Bacteriology of chronic sinusitis after amoxicillinclavulanate potassium therapy RONG-SAN JIANG, MD, JINQ-WEN JANG, MD, and CHEN-YI HSU, MD, Taichung, Taiwan, Republic of China
The bacteriology of chronic sinusitis was studied after amoxicillin-clavulanate potassium therapy. Patients with chronic sinusitis were randomly divided into 2 groups. In the study group, 90 patients were given a 2-week course of amoxicillin-clavulanate potassium before functional endoscopic sinus surgery. In the control group, 113 patients did not take any antibiotics within 2 weeks before the surgery. Swab specimens were taken from the maxillary and ethmoid sinuses during surgery and sent for aerobic and anaerobic culture. In the study group, the culture rates of maxillary and ethmoid sinuses were 45.6% and 28.9%, respectively. In the control group, the culture rates of maxillary and ethmoid sinuses were 53.1% and 34.5%, respectively. The culture rates between the control group and the study group were not significantly different, either for the maxillary sinus or the ethmoid sinus. This showed that treatment with amoxicillin-clavulanate potassium did not change the bacteriology of chronic sinusitis. (Otolaryngol Head Neck Surg 2001;124:683-6.)
Amoxicillin-clavulanate potassium is one of the antibiotics most commonly used in the treatment of chronic sinusitis.1 Most organisms isolated in chronic sinusitis have been shown to produce beta-lactamase, which is responsible for the failure of penicillin therapy in sinusitis.2 Amoxicillin-clavulanate potassium is a combination of amoxicillin with clavulanate potassium, an agent that inactivates beta-lactamase enzymes.3 Therefore, it can be used against most of the aerobic and anaerobic bacteria of chronic sinusitis. Its efficacy in treating chronic
From the Departments of Otolaryngology (Drs Jiang and Hsu) and Clinical Microbiology (Dr Jang), Taichung Veterans General Hospital, and the Department of Medicine (Dr Jiang), Chung-Shan Medical and Dental College. Presented at the 5th Japan-Taiwan Conference in Otolaryngology–Head and Neck Surgery, Sapporo (Japan), October 21-22, 1999. Reprint requests: Rong-San Jiang, MD, Department of Otolaryngology, Taichung Veterans General Hospital, Taichung, Taiwan 40705, Republic of China. Copyright © 2001 by the American Academy of Otolaryngology– Head and Neck Surgery Foundation, Inc. 0194-5998/2001/$35.00 + 0 23/77/115059 doi:10.1067/mhn.2001.115059
sinusitis has also been demonstrated in many studies.4 However, the influence of amoxicillin-clavulanate potassium treatment on the bacteriology of chronic sinusitis has rarely been reported in the literature. METHODS AND MATERIALS
A prospective study was conducted in Taichung Veterans General Hospital between June 1996 and October 1998. Patients with chronic sinusitis in whom medical treatment had failed and who were willing to undergo functional endoscopic sinus surgery (FESS) for surgical treatment were included in this study. The diagnosis of chronic sinusitis was based on a history of sinusitis for more than 3 months, the findings on nasal endoscopy, and an examination of computed tomography (CT). The definition of medical failure was that the sinusitis symptoms, usually rhinorrhea and/or postnasal drip, persisted after maximal medical therapy. The maximal medical therapy included at least 2 courses of 2 weeks of antibiotics and adjuvant mucolytic agents. The indications for FESS consisted of persistent sinusitis symptoms after maximal medical therapy and abnormal findings on nasal endoscopy and/or CT. The eligible patients were randomly divided into 2 groups. In the study group, the patients were given a course of amoxicillin-clavulanate potassium (1 tablet every 8 hours for 2 weeks) until the day before FESS as preoperative preparation. In the control group, the patients were asked not to take any antibiotics within 2 weeks before FESS. This project was approved by the institutional review board of Taichung Veterans General Hospital; informed consent was obtained from all patients. Before surgery, the face, including the oral mucosa and nasal cavity, was disinfected with a 10% povidoneiodine solution. During the surgery, sublabial endoscopy was used to examine the maxillary sinus on the side that had more severe disease based on CT films, or to examine the side of the nasal cavity undergoing FESS first because of septal deviation. At that time, a swab specimen was collected through the cannula. After antroscopy, endoscopic endonasal surgery began in the same side of the nasal cavity. The standard procedures described by Kennedy5 were applied. When the ethmoid bulla was removed, a clean cannula was placed into the anterior ethmoid cavity. A sterile cotton-tipped stick was passed through the cannula to obtain the spec683
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Table 1. Culture rates in the study group Maxillary sinus
Type of isolates/culture rate
Pure aerobic and facultative growth Pure anaerobic growth Mixed aerobic and facultative growth Mixed aerobic and anaerobic growth No bacterial growth Positive rate of culture
Table 2. Bacteriology in the study group Ethmoid sinus
No. of specimens
No. of specimens
34 2 3 2 49 45.6%
23 1 2 — 64 28.9%
imens from the anterior ethmoid cavity, thus eliminating the risk of contamination by touching the nasal vestibule and mucosa. The collected specimens were placed into a Thanswab tube containing 5 mL Amies charcoal medium for aerobes and anaerobes and then transferred to the clinical microbiology laboratory. The culture procedures have been described in our previous article.6 Fungal culture was not done in this study. RESULTS
In the study group, 23 patients who did not complete the 2-week amoxicillin-clavulanate potassium course because of drug intolerance or forgetfulness, and 2 patients whose final diagnoses were fungal sinusitis based on pathologic reports were excluded from the analysis of bacteriological results. In the control group, 2 patients were dropped from the study because of taking antibiotics to relieve the sinusitis symptoms within 2 weeks before FESS. Finally, 90 patients were included in the study group and 113 patients in the control group. There were 57 male and 33 female patients in the study group, and their ages ranged from 6 to 75 years old, with a mean age of 37.9 years. In the control group, 70 patients were male and 43 were female. Their ages ranged from 5 to 84 years old, with a mean age of 37.7 years. Nasal polyps were found in 39 patients in the study group and in 41 patients in the control group. However, purulent exudate was not obvious in the nasal cavity during FESS in either group. The bacteriologic results of the study group are shown in Tables 1 and 2. Bacteria grew from specimens from the maxillary sinuses of 41 patients. The culture rate was 45.6% (41 of 90). The most commonly recovered bacteria were Streptococcus viridans and Hemophilus influenzae. In comparison, bacteria grew from specimens from the ethmoid sinuses of 26 patients. The positive culture rate was 28.9%. The most commonly recovered bacteria were Staphylococcus epidermidis and Citrobacter diversus. In the aspect of drug sensitivity, the recovered bacteria from specimens from
Maxillary Ethmoid sinus sinus
Species
Aerobic and facultative bacteria Gram-positive Streptococcus viridans Staphylococcus epidermidis Staphylococcus aureus Staphylococcus not aureus Enterococcus Gram-negative Hemophilus influenzae Pseudomonas aeruginosa Citrobacter diversus Hemophilus parainfluenzae Klebsiella pneumoniae Escherichia coli Enterobacter aerogenes Nonfermentative gram-negative bacillus Acinetobacter baumannii Morganella morganii Klebsiella oxytoca Klebsiella ozaenae Total aerobic and facultative bacteria Anaerobic bacteria Gram-positive Anaerobic gram-positive bacillus Gram-negative Veillonella parvula Veillonella sp Prevotella loescheii Total anaerobic bacteria Total bacterial isolates
No. of isolates
No. of isolates
20 2 1 – 1
1 6 2 1 –
9 4 – 2 1 1 – – – – – – 41
2 2 4 – 2 – 1 1 1 1 1 1 26
1
1
1 1 1 4 45
– – – 1 27
the maxillary sinus were all sensitive to amoxicillinclavulanate potassium in 32 patients. One or more recovered bacteria were resistant to amoxicillin-clavulanate potassium in the other 9 patients. The sensitivity rate was 78.0%. In specimens from the ethmoid sinuses, the bacteria recovered were all sensitive to amoxicillinclavulanate potassium in 13 patients. The sensitivity rate was 50% (13 of 26). Overall, the culture results were the same between the specimens of the maxillary and ethmoid sinuses in 37 (41.1%) of 90 patients. The results of bacterial studies in the control group are shown in Tables 3 and 4. Bacteria grew from specimens from the maxillary sinuses in 60 patients. The culture rate was 53.1% (60 of 113). The most commonly recovered bacteria were Streptococcus viridans and Hemophilus influenzae. In contrast, bacteria grew from specimens from the ethmoid sinuses in 39 patients. The culture rate was 34.5%. The most commonly recovered bacteria were Staphylococcus aureus and Hemophilus
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Table 3. Culture rates in the control group
Type of isolates/culture rate
Pure aerobic and facultative growth Pure anaerobic growth Mixed aerobic and facultative growth Mixed aerobic and anaerobic growth No bacterial growth Positive rate of culture
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Table 4. Bacteriology in the control group
Maxillary sinus
Ethmoid sinus
No. of specimens
No. of specimens
50 2 5 3 53 53.1%
36 1 2 – 74 34.5%
influenzae. In the aspect of drug sensitivity, the recovered bacteria from specimens of the maxillary sinus were all sensitive to amoxicillin-clavulanate potassium in 44 patients. One or more recovered bacteria were resistant to amoxicillin-clavulanate potassium in the other 16 patients. The sensitivity rate was 73.3%. In specimens from the ethmoid sinus, recovered bacteria were all sensitive to amoxicillin-clavulanate potassium in 24 patients. The sensitivity rate was 61.5% (24 of 39). Overall, the culture results were the same between the specimens of maxillary and ethmoid sinuses in 48 of 113 patients (42.5%). The results of bacterial cultures of the study group were compared with those of the control group. The culture rates were not significantly different between the study and control groups, whether from specimens from the maxillary sinus (P = 0.286) or from those from the ethmoid sinus (P = 0.394). Neither was the sensitivity of recovered bacteria to amoxicillin-clavulanate potassium significantly different between the study and control groups, whether from specimens from the maxillary sinus (P = 0.590) or from those from the ethmoid sinus (P = 0.358). Moreover, the ratio of same results between maxillary sinus specimens and ethmoid sinus specimens was also not significantly different between the study and control groups (p = 0.845). DISCUSSION
Antibiotics have played an important role in the treatment of infectious diseases, including chronic sinusitis. When antibiotic treatment was the treatment of choice for acute sinusitis, Robinson et al7 suggested that repeated antibiotic therapy was ineffective in the treatment of chronic sinusitis. However, a consensus has not been reached regarding the influence of antibiotic therapy on the bacteriology of chronic sinusitis. In an article by Orobello et al,8 antibiotic therapy did not alter the sinus bacteria. The same conclusion was also reached by Goldenhersh et al.9 Conversely, Tinkelman
Species
Aerobic and facultative bacteria Gram-positive Streptococcus viridans Staphylococcus epidermidis Staphylococcus aureus Streptococcus pneumoniae Enterococcus faecalis Staphylococcus not aureus Enterococcus Corynebacterium sp Bacillus circulans Moraxella catarrhalis Gram-positive bacillus Gram-negative Hemophilus influenzae Citrobacter diversus Hemophilus parainfluenzae Klebsiella pneumoniae Enterobacter aerogenes Acinetobacter baumannii Pseudomonas cepacia Pseudomonas sp Pseudomonas aeruginosa Morganella morganii Serratia marcescens Total aerobic and facultative bacteria Anaerobic bacteria Gram-positive Propionibacterium acnes Anaerobic gram-positive coccus Gram-negative Veillonella parvula Capnocytophaga sp Total anaerobic bacteria Total bacterial isolates
Maxillary sinus
Ethmoid sinus
No. of isolates
No. of isolates
29 7 3 2 — — 1 1 1 — —
3 4 7 3 3 2 — 1 — 1 1
12 — 2 1 1 1 1 1 — — — 63
7 4 — 1 — — — — 1 1 1 40
2 1
1 —
2 1 6 69
— — 1 41
and Silk10 mentioned that antibiotic therapy resulted in the eradication of anaerobes. Recently, organisms isolated in chronic sinusitis have been found in increasing frequency to produce beta-lactamase. Therefore, antibiotics, which are effective against beta-lactamase, have been recommended as the drugs of choice in treating chronic sinusitis. Amoxicillin-clavulanate potassium is one of them.2 However, in this study, patients treated with amoxicillin-clavulanate potassium did not demonstrate a favorable bacteriologic response when compared with untreated patients. Whether in maxillary sinus or in ethmoid sinus specimens, amoxicillin-clavulanate potassium did not eradicate significantly more bacteria.
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Although Tinkelman and Silk10 thought that antibiotic therapy resulted in the eradication of anaerobes, this did not occur in our patients. Furthermore, the sensitivity of recovered bacteria to amoxicillin-clavulanate potassium did not have a significant difference between the study and control groups. This implied that amoxicillin-clavulanate potassium did not select sinus pathogens and leave resistant bacteria in the sinuses. Compared with our previous study,11 ampicillin therapy seemed to change the bacteriology of chronic sinusitis. The difference in outcome between ampicillin and amoxicillin-clavulanate potassium therapy might result from the difference in the antibiotics themselves or in the study designs. In our previous article, the study and control groups did not come from the same time period. Therefore, further studies are needed to clarify the roles and mechanisms of different antibiotics in the bacteriology of chronic sinusitis before a definite conclusion about the function of antibiotic therapy in chronic sinusitis can be reached. Another point that needs to be addressed is the selection of patients. In this study, the patients included were those with chronic sinusitis that had failed to respond to medical treatment. All patients in the study and control groups had received repeated antibiotic treatment previously. As a result, poor efficacy of amoxicillin-clavulanate potassium therapy was expected in these patients. However, because all patients had stopped antibiotic therapy for at least 1 week before taking amoxicillinclavulanate potassium, previous antibiotic treatment should not have affected the bacteriologic results of amoxicillin-clavulanate potassium therapy. Therefore, the reason that amoxicillin-clavulanate potassium therapy did not change the bacteriology might have been the ineffectiveness of amoxicillin-clavulanate potassium in these patients. This might also give evidence to justify
the role of surgical treatment in chronic sinusitis patients who have failed to respond to medical treatment. CONCLUSION
In this study, it was shown that treatment with amoxicillin-clavulanate potassium did not change the bacteriology of chronic sinusitis if those patients with chronic sinusitis already failed to respond to medical treatment including repeated antibiotic therapy. Therefore, although antibiotic therapy does play a role in the treatment of some patients with chronic sinusitis, surgical therapy might be necessary for those patients with chronic sinusitis failing to respond to medical treatment. REFERENCES 1. Brook I. Microbiology and management of sinusitis. J Otolaryngol 1996;25:249-56. 2. Brook I, Yocum P, Frazier EH. Bacteriology and β-lactamase activity in acute and chronic maxillary sinusitis. Arch Otolaryngol Head Neck Surg 1996;122:418-23. 3. Fairbanks DNF. Bacteriology and antibiotics. Otolaryngol Clin North Am 1993;26:549-59. 4. Brook I, Thompson DH, Frazier EH. Microbiology and management of chronic maxillary sinusitis. Arch Otolaryngol Head Neck Surg 1994;120:1317-20. 5. Kennedy DW. Functional endoscopic sinus surgery: technique. Arch Otolaryngol 1985;111:643-9. 6. Jiang RS, Hsu CY, Leu JF. Comparison of the bacteriologies between the ethmoid and maxillary sinuses in chronic paranasal sinusitis. J Otolaryngol Soc ROC 1993;28:308-17. 7. Robinson PJ, East CA, Scott GM. Recent advances in the microbiology of sinusitis and their relation to persistent ethmoidal inflammation. Am J Rhinol 1990;4:83-5. 8. Orobello PW, Park RI, Belcher LJ, et al. Microbiology of chronic sinusitis in children. Arch Otolaryngol Head Neck Surg 1991;117:980-3. 9. Goldenhersh MJ, Rachelefsky GS, Dudley J, et al. The microbiology of chronic sinus disease in children with respiratory allergy. J Allergy Clin Immunol 1990;85:1030-9. 10. Tinkelman DG, Silk HJ. Clinical and bacteriologic features of chronic sinusitis in children. Am J Dis Child 1989;143:938-41. 11. Jiang RS, Hsu CY. Bacteriology of chronic sinusitis after ampicillin therapy. Am J Rhinol 997;11:467-71.