0
We're unable to sign you in at this time. Please try again in a few minutes.
Retry
We were able to sign you in, but your subscription(s) could not be found. Please try again in a few minutes.
Retry
There may be a problem with your account. Please contact the AMA Service Center to resolve this issue.
Contact the AMA Service Center:
Telephone: 1 (800) 262-2350 or 1 (312) 670-7827  *   Email: subscriptions@jamanetwork.com
Error Message ......
Original Article |

The Significance of Streptococcus anginosus Group in Intracranial Complications of Pediatric Rhinosinusitis FREE

Michael W. Deutschmann, MD; Devon Livingstone, BSc; John J. Cho, MD; Otto G. Vanderkooi, MD; James T. Brookes, MD
[+] Author Affiliations

Author Affiliations: Sections of Otolaryngology–Head and Neck Surgery (Drs Deutschmann, Cho, and Brookes) and Pediatric Surgery (Dr Brookes), Department of Surgery, and Section of Infectious Diseases, Department of Pediatrics, and Departments of Microbiology and Infectious Diseases and Pathology and Laboratory Medicine (Dr Vanderkooi) University of Calgary, Calgary, Alberta, Canada. Mr Livingstone is a medical student at the University of Calgary.


JAMA Otolaryngol Head Neck Surg. 2013;139(2):157-160. doi:10.1001/jamaoto.2013.1369.
Text Size: A A A
Published online

Objective To assess the significance of the Streptococcus anginosus group in intracranial complications of pediatric patients with rhinosinusitis.

Design Retrospective cohort study.

Setting Tertiary pediatric hospital.

Patients A 20-year review of medical records identified patients with intracranial complications resulting from rhinosinusitis. In the 50 cases identified, S anginosus was the most commonly implicated bacterial pathogen in 14 (28%). Documented data included demographics, cultured bacteria, immune status, sinuses involved, type of intracranial complication, otolaryngologic surgical and neurosurgical intervention, type and duration of antibiotics used, and resulting neurologic deficits. Complications and outcomes of cases of S anginosus group–associated rhinosinusitis were compared with those of other bacteria.

Main Outcome Measures The severity and outcomes of intracranial complications of pediatric rhinosinusitis due to S anginosus group bacteria compared with other bacteria.

Results Infection caused by the S anginosus group resulted in more severe intracranial complications (P = .001). In addition, patients with S anginosus group–associated infections were more likely to require neurosurgical intervention (P < .001) and develop long-term neurologic deficits (P = .02). Intravenous antibiotics were administered for a longer duration (P < .001) for S anginosus group–associated infections.

Conclusions Rhinosinusitis associated with the S anginosus group should be considered a more serious infection relative to those caused by other pathogens. Streptococcus anginosus group bacteria are significantly more likely than other bacteria to cause more severe intracranial complications and neurologic deficits and to require neurosurgical intervention. A low threshold for intervention should be used for infection caused by this pathogen.

Pediatric rhinosinusitis is relatively common. Most cases are caused by Streptococcus pneumoniae, Haemophilus influenzae, Moraxella catarrhalis, and, less commonly, Staphylococcus aureus and Streptococcus pyogenes.1 The increasing number of children attending day care facilities has led to an increasing incidence of this disease.2 Complications associated with rhinosinusitis, although potentially devastating, are rare. Intracranial and orbital complications occur via direct extension from the sinuses or hematogenous spread. Approximately 3% of pediatric patients hospitalized with rhinosinusitis develop an intracranial complication.3 These infections include meningitis, epidural abscess, subdural abscess, brain abscess, and cavernous sinus thrombosis.4Streptococcus and Staphylococcus are frequently associated with these diseases.5

The Streptococcus anginosus group, previously known as the Streptococcus milleri group, is from the Streptococcus family, which is known to be a cause of serious infections.6 This group includes S anginosus, S intermedius, and S constellatus. The S anginosus group has been shown5 to be a major causative factor of intracranial infections in adults, particularly those in which acute bacterial rhinosinusitis is the inciting infection. The Streptococcus family produces many enzymes and works synergistically with anaerobic bacteria to cause tissue necrosis and abscess formation.7,8

At the Alberta Children's Hospital, Calgary, we have observed several severe intracranial complications from rhinosinusitis caused by the S anginosusgroup. We reviewed the medical records of all patients who had an intracranial complication of rhinosinusitis to determine whether the disease severity and outcomes were worse when the S anginosus group was the causative organism.

A review of medical records from patients at the Alberta Children's Hospital was conducted. Ethics approval was received from the Conjoint Health Research Ethics Board of the University of Calgary.

Demographic and personal health information was collected from hospital records and health records, including data regarding intracranial complications of pediatric rhinosinusitis as well as the medical and surgical interventions undertaken to treat the infection in each patient.

Children aged 1 day to less than 18 years were included. All patients must have been admitted to Alberta Children's Hospital between January 1, 1991, and December 31, 2010, with an intracranial complication of acute bacterial rhinosinusitis. Patients who were immunocompromised when they developed the infection were excluded from analysis.

In all statistical analyses, variables and outcomes of patients with rhinosinusitis caused by the S anginosus group were compared with those caused by other organisms. Primary outcome variables included age, sex, type of intracranial complication, duration of hospital stay, duration of antibiotic use, surgical intervention requirement, and permanent neurologic deficits due to intracranial complications of the infection.

Descriptive statistics were tabulated for all variables in the presence and absence of S anginosus group rhinosinusitis. A 2-sided Fisher exact test was conducted on all categorical variables (sex, adenoidectomy, sinus involvement, intracranial complication, concurrent orbital complication, otolaryngologic surgical intervention, neurosurgical intervention, and neurologic deficits). Frequency distribution tables were created for continuous variables (length of hospital stay, age, and duration of antibiotic use) including analysis of variance, skew, and kurtosis. A 2-sample unpaired t test was conducted to determine the statistical significance of relationships between S anginosus group–associated infection and continuous primary outcome variables. Ninety-five percent confidence intervals were calculated on the basis of binomial distribution. Simple logistic regression analysis was performed to assess variables that may have confounded a significant outcome on univariate analysis.

Fifty-five patients meeting the inclusion criteria were identified; 4 patients were excluded because they were immunocompromised, and 1 patient was excluded because of death during admission to the hospital. There were no significant differences in sex, age, duration of hospitalization, or location of rhinosinusitis between the S anginosus group and the comparative group. Fourteen patients had rhinosinusitis due to the S anginosus group (Table 1). It was the most commonly implicated bacterial pathogen, accounting for 14 of the 50 cases (28%)of acute rhinosinusitis with intracranial complication. Table 1 reports the descriptive statistics of patient demographics and characteristics analyzed.

Table Graphic Jump LocationTable 1. Patient Demographics and Characteristicsa

Rhinosinusitis with intracranial complications of all causes was significantly more common in males (36 patients [72%]) than in females (14 [28%]) (P = .03). Streptococcus pneumoniae was the second most common bacterial cause of rhinosinusitis with intracranial complications, accounting for 10 cases (20%). A descriptive statistical analysis of the neurosurgical, otolaryngologic surgical, and antibiotic interventions is reported in Table 2.

Table Graphic Jump LocationTable 2. Medical and Surgical Interventions

Patients with S anginosus group–associated rhinosinusitis were more likely to require neurosurgical intervention compared with patients with infections caused by other organisms (9 patients [64%] vs 5 [14%]; P < .001). There was no significant difference between the groups for otolaryngologic surgical intervention. Intravenous antibiotics were administered a mean of 20 days longer in the S anginosus group (95% CI, 11-28 days; t48 = 4.53; P < .001). There was no significant difference between the groups for oral antibiotic administration.

The complications and sequelae resulting from rhinosinusitis are listed in Table 3. All patients had intracranial complications; however, those with S anginosus group–associated infections were more likely to develop complications other than meningitis (P = .001) (Table 3). Only 2 of 14 intracranial complications (14%) resulting from rhinosinusitis due to the S anginosus group were meningitis compared with 21 of 36 patients (58%) when the complications were caused by other organisms. Patients with S anginosus group–associated rhinosinusitis were also more likely to develop permanent neurologic deficits (P = .02) (Table 3). There was no significant difference between the groups for concurrent orbital infection.

Eight of the 10 S pneumoniae cases occurred after 2002, when the 7-valent pneumococcal conjugate vaccine was introduced in Alberta. Interestingly, 10 of the 14 S anginosus cases occurred after 2002.

Multivariable analysis was performed to look at the risk of surgical intervention during infections caused by S anginosus compared with all other bacteria. A simple logistic regression controlled for severity of the infection (ie, abscess vs nonabscess) showed increased odds of surgical intervention when S anginosus was the pathogen (odds ratio, 5.5; 95% CI, 0.8-40.5; P = .09).

Streptococcus anginosus group is known to be particularly aggressive and is generally susceptible to penicillin, ampicillin, erythromycin, and tetracycline.5 Our study shows that intracranial complications resulting from pediatric rhinosinusitis caused by S anginosus are significantly more likely to require neurosurgical intervention and a longer duration of intravenous antibiotics. In addition, these infections are more likely to cause more severe intracranial complications and permanent neurologic deficits. Simple logistic regression analysis showed that the risk of requiring surgical intervention is higher in the S anginosus group regardless of whether an abscess is present. To date, there have been no studies comparing the severity of S anginosus with other bacteria in causing intracranial complications associated with pediatric rhinosinusitis. One study5 found that patients with S anginosus –associated intracranial infections caused by rhinosinusitis were common; however, further variables associated with S anginosus and other bacteria beyond the hospital length of stay were not analyzed.

Extracellular enzymes are generated by the bacteria and might be a factor in its potent virulence. It has been shown911 that this group is able to produce several enzymes, including hyaluronidase, deoxyribonuclease, and chondroitin sulfatase. These enzymes are capable of causing tissue liquefaction and leading to abscess formation. It also has been shown7,8 that S anginosus group organisms can act synergistically with anaerobic bacteria to cause worse abscesses. This may explain why the S anginosus group caused significantly worse intracranial infections compared with other organisms. A recent study12 has shown that brain abscesses caused by the S anginosus group can be treated successfully with cefotaxime and metronidazole, as well as rifampin, if the Glasgow Coma Scale score is less than 11.

A likely explanation for S anginosus –associated infections requiring a longer duration of intravenous antibiotic therapy is the increased likelihood of abscesses. At our institution, patients with abscesses routinely receive 4 to 6 weeks of intravenous antibiotics compared with only 2 weeks for those with meningitis. This variability makes the type of infection a confounding factor in determining whether the duration of intravenous antibiotic therapy is significantly different between the S anginosus group and other organisms.

The H influenzae type b vaccine has dramatically reduced the incidence of meningitis caused by this organism. Our study did not have any such cases, so we cannot comment on whether the vaccine has changed the incidence of H influenzae –associated meningitis resulting from rhinosinusitis.

The widespread use of the multivalent pneumococcal vaccine has dramatically changed the bacteriology of rhinosinusitis.13,14 This could explain the recent prominence of S anginosus as a cause of intracranial infections secondary to rhinosinusitis. However, these studies did not comment on the S anginosus group. Interestingly, our study had more cases of S pneumoniae and S anginosus after the introduction of the 7-valent pneumococcal conjugate vaccine. It is possible these more recent S pneumoniae cases were caused by subtypes that do not express the antigens found in the vaccine. Studies would be necessary to determine this.

In conclusion, S anginosus group–associated rhinosinusitis should be considered a serious infection in children because of its prevalence in severe intracranial complications, with more neurologic deficits, greater likelihood of neurosurgical intervention, and longer durations of intravenous antibiotic therapy compared with other bacteria. Early and aggressive interventions are required when treating these virulent infections.

Correspondence: James T. Brookes, MD, Section of Pediatric Surgery, Department of Surgery, Alberta Children's Hospital, 2888 Shaganappi Trail NW, Calgary, AB T3B 6A8, Canada.

Submitted for Publication: August 10, 2012; final revision received October 8, 2012; accepted October 29, 2012.

Author Contributions: All authors had full access to all the data in the study and take responsibility for the integrity of the data and the accuracy of the data analysis. Study concept and design: Deutschmann, Cho, Vanderkooi, and Brookes. Acquisition of data: Deutschmann and Livingstone. Analysis and interpretation of data: Deutschmann, Livingstone, Vanderkooi, and Brookes. Drafting of the manuscript: Deutschmann, Livingstone, Cho, Vanderkooi, and Brookes. Critical revision of the manuscript for important intellectual content: Deutschmann, Cho, Vanderkooi, and Brookes. Statistical analysis: Livingstone and Vanderkooi. Obtained funding: Deutschmann. Administrative, technical, and material support: Deutschmann. Study supervision: Cho, Vanderkooi, and Brookes.

Conflict of Interest Disclosures: None reported.

Previous Presentation: This work was presented as a poster at the spring meeting of the American Society of Pediatric Otolaryngology; April 19, 2012; San Diego, California.

Wald ER. Microbiology of acute and chronic sinusitis in children and adults.  Am J Med Sci. 1998;316(1):13-20
PubMed   |  Link to Article
Johnson DL, Markle BM, Wiedermann BL, Hanahan L. Treatment of intracranial abscesses associated with sinusitis in children and adolescents.  J Pediatr. 1988;113(1, pt 1):15-23
PubMed   |  Link to Article
Clayman GL, Adams GL, Paugh DR, Koopmann CF Jr. Intracranial complications of paranasal sinusitis: a combined institutional review.  Laryngoscope. 1991;101(3):234-239
PubMed   |  Link to Article
Oxford LE, McClay J. Complications of acute sinusitis in children.  Otolaryngol Head Neck Surg. 2005;133(1):32-37
PubMed   |  Link to Article
Rankhethoa NM, Prescott CA. Significance of Streptococcusmilleri in acute rhinosinusitis with complications.  J Laryngol Otol. 2008;122(8):810-813
PubMed   |  Link to Article
Ruoff KL. Streptococcus anginosus (“ Streptococcus milleri ”): the unrecognized pathogen.  Clin Microbiol Rev. 1988;1(1):102-108
PubMed
Nagashima H, Takao A, Maeda N. Abscess forming ability of Streptococcus milleri group: synergistic effect with Fusobacterium nucleatum Microbiol Immunol. 1999;43(3):207-216
PubMed
Shinzato T, Saito A. A mechanism of pathogenicity of “ Streptococcus milleri group” in pulmonary infection: synergy with an anaerobe.  J Med Microbiol. 1994;40(2):118-123
PubMed   |  Link to Article
Unsworth PF. Hyaluronidase production in Streptococcusmilleri in relation to infection.  J Clin Pathol. 1989;42(5):506-510
PubMed   |  Link to Article
Jacobs JA, Stobberingh EE. Hydrolytic enzymes of Streptococcus anginosus, Streptococcus constellatus and Streptococcus intermedius in relation to infection.  Eur J Clin Microbiol Infect Dis. 1995;14(9):818-820
PubMed   |  Link to Article
Shain H, Homer KA, Beighton D. Degradation and utilisation of chondroitin sulphate by Streptococcus intermedius J Med Microbiol. 1996;44(5):372-380
PubMed   |  Link to Article
Kowlessar PI, O’Connell NH, Mitchell RD, Elliott S, Elliott TS. Management of patients with Streptococcus milleri brain abscesses.  J Infect. 2006;52(6):443-450
PubMed   |  Link to Article
Benninger MS, Manz R. The impact of vaccination on rhinosinusitis and otitis media.  Curr Allergy Asthma Rep. 2010;10(6):411-418
PubMed   |  Link to Article
Brook I, Gober AE. Frequency of recovery of pathogens from the nasopharynx of children with acute maxillary sinusitis before and after the introduction of vaccination with the 7-valent pneumococcal vaccine.  Int J Pediatr Otorhinolaryngol. 2007;71(4):575-579
PubMed   |  Link to Article

Figures

Tables

Table Graphic Jump LocationTable 1. Patient Demographics and Characteristicsa
Table Graphic Jump LocationTable 2. Medical and Surgical Interventions

References

Wald ER. Microbiology of acute and chronic sinusitis in children and adults.  Am J Med Sci. 1998;316(1):13-20
PubMed   |  Link to Article
Johnson DL, Markle BM, Wiedermann BL, Hanahan L. Treatment of intracranial abscesses associated with sinusitis in children and adolescents.  J Pediatr. 1988;113(1, pt 1):15-23
PubMed   |  Link to Article
Clayman GL, Adams GL, Paugh DR, Koopmann CF Jr. Intracranial complications of paranasal sinusitis: a combined institutional review.  Laryngoscope. 1991;101(3):234-239
PubMed   |  Link to Article
Oxford LE, McClay J. Complications of acute sinusitis in children.  Otolaryngol Head Neck Surg. 2005;133(1):32-37
PubMed   |  Link to Article
Rankhethoa NM, Prescott CA. Significance of Streptococcusmilleri in acute rhinosinusitis with complications.  J Laryngol Otol. 2008;122(8):810-813
PubMed   |  Link to Article
Ruoff KL. Streptococcus anginosus (“ Streptococcus milleri ”): the unrecognized pathogen.  Clin Microbiol Rev. 1988;1(1):102-108
PubMed
Nagashima H, Takao A, Maeda N. Abscess forming ability of Streptococcus milleri group: synergistic effect with Fusobacterium nucleatum Microbiol Immunol. 1999;43(3):207-216
PubMed
Shinzato T, Saito A. A mechanism of pathogenicity of “ Streptococcus milleri group” in pulmonary infection: synergy with an anaerobe.  J Med Microbiol. 1994;40(2):118-123
PubMed   |  Link to Article
Unsworth PF. Hyaluronidase production in Streptococcusmilleri in relation to infection.  J Clin Pathol. 1989;42(5):506-510
PubMed   |  Link to Article
Jacobs JA, Stobberingh EE. Hydrolytic enzymes of Streptococcus anginosus, Streptococcus constellatus and Streptococcus intermedius in relation to infection.  Eur J Clin Microbiol Infect Dis. 1995;14(9):818-820
PubMed   |  Link to Article
Shain H, Homer KA, Beighton D. Degradation and utilisation of chondroitin sulphate by Streptococcus intermedius J Med Microbiol. 1996;44(5):372-380
PubMed   |  Link to Article
Kowlessar PI, O’Connell NH, Mitchell RD, Elliott S, Elliott TS. Management of patients with Streptococcus milleri brain abscesses.  J Infect. 2006;52(6):443-450
PubMed   |  Link to Article
Benninger MS, Manz R. The impact of vaccination on rhinosinusitis and otitis media.  Curr Allergy Asthma Rep. 2010;10(6):411-418
PubMed   |  Link to Article
Brook I, Gober AE. Frequency of recovery of pathogens from the nasopharynx of children with acute maxillary sinusitis before and after the introduction of vaccination with the 7-valent pneumococcal vaccine.  Int J Pediatr Otorhinolaryngol. 2007;71(4):575-579
PubMed   |  Link to Article

Correspondence

CME
Also Meets CME requirements for:
Browse CME for all U.S. States
Accreditation Information
The American Medical Association is accredited by the Accreditation Council for Continuing Medical Education to provide continuing medical education for physicians. The AMA designates this journal-based CME activity for a maximum of 1 AMA PRA Category 1 CreditTM per course. Physicians should claim only the credit commensurate with the extent of their participation in the activity. Physicians who complete the CME course and score at least 80% correct on the quiz are eligible for AMA PRA Category 1 CreditTM.
Note: You must get at least of the answers correct to pass this quiz.
Please click the checkbox indicating that you have read the full article in order to submit your answers.
Your answers have been saved for later.
You have not filled in all the answers to complete this quiz
The following questions were not answered:
Sorry, you have unsuccessfully completed this CME quiz with a score of
The following questions were not answered correctly:
Commitment to Change (optional):
Indicate what change(s) you will implement in your practice, if any, based on this CME course.
Your quiz results:
The filled radio buttons indicate your responses. The preferred responses are highlighted
For CME Course: A Proposed Model for Initial Assessment and Management of Acute Heart Failure Syndromes
Indicate what changes(s) you will implement in your practice, if any, based on this CME course.
Submit a Comment

Multimedia

Some tools below are only available to our subscribers or users with an online account.

Web of Science® Times Cited: 3

Related Content

Customize your page view by dragging & repositioning the boxes below.

Articles Related By Topic
Related Collections
JAMAevidence.com

Users' Guides to the Medical Literature
Clinical Resolution

Users' Guides to the Medical Literature
Clinical Scenario