Supplemental digital content is available for this article. Direct URL citations appear in the printed text and are provided in the HTML and PDF versions of this article on the journal’s website (www.pidj.com).
Influenza and bacterial coinfections or secondary infections are important causes of morbidity and mortality among children. In the United States from 2010 to 2016, 675 influenza-related pediatric deaths were reported and for children 5–17 years old an annual estimated 1,000,000 to 3,600,000 influenza-associated outpatient medical visits and 5000 to 19,000 hospitalizations occurred.1,2 Common bacterial complications following infection with influenza A and B viruses in children involve the upper and lower respiratory tracts, especially acute otitis media and pneumonia.3,4 Less often cardiac, musculoskeletal and neurologic complications are reported in children following influenza.3,5,6 The predominant bacterial pathogens causing influenza-related complications include Streptococcus pneumoniae, Staphylococcus aureus and Streptococcus pyogenes.3,7 Little has been reported regarding the potential role of influenza virus infection in predisposing children to uncommon serious or complicated secondary bacterial infections of the head and neck region.
We reviewed pediatric patients diagnosed with influenza during the 2017 to 2018 influenza season and hospitalization at Texas Children’s Hospital (TCH) with a head or neck infection. The main objective of this study was to describe the epidemiology, clinical manifestations and outcomes of children presenting with serious or complicated head and neck infections during or following influenza infection.
We performed a retrospective review of pediatric patients hospitalized at TCH with bacterial head or neck infections following influenza infection between October 1, 2017 and March 30, 2018. The consultation database of the pediatric infectious diseases service at TCH was queried for patients using the search terms: sinusitis, orbital cellulitis, mastoiditis, retropharyngeal abscess, peritonsillar abscess, deep neck abscess, subdural empyema, Lemierre’s syndrome and Pott’s puffy tumor. Based upon medical records review and International Classification of Diseases, 10th revision codes, patients were included in this study if they had a head or neck infection and reported a diagnosis of influenza (eg, a positive rapid influenza diagnostic test, RIDT) in the 30 days preceding hospital admission. Demographic and clinical information was obtained from the electronic medical records system. Age, gender, clinical presentation, immunization history, microbiologic data and treatment agents and duration were recorded when available for each patient. This study was approved by the Baylor College of Medicine Institutional Review Board.
Lemierre’s syndrome was defined as septic thrombophlebitis of the internal jugular vein. Children were classified as being at higher-risk for influenza-related complications according to the criteria defined by the Advisory Committee on Immunization Practices.8 Patients were considered to have received influenza vaccination if a single dose was administered at least 14 days before illness onset.
Forty-four patients with bacterial head or neck infections were identified. Seven patients reported a preceding influenza infection (Text, Supplemental Digital Content 1, http://links.lww.com/INF/D431, which describes patients without preceding influenza infection). One patient with orbital cellulitis was excluded due to a time to hospitalization of greater than 30 days from diagnosis of influenza (40 days). Six patients met inclusion criteria and their clinical characteristics are described in Table 1.
The male to female ratio was 5:1 and the median age was 11.6 years (range: 1.7–13.9 years). Five patients were diagnosed with influenza during a period of high influenza activity in the Houston area (1 in November, 3 in December, 1 in January), while 1 patient was diagnosed in February. The median time from influenza diagnosis to hospital admission was 4.5 days (range: 1–6 days). RIDT results were available through chart review for 3 patients, all of whom were positive for influenza A. The remaining 3 patients reported positive RIDTs performed at urgent care centers outside of TCH. Five patients reported taking oseltamivir. Immunization records were available for 5 patients, and only 1 patient had received seasonal influenza vaccination. Two patients were at higher-risk for influenza-associated complications (1 due to age 6–59 months and 1 due to asthma).
Our 6 patients were admitted with head and neck infections, including: orbital cellulitis (3), retropharyngeal abscess (2) and 1 of each of the following: Lemierre’s syndrome, peritonsillar abscess, Pott’s puffy tumor and subdural empyema; 4 also had sinusitis. Computed tomography scans were performed in each case (see Fig. 1, which depicts select images from 3 patients). All patients required a surgical procedure: endoscopic sinus surgery (3), incision and drainage of abscess (2) or craniotomy with washout (1). Operative specimens were sent for aerobic and anaerobic cultures for all patients, fungal culture for 4 patients and mycobacteria culture for 1 patient. A single pathogen was established in 2 patients who were also bacteremic: methicillin-resistant S. aureus and Streptococcus intermedius. Two patients had polymicrobial infections (Table 1). One patient had a S. anginosus group isolate resistant to penicillin (minimum inhibitory concentration, 4.0 µg/mL) and ampicillin (minimum inhibitory concentration, 8.0 µg/mL). Three patients had testing for corespiratory viral pathogens including: parainfluenza virus, adenovirus, human metapneumovirus and respiratory syncytial virus; all were negative.
The median duration of hospitalization was 22 days (range: 5–35 days). Three patients required care in the pediatric intensive care unit (PICU). All patients had a peripherally inserted central catheter placed for prolonged parenteral antimicrobial therapy ranging from 3.5 to 6 weeks. The patient with Pott’s puffy tumor was readmitted 2 weeks following discharge for 1 day because of nausea, emesis and postnasal drip. All patients completed antibiotic treatment successfully and had favorable outcomes. The patient with Lemierre’s syndrome continues to receive anticoagulation.
We performed a retrospective review of children hospitalized with serious or complicated head and neck infections following infection with influenza virus from October 2017 through March 2018 at a large pediatric referral hospital. We suggest that serious or complicated bacterial head and neck infections may represent an underrecognized coinfection or secondary complication of infection with influenza virus.
During the 2017 to 2018 influenza season, the TCH laboratory reported 1209 positive influenza tests (985 and 224 were influenza A and B, respectively) and 392 children were admitted to TCH with influenza. Three of the 6 patients who met inclusion criteria were diagnosed with orbital cellulitis. In 1978, Harley et al reported a case series of 3 patients (6, 11 and 19 years of age) admitted with orbital cellulitis in a 1-week period during an influenza A virus epidemic.9 We also report 1 patient with recent influenza infection presenting with Lemierre’s syndrome caused by methicillin-resistant S. aureus. We found only 1 published case of a 4-year-old male with Lemierre’s syndrome and concurrent influenza A (H1N1) infection.10
The pathogenesis of bacterial coinfection and secondary infections in the setting of influenza infection is complex and incompletely understood. Influenza A appears to be the primary influenza type preceding secondary bacterial infections, especially with seasonal subtypes containing neuraminidase N2.11 Bacterial coinfection often occurs within the first 6 days of influenza infection, which is similar to our observation of a median of 4.5 days from influenza diagnosis to hospital admission.7 During the 2009 pandemic influenza A (H1N1), one third of critically ill children (274 of 838) had evidence of a bacterial coinfection, defined as a bacterial pneumonia or other evidence of bacterial infection within 72 hours of PICU admission.12 Dawood et al reported that 40% (2731 of 6769) of children hospitalized with seasonal or pandemic influenza from 2003 to 2010 were diagnosed with a sinorespiratory complication. Pneumonia (1862, 23%) was the most common complication, and although rare, acute tracheitis (21, <1%) and sinusitis (9, <1%) were also observed.3 Gutierrez et al reported 3 pediatric patients who were hospitalized within 2 months of influenza virus infection with streptococcal tonsillitis (2) and otomastoiditis with pansinusitis (1).13
Of our 6 patients, only 1 had received seasonal influenza immunization. The Advisory Committee on Immunization Practices recommends annual influenza vaccination for all children 6 months of age or older in the absence of contraindications.8 The disease burden of children hospitalized with influenza and the potential for severe bacterial complications underscore the importance of prevention and treatment of influenza infection. Ferdinands et al reported that influenza vaccination among US children during the 2010 to 2012 influenza seasons was associated with a 74% reduction in the risk of admission to the PICU for influenza infection.14 Immunization against S. pneumoniae may also reduce influenza-related pneumonias.15
Our study has several limitations. We were unable to confirm the diagnosis of influenza for 3 patients who presented to urgent care centers outside of TCH. We may have underestimated the number of patients with influenza and secondary head and neck complications as RIDTs may yield false negative results during times of high influenza activity. Conversely, false positive results may have been encountered during times of low influenza activity, although most of our patients presented during peak influenza season. Additionally, we would have missed patients admitted with head and neck infections for whom an infectious diseases consult was not obtained or who did not report a history of influenza infection.
In summary, we describe the clinical manifestations and outcomes of 6 children hospitalized with head or neck infections following influenza virus infection. We hypothesize that serious bacterial head and neck infections may represent an underrecognized coinfection or secondary complication of infection with influenza virus. Influenza infection may also be underrecognized in patients presenting with head and neck infections during influenza season as their preceding influenza symptoms may be attributed solely to their head or neck infection.
1. Shang M, Blanton L, Brammer L, et al. Influenza
Deaths in the United States, 2010–2016. Pediatrics. 2018;141:e20172918.
2. Rolfes MA, Foppa IM, Garg S, et al. Annual estimates of the burden of seasonal influenza
in the United States: a tool for strengthening influenza
surveillance and preparedness. Influenza
Other Respir Viruses. 2018;12:132–137.
3. Dawood FS, Chaves SS, Pérez A, et al; Emerging Infections Program Network. Complications and associated bacterial coinfections among children hospitalized with seasonal or pandemic influenza
, United States, 2003-2010. J Infect Dis. 2014;209:686–694.
4. Peltola V, Ziegler T, Ruuskanen O. Influenza
A and B virus infections in children. Clin Infect Dis. 2003;36:299–305.
5. Wilking AN, Elliott E, Garcia MN, et al. Central nervous system manifestations in pediatric
patients with influenza
A H1N1 infection during the 2009 pandemic. Pediatr Neurol. 2014;51:370–376.
6. Agyeman P, Duppenthaler A, Heininger U, et al. Influenza
-associated myositis in children. Infection. 2004;32:199–203.
7. Chertow DS, Memoli MJ. Bacterial coinfection in influenza
: a grand rounds review. JAMA. 2013;309:275–282.
8. Grohskopf LA, Sokolow LZ, Broder KR, et al. Prevention and Control of Seasonal Influenza
with Vaccines: Recommendations of the Advisory Committee on Immunization Practices - United States, 2017-18 Influenza
Season. MMWR Recomm Rep. 2017;66:1–20.
9. Harley MJ, Guerier TH. Orbital cellulitis related to an influenza
A virus epidemic. Br Med J. 1978;2:13–14.
10. Porquet-Bordes V, Guillet E, Cammas B, et al. [Lemierre syndrome and influenza
A (H1N1)]. Arch Pediatr. 2011;18:413–415.
11. Peltola VT, Boyd KL, McAuley JL, et al. Bacterial sinusitis and otitis media following influenza
virus infection in ferrets. Infect Immun. 2006;74:2562–2567.
12. Randolph AG, Vaughn F, Sullivan R, et al; Pediatric
Acute Lung Injury and Sepsis Investigator’s Network and the National Heart, Lung, and Blood Institute ARDS Clinical Trials Network. Critically ill children during the 2009-2010 influenza
pandemic in the United States. Pediatrics. 2011;128:e1450–e1458.
13. Gutierrez C, Nazar GA, Torres JP. Otolaryngological complications in patients infected with the influenza
A (H1N1) virus. Otolaryngol Head Neck Surg. 2012;146:478–482.
14. Ferdinands JM, Olsho LE, Agan AA, et al; Pediatric
Acute Lung Injury and Sepsis Investigators (PALISI) Network. Effectiveness of influenza
vaccine against life-threatening RT-PCR-confirmed influenza
illness in US children, 2010-2012. J Infect Dis. 2014;210:674–683.
15. Madhi SA, Klugman KP; Vaccine Trialist Group. A role for Streptococcus pneumoniae in virus-associated pneumonia. Nat Med. 2004;10:811–813.