Efektivitas Antibiotik Inhalasi pada Pasien Ventilator Associated Pneumonia: Kajian Sistematis dan Meta-Analisis
Abstract
Antibiotik inhalasi dapat menjadi tambahan dalam terapi ventilator associated pneumonia (VAP) karena menghantarkan antibiotik secara langsung ke dalam lokasi infeksi di paru-paru untuk menyediakan konsentrasi antibiotik yang adekuat di paru-paru, sedangkan antibiotik intravena (IV) bekerja secara sistemik. Food and Drug Administration (FDA) dan European Medicine Agency sudah menyetujui beberapa antibiotik inhalasi sebagai terapi cystic fibrosis, tetapi belum ada antibiotik inhalasi yang disetujui untuk penggunaan VAP walaupun sudah ditemukan bukti yang mendukung. Tujuan ditulisnya kajian ini adalah untuk mengkaji efektivitas antibiotik inhalasi baik sebagai terapi adjuvan dengan IV ataupun terapi substitusi dalam pengobatan VAP. Efektivitas yang diteliti meliputi clinical cure, microbial cure, dan mortalitas. Penelitian ini merupakan kajian literatur dan meta-analisis yang menggunakan artikel dengan desain randomized control trial (RCT). Proses penelusuran pustaka dilakukan dengan menggunakan basis data PubMed. Kualitas artikel yang diinklusi dinilai dengan Critical Appraisal Skill Programme (CASP) checklist dan reputasi jurnal. Total terdapat 7 penelitian yang diikutsertakan dalam kajian akhir dan meta-analisis. Hasil meta-analisis antibiotik inhalasi sebagai terapi adjuvan maupun substitusi tidak menunjukan hasil positif pada tingkat kesembuhan klinis (RR=1,07; 95% CI=0,86–1,32) dan mortalitas (RR=1,09; 95% CI=0,83–1,43). Hasil meta-analisis penggunaan antiobiotik inhalasi sebagai terapi adjuvan menunjukan hasil positif dalam mengeradikasi mikroba (RR=1,56; 95% CI=1,13–2,17), namun tidak menunjukkan keuntungan dalam eradikasi mikroba apabila digunakan sebagai terapi substitusi (RR=1,21; 95% CI=0,86–1,71). Dapat disimpulkan bahwa penggunaan antibiotik inhalasi sebagai terapi adjuvan ataupun monoterapi tidak efektif dalam memperbaiki tingkat kesembuhan klinis dan mortalitas pasien VAP, namun penggunaan antibiotik inhalasi sebagai adjuvan mampu mengeradikasi mikroba lebih baik dibandingkan tanpa antibiotik inhalasi.
Kata kunci: Antibiotik, inhalasi, aerosol, pneumonia, ventilator mekanis
Effectiveness of Inhaled Antibiotics in Ventilator Associated Pneumonia: A Systematic Review and Meta-Analysis
Abstract
Inhaled antibiotics are adjunct to ventilator-associated pneumonia (VAP) therapy because they are delivered directly to the infection site of the lungs, while intravenous (IV) antibiotics work systematically. The Food and Drug Administration (FDA) and the European Medicine Agency have approved several inhaled antibiotics for cystic fibrosis treatment. However, none have been approved for VAP use, even with supporting evidence. Therefore, this study aimed to evaluate the effect of inhaled antibiotics as adjuvant therapy with IV or substitute in the treatment of VAP. The effect was measured based on clinical cure, microbial cure, and mortality. This study is a literature review and meta-analysis using a randomized control trial (RCT) design. The parameters measured were a clinical cure, microbial cure, and mortality. Furthermore, the literature search was conducted using the PubMed database. The included articles’ quality was assessed using the Critical Appraisal Skill Program (CASP) checklist and the journal’s reputation. Furthermore, 7 studies were included in the final review and meta-analysis. The results showed that the meta-analysis of inhaled antibiotics as adjuvant or substitution therapy is negative on clinical cure rates (RR=1,07; 95% CI=0,86–1,32) and mortality (RR=1,09; 95% CI=0,83–1,43). The analysis of inhaled antibiotics as adjuvant therapy was positive in microbiological cure (RR=1,56; 95% CI=1,13–2,17) but has no benefit as substitution therapy (RR=1,21; 95% CI=0,86–1,71). It can be concluded that using inhaled antibiotics as adjuvant therapy or monotherapy is ineffective in improving the clinical cure rate and mortality of VAP patients while using it as an adjuvant alone can eradicate microbes better.
Keywords: Antibiotics, inhalation, aerosol, pneumonia, mechanical ventilator
Keywords
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Bassetti M, Taramasso L, Giacobbe DR, Pelosi P. Management of ventilator-associated pneumonia: Epidemiology, diagnosis and antimicrobial therapy. Expert Rev Anti Infect Ther. 2012;10(5):585–96. doi: 10.1586/eri.12.36
Bassetti M, Luyt CE, Nicolau DP, Pugin J. Characteristics of an ideal nebulized antibiotic for the treatment of pneumonia in the intubated patient. Ann Intensive Care. 2016;6(1):35. doi: 10.1186/s13613-016-0140-x
Zhang C, Berra L, Klompas M. Should aerosolized antibiotics be used to treat ventilator-associated pneumonia?. Respir Care. 2016;61(6):737–48. doi: 10.4187/respcare.04748
Daniels LM, Juliano J, Marx A, Weber DJ. Inhaled antibiotics for hospital-acquired and ventilator-associated pneumonia. Clin Infect Dis. 2017;64(3):386–7. doi: 10.1093/cid/ciw726
Lu Q, Girardi C, Zhang M, Bouhemad B, Louchahi K, Petitjean O, et al. Nebulized and intravenous colistin in experimental pneumonia caused by Pseudomonas aeruginosa. Intensive Care Med. 2010;36(7):1147–55. doi: 10.1007/s00134-010-1879-4
Moghaddam OM, Lahiji MN, Talebi-Taher M, Mahmoodiyeh B. Effect of inhaled colistin on the treatment of ventilator-associated pneumonia due to multi-drug resistant acinetobacter. Tanaffos. 2019;18(1):66–73.
CASP. CASP randomised controlled trial standard checklist [Diakses pada: 13 Oktober 2020]. Tersedia dari: https://casp-uk.net/wp-content/uploads/2020/10/CASP_RCT_Checklist_PDF_Fillable_Form.pdf
ARHQ. Cochrane risk of bias tool for randomized controlled trials. [Diakses pada: 27 Maret 2022]. Tersedia dari: https://methods.cochrane.org/bias/assessing-risk-bias-included-studies
Elsevier. About scopus, 2018 [Diakses pada: 12 Juli 2020]. Tersedia dari: http:// www.elsevier.com/solutions/scopus.
Elsevier. Content policy and selection Elsevier [Diakses pada: 27 Maret 2022]. Tersedia dari: https://www.elsevier.com/solutions/scopus/how-scopus-works/content/content-policy-and-selection
Liu C, Zhang YT, Peng ZY, Zhou Q, Hu B, Zhou H, et al. Aerosolized amikacin as adjunctive therapy of ventilator-associated pneumonia caused by multidrug-resistant gram-negative bacteria: A single-center randomized controlled trial. Chin Med J (Engl). 2017;130(10):1196–201. doi: 10. 4103/0366-6999.205846
Rattanaumpawan P, Lorsutthitham J, Ungprasert P, Angkasekwinai N, Thamlikitkul V. Randomized controlled trial of nebulized colistimethate sodium as adjunctive therapy of ventilator-associated pneumonia caused by gram-negative bacteria. J Antimicrob Chemother. 2010;65(12):2645–9. doi: 10.1093/jac/dkq360
Kollef MH, Ricard JD, Roux D, Francois B, Ischaki E, Rozgonyi Z, et al. A randomized trial of the Amikacin fosfomycin inhalation system for the adjunctive therapy of gram-negative ventilator-associated pneumonia: IASIS trial. Chest. 2017;151(6):1239–46. doi: 10.1016/j.chest.2016.11.026
Lu Q, Yang J, Liu Z, Gutierrez C, Aymard G, Rouby JJ, et al. Nebulized ceftazidime and amikacin in ventilator-associated pneumonia caused by Pseudomonas aeruginosa. Am J Respir Crit Care Med. 2011;184(1):106–15. doi: 10.1164/rccm.201011-1894OC
Ammar M, Abdalla W. Effect of extended infusion of meropenem and nebulized amikacin on Gram-negative multidrug-resistant ventilator-associated pneumonia. Saudi J Anaesth. 2018;12(1):89–94. doi: 10.4103/sja.SJA_148_17
Palmer LB, Smaldone GC. Reduction of bacterial resistance with inhaled antibiotics in the intensive care unit. Am J Respir Crit Care Med. 2014;189(10):1225–33. doi: 10.1164/rccm.201312-2161OC
Abdellatif S, Trifi A, Daly F, Mahjoub K, Nasri R, Ben Lakhal S. Efficacy and toxicity of aerosolised colistin in ventilator-associated pneumonia: A prospective, randomised trial. Ann Intensive Care. 2016;6(1):26. doi: 10.1186/s13613-0160127-7
Zampieri FG, Nassar AP, Gusmao-Flores D, Taniguchi LU, Torres A, Ranzani OT. Nebulized antibiotics for ventilator-associated pneumonia: A systematic review and meta-analysis. Crit Care. 2015;19(1):150. doi: 10.1186/s13054-015-0868-y
Gursel G, Demirtas S. Value of APACHE II, SOFA and CPIS scores in predicting prognosis in patients with ventilator-associated pneumonia. Respiration. 2006;73(4):503–8. doi: 10.1159/000088708
Russell CJ, Shiroishi MS, Siantz E, Wu BW, Patino CM. The use of inhaled antibiotic therapy in the treatment of ventilator-associated pneumonia and tracheobronchitis: A systematic review. BMC Pulm Med. 2016;16(1):10–6. doi: 10.1186/s12890-016-0202-8
Luyt CE, Hékimian G, Bréchot N, Chastre J. Aerosol therapy for pneumonia in the intensive care unit. Clin Chest Med. 2018;39(4):823–36. doi: 10.1016/j.ccm.2018.08.005
DOI: https://doi.org/10.15416/ijcp.2022.11.1.51
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