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Topical Antibiotic Therapy for Recalcitrant Sinusitis

1999; Wiley; Volume: 109; Issue: 4 Linguagem: Inglês

10.1097/00005537-199904000-00029

1531-4995

David W. Leonard, William E. Bolger,

Pneumonia and Respiratory Infections

Recurrent sinusitis that is “recalcitrant” to medical and surgical treatment can be a frustrating clinical entity to treat. Ostial occlusion with secondary bacterial infection is accepted as the primary etiologic factor in sinusitis. Bacterial infection of the sinuses can result in sinus membrane thickening, a change in mucin composition, and a change in mucus pH. Such local factors may be important in cases of recalcitrant sinusitis in patients who have already undergone functional sinus surgery. These factors could negatively influence the effectiveness of systemic antibiotic therapy. Much as the treatment of otitis externa involves debridement and removal of purulent material from the site of infection followed by topical antibiotics, the use of topical antibiotics in select patients with sinusitis would appear logical. In this light, we wish to consider the use of topical antibiotic therapy in patients with recalcitrant sinusitis. In contrast to systemic antibiotic therapy, topical application of antibiotic to the sinus membranes offers the potential benefit of high concentration of drug at the site of infection with low blood levels and hence, low potential for systemic side effects. Although topical antibiotic therapy has been very effective in the treatment of otitis externa, acne, bacterial conjunctivitis, and select pulmonary infections, this treatment has not been accepted for sinusitis.1.-6. In addition, there have been relatively few reports of topical antibiotic use in the treatment of sinusitis. Recently, there has been an increased interest in the concept of topically applied antibiotics in the treatment of sinusitis. Kobayashi and Baba7. studied nebulization therapy in chronic sinusitis. They used an ultrasound-type inhaler and studied an aminoglycoside, fosfomycin, and cefmenoxine therapy administered three times per week. Their findings suggested that in patients without previous sinus surgery, the nebulized medications' main effect is in the nose, and works only indirectly on the maxillary sinuses: no evidence of antibiotic penetration into the maxillary sinus could be confirmed experimentally. Therefore access to the affected tissue may be an important consideration in topical antibiotic therapy. Following endoscopic surgery, obstruction is removed and the sinuses communicate freely with the nasal cavity. This would greatly enhance access to the sinuses and hence, drug delivery. Therefore a reconsideration of topical therapy in sinusitis seems warranted in this patient population. In addition to access, other factors such as dose, concentration, and method of drug delivery are important in topical antibiotic therapy. A study by Sykes et al.8. exemplifies the importance of dose. Two groups of patients with chronic mucopurulent rhinosinusitis were treated with a nasal spray containing dexamethasone-tramazoline-neomycin or dexamethasone-tramazoline. A metered dose delivered 20 μg dexamethasone, 120 μg tramazoline, and 100 μg neomycin. No significant difference was seen in patients receiving neomycin. It is likely that the concentration and total dose of neomycin were insufficient. Studies of antibiotic irrigation solutions show that 1.0 mg/mL of neomycin is needed to kill 100% of Staphylococcus aureus, and 5.0 mg/mL is needed for Staphylococcus epidermitis in vitro.9. Coly-Mycin (Parke-Davis, Morris Plains, NJ), a well-recognized effective treatment for otitis externa and chronic otitis media with perforation, contains 3.3 mg/mL of neomycin, an approximately 3200% increase in total dose over that studied by Sykes et al.8. The concentration of aminoglycoside solution recommended for sinonasal irrigation4. is smaller by a factor of 18 compared with Coly-Mycin. In light of the ineffectiveness of the lower doses studied by Sykes et al.,8. further study seems warranted. We have avoided gentamicin due to potential toxicity. Monitoring of serum drug levels would be indicated to ensure low risk of otologic or renal toxicity, and its potential negative effect on olfactory neuroepithelium is an additional consideration. Frequency of topical antibiotic administration is also important. Elledge et al.10. demonstrated that topical oral clindamycin reduced bacterial counts of oral flora for up to 4 hours, while Grandis et al.11. documented an effect for up to 8 hours. The optimal dosing frequency for sinusitis using topical antibiotics would be best determined scientifically through studies similar to those of Elledge et al.10. and Grandis et al.11. The method of topical drug delivery is also an important consideration. Rebhun12. studied a topical antibiotic spray in sinusitis; however, his results are confounded by initial treatment with 2 weeks of oral antibiotic therapy. Also, some of his patients had prior sinus surgery and others had not. A comparison of sprays, nebulization, Praetz irrigation, and mechanical or bulb syringe gross irrigation in delivering medication to the deeper recesses of the sinuses is indicated. This is especially true given the lack of published clinical research in this area. We wish to communicate our 5-year experience with topical ceftazidime in the treatment of patients with recalcitrant gram negative sinusitis who have failed to respond to conventional medical and surgical treatment. Although the following patient's medical care was complex and atypical, her case presentation highlights the fact that topical antibiotic therapy was effective despite her failing oral and intravenous antibiotic therapy. She did receive our typical dosing for topical antibiotics. A 50-year-old woman was referred to our care by her local otolaryngologist, complaining of persistent facial discomfort, sinus drainage, and facial swelling. Over the previous 3 months, her sinusitis was treated with a 3-week course of oral ciprofloxin, a 3-week course of lomefloxacin, and intravenous intravenous imipenemcilastatin 500 mg every 8 hours. Before this latest episode of chronic sinusitis, she suffered at least six prolonged episodes of sinusitis per year despite numerous sinus surgeries, with intravenous antibiotics frequently required, as oral antibiotics offered little relief. A previous allergy workup was negative. Her past surgical history was remarkable for 13 previous operations of the paranasal sinuses from 1979 to 1992, including multiple intranasal and external ethmoidectomies, sphenoidectomies, nasal antral windows, Caldwell-Luc procedures, and two osteoplastic flap procedures with fat obliteration of the frontal sinus. Past medical history was significant for steroid-dependent asthma, hypertension, and gastroesophageal reflux. On physical examination, she was afebrile and her vital signs were normal. Slight facial edema and cutaneous venous congestion of the upper thorax was evident. A Hickman catheter was present. Nasal endoscopy revealed extensive postsurgical changes, scant septations of resected ethmoid cells, lateral displacement of the right middle turbinate remnant, and open maxillary and sphenoid sinuses. Mucopurulent secretion was noted in the left middle meatus anteriorly and in the right middle meatus posteriorly. Endoscopically guided cultures of the left maxillary sinus mucopus were obtained. This revealed Pseudomonas aeruginosa, despite the previous intravenous therapy, which was resistant to ciprofloxin, mezlocillin, gentamicin, amikacin, tobramycin, ceftriaxone, cefotaxime, and aztreoman, but sensitive to ceftazidime. On admission, an intravenous infusion of heparin was instituted for a suspected subclavian or superior vena cava thrombosis. A venogram demonstrated complete thrombosis of the left subclavian and bracheocephalic veins with extension to the left axillary vein, with extensive collateralization. The thrombus extended into the superior vena cava with partial occlusion of the right subclavian. Because the Hickman catheter was nonfunctional and the tip was involved with the thrombus, it was removed with negative cultures of the tip. Computed tomography (CT) scan of the sinuses revealed extensive postoperative changes, slight mucosal thickening of the ethmoids, and soft tissue density of the left maxillary sinus, with no evidence of mucopyocele or bony erosion. Bone scan and gallium scan of the sinuses revealed only ethmoid and maxillary enhancement. Osteomyelitis of the frontal bone was not evident, and the soft tissue from previous osteoplastic frontal sinus surgeries did not appear infected. Further laboratory evaluation showed a negative HIV test result, and repeat formal allergy/immunology evaluation at our institution was negative for allergy and revealed only a mild hypogammaglobulinemia of one subgroup that was determined to be clinically insignificant. The heparin infusion was temporarily discontinued and endoscopic sinus surgery was performed, directed to the abnormal areas. Each maxillary sinus was opened more anteriorly into the region of the natural ostia. The right maxillary sinus was noted to contain thick inspissated mucin, which was removed, in addition to the mucopus noted in each maxillary sinus. Scar tissue was removed at the previous sphenoidotomy sites, enlarging these openings. One residual ethmoid cell was noted in the right agger nasi region lateral and posterior to the middle turbinate remnant that had scarred to the lateral nasal wall and periorbita. The mucosa within this cell was slightly thickened. The frontal recess area appeared closed as expected due to the previous frontal sinus obliteration procedures. Preoperative evaluation to include bone scan, gallium scan, and magnetic resonance imaging (MRI) scar failed to rule out conclusively frontal sinus disease. Therefore sinoscopy of the frontal sinus was performed through a small trephine, which revealed fibrous tissue without signs of infection. Intraoperative cultures from the maxillary sinuses subsequently revealed P aeruginosa, and fungal cultures were negative. His topathologic analysis revealed chronically inflamed respiratory tract mucosa with fibrosis; fungal elements were not present. Postoperatively heparin therapy was reinstituted, and ultimately the patient was placed on a regimen of warfarin. The recovered Pseudomonas strain was found to be resistant to quinolones, indicating a need for IV therapy. However peripheral venous access for IV therapy was poor, and central venous access was to be avoided in light of the central venous thrombosis. Therefore topical antibiotic treatment was considered. The bacterial strain was highly sensitive to ceftazidime therefore a topical solution for irrigation consisting of 6 g ceftazidime in 1 L normal saline was prescribed. Three hundred milliliters were irrigated into the nostrils three times a day. At the 1- and 2-week follow-up examinations the mucopus was noted to have resolved, as did the inflammatory changes of the sinus membranes. The patient was seen in our clinic on five occasions over the 18 months after treatment. Her sinuses have been by her report greatly improved. She had required topical antibiotic treatment on one other occasion and responded equally well. She continues to suffer occasional sinus infections; however, these were managed successfully with oral medications. Our patient presented with a chronic sinus infection due to P aeruginosa that had been recalcitrant to numerous oral antibiotics and sinus surgeries. Infection with Pseudomonas species, in particular, may be extremely difficult to treat, sometimes requiring more than 6 weeks of intravenous antibiotic therapy.13. The superior vena cava obstruction, as well as the antibiotic resistance of the Pseudomonas organism, severely limited possible treatment regimes: intravenous access was limited to the lower extremities, and ceftazidime, the only antibiotic the bacteria was sensitive to, was not available in oral form. Therefore topical antibiotic treatment appeared a logical alternative in this case. Because of the wide variability of topical antibiotic concentrations in the few reports discussed previously, we have paid particular attention to finding the “correct” antibiotic concentration. We use a 0.1% solution, or 300 mg of drug in 300 mL of saline, for each irrigation session. This concentration compares with commercially available otologic and ophthalmologic preparations that have been shown to be highly effective. In our experience, treatment of sinusitis with topical antibiotic irrigation solutions in select patients who have previously undergone endoscopic sinus surgery is successful. Over the past 5 years we have treated 50 patients. The only complication was in one patient who complained of a stinging sensation intranasally, which persisted despite dilution of the antibiotic solution by 50%. We currently dispense 6 g of ceftazidime in 60 mL of bacteriostatic saline, which is kept refrigerated until ready for use. This “stock solution” is diluted 3 mL in 300 mL of saline, and the nasal and sinus cavities irrigated three times daily. The treatment is guided by endoscopically directed culture results with antibiotic sensitivities. No resistance to ceftazidime has developed thus far. Further study to better delineate appropriate dosage and response to treatment is warranted. The tenets of topical therapy that we follow are 1) that the topical antibiotic must be able to reach the site of infection, 2) that the antibiotic concentration must be sufficient, 3) that the antibiotic dosing interval must be frequent enough, and 4) that the antibiotic spectrum of coverage must be appropriate to the suspected organism and ideally is guided by endoscopically directed culture results. We wish to communicate our preliminary experience with a topical antibiotic preparation in patients with recalcitrant chronic sinusitis. We have used this preparation in more than 50 patients during the past 5 years and found it to be a useful adjunct to therapy. The treatment is well tolerated and has little morbidity or risk. We emphasize the need to monitor response to the topical antibiotic solution with serial endoscopic examinations in the clinic setting.