Am 1 Otolaryngol
12:292-296, 1991
Pharyngeal and Tonsil Infections Caused by Non-Group A Streptococcus JAMES PATRICK DUDLEY, MD, AND JOELSERCARZ, MD
Non-group A streptococci are members of the genus Streptococcus but do not share the notoriety of their cousin from group A. Most physicians, including otolaryngologists and head and neck surgeons, do not associate them with upper respiratory tract and head and neck infections. Some laboratories do not bother to report their presence on culture. At the University of California, Los Angeles they have been shown to cause (1) tonsillitis, painful tonsils lacking exudate and erythema (group C, one case; group F, one case), (2) acute nonexudative tonsillitis (group B, two cases: group C, one case; group F, one case), and (3) acute exudative tonsillitis (group C, one case). It should be remembered when there is a report of their presence that they are usually vulnerable to penicillin and its analogs. By judicious use of these drugs, morbidity can be diminished. AM J OTOLARYNGOL 12:292-296. Copyright 0 1991 by W.B. Saunders Company Key words: non-group A Streptococcus, pharyngitis, tonsillitis.
pathogens at work in such cases. Recently, Brook and Grober have implicated an anaerobe, Bacteroides melaninogenicus, as a cause of acute tonsillitis.7 Another study reported that Mycoplasma pneumoniae was recovered in 16% of acute sore throat cases.’ There is evidence, however, that non-group A streptococci may also act as pathogens in the upper respiratory tract and on mucosal surfaces. Since most clinical microbiologic laboratories only test for group A Streptococcus when betahemolysis is seen, the presence of non-group A streptococci may go undetected. The significance of these organisms as a cause of pharyngotonsillitis is their susceptibility to penicillin and penicillin analogs. We studied non-group A streptococcal pharyngotonsillitis, documented its resolution with antibiotics, and investigated the role of these infections in upper respiratory tract disease.
Pharyngitis and tonsillitis are frequent diagnoses made by otolaryngologists and primary care physicians1 Determining the etiology of these infections is often very frustrating. Although group A beta-hemolytic Streptococcus has been identified in the past as the leading and only bacteria causing these infections and has even been reported to cause 30% to 40% of pharyngeal and tonsillar infections,’ most clinicians know this is not the case except in instances in which an epidemic of throat infection may be caused by this organism, eg, in college dormitories or in military installations.394 Viruses have always been named as the other and probably chief microbial cause of pharyngotonsillitis. There is very little proof, however, that this is the case. In a study involving 2,559 boys admitted to a detention center over a 5-year period, 421 developed acute tonsillitis. In this group, virus was recovered from only two patients.5 As Hovelius et al observed, “One cannot conclude that patients from whom no bacteria have been isolated have a viral infection.“” It would appear that there are other microbial
MATERIALS AND METHODS Throat cultures were obtained from six adult patients who complained of a sore throat. None had fever. All had slightly tender jugulodigastric adenopathy, but there were no other symptoms or signs. They were seen in the private patient head and neck clinic at the University of California, Los Angeles (UCLA) over a period of 12 months but were not consecutive cases. There were 95 patients with a complaint of sore throat seen by one of the authors (J.P.D.) during that 12-month period. Of this number, 34 had acute tonsillitis. Cultures were sent to the clinical microbiologic laboratory at UCLA
Receivedfrom the Department of Surgery, Division Head and Neck Surgery, University of California, Los Angeles Medical Center Los Angeles, CA. Address correspondence and reprint requests to James Patrick Dudlev, MD, Wall Medical Group, 2001 Union St, Suite 550, San Francisco, CA 94123. Copyright 0 1991 by W.B. Saunders Company 0196-0709l9111205-0001$5.00l0 292
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Hospital. Each was plated on blood agar and MacConky’s agar. As was routine with cultures obtained by this author, the laboratory tested all Streptococcus antigens A, B, C, F, and G when beta-hemolysis was seen. In each of six patients with symptomatic tonsillitis, non-group A Streptococcus was identified. One patient had exudative tonsillitis. In three of the six patients, these streptococci were isolated in pure culture. In the other patients, many non-group A streptococci were isolated with only a few other normal flora present. In one of the patients an antistreptolysin-0 (ASO) titer was obtained during the patient’s illness.
RESULTS Group 6 Streptococcus. Two patients were seen with tonsillitis caused by group B Streptococcus. One produced a pure culture of group B Streptococcus. There was no exudate present, but this patient demonstrated an elevated AS0 titer of 170 Todd units (normal, ~120). From the second patient with a similar clinical picture, many group B streptococci were isolated with a few colonies of Neisseria sp.
Group C Streptococcus. Two patients were seen. In one patient with exudative tonsillitis, group C Streptococcus was obtained in pure culture. In the other, a mild case of tonsillitis, many group C streptococci were recovered with a few colonies of oropharyngeal flora (Neisseria sp and alpha-streptococci). Group F Streptococcus. Two patients were seen. Neither involved exudate; however, both were was symptomatic and yielded moderate numbers of group F streptococci from tonsil cultures with only a few normal oral flora (alphastreptococci and a few Neisseria sp). All six patients were treated with penicillin or ampicillin. Symptoms subsided within 2 days in every case. Antibiotics were continued for 4 to 10 days. In the two patients with group B Streptococcus, follow-up cultures were obtained. In neither instance was group B Streptococcus isolated on follow-up culture. DISCUSSION Six adult patients presented with sore throat symptoms and evidence of pharyngitis and/or tonsillitis. From each of these patients a non-group A, beta-hemolytic Streptococcus was isolated. There is always a question of the significance of the culture of an organism from the upper respiratory that which might be considered normal flora. There appears to be some evidence that the presence of organisms in larger numbers correlates with infection, while organisms present in smaller numbers correlate with normal flora or
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Quinn and “the carrier state.“g Interestingly, Lowry noted in a study of children with clinical streptococcal disease that they were unable to isolate group A Streptococcus in some patients despite the clinical evidence of disease.’ However, they were able to isolate groups C and G in large numbers from some children in whom group A could not be isolated. This seemed to point to the possibility that groups C and G streptococci (and perhaps other non-group A streptococci) are able to produce mucosal (pharyngeal) disease. Most observers feel that the isolation of an organism in pure culture from a patient with symptomatic disease implies that the organism is playing a major role in the infection. Indeed, in two of the patients, this was the case. In one patient with acute nonexudative tonsillitis, group B Streptococcus was isolated in pure culture. In that patient, an elevated AS0 titer was also present. A repeat culture following treatment failed to isolate group B Streptococcus from that patient. These two findings, an elevated AS0 titer and failure to isolate the organism on a second culture, appear to lend credence to the toxic capability of group B Streptococcus in the pharynx. Group C Streptococcus was isolated in pure culture from another patient with exudative tonsillitis. Group B Streptococcus is well known as a cause of serious infections in newborn infants. In infants it can produce meningitis, pneumonia, and bacteremia. However, it appears that group B Streptococcus is also capable of inducing disease in the respiratory tract. In 1942, Wheeler and Foley recovered group B Streptococcus from the middle ears of two patients with otitis media, and they also recovered group B Streptococcus from their spinal fluid. lo In 1947, three patients with group B-induced tonsillitis were reported.” A report of an epiglottal abscess from which group B Streptococcus was isolated in pure culture when aspirated would again seem to indicate that it has the ability to induce upper respiratory tract disease.l’ Group B Streptococcus has been cultured from the throats of 4% of children with acute pharyngitis,13 but there is virtually no information concerning its presence in adults. One study of group B streptococcal infections in hospitalized adult males found 24 with acute infections, but no group B upper respiratory infections were identified in this group.14 It appears that the two cases of acute tonsillitis presented here and the three patients reported in 194711 are the first documented cases of group B streptococcal pharyngeal infection. The symptoms of both patients in our study responded to treatment with penicillin. Although the killing of group B Streptococcus is accelerated when penicillin is combined with gen-
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tamicin,15 penicillin by itself appears to be adequate therapy for these pharyngeal infections. Group C Streptococcus. The presence of group C Streptococcus in the oropharynx has been known for 50 years.‘” It can be found in small numbers in the oropharynx of 1% of healthy young adult men.17 The recovery of group C Streptococcus from the throats of six patient with clinical tonsillitis was reported in 1947,ll although exudate was present in only three. All had elevated AS0 titers. It has been associated with food-borne infectionla~lg: cheesel’ and milklg have been identified as the vehicles for this organism. Non-epidemic tonsillar infection has been reported from time to time. Hutchinson reported six patients with exudative tonsillitis and 33 with “mild tonsillitis” from whom group C Streptococcus was isolated in pure culture.” Fulgitini et al described recurrent group C tonsillitis in a l5year-old boy who required tonsillectomy to cure his diseasee21 When it occurs it can be very contagious, as evidenced by a report of 21 cases of group C Streptococcus-induced pharyngitis at a boarding school. 22 In seven of these patients an exudate was present. It may not always be a benign disease. Stamm and Cobbs reported a healthy male with exudative tonsillitis who ultimately died of group C streptococcal pneumonia.23 It has been found in pure culture in two patients with sinusitis, one of whom died of meningitis.24 It also has been found in an aspirated neck mass from an acutely ill child with pharyngitis,25 in acute epiglottitis2” [it was isolated from the blood and the epiglottitis), in a peritonsillar abscess,27 and in a middle ear infection that resulted in subdural empyema.28 Group C Streptococcus was isolated from the middle ear effusion of a 77-year-old woman who died of meningitis.2g Although it rarely invades upper respiratory mucosa, thus causing bacteremia, it was noted as the source of bacteremia in two children with pharyngitis.30 One of the most disturbing features of this microorganism is its ability to induce glomerulonephritis following minor upper respiratory tract disease.1gp31,32The pharyngeal infections that led to glomerulonephritis were probably transmitted through animal contact and the particular group C strain was Streptococcus zooepidemicus. Group F Streptococcus. Group F streptococci were isolated from the oropharynx in 190633 and 1935,34 and from the nasopharynx in 1934.35 It appears that they have been long considered part of the normal flora of the upper respiratory tract.36-38 They have recently been isolated from abscesses,3g most of which were in the abdominal cavity or urinary tract, although 27 were in the
NON-GROLJPASTREPTOCOCCALPHARYNGITIS
head and neck.3g This organism has also been identified as a cause of sinusitis.36,40,41 Group F Streptococcus has caused bacteremia in two patients with exudative tonsillitis.36 It has been identified as a cause of exudative tonsillitis in seven patients,” yet it has received little attention as a pathogen. Although there is a low incidence of its recovery of this organism from children,13 there appears to be a higher incidence of its recovery in adults.41p42 Since there is not as much academic interest in adult pharyngitis/tonsillitis, the seeming absence of group F Streptococcus in many reports may help to explain why this organism’s pathogenic potential has gone unnoticed. Group G Streptococcus. Group G Streptococcus was first noted by Lancefield and Hare in 1934.43 No patients with group G streptococcal pharyngitis or other head and neck infection were identified in this study. However, group G organisms have been reported as a cause of pharyngitis. Among a group of military recruits, four cases of pharyngitis (one of them exudative) were associated with group G Streptococcus.” Three of the four patients had elevated AS0 titers. The largest number of patients with group G-induced pharyngitis was reported in connection with a college outbreak in 1969.44 Of 502 students diagnosed with acute pharyngitis, group G Streptococcus was isolated in 155. Twenty-three of these had exudates. Another college outbreak of acute pharyngitis involving 68 students was reported in 1982.45 Most of these patients had exudative pharyngitis and/or tonsillitis with fever. An outbreak of pharyngitis in 10 patients reported in 1982 was thought to be due to group G Streptococcuscontaminated food.4” Although bacteremia apparently is uncommon, it can occur in head and neck cancer patients from whom the organism can be isolated in the upper respiratory tract.47,48 Despite the low incidence of bacteremia in healthy patients, there is some evidence that a surface protein of group G Streptococcus4’ is capable of producing glomerulonephritis.50~5* Although penicillin has been the standard medication used against this organism when it has been found to be a pathogen, beta-lactam antibiotics seem to be a more effective form of treatment.52 Erythromycin does not appear to be a valuable drug in the treatment of this microorganism. 53 In severe infections such as abscesses in the upper respiratory tract, penicillin should be combined with an aminoglycocide.54 Increase in AS0 titer has been used as a sine qua non in the diagnosis of streptococcal infection. Interestingly, Krober et al have found an elevated AS0 titer in 17% of patients with tonsilli-
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tis in whom group A organisms were not founde5’ This appears to offer further evidence that other non-group A streptococci might be causative agents in some cases of pharyngotonsillitis. However, Kaplan et al, while trying to differentiate between infection and the carrier state, found that as few as IO colonies are capable of inducing a serologic response,56 suggesting that an elevated titer might not be an ideal indication of infection. Clinical symptoms and culture results may be better indicators, If culture results are important, a complete streptococcal cultural screen would be of more value to determine if antibiotic treatment would diminish morbidity. Brook et al found concordance between surface and core tonsil cultures in two of the non-group A streptococci.57 The mechanism by which apparently commensal microorganisms exist on the surface of asymptomatic tonsils and pharyngeal mucosa and at other times become pathogens remains unknown. Although all of these microorganismscommensals and pathogens-are capable of adherence to host pharyngeal epithelium, it has been postulated that a kind of synergism is established among all of these microorganisms that prevents pathogens from overwhelming commensals.58 Whether a “priority of colonization”5g is the secret of this microbial truce is uncertain; that is, the organisms that were there first are the ones most likely to prevail. There also may be another mechanism at work called “bacterial load.““’ In this scenario, microorganisms that are present in small numbers and are acting as commensals may “overload” the system and produce toxicity when their numbers increase. Searching for potentially pathogenic microorganisms may provide the answer. It will require a vertical prospective study, using a large group of subjects who will act as their own controls, that will investigate the variety of aerobes on noninfected and infected tonsillar and pharyngeal mucosa. This may provide further information about the pathogenesis of non-group A streptococci in the pharynx. References I. Marsland DW, Wood M, Mayo F: A data bank for patient care, curriculum, and research in-family practice: 526,i96 patient problems. J Family Pratt 1976; 3:25-28,37-38 2. Peter G, Smith AC; Group A streptococcal infection of the skin and pharynx. N Engl J Med 1977; 297:311-317 3. Strauss E: Role of B-hemolytic streptococci in common respiratory disease. Am J Public Health 1945; 35:675-682 4. Eggenberger K, Christen JP, Delarue C, et al: Streptococcal pharyngitis-tonsillitis in Swiss children. Diagnosis and management. Paediatrician 1980; 9:295-308 5. Colling A, Kerr I, Maxted WR, et al: Streptococcal infection in a junior detention center: A five year study. J Hyg (Lond) 1980; 85:331-341 6. Hovelius B, Bygren P, Christensen Mardh PA: Respiratory
tract infections at a community care centre-With emphasis on group A streptococci. Stand J Infect Dis 1983; 39:59-67 (suppl) 7. Brook I, Grober AE: Bacteroides melaninogenicus. Its recovery from tonsils of children with acute tonsillitis. Arch Otolaryngol 1983; 109:818-820 8. Mardh PA, Hovelius B, Nordenfelt E, et al: The incidence and aetiology of respiratory tract infections in general practice-with emphasis on Mycoplasma pneumoniae. Infection 1976; 41:40-48 (suppl] 9. Quinn RW, Lowry PN: The anatomical area of involvement in streptococcal infections and the carrier state. Yale J Biol Med 1970; 43:1-10 10. Wheeler SM, Foley GE: A note on non-group-A streptococci associated with human infection. J Bacterial 1943; 46:391-392 11. Commission on Acute Respiratory Diseases: The role of Lancefield groups of beta-hemolytic streptococci in respiratory infections. N Engl J Med 1947; 236:157-166 12. Ridgeway NA, Perlman PE, Verghese A, et al: Epiglottic abscess due to group B Streptococcus. Ann Otol Rhino1 Laryngo1 1984; 93:277-278 13. Brook I: Distribution of beta haemolytic streptococci in pharyngitis specimens obtained from children. Microbios 1983; 36:169-172 14. Dworzack DL, Hodges GR, Barnes WG, et al: Group B streptococcal infections in adult males. Am J Med Sci 1979; 277~67-73 15. Swingle HM, Bucciarelli RL, Ayoub EM: Synergy between penicillins and low concentrations of gentamicin in the killing of group B streptococci. J Infect Dis 1985; 152:515-520 16. Hare R: The classification of haemolytic streptococci from the nose and throat of normal human beings by means of precipitin and biochemical tests. 1 Path01 Bacterial 1935; 41:499-512
17. Griffith F: The serological classification of Streptococcus pyogenes. J Hyg (Land) 1934; 34:542-592 18. Group C streptococcal infections associated with eating homemade cheese--New Mexico. MMWR 1983; 32:501-516 19. Duca E, Teodorovici GR, Radu C, et al: A new nephritogenic streptococcus. J Hyg (Land] 1969: 67:691-698 20. Hutchinson RI: Pathogenicity of group A (Lancefield) haemolytic Streptococcus. Br Med J 1946: 2:575-576 21. Fulginiti VA, Ey JL, Ryan KJ: Recurrent group C streptococcal tonsillitis in an adolescent male requiring tonsillectomy. Clin Pediatr 1980; x9:829-830 22. Benjamin JT, Perriello VA, Jr: Pharyngitis due to group C hemolytic streptococci in children. J Pediatr 1976; 89:254-256 23. Stamm AM, Cobbs GC: Group C streptococcal pneumonia. Report of a fatal case and review of the literature. Rev Infect Dis 1980; 2:889-897 24. Arditi M, Shulman ST, Davis AT, et al: Group C B-hemolytic streptococcal infections in children: Nine pediatric cases and review. Rev Infect Dis 1989; 11:34-45 25. Kohler W, Cederberg A: Streptococcus zooepidemicus (group C streptococci) as a cause of human infection. Stand J Infect Dis 1976, 8:217-218 26. Schwartz RH, Knerr RJ, Hermansen K, et al: Acute epiglottitis caused beta-hemolytic group C streptococci. Am J Dis Child 1982; 136558-559 27. Flodstrom A, Hallander HO: Microbiological aspects on peritonsillar abscesses. Stand J Infect Dis 1976; 8:157-160 28 Layon J, McCulley D: Subdural empyema and group C Streptococcus. South Med J 1985; 78:64-67 29. Patey 0, Buisson CB, Sousy CJ: Group C streptococcal meningitis in adults. Rev Infect Dis 1990; 12:157-158 30. Kuskie MR: Group C streptococcal infections. Pediatr Infect Dis J 1987; 6:856-859 31. Barnham M, Thornston TJ. Lange K: Nephritis caused by Streptococcus zooepidemicus (Lancefield group C). Lancet 1983; 1:945-948 32. Barnham M, Ljunggren A, McIntyre M: Human infection with Streptococcus zooepidemicus (Lancefield group C): Three case reports. Epidemiol Infect 1987; 98:183-190 33. Andrewes FW, Horder TJ: A study of the streptococci pathogenic for man. Lancet 1906; 2:708-713 34. Hare R, Maxted WR: The classification of haemolytic streptococci from the stools of normal pregnant women and of
296 cases of scarlet fever by means of precipitin and biochemical tests. J Bacterial 1935; 41:513-520 35. Long PH, Bliss EA, Walcott CF: Studies upon minute hemolytic streptococci II. The distribution of minute hemolytic streptococci in normal and diseased human beings. J Exp Med 1934; 60:633-641 36. Poole PM, Wilson G: Occurrence and cultural features of Streptococcus milleri in various body sites. J Clin Path01 1979; 32:764-768 37. Wort AJ: Observations on group-F streptococci from human sources. J Med Microbial 1975; 8:455-457 38. Ingham HR, Sisson PR: Isolates of group F Streptococcus. Am J Clin Path01 1977; 68:798 39. Libertin CR, Hermans PE, Washington JA II: Betahemolytic group F streptococcal bacteremia: A study and review of the literature. Rev Infect Dis 1985; 7:498-503 40. Bliss EA: Studies upon minute hemolytic streptococci III. Serological differentiation. J Bacterial 1937; 33:625-642 41. Plummer H: A serological and biochemical study of hemolytic streptococci. J Immunol 1941; 42:91-107 42. Righter J, Zwerver J: Infections caused by group F streptococci. Can Med Assoc J 1981; 125:1008-1010 43. Lancefield R, Hare R: The serological differentiation of pathogenic and non-pathogenic strains of hemolytic streptococci from parturient women. J Exp Med 1935; 61:335-349 44. Hill HR, Caldwell GG, Wilson E, et al: Epidemic of pharyngitis due to streptococci of Lancefield group G. Lancet 1969; 2:371-374 45. McCue iD: Group G streptococcal pharyngitis. Analysis of an outbreak at a college. JAMA 1982; 248:1333-1336 46. Stryker WS, Fraser DW, Facklam RR: Foodborne outbreak of group G streptococcal pharyngitis. Am J Epidemiol 1982; 116:533-540 47. Armstrong D, Blevins A, Louria DB, et al: Groups B, C, and G streptococcal infections in a cancer hospital. Ann N Y Acad Sci 1970: 174:511-522
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48. Tuazon CU: Case report group G Streptococcus. Am J Med Sci 1980; 279:121-124 49. Bisno AL, Craven DE, McCabe WR: M proteins of group G streptococci isolated from bacteremic human infections. Infect Immun 1987; 55:753-757 50. Gnann J, Jr, Gray BM, Griffin FM, Jr, et al: Acute glomerulonephritis following group G streptococcal infection. J Infect Dis 1987; 156:411-412 51. Maxted WR, Potter EV: The presence of type 12 M-protein antigen in group G streptococci. J Gen Microbial 1967; 49:119-125 52. Watsky KL, Kollisch N, Densen P: Group G streptococcal bacteremia. The clinical experience at Boston University Medical Center and a critical review of the literature. Arch Intern Med 1985; 145:58-61 53. Ancona RJ, Thompson TR, Ferrieri P: Group G streptococcal sepsis in a new born infant. J Clin Microbial 1979; 10:758-759 54. Vartian C, Lerner PI, Shlaes DM, et al: Infections due to Lancefield group G streptococci. Medicine 1985; 64:75-88 55. Krober MS, Bass JW, Michels GN: Streptococcal pharyngitis. JAMA 1985; 253:1271-1274 56. Kaplan EL, Top FH, Jr, Dudding BA, et al: Diagnosis of streptococcal pharyngitis. Differentiation of active infection from the carrier state in the symptomatic child. J Infect Dis 1971; 123:490-501 57. Brook I, Yocum P, Shah K: Surface vs core-tonsillar aerobic and anaerobic flora in recurrent tonsillitis. JAMA 1980; 244:1696-1698 58. Sprunt K, Leidy GA, Redman W: Prevention of bacterial overgrowth. J Infect Dis 1971; 123:1-10 59. Wickman K: Studies of bacterial interference in experimentally produced burns in guinea pigs. Acta Path01 Microbiol Stand [B] Microbial Immunol 1970: 78:15-28 60. Krizck TJ, Robson MC: Biology of surgical infection. Surg Clin North Am 1975; 55:1261-1267
12:292-296, 1991
Pharyngeal and Tonsil Infections Caused by Non-Group A Streptococcus JAMES PATRICK DUDLEY, MD, AND JOELSERCARZ, MD
Non-group A streptococci are members of the genus Streptococcus but do not share the notoriety of their cousin from group A. Most physicians, including otolaryngologists and head and neck surgeons, do not associate them with upper respiratory tract and head and neck infections. Some laboratories do not bother to report their presence on culture. At the University of California, Los Angeles they have been shown to cause (1) tonsillitis, painful tonsils lacking exudate and erythema (group C, one case; group F, one case), (2) acute nonexudative tonsillitis (group B, two cases: group C, one case; group F, one case), and (3) acute exudative tonsillitis (group C, one case). It should be remembered when there is a report of their presence that they are usually vulnerable to penicillin and its analogs. By judicious use of these drugs, morbidity can be diminished. AM J OTOLARYNGOL 12:292-296. Copyright 0 1991 by W.B. Saunders Company Key words: non-group A Streptococcus, pharyngitis, tonsillitis.
pathogens at work in such cases. Recently, Brook and Grober have implicated an anaerobe, Bacteroides melaninogenicus, as a cause of acute tonsillitis.7 Another study reported that Mycoplasma pneumoniae was recovered in 16% of acute sore throat cases.’ There is evidence, however, that non-group A streptococci may also act as pathogens in the upper respiratory tract and on mucosal surfaces. Since most clinical microbiologic laboratories only test for group A Streptococcus when betahemolysis is seen, the presence of non-group A streptococci may go undetected. The significance of these organisms as a cause of pharyngotonsillitis is their susceptibility to penicillin and penicillin analogs. We studied non-group A streptococcal pharyngotonsillitis, documented its resolution with antibiotics, and investigated the role of these infections in upper respiratory tract disease.
Pharyngitis and tonsillitis are frequent diagnoses made by otolaryngologists and primary care physicians1 Determining the etiology of these infections is often very frustrating. Although group A beta-hemolytic Streptococcus has been identified in the past as the leading and only bacteria causing these infections and has even been reported to cause 30% to 40% of pharyngeal and tonsillar infections,’ most clinicians know this is not the case except in instances in which an epidemic of throat infection may be caused by this organism, eg, in college dormitories or in military installations.394 Viruses have always been named as the other and probably chief microbial cause of pharyngotonsillitis. There is very little proof, however, that this is the case. In a study involving 2,559 boys admitted to a detention center over a 5-year period, 421 developed acute tonsillitis. In this group, virus was recovered from only two patients.5 As Hovelius et al observed, “One cannot conclude that patients from whom no bacteria have been isolated have a viral infection.“” It would appear that there are other microbial
MATERIALS AND METHODS Throat cultures were obtained from six adult patients who complained of a sore throat. None had fever. All had slightly tender jugulodigastric adenopathy, but there were no other symptoms or signs. They were seen in the private patient head and neck clinic at the University of California, Los Angeles (UCLA) over a period of 12 months but were not consecutive cases. There were 95 patients with a complaint of sore throat seen by one of the authors (J.P.D.) during that 12-month period. Of this number, 34 had acute tonsillitis. Cultures were sent to the clinical microbiologic laboratory at UCLA
Receivedfrom the Department of Surgery, Division Head and Neck Surgery, University of California, Los Angeles Medical Center Los Angeles, CA. Address correspondence and reprint requests to James Patrick Dudlev, MD, Wall Medical Group, 2001 Union St, Suite 550, San Francisco, CA 94123. Copyright 0 1991 by W.B. Saunders Company 0196-0709l9111205-0001$5.00l0 292
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Hospital. Each was plated on blood agar and MacConky’s agar. As was routine with cultures obtained by this author, the laboratory tested all Streptococcus antigens A, B, C, F, and G when beta-hemolysis was seen. In each of six patients with symptomatic tonsillitis, non-group A Streptococcus was identified. One patient had exudative tonsillitis. In three of the six patients, these streptococci were isolated in pure culture. In the other patients, many non-group A streptococci were isolated with only a few other normal flora present. In one of the patients an antistreptolysin-0 (ASO) titer was obtained during the patient’s illness.
RESULTS Group 6 Streptococcus. Two patients were seen with tonsillitis caused by group B Streptococcus. One produced a pure culture of group B Streptococcus. There was no exudate present, but this patient demonstrated an elevated AS0 titer of 170 Todd units (normal, ~120). From the second patient with a similar clinical picture, many group B streptococci were isolated with a few colonies of Neisseria sp.
Group C Streptococcus. Two patients were seen. In one patient with exudative tonsillitis, group C Streptococcus was obtained in pure culture. In the other, a mild case of tonsillitis, many group C streptococci were recovered with a few colonies of oropharyngeal flora (Neisseria sp and alpha-streptococci). Group F Streptococcus. Two patients were seen. Neither involved exudate; however, both were was symptomatic and yielded moderate numbers of group F streptococci from tonsil cultures with only a few normal oral flora (alphastreptococci and a few Neisseria sp). All six patients were treated with penicillin or ampicillin. Symptoms subsided within 2 days in every case. Antibiotics were continued for 4 to 10 days. In the two patients with group B Streptococcus, follow-up cultures were obtained. In neither instance was group B Streptococcus isolated on follow-up culture. DISCUSSION Six adult patients presented with sore throat symptoms and evidence of pharyngitis and/or tonsillitis. From each of these patients a non-group A, beta-hemolytic Streptococcus was isolated. There is always a question of the significance of the culture of an organism from the upper respiratory that which might be considered normal flora. There appears to be some evidence that the presence of organisms in larger numbers correlates with infection, while organisms present in smaller numbers correlate with normal flora or
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Quinn and “the carrier state.“g Interestingly, Lowry noted in a study of children with clinical streptococcal disease that they were unable to isolate group A Streptococcus in some patients despite the clinical evidence of disease.’ However, they were able to isolate groups C and G in large numbers from some children in whom group A could not be isolated. This seemed to point to the possibility that groups C and G streptococci (and perhaps other non-group A streptococci) are able to produce mucosal (pharyngeal) disease. Most observers feel that the isolation of an organism in pure culture from a patient with symptomatic disease implies that the organism is playing a major role in the infection. Indeed, in two of the patients, this was the case. In one patient with acute nonexudative tonsillitis, group B Streptococcus was isolated in pure culture. In that patient, an elevated AS0 titer was also present. A repeat culture following treatment failed to isolate group B Streptococcus from that patient. These two findings, an elevated AS0 titer and failure to isolate the organism on a second culture, appear to lend credence to the toxic capability of group B Streptococcus in the pharynx. Group C Streptococcus was isolated in pure culture from another patient with exudative tonsillitis. Group B Streptococcus is well known as a cause of serious infections in newborn infants. In infants it can produce meningitis, pneumonia, and bacteremia. However, it appears that group B Streptococcus is also capable of inducing disease in the respiratory tract. In 1942, Wheeler and Foley recovered group B Streptococcus from the middle ears of two patients with otitis media, and they also recovered group B Streptococcus from their spinal fluid. lo In 1947, three patients with group B-induced tonsillitis were reported.” A report of an epiglottal abscess from which group B Streptococcus was isolated in pure culture when aspirated would again seem to indicate that it has the ability to induce upper respiratory tract disease.l’ Group B Streptococcus has been cultured from the throats of 4% of children with acute pharyngitis,13 but there is virtually no information concerning its presence in adults. One study of group B streptococcal infections in hospitalized adult males found 24 with acute infections, but no group B upper respiratory infections were identified in this group.14 It appears that the two cases of acute tonsillitis presented here and the three patients reported in 194711 are the first documented cases of group B streptococcal pharyngeal infection. The symptoms of both patients in our study responded to treatment with penicillin. Although the killing of group B Streptococcus is accelerated when penicillin is combined with gen-
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tamicin,15 penicillin by itself appears to be adequate therapy for these pharyngeal infections. Group C Streptococcus. The presence of group C Streptococcus in the oropharynx has been known for 50 years.‘” It can be found in small numbers in the oropharynx of 1% of healthy young adult men.17 The recovery of group C Streptococcus from the throats of six patient with clinical tonsillitis was reported in 1947,ll although exudate was present in only three. All had elevated AS0 titers. It has been associated with food-borne infectionla~lg: cheesel’ and milklg have been identified as the vehicles for this organism. Non-epidemic tonsillar infection has been reported from time to time. Hutchinson reported six patients with exudative tonsillitis and 33 with “mild tonsillitis” from whom group C Streptococcus was isolated in pure culture.” Fulgitini et al described recurrent group C tonsillitis in a l5year-old boy who required tonsillectomy to cure his diseasee21 When it occurs it can be very contagious, as evidenced by a report of 21 cases of group C Streptococcus-induced pharyngitis at a boarding school. 22 In seven of these patients an exudate was present. It may not always be a benign disease. Stamm and Cobbs reported a healthy male with exudative tonsillitis who ultimately died of group C streptococcal pneumonia.23 It has been found in pure culture in two patients with sinusitis, one of whom died of meningitis.24 It also has been found in an aspirated neck mass from an acutely ill child with pharyngitis,25 in acute epiglottitis2” [it was isolated from the blood and the epiglottitis), in a peritonsillar abscess,27 and in a middle ear infection that resulted in subdural empyema.28 Group C Streptococcus was isolated from the middle ear effusion of a 77-year-old woman who died of meningitis.2g Although it rarely invades upper respiratory mucosa, thus causing bacteremia, it was noted as the source of bacteremia in two children with pharyngitis.30 One of the most disturbing features of this microorganism is its ability to induce glomerulonephritis following minor upper respiratory tract disease.1gp31,32The pharyngeal infections that led to glomerulonephritis were probably transmitted through animal contact and the particular group C strain was Streptococcus zooepidemicus. Group F Streptococcus. Group F streptococci were isolated from the oropharynx in 190633 and 1935,34 and from the nasopharynx in 1934.35 It appears that they have been long considered part of the normal flora of the upper respiratory tract.36-38 They have recently been isolated from abscesses,3g most of which were in the abdominal cavity or urinary tract, although 27 were in the
NON-GROLJPASTREPTOCOCCALPHARYNGITIS
head and neck.3g This organism has also been identified as a cause of sinusitis.36,40,41 Group F Streptococcus has caused bacteremia in two patients with exudative tonsillitis.36 It has been identified as a cause of exudative tonsillitis in seven patients,” yet it has received little attention as a pathogen. Although there is a low incidence of its recovery of this organism from children,13 there appears to be a higher incidence of its recovery in adults.41p42 Since there is not as much academic interest in adult pharyngitis/tonsillitis, the seeming absence of group F Streptococcus in many reports may help to explain why this organism’s pathogenic potential has gone unnoticed. Group G Streptococcus. Group G Streptococcus was first noted by Lancefield and Hare in 1934.43 No patients with group G streptococcal pharyngitis or other head and neck infection were identified in this study. However, group G organisms have been reported as a cause of pharyngitis. Among a group of military recruits, four cases of pharyngitis (one of them exudative) were associated with group G Streptococcus.” Three of the four patients had elevated AS0 titers. The largest number of patients with group G-induced pharyngitis was reported in connection with a college outbreak in 1969.44 Of 502 students diagnosed with acute pharyngitis, group G Streptococcus was isolated in 155. Twenty-three of these had exudates. Another college outbreak of acute pharyngitis involving 68 students was reported in 1982.45 Most of these patients had exudative pharyngitis and/or tonsillitis with fever. An outbreak of pharyngitis in 10 patients reported in 1982 was thought to be due to group G Streptococcuscontaminated food.4” Although bacteremia apparently is uncommon, it can occur in head and neck cancer patients from whom the organism can be isolated in the upper respiratory tract.47,48 Despite the low incidence of bacteremia in healthy patients, there is some evidence that a surface protein of group G Streptococcus4’ is capable of producing glomerulonephritis.50~5* Although penicillin has been the standard medication used against this organism when it has been found to be a pathogen, beta-lactam antibiotics seem to be a more effective form of treatment.52 Erythromycin does not appear to be a valuable drug in the treatment of this microorganism. 53 In severe infections such as abscesses in the upper respiratory tract, penicillin should be combined with an aminoglycocide.54 Increase in AS0 titer has been used as a sine qua non in the diagnosis of streptococcal infection. Interestingly, Krober et al have found an elevated AS0 titer in 17% of patients with tonsilli-
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DUDLEY AND SERCARZ
tis in whom group A organisms were not founde5’ This appears to offer further evidence that other non-group A streptococci might be causative agents in some cases of pharyngotonsillitis. However, Kaplan et al, while trying to differentiate between infection and the carrier state, found that as few as IO colonies are capable of inducing a serologic response,56 suggesting that an elevated titer might not be an ideal indication of infection. Clinical symptoms and culture results may be better indicators, If culture results are important, a complete streptococcal cultural screen would be of more value to determine if antibiotic treatment would diminish morbidity. Brook et al found concordance between surface and core tonsil cultures in two of the non-group A streptococci.57 The mechanism by which apparently commensal microorganisms exist on the surface of asymptomatic tonsils and pharyngeal mucosa and at other times become pathogens remains unknown. Although all of these microorganismscommensals and pathogens-are capable of adherence to host pharyngeal epithelium, it has been postulated that a kind of synergism is established among all of these microorganisms that prevents pathogens from overwhelming commensals.58 Whether a “priority of colonization”5g is the secret of this microbial truce is uncertain; that is, the organisms that were there first are the ones most likely to prevail. There also may be another mechanism at work called “bacterial load.““’ In this scenario, microorganisms that are present in small numbers and are acting as commensals may “overload” the system and produce toxicity when their numbers increase. Searching for potentially pathogenic microorganisms may provide the answer. It will require a vertical prospective study, using a large group of subjects who will act as their own controls, that will investigate the variety of aerobes on noninfected and infected tonsillar and pharyngeal mucosa. This may provide further information about the pathogenesis of non-group A streptococci in the pharynx. References I. Marsland DW, Wood M, Mayo F: A data bank for patient care, curriculum, and research in-family practice: 526,i96 patient problems. J Family Pratt 1976; 3:25-28,37-38 2. Peter G, Smith AC; Group A streptococcal infection of the skin and pharynx. N Engl J Med 1977; 297:311-317 3. Strauss E: Role of B-hemolytic streptococci in common respiratory disease. Am J Public Health 1945; 35:675-682 4. Eggenberger K, Christen JP, Delarue C, et al: Streptococcal pharyngitis-tonsillitis in Swiss children. Diagnosis and management. Paediatrician 1980; 9:295-308 5. Colling A, Kerr I, Maxted WR, et al: Streptococcal infection in a junior detention center: A five year study. J Hyg (Lond) 1980; 85:331-341 6. Hovelius B, Bygren P, Christensen Mardh PA: Respiratory
tract infections at a community care centre-With emphasis on group A streptococci. Stand J Infect Dis 1983; 39:59-67 (suppl) 7. Brook I, Grober AE: Bacteroides melaninogenicus. Its recovery from tonsils of children with acute tonsillitis. Arch Otolaryngol 1983; 109:818-820 8. Mardh PA, Hovelius B, Nordenfelt E, et al: The incidence and aetiology of respiratory tract infections in general practice-with emphasis on Mycoplasma pneumoniae. Infection 1976; 41:40-48 (suppl] 9. Quinn RW, Lowry PN: The anatomical area of involvement in streptococcal infections and the carrier state. Yale J Biol Med 1970; 43:1-10 10. Wheeler SM, Foley GE: A note on non-group-A streptococci associated with human infection. J Bacterial 1943; 46:391-392 11. Commission on Acute Respiratory Diseases: The role of Lancefield groups of beta-hemolytic streptococci in respiratory infections. N Engl J Med 1947; 236:157-166 12. Ridgeway NA, Perlman PE, Verghese A, et al: Epiglottic abscess due to group B Streptococcus. Ann Otol Rhino1 Laryngo1 1984; 93:277-278 13. Brook I: Distribution of beta haemolytic streptococci in pharyngitis specimens obtained from children. Microbios 1983; 36:169-172 14. Dworzack DL, Hodges GR, Barnes WG, et al: Group B streptococcal infections in adult males. Am J Med Sci 1979; 277~67-73 15. Swingle HM, Bucciarelli RL, Ayoub EM: Synergy between penicillins and low concentrations of gentamicin in the killing of group B streptococci. J Infect Dis 1985; 152:515-520 16. Hare R: The classification of haemolytic streptococci from the nose and throat of normal human beings by means of precipitin and biochemical tests. 1 Path01 Bacterial 1935; 41:499-512
17. Griffith F: The serological classification of Streptococcus pyogenes. J Hyg (Land) 1934; 34:542-592 18. Group C streptococcal infections associated with eating homemade cheese--New Mexico. MMWR 1983; 32:501-516 19. Duca E, Teodorovici GR, Radu C, et al: A new nephritogenic streptococcus. J Hyg (Land] 1969: 67:691-698 20. Hutchinson RI: Pathogenicity of group A (Lancefield) haemolytic Streptococcus. Br Med J 1946: 2:575-576 21. Fulginiti VA, Ey JL, Ryan KJ: Recurrent group C streptococcal tonsillitis in an adolescent male requiring tonsillectomy. Clin Pediatr 1980; x9:829-830 22. Benjamin JT, Perriello VA, Jr: Pharyngitis due to group C hemolytic streptococci in children. J Pediatr 1976; 89:254-256 23. Stamm AM, Cobbs GC: Group C streptococcal pneumonia. Report of a fatal case and review of the literature. Rev Infect Dis 1980; 2:889-897 24. Arditi M, Shulman ST, Davis AT, et al: Group C B-hemolytic streptococcal infections in children: Nine pediatric cases and review. Rev Infect Dis 1989; 11:34-45 25. Kohler W, Cederberg A: Streptococcus zooepidemicus (group C streptococci) as a cause of human infection. Stand J Infect Dis 1976, 8:217-218 26. Schwartz RH, Knerr RJ, Hermansen K, et al: Acute epiglottitis caused beta-hemolytic group C streptococci. Am J Dis Child 1982; 136558-559 27. Flodstrom A, Hallander HO: Microbiological aspects on peritonsillar abscesses. Stand J Infect Dis 1976; 8:157-160 28 Layon J, McCulley D: Subdural empyema and group C Streptococcus. South Med J 1985; 78:64-67 29. Patey 0, Buisson CB, Sousy CJ: Group C streptococcal meningitis in adults. Rev Infect Dis 1990; 12:157-158 30. Kuskie MR: Group C streptococcal infections. Pediatr Infect Dis J 1987; 6:856-859 31. Barnham M, Thornston TJ. Lange K: Nephritis caused by Streptococcus zooepidemicus (Lancefield group C). Lancet 1983; 1:945-948 32. Barnham M, Ljunggren A, McIntyre M: Human infection with Streptococcus zooepidemicus (Lancefield group C): Three case reports. Epidemiol Infect 1987; 98:183-190 33. Andrewes FW, Horder TJ: A study of the streptococci pathogenic for man. Lancet 1906; 2:708-713 34. Hare R, Maxted WR: The classification of haemolytic streptococci from the stools of normal pregnant women and of
296 cases of scarlet fever by means of precipitin and biochemical tests. J Bacterial 1935; 41:513-520 35. Long PH, Bliss EA, Walcott CF: Studies upon minute hemolytic streptococci II. The distribution of minute hemolytic streptococci in normal and diseased human beings. J Exp Med 1934; 60:633-641 36. Poole PM, Wilson G: Occurrence and cultural features of Streptococcus milleri in various body sites. J Clin Path01 1979; 32:764-768 37. Wort AJ: Observations on group-F streptococci from human sources. J Med Microbial 1975; 8:455-457 38. Ingham HR, Sisson PR: Isolates of group F Streptococcus. Am J Clin Path01 1977; 68:798 39. Libertin CR, Hermans PE, Washington JA II: Betahemolytic group F streptococcal bacteremia: A study and review of the literature. Rev Infect Dis 1985; 7:498-503 40. Bliss EA: Studies upon minute hemolytic streptococci III. Serological differentiation. J Bacterial 1937; 33:625-642 41. Plummer H: A serological and biochemical study of hemolytic streptococci. J Immunol 1941; 42:91-107 42. Righter J, Zwerver J: Infections caused by group F streptococci. Can Med Assoc J 1981; 125:1008-1010 43. Lancefield R, Hare R: The serological differentiation of pathogenic and non-pathogenic strains of hemolytic streptococci from parturient women. J Exp Med 1935; 61:335-349 44. Hill HR, Caldwell GG, Wilson E, et al: Epidemic of pharyngitis due to streptococci of Lancefield group G. Lancet 1969; 2:371-374 45. McCue iD: Group G streptococcal pharyngitis. Analysis of an outbreak at a college. JAMA 1982; 248:1333-1336 46. Stryker WS, Fraser DW, Facklam RR: Foodborne outbreak of group G streptococcal pharyngitis. Am J Epidemiol 1982; 116:533-540 47. Armstrong D, Blevins A, Louria DB, et al: Groups B, C, and G streptococcal infections in a cancer hospital. Ann N Y Acad Sci 1970: 174:511-522
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48. Tuazon CU: Case report group G Streptococcus. Am J Med Sci 1980; 279:121-124 49. Bisno AL, Craven DE, McCabe WR: M proteins of group G streptococci isolated from bacteremic human infections. Infect Immun 1987; 55:753-757 50. Gnann J, Jr, Gray BM, Griffin FM, Jr, et al: Acute glomerulonephritis following group G streptococcal infection. J Infect Dis 1987; 156:411-412 51. Maxted WR, Potter EV: The presence of type 12 M-protein antigen in group G streptococci. J Gen Microbial 1967; 49:119-125 52. Watsky KL, Kollisch N, Densen P: Group G streptococcal bacteremia. The clinical experience at Boston University Medical Center and a critical review of the literature. Arch Intern Med 1985; 145:58-61 53. Ancona RJ, Thompson TR, Ferrieri P: Group G streptococcal sepsis in a new born infant. J Clin Microbial 1979; 10:758-759 54. Vartian C, Lerner PI, Shlaes DM, et al: Infections due to Lancefield group G streptococci. Medicine 1985; 64:75-88 55. Krober MS, Bass JW, Michels GN: Streptococcal pharyngitis. JAMA 1985; 253:1271-1274 56. Kaplan EL, Top FH, Jr, Dudding BA, et al: Diagnosis of streptococcal pharyngitis. Differentiation of active infection from the carrier state in the symptomatic child. J Infect Dis 1971; 123:490-501 57. Brook I, Yocum P, Shah K: Surface vs core-tonsillar aerobic and anaerobic flora in recurrent tonsillitis. JAMA 1980; 244:1696-1698 58. Sprunt K, Leidy GA, Redman W: Prevention of bacterial overgrowth. J Infect Dis 1971; 123:1-10 59. Wickman K: Studies of bacterial interference in experimentally produced burns in guinea pigs. Acta Path01 Microbiol Stand [B] Microbial Immunol 1970: 78:15-28 60. Krizck TJ, Robson MC: Biology of surgical infection. Surg Clin North Am 1975; 55:1261-1267
