Streptococcus pneumoniae (SP) is an uncommon but potentially serious neonatal pathogen. Previous studies stressed that early-onset SP disease is similar to neonatal group B streptococcus (GBS) infections.1,2 Most reported cases occurred during the first 3 weeks of life, and poorer outcomes are most often seen in cases of early sepsis, especially when followed by maternal bacteremia.3 S. pneumoniae soft tissue infection as a manifestation of early-onset neonatal pneumococcal infection is not well documented.
We report a case of a term neonate with a unique presentation on the second day of life of pneumococcal sepsis with soft tissue cellulitis at the nape of the neck that progressed into a neck abscess occurring concurrently with puerperal pneumococcal bacteremia. We also provide a review of the literature on previously reported cases of early-onset neonatal pneumococcal infections.
A term male neonate was born to a 39-year-old G2P0 + 1 mother after 5 years of infertility. The mother was healthy throughout pregnancy, and a perinatal screen for GBS status was negative. An artificial rupture of membranes was performed in the delivery room. The mother had an uncomplicated vaginal delivery at 38 weeks' gestation, and the baby weighed 3.9 kg. The Apgar score was 8 and 9 at 1 and 5 minutes, respectively. Three hours postpartum, the mother complained of fever and abdominal pain. Her temperature reached 39°C, and she had uterine tenderness on examination. Blood, urine, and high vaginal swab cultures were taken, and the patient was administered ceftriaxone and gentamicin. The baby remained healthy initially, but at 30 hours of age, he was grunting and restless. Physical examination showed an irritable baby with diffuse swelling and redness and hotness of skin at the nape of the neck that was diagnosed on the clinical picture as cellulitis. There were no scalp lesions. The swelling continued to increase over the next 48 hours with a positive fluctuation sign.
A sepsis workup was performed, including blood, urine, and spinal fluid cultures. Initial laboratory testing of the newborn revealed leukopenia of 1900 cell/mm3, neutropenia of 1000 cells/mm3, thrombocytopenia of 108,000/mm3, and C-reactive protein of 127 mg/L. A cerebrospinal fluid examination was normal. The result of the chest x-ray was normal. The baby was administered ampicillin and gentamicin. Blood culture in an automated blood culture system was positive after 10 hours of incubation. A pure growth of gram-positive, catalase-negative cocci was identified later as SP. The isolate was sensitive to penicillin (minimum inhibitory concentration [MIC], 0.004), cefotaxime (MIC, 0.023), and vancomycin. S. pneumoniae was also isolated from the maternal blood culture. The high vaginal swab taken from the mother was negative. Molecular capsular serotyping of the isolates was performed using a multiplex polymerase chain reaction panel and showed that both isolates were serotype 1. A neck ultrasound was performed on the neonate's second day of life and showed diffuse soft tissue swelling with no definite collection and no lymphadenitis. Despite antibiotic treatment, at 1 week of age, the infant's nape swelling progressed into an abscess (Fig. 1) that required surgical drainage. A magnetic resonance imaging of the neck and back was performed to exclude sinus tract abnormalities and showed a normal finding. The infant recovered smoothly, completed a 2-week course of penicillin G, and was doing well on follow-up. Further evaluation did not reveal hypogammaglobulinemia, complement deficiency, or asplenia. The mother recovered uneventfully.
We reviewed the English literature from 1970 to 2017 using MEDLINE for cases of early-onset neonatal pneumococcal infection. The search terms “neonate” or “newborn” and “streptococcus pneumoniae” were used. In addition, we searched the references of these reports for additional cases. Those with late-onset disease (occurring after the seventh day of life) were further excluded. There were 24 reports of culture-confirmed SP in neonates younger than 7 days, with a total of 60 neonates. Table 1 summarizes the cases of early-onset neonatal sepsis (EONS) due to SP, along with the current case, in regard to clinical presentation, SP serotypes involved, maternal status, and neonatal outcome. The first case was reported in 1972,4 with the largest series consisting of 9 cases reported in 2016.24 Some case reports did not provide details on maternal high vaginal swab screening specifically for SP. In 75% of the neonates, signs of infection occurred within 48 hours after birth. Exposure to identified and potential risk factors for early-onset SP infection including premature rupture of membrane (n = 18 cases), perinatal maternal illness (n = 18), and chorioamnionitis (n = 2) was reported. Maternal pneumococcal pneumonia, meningitis, and endometritis were reported in 7 cases. Maternal vaginal colonization with SP was documented in 24 cases, of which 15 were asymptomatic.
Bacteremia was present in most early-onset cases, whereas pneumonia (n = 30) and meningitis (n = 18) were the most frequent concurrent clinical presentations. Twenty-two neonates reportedly died within 4 days of presentation; of those, 12 corresponding mothers were asymptomatic.
Serotype distribution was documented in 20 cases, including serotypes 3 (n = 4), 19F (n = 3), 7F (N = 2), 8 (n = 2), 9V (n = 2), 11A (n = 2), 7C (N = 1), 18 (n = 1), 19 (n = 1), 19A (n = 1), and 23F (n = 1). All 3 19F serotypes were penicillin resistant.
S. pneumoniae infections in neonates are a recognized but uncommon cause of neonatal sepsis. S. pneumoniae has been reported to account for 1% to 11% of all neonatal septicemias,26–28 with maternal and neonatal sepsis rates of 0.04 and 0.06 per 1000 livebirths, respectively, compared with an incidence of 0.5 to 1.5 per 1000 livebirths with GBS.2,27,29
S. pneumoniae infection is clinically indistinguishable from other causes of early neonatal infection, and prenatal bacteriology results may not be available for antibiotic prophylaxis as they are for GBS. Skin and soft tissue involvement is a unique presentation of neonatal sepsis.30 Clinical presentation range from cellulitis or abscess to necrotizing fasciitis.
Pneumococci are not present in the normal vaginal flora. However, they may settle in the flora transiently. The rarity of vaginal carriage of this organism (0.03%–0.75%) suggests a higher invasion-to-colonization ratio than GBS. In a normal vaginal flora and hormonal environment, the adhesive capacity of pneumococci to genital tract epithelial cells and immunological mucosal defense mechanisms are all likely to influence colonization.12 Colonization of the lower genital tract can occur through orogenital contact in a nasopharynx carrier or in the context of pneumococcal upper respiratory infection. Most mothers found to be carriers of this organism are asymptomatic at the time of delivery. However, pelvic infection can occur, especially if a predisposing condition exists (eg, the presence of an intrauterine contraceptive device, a recent birth, or gynecologic surgery).27 Low pneumococcal antibody titers have been demonstrated in mothers of affected neonates, and there is a higher risk of recurrent infection in subsequent childbirths.11
The mechanisms of transmission of early and late infections are not entirely clear, but vertical transmission (eg, maternal bacteremia, chorioamnionitis, prolonged membrane rupture, and cervicovaginal colonization) has been shown to predominate in early cases, whereas horizontal transmission dominates in late cases, although these patterns are not exclusive.12,31 Pneumococcal pneumonia, meningitis, endometritis, and clinical amnionitis during labor are important risk factors for neonatal disease.28,32 In our case, the suprapubic pain reported by the mother a few hours after delivery may have represented endometritis. The infection was presumed to be acquired from the mother intra partum, either transplacentally or via ascending infection, given the rapidity of the onset of the disease in the infant and the fact that the mother was clinically healthy before delivery. Endometritis progressing to bacteremia developed in the mother postpartum manifested clinically as maternal fever and abdominal pain.
Simultaneous maternal and neonatal sepsis with SP has been previously described. Maternal pneumococcal bacteremia at the time of delivery or exchange of respiratory secretions between the mother and her child in the postnatal period can cause simultaneous pneumococcal disease affecting both mother and infant.15 There are rare reports of neonatal sepsis with pneumococci by vaginal transmission and endometritis. Westh et al29 in 1990 reviewed the scientific literature and documented 36 cases of female genital tract pneumococcal infection and 23 cases of concurrent neonatal pneumococcal disease in conjunction with maternal infection. The use of an intrauterine device and recent birth and gynecologic surgery were identified as risk factors for genital tract infection.
Most neonates in case reports of pneumococcal septicemia had an early onset of symptoms less than 48 hours after birth, indicating that they were infected before delivery or during the intrapartum period.2,13,33 This is in contrast to a review by Hoffman et al28 in which the mean age (±SD) of presentation was 18 days.
The symptoms of SP vary depending on the postnatal age at the time of infection.2,28 Early-onset SP has strikingly similar characteristics to early-onset GBS bacteremia, with manifestations of acute respiratory distress with underlying pneumonia and severe hypotension and leukopenia, but with a more serious prognosis.2,3,28,34
Other reported clinical presentations include bacterial meningitis and severe focal infections such as septic arthritis, osteomyelitis, and otitis media. Late-onset SP infection occurs between the second and fourth weeks, whereas GBS spans the age spectrum between 7 days and 3 months after birth.17–19
A recent report on neonatal SP described 19 cases of invasive pneumococcal disease (IPD) in neonates between 2009 and 2013, all of which showed early-onset disease characterized by bacteremia associated with either pneumonia or meningitis. None of the reported cases, whether early or late onset, had skin or soft tissue infections.24 Localized abscesses as a consequence of hematogenous seeding during neonatal septicemia are uncommon. In our neonate patient, who had no previously identified risk factors, pneumococcal sepsis was diagnosed on the second day of life with evidence of soft tissue infection manifesting as cellulitis that progressed to abscess despite appropriate antibiotic treatment. This is notably an infrequent manifestation of IPDs either in the neonatal period or in early infancy.35
Group B streptococcus cellulitis-adenitis syndrome in neonates is well documented in the literature and is predominantly located in the submandibular region; however, in isolated cases, cellulitis was found in the preauricular, cervical, genian, or inguinal regions.36,37 In a recent report by Tiwari et al38 on a series of skin and soft tissue infections in 41 neonates, the most commonly isolated organism was Staphylococcus aureus followed by Klebsiella pneumoniae. None of the infections were caused by SP.
When the serogroup distribution of isolates of SP has been investigated, invasive perinatal disease has been documented in types 1 to 12, 14, 17 to 19, 23, 27, 28, 31, and 39, some of which are poorly addressed by current pneumococcal vaccines.2,13,28,29,34 In the case we described, the strains from both the mother and the child were identical and shown to be the same, serotype 1 indicating maternal to neonatal transmission.
Pneumococcal vaccination during the last gestational trimester could reduce neonatal infections; however, currently there is insufficient evidence to recommend maternal vaccination owing to the low quality of trials and small sample size.39
Reduced susceptibility of SP isolates to penicillin and to third-generation cephalosporins has been noted in neonatal infection in earlier reports, although the proportion of nonsusceptible strains may be somewhat lower than that seen in nonneonatal invasive pediatric SP infection.11,33
Fortunately, there is little evidence that nonmeningeal infection requires use of non–β-lactam antibiotics, unless penicillin MIC values are greater than 2 mg/mL. In the clinical case series reported by Hoffman et al,28 21.4% of neonatal SP isolates were penicillin nonsusceptible and 3.6% were ceftriaxone nonsusceptible. In areas where SP resistance is a significant problem, serious consideration should be given to adding vancomycin and/or high-dose cefotaxime to the antibiotic regimens if SP is considered the cause of the neonatal sepsis particularly where meningitis cannot be excluded.
Because high colonization is a major risk factor for pneumococcal EONS, positive cultures from maternal vaginal samples or from newborn surface swabs should be considered pathologic and treated similarly to GBS disease.16,23 Microbiology laboratories should consider reporting the presence of SP in a vaginal screening culture performed for GBS.
In summary, this case of SP illustrates the importance of considering a wide range of potential pathogens in the differential diagnosis of neonatal sepsis. Although rare, SP can result in significant illness in the newborn. Despite the similarities in the manifestations between GBS and SP sepsis, the latter seems to be more virulent and of marked severity, resulting in significant neonatal mortality.
Enhanced surveillance for IPD during the neonatal period over extended periods would help to define the epidemiology of this condition and trends in the serotypes involved as well as the emergence of more antibiotic-resistant strains.
We acknowledge the support of Dr Ahmad Albarraq and colleagues from Microbiology Department, King Saud University, who performed serotyping on the isolates, and the support of Professor A. Alnemri and colleagues at the neonatal intensive care unit, who provided clinical care for the baby reported and for permission to report this case.
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