Philip A. Brunell, MD: I am joined by a distinguished group of ophthalmologists and otolaryngologists to discuss the optimal therapy of both external ear and eye infections in pediatric patients. How can the various causes of red eye be distinguished?
David B. Granet, MD: Physicians can effectively treat patients with red eye by using the normal subjective, objective, assessment and plan (SOAP) approach.
The greatest concern of most pediatricians who are not ophthalmologists is not to impair vision. There are certain steps that are useful for diagnosing red eye, such as checking the patient’s vision, looking at the pupil, taking a good patient history, getting a family history, examining the mechanism of injury and checking the red reflex. These steps also prevent missing severe problems.
It must be determined whether the red eye is unilateral or bilateral. Allergies tend to occur bilaterally, whereas infections tend to occur unilaterally.
Richard Eiferman, MD: Laboratory results can also be helpful. If discharge is present, a culture can be done to determine the microorganism involved. If a significant amount of polymorphonuclear leukocytes (PMNs) and bacteria are present on the smear, the odds are fairly high that the patient has bacterial conjunctivitis. On the other hand, a mononuclear condition that presents with a watery discharge suggests a viral infection. If a significant amount of eosinophils is seen, then the cause of irritation is an allergen.
Harold Katz, MD: It is important to look at the patient’s history. For example, if the child has a history of allergic rhinitis and the child’s eyes always become red at certain times of the year, the child may have an allergic conjunctivitis.
Exposure to other children who have red eyes may indicate viral conjunctivitis. Signs and symptoms of viral conjunctivitis include a pre-auricular lymph node and a watery discharge.
On the other hand, a mucopurulent or a purulent discharge should be considered to be symptoms of bacterial conjunctivitis. The patient’s eye should be cultured and intensive topical antibiotic therapy should be started.
Granet: As supported by a multitude of studies in the literature, it is important to remember that conjunctivitis is mostly viral in adults, but bacterial in children.
Brunell: Do you culture every case of purulent conjunctivitis?
Katz: I differentiate between a mild mucopurulent and a moderate to severe purulent conjunctivitis. If the discharge is mild, performing a culture may not be necessary. On the other hand, if the conjunctivitis is severe, a culture should be performed. All cases of ophthalmia neonatorum should also be cultured.
Brunell: Is culturing beyond the neonatal period going to change your therapy?
Katz: Yes. For example, if a culture is performed and the patient’s condition is worsening, it is possible that the organism is resistant to the antibiotic being used. But culturing is not as important as it was in the past, because potent broad-spectrum antibiotics are available. Physicians can be confident that antibiotics such as the ophthalmic fluoroquinolones cover the vast majority of potential pathogens.
Brunell: Do ophthalmologists subscribe to the dictum that if a patient presents with pharyngitis, conjunctivitis, and a pre-auricular node, the condition is adenoviral? If otitis media accompanies conjunctivitis, is the infection Haemophilus?
Eiferman: Yes, generally speaking.
Katz: Occasionally, viral conjunctivitis can be severe, resulting in formation of membranes and pseudomembranes that consist of fibrin adherent to the conjunctival surface. In these cases, permanent scarring of the conjunctiva may result. Therefore, in some cases, treatment of viral conjunctivitis with a combination antibiotic/steroid type drop, such as a Tobradex (tobramycin dexamethasone, Alcon) may be necessary. In cases where we are removing fibrin membranes, a topical antibiotic/steroid combination can be used to decrease the inflammatory response and the formation of membranes and pseudomembranes. This regimen can also prevent any bacterial super-infection.
Granet: Can steroids be hazardous when used in the eye?
Katz: No. Upon examination of the eye, if a whitish membrane on the conjunctiva’s surface is observed, the patient should be immediately referred to an ophthalmologist for further care.
Eiferman: I do not see a place for corticosteroids in treating eye infections outside the hands of ophthalmologists.
Brunell: How can corneal ulcers be recognized?
Katz: On pen-light examination of the eye, a white spot may be seen in the cornea, or the cornea may appear cloudy instead of crystal clear.
Eiferman: Using the 40 D setting on an ophthalmoscope allows the cornea to be examined in greater detail. Corneal ulcers are potentially blinding and such cases must be referred to an ophthalmologist.
Granet: The cornea should always be clear. The final common pathway of corneal pathology is opacity. Patients who have a new white spot, opacity, on the cornea must be referred to an ophthalmologist for further evaluation.
Brunell: What are the bacterial organisms of concern in a child’s eye?
Eiferman: The organisms of concern are Staphylococcus, Streptococccus pneumoniae and Haemophilus influenzae.
Katz: I would probably reverse the order in children. In adults, Staphylococcus aureus is the most common organism cultured from cases of bacterial conjunctivitis. In children, H. influenzae is a more commonly isolated organism.
Brunell: In older literature, Staphylococcus is common, but in some of the more recent pediatric studies, many of the Staphylococcus isolates were skin contaminants acquired from specimen collection. Staphylococcus may be less of a factor than previously thought.
Katz: Typically, the normal flora of the lids and conjunctiva is Staphylococcus epidermidis.
Brunell: A smear may be useful because it will show the predominant organism, rather than the contaminant that grows on the plate. However, a child presenting for the first time will probably not be cultured. The child will be treated empirically.
Please discuss Pseudomonas because this organism is unfamiliar to pediatricians.
Katz: Pseudomonas is not a common cause for conjunctivitis in children or adults, but it is a relatively common organism isolated from corneal ulcers. Sometimes a child may have what appears to be conjunctivitis, but the condition may actually be a corneal ulcer. Corneal ulcers can be difficult to treat, because they can be caused by pathogenic organisms such as Pseudomonas aeruginosa, S. aureus, S. pneumoniae or, they may even be polymicrobial.
Brunell: Are you satisfied with topical fluoroquinolones in terms of treating the organisms that cause conjunctivitis?
Katz: Topical fluoroquinolones provide
excellent coverage of organisms of concern, such as Staphylococcus,
S. pneumoniae, and Pseudomonas. Ciprofloxacin in particular
offers broad-spectrum coverage that is effective against gram-positive
organisms. It is also effective against P. aeruginosa.
Topical fluoroquinolones have other properties that make them useful in treating ocular infections in adults and children. My colleagues and I performed a study in which we compared two of the most commonly used topical fluoroquinolones, ciprofloxacin and ofloxacin, with regard to how quickly they could eradicate organisms from the ocular surface. The study was performed using normal human subjects. With ciprofloxacin, the results showed a 97% reduction of the conjunctival flora at 15 minutes, 98% reduction at 30 minutes, 98% reduction at one hour, and a 98% reduction at two hours. With ofloxacin, the reduction of organisms was less at each point compared with ciprofloxacin. In addition, the greater effectiveness of ciprofloxacin was statistically significant at each point compared to ofloxacin. Therefore, ciprofloxacin has the advantage of providing broad-spectrum coverage, tremendous potency against the pathogens of concern and rapid killing of organisms. All of these properties make it an effective agent for treating ocular infections in children.
Eiferman: In our laboratory, we have performed kill curves in vitro. We found that the difference between ciprofloxacin and other fluoroquinolones is dramatic. Four log unit reductions were seen in organisms within five to 10 minutes. This is critical when sterilizing the ocular surface of a child. While the available fluoroquinolones are not perfect, they have a broader spectrum of activity than the other available antibiotics (Figure 1).1
Granet: The impact of how quickly ciprofloxacin kills an organism is important when treating children, because children <3 years old have a greater risk of developing serious complications from infections. For example, the eyelid can become involved in a preseptal cellulitis, which is problematic. Because ciprofloxacin has dramatic kill curves and covers the vast majority of organisms, it can be considered a first-line drug that may prevent this complication.
Katz: It is important to begin treating with an
antibiotic that has the greatest chance of eliminating the pathogenic organisms
and effectively treating the infection, especially in cases that have not been
cultured (Figure 2).
Certain organisms can penetrate through an intact corneal epithelium and cause infection in the cornea. However, as long as the corneal epithelium is intact, even though there may be a severe conjunctivitis, the pathogenic organisms will not penetrate through the corneal epithelium into the cornea.2
Brunell: What special considerations are involved in treating children?
Eiferman: I prefer using antibiotic ointment than drops for young children. It is difficult to give drops to a small child who cries them out. But if an ointment is administered in the child’s eye, even if all of it does not get in, it is formulated to melt at body temperature.
I do not use sulfa because sulfa is only active in an acidic pH and causes burning when it is administered. Also, a certain percentage of the population is allergic to sulfa. Much better drugs are available.
Brunell: Does everyone agree that ointments are better than drops?
Granet: I believe that the age of the child should be considered when deciding to administer ointments or drops. However, ointments work well on children <5 years old.
I tell parents to administer the ointment when the child is asleep. With drops, I suggest children lie flat and close their eyes. Then, I make a small puddle in the medial canthus between the eye and the nose. I instruct the children to open their eyes and the drop rolls in.
It is important to administer a medication that will work rapidly while it is in the eye, in case the contact time is diminished. Administering a medicine that stings or is difficult to instill will not be effective.
Eiferman: I agree. I conducted studies in which we instilled radioactive labeled tears and they are out of the eye in exactly 10 minutes.3
Katz: However, studies have shown that one drop of ciprofloxacin can maintain a therapeutic tear level for as long as 12 hours.4
Eiferman: That is true. High tear film levels are achieved due to the unique binding properties of fluoroquinolones in eye cells.
Ciprofloxacin is supplied at 3 mg percent which is a significant dose and above the minimal inhibitory concentration (MICs) in most organisms.
Granet: Using a fluoroquinolone as a first-line treatment raises the issue of resistance. My understanding is that 106 organisms can be found in a bacterial conjunctivitis versus 1012 in a systemic. But, greater concentrations of the antibiotic are being put in the eye so organisms are killed quickly. Therefore, resistance is less likely to be a concern.
Eiferman: I agree. There has been little emergence of resistance to fluoroquinolones in ophthalmic literature.
In our original Ciloxan (ciprofloxacin, Alcon) studies, a significant amount of organisms were resistant in vitro. I always tell residents, “Treat the patient, do not treat the lab report.” If the patient’s cornea is improving despite the fact that there is microbial resistance, which is based on serum and not on tear film levels, the therapy must not be changed.1
Brunell: It is important to remember that the breakpoints in defining bacterial resistance are based on what can be achieved with systemic therapy. A significant amount of ciprofloxacin can be delivered into the conjunctivae even though organisms would be resistant in vitro.
Katz: Resistance occurs at a lower frequency with fluoroquinolones because a chromosomal mutation is required rather than the transmission of plasmids. The greater the ratio between the concentration of antibiotic and the MIC, the less likely there is a chance that resistance will develop.
There are basic principles to follow to avoid the development of resistance: using antibiotics only for suspected bacterial infections and only using the antibiotic for the shortest period of time that is absolutely necessary. A true infection should be treated for five to seven days and then the antibiotic should be stopped.
Granet: I agree. Realistically, when a parent of a 4-year-old child is required to administer one drop in the child’s eye four times a day, from a compliance standpoint, the child will probably not receive the antibiotic four times a day. With fluoroquinolones, it is reassuring to know that even if the parent administers the drop two or three times a day, the antibiotic is potent enough to be effective.
Brunell: With some of the older antibiotics used, there seems to be a disparity between when a bacterial cure is present and when a clinical recovery is present. When does recovery begin and is that the point when parents should stop using the drug?
Katz: When treating with an effective antibiotic, a rapid reduction in the number of organisms will be observed if the patient is recultured several days later. The signs and symptoms will also begin to diminish. Usually, the signs and symptoms after three to five days of bacterial conjunctivitis resolve on appropriate therapy. In fact, studies have shown that ciprofloxacin can cure bacterial conjunctivitis in as few as three days.5
Brunell: When can children with conjunctivitis return to school or day care?
Granet: A child with viral conjunctivitis is probably not shedding the virus after two to three days. However, schools prefer the children to be receiving some type of medication before returning.
Katz: However, an adenoviral conjunctivitis, such as epidemic keratoconjunctivitis (EKC), can be more serious. Not only is EKC highly contagious, but it can also have sequelae, such as corneal subepithelial infiltrates that can take one to two years to resolve. Studies have shown that live viruses can be shed for two weeks or more in children with EKC. Children with viral conjunctivitis often must be kept out of school longer than those with bacterial conjunctivitis.
Granet: The warning sign of EKC is a chronic red eye that appears to be getting worse instead of better despite treatment. In these cases, the child must be referred to an ophthalmologist.
Brunell: What precautions should families be advised to take to prevent spread of an infection?
Katz: Unfortunately, conjunctivitis often spreads throughout a family. Therefore, pillows, sheets and towels must not be shared with other family members. When an entire family presents with red eyes, they probably have viral conjunctivitis.
Viral conjunctivitis can be spread easily in the physician’s office, as well. If a child comes in with a red eye, it is important that the child be placed immediately into an examination room so that the child does not spread the condition to other children in the waiting area.
Granet: We have discussed using fluoroquinolones as a first-line drug treatment option, but there is concern with fluoroquinolone use in small children. Should fluoroquinolones be used in younger children?
Katz: Ciloxan has been approved for use in children >1 year old by the Food and Drug Administration (FDA). There is no concern regarding fluoroquinolones having any systemic side effects because the systemic absorption is minimal with ocular dosing.
Brunell: This is an important point because the FDA is strict about the use of fluoroquinolones systemically.
Eiferman: The only reason for the FDA to restrict topical fluoroquinolone eye preparations in children <1 year old is that these children were not tested.
Katz: Fluoroquinolones are ideal for children because of their broad spectrum of activity against all of the organisms of concern, such as H. Influenzae, Streptococcus and Staphylococcus. Ciprofloxacin, in particular, is highly potent against organisms of bacterial conjunctivitis.
Eiferman: Not only is a topical fluoroquinolone an effective antibiotic, but it is also prepared in a good vehicle. The drug is comfortable in the eye and it does not sting or burn. I recently had an eye infection, which felt as though I had sandpaper in my eye. I used ciprofloxacin for one to two hours and saw a dramatic improvement within one day.
Brunell: Please expand on fluoroquinolones’ mechanism of action.
Eiferman: Fluoroquinolones work by inhibiting the DNA gyrase. By knocking out the DNA gyrase, an almost immediate effective kill is achieved in the eye rather than trying to break up the patient’s cell wall metabolism or interfering with ribosomal protein synthesis. If the DNA level can be reached, fluoroquinolones work rapidly and are unlikely to develop resistance. There also appears to be some type of inherent binding property to the conjunctiva and to the cornea, which gives high tear levels. On the other hand, bacteriosterostatic antibiotics, trimethoprine sulfate and polymycin B, will only inhibit growth of bacteria and, therefore, require longer treatment.
Brunell: Have you experienced any adverse reactions when treating the eye with fluoroquinolones?
Katz: Almost never. Ciprofloxacin is a non-toxic topical antibiotic with a low incidence of allergic reactions. Ciprofloxacin is unlike antibiotic preparations containing neomycin which may cause allergic reactions. If an antibiotic containing neomycin or gentamicin is used and the eye does not improve, it may not be clear whether an allergic reaction is occurring or whether the infection is not responding to therapy. With ciprofloxacin, allergic reactions are unlikely.
Brunell: Please explain the inhibitory quotient (IQ).
Katz: The IQ is the ratio of the antibiotic concentration in the target tissue to the MIC-90 of a particular organism. Generally, an IQ >4 is preferred, because otherwise the antibiotic may inhibit the growth of the organism, but not kill it.
Ciprofloxacin has favorable IQ values, because it achieves a high tear film level, and it effectively penetrates into the cornea.
Brunell: What ratios do you achieve in the tear film?
Eiferman: The levels achieved in both the tear film and the cornea are high. We must always be looking at minimal bacteriocidal concentrations (MBC)-99s, not MIC-50s.
Brunell: Let’s begin our discussion on ear infections by defining the common types of ear conditions.
David E. Karas, MD: I believe it is helpful to categorize otitis media (OM) into groups. Otitis media with effusion (OME) is a condition in which fluid is present behind the ear, but the ear appears to be uninfected. Another group of ear infections is acute otitis media (AOM) where fluid is present and the ear is infected. Otitis externa is an infection of the external canal causing pain on manipulation of the ear and edema of the canal. AOM with a tympanotomy tube in place causes purulent drainage from the tympanotomy tube.
Brunell: The most common problem pediatricians face is determining whether the condition is OM that is draining or otitis externa.
Gerald D. Capoot, MD: Most cases of otitis externa do not have as aggressive a drainage as with a tube or a perforated eardrum from AOM.
David S. Haynes, MD: If a tube is in place, the presence of otorrhea indicates that the condition stems from a middle ear source until proven otherwise and probably is not otitis externa. However, diagnosis is difficult if no tube is in place, but purulent otorrhea is present. I have seen patients treated for otitis externa who have had an underlying cholesteatoma.
Karas: The following tips can help in diagnosing a patient, even if there is no history of tympanotomy tube placement. If the patient had severe pain and immediately felt better, which is the time when the parents noted the drainage, this may indicate an AOM that has subsequently ruptured the drum and now there is drainage through the canal.
In patients who present with either otitis externa or AOM, it is easy to think of them in two categories even if the diagnosis is unclear. One category is if the eardrum cannot be seen. The second category is if the canal is significantly smaller. A wick must be placed in those patients to help deliver the antibiotic. If the canal is not edematous, then these patients can be treated with just drops and/or cleaning to the extent possible. The condition may not be able to be evaluated until it settles and the child can return for further evaluation of the eardrum.
Haynes: Patient history is critical, especially if otorrhea is present and the child has had an operation, such as a tympanic membrane (TM) reconstruction, tympanoplasty or tympanomastoidectomy. The condition is not otitis externa until proven otherwise. If the patient has had a history of multiple AOMs or previous surgery, the diagnosis is a TM or middle ear infection until proven otherwise. A patient with no history of an operation, tubes or infections, just sudden pain and inflammation, is most likely to have an otitis externa or swimmer’s ear infection.
Karas: It is important to use a steroid in otitis externa patients, especially the patients who have swollen canals, because the steroid is going to help them heal faster. A steroid decreases the edema so there is less resistance for the drops getting into the ear.
I administer Cipro HC otic (ciprofloxacin hydrochloride/hydrocortisone otic suspension, Alcon), as well as a steroid, because it has a broad spectrum for covering the resistant organisms that are likely to present in otitis externa.
I do not administer Cortisporin (neomycin and polymycin B, Monarch Pharmaceuticals) because of neomycin allergy. Neomycin allergy may present as persistent otitis externa, but the patient does not seem to get better with the drops. Treatment with a steroid makes a significant difference for decreasing pain.
Brunell: In a child who has a tympanotomy tube and develops OM, how does one distinguish whether discharge is due to AOM or otitis externa?
Capoot: That is a good point that brings up bacteriology of these various infections. In AOM with an intact eardrum, the bacteria comes from the nasopharynx via the eustachian tube. The most common bacteria are S. pneumoniae. The second most common bacteria are H. influenzae, and the third most common are Moraxella catarrhalis. These three bacteria account for approximately 75% to 80% of the bacteria seen in OM in an intact eardrum.
Otitis externa is predominantly P. aeruginosa, with the second most prevalent bacteria being S. aureus.
Karas: Bacteria found in drainage can differ according to age. In older patients, external organisms such as Pseudomonas and Staphylococcus will likely be present. In younger patients, organisms from the middle ear contamination is more likely to come from the nasopharynx, as well as H. influenzae or S. pneumoniae.
Brunell: Does the time after the placement of tubes influence your treatment?
Karas: Not particularly. I find that I treat patients aggressively with drops. But it is important to clean the ear of any debris, because often, there is a significant amount of debris or pus in the canal that the drops cannot physically penetrate. I suction children’s ears if they are draining to clear debris.
If pus is abundant, I tell parents to mop up pus and debris with a cotton swab before putting in drops.
I also flush patients’ ears with half-strength vinegar. Flushing debrides much of the pus out of the ear before inserting the antibiotic drop 30 minutes later.
Brunell: Is vinegar washing tolerated in otitis externa cases?
Karas: Vinegar washing is less painful in otitis externa because the eardrum is intact. However, any type of manipulation of the pinna or the canal is painful.
Brunell: Does the type of tubes placed in a child’s ear affect the amount of otorrhea?
Karas: I prefer the Boston Medivent tube (Smith and Nephew Richards Inc., Memphis, Tenn.) because it ventilates well and it allows easy examination of the ear from a variety of angles.
Haynes: Some physicians have suggested using a colored tube, because it is easier to see when it is starting to come out of the TM.
Capoot: I always use collar button tubes the first time I put tubes in a child’s ear. If I put them in the anterior quadrant, the average time that the tubes will stay in place is one year.
But 15% to 20% of children will require repeat tubes. If a child requires repeat tubes, I start thinking of tubes that stay in for longer periods. I use a T tube type placement, which has a larger flange that makes it more difficult to push out, and is more likely to stay in for five to 10 years.
In children who require repeat tympanotomy and tube insertion, I will do an adenoidectomy to improve eustacian tube function.
Brunell: Do tubes differ in terms of hearing?
Haynes: Hearing is much better with a tube than hearing of an ear with effusion. The effusion causes approximately 30 dB of conductive loss, which can drop patients from normal hearing to just below speech thresholds. One of the main reasons for inserting tubes is to eliminate the 30 dB conductive loss.
When the tubes come out at eight to 14 months, parents often ask, “Why couldn’t tubes be put in that lasted longer?” I tell parents that the tube must come out at this time because a long-standing tube could cause a draining ear or a perforation of the eardrum.
Capoot: My concern with using long lasting tubes, such as T tubes, is that when they extrude spontaneously, there is a 30% likelihood of perforation. Perforation can result in another surgical procedure to close the perforation, either with a patch or a formal tympanoplasty.
Brunell: What is your therapeutic regimen following tympanotomy?
Capoot: I use ciprofloxacin drops. I will use drops in the operating room and then I will give the patient a prescription for Cipro HC otic drops to use three drops, twice a day for two days.
Brunell: What precautions must patients with tubes take when swimming?
Karas: I allow children with tubes to swim. I tell them to avoid getting water in their ears, but I find that for the most part, it does not make a bit of difference. I do not like lake water because lake water tends to have higher bacterial counts. Studies show a likelihood of tube otorrhea with lake swimming, but it also depends on the type of tubes. The T tubes are more difficult for water to penetrate.6
Capoot: I tell parents that a child with tubes can get an infection in the ear from contaminated water entering the ear from bathing or swimming. This can allow the germs to get through the tube causing an infection.
Karas: Children who have problems with tube otorrhea or drainage must be diligent about not getting water in their ears because that will aggravate the problem. Also, children with chronic otorrhea must wear plugs. I suggest a disposable plug, such as a cotton ball with petroleum jelly. I also recommend sterilizing nondisposable plugs after each use.
Brunell: What resistant organisms do you try to cover?
Karas: The most likely organisms are the external pathogens — Pseudomonas and Staphylococcus. Ciprofloxacin otic works well in the ear and is significantly above MICs for Staphylococcus or Pseudomonas.7
Haynes: None of the eardrops prior to Floxin otic (ofloxin otic, Daiichi Pharmaceutic Corp.) were sterile. We used neomycin and polymycin B drops in surgery, in a sterile field, without knowing that they were not sterile.
Capoot: Regardless of the cause of the ear drainage, the primary bacteria, Pseudomonas, Staphylococcus, S. pneumoniae, H. influenzae and M. catarrhalis, are easily controlled and killed by ciprofloxacin and ofloxacin.
When comparing Floxin otic and Cipro HC otic, Cipro HC otic is favorable in terms of compliance, because of the shorter duration of use, as well as the shorter duration with which the affected ear must be held upright to get proper diffusion of the drops. According to the package inserts, the ear must be upright for only 30 to 60 seconds for Cipro HC otic and five minutes for Floxin otic.
Also, strong data show that ciprofloxacin is eight to 16 times stronger in its ability to kill Pseudomonas with respect to its MIC levels. Other important information is obtained from kill curves which are graphs that show how quickly an antibiotic reaches a MBC against a given bacteria. A kill curve shows that the MBC for ciprofloxacin against P. aeruginosa is reached at 10 minutes, whereas the MBC is never reached with Floxin.
In terms of S. aureus, the second most common bacteria, the MBC levels are reached in 15 minutes with ciprofloxacin, but with ofloxacin, MBC levels are not reached for 95 minutes.
Similarly, with S. pneumoniae, the third most common bacteria found in the draining ear, the MBC is reached with ciprofloxacin within 10 minutes, but the MBC is not reached with ofloxacin for 45 minutes. (Data on file, Alcon laboratories, Inc.)
The kill curves show why ciprofloxacin drops are superior against pathogens of the draining ear.
Brunell: It is important to point out that ciprofloxacin is not the drug of choice to use for systemic Staphylococcal infections because adequate concentrations may not be achieved. However, a significant amount of the antibiotic is being delivered locally so that a high cure rate can be achieved with fluoroquinolone-containing eardrops.
Haynes: With the advent of the new generation fluoroquinolones, I have asked colleagues what is the most effective fluoroquinolone for primarily treating Pseudomonas. I am told that it remains ciprofloxacin, which is the antimicrobial in Cipro HC otic.
Brunell: When laboratory reports on resistance are received, the reports are relative to giving drugs systemically and the blood level that can be achieved. The levels being achieved in the ear by delivering the antibiotic directly are far in excess of what is required to eliminate the organism.
Patient compliance with treatments is a concern. If children are feeling better they may be less likely to continue therapy as long as needed to have a healthy external ear canal.
Capoot: Compliance is an important issue. The package insert on the antibiotic drops gives important information as far as probable compliance. For example, the instructions for ofloxacin otic solution indicate the insertion of five drops for children and 10 for adults, twice a day for 10 to 14 days, depending on the type and cause of the drainage. The package insert also instructs that the infected ear be held upright for five minutes. However, it is difficult to achieve that compliance in an 18-month-old infant.
Cipro HC otic has several advantages over other fluoroquinolones. The indication for Cipro HC is three drops in the infected ear twice a day for seven days. The package insert states that only seven days are appropriate for most treatments, which is a much shorter time than Floxin otic or Cortisporin otic. The other advantage Cipro HC otic offers is that the infected ear must be held upright for only 30 to 60 seconds for adequate dispersion of the antibiotic drop according to the package insert.
Brunell: One of the problems with otitis externa, especially in the younger children, is the pain it causes. I believe better distribution of drops is achieved by pulling on the external ear. However, if the external ear of a child with otitis externa is pulled, he or she is not going to allow you near the ear again for another dose.
Capoot: For that reason, it is more important to use an antibiotic drop, such as Cipro HC otic, that has excellent dispersion.
Brunell: Are there any conditions that pediatricians may misdiagnose?
Haynes: The major misdiagnosis I see is a patient with cholesteatoma, who is treated for otitis externa for a long time. These patients have a retracted TM, which has formed a cholesteatoma, and have been treated for intermittent otorrhea when this retraction pocket would discharge. It is a common diagnosis and a common misdiagnosis. If these cases could be diagnosed earlier, better hearing results would be achieved. But most of the time, pediatricians do an excellent job in referring those patients.
Karas: I am concerned with the older patient who has had recurrent drainage. I look closely for evidence of a possible cholesteatoma because I do not want to miss that diagnosis.
In post-tube otorrhea patients, I do not use systemic antibiotics. I treat most of these patients with eardrops.
Capoot: It is becoming the standard of care that a draining ear should be treated with only drops or drops used as a first-line treatment. The American Academy of Otolaryngology’s June 1999 bulletin reported that a panel of 11 otolaryngologists examined the use of antibiotics in the draining ear. The panel concluded, “That in the absence of systemic infection or a severe or serious underlying disease, topical antibiotics should be used alone as first line for infected tympanotomy tubes, otitis externa and chronic suppurative otitis media. For the majority of the patients with these conditions, the panel could cite no evidence that systemic antibiotics alone or in combination with topical preparations improved the treatment outcomes compared to using topical antibiotics alone.”8
In my personal experience, antibiotic drops, especially the fluoroquinolones, are being used exclusively with success.
Brunell: Aminoglycosides adversely affect hearing. Have you seen any cases of this?
Haynes: Approximately six times a year, I see patients who have been treated with systemic aminoglycosides and have developed a complication. These patients are more likely to acquire vestibular toxicity and dizziness as opposed to cochlear toxicity.
Aminoglycoside-containing drops have been used in ears for many years. Now that we know that Cipro HC otic and Floxacin otic are not ototoxic, we have the option to discontinue aminoglycosides.
In the case of AOM with pus in the middle ear space, the round window membrane is impermeable to the infection and to the drops administered. If there is not AOM with pus, labyrinthitis will present. I can count the number of times I have seen a labyrinthitis from an AOM on two hands, and that is impermeable and the products of the infection. Also, in this case, the actual bacteria do not cross the round window membrane so the antibiotics generally will not either.
Karas: One aspect I like about TobraDex, an aminoglycoside drop, is the dexamethasone. Dexamethasone is an effective steroid. In the future, I would like to see a preparation that contains ciprofloxacin as well as dexamethasone, because it would be exceptionally effective in decreasing granulation tissue. A combination of the two would be helpful especially in granulation tissue that is obstructing a tympanotomy tube. The obstruction means that the antibiotic drops cannot physically get into the middle ear as easily until you reduce the granulation tissue.
Capoot: Now that fluoroquinolone drops are available, we must seriously look at the potential for ototoxicity of the aminoglycoside drops, including Cortisporin optic.
Current literature has emphasized that aminoglycosides should not be used in the ear. A 1999 issue of Laryngoscope discussed the ototoxicity of topical gentamicin preparations. “Physicians should consider the potential for ototoxicity of gentamicin-containing eardrops, and by extrapolation, all topical aminoglycoside drops used for longer than seven days in patients with a TM defect. These preparations should not be used in the presence of healthy middle ear mucosa and should be discontinued shortly after the discharge is stopped.”9
Haynes: I still use aminoglycoside-containing drops based on my experience and the data on the off-label use of drops, which means that there is no indication in the package insert to use this in the ear.
For example, I learned about Ciloxan drops from pediatricians who learned to use them from ophthalmologists. I use Ciloxan, three drops twice a day in the ear with no reported incidence of any kind of ototoxicity.
Brunell: A legal issue is that the package insert of Cipro HC otic states, “This non-sterile product should not be used if the TM is perforated.” However, the FDA says not to use it in children under age one.
Capoot: This is an important point because many physicians are concerned about what package inserts state. I called Bayer Pharmaceuticals, manufacturer of Cipro HC, to discuss my concerns. I received a fax back from the scientific affairs department stating: “I spoke with the Cipro experts at the home office. The reason that Cipro HC otic is not recommended for use in patients with a perforated TM is that it was not studied in this population.” Therefore, the statement in the package insert is overstated. It probably should be more appropriately stated that it has not been investigated for this particular use.
Brunell: I would strongly recommend that one consult a lawyer on legal affairs and a physician for medical problems. I believe that in the future, these issues will be addressed with the next generation of ciprofloxacin otic drops.
I would like to thank the faculty for their participation today and Alcon Laboratories, Inc., for their sponsorship of this symposium.
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