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Carbapenem-Resistant Acinetobacter baumannii in Adult Intensive Care Units: Risk Factors for Colonization and Infection/Yetiskin Yogun Bakim Unitelerinde Karbapenem-Direncli Acinetobacter baumannii: Kolonizasyon ve Enfeksiyon icin Risk Faktorleri.

Introduction

Healthcare-associated infections caused by carbapenem-resistant Acinetobacter baumannii (CRAB) have been reported worldwide [1-3]. Because of their abilities to survive on inanimate hospital surfaces and to gain antimicrobial resistance, these microorganisms can cause severe infections and even outbreaks in high-risk units of hospitals, such as intensive care units (ICUs). As a result of these invasive infections, increased morbidity and mortality have been reported in predisposed patients [4,5]. Moreover, because A. baumannii can easily disseminate from patients to the hospital environment, the control of this microorganism within the ICU can be problematic [6]. Ambler class D oxacillinases (OXA enzymes) with carbapenem hydrolyzing activity, have become one of the main sources of resistance in A. baumanii during the recent years [7]. Among the genes encoding OXA-type carbapenemases, there are four main subgroups associated with A. baumannii: the chromosomally located intrinsic [bla.sub.OXA-51]-like and the acquired [bla.sub.OXA-23]-like, [bla.sub.OXA-40-like], [bla.sub.OXA-58-like] [8,9].

In previous studies, the risk factors for colonization and infection by CRAB have been outlined [2-5,10]. However, more data regarding monoclonal spread, either by colonization/infections or environmental contamination caused by CRAB, are needed to develop the best methods for managing this microorganism. Rapid investigation of the clonal relationships between strains could help to prevent outbreaks by the undertaking of necessary infection control precautions in hospitals.

The aims of the present study were as follows: (1) to determine the risk factors for colonization and/or infection caused by CRAB; (2) to determine the oxacillinase genes responsible for carbapenem resistance and evaluate antimicrobial resistance patterns; and (3) to analyze the genetic similarities of the isolates.

Materials and Methods

Settings

This prospective observational study was performed in a Turkish State Research and Training Hospital from May 2012 to April 2013. This is a 1200 bed capacity, tertiary-level reference hospital, serving not only a population of 5,445,000 inhabitants but also the surrounding cities. There are 6 major ICUs (3 medical/surgical, cardiac, neurosurgery, cardiovascular and thoracic) in the hospital, and this study was performed in two of them, which were medical/surgical ICUs (M/S ICU-1, M/S ICU-2). Either medical or surgical patients were admitted to these ICUs. These ICUs were in open structure and there were 12 and 6 beds at M/S ICU-1 and M/S ICU-2, respectively, and in M/S ICU-1, two isolation beds were available. The patient-to- nurse ratios was 2:1 for the daytime shifts and 3:1 for the night shifts. Due to the lack of staff in these ICUs, there were not enough personnel in night shifts. On the other hand these ICUs met the level 3 ICU criteria. An infection control program was implemented that included the review and implementation of infection control protocols, the use of educational sessions, and the regular reporting of surveillance results. An antibiotic restriction policy has been applied in the hospital, and according to this restriction, a prior consultation with an infectious disease specialist was required for carbapenems, piperacillin/tazobactam, intravenous quinolones, glycopeptids and colistin.

Study Design, Variables and Definitions

All adult patients [greater than or equal to]18 years old who were hospitalized in the M/S ICU for more than 48 hours were included in the study and screened for CRAB acquisition. At admission to the ICUs, active surveillance cultures (urine, blood, nasal, rectal swabs and/or sputum) were obtained from all of the patients. Rectal swab cultures were obtained weekly until discharge. When CRAB strains were isolated only from rectal swab cultures, without any sign of infection, the patients were considered colonized. Patients who were considered as colonized could not be isolated from other patients due to lack of enough physical space in the ICUs. Clinical samples were obtained from bronchoaspirate, urine, bronchoalveolar lavage, blood and other biological fluids. Only the initial isolate recovered from each patient was included in the study. It should be noted that, in isolating CRAB from a clinical sample, together with the presence of clinical signs of infection, the patient was considered infected when all of the other sources of infection were excluded. When it was not possible to identify whether the status of the patient was infected or colonized, the patient was considered colonized only. Healthcare-associated infections like ventilator-associated pneumonia, urinary tract infection or blood stream infections were classified by using CDC criteria in patients during the study period [11].

Weekly environment cultures from bed heads, infusion pumps, trolleys, manometers, door handles, soap dispensers, taps, shelves, and sink tops and hand cultures from healthcare personnel were also performed. Swabs moistened with brain-hearth infusion broth (BHI) supplemented with 0.5% beef extract were used in environmental sampling. Then swabs were dipped back into BHI. A 100[micro]l sample of the BHI was inoculated on to 5% sheep blood agar and incubated in ambient air at 37[degrees]C over nightly. Patients hospitalized for less than 48 hours in the ICU or who had an infection due to A. baumannii at admission were excluded from the study.

The following data were collected: age, sex, chronic underlying conditions (diabetes, chronic pulmonary diseases, cardiopulmonary diseases, solid tumors, hematological diseases, immunologic status), the reason for admission to the ICU, the presence of community-acquired infection, previous antibiotic usage, ICU length of stay before the isolation of A. baumannii, therapy, recent surgery, the presence of invasive procedures (parenteral nutrition, intubation or tracheotomy, and central venous catheter), and the presence of nosocomial infection according to the CDC criteria.

For this study, a file has been prepared for the Scientific Research Support Board of our hospital. In this file, the Declaration of Helsinki was signed by all researchers who participated in the study. Since it is an observational, prospective study, in the form of routine examinations for the patient that does not constitute an extra risk, additional ethics committee approval was waived.

For the detection of CRAB in rectal swabs, a modification of the CDC's protocol was used. Rectal swabs were incubated overnight in 5 mL of trypticase soy broth with a 10 [micro]g ertapenem disc. Then, 100 [micro]l of the incubated broth was subcultured on an Eosin methylene blue (EMB) agar plate. After that, EMB agar was examined for lactose-nonfermenting bacteria. Identification of the isolates, was done with a Vitek 2 (bioMerieux, France) system. A Maldi Biotyper (Bruker Daltonics, Germany) was used to confirm isolates as A. baumannii. Vitek GN AST cards were used to determine susceptibility to ampicillin-sulbactam (SAM), piperacillin (PIP), piperacillin-tazobactam (TZP), ceftazidime (CAZ), cefoperazone-sulbactam (CES), cefepime (FEP), imipenem (IPM), meropenem (MEM), amikacin (AMK), gentamicin (GEN), netilmicin (NET), ciprofloxacin (CIP), levofloxacin (LVX), tetracycline (TET), tigecycline (TGC), colistin (CST) and trimethoprim-sulfamethoxazole (SXT). The MICs of IPM, MEM, TGC and CST were additionally determined by E-test strips (bioMerieux, France). They were interpreted according to the Clinical and Laboratory Standards Institute (CLSI) breakpoints, except for TGC, for which the European Committee on Antimicrobial Susceptibility Testing (EUCAST) MIC breakpoints for Enterobacteriaceae were used [12,13]. Escherichia coli ATCC 25922 and Pseudomonas aeruginosa ATCC 27853 were used as reference strains. To investigate the most common carbapenemase genes, a multiplex PCR was performed for [bla.sub.OXA-23]-like, [bla.sub.OXA-40-like], [bla.sub.OXA-51-like] and [bla.sub.OXA-58-like] genes with the hyplex[R] CarbOxa ID test system (Amplex Diagnostics GmbH, Gars-Bahnhof, Germany), according to the manufacturer's instructions. Typing of isolates was performed using a semi-automated rep-PCR DiversiLab System (bioMerieux, France), following the manufacturer's instructions. The results were analyzed with DiversiLab software, using the modified Kullback-Leibler statistical method to determine distance matrices and the unweighted pair group method with arithmetic averages (UPGMA) to create a dendrogram. Isolates that clustered at >95% were considered related.

Statistical Analysis

A univariate analysis was performed to determine the variables associated with colonization and infection with CRAB. Contingency tables were analyzed by the two-tailed chi-square test or Fisher's test. Differences were considered significant at a p-value of [less than or equal to]0.05. Quantitative variable differences between case and control patients were compared by Student's t-test. A multiple-regression logistic model was performed to identify the potential independent risk factors for colonization/infection. Exposure variables with a p-value [less than or equal to]0.1 in the univariate analysis were included and selected using a stepwise backward process.

Results

During the study period, 310 patients were screened. One hundred fifty-one (48.7%) of them were male, the mean age was 66.9[+ or -] 17.8 years old, and the mean length of the hospital stay was 17.5[+ or -] 21.7 days (2-150 days). Demographic variables, comorbid conditions, invasive procedures, and the use of antimicrobials and other drugs are presented in detail in Table 1.One hundred three (33.2%) of the patients were colonized with CRAB. Infection occurred in 48 (43.7%) of the colonized patients, and the clinical infection versus asymptomatic carriage ratio was approximately 1:2.

CRAB colonization was detected in 103 patients, and the mean duration of time for colonization was 14.2[+ or -]10.3 days (3-55 days). The frequencies of predisposing factors were compared to investigate potential risk factors for CRAB colonization, and the results are shown in Table 2. The significant quantitative variables were found to be the mean length of ICU stay and APACHE II score at admission (Table 2). Other qualitative variables that showed statistical significance were the presence of a central venous catheter or PEG, intubation, previous history of ICU admission and the administration of carbapenems (p<0.05). Status of unconsciousness (p=.049 OR: 2.37 [95% CI: 1.35-4.14]), length of ICU stay (p=.000 OR: 0,95 [95% CI:0,93-0,98]) and prior history of carbapenem use (p=.003, OR 2.45 [95% CI: 1.36-4.41]) were found as the independent risk factors for CRAB colonization.

A total of 48 patients had infections caused by CRAB. In rectal samples of all the infected patients CRAB was isolated. The ratio between CRAB colonisation to infection was calculated approximately as, 2:1. Similar risk factors found significant for CRAB colonization were also detected to be significant for CRAB infection (Table 3). Unlike CRAB-colonized patients, CRAB infection were more detected on patients who were mechanically ventilated and enterally fed (p<0.05). When the multivariate analysis was performed for risk factors for CRAB infection, CRAB colonization (p=.000, OR 8.25 [95% CI: 3.51-19,40]), mechanical ventilator use (p=.016, OR 3.38 [95% CI: 1.25-9,149]), length of ICU stay (p=.000, OR 0.97 [95% CI: -0.96- -0.98]), and prior history of carbapenem use (p=.000, OR 2.63 [95% CI: 1.19-5,86]) were detected as independent risk factors. The morality rates in infected patients at 14 days and 30 days were detected to be higher than in controls (p<0.05).

Infection due to CRAB was detected approximately 19.2[+ or -]14.6 days after admission. The most frequent site of infection detected in these ICU patients were ventilator associated pneumonia (74.5%), surgical site infections (14.6%) and blood stream infections (10.6%).

During the study period, 103 CRAB strains were isolated from rectal swab samples and 48 from clinical samples from patients. CRAB isolates were most frequently isolated from tracheal aspirate/sputum samples (36 of the cases), followed by surgical wounds (7 of the cases) and blood (5 of the cases).

A. baumannii was isolated 19 (25%) times from the 76 different environmental samples collected during the study period. These A. baumannii isolates were also included to our study. There were no A. baumannii strains isolated from hand cultures of the staff.

All strains isolated from clinical samples and rectal swabs were found to be resistant to PIP, TZP, CAZ, FEP, IPM, MEM, CIP and LEV; 99.25% of isolates were resistant to SAM, 83.85% were resistant to CES, 68.31% were resistant to AMK, 61.27% were resistant to GEN, 25.78% were resistant to NET, 78.20% were resistant to TET, 20.30% were resistant to TGC, and 67.61% were resistant to SXT. Of the isolates, 99.27% were susceptible to CST, which was the most active agent against all of the isolates.

When analyzed by multiplex-PCR, all of the isolates, including the isolates from environmental samples, were found to harbour the [bla.sub.OXA-23] and [bla.sub.OXA-51] genes; in contrast, the [bla.sub.OXA-40] and [bla.sub.OXA-58] genes were not detected in any of them.

Molecular typing of 157 CRAB isolates (102 from rectal swabs, 36 from clinical samples, 19 from environmental samples) was performed using the DiversiLab system. We tried to study all of the samples with DiversiLab system but we got valid results from only 157 of the samples. Using a similarity index of >95%, 129 (82.17%) isolates (86 from rectal samples, 25 from clinical samples and 18 from the environmental samples) were clustered into one large cluster (Figure 1). The majority of the CRAB isolates in the cluster (97.67%) were multidrug resistant.

Discussion

Hospital acquired infections due to CRAB cause serious problems in ICUs; moreover, they tend to spread to the other parts of hospitals [1-3]. In order to develop the best means of managing this microorganism, more data regarding monoclonal spread, either colonization or infections, caused by CRAB are needed. With this present study, comprehensive information about the molecular and clinical epidemiology, antimicrobial susceptibility patterns and monoclonal spread of CRAB was provided.

In the pathogenesis of hospital-acquired infections, most of the time, colonization is the first step. In our study colonization appeared approximately in two weeks time. The length of ICU stay was an important factor for CRAB colonization or infection, and the colonization ratio increased when the length of stay was extended [2, 14]. At the end of our study, we detected that the mean length of stay in the ICU of the colonized or infected patients was longer than that of the non-infected and non-colonized patients. A high APACHE II score, a presence of invasive devices and a history of previous ICU hospitalization were all significant risk factors by the univariate analysis for both CRAB colonization and infection. Reduced consciousness on physical examination was a risk factor for both colonization and infection by CRAB. As these types of patients can have impaired nasopharyngeal protective mechanisms, and they require intubation more than others, microorganisms are easily able first to colonize and then to infect the host. The current study showed that invasive procedures, such as intubation and colonization with CRAB, were independent risk factors, as seen by the multivariate analysis of CRAB infection. In most studies investigating the pathogenesis of ventilator-associated pneumonia, it has been shown that intubation tubes could be colonized easily by microorganisms, and after this step, infection could occur [15-18]. Our study results were consistent with these studies.

Previous studies have repeatedly shown that, there is a correlation between antibiotic exposure and multidrug resistance emergence [2, 19, 20]. Antibiotics generate resistance, and they have a selective pressure effect on resistance genes. As a result of our study only carbapenem use was found to be an independent risk factor for infections caused by CRAB.

In some of the studies, increased mortality and prolonged hospital and ICU stays were detected due to CRAB, but mortality rate was not found to be high when the severity of illness or underlying conditions was controlled for [10,20].In our study, the mortality rate was higher in both CRAB-colonized and CRAB-infected patients. For treatment of CRAB-infected patients, only CST could be used. During the study period, due to the reimbursement rules in Turkey, CST was administered only when the infection was documented microbiologically; this situation caused a time gap for treatment between the beginning of infection and its microbiologic documentation. We believe that this late beginning of treatment might have caused the high mortality rate.

In our study, CRAB was isolated from clinical samples, surveillance cultures and the environment. As a result of the analysis of these CRAB strains, all of them possessed the [bla.sub.OXA-51] gene and [bla.sub.OXA-23] gene, and none of them harboured the [bla.sub.OXA-40] and [bla.sub.OXA-58] genes, similar to previous studies from our region [21, 22]. The [bla.sub.OXA-51] gene is an intrinsic chromosomal gene naturally occurring in all A. baumanni strains [8, 23]. Among various mechanisms of carbapenem resistance OXA enzymes have become one of the main sources of resistance in recent years [7]. OXA-23 enzymes spread to many worldwide location, including Europe (including Turkey), Asia, and South America [22-27]. Between 1999 to 2009, the CRAB isolates from several Mediterranean countries, including Greece, Turkey and Italy, predominantly carried the [bla.sub.OXA-58] carbapenemase gene. Since 2009, OXA-58 has been increasingly replaced by OXA-23 in these countries [28]. Perez et al. reported that global spread of CRAB was associated with a multidrug-resistant clone designated as European or International clone II, which harbours the [bla.sub.OXA-23] gene [25]. According to our results, although all of the isolates harboured the [bla.sub.OXA-51] gene, OXA-23 was the main oxacillinase enzyme for resistance to carbapenems in CRAB strains isolated from our hospital.

As a result of our study, when analyzed by rep-PCR, the CRAB isolates formed one large cluster in our hospital. In previous studies, it was observed that A. baumannii outbreaks usually originated from a single clone or a single dominant clone [8,29,30]. CRAB isolates isolated from 18 of the 19 environmental samples (94,74%) were in the large cluster. This finding suggested that the environment acted as a reservoir in the spread of CRAB in the hospital. Similar results have been reported before [29]. Our data suggested that cross-contamination between patients and environmental surfaces caused the persistence of CRAB in our hospital.

In our study, CRAB isolates were found to be highly resistant to the majority of the tested antibiotics. CST was the most effective antibiotic. TGC and NET were found to be the next most effective antibiotics after CST. In several studies conducted worldwide, as well as our country, CST and TGC were reported to be most effective antimicrobial agents against multidrug resistant A. baumannii [8, 20, 27, 29, 31]. In our study, all of the isolates were resistant to IPM and MEM. Resistance to carbapenems is usually accompanied by resistance to other antibiotics, thus limiting the options for therapy [27,29]. In agreement with these data, we found that the CRAB isolates were also highly resistant to many antibiotics in general use. The majority of the isolates in the dominant clone were multidrug resistant.

As an additional note, CRAB rates of our patients were found to be higher in the 10%, 25%, 50% and 75% percentiles than the UHESA (National Hospital Infections Surveying System) report percentiles and the same in the 90% percentile (100), as in the other education and research hospitals in 2012-2013.

There were some limitations of this study. First of all, due to economic inadequacy study was designed for a limited duration and only limited number of patients was included to the study.

Similarly, active surveillance cultures could not be performed as frequent as desired, this was especially important to detect the specific day of CRAB colonization accurately. Also, hand hygiene rates have not been checked during our study. Besides these facts, although the patients were followed closely for their clinical status and microbiological results, it was sometimes very difficult to decide whether the patients were colonised or infected. Forty-eight hours after hospitalization, CRAB screening was performed. No screening was done at the first hospitalization. Also the previous year's CRAB isolation rate in the ICUs which we conducted our study has not been recorded. So, we did not have the opportunity to compare our results to previous year's. The strengths of our study include that this was a prospective study and performed at two differently located ICUs, reference techniques were used for processes like identifying A. baumannii, testing the antimicrobial susceptibility pattern and determining the molecular typing of the isolates.

Conclusions

In conclusion, by using rapid diagnostic methods, we detected that most of our patients were colonized and/or infected with only one clone of CRAB. In addition, strains belonging to this large clone were also isolated from environmental cultures. All of these facts indicated to us that healthcare personnel compliance with infection control measures was relatively poor. Although CRAB was not isolated from healthcare workers' hands, we believe that, after the contamination of the environment with CRAB, healthcare personnel's hands were the responsible agent for the spread of the microorganism in the hospital.

Acknowledgements

Conflict of interest statement: None declared.

Funding sources: This study was funded by Scientific Research Support Board of Ankara Numune Training and Research Hospital. The funding source had no involvement in study design; in the collection, analysis and interpretation of data; in the writing of the report; and in the decision to submit the article for publication. The funding source only provided necessary budget to supply equipment for laboratory tests.

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Neriman Aksu Koca (1), Irmak Baran (1), Meltem Arzu Yetkin (2), Dilek Kanyilmaz (3), Ipek Mumcuoglu (1), Hatice Yagmurdur (4), Aliye Bastug (2), Sema Alacam (1), Nevzat Mehmet Mutlu (4), Hurrem Bodur (2),

(1) Ankara Numune Training and Research Hospital, Medical Microbiology Laboratory, Ankara, Turkey.

(2) Ankara Numune Training and Research Hospital, Clinic of Infectious Diseases and Clinical Microbiology, Ankara, Turkey.

(3) Ankara Numune Training and Research Hospital, Infection Control Committee, Ankara, Turkey.

(4) Ankara Numune Training and Research Hospital, Clinic of Anesthesiology, Reanimation and Intesive Care, Ankara, Turkey.

Corresponding author: Irmak Baran MD, Ankara Numune Training and Research Hospital, Medical Microbiology, Ankara, Turkey

Phone: +905326436175

E-mail: irmakmor@yahoo.com

13.12.2017

28.08.2018

Part of this study was presented as a poster presentation in 24th ECCMID in May 2014.

Running title: Carbapenem-resistant A. baumannii in ICU

Part of this study was presented as a poster presentation in 24th ECCMID in May 2014.

DOI: 10.4274/mjima.2018.25
Table 1: Epidemiologic and Predisposing Features of Patients Colonized
or Infected with A. baumannii

Variable                          Whole set of patients
                                  N=310 (%)

Male sex                          151 (48.7)
Median age, years                  66.9[+ or -] 17.8
APACHE II at admission             17.47[+ or -] 7.24
Concomitant diseases
Chronic non-fatal CVD ([dagger])  110 (35.5)
Diabetes mellitus                  72 (23.2)
Chronic pulmonary disease          51 (16.5)
Cancer                             57 (18.4)
Neurologic disability              76 (24.5)
Central venous catheter           213 (68.7)
Mechanical ventilation            169 (54.5)
PEG ([double dagger])              22 (7.1)
Enteral feeding                   193 (62.3)
Parenteral nutrition              139 (44.8)
Trauma                             61 (19.7)
Surgery                            95 (30.6)
Steroid usage                      81 (26.1)
Unconsciousness on physical       169 (54.5)
examination
Prior history of ICU admission     61 (19.7)
Mean duration of length of stay    17.54[+ or -]21.69
Prior antibiotic usage
Piperacillin/tazobactam            76 (24.5)
Cephalosporin                      76 (24.5)
Carbapenem                         87 (28.1)
Fluoroquinolones                   46 (14.8)
Mortality in 30 days              102 (32.9)

Variable                          Colonized with CRAB (*)
                                  N=103 (%)

Male sex                          54 (52.4)
Median age, years                 69.1[+ or -] 16.4
APACHE II at admission            19.52[+ or -] 6.66
Concomitant diseases
Chronic non-fatal CVD ([dagger])  41 (39.8)
Diabetes mellitus                 31 (30.1)
Chronic pulmonary disease          7 (6.8)
Cancer                            16 (15.5)
Neurologic disability             32 (31.1)
Central venous catheter           90 (87.4)
Mechanical ventilation            74 (71.8)
PEG ([double dagger])             15 (14.6)
Enteral feeding                   82 (79.6)
Parenteral nutrition              51 (49.5)
Trauma                            24 (23.3)
Surgery                           36 (35.0)
Steroid usage                     17 (16.5)
Unconsciousness on physical       36 (65.0)
examination
Prior history of ICU admission    32 (31.1)
Mean duration of length of stay   30.43[+ or -]28.29
Prior antibiotic usage
Piperacillin/tazobactam           28 (27.2)
Cephalosporin                     18 (17.5)
Carbapenem                        46 (44.7)
Fluoroquinolones                  12 (11.7)
Mortality in 30 days              46 (44.7)

Variable                          Infected with CRAB (*)
                                  N=48 (%)

Male sex                          25 (52.1)
Median age, years                 71.6[+ or -] 14.9
APACHE II at admission            20.26[+ or -] 4.91
Concomitant diseases
Chronic non-fatal CVD ([dagger])  21 (43.8)
Diabetes mellitus                 15 (31.3)
Chronic pulmonary disease          3 (6.3)
Cancer                             6 (12.5)
Neurologic disability             18 (37.5)
Central venous catheter           44 (91.7)
Mechanical ventilation            42 (87.5)
PEG ([double dagger])              7 (14.6)
Enteral feeding                   44 (91.7)
Parenteral nutrition              28 (58.3)
Trauma                            15 (31.3)
Surgery                           16 (33.3)
Steroid usage                      9 (18.8)
Unconsciousness on physical       30 (62.5)
examination
Prior history of ICU admission    14 (29.2)
Mean duration of length of stay   41.00[+ or -]27.22
Prior antibiotic usage
Piperacillin/tazobactam           13 (27.1)
Cephalosporin                      4 (8.3)
Carbapenem                        27 (56.3)
Fluoroquinolones                   2 (4.2)
Mortality in 30 days              32 (66.7)

(*) = Carbapenem-resistant A. baumannii
([dagger]) = Cardiovasculardisease
([double dagger]) =Percutaneous endoscopic gastrostomy

Table 2: Matched univariate and multivariate analyses of risk factors
for CRAB (*) colonization ([dagger])

                                   CRAB (*)           Not CRAB (*)
                                   colonized          colonized
                                   N=103              N=207

Age (years)                        69.08[+ or -]16.4   65.9[+ or -]18,4
Male sex                           54                  97
APACHE II score                    19.5[+ or -]6.8     16.4[+ or -]7.3
Comorbid conditions
Chronic pulmonary disease           7                  15
Chronic cardiovascular             41                  66
disease
Diabetes mellitus                  31                  41
Neurologic disability              32                  49
Renal failure                       2                  10
Cancer                             16                  41
Predisposing factors
Central venous catheter            90 (87.4)          123 (59.4)
Mechanical ventilator              74 (71.8)           95 (45.9)
Presence of PEG ([double dagger])  15 (14.6)            7 (3.4)
Parenteral nutrition               51 (49.5)           88 (42.5)
Enteral feeding                    82 (79.6)          111 (53.6)
Immunosuppression                   8 (7.8)            15 (7.2)
Being on hemodialysis              12 (11.7)           19 (9.2)
Surgery                            36 (35.0)           59 (28.5)
Previous history of ICU            32 (31.1)           29 (14.0)
hospitalization
Length of ICU stay (days)          30.4[+ or -]28.2    11.2[+ or -]13.6
Reduced consciousness on           67 (65.0)           74 (35.7)
physical examination
Prior antibiotic usage
Piperacillin/tazobactam            28 (27.2)           48 (23.2)
Cephalosporin                      18 (17.5)           58 (28.0)
Carbapenem                         46 (44.7)           41 (19.8)
Fluoroquinolones                   12 (11.7)           34 (16.4)
Mortality in 30 days               46 (44.7)           56 (27.1)

                                   Univariate  Multivariate analysis
                                   analysis
                                   p           p       OR
                                                      (95% CI)

Age (years)                        0.139
Male sex                           0.399
APACHE II score                    0.000
Comorbid conditions
Chronic pulmonary disease          1.00
Chronic cardiovascular             0.205
disease
Diabetes mellitus                  0.047
Neurologic disability              0.172
Renal failure                      0.349
Cancer                             0.437
Predisposing factors
Central venous catheter            0.000       0.194  1.62(0.74-3.31)
Mechanical ventilator              0.000       0.913  1.04(0.53-2.02)
Presence of PEG ([double dagger])  0.000       0.724  1.26(0.35-4.55)
Parenteral nutrition               0.276
Enteral feeding                    0.000       0.771  1.11(0.54-2.20)
Immunosuppression                  0.823
Being on hemodialysis              0.548
Surgery                            0.295
Previous history of ICU            0.01        0.521  1.27(0.64-2.54)
hospitalization
Length of ICU stay (days)          0.000       0.000  0.95(0.93-0.98)
Reduced consciousness on           0.000       0.049  2.37(1.35-4.14)
physical examination
Prior antibiotic usage
Piperacillin/tazobactam            0.484
Cephalosporin                      0.050
Carbapenem                         0.000       0.003  2.45(1.36-4.41)
Fluoroquinolones                   0.311
Mortality in 30 days               0.005

(*) = Carbapenem-resistant A. baumannii
([dagger]) = Data are expressed as numbers (%) of patients except where
stated.
([double dagger]) =Percutaneous endoscopic gastrostomy

Table 3: Matched univariate and multivariate analyses of risk factors
for CRAB (*) infection ([dagger])

                                   Infected with     Not  infected
                                   CRAB (*)          with CRAB (*)
                                   N=48              N=262

Age (years)                        71.6[+ or -]14.0   66.1[+ or -]18.2
Male sex                           25 (52.1)         126 (48.1)
APACHE II score                    20.3[+ or -]4.9    16.9[+ or -]7.5
Comorbid conditions
Chronic pulmonary disease           3 (6.3)           19 (7.3)
Chronic cardiovascular disease     21 (43.8)          86 (32.8)
Diabetes mellitus                  15 (31.3)          57 (21.8)
Neurologic disability              18 (37.5)          63 (24.0)
Cancer                              6 (12.5)          51 (19.5)
Predisposing factors
Central venous catheter            44 (91.7)         169 (64.5)
Mechanical ventilator              42 (87.5)         127 (48.5)
Presence of PEG ([double dagger])   7 (14.6)          15 (5.7)
Parenteral nutrition               28 (58.3)         111 (42.4)
Enteral feeding                    44 (91.7)         149 (56.9)
Immunosuppression                   5 (10.4)          18 (6.9)
Surgery                            16 (33.3)          79 (30.2)
Previous history of ICU stay       14 (29.2)          47 (17.9)
Length of ICU stay (days)          41.0[+ or -]27.2   13.2[+ or -]17.5
Reduced consciousness on           30 (62.5)         111 (42.4)
physical examination
Prior antibiotic usage
Piperacillin/tazobactam            13 (27.1)          63 (24.0)
Carbapenem                         27 (56.3)          60 (22.9)
Colonization with CRAB (*)         39 (81.3)          57 (21.8)
Mortality in 30 days               32 (66.7)          70 (26.7)

                                   Univariate  Multivariate analysis
                                   analysis
                                   p           p       OR
                                                      (95% CI)

Age (years)                        0.051
Male sex                           0.644
APACHE II score                    0.000       0.849  0.99 (0.93-1.06)
Comorbid conditions
Chronic pulmonary disease          1.00
Chronic cardiovascular disease     0.186
Diabetes mellitus                  0.192
Neurologic disability              0.072
Cancer                             0.314
Predisposing factors
Central venous catheter            0,000       0.965  0.97 (0.25-3.71)
Mechanical ventilator              0.000       0.016  3.38 (1.25-9.14)
Presence of PEG ([double dagger])  0.058
Parenteral nutrition               0.057
Enteral feeding                    0.000
Immunosuppression                  0.373
Surgery                            0.734
Previous history of ICU stay       0.078
Length of ICU stay (days)          0.004       0.000  0.97 (0.96-0.98)
Reduced consciousness on           0.012       0.345  0.64(0.26-1.61)
physical examination
Prior antibiotic usage
Piperacillin/tazobactam            0.715
Carbapenem                         0.000       0.018  2.63(1.19-5.86)
Colonization with CRAB (*)         0.000       0.000  8.25 (3.51-19.40)
Mortality in 30 days               0,000

(*) = Carbapenem-resistant A. baumannii
([dagger]) =Data are expressed as numbers (%) of patients except where
stated.
([double dagger]) =Percutaneous endoscopic gastrostomy
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Title Annotation:Research article
Author:Koca, Neriman Aksu; Baran, Irmak; Yetkin, Meltem Arzu; Kanyilmaz, Dilek; Mumcuoglu, Ipek; Yagmurdur,
Publication:Mediterranean Journal of Infection, Microbes and Antimicrobials
Article Type:Report
Date:Jan 1, 2018
Words:6051
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