Tingkat Resistensi Enterobacteriaceae terhadap Quinolone: Kajian terhadap Isolat Klinis Penghasil dan Bukan Penghasil AmpC Beta-Laktamase

Stefani Anindita Paramitasanti Pramana Gentur Sutapa, Prof. Dr. dr. Osman Sianipar, DMM., M.Sc., Sp.PK, Subsp. P.I.(K), Subsp. Onk.(K); Dr. dr. Teguh Triyono, M.Kes., Sp.PK, Subsp. B.D.K.T.(K), Subsp. K.V.(K)

2025 | Tesis | S2 Kedokteran Klinik

Latar belakang: Quinolone merupakan antibiotik sintetis yang penggunaannya luas. Prevalensi Enterobacteriaceae yang resisten terhadap antibiotik Quinolone dilaporkan cukup tinggi, berkisar 18-55%. Enterobacteriaceae penghasil AmpC Beta-laktamase merupakan salah satu kuman penting yang berperan dalam penyebaran resistensi antibiotik multiobat karena memiliki plasmid yang dapat menyebarkan ke kuman lainnya. Penyebaran resistensi antibiotik Quinolone juga dilaporkan dapat melalui plasmid, yakni melalui gen plasmid mediated quinolone resistance (PMQR). Enterobacteriaceae penghasil extended spectrum beta lactamase (ESBL) dilaporkan memiliki hubungan dengan penyebaran gen PMQR. Penelitian tentang hubungan resistensi antibiotik Quinolone pada Enterobacteriaceae penghasil AmpC Beta-laktamase belum banyak dilaporkan.

Tujuan: Mengevaluasi tingkat resistensi isolat klinis Enterobacteriaceae penghasil AmpC Beta-laktamase terhadap antibiotik Quinolone.

Metode: Penelitian ini merupakan studi observasional potong lintang di RSUP Dr. Sardjito dengan subjek penelitian adalah isolat klinis Enterobacteriaceae (E. coli, K. pneumoniae, dan P. mirabilis) berdasarkan hasil kultur identifikasi alat Vitek 2 Compact. Isolat klinis diuji dengan AmpC disc test menggunakan larutan phenylboronic acid (PBA) untuk mengidentifikasi kemampuannya menghasilkan AmpC Beta-laktamase dan akan dikelompokkan menjadi dua kelompok. Uji kepekaan antibiotik quinolone dilakukan dengan metode microdilution broth otomatis dengan Vitek 2 Compact. Uji proporsi dua populasi dilakukan untuk menilai perbedaan tingkat resistensi quinolone di antara kedua kelompok. Uji variabel kategorik menggunakan uji Chi-Square dan Fisher Exact test dengan batas kemaknaan p<0>

Hasil: Sebanyak 109 isolat klinis terkumpul pada penelitian ini, 43,12% penghasil AmpC Beta-laktamase dan 56,88% bukan penghasil AmpC Beta-laktamase. Tingkat resistensi Enterobacteriaceae terhadap quinolone sebesar 74,3%. Enterobacteriaceae penghasil AmpC Beta-laktamase memiliki tingkat resistensi terhadap quinolone sebesar 89,36%, lebih tinggi dibanding bukan penghasil AmpC Beta-laktamase sebesar 62,90% (p=0,002).

Simpulan: Enterobacteriaceae penghasil AmpC Beta-laktamase memiliki tingkat resistensi terhadap quinolone secara signifikan lebih tinggi dibandingkan bukan penghasil AmpC Beta-laktamase.

Background: Quinolone is a widely used synthetic antibiotic. The prevalence of Enterobacteriaceae resistant to quinolone antibiotics is reported to be quite high, ranging from 18-55%. AmpC Beta-lactamase-producing Enterobacteriaceae are one of the important germs that play a role in the spread of multidrug resistance because they have plasmids that can spread to other germs. The spread of quinolone resistance is also reported to be through plasmids, namely through the plasmid mediated quinolone resistance (PMQR) gene. Enterobacteriaceae producing extended spectrum beta lactamase (ESBL) is reported to have an association with the spread of PMQR genes. Research on the relationship of quinolone antibiotic resistance in AmpC Beta-lactamase-producing Enterobacteriaceae has not been widely reported.

Objective: To evaluate the resistance rates of AmpC Beta-lactamase-producing Enterobacteriaceae to quinolone antibiotics

Methods: This study is a cross-sectional observational study at Dr. Sardjito General Hospital with the research subjects being clinical isolates of Enterobacteriaceae (E. coli, K. pneumoniae, and P. mirabilis) based on the results of Vitek 2 Compact culture identification. Clinical isolates were tested with the AmpC disc test using phenylboronic acid (PBA) solution to identify their ability to produce AmpC Beta-lactamase and were grouped into two groups. Quinolone antibiotic susceptibility testing was performed using the automatic microdilution broth method with Vitek 2 Compact. A two-population proportion test was performed to assess the difference in quinolone resistance levels between the two groups. Categorical variables were tested using the Chi-Square test and Fisher's Exact test with a significance level of p<0>

Result: A total of 109 clinical isolates were collected in this study, 43.12% of which produced AmpC Beta-lactamase and 56.88% did not produce AmpC Beta-lactamase. The resistance rate of Enterobacteriaceae to quinolones was 74.3%. Enterobacteriaceae producing AmpC Beta-lactamase had a resistance rate to quinolones of 89.36%, which was higher than that of non-AmpC Beta-lactamase producers at 62.90% (p=0.002).

Conclusion: AmpC Beta-lactamase–producing Enterobacteriaceae have significantly higher quinolone resistance rates than non–AmpC Beta-lactamase–producing clinical isolates.

Kata Kunci : Enterobacteriaceae, AmpC Beta-laktamase, resisten quinolone, PMQR