Apnea, Cyanosis, and Septic Shock in a Term Neonate

Introduction

Haemophilus influenzae is a bacteria that colonizes the human respiratory tract and is spread from human to human through airborne droplets as well as direct contact with secretions. It is a small, nonmotile, gram-negative coccobacilli that has both encapsulated and nonencapsulated forms.¹ H influenzae serotype b (Hib; an encapsulated form) causes serious bacteremia, meningitis, epiglottitis, septic arthritis and osteomyelitis in children younger than 5 years of age. With the introduction of the Hib vaccine in the United States, the burden of invasive disease has shifted from largely serotype b strain to primarily of the nontypeable strains.

Case Presentation

A 10-day-old infant boy was transferred to our hospital for management of acute respiratory failure and progressive septic shock. He was well until day of life 9, when he suddenly developed cough, perioral cyanosis, and gagging with feeding. The following day, he continued to have persistent cough with increased work of breathing and was brought to the emergency department (ED).

The patient was born in the United States, although the mother lived in Yemen until the seventh month of pregnancy, receiving prenatal care throughout this time. The parents were in a consanguineous marriage. There was a maternal history of 2 previous miscarriages and previous infant death at 3 months of age due to sudden infant death syndrome. Patient was born at 37 weeks of gestation via uncomplicated normal spontaneous vaginal delivery and had an unremarkable newborn nursery course. Birth weight was 2715 g (seventh percentile), head circumference 32 cm (second percentile), and length 45.7 cm (third percentile). The infant was discharged home with his mother on day of life 2.

On presentation to the ED, his weight was 2.6 kg and his vital signs were rectal temperature of 98.1°F, heart rate of 148/min, respiratory rate of 52/min, with oxygen saturation of 97% in room air. Within 5 minutes of triage, the infant became cyanotic, unresponsive, stiff, and bradycardic requiring chest compressions and bag valve mask ventilation. He achieved return of spontaneous circulation after 30 seconds but remained lethargic. Physical examination showed a mottled infant with poor peripheral perfusion. There were no signs of external trauma. He had copious nasal and oropharyngeal secretions. His lungs, heart, and abdominal examinations were unremarkable. His neurologic examination was nonfocal. In the ED, he continued to have frequent apneic episodes requiring endotracheal intubation. Laboratory evaluation included a normal complete blood count (white blood cell count 5500/µL, hemoglobin 14.9 g/dL, hematocrit 42.6%, platelets 213 000/µL), normal basic metabolic panel (sodium 134 mmol/L, potassium 4.9 mmol/L, chloride 95 mmol/L, bicarbonate 21 mmol/L, blood urea nitrogen 11 mg/dL, creatinine <0.46 mg/dL), normal C-reactive protein (0.50 mg/L), and negative rapid polymerase chain reaction testing for respiratory syncytial virus and influenza. Blood culture was sent prior to empiric antibiotic administration of intravenous ampicillin and cefotaxime. The infant was admitted to the pediatric intensive care unit for further management of acute respiratory failure secondary to septic shock.

Hospital Course

In the pediatric intensive care unit, the infant developed acute decompensated shock requiring dopamine and epinephrine drips. Echocardiogram showed normal heart function and was negative for valvular vegetations. Initial chest x-ray on admission showed multiple opacities involving both upper lobes and the right lung base, suspicious for multifocal infection. On hospital day 2, the blood culture was reported positive for H influenzae that was unable to be typed at the time. Antibiotics were changed to intravenous ampicillin/sulbactam as there was a shortage of cefotaxime in our institution. The respiratory viral polymerase chain reaction panel was positive for Enterovirus/rhinovirus. Lumbar puncture was performed; cerebral spinal fluid showed a gram stain without cells or organisms, protein of 88 mg/dL, glucose of 51 mg/dL, and a cell count with 0 white blood cells and 2 red blood cells. Cerebrospinal fluid culture was later reported as negative. On hospital day 5, his respiratory status improved and he was extubated. On hospital day 6, the New York State Department of Health reported that the initial blood culture was growing Hib.

The patient was transferred to the general pediatrics unit on hospital day 6. Overall, his clinical status improved, and he was discharged home with rifampin for 4 days after completion of 10 days of intravenous antibiotics. The patient had a total of 16 household contacts who required chemoprophylaxis with rifampin. He lived at home with his mother, father, 3 aunts, 3 uncles, and 8 children including his brother and 7 cousins, ages 1.5 months, 7 months, 3 years, 5 years, 8 years, 12 years, and 13 years. Close follow-up was recommended for all children involved.

Final Diagnosis

The final diagnosis was Hib septic shock.

Discussion

Haemophilus influenzae serotype b infection is a national notifiable disease, and according to the Centers for Disease Control and Prevention, there were only 2 confirmed serotype b infections in children less than 1 year of age in the United States in 2016.² From 2012 to 2017 in New York City, there was 1 case of Hib in a child younger than 2 years of age (occurring in 2012). There were no cases of Hib in neonates <30 days old during this period.^3-5 In the United States in 2017, there was a rate of 0.19/100 000 cases of invasive Hib in children younger than 5 years of age.⁶

Haemophilus influenzae serotype b vaccines provide protection against serious illnesses by stimulating a humoral immune response as well as eliminating nasopharyngeal colonization of Hib. In countries with widespread vaccine use, newborns are protected against Hib due to maternal antibodies. As the maternal antibody levels decline, children can become susceptible to invasive Hib infection from around age 3 months to 3 years.⁷

Haemophilus influenzae serotype b is a rare cause of systemic infection in neonates, with very few cases reported in the literature. Of those few cases, most postulate neonatal infection occurs in infants whose mothers lack immunity to Hib, with some cases growing Hib from the mother’s cervix or placenta. It is also common for women to be colonized by Hib in the nasopharynx, so whether infant is infected at birth or postpartum, or by mother at all, is unclear.²

In the United States, the majority of Hib infections after the implementation of vaccinations are in children older than 2 months of age, those who are unimmunized, or in children with immunological deficiency. Immigrants, refugees, or those traveling frequently are at greater risk of disease. Places with decreased vaccination compliance or decreased availability are of particular importance as low vaccination rates in a community prevent the development of herd immunity in unvaccinated members of the population. Obtaining a thorough travel history, documenting which countries patients have traveled, specific vaccination status, as well as household contact travel history should always be unveiled during the encounter.

According to the World Health Organization and the United Nations International Children’s Emergency Fund, it is estimated that in the country of Yemen, only 60% to 70% of infants or less received full coverage for Hib as of July 2017.⁸ In the United States, it is estimated that 93% of infants by the age of 1 are covered. Other countries with low Hib vaccination coverage include Afghanistan at 65%, Central African Republic at 47%, Haiti at 53%, Nigeria at 49%, and South Sudan at only 26% vaccination coverage. By the end of 2016, Hib vaccination has been introduced to 191 countries, and global coverage is estimated at about 70%.⁹

In general, the treatment of Hib infections is a β-lactam antimicrobial agent. Ampicillin (if the strain is β-lactamase negative) or a second- or third-generation cephalosporin are the preferred agents. Alternative options include fluoroquinolones, macrolides, tetracyclines, and aminoglycosides.¹⁰ Beta-lactamase–negative, ampicillin-resistant Hib is rising in prevalence in certain regions such as Japan and Spain, although its prevalence in the United States remains low. There have also been reports of increased prevalence of nontypeable H influenzae strains with resistance to ampicillin and other β-lactam agents.^1,10

Children younger than 2 months of age who develop invasive Hib disease can still develop subsequent infections, because at this age, children do not consistently develop protective antibody levels. These children will require Hib vaccine doses according to the age-appropriate schedule for unimmunized children.⁹

Household contacts of persons infected with Hib disease are at increased risk for developing secondary disease, especially children <12 months of age. Chemoprophylaxis with rifampin is recommended in all those living with a patient with Hib disease as well as child care contacts.¹¹ Rifampin eradicates nasopharyngeal colonization of disease and decreases risk of further spread of infection. It is also important for patients treated for Hib disease to receive chemoprophylaxis at hospital discharge, unless treatment of primary disease consisted of cefotaxime or ceftriaxone, which eradicates Hib colonization after disease.¹⁰

Conclusion

Although Hib disease is rare since the implementation of universal Hib vaccination, this case emphasizes the importance of including Hib in the differential diagnosis of neonatal sepsis and the importance of appropriate treatment as well as prophylaxis in close contacts, especially in special populations where the vaccination rates are not as high as in the United States. Clinicians must remember to take a thorough travel history as well as vaccination and immigration history. Recognition and knowledge of the disease is essential to prevent further spread by providing the appropriate prophylaxis to close contacts.