Management of post-tympanostomy tube otorrhea in children.

Dr. Scott Manning: Estimates of the incidence of post-tympanostomy tube otorrhea (PTTO) vary widely, but a range of 16 to 30% seems likely. (1-3) The incidence of recurrent PTTO ([greater than or equal to]3 episodes) is 7 to 15%, and the incidence of persistent PTTO (>3 wk) is 3 to 4%. (2,3) Drainage during the immediate postoperative period is not considered to constitute PTTO. Rosenfeld et al showed in a quality-of-life study that PTTO certainly has a deleterious effect on parents' satisfaction with their child's care. (4)

Etiologic factors in PTTO are viral illness and acute otitis media (AOM). Ruohola et al found that in children younger than 6 years of age, PTTO was almost always preceded by an upper respiratory infection. (5) Two prospective studies suggest that swimming does not appear to be a cause of PTTO, and that earplugs conferred a very small benefit in terms of preventing PTTO in swimmers. (6,7) The results of perioperative antibiotic administration for PTTO prophylaxis have been mixed. Nawasreh and Al-Wedyan in Saudi Arabia found that perioperative ciprofloxacin drops lowered the rate of postoperative otorrhea from 16 to 8%, (8) but other studies have indicated that the benefit of topical antibiotic prophylaxis in general is small. (9) Other uncommon causes are allergy" and perhaps biofilms, (11,12) which we will cover later in this discussion.

Microbiology

Dr. Manning: PTTO may begin as simple AOM with Streptococcus pneumoniae, Haemophilus influenzae, or Moraxella catarrhalis, but as continued drainage changes the environment of the ear canal, it is possible that new pathogens (e.g., Pseudomonas aeruginosa or Staphylococcus aureus) emerge and dominate. (13) As the local immune defense mechanisms are diminished, the bacteria proliferate.

The incidence of methicillin-resistant Saureus (MRSA), including community-acquired MRSA, continues to rise as a response to systemic antibiotic use. (14,15) In a study of PTTO, Coticchia and Dohar compared 17 children with MRSA and 19 children with methicillin-sensitive S aureus and found that the children with MRSA had received more systemic antibiotic treatment before and after tube placement. (15) We do not know if MRSA is associated with topical antibiotic therapy. I would doubt that it is, because topical therapy is generally short-term therapy.

Topical quinolones are effective for treating PTTO. Goldblatt et al showed that topical ofloxacin was more effective than oral amoxicillin/clavulanate when S aureus or P aeruginosa was present (although the two were equal when S pneumoniae, M catarrhalis, or H influenzae was present). (16)

In turn, Roland et al reported that a topical quinolone/ steroid was superior to quinolone monotherapy. (17) They randomized 599 children with AOM through tympanostomy tubes to receive either 4 drops of ciprofloxacin/dexamethasone twice daily for 7 days or 5 drops of ofloxacin twice daily for 10 days. At day 8 (test-of-cure visit), patients in the ciprofloxacin/dexamethasone group had significantly higher rates of both clinical cure (90 vs. 78%) and microbiologic cure (92 vs. 82%). The combination was also significantly superior in terms of clinical cure at follow-up visits on day 3 (p < 0.0001), day 11 (p < 0.0001), and day 18 (p = 0.0023). Patients in the quinolone/steroid group also experienced fewer treatment failures (4.4 vs. 14.1%; p = 0.0017) and less time to cessation of otorrhea (4 vs. 6 days; p = 0.0187). (A similar comparison of ciprofloxacin alone with ciprofloxacin/dexamethasone also favored the combination. (18))

A companion study in the same population of 599 children revealed that ciprofloxacin/dexamethasone was superior to ofloxacin alone in the treatment of granulation tissue, which had been present in 90 patients. (19) Ciprofloxacin/dexamethasone was significantly superior in reducing granulation tissue at the day-11 end-of-therapy visit (81.3 vs. 56.1%; p = 0.0067) and the day- 18 test-of-cure visit (91.7 vs. 73.2%; p = 0.0223).

Perioperative antibiotic prophylaxis

Dr. Manning: I wonder if any of the panelists here normally administer ototopical drops when you put tubes in. If so, which drops do you use? Do you send the parents home with a bottle of drops and tell them that if there is a problem, they should try the drops before calling you?

Dr. Ann Edmunds: If I'm performing a routine ear surgery, I don't usually use a perioperative antibiotic, but if there is heavy pus or thick fluid, then I do use drops. And, yes, I do send the parents home with instructions on how to use the drops if need be. It is so important to give good instructions. If the parent isn't placing them properly, the drops don't go where they're supposed to go and the entire exercise can be futile.

Dr. Billy Giles: I use ciprofloxacin/dexamethasone during surgery if the middle ear contains fluid. I usually give the parents a prescription for ciprofloxacin/dexamethasone to use in case one of the ears begins to drain at some point in the future. I tell the parents to call me if the draining doesn't stop in 3 days, and I see them within a week after that. I often obtain a culture during surgery so I know exactly which organism to treat. If the drainage hasn't stopped by the time they come to the office, then I switch to a systemic antibiotic.

Dr. Ramzi T. Younis: Before I would consider switching to a systemic antibiotic after 10 days of drainage, I would bring the patient in and suction the ear clean.

Biofilms and tube coatings

Dr. Younis: There is much we do not understand about biofilms. A bacterial biofilm is a polysaccharide formation that is believed to be an important mediator of infection at the site of implanted material. Organisms within the polysaccharide are relatively resistant because a glycocalyx slime layer produced by bacterial colonies may be impermeable to antibiotics or it may physically alter an antibiotic and render it biologically inactive. Most resistance involves Staphylococcus and Pseudomonas spp. Perhaps as we learn more about this phenomenon, we will understand its role in PTTO.

The type of material that a tympanostomy tube is made of has been shown in some studies to influence the development of biofilms:

Synthetics. Researchers at the University of Maryland conducted three comparisons of various silicone and plastic tubes:

* In 1998, they reported that ionized, processed silicone tubes were resistant to Pseudomonas adhesion. (20) These tubes, as well as those made of fluoroplastic, were very resistant to Staphylococcus contamination. Untreated silicone and silver-oxide-treated silicone tubes were more susceptible to biofilm formation.

* The following year, they reported their comparison of silicone, silver-oxide-impregnated silicone, fluoroplastic, silver-oxide-impregnated fluoroplastic, and ion-bombarded silicone tubes in guinea pigs whose middle ears were inoculated with S aureus. (21) Again, biofilms developed on all tubes except the ion-bombarded silicone tubes.

* An in vitro study published in 2000, a phosphorylcholine-coated fluoroplastic tube resisted both S aureus and P aeruginosa, while an untreated fluoroplastic tube resisted only S aureus and a silver-oxide-impregnated fluoroplastic tube resisted neither. (22)

Although silver-treated tubes did not do well in these studies, silver coating has been shown to reduce bacterial contamination on heart valve prostheses, (23) urinary catheters, (24) and facial plastic bioimplants. (25)

Albumin. In 2003, Kinnari et al published the results of their in vitro study of the use of tympanostomy tubes coated with human serum albumin. (26) They found that the albumin markedly inhibited the binding of fibronectin, which was used to represent otorrheic fluid. Two years later, Kinnari and Jero published the results of a prospective, randomized clinical trial in 170 humans. (27) Again, albumin coating markedly inhibited the incidence of tube adherence, and the authors suggested that the effect might last as long as 8 months.

Polylactic acid. Just this year, Ludwick et al reported the results of their in vitro investigation to determine if polylactic acid has bacteriostatic properties that might make it a good material with which to manufacture tympanostomy tubes. (28) They concluded that it does.

Dr. John Rutka: Biofilms have their proponents and their skeptics, and I am of the latter. I tell my residents to think long and hard before removing a tube because of biofilm concerns. It seems to me that biofilms are used as an explanation for a problem that someone is unable to solve. If you don't know what to do, blame it on biofilms. No one has ever shown that you cannot eradicate these organisms if you exceed the concentration required to kill the planktonic form. Proponents keep floating this idea that biofilms must be super-resistant. But there are no data to support this. In fact, there are a lot of data to the contrary.

Dr. Giles: I was once involved in a study in which we tried to determine if we could reduce the rate of tracheitis in tracheotomized children by treating the surface of their tubes. But we saw no difference.

Biofilms represent an area of our knowledge of how the body and pathogens interact with each other and with foreign objects such as medical devices. There is so much we do not understand right now, and exciting new developments in infectious diseases and immunology will parallel our increased knowledge of this phenomenon. My understanding is that if an infection persists in an area where there is a foreign body, a physician must consider the risk/benefit ratio of removing or replacing the device or attempting to clear the infection while the device remains in place. If long and multiple attempts to clear such an infection are unsuccessful, the option of removing or replacing the device becomes more and more the likely proper action.

Tube removal

Dr. Younis: In 2005, Adkins and Friedman looked at the surgical indications for tube removal and the subsequent outcomes in 82 children (111 ears). (29) The most common indication by far was prolonged intubation (61.3 % of cases), followed by otorrhea or recurrent infection (21.6%). Two-thirds of patients were also treated with "techniques for encouraging perforation closure," which included freshening the edges of the perforation and applying Gelfoam and/or Gel film. The overall perforation closure rate was 87.0%. Techniques to encourage healing had no effect on outcomes. The authors concluded, "The overwhelming majority of patients who undergo surgical removal of tubes will show complete tympanic membrane healing independent of technique at time of removal, duration of intubation, patient age, or indication for removal."

Three years earlier, Schwartz et al reported their retrospective study of different treatments administered during tube removal in 109 children (162 ears). (30) At follow-up, 93% of the ears had healed. The authors suggested that 25 % trichloroacetic acid might be beneficial in promoting healing; a large randomized clinical trial is needed.

Uncertainty surrounds the timing of tube removal. Several studies have addressed the issue:

* Iwaki et al reviewed the medical records of 137 children (220 ears) who had otitis media with effusion (OME). (31) They concluded that patients younger than 6 years of age might be better off if their tubes are left in place until they reach the age of 8 years.

* Nichols et al studied the effects of prolonged tube retention on tympanic membrane healing in 67 children (99 ears). (32) They found that the failure-to-heal rate was significantly higher in children whose tubes had been in place for 3 years or longer.

* Similarly, Lentsch et al obtained data on 201 children (273 ears) and found that persistent perforations were more common in those whose tubes had been in place for more than 3 years (15 vs. 3%). (33)

* Finally, El-Bitar et al studied 126 children whose tubes had been in place for at least 2 years. (34) They reported that complications of tube retention were high overall and more common in patients older than 7 years than in younger patients.

Dr. Rick A. Friedman: Parents sometimes ask me to remove a tube that's been in place for 3 years. But if the tube is dry and the child is not having any problem, why subject the child to general anesthesia in order to remove it? I prefer to leave the tube and let it extrude naturally.

Dr. Younis: We know that complication rates are higher when tubes are removed surgically.

Dr. Harvey Coates: In Australia, children love to swim, and parents grow tired of putting in ear protection and taking other precautions after a tube has been in place for 3 or 4 years. So if the child is past the disease process, we put them under general anesthesia and remove the tube surgically. We lightly circumcise the edge of the perforation, and we place an inlay tragal cartilage graft. This takes only 15 minutes, and the success rate is high. The child can resume swimming in 6 weeks.

Perforation repair

Dr. Younis: Gelfoam, Gelfilm, paper, and tape have all been used to patch perforations following tube removal, and I don't know if there is any consensus as to whether one is better than another. (32,35,36) Personally, I prefer to use fat.

Dr. Joseph E. Dohar: In the animal models we have studied, there's little question that a scaffold of some sort is beneficial. If you don't put in a scaffold to support epithelialization, the only way the tympanic membrane can heal is by cicatricial contraction via the intermediate matrix that contains the myofibroblast. That is a very long and slow process. I have not done any comparative studies, but from a basic science standpoint, it makes sense that a scaffold would be valuable. The only scaffold that might have an advantage over any of the others is hyaluronic acid. Hyaluronic acid has a more fluid matrix, and fibroblast migration across it is substantially better than it is for cigarette paper and Gelfoam. The drawback is that hyaluronic acid is so expensive.

Classifying otorrhea

Dr. Younis: Finally, I firmly believe that we need a classification system for otorrhea. We have classifications for everything else, why not otorrhea? I prefer a system that is similar to the system used for sinusitis. The three types are acute, intermittent, and chronic. Each of these has three subcategories: untreated, previously treated, and refractory to treatment. What we need is to establish a consensus to define the parameters of each of the nine types.

References

(1.) Daniel SJ, Kozak FK, Fabian MC, et al. Guidelines for the treatment of tympanostomy tube otorrhea. J Otolaryngol 2005;34:S60-S63.

(2.) Rosenfeld RM. Surgical prevention of otitis media. Vaccine 2000; 19(suppl 1):S134-S139.

(3.) Gates GA, Avery C, Prihoda TJ, Holt GR. Delayed onset post-tympanotomy otorrhea. Otolaryngol Head Neck Surg 1988;98: 111-15.

(4.) Rosenfeld RM, Bhaya MH, Bower CM, et al. Impact of tympanostomy tubes on child quality of life. Arch Otolaryngol Head Neck Surg 2000; 126:585-92.

(5.) Ruohola A, Heikkinen T, Meurman O, et al. Antibiotic treatment of acute otorrhea through tympanostomy tube: Randomized doubleblind placebo-controlled study with daily follow-up. Pediatrics 2003;111:1061-7.

(6.) Goldstein NA, Mandel EM, Kurs-Laskey M, et al. Water precautions and tympanostomy tubes: A randomized controlled trial. Laryngoscope 2005; 115:324-30.

(7.) Salata JA, Derkay CS. Water precautions in children with tympanostomy tubes. Arch Otolaryngol Head Neck Surg 1996;122: 276-80.

(8.) Nawasreb O, Al-Wedyan IA. Prophylactic ciprofloxacin drops after tympanostomy tube insertion. Saudi Med J 2004;25:38-40.

(9.) Garcia P, Gates GA, Schectman KB. Does topical antibiotic prophylaxis reduce post-tympanostomy tube otorrhea? Ann Otol Rhinol Laryngol 1994; 103:54-8.

(10.) Dohar JE. All that drains is not infectious otorrhea. Int J Pediatr Otorhinolaryngol 2003;67:417-20.

(11.) Bothwell MR, Smith AL, Phillips T. Recalcitrant otorrhea due to Pseudomonas biofilm. Otolaryngol Head Neck Surg 2003;129: 599-601.

(12.) Ehrlich GD, Veeh R, Wand X, et al. Mucosal biofilm formation on middle-ear mucosa in the chinchilla model of otitis media. JAMA 2002;287:1710-15.

(13.) Dohar J. Microbiology of otorrhea in children with tympanostomy tubes: Implications for therapy. Int J Pediatr Otorhinolaryngol 2003; 67:1317-23.

(14.) Hwang JH, Chu CK, Liu TC. Changes in bacteriology of discharging ears. J Laryngol Otol 2002; 116:686-9.

(15.) Coticchia JM, Dohar JE. Methicillin-resistant Staphylococcus aureus otorrhea after tympanostomy tube placement. Arch Otolaryngol Head Neck Surg 2005;131:868-73.

(16.) Goldblatt EL, Dobar J, Nozza RJ, et al. Topical ofloxacin versus systemic amoxicillin/clavulanate in purulent otorrhea in children with tympanostomy tubes. Int J Pediatr Otorhinolaryngol 1998;46:91-10l.

(17.) Roland PS, Kreisler LS, Reese B, et al. Topical ciprofloxacin/dexamethasone otic suspension is superior to ofloxacin otic suspension in the treatment of children with acute otitis media with otorrhea through tympanostomy tubes. Pediatrics 2004; 113:e40-6.

(18.) Roland PS, Anon JB, Moe RD, et al. Topical ciprofloxacin/dexamethasone is superior to ciprofloxacin alone in pediatric patients with acute otitis media and otorrhea through tympanostomy tubes. Laryngoscope 2003; 113:2116-22.

(19.) Roland PS, Dohar JE, Lanier BJ, et al. Topical ciproftoxacin/dexamethasone otic suspension is superior to ofloxacin otic suspension in the treatment of granulation tissue in children with acute otitis media with otorrhea through tympanostomy tubes. Otolaryngol Head Neck Surg 2004; 130:736-41.

(20.) Biedlingmaier JE Samaranayake R, Whelan E Resistance to biofilm formation on otologic implant materials. Otolaryngol Head Neck Surg 1998; 118:444-51.

(21.) Saidi IS, Biedlingmaier JF, Whelan P. In vivo resistance to bacterial biofilm formation on tympanostomy tubes as a function of tube material. Otolaryngol Head Neck Surg 1999; 120:621-7.

(22.) Berry JA, Biedlingmaier JF, Whelan PJ. In vitro resistance to bacterial biofilm formation on coated fluoroplastic tympanostomy tubes. Otolaryngol Head Neck Surg 2000; 123:246-51.

(23.) Kjaergard HK, Tingleff J, Abildgaard U, Pettersson G. Recurrent endocarditis in silver-coated heart valve prosthesis. J Heart Valve Dis 1999;8:140-2.

(24.) Rosch W, Lugauer S. Catheter-associated infections in urology: Possible use of silver-impregnated catheters and the Erlanger silver catheter. Infection 1999;27(suppl 1):S74-7.

(25.) Malaisrie SC, Malekzadeh S, Biedlingmaier JE In vivo analysis of bacterial biofilm formation on facial plastic bioimplants. Laryngoscope 1998;108:1733-8.

(26.) Kinnari TJ, Salonen EM, Jero J. Durability of the binding inhibition of albumin coating on tympanostomy tubes. Int J Pediatr Otorbinolaryngol 2003;67:157-64.

(27.) Kinnari TJ, Jero J. Experimental and clinical experience of albumin coating of tympanostomy tubes. Otolaryngol Head Neck Surg 2005;133:596-600.

(28.) Ludwick JJ, Rossmann SN, Johnson MM, Edmonds JL. The bacteriostatic properties of ear tubes made of absorbable polylactic acid. Int J Pediatr Otorbinolaryngol 2006;70:407-10.

(29.) Adkins AP, Friedman EM. Surgical indications and outcomes of tympanostomy tube removal. Int J Pediatr Otorhinolaryngol 2005; 69:1047-51.

(30.) Schwartz KM, Orvidas LJ, Weaver AL, Thieling SE. Ventilation tube removal: Does treatment affect perforation closure? Otolaryngol Head Neck Surg 2002; 126:663-8.

(31.) Iwaki E, Saito T, Tsuda G, et al. Timing for removal of tympanic ventilation tube in children. Auris Nasus Larynx 1998;25:361-8.

(32.) Nichols PT, Ramadan HH, Wax MK, Santrock RD. Relationship between tympanic membrane perforations and retained ventilation tubes. Arch Otolaryngol Head Neck Surg 1998; 124:417-19.

(33.) Lentsch EJ, Goudy S, Ganzel TM, et al. Rate of persistent perforation after elective tympanostomy tube removal in pediatric patients. Int J Pediatr Otorhinolaryngol 2000;54:143-8.

(34.) El-Bitar MA, Pena MT, Choi SS, Zalzal GH. Retained ventilation tubes: Should they be removed at 2 years? Arch Otolaryngol Head Neck Surg 2002; 128:1357-60.

(35.) Hekkenberg RJ, Smitheringale AJ. Gelfoam/Gelfilm patching following the removal of ventilation tubes. J Otolaryngol 1995;24: 362-3.

(36.) Saito T, Iwaki E, Kohno Y, et al. Prevention of persistent ear drum perforation after long-term ventilation tube treatment for otitis media with effusion in children. Int J Pediatr Otorhinolaryngol 1996;38:31-9.

Panel discussion based on presentations by Scott Manning, MD, and Ramzi T. Younis, MD, FICS