1. Introduction

Acinetobacter species, specifically its most known and studied species, Acinetobacter baumanii (A.baumannii), is undoubtly recognized and on the forefront of the most feared pathogen in ICU settings worldwide ^{[1, 2, 3]}. The well-known capability of acquiring resistance against various types of antibiotics and the survival characteristic under wide range of environmental conditions are not only perilling infected patients, but also threaten physicians ^{[2, 3]}. Underlying severity of illness has been documented as one of the risk factors for colonization with Acinetobacter species ^[3], but studies regarding the cut-off value of such scoring systems in predicting risk of A.baumannii colonization/infection are scarce. APACHE-II (Acute Physiology and Chronic Health Evaluation II) is one of the well-known scoring system that was found useful for classifying patients according to their disease severity ^[4], and still widely used among Indonesian ICU (Intensive Care Unit).

In the last decades, the emergence and rapid spread of Multidrug-resistant (MDR) A.baumannii have caused a serious clinical problem worldwide ^{[1, 2, 3]}. Ironically, the drug resistance pattern of A.baumannii in Indonesia, which is very critical concerning the management of infection against this pathogen, is lacking.

Therefore, the main objectives of this study were to evaluate the role of APACHE-II score in predicting A.baumannii colonization/infection and its antimicrobial resistance pattern in our teaching hospital setting.

2. Materials and Methods

A retrospective, case control investigation was performed using ICU patient’s records from January 2013 through December 2014 in Siloam Hospital Lippo Village, Tangerang, Indonesia. The case group was defined by patients admitted to ICU with positive culture of A.baumannii from any parts of body, including the excretions of secretions. Any patients in ICU with positive culture of microorganisms other than A. baumannii were classified as the control group.

The identification and antimicrobial susceptibilities of the isolates were done with Vitex-2 System® (bioMérieux, France). Zone diameter and MIC interpretive criteria for all antimicrobial agents based on the standards of Clinical Laboratory Standards Institute. Escherichia coli ATCC^® 25922, Pseudomonas aeruginosa ATCC^® 27853 were used as control strain, and Escherichia coli ATCC^® 35218 for β-lactam/β-lactamase inhibitor combinations ^[5].

The multi-drug resistance (MDR) defined as A. baumannii who was resistant to penicillin, cephalosporin, fluoroquinolone and aminoglycoside type antibotics. Extensive-drug resistance (XDR) defined as MDR along with the carbapenem resistance. Polymyxin and tigecycline resistance along with XDR was defined as Pan Drug Resistance (PDR) ^[6].

The data of both groups were collected from medical and microbiological records that include the patient demographic details, diagnosis and disease classification, the length of ICU stay, antimicrobial susceptibility patterns, and its outcome. APACHE-II score was calculated based on existing clinical data at 24-hour after cultures were obtained.

Independent T-test analysis was used to look for mean difference of APACHE-II score and length of ICU stay, between the positive A.baumannii and non-A.baumanii colonization groups. Correlation of outcome between the two groups was analysed using Pearson chi-square. The APACHE-II cut off point and diagnostic value was calculated with the Receiver Operator Characteristic (ROC) curve analysis. Statistical analyses were performed using SPSS Statistics 17^th version (SPSS Inc, 17).

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Figure 1. ROC curve for predicting A.baumanii colonization/infection

3. Results

From January 2013 through December 2014, there were 53 patients with A.baumannii colonization/infection. Of 53 patients, 14 had either missing or incomplete information. The characteristics of study population (n= 98) were shown in Table 1. The non-A.baumannii group isolate was consisted of Candida spp. (27/59), Pseudomonas spp. (11/59), Klebsiella spp. (10/59), Staphylococcus spp. (6/59), Escherichia coli (3/59), Aeromonas hydrophila (1/59) and Kodamaea Ohmeri (1/59).

Table 1. Characteristics of the study population with A.baumanii and non-A.baumanii colonization/infection (January 2013-December 2014)¹

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The majority site of A.baumanii and non-A.baumannii isolation were from the respiratory tract (sputum and bronchial fluid), accounting for 34/39 (87.1%) and 56/59 (94.9%) of all patients analysed (Table 1). A.baumanii or non-A.baumanii colonization in the wound, blood, cerebrospinal fluid, and urine were less common for both samples (Table 1).

Patients with A.baumannii colonization/infection have a significantly higher mean of APACHE-II score than non-A.baumanni group, 25.72 ± 6.20 and 23.07 ± 6.05 (p=0.038), respectively. The study found that APACHE-II score of ≥ 23 defined predicting A.baumanii colonization/infection with sensitivity of 74.4%, specificity 50.8%, accuracy level 75.0%, and likelihood ratio (LR) 1.5 as shown in Table 2.

The antibiotic susceptibility level of A.baumannii to 20 antibiotic regimens was shown in Table 3. Only 1 out of 39 samples considered MDR A.baumannii. The highest susceptibility level was shown by tigecycline (82.1%) and amikacin (84.6%). Carbapenem-Resistant A.baumannii was found in 29/39 (74.4%) samples. Trimetoprim/sulfamethoxazole was 56,4% susceptible to A.baumannii.

Table 2. Diagnostic value of various cut-off point of the APACHE-II in predicting risk of A.baumannii colononization/infection

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Table 3. Antibiotics susceptibility patterns of A.baumanii

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4. Discussion

APACHE II score and its studies regarding its role in predicting A.baumannii colonization/infection were scarce. Several studies concerning APACHE II score and increased risk of mortality rate in A.baumannii colonization/infection, and APACHE II score and increased risk of A.baumannii bacteremia were well documented ^{[7, 8, 9, 10]}. Higher mean of APACHE II score or modified APACHE II in patients with A.baumannii colonization/infection were also documented previously and in accordance with the result of this present study ^[11], but its cut-off value in depicting risk of A.baumannii acquisition was never been studied.

There were two cut-off value worthy to be considered, those were, higher or equal to 23 and ≥ 27. Both scores had their own strengths and weaknesses. APACHE II score higher or equal to 23 had lower specificity (53.8% vs. 78.0%), lower odds ratio (OR) and positive likelihood ratio (3.00 vs 3.75 and 1.51 vs. 2.45), but had higher sensitivity (74.4% vs. 53.8%), and more negative likelihood ratio (0.50 vs 0.59) than APACHE II score higher or equal to 27, respectively. The sensitivity and specificity of this APACHE II score may not matter much, but the result of odd ratio, LR+, and LR- may depict risk of A.baumannii colonization/infection. APACHE II score ≥ 23 can be used as a threshold of increased moderate risk of colonization/infection by A.baumannii (OR 3.00; LR+ 1.5), while score below the cut-off value may be considered low risk. ^[12]. APACHE II score ≥ 27 were more specific and implied a greater risk of colonization/infection by A.baumannii (OR 3.7; LR+ 2.45). We suggest using cut off value greater or equal to 23 as a cut-of value of an increased moderate risk of A.baumannii colonization/infection in ICU settings. Together with previously documented risk factors ^{[3, 10]}, such as, prolonged length of hospital stay, use of mechanical ventilation, colonization pressure, prior antibiotic therapy, recent surgery, and invasive procedures, a score of APACHE II ≥ 23 increase risk greatly to A.baumannii colonization/infection. A cut off value of ≥ 23 may not be used as an indication of empirical antibiotic therapy against A.baumanii, as study conducted in Taiwan concluded that only patients with high APACHE II score had therapeutic benefit (OR for patients with scores > 25 and ≤ 35, 0.16 [95% CI, 0.07–0.37]; OR for those with scores > 35, 0.06; 95% CI, 0.01–0.25) ^[13].

Only 1 out of 39 isolates was considered as MDR-Acinetobacter species in this current study. These inconsistencies with previous studies, where MDR Acinetobacter isolates were found in majority or all isolates ^{[11, 14]}, may be resulted because of different definition of multi-drug resistant used in the studies. Previous study conducted by Emine et al., 2009 in Turkey used the definition of MDR as diminished susceptibility to 2 or more of the following 5 antibiotic classes: antipseudomonal cephalosporins, antipseudomonal fluoroquinolones, carbapenems, β-lactam–β-lactamase inhibitor combinations, and aminoglycosides which were suggested by Paterson, 2006 ^{[11, 15]}. In this current study, MDR-Acinetobacter was defined as resistant against penicillin, cephalosporin, aminoglycoside, and fluoroquinolone ^[5], whereas resistant against more than three classes of antibiotics was categorized as MDR-Acinetobacter in study by Dent et al., 2010 ^[14]. To date, internationally, there are no accepted definitions to describe the extent of antimicrobial resistance among Acinetobacter species. Thus, a great confusion of the terms was ensued and the urgency of clarifying the definition was enforced more than ever ^[16].

The highest susceptibility level was shown by tigecycline (82.1%) and amikacin (84.6%) from this study. Amikacin and trimethoprim-sulfamethoxazole susceptibility level of this study differed greatly from the other studies. Amikacin susceptibility is still high (84.6%) compared to 15% in Emine et al., 2009 and 3% in Ntusi et al., 2012 ^{[9, 11]}. Low susceptibility of Acinetobacter to trimethoprim-sulfamethoxazole (18.5%) was found by Ntusi et al., 2012 in South Africa, while only 43.6% trimethoprim-sulfamethoxazole-resistant strain was isolated in this current study ^[9]. An inconsistent finding was found in the Indonesian studies in neonatal intensive care unit ^[17]. The different patterns of antimicrobial resistance may represent patterns of antibiotics usage in each hospital. While more studies of A.baumannii antimicrobial resistance pattern in Indonesia were needed, amikacin and tigecycline may still be considered as antibiotics of choice in treating A.baumannii infection in this local hospital. The isolation rate carbapenem-resistant strains were similar with other studies, ranging from 69-89% of all isolates ^{[9, 18]}. The high rates of resistance against carbapenems may be an indication of inappropriate or overuse of carbapenems in the hospital. This emerging resistance should not be taken lightly and must be acted upon promptly by the international health care community ^{[17, 19]}.

This study had several limitations. First, the limited methodological study design in assessing risk factors for A. baumannii acquisition may lead to selection bias, especially because of the undocumented colonization pressure and the usage of invasive equipment, such as central venous catheter (CVC), endotracheal tube (ETT), and ventilator. Second, no classification between colonization and infection of A.baumannii may statistically influence the result this study. Last, the small sample size may have affected the power of the study.

5. Conclusions

APACHE-II score was strongly correlated with A.baumannii colonization/infection and a cut-off value of APACHE II score ≥ 23 may be used to depict increased moderate risk of acquiring A.baumannii colonization/infection. No accepted definitions to describe the extent of antimicrobial resistance among Acinetobacter species may resulted in discrepancies of the prevalence of MDR-Acinetobacter, therefore the need to clarify the definition was enforced. While the use carbapenems against A. baumannii infection was not recommended, tigecycline and amikacin may be considered as antibiotics choice in treating A.baumannii infection in this local hospital.

Acknowledgement

The authors would like to express our grateful to Siloam Hospital Lippo Village for their support in this study.

Author’s Contributions

All authors equally contributed in this work.

Statement of Competing Interest

The authors have no competing interest.

Ethic

This article is original and contains unpublished material. All authors have read and approved the final manuscript and no ethical issued involved.

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