Perlindungan antibiotik empirik untuk patogen atipikal bagi pneumonia jangkitan komuniti dalam kalangan dewasa di hospital
Abstract
Background
Community‐acquired pneumonia (CAP) is caused by various pathogens, traditionally divided into 'typical' and 'atypical'. Initial antibiotic treatment of CAP is usually empirical, customarily covering both typical and atypical pathogens. To date, no sufficient evidence exists to support this broad coverage, while limiting coverage is bound to reduce toxicity, resistance and expense.
Objectives
The main objective was to estimate the mortality and proportion with treatment failure using regimens containing atypical antibiotic coverage compared to those that had typical coverage only. Secondary objectives included the assessment of adverse events.
Search methods
We searched the Cochrane Central Register of Controlled Trials (CENTRAL) Issue 3, 2012 which includes the Acute Respiratory Infection Group's Specialized Register, MEDLINE (January 1966 to April week 1, 2012) and EMBASE (January 1980 to April 2012).
Selection criteria
Randomized controlled trials (RCTs) of adult patients hospitalized due to CAP, comparing antibiotic regimens with atypical coverage (quinolones, macrolides, tetracyclines, chloramphenicol, streptogramins or ketolides) to a regimen without atypical antibiotic coverage.
Data collection and analysis
Two review authors independently assessed the risk of bias and extracted data from included trials. We estimated risk ratios (RRs) with 95% confidence intervals (CIs). We assessed heterogeneity using a Chi2 test.
Main results
We included 28 trials, encompassing 5939 randomized patients. The atypical antibiotic was administered as monotherapy in all but three studies. Only one study assessed a beta‐lactam combined with a macrolide compared to the same beta‐lactam. There was no difference in mortality between the atypical arm and the non‐atypical arm (RR 1.14; 95% CI 0.84 to 1.55), RR < 1 favors the atypical arm. The atypical arm showed an insignificant trend toward clinical success and a significant advantage to bacteriological eradication, which disappeared when evaluating methodologically high quality studies alone. Clinical success for the atypical arm was significantly higher for Legionella pneumophilae (L. pneumophilae) and non‐significantly lower for pneumococcal pneumonia. There was no significant difference between the groups in the frequency of (total) adverse events, or those requiring discontinuation of treatment. However, gastrointestinal events were less common in the atypical arm (RR 0.70; 95% CI 0.53 to 0.92). Although the trials assessed different antibiotics, no significant heterogeneity was detected in the analyses.
Authors' conclusions
No benefit of survival or clinical efficacy was shown with empirical atypical coverage in hospitalized patients with CAP. This conclusion relates mostly to the comparison of quinolone monotherapy to beta‐lactams. Further trials, comparing beta‐lactam monotherapy to the same combined with a macrolide, should be performed.
PICO
Plain language summary
Rawatan antibiotik awal untuk perlindungan patogen ‘atipikal’ bagi pneumonia jangkitan komuniti dalam kalangan dewasa di hospital
Pneumonia adalah jangkitan paru‐paru serius yang sering dirawat dengan antibiotik. Bakteria yang menyebabkan pneumonia jangkitan komuniti (CAP, pneumonia yang dijangkiti di luar persekitaran penjagaan kesihatan) terbahagi kepada ‘tipikal’ dan ‘atipkal’ yang memerlukan rawatan antibiotik yang berbeza. Bakteria atipikal termasuk: Legionella pneumophila (L. pneumophila), Mycoplasma pneumoniae (M . pneumoniae) dan Chlamydia pneumoniae(C. pneumoniae). Agen ‘tipikal’ utama menyebabkan CAP adalah Streptococcus pneumoniae (S. pneumoniae). Biasanya adalah mustahil untuk menentukan bakteria mana yang berpotensi menyebabkan CAP, agar rawatan antibiotik yang empirik melindungi kedua‐dua bakteria tipikal dan atipikal. Walaupun perlindungan tipikal penting, keperluan atipikal masih belum terbukti. Di dalam versi ulasan terdahulu, kami menunjukkan tiada kelebihan untuk perlindungan bakteria atipikal. Oleh kerana garis panduan semasa untuk rawatan pneumonia dan bukti sedia ada tidak konsistenan, kami mengambil langkah mengemaskini kajian sistematik ini.
Ulasan Cochrane ini melihat kajian‐kajian yang membandingkan rejim antibiotik perlindungan atipikal dengan rejim yang tidak, terhad kepada orang dewasa dengan CAP dihospital. Kami memasukkan 28 kajian melibatkan 5939 pesakit. Bagi rejimen yang diuji, tiada kelebihan rejimen‐rejimen perlindungan bakteria atipikal di dalam hasil major yang diuji ‐ mortaliti dan efikasi klinikal. Tiada perbezaan signifikan di antara kedua‐kedua kumpulan dalam kekerapan peristiwa buruk atau kumpulan yang perlu menamatkan rawatan. Walau bagaimanapun, masalah gastrousus kurang lazim dalam lengan atipikal.
Terdapat pembatasan di dalam ulasan ini kerana satu kajian tunggal membandingkan penambahan antibiotik atipikal kepada antibiotik tipikal, persoalan utama dalam amalan klinikal; kebanyakan kajian membandingkan antibiotik atipikal tunggal dengan antibiotik tipikal tunggal. Tujuh belas daripada 27 kajian adalah label terbuka, 21 daripada 27 kajian ditaja oleh syarikat farmaseutikal kecuali satu kajian dijalankan oleh pengilang antibiotik atipikal.
