection can occur through bacteremia or through the genitourinary tract.^7,8

In the literature, there are few neonatal melioidosis reports.^4,9–12 Newborns can be infected through vertical transmission (transplacentally or in the birth canal), during breastfeeding¹³ and by postpartum exposure,^6,10,14 especially in cases of contamination of the umbilical cord due to unsterile instruments.¹⁵ In this case, given that the samples collected at birth were negative, we consider that vertical transmission occurred through the birth canal. Infection in neonates usually presents as pneumonia, bacteremia, or meningitis and less frequently as abscesses in multiple organs or intracranial hemorrhage.^10,11,16,17 Neonatal melioidosis has a high mortality rate that can reach 70%.^18–20 Every mother of a child with melioidosis should be evaluated for the presence of B. pseudomallei. Although in this case, the presence of B. pseudomallei in the newborn’s blood was not reported, the finding of highly related isolate in the mother’s blood and the newborn’s endotracheal aspirate cultures confirms perinatal transmission, and there was no apparent evidence of placental infection. Although there was also concomitant infection with C. albicans, we hypothesize that the pulmonary findings were attributable to the presence of B. pseudomallei and not to the fungal infection.

Our sequencing analyses of B. pseudomallei indicate a new ST, ST1748. In Colombia, different STs have been reported (ST1456, ST349, ST92, and ST518),²¹ suggesting genetic diversity among B. pseudomallei isolates. This observation correlates with the high rates of recombination and genomic plasticity observed in this bacterium.^22,23

The B. pseudomallei genome contains several genes that encode multiple resistance mechanisms (ambler class A, B, and D β-lactamases; outer membrane porins; and efflux pumps; among others). Similar to results reported by other authors, although both isolates were carrying the OXA-57 gene, a class D β-lactamase, they were susceptible to ceftazidime and carbapenem.^24,25

This disease requires a long treatment course because of the risk of recurrence that includes two phases. In the intensive phase, induction involves ceftazidime, imipenem, or meropenem IV for 10–14 days. However, antimicrobial stewardship recommends that carbapenems should be used in only the most compromised patients. During the eradication phase, trimethoprim–sulfamethoxazole is orally administered for 3–6 months. Doxycycline and amoxicillin–clavulanate are used for the management of patients with contraindications or isolated trimethoprim–sulfamethoxazole–resistant microorganisms.²⁶ There is little evidence regarding the treatment of melioidosis in pregnant women and newborns. There are two issues that make the treatment of this condition challenging. First, there may be a persistent infection in the placenta, which would increase the risk of recurrence of melioidosis in pregnant women; this is why some authors recommend prolonging parenteral therapy and close monitoring once therapy is suspended. On the other hand, the use of trimethoprim–sulfamethoxazole is contraindicated during the first and third trimesters of pregnancy and in newborns. Amoxicillin–clavulanate therapy (the therapy of choice during the eradication phase) is associated with an increased relapse risk. There is a case report of the successful use of trimethoprim–sulfamethoxazole in a neonate during the eradication phase.²⁷

In conclusion, although gestational and neonatal melioidoses are uncommon clinical presentations, this first-ever case report in the Americas makes it necessary to consider when determining a differential diagnosis in women from endemic areas of the Americas and in women returning from endemic areas. The report of the complete genome sequence of B. pseudomallei in Colombia provides new knowledge about the molecular epidemiology of this microorganism in the country.