Ventilatör ilişkili pnömoni etkeni çok ilaca dirençli Acinetobacter baummannii suşlarında sefoperazon-sulbaktam ile netilmisin kombinasyonunun in-vitro sinerjistik etkisi

Çoklu ilaç dirençli (ÇİD) Acinetobacter baumannii suşları son yıllarda yoğun bakım ünitelerinde (YBÜ), özellikle ventilatör ilişkili pnömoni (VİP) etkeni olarak giderek artan oranda morbidite ve mortaliteye neden olmaktadır. Ülkemizde bir çok merkezde olduğu gibi hastanemizde de ÇİD-A.baumannii izolatlarına en etkili antibiyotikler arasında sefoperazon-sulbaktam ve netilmisin bulunmaktadır ve sıklıkla kombine tedavi olarak kullanılmaktadır. Çalışmamızda Ocak-Haziran 2006 tarihleri arasında 5 farklı YBÜ’den VİP etkeni olarak izole edilmiş 25 ÇİD-A.baumannii izolatının sefoperazon-sulbaktam ve netilmisine in-vitro duyarlılıkları ve sinerjistik aktiviteleri E-test yöntemiyle incelenmiştir. Fraksiyone inhibitör konsantasyon indeksi ise FIC=MİKAB/MİKA+MİKBA/MİKB formülü ile hesaplanmıştır. MİK50 ve MİK90 değerleri sefoperazon-sulbaktam için sırasıyla 24 µg/ml ve 256 µg/ml, netilmisin için ise 2 µg/ml ve 16 µg/ml olarak bulunmuştur. Suşların % 44’ü sefoperazon-sulbaktama, % 8’i netilmisine dirençli olarak saptanmıştır. FIC indeksine göre çalışılan suşların hiçbirinde sinerjistik veya antagonistik etki gözlenmemiştir. Sekiz suşta (% 32) additif, 17 suşta (% 68) ise indifferent etki saptanmıştır. Sonuç olarak ÇİD-A.baumannii infeksiyonlarında sefoperazon-sulbaktam ile netilmisin kombinasyonu önemli bir avantaj sağlamamakta gibi görünmektedir. Ancak dezavantaj da oluşturmadığından orta duyarlılık gösteren suşlarda kombinasyon düşünülebilir. Kombinasyonda sağlanacak sinerjistik etki suşa özel olduğundan ideal yaklaşım, kombinasyon uygulanacak her hastada etkinin in-vitro değerlendirilmesidir.

Anahtar Kelimeler:

Sulbaktam, İlaç direnci, çoklu, bakteriyel, Acinetobacter baumannii, Pnömoni, ventilatör ilişkili, Sefoperazon, İlaç kombinasyonları, Mikrobiyal duyarlılık testleri, Netilmisin

In vitro synergistic effect of cefoperazone-sulbactam and netilmicin combination in multidrug resistant Acinetobacter baumannii strains isolated from ventilator associated pneumonia

Multidrug resistant (MDR) Acinetobacter baumannii, recently, leads to an increasing morbidity and mortality in intensive care units (ICU), especially related to ventilator associated pneumonia (VAP). Cefoperazone-sulbactam and netilmicin are most effective antimicrobials against MDR-A.baumannii isolates in our hospital as well as in many centers in Turkey, and they are frequently used as combined therapy. Twenty five MDR-A.baumannii strains isolated from VAP cases in 5 different ICUs between January and June 2006 were enrolled in the study. In vitro susceptibilities and synergistic activities of the isolates for cefoperazone-sulbactam and netilmicin were tested by E-test method. Fractional inhibitory concentration index was calculated with the formula: FIC= MICAB/MICA+MICBA/MICB. MIC50 and MIC90 values were determined as 24 µg/ml and 256 µg/ml for cefoperazone-sulbactam, and 2 µg/ml and 16 µg/ml for netilmicin, respectively. Of the strains, 44 % were resistant to cefoperazone-sulbactam, and 8 % to netilmicin. None of the isolates revealed synergistic or antagonistic activity according to the FIC index. Additive activity was seen in 8 (32 %), and indifferent activity in 17 (68 %) isolates. In conclusion, the combination of cefoperazone-sulbactam and netilmicin does not seem to have advantage in the treatment of MDR-A.baumannii infections. Nevertheless, since it does not also have any disadvantage, it can be considered in the treatment of Acinetobacter infections which developed with intermediate susceptible strains. Since the synergistic activity is specific to the strain, ideal approach is in vitro evaluation of the activity for each patient.

Keywords:

Sulbactam, Drug Resistance, Multiple, Bacterial, Acinetobacter baumannii, Pneumonia, Ventilator-Associated, Cefoperazone, Drug Combinations, Microbial Sensitivity Tests, Netilmicin,

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1. Akan OA: Acinetobacter baumannii izolatlarının antibiyotik direnci: 2002 yılı ibni Sina Hastanesi verileri, Mikrobiyol Bült 2003;37(4):241-6.
2. Arda B, Sipahi OR, Yamazhan T et al: Short-term effect of antibiotic control policy on the usage patterns and cost of antimicrobials, mortality, nosocomial infection rates and antibacterial resistance, J Infect 2007; 55(1):41-8.
3. Chastre J: Infections due to Acinetobacter baumannii in the ICU, Semin Respir Crit Care Med 2003;24(1):69-78.
4. Clark NM, Patterson J, Lynch JP 3rd: Antimicrobial resistance among Gram-negative organisms in the intensive care unit, Curr Opin Crit Care 2003;9(5):413-23.
5. Clinical and Laboratory Standards Institute: Performance Standards for Antimicrobial Susceptibility Testing; Seventeenth Informational Supplement, CLSI document M100-S17, CLSI, Wayne, Pennsylvania (2007).
6. Ferrara AM: Potentially multidrug-resistant nonfermentative Gram-negative pathogens causing nosocomial pneumonia, Int J Antimicrob Agents 2006;27(3):183-95.
7. Garnacho J, Sole-Violan J, Sa-Borges M, Diaz E, Rello J: Clinical impact of pneumonia caused by Acinetobacter baumannii in intubated patients: A matched cohort study, Crit Care Med 2003;31(10):2478-82.
8. Joly-Guillou ML, Decré D, Herrman JL, Bourdelier E, Bérgogne-Bérézin E: Bactericidal in vitro activity of beta-lactams and beta-lactamase inhibitors, alone or associated, against strains of Acinetobacter baumannii: effect of combination with aminoglycosides, J Antimicrob Chemother 1995;36(4):619-29.
9. Korten V, Ulusoy S, Zarakolu P, Mete B and Turkish MYSTIC Study Group: Antibiotic resistance surveillance over a 4-year period (2000-2003) in Turkey: results of the MYSTIC Program, Diagn Microbiol Infect Dis 2007;59(4):453-7.
10. Savov E, Chankova D, Vatcheva R, Dinev N: In vitro investigation of the susceptibility of Acinetobacter baumannii strains isolated from clinical specimens to ampicillin-sulbactam alone and in combination with amikacin, Int J Antimicrob Agents 2002;20(5):390-2.
11. Timurkaynak F, Can F, Kurt Azap O, Demirbilek M, Arslan H, Ozbalıkcı Karaman S: In vitro activities of non-traditional antimicrobials alone or in combination against multidrug-resistant strains of Pseudomonas aeruginosa and Acinetobacter baumannii isolated from intensive care units, Int J Antimicrob Agents 2006;27(3):224-8.
12. Tripodi MF, Durante-Mangoni E, Fortunato R, Utili R, Zarrilli R: Comparative activities of colistin, rifampicin, imipenem and sulbactam/ampicillin alone or in combination against epidemic multidrug-resistant Acinetobacter baumannii isolates producing OXA-58 carbapenemases, Int J Antimicrob Agents 2007;30(6):537-40.
13. Turner PJ, Greenhalgh JM and MYSTIC Study Group (Europe): The activity of meropenem and comparators against Acinetobacter strains isolated from European hospitals, 1997-2000, Clin Microbiol Infect 2003;9(6):563-7.
14. Yücesoy M, Yuluğ N, Kocagöz S, Ünal S, Çetin S, Çalangu S and Study Group: Antimicrobial resistance of gram-negative isolates from intensive care units in Turkey: Comparison to previous three years, J Chemother 2000;12(4):294-8.