International Elsevier
PEDOT
Journal of Pediatric
Uiorhinolaryngology,
123
20 (1990) 123-126
00670
Enterococcus faecalis and otitis media with effusion.
How to treat James Patrick Department
Dudley
and Joel Sercarz
of Surgery, Divison of Head and Neck Surgery Los Angeles, CA 90024 (U.S.A.)
UCLA Medical Center,
(Received 6 February 1990) (Revised version received 6 July 1990) (Accepted 31 July 1990)
Key words: Otitis media with effusion;
Enterococcus faecalis
Abstract Although microorganisms are cultured in only one out of 3 middle ear effusions, viable and non-viable bacteria are presumed to be responsible in part for otitis media with effusion (OME). Because of this association, antibiotics in sublethal, bacteriostatic, or bacteriocidal concentrations are frequently used as non-surgical therapy for OME. Antibiotic treatment is predicated on the assumption that microorganisms responsible for OME are the same ones which produce acute otitis media. This may not always be the case. Enterococcus faecalis (formerly known as /3-hemolytic group D Streptococcus) was isolated in pure culture from 3 middle ears of two patients with OME. The significance of the isolation of this bacteria, an enteric organism which is infrequently found in upper respiratory tracts, is its lack of susceptibility to the usually prescribed oral antibiotics. In each of the children, failure to respond to antibiotics led to tympanocentesis and culture followed by middle ear drainage with insertion of middle ear ventilating tubes. Unless intravenous antibiotics are used, surgical drainage should be the procedure of choice when E. faecalis is found in the middle ear.
Introduction Enterococcus faecalis, formerly known as group D Streptococcus microorganism with which otolaryngologists/head and neck surgeons
Correspondence: Medical Center,
J.P. Dudley, Department of Surgery, Los Angeles, CA 90024, U.S.A.
0165-5876/90/$03.50
0 1990 Elsevier Science Publishers
Divison
of Head
B.V. (Biomedical
and
Neck
Division)
[lo], have
Surgery,
is a little
UCLA
124
familiarity. Schaberg termed them ‘the Benedict Arnolds of the streptococci’ [9]. This is because these Gram-positive cocci have ‘chosen to abandon their cousins’ [9], the other streptococci in the upper respiratory tract, and become part of the normal flora of the gastrointestinal tract. Consequently, it is rare that these bacteria have been associated with disease in the upper respiratory tract. Two episodes of E. faecalis-induced tonsillitis and pharyngitis were reported 37 years ago [14]. In each patient E. faecalis was isolated in pure culture. Other than being found in mixed cultures, there has been no information concerning the pathologic potential of this organism on upper respiratory membrane. Although isolation of E. faecalis in pure culture is unusual (except from the urinary tract and from the blood in the presence of endocarditis) [6], they were found in pure culture from 3 middle ears of two children. They were identified by growth on bile esculin agar and growth in 6.5% sodium chloride. Further identification was made using the Vitec (McDonnell Douglas, Los Angeles). The significance of E. faecalis as a pathogen, its unusual susceptibility pattern, its erratic response to antibiotics, its ability to induce bacteremia, and the treatment options when it is isolated from the upper respiratory tract are discussed.
Case reports Case I
A 2-year-old female with a history of severe reactive airway disease had a 6 month history of intermittent acute otitis media and otitis media with effusion. Numerous tympanograms demonstrated high acoustic impedance (over 7000 ohms) indicating the presence of middle ear fluid bilaterally. When seen in consultation, the patient had been on antibiotics almost continuously but had taken no antimicrobial therapy for 3 weeks. The tympanic membranes were dull and bulging. A tympanocentesis was performed which demonstrated E. faecalis in pure culture from each middle ear. They were not seen on Gram stain. Each ear canal culture, taken as a background culture, grew only normal skin flora. The patient underwent bilateral myringotomies with insertion of middle ear ventilating tubes. The material removed from the middle ear was mucoid in character. The tubes remained patent until she was lost to follow-up one year later. Case 2 A 3-year-old male with cystic fibrosis was seen in consultation for persistent otitis media with effusion. The exact duration of his chronic otitis media was uncertain although it was noticed by a physician at least 4 months previously. He had not been on any antimicrobial agent for two weeks prior to this examination. His tympanic membranes were gray in color and were bulging slightly. A tympanogram revealed high acoustic impedance bilaterally (over 7000 ohms). A tympanocentesis was done on each middle ear. One middle ear culture showed no growth. The other showed pure culture of E. faecafis with no organisms seen on Gram stain. Ear canal cultures showed normal skin flora. Bilateral myringotomies were per-
125
formed, mucoid material was suctioned from each middle ear, and middle ear ventilating tubes were inserted in each ear. The child was followed for 6 months until his parents moved out of the city.
Discussion The two children described in this report were class III anesthetic risks. The first child had severe bronchospastic disease related to asthma. She required frequent hospitalizations for control of her asthma. The second child had cystic fibrosis, and he was frequently hospitalized for pulmonary toilet. In considering the risk of anesthesia, a question might arise: wouldn’t it be less risky to do nothing? In the anesthesia made maintenance of her airway first paqent the use of halothan relatively easy during the procedure. As with many asthmatic children who undergo surgery, the dangers of induction in emergence were minimized by the use of intravenous. lidocaine. Anesthetic risks in the second child were minimized by increased efforts at pulmonary toilet prior to surgery. Minimal amounts of an inhalational agent were used but were supplemented with both rectal and intravenous barbiturates. It was necessary to intubate the second child in order to assure control of pulmonary secretions. Many children can apparently coexist with otitis media with effusion for long periods of time with no serious complications. E. faecalis is, however, a very different bacteria from others that can be found in such effusions. It appears to be able to invade respiratory mucosa and produce bacteremia [2,14]. In a report from the 1940s. E. faecalis was cultured from the sinuses in a case of E. faecabs bacteremia; the patient died [14]. This ability to induce bacteremia from a mucosal source in the upper respiratory tract is unusual for most microorganisms. Although the mechanism by which E. faecalis can invade mucosa and cause bacteremia is uncertain, microbial adherence is an initial step in this process. It has an unusual adherence mechanism due to a unique surface protein [7], and it adheres more avidly than many other Gram-positive or Gram-negative bacteria [3]. The adherence properties seem to be part of a virulence mechanism in urinary tract infections where bacteremia is a frequent outcome [4]. Thus, it appears that E. faecalis can cause bacteremia when isolated from certain upper respiratory tract sites. It is interesting to speculate as to whether upper respiratory sites could be an occult source of E. faecalis bacteremia since it is not thought to be a pathogen in the upper respiratory tract. A report outlining the cause of E. faecalis bacteremia in 114 patients failed to find the source in almost half of the patients [2]. Since E, faecalis bacteremias are extremely difficult to treat and frequently fatal [2], elimination of a possible source of seeding was done in each of the two patients described here. The reasons for the persistence of most middle ear effusions remain unknown. Although most appear to disappear spontaneously after 12 weeks of observation [ll], some are very persistent. In the two patients described here a variety of antimicrobial agents were used. None of them sterilized the middle ears. Unfor-
126
tunately E. faeculis have a tolerance for cell wall antibiotics [5]. Thus, penicillin and ampicillin are bacteriostatic and not bacteriocidal. Even if satisfactory levels of antibiotics can be achieved in the middle ear, E. fuecalis might persist. If, for any reason, surgery cannot be done, the addition of an aminoglycoside such as gentamicin is often effective [6] despite high level resistance to gentamicin alone [8]. A glycopeptide such as vancomycin in combination with an aminoglycoside is an option for penicillin allergic patients [12]. Vancomycin, although originally uniformally successful, has become less successful because of plasmid mediated resistance [13]. Although ciprofloxacin has in vitro activity against E. faeculis [l], it does not as yet have FDA approval for use in children. Since antibiotics may not sterilize an E. faeculis middle ear, surgical drainage became necessary in these two patients despite anesthetic risks.
References 1 Femandez-Guerrero, M., Rouse, MS., Henry, N.K., Geraci, J.E. and Wilson, W.R., In vitro and in vivo activity of ciprofloxacin against enterococci isolated from patients with infective endocarditis, Antimicrob. Agents Chemother., 31 (1987) 430-433. 2 Garrison, R.N., Fry, D.E., Berberich, S. and Polk, H.C., Enterococcal bacteremia. Clinical implications and determinants of death, Ann. Surg., 196 (1982) 43-47. 3 Gould, K., Ram&z-Ronda, C.H., Holmes, R.K. and Sanford, J.P., Adherence of bacteria to heart valves in vitro, J. Clin. Invest., 56 (1975) 1364-1370. 4 Guzman, C.A., Pruzzo, C., LiPira, G. and Calegari, L., Role of adherence in pathogenesis of Enterococcusfaecalis urinary tract infections and endocarditis, Infect. Immun., 57 (1989) 1834-1838. 5 Hindes, R.G., Willey, S.H., Eliopoulous, G.M., Rice, L.B., Eliopoulous, CT., Murray, B.E. and Mollering, R.C., Treatment of experimental endocarditis caused by a /%lactamase-producing strain of Enterococcus fuecalis with high level resistence to gentamicin, Antimicrob. Agents Chemother., 33 (1989) 1019-1022. 6 Kaye, D., Enterococci. Biologic and epidemiologic characteristics and in vitro susceptibility, Arch. Intern. Med., 142 (1982) 2006-2009. 7 Kurl, D.N., Haataja, S. and Fume, J., Hemagglutination activity of group B, C, D, and G streptococci: demonstration of novel sugarspecific cell-binding activities in Streptococcus sub, Infect. Immun., 57 (1989) 384-389. 8 Mederski-Samoraj, B.D. and Murray, B.E., High-level resistence to gentamicin in clinical isolates of enterococci, J. Infect. Dis., 147 (1983) 751-757. 9 Schaberg, D., Global patterns of resistance to antimicrobial agents in selected pathogens, 28th Interscience Conference on Antimicrobials and Chemotherapy, October 24, 1988, Los Angeles, California. 10 Schleifer, K.H. and Kilpper, R., Transfer of Streptococcw faecah and Streptococw fuecium to the genus Enterococcus nom. rev. as Enterococcus faecalis comb. nov. and Enterococcus faecium comb. nov., Int. J. System. Bacterial., 34 (1984) 31-34. 11 Schwartz, R.H., Rodriguez, W.J. and Gnmdfast, K.M., Duration of middle ear effusion after acute otitis media, Pediatr. Infect. Dis., 3 (1984) 204-207. 12 Shlaes, D.M., Bouvet, A., Devine, C., Shlaes, J.H., Al-obeid, S. and Williamson, R., Inducible, transferrable resistence to vanwmyin in Enterococcus faecalis A256, Antimicrob. Agents Chemother., 33 (1989) 198-203. 13 Uttley, A.H., Collins, C.H., Nasio, J. and George, R.C., Vancomycin resistant enterococci, Lancet 1 (1988) 57-58. 14 Wheeler, SM. and Foley, G.E., A note on non-group A steptococci associated with human infection, J. Bacterial., 46 (1943) 391-392.
PEDOT
Journal of Pediatric
Uiorhinolaryngology,
123
20 (1990) 123-126
00670
Enterococcus faecalis and otitis media with effusion.
How to treat James Patrick Department
Dudley
and Joel Sercarz
of Surgery, Divison of Head and Neck Surgery Los Angeles, CA 90024 (U.S.A.)
UCLA Medical Center,
(Received 6 February 1990) (Revised version received 6 July 1990) (Accepted 31 July 1990)
Key words: Otitis media with effusion;
Enterococcus faecalis
Abstract Although microorganisms are cultured in only one out of 3 middle ear effusions, viable and non-viable bacteria are presumed to be responsible in part for otitis media with effusion (OME). Because of this association, antibiotics in sublethal, bacteriostatic, or bacteriocidal concentrations are frequently used as non-surgical therapy for OME. Antibiotic treatment is predicated on the assumption that microorganisms responsible for OME are the same ones which produce acute otitis media. This may not always be the case. Enterococcus faecalis (formerly known as /3-hemolytic group D Streptococcus) was isolated in pure culture from 3 middle ears of two patients with OME. The significance of the isolation of this bacteria, an enteric organism which is infrequently found in upper respiratory tracts, is its lack of susceptibility to the usually prescribed oral antibiotics. In each of the children, failure to respond to antibiotics led to tympanocentesis and culture followed by middle ear drainage with insertion of middle ear ventilating tubes. Unless intravenous antibiotics are used, surgical drainage should be the procedure of choice when E. faecalis is found in the middle ear.
Introduction Enterococcus faecalis, formerly known as group D Streptococcus microorganism with which otolaryngologists/head and neck surgeons
Correspondence: Medical Center,
J.P. Dudley, Department of Surgery, Los Angeles, CA 90024, U.S.A.
0165-5876/90/$03.50
0 1990 Elsevier Science Publishers
Divison
of Head
B.V. (Biomedical
and
Neck
Division)
[lo], have
Surgery,
is a little
UCLA
124
familiarity. Schaberg termed them ‘the Benedict Arnolds of the streptococci’ [9]. This is because these Gram-positive cocci have ‘chosen to abandon their cousins’ [9], the other streptococci in the upper respiratory tract, and become part of the normal flora of the gastrointestinal tract. Consequently, it is rare that these bacteria have been associated with disease in the upper respiratory tract. Two episodes of E. faecalis-induced tonsillitis and pharyngitis were reported 37 years ago [14]. In each patient E. faecalis was isolated in pure culture. Other than being found in mixed cultures, there has been no information concerning the pathologic potential of this organism on upper respiratory membrane. Although isolation of E. faecalis in pure culture is unusual (except from the urinary tract and from the blood in the presence of endocarditis) [6], they were found in pure culture from 3 middle ears of two children. They were identified by growth on bile esculin agar and growth in 6.5% sodium chloride. Further identification was made using the Vitec (McDonnell Douglas, Los Angeles). The significance of E. faecalis as a pathogen, its unusual susceptibility pattern, its erratic response to antibiotics, its ability to induce bacteremia, and the treatment options when it is isolated from the upper respiratory tract are discussed.
Case reports Case I
A 2-year-old female with a history of severe reactive airway disease had a 6 month history of intermittent acute otitis media and otitis media with effusion. Numerous tympanograms demonstrated high acoustic impedance (over 7000 ohms) indicating the presence of middle ear fluid bilaterally. When seen in consultation, the patient had been on antibiotics almost continuously but had taken no antimicrobial therapy for 3 weeks. The tympanic membranes were dull and bulging. A tympanocentesis was performed which demonstrated E. faecalis in pure culture from each middle ear. They were not seen on Gram stain. Each ear canal culture, taken as a background culture, grew only normal skin flora. The patient underwent bilateral myringotomies with insertion of middle ear ventilating tubes. The material removed from the middle ear was mucoid in character. The tubes remained patent until she was lost to follow-up one year later. Case 2 A 3-year-old male with cystic fibrosis was seen in consultation for persistent otitis media with effusion. The exact duration of his chronic otitis media was uncertain although it was noticed by a physician at least 4 months previously. He had not been on any antimicrobial agent for two weeks prior to this examination. His tympanic membranes were gray in color and were bulging slightly. A tympanogram revealed high acoustic impedance bilaterally (over 7000 ohms). A tympanocentesis was done on each middle ear. One middle ear culture showed no growth. The other showed pure culture of E. faecafis with no organisms seen on Gram stain. Ear canal cultures showed normal skin flora. Bilateral myringotomies were per-
125
formed, mucoid material was suctioned from each middle ear, and middle ear ventilating tubes were inserted in each ear. The child was followed for 6 months until his parents moved out of the city.
Discussion The two children described in this report were class III anesthetic risks. The first child had severe bronchospastic disease related to asthma. She required frequent hospitalizations for control of her asthma. The second child had cystic fibrosis, and he was frequently hospitalized for pulmonary toilet. In considering the risk of anesthesia, a question might arise: wouldn’t it be less risky to do nothing? In the anesthesia made maintenance of her airway first paqent the use of halothan relatively easy during the procedure. As with many asthmatic children who undergo surgery, the dangers of induction in emergence were minimized by the use of intravenous. lidocaine. Anesthetic risks in the second child were minimized by increased efforts at pulmonary toilet prior to surgery. Minimal amounts of an inhalational agent were used but were supplemented with both rectal and intravenous barbiturates. It was necessary to intubate the second child in order to assure control of pulmonary secretions. Many children can apparently coexist with otitis media with effusion for long periods of time with no serious complications. E. faecalis is, however, a very different bacteria from others that can be found in such effusions. It appears to be able to invade respiratory mucosa and produce bacteremia [2,14]. In a report from the 1940s. E. faecalis was cultured from the sinuses in a case of E. faecabs bacteremia; the patient died [14]. This ability to induce bacteremia from a mucosal source in the upper respiratory tract is unusual for most microorganisms. Although the mechanism by which E. faecalis can invade mucosa and cause bacteremia is uncertain, microbial adherence is an initial step in this process. It has an unusual adherence mechanism due to a unique surface protein [7], and it adheres more avidly than many other Gram-positive or Gram-negative bacteria [3]. The adherence properties seem to be part of a virulence mechanism in urinary tract infections where bacteremia is a frequent outcome [4]. Thus, it appears that E. faecalis can cause bacteremia when isolated from certain upper respiratory tract sites. It is interesting to speculate as to whether upper respiratory sites could be an occult source of E. faecalis bacteremia since it is not thought to be a pathogen in the upper respiratory tract. A report outlining the cause of E. faecalis bacteremia in 114 patients failed to find the source in almost half of the patients [2]. Since E, faecalis bacteremias are extremely difficult to treat and frequently fatal [2], elimination of a possible source of seeding was done in each of the two patients described here. The reasons for the persistence of most middle ear effusions remain unknown. Although most appear to disappear spontaneously after 12 weeks of observation [ll], some are very persistent. In the two patients described here a variety of antimicrobial agents were used. None of them sterilized the middle ears. Unfor-
126
tunately E. faeculis have a tolerance for cell wall antibiotics [5]. Thus, penicillin and ampicillin are bacteriostatic and not bacteriocidal. Even if satisfactory levels of antibiotics can be achieved in the middle ear, E. fuecalis might persist. If, for any reason, surgery cannot be done, the addition of an aminoglycoside such as gentamicin is often effective [6] despite high level resistance to gentamicin alone [8]. A glycopeptide such as vancomycin in combination with an aminoglycoside is an option for penicillin allergic patients [12]. Vancomycin, although originally uniformally successful, has become less successful because of plasmid mediated resistance [13]. Although ciprofloxacin has in vitro activity against E. faeculis [l], it does not as yet have FDA approval for use in children. Since antibiotics may not sterilize an E. faeculis middle ear, surgical drainage became necessary in these two patients despite anesthetic risks.
References 1 Femandez-Guerrero, M., Rouse, MS., Henry, N.K., Geraci, J.E. and Wilson, W.R., In vitro and in vivo activity of ciprofloxacin against enterococci isolated from patients with infective endocarditis, Antimicrob. Agents Chemother., 31 (1987) 430-433. 2 Garrison, R.N., Fry, D.E., Berberich, S. and Polk, H.C., Enterococcal bacteremia. Clinical implications and determinants of death, Ann. Surg., 196 (1982) 43-47. 3 Gould, K., Ram&z-Ronda, C.H., Holmes, R.K. and Sanford, J.P., Adherence of bacteria to heart valves in vitro, J. Clin. Invest., 56 (1975) 1364-1370. 4 Guzman, C.A., Pruzzo, C., LiPira, G. and Calegari, L., Role of adherence in pathogenesis of Enterococcusfaecalis urinary tract infections and endocarditis, Infect. Immun., 57 (1989) 1834-1838. 5 Hindes, R.G., Willey, S.H., Eliopoulous, G.M., Rice, L.B., Eliopoulous, CT., Murray, B.E. and Mollering, R.C., Treatment of experimental endocarditis caused by a /%lactamase-producing strain of Enterococcus fuecalis with high level resistence to gentamicin, Antimicrob. Agents Chemother., 33 (1989) 1019-1022. 6 Kaye, D., Enterococci. Biologic and epidemiologic characteristics and in vitro susceptibility, Arch. Intern. Med., 142 (1982) 2006-2009. 7 Kurl, D.N., Haataja, S. and Fume, J., Hemagglutination activity of group B, C, D, and G streptococci: demonstration of novel sugarspecific cell-binding activities in Streptococcus sub, Infect. Immun., 57 (1989) 384-389. 8 Mederski-Samoraj, B.D. and Murray, B.E., High-level resistence to gentamicin in clinical isolates of enterococci, J. Infect. Dis., 147 (1983) 751-757. 9 Schaberg, D., Global patterns of resistance to antimicrobial agents in selected pathogens, 28th Interscience Conference on Antimicrobials and Chemotherapy, October 24, 1988, Los Angeles, California. 10 Schleifer, K.H. and Kilpper, R., Transfer of Streptococcw faecah and Streptococw fuecium to the genus Enterococcus nom. rev. as Enterococcus faecalis comb. nov. and Enterococcus faecium comb. nov., Int. J. System. Bacterial., 34 (1984) 31-34. 11 Schwartz, R.H., Rodriguez, W.J. and Gnmdfast, K.M., Duration of middle ear effusion after acute otitis media, Pediatr. Infect. Dis., 3 (1984) 204-207. 12 Shlaes, D.M., Bouvet, A., Devine, C., Shlaes, J.H., Al-obeid, S. and Williamson, R., Inducible, transferrable resistence to vanwmyin in Enterococcus faecalis A256, Antimicrob. Agents Chemother., 33 (1989) 198-203. 13 Uttley, A.H., Collins, C.H., Nasio, J. and George, R.C., Vancomycin resistant enterococci, Lancet 1 (1988) 57-58. 14 Wheeler, SM. and Foley, G.E., A note on non-group A steptococci associated with human infection, J. Bacterial., 46 (1943) 391-392.
