الفهرس 
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Abstract
Infection is the leading cause of death in medical intensive care units (ICUs) and accounts for 40% of all ICU expenditures. ICU patients are more likely than ward patients to acquire infections while hospitalized with an attributable mortality up to 25%.
ICU patients are highly vulnerable to nosocomial infection because of devices, immune compromise caused by underlying diseases or medications, poor nutritional states, uncontrolled hyperglycemia, and sepsis, which can lead to a paradoxical immune suppression. Multidrug-resistant (MDR) pathogens represent a substantial proportion of nosocomial infections in the ICU.
The reservoirs of resistant organisms include niches in the human microbiome, the microbiota of skin, respiratory epithelium, and the gastrointestinal tract which are altered within a few days in the hospital. Patients who are colonized with resistant bacteria serve inadvertently as potential reservoirs for transmission, colonization pressure.
Carbapenems are bactericidal β-lactam antimicrobials with proven efficacy in severe infections caused by extended spectrum β-lactamase (ESBL) producing bacteria.
Carbapenem-resistant Enterobacteriaceae (CRE) is an emerging problematic infectious agent, with reports of its prevalence worldwide.Invasive infections caused by CRE are associated with high mortality rates of about 40%–50%.
Patients admitted to the intensive care unit (ICU) are at high-risk of contracting infection caused by multidrug-resistant microorganisms, and often receive empirical broad-spectrum antibiotics, including carbapenem. These patients have a high-risk of CRE colonization, and subsequent CRE infection.
The Centers for Disease Control and Prevention (CDC) have emphasized that healthcare facilities must intervene to prevent CRE transmission.Active surveillance culture of CRE (ASC-CRE) in high-risk units has been reported to significantly reduce nosocomial transmission of carbapenem-resistant Klebsiella pneumoniae colonization and infection. Active surveillance in ICUs is a highly cost-effective means of decreasing CRE infection and mortality in areas with low CRE prevalence. Thus, ASC-CRE is recommended in high-risk settings, such as ICUs, to prevent CRE outbreaks or invasive infections.
Therefore the aim of this study was determination the incidence of intestinal colonization with Carbapenem resistant GNB in the ICU adult patients in a governmental general hospital, their risk factors, the causative pathogens and their outcome.
This work is a prospective study where 150 adult patients admitted to the adult ICU represented the study population. The ICU received patients from the emergency department and wards of the same hospital as well as referrals from other hospitals.
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Full history data of each patient was taken, in addition, 2 rectal swabs were collected: The first during the first 24 hours of ICU admission. The second after 4 days (or within the first week) of admission. Each swab was cultured on chromogenic agar, in the presence and absence of meropenem (1 mg/L) for the isolation and identification of CR-GNB. The antimicrobial sensitivity of bacterial isolates to 3rd generation ceph [ceftazidime (CAZ), ceftriaxone (CRO), and Cefotaxime) , amoxicillin/clavulanic acid (AMC) and carbapenem meropenem (MEM) (10 lg)] was done using the Kirby–Bauer disc diffusion method. The prevalence of carbapenemase activity based on phenotypic tests was confirmed using : a) Boronic acid synergy test and b) Ethylene diammine tetra acetic acid (EDTA) test. the Risk factors associated with the 150 ICU patients included in the study and the characteristics of patients that acquired (HAI) was examined
The results of this study showed the following:
1- Regarding the types of organisms colonizing ICU patients on admission the present study documented that from 150 ICU patients included in the study, 146(97.33%), 116 (77.33%), 7 (4.67%) and 3 (2%) were isolated and were found to be E.coli, K.pneumoniae, Ps.aeruginosa, and Acinetobacter spp., respectively. At discharge rectal swabs from 113 ICU patients were taken, also the E.coli was the most isolated (95.5%) followed by K.pneumoniae (72.5%), Ps.aeruginosa (1.7%), and Acinetobacter spp. (0.8%).
2- The antimicrobial sensitivity of bacterial isolates to 3rd generation cephalosporines (ceftazidime (CAZ), ceftriaxone (CTR), and Cefotaxime (CTX), amoxicillin/clavulanic acid (AMC) and carbapenem, meropenem (MRP) (10 lg), using the Kirby–Bauer disc diffusion method. Using current breakpoints recommended by CLSI (M100-S29) for 3rd generation cephalosporins 30.1 -47.2% of E.coli, 34.6-60.3% of K.pneumoniae, 57.1 -100% of Ps.aeruginosa and 100% of Acinetobacter spp. were resistant, in addition most of the isolates ( 86-100%) were resistant to amoxicillin/clavulanic acid (AMC). Resistance to meropenem was found in 16 GNB isolates; 13 K.pneumoniae, 1 Ps.aeruginosa, 2 Acinetobacter spp.
3- The Susceptibility of CR-GNB to 3rd generation cephalosporins, AMC, cefoxitin (CX), cefepime (FEP) and tazobactam (PIT), showed that all (100%) the 16 CR-GNB isolated from rectal swabs during the study period were resistant to the tested antibiotics. No ESBL production was detected among this type of bacteria isolates.
4- This study also demonstrate The prevalence of carbapenemase activity based on phenotypic tests was confirmed using : a) Boronic acid synergy test and b) Ethylene diammine tetra acetic acid (EDTA) test. Carbapenamase activity was detected by Boronic acid alone in 11/16 CR-GNB (68.75%) KPC [8 K.pneumoniae, 2 Acinetobacter spp. & 1 Ps.aeruginosa], whereas metallo-β-lactamase (MBL) only was detected in 2 K.pneumoniae (12.5%) of carbapenemase-positive isolates MBL. In addition, 2 K.pneumoniae isolates (12.5%) produced combination of KPC and MPL enzymes, making a total of 25% of the strains producing MBL enzyme and a total of 81.25% of the strains producing KPC enzyme. On the other hand one K.pneumoniae isolate (6.25%) was not affected by EDTA or Boronic acid.
5- The study shows the risk factors associated with the 150 ICU patients included in the study. Male patients represented (55.3%) of the ICU patients and (44.6%) were female patients with age ranges from 20 to 80 years with 58% of them had age range 51- 80 years. Of the 150 patients, 40 (26.6%) had received antibiotics 1 month before.
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About 73.3% of the studied patients were referred from the emergency room and the average length of stay (>4days) was 40% and was 60% <4days.
6- Regarding the cause of admission, the most prevalent cause was Heart diseases (48.6%), followed by Diabetes mellitus (36%), Respiratory diseases (26.6%), Malignancy (18%), the rest of clinical conditions ranged from 16 -0.6%.
7- As for the CR-GNB rectal carriage of patients , out of 150 rectal swabs screened for carbapenem resistance (CR), A total of 13 isolates (10 K.pneumoniae, 1 Ps.aeruginosa, 2 Acinetobacter spp.) were identified from rectal swabs of 11 patients with a carriage rate of 7.33% (11/150). All the carriers had a single organism except 2 who showed the growth of both K.pneumoniae and Acinetobacter spp. In addition at discharge, 3 CR K.pneumoniae. Isolates were obtained from rectal swabs of 3 patients who were CR negative on admission raising the carriage rate to 9.33% (14/150).
8- Comparison between Risk factors associated with colonized and non-colonized patients with CR-GNB on admission shows that long duration of hospital stay and old age were found to be significant risk factors for colonization with CR-GNB. (p=0.007*&P=0.033) respectively. All colonized CR-GNB patients (100%) have age ≥ 40y and 85.7% with long duration of hospital stay. On the other hand, No significant correlation was found with gender , history of previous hospitalization, antibiotic intake or Hospital acquired infection (P>0.05). The history of antibiotic usage was present in 4 (28.5%) and 36 (26.4%) of colonized and non-colonized patients respectively, History of previous hospitalization was found in 3 (21.4) and 40 (29.4%) of colonized and non-colonized patients respectively. Heart disease (57.%), Diabetes mellitus (35.7%) and Respiratory disease (35.7%) were the most common cause of admission of both patient groups.
9- Regarding the outcome of colonized and non-colonized CR-GNB patients on admission. Out of the 14 patients with CR-GNB, 8 discharged, 3 transferred to other hospitals and 3 died. While 71/136 CS-GNB patients discharged, 42 transferred to other hospitals and 32 died. No significant difference was found regarding the outcome of both groups of patients P= 0.743.
10- Hospital acquired infection was found in14/150 ICU patients included in the study. Regarding the demographic data and characteristics of patients that acquired (HAI). The male form 78.5% (11/14) of them and 21.4% (3/14) were female. The duration of hospital stay was ≥6 days in 35.7% (5/14) of cases and was ≥5 days in 78.5% (11/14) of cases. In addition, 78.5% of cases aged >65ys.
11- The majority of the HAI infections were VAP (6/14, 42.8%), CABSI (6/14, 42.8%), followed by CAUTIs (4/14, 28.5%), and Sever UTI (2/14, 14.25%). The bacteria responsible for the infection were E.coli (4/14, 28.5%), Ps.aeruginosa (3/14, 21.4%), followed by Acinetobacter spp., K.pneumoniae, S.aureus, CONS (each 2/14, 14.25%). Diabetes mellitus was the main underlying disease among the HAI cases (11/14, 78.5%) followed by heart and respiratory disease (8/14, 57.1% & 7/14, 50% respectively).
12- Regarding the correlation of HAI with rectal carriage of CR-GNB, no statistically significant correlation between HAI and CRE colonization as out of the 14 ICU patients that acquired hospital infection only one (7.1%) of them was CR-GNB colonizer while the remaining 13(92.8%) patients were CS-GNB. (p>0.05).