In Vitro Susceptibility Of Tigecycline Among Acinetobacter Baumanii Clinical Isolates From a Hospital in Indonesia

Acinetobacter baumanii (A. baumanii) has arisen as the most important cause of nosocomial infection, typically in severely ill patients with many comorbidities and medical supportive devices. Tigecycline is a therapeutic option for treating this infection because of its potential ability against wide spectrum of bacterias, including multi-drug resistance A. baumannii (MDRAB). Our study determine the in vitro susceptibility of tigecycline against A. baumanii isolates and the emergence of MDRAB. The frequency of isolates that were not inhibited at MIC ≤ 0.5 μg/ml was 50.46%, at MIC = 1μg/ml was 2.38%, and at MIC = 2 μg/ml was 19.07%. The susceptibility rate of tigecycline against A. baumanii was 68.27% in 2015, 79.58% in 2016, and 67.87% in 2017. In vitro result demonstrated that tigecycline had good value of MIC against A. baumanii at the range of 0.5 to 2 μg/ml.


Introduction
A. baumanii is a pleomorphic Gram negative bacilli, that accounts for approximately 17.44% of reported nosocomial infections in Indonesia. 1 This organism typically affects immunocompromised patients with medical devices, with high incidences and difficult-totreat infection due to the resistance of the bacteria.In the past decades, the rise of severe infection by this bacteria was related to the lower proportion of susceptible A. baumanii isolates which induced high mortality. 2,3er the past few decades, clinicians have noticed a significant increase in the rate of multidrug resistance A. baumannii (MDRAB).The emergence of this multi-drug resistant organism has impacted on the choice of antibiotic therapy which becoming limited, and subsequently to prolonged length-of-stay along with inflated general costs of hospitalization.[4][5] Tigecycline, a newer derivate minocycline, is a glycylcyclines that strongly counter a broad range of both Gram negative and positive

Faculty of Medicine Universitas Pelita Harapan
Jl. Boulevard Jend.Sudirman, Lippo Karawaci, Tangerang, Indonesia.Tel: +62-21-54210130; Fax: +62-21-54210133; Email: veronica.wiwing@uph.edubacterial activity, including Acinetobacter spp and multiple isolates. 4,6 Information regarding this organism and their antibiotic susceptibility profiles among hospitalized patients in Indonesia is scarce.In our hospital, the multi-drug resistant organisms was prevalent across both Gram positive and negative bacterial genera due to excessive antibiotic use.Thus, the objective of the present study was to appraise in vitro susceptibility of tigecycline against A. baumanii isolates and the emergence of MDRAB.

Materials and Methods
This study involved 692 clinical isolates of A. baumanii from patients in a hospital located in Tangerang, Indonesia from January 2015 to December 2017.This was a retrospective descriptive study on microbiology laboratory data with one isolate for each patient.Acinetobacter baumanii identification and antibiotic susceptibility testing was evaluated by colony morphological features, Gram-staining and the VITEX-2 Compact® (Biomérieux, France) system.The frequency of A. baumanii was higher in year 2016.As the number of isolates of A. baumanii decreased from January -June 2016 period to July -December 2017, the tigecycline sensitivity against it increased for the same period (Figure 1).From a total of 692 A. baumanii isolates, tigecycline MIC ranged from ≤ 0.5 to ≥ 8 µg/ml (Table 2.).Most of A. baumanii isolated in the study were multi-drug resistant with good susceptibility to tigecycline.Detailed result the activity of tigecycline were shown in  During the past decades, the incidence of multidrug resistance A. baumanii particularly carbapenem-resistant has accounted for approximately 93% of reported infection in hospital setting. 11 Several studies from different geographical regions found that the prevalence of MDRAB infection/colonization varied from 17.2% to 92.89%. 1,10-14,Thus, tigecycline is considered as the last option in the management of clinical infection caused by MDRAB.Tigecycline MIC for A. baumanii in this study varied from ≤ 0.5 to ≥ 8 µg/ml, that was comparable with a study by Talaga K, et al. which found that ESBL-producing A. baumanii, likewise isolates non-carbapenemases, had the highest MIC level of 8.0 µg/ml; for AmpCproducing A. baumanii the highest MIC level was 6.0 µg/ml; and for MBL-producing isolates the MIC level was 2.0 µg/ml. 2 Since there was no reference MIC value for in vitro tigecycline susceptibility against A. baumanii, a suitable congruence of various tigecycline MIC value sensitivity test by Pieewngam and Kiratisin was used, with sensitive at MIC ≤ 0,5 and resistant at MIC > 2 µg/ml. 2,15These values were different with EUCAST reference which MIC ≥ 1 µg/ml was regarded as resistant as these resistant strains do not have mutation that enables them to acquire resistance. 2e present study noted that tigecycline had a good in vitro activity against all isolates tested.On the other side, previous studies conducted in other province in Indonesia and India revealed high susceptibility of tigecycline (75% and 82 -88% respectively), although a sharp decline in the recent years has been marked. 1,10,12,17Previous study by Chen et al detect a decreased susceptibility rate for A. baumanii (55.3% in 2009 and 73.4% in 2010). 17most all A. baumanii were obtained from respiratory tract of inpatients ward (78.03%).

Conclusion
As tigecycline demonstrated good value of MIC in this study, ranging between ≤ 0,5 to ≤ 2 µg/ml, it could be considered an effective antibiotic against A. baumanii, especially MDRAB.Due to the absence of bactericidal activity of tigecycline, these result must be interpreted cautiously before using tigecycline for infection due to MDR organisms, particularly MDRAB.The susceptibility rate of tigecycline against MDR isolates is alarming, thus wise consumption is warranted to prevent further increase of MDR organism.

Figure 1 .
Figure 1.Number of isolates and tigecycline sensitivity against A. Baumanii from January 2015 -December 2017

Table 1 .
General features of A. baumanii isolates from clinical specimen (n total = 692)

Table 2 .
In vitro activity of tigecycline against A. baumanii isolates