副鼻腔炎

Nelson Pediatrics 16th ed. では副鼻腔炎において細菌性の割合は0.5~2%と書かれており、抗菌薬治療が奏効する例は少ない。

しかしウイルス性の場合であれば、通常10日程度で軽快することが多いので、アメリカでは10 days rule があり、10日を超えた副鼻腔炎では、抗菌薬による治療も考慮する。

(”膿性”鼻汁と表現されることがあるドロッとした鼻汁になると、すぐに抗菌薬を使う医師がいるが、ドロッとしてくるのはサイトカインによって起こる現象で、ウイルス性でも起こる。膿瘍を排膿切開したことがある者なら判ると思うが、”膿”は蕩味程度の弱い粘性しかなく、ドロッとしている粘性はムコ多糖類によるもので、白色~黄色はリンパ球を含む白血球の色である。細菌がいなくてもドロッとするので抗菌薬を使う指標にはならない。)

この場合はペニシリン系抗菌薬で治療することになる。

2~3日で著効すれば、細菌性ということになる。2~3日で著効しない場合は、それ以上ペニシリン系を続けても無駄である。

日本鼻科学会から「急性鼻副鼻腔炎診療ガイドライン」というものが出ているが、EBMのレベルが低く、殆ど参考にならない。

一方で、マクロライド系抗菌薬には抗炎症作用があり、その有用性は以前から指摘されてきた。

1998年には、名古屋市立大学耳鼻咽喉科の羽柴基之氏らが、「慢性副鼻腔炎に対するマクロライドの長期投与ガイドライン(試案)」を発表。実施方法を記載しており、成人であれば、エリスロマイシン400-600mg、クラリスロマイシン200-400mg、ロキシスロマイシン150-300mg、小児であればエリスロマイシン8-12mg/kg、クラリスロマイシン4-8mg/kgを投与すると解説。投与期間は3カ月の投与で無効であれば他治療を検討し、有効である場合も3-6カ月をめどに切り上げると示していた。

一方でマクロライド系抗菌薬は副鼻腔炎には無効という報告もある。

オランダの無作為化比較試験によると、低用量のアジスロマイシンを3カ月以上投与しても、慢性副鼻腔炎に対するプラセボを超える有効性は確認されなかった

Lack of efficacy of long-term, low-dose azithromycin in chronic rhinosinusitis: a randomized controlled trial.

Videler WJ1, Badia L, Harvey RJ, Gane S, Georgalas C, van der Meulen FW, Menger DJ, Lehtonen MT, Toppila-Salmi SK, Vento SI, Hytönen M, Hellings PW,Kalogjera L, Lund VJ, Scadding G, Mullol J, Fokkens WJ.

Allergy. 2011 Nov;66(11):1457-68. doi: 10.1111/j.1398-9995.2011.02693.x. Epub 2011 Sep 2.


Abstract

In persistent chronic rhinosinusitis (CRS), conventional treatment is often insufficient. Long-term, low-dose administration of macrolides has been suggested as a treatment option. The MACS (Macrolides in chronic rhinosinusitis) study is a randomized placebo-controlled trial evaluating the efficacy of azithromycin (AZM) in CRS.

We describe a group of patients with recalcitrant CRS with and without nasal polyps unresponsive to optimal medical and (in 92% also) surgical treatment. Patients were treated with AZM or placebo. AZM was given for 3 days at 500 mg during the first week, followed by 500 mg per week for the next 11 weeks. Patients were monitored until 3 months post-therapy. The assessments included Sino-Nasal Outcome Test-22 (SNOT-22), a Patient Response Rating Scale, Visual Analogue Scale (VAS), Short Form-36 (SF-36), rigid nasal endoscopy, peak nasal inspiratory flow (PNIF), Sniffin' Sticks smell tests and endoscopically guided middle meatus cultures.

Sixty patients with a median age of 49 years were included. Fifty per cent had asthma and 58% had undergone revision sinus surgery. In the SNOT-22, Patient Response Rating Scale, VAS scores and SF-36, no significant difference between the AZM and the placebo groups was demonstrated. Nasal endoscopic findings, PNIF results, smell tests and microbiology showed no relevant significant differences between the groups either.

At the investigated dose of AZM over 3 months, no significant benefit was found over placebo. Possible reasons could be disease severity in the investigated group, under-dosage of AZM and under-powering of the study. Therefore, more research is urgently required.


PMID: 21884529 [PubMed - indexed for MEDLINE]

ほかの海外の報告でも抗菌薬の長期投与に有効性がある可能性を指摘しつつも、エビデンスは十分ではないと指摘。課題が残ると解説している

What is the proper role of oral antibiotics in the treatment of patients with chronic sinusitis?

Adelson RT, Adappa ND.

Curr Opin Otolaryngol Head Neck Surg. 2013 Feb;21(1):61-8. doi: 10.1097/MOO.0b013e32835ac625.


Abstract

PURPOSE OF REVIEW:

Chronic rhinosinusitis is a common illness for which systemic antibiotics are frequently prescribed, although high-level evidence for this practice is largely lacking. We review the available literature addressing the proper role of oral antibiotics in the treatment of chronic rhinosinusitis.


RECENT FINDINGS:

Chronic rhinosinusitis is an incompletely understood disease process for which the role of antibiotics remains difficult to define despite its historical prominence. There is no high-level evidence to support the use of oral antibiotics in chronic rhinosinusitis. Placebo-controlled studies of macrolide antibiotics indicate either no effect or limited degrees of improvement. Recent literature has identified that sinusitis refractory to medical therapy may represent an odontogenic source, and this should be addressed by dental surgery rather than by additional antibiotics.


SUMMARY:

Oral antibiotics can be prescribed most confidently for the management of chronic rhinosinusitis when purulent exacerbations of disease are detected endoscopically and antibiotic choices are directed by culture. Long-term macrolide antibiotic therapy, acting through immunomodulatory pathways, may be of benefit in chronic rhinosinusitis patients with low immmunoglobulin E levels. Odontogenic sources of sinusitis are best detected by a computed tomography scan and treated through dental surgery. There is no high-level experimental evidence to support the use of oral antibiotics in the management of chronic rhinosinusitis. The challenge continues to be the inability to perform double-blinded studies, as both patients and physicians are generally unwilling to participate in chronic sinusitis treatment studies with a placebo arm, given the deep-seated belief of oral antibiotic efficacy in treatment.

PMID: 23299120 [PubMed - indexed for MEDLINE]

Long-term low-dose antibiotics in recalcitrant chronic rhinosinusitis: a retrospective analysis.

Videler WJ1, van Hee K, Reinartz SM, Georgalas C, van der Meulen FW, Fokkens WJ.

Rhinology. 2012 Mar;50(1):45-55. doi: 10.4193/Rhino11.123.


Abstract

INTRODUCTION:

In recalcitrant Chronic RhinoSinusitis (CRS) treatment with intranasal corticosteroids, short-term antibiotics and even sinus surgery is frequently insufficient. Long-term low-dose administration of antibiotics has been suggested as a treatment option in these patients. We analysed the outpatient clinic population treated with different long-term low-dose antibiotics at the AMC Amsterdam.


PATIENTS AND METHODS:

Eligible patients, who were treated with trimethoprim-sulfamethoxazole or macrolides, were retrospectively identified from our outpatient clinic in 2009. The two main outcome measures were sinonasal complaints and nasal endoscopic findings. A 5-point grading scale was used to score the results compared with the pre-treatment situation. This was measured at several time-points during, and after the antibiotic course, and at the end of the follow-up term.


RESULTS:

Seventy-six patients were included, 53 per cent had asthma and all of them had undergone sinus surgery. Seventy-eight per cent showed improvement of the symptoms, and 84 per cent demonstrated improvement of the sinonasal mucosa at the end of the course. No significant difference was found between the trimethoprim-sulfamethoxazole and macrolide group.

DISCUSSION:

Long-term low-dose treatment with antibiotics seems to improve CRS symptoms and the appearance of the sinonasal mucosa on nasal endoscopy. However, at this stage, strong conclusions are immature because no placebo-group has been included. Despite increasing use of long-term low-dose treatment of recalcitrant CRS in referral centres, hard clinical evidence is lacking. More research is urgently required.

PMID: 22469605 [PubMed - indexed for MEDLINE]