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Address for correspondence : Jong Woo Chung, MD, Department of Otolaryngology, Asan Medical Center, University of Ulsan, College of Medicine, 388-1 Pungnap 2-dong, Songpa-gu, Seoul 138-736, Korea
Tel : +82-2-3010-3718, Fax : +82-2-489-2773, E-mail : jwchung@amc.seoul.kr
Introduction
Since the initial description of maligotitis externa,1) the morbidity and mortality of this disease have significantly decreased. Increased awareness by clinicians has led to earlier diagnosis and treatment, decreasing the rate of complications.2,3) Pawith otitis externa and diabetes or immunosuppressive illnesses are treated more aggressively than the average patient with otitis externa. In a number of patients with diabetes or immunosuppressive illnesses, persistent otitis externa is refractory to medical treatment. Aggressive infections are usually treated with hospitalization and long-term intraveantibiotics.
Following the introduction of ciprofloxamany patients with early stages of malignant otitis due to Pseudomonas no longer required hospitalization and were successfully treated as outpatients.3) More recently, however, we have noticed an increasing number of malignant external otitis (MEO) patients with methicillin-resistant Staphylococcus aureus (MRSA) or ciprofloxacin-resistant Pseudomonas (CRP). To assess the clinical changes over time of MEO, we reviewed the medical records of 22 patients diagnosed with MEO and analyzed their bacteriology, extent of disease, laboratory findings, imaging studies and the results of treatment.
Subjects and Methods
A total of 22 patients with the diagnosis of MEO were admitted to the Department of Otolaryngology, Asan Medical Center (Seoul, Korea), from 1989 to 2006. At admission, all patients had otalgia, physical manifestations (granulations of the inferior canal wall and/or edema), and were positive for bacteria cultured from the ear; in addition, almost all of the patients had a history of diabetes/malignancy. All patients were hospitalized for daily cleaning and intermittent debridement of the ear and for intravenous antibiotic therapy.
Bacteriological examination of the discharge from each subject's ear was performed at the time of first visit to the hospital. The swabs were inoculated on McKonkey agar, blood agar and chocolate agar plates, which were examined after 48 hours and after 7 days. Laboratory tests of each patient's blood samples and imaging modalities, including CT, MRI, and gallium scans, were performed for diagnosis and follow up.
Results
Sixteen male and six female patients were included in this study (Table 1). Mean patient age was 69.7 years (range, 50 -87 years). All patients were hospitalized, for an average of 46.6 days (range, 8-180 days). Of the 22 patients, 20
(90.9%) had a history of diabetes on admission. One patient
(5%) had no history of diabetes, but suffered from bowel dysfunction for 6 months caused by iatrogenic bowel perforation. One patient had a history of rectal cancer managed by surgery and chemotherapy. The duration of symptoms and hospitalization tended to be longer in patients with disease extending into the skull base than in patients with disease confined to the external auditory canal (EAC) and mastoid cavity though there was no statistical significance (Table 2).
The main symptoms on admission were persistent pain and drainage. Three patients
(13.6%) had facial weakon the involved side. All patients had edema, purulent drainage, and granulations filling the ear canal. Perforation of tympanic membrane (TM) was found in three patients; all others had intact TM. Patients' data including the extent of disease, duration of treatment and outcome of treatment were summarized in Table 3.
Bacterial culture and sensitivity tests identified Pseudomonas aeruginosa in 10 of the 22 patients
(45.5%). Of these 10,
7(70%) had cultures resistant to ciprofloxacin. An additional 9 patients
(40.9%) were infected with Staphylococcus aureus; of these, 8
(88.9%) were resistant to methicillin (Table 4). Two patients had both CRP and MRSA. Of the 22 patients, 4
(18.2%) had sterile results, and 1
(4.5%) had infections with enterococcus. Seven out of 8 MRSA strains appeared in the past 3 years. Five out of 7 CRP strains appeared in the past 3 years. Data analysis revealed a significant trend toward increasresistance over time (Table 5).
Estimated sedimentation rate (ESR) increased in all 22 patients, but remained high in 11 even after clinical signs and symptoms. In the remaining 11 patients, ESR decreased with improvement of symptoms. There was no relationship between initial level of ESR and degree of disease spread on MRI. The resolution of symptoms or physical findings did not correlate with the level of ESR.
All 22 patients were initially treated with ciprofloxacin. Following the identification of the infecting microorganisms in each patient, each was treated with the appropriate antibiotics, for example ceftazidime for patients with CRP and vancomycin for patients with MRSA. All the patients with inflammation confined to the EAC and middle ear were cured by frequent cleansing and local debridement, plus antibiotics. Three patients, however, needed more aggressive surgical intervention. Oneunderwent cortical mastoidectomy, due to the destruction of the posterior bony canal of the EAC with inflammation extending into the mastoid cavity. Two underwent petrosectomy due to intractable pain and headache.
All patients were examined using imaging modalities, including computertomography (CT), magnetic resonance imaging (MRI)(Fig. 1) and gallium scan. From the findings of CT and MRI of temporal bone, patients whose MEO confined to EAC and mastoid in 9
(40.9%) and MEO extending to the skull base in 13
(59.1%) as shown in Table 2 and 3.
Nineteen out of the 22 underwent gallium scans, and 16 showed increased gallium uptake at the skull base. In the remaining three patients, there was no increase of gallium uptake, although these patients had acute symptoms and MRI showed inflammatory lesions in the skull base. Follow up gallium scans were performed in 5 patients one week to one month after symptoms disappeared, but only 2 patients showed decreased gallium uptake (Fig. 2).
Follow up MRI was performed in 6 patients after symptoms (otalgia, headache) and physical signs (discharge, swelling of external auditory canal) disappeared. These patients showed a decrease or disappearance of signal intensity of the original inflammatory lesion. In the patient whose symptoms became aggravated, MRI showed increased signal intensity at the bone marrow portion of the petrous apex.
Of the 22 patients, 18 (81.8%) were cured by a combination of intravenous antibiotics and debridement and remain alive without disease. Two of the 13 patients with inflammation extending into the skull baseunderwent petrosectomy due to intractable pain and headache. Following surgery, one patient suffered from intermittent headache and died one year later. In the other patient, headache was much decreased, but inflammation in thepetrous apex still remained; this patient has been alive with disease for 3 years. One other patient is alive with disease confined to the ipsilateral petrous bone and clivus after long-term use (12 weeks) of intravenous antibiotics. One another patient was managed in his old age and died 2 yrs after the treatment. However, the cause of death was not known (Table 3).
Discussion
We have shown here that, in patients with MEO, the increase in antibiotic resistant strains is associated with more aggressive treatment modalities. Of the 22 patients, 15 had resistant microorganisms; of these 15, 9 had inflammations at the skull base (petrous and sphenoid bone).
Earlier diagnosis and more rapid treatment have resulted in decreased morbidity and mortality from MEO. Before the introduction of ciprofloxacin, patients with MEO were admitted for a minimum 6-week course of intravenous therapy with an aminoglycoside and semisynthetic penicillin. After ciprofloxacin was shown to be effective for pseudomonas MEO,4,5) patients diagnosed with early stages of the disease could be treated on an outpatient basis. Although hospitalization and intravenous antibiotic therapy for long periods of time can be avoided in most patients, there has been a recent increasein the number of patients with MEO resulting from CPR and MRSA. This concern prompted our retrospective analysis to determine whether resistance is increasing and whether any comorbidity is associated with the resistance. In agreement with previous results,7) we found that the incidence of bacteria resistant to oral antibiotics (CPR and MRSA) has increased over time, with treatment duration (days in hospital) of these patients tending to be longer than that of patients with bacteria sensitive to antibiotics (ciprofloxacin-sensitive pseudomonas and methicillin-sensitive staphylococcus aureus), although the difference was not statistically significant.
Widespread community use of oral ciprofloxacin for upper respiratory infections and routine topical use of ciprofloxacin for external ear infections may contribute to the increase in MEO due to CRP.6) If bacteria in culture show resistance to oral antibiotics, early aggressive treatment with intravenous antibiotics is recommended.
The decision of when to stop treatment depends on the resolution of the inflammation. This decision cannot be based on otoscopy alone because it does not include assessment of deeper infection of the skull base, which may be much slower to resolve. High-resolution CT can show the location and the extent of the disease process. Structural imaging can define the destruction of the cortex of the bone and extension into the soft tissues inferior to the EAC and skull base. Small cortical erosions are better visualized with CT scans. Although useful in initial diagnosis, this investigation has little or no role in monitoring the resolution of the disease, because remineralization is required before the bony changes can return to normal.8)
Gallium citrate is absorbed by macrophages and reticular endothelial cells. However, although gallium citrate is a sensitive indicator of infection, it is essentially a nonspecific technique. In the presence of infection, there is an increased uptake of gallium, which may occur in soft tissue or bone. Uptake quickly returns to normal after the infection has cleared. Although gallium scans appear to be highly sensitive indicators of disease resolution,8) they are relatively expensive and time-consuming. Furthermore, we have shown here that the correlation betweengallium scans and clinical findings is not satisfactory. We found that MRI showed a higher sensitivity
(93%) than gallium scans, and was more specific for extent of disease and symptoms. MRI scans can show soft tissue involvement, including the meninges and the parotid area.8) In addition, clinical improvement is better correlated with MRI than with gallium scans in this study.
The role of surgery was primarily for debridement. This was performed in the hospital wards to remove granulations and devitalized tissues, and to take biopsies if the diagnosis was questionable. Among the threepatients who underwent extensive debridement of the temporal bone, one was cured after aggressive surgery and antibiotic therapy and one is alive with disease.
Conclusion
Malignant external otitis with skull base osteomyelitis is likely curable with long-term, high-dose antibiotics, with the treatment regime dependent on microbiological findings. Culture results showed an increasing incidence over time of antibiotic resistant bacteria, including CRP and MRSA, indicating the importance of early treatment with intravenous antibiotics. The most sensitive imaging modality was MRI. If the disease extends to the skull base and does not respond to long term intravenous antibiotics, surgery should be considered.
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