Antibiotik untuk eksaserbasi penyakit kronik pulmonari obstruktif
Abstract
Background
Many patients with an exacerbation of chronic obstructive pulmonary disease (COPD) are treated with antibiotics. However, the value of antibiotics remains uncertain as systematic reviews and clinical trials have shown conflicting results.
Objectives
To assess the effects of antibiotics in the management of acute COPD exacerbations on treatment failure as observed between seven days and one month after treatment initiation (primary outcome) and on other patient‐important outcomes (mortality, adverse events, length of hospital stay).
Search methods
We searched the Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE, EMBASE and other electronically available databases up to September 2012.
Selection criteria
Randomised controlled trials (RCTs) in people with acute COPD exacerbations comparing antibiotic therapy and placebo with a follow‐up of at least seven days.
Data collection and analysis
Two review authors independently screened references and extracted data from trial reports. We kept the three groups of outpatients, inpatients and patients admitted to the intensive care unit (ICU) separate for benefit outcomes and mortality because we considered them to be clinically too different to be summarised in one group. We considered outpatients to have a mild to moderate exacerbation, inpatients to have a severe exacerbation and ICU patients to have a very severe exacerbation. Where outcomes or study details were not reported we requested missing data from the authors of the primary studies. We calculated pooled risk ratios (RR) for treatment failure, Peto odds ratios (OR) for rare events (mortality and adverse events) and weighted mean differences (MD) for continuous outcomes using fixed‐effect models. We used GRADE to assess the quality of the evidence.
Main results
Sixteen trials with 2068 participants were included. In outpatients (mild to moderate exacerbations), there was evidence of low quality that antibiotics did statistically significantly reduce the risk for treatment failure between seven days and one month after treatment initiation (RR 0.75; 95% CI 0.60 to 0.94; I2 = 35%) but they did not significantly reduce the risk when the meta‐analysis was restricted to currently available drugs (RR 0.80; 95% CI 0.63 to 1.01; I2 = 33%). Evidence of high quality showed that antibiotics statistically significantly reduced the risk of treatment failure in inpatients with severe exacerbations (ICU not included) (RR 0.77; 95% CI 0.65 to 0.91; I2 = 47%) regardless of whether restricted to current drugs. The only trial with 93 patients admitted to the ICU showed a large and statistically significant effect on treatment failure (RR 0.19; 95% CI 0.08 to 0.45; high‐quality evidence).
Evidence of low‐quality from four trials in inpatients showed no effect of antibiotics on mortality (Peto OR 1.02; 95% CI 0.37 to 2.79). High‐quality evidence from one trial showed a statistically significant effect on mortality in ICU patients (Peto OR 0.21; 95% CI 0.06 to 0.72). Length of hospital stay (in days) was similar in the antibiotics and placebo groups except for the ICU study where antibiotics statistically significantly reduced length of hospital stay (mean difference ‐9.60 days; 95% CI ‐12.84 to ‐6.36 days). One trial showed no effect of antibiotics on re‐exacerbations between two and six weeks after treatment initiation. Only one trial (N = 35) reported health‐related quality of life but did not show a statistically significant difference between the treatment and control group.
Evidence of moderate quality showed that the overall incidence of adverse events was higher in the antibiotics groups (Peto OR 1.53; 95% CI 1.03 to 2.27). Patients treated with antibiotics experienced statistically significantly more diarrhoea based on three trials (Peto OR 2.62; 95% CI 1.11 to 6.17; high‐quality evidence).
Authors' conclusions
Antibiotics for COPD exacerbations showed large and consistent beneficial effects across outcomes of patients admitted to an ICU. However, for outpatients and inpatients the results were inconsistent. The risk for treatment failure was significantly reduced in both inpatients and outpatients when all trials (1957 to 2012) were included but not when the analysis for outpatients was restricted to currently used antibiotics. Also, antibiotics had no statistically significant effect on mortality and length of hospital stay in inpatients and almost no data on patient‐reported outcomes exist. These inconsistent effects call for research into clinical signs and biomarkers that help identify patients who benefit from antibiotics and patients who experience no effect, and in whom downsides of antibiotics (side effects, costs and multi‐resistance) could be avoided.
PICO
Plain language summary
Antibiotik untuk eksarserbasi penyakit kronik pilmonari obstruktif
Penyakit kronik obstruktif pulmonari (COPD) adalah satu keadaan kronik, sering disebabkan oleh merokok, yang menjejaskan laluan udara masuk dan keluar dari paru‐paru. Eksaserbasi COPD didefinisi sebagai gejala‐gejala pesakit yang berterusan bertambah buruk daripada keadaan yang stabil dan lazim dilaporkan gejala‐gejala seperti nafas tercungap‐cungap, batuk, peningkatan penghasilan kahak dan perubahan warna kahak. Antibiotik sering dipreskripsi untuk eksaserbasi dalam kalangan pesakit COPD walaupun punca eksaserbasi sukar untuk ditentukan (virus, bakteria, alam sekitar). Kami telah membuat ulasan kajian sistematik ini untuk mencari bukti kukuh tentang penggunaan antibiotik bagi eksaserbasi COPD dan jika manfaat mengambil antibiotik bagi individu melebihi potensi mudarat dalam kalangan pesakit dan risiko untuk bakteria resistan terhadap populasi.
Kami mendapati 16 kajian rawak yang membandingkan antibiotik dengan plasebo terhadap 2068 pesakit COPD yang mengalami pelbagai tahap keterukan eksaserbasi. Analisis menunjukkan antibiotik mengurangkan kegagalan rawatan (tiada penambahbaikan) berbanding plasebo bagi pesakit di dalam hospital dengan eksaserbasi yang teruk. Bukti penggunaan antibiotik bagi pesakit luar dengan eksaserbasi ringan hingga sederhana adalah kurang jelas kerana analisis menunjukkan pengurangan kegagalan rawatan apabila semua kajian dan antibiotik telah dipertimbangkan, namun analisis tidak menunjukkan kesan apabila terhad kepada penggunaan antibiotik semasa. Tempoh tinggal di hospital dan mortaliti tidak dikurangkan dengan penggunaan antibiotik dalam kalangan pesakit yang dimasukkan ke hospital kecuali bagi mereka yang memerlukan rawatan di unit rawatan rapi. Pesakit yang dirawat dengan antibiotik mengalami cirit‐birit dua kali ganda berbanding dengan pesakit yang menerima plasebo. Keterukan COPD tersirat tidak dapat dibandingkan antara kajian kerana fungsi paru‐paru dan parameter lain yang dilaporkan tidak konsisten antara kajian.
Bukti terkini menunjukkan bahawa antibiotik dapat mengurangkan kegagalan rawatan dalam kalangan pesakit yang dimasukkan ke hospital untuk rawatan eksaserbasi COPD, dan sebahagian kecil bagi pesakit luar. Mortaliti hanya dikurangkan dengan antibiotik bagi pesakit yang mengalami eksaserbasi serius, yang memerlukan rawatan di unit rawatan rapi. Kesan antibiotik yang bersifat sederhana dan tidak konsisten ke atas kegagalan rawatan mencadangkan bahawa antibiotik hanya berkesan dalam sesetengah pesakit dan bukan dalam semua pesakit. Kajian bermutu tinggi masa akan datang harus meninjau bagaimana terapi antibiotik boleh disasarkan kepada pesakit yang mendapat manfaat menggunakan tanda‐tanda klinikal (contohnya kahak yang bernanah) atau "biomarkers" sewaktu pesakit berjumpa dengan doktor di penjagaan primer atau di jabatan kecemasan.
