الفهرس 
INTRODUCTION & AIMS OF THE STUDYOnly 14 pages are availabe for public view
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Abstract
Urinary tract infection is a major public health problem in community and hospitals. It is the fourth most common type of healthcare-associated infections. The Enterobacteriaceae are the most common cause of UTIs, among which E. coli accounts for about 80% of the total causative agents.
The worldwide irrational use of antibiotics has resulted in the spread of antibiotic resistance among GNB which is another major health problem. One of the AMR mechanisms used by Enterobacteriaceae is the production of enzymes called β-lactamases inactivating β-lactam antibiotics. These enzymes include extended spectrum β-lactamases (ESBLs) which are β-lactamases having the ability to hydrolyze extended-spectrum cephalosporins and monobactams and are inhibited by β-lactamase inhibitors, but they cannot hydrolyze carbapenems efficiently.
The risk factors for infection with ESBL producing organisms include prolonged hospital stays (more than seven days), prior antibiotic administration, ventilatory support, hemodialysis, poor nutritional status, and recent surgery.
ESBL production is associated with severe adverse clinical and economic outcomes as it causes a delay in effective antibiotic therapy and an increase in length of hospital stay leading to higher morbidity, mortality, and overall healthcare costs. Thus, their rapid detection is of great importance.
The present study aimed to:
Evaluate NDP test as a rapid and direct method for detection of ESBL producing organisms among urinary tract infected patients by
Phenotypic detection of ESBL producing GNB directly from urine by NDP test
Isolation and phenotypic detection of ESBL producing bacteria by MDDST.
Comparing the results of NDP test and MDDST for ESBL detection
Determining the effect of using NDP test guided antibiotic therapy on length of therapy (LOT), and cost.
The present cross sectional study and randomized control trial were conducted over a period of ten months from June 2018 to April 2019. Urine samples were collected aseptically using CCMS from 152 SUTI patients due to GNB ≥ 105 cfu/ml and sent immediately to the laboratory for processing.
Samples were cultured and bacteria were isolated using BA and MacConkey’s agar and identification of isolated colonies was performed according to standard microbiological methods.
The isolates were subjected to antibiotic susceptibility testing by disc diffusion method and to ESBL detection using MDDST.
All samples were tested for ESBL production directly using NDP test.
Patients enrolled in the present parallel double blind randomized control trial were randomly divided into two study groups (A and B)
Summary, C onclusion and Recommendations
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group A: Starting with 76 patients, they ended to 45 patients due to either death or follow up failure during therapy. These patients started or changed antibiotic treatment according to culture results.
group B: Starting with 76 patients, they ended to 50 patients who started or changed their antibiotic treatment according to NDP test results first. Then, either remained or changed according to culture results.
These 95 enrolled patients, who completed treatment, were observed for at least 5 days based on clinical cure. During this follow up period, the LOT and the total cost for both study groups were recorded.
The results of the present study revealed that:
1. Among the 152 GNB ≥105 cfu/ml isolated from urine of SUTI patients, Enterobacteriaceae represented 88.16% of the total isolates. E. coli was the most common organism isolated whether from Com-UTI (62.07%) or HAUTI (41.67%) followed by K. pneumoniae.
2. According to susceptibility testing carried on the 152 GNB ≥105 cfu/ml, 34.21% were considered to be carbapenemase producer as being resistant or intermediate to either imipenem or meropenem or both. 3. Among the antimicrobials that were tested for all GNB isolated from HAUTI patients, the most effective antibiotics were fosfomycin and colistin followed by aminoglycosides, nitrofurantoin and carbapenems, whereas, the highest resistance was recorded for cefotaxime (91.43%) and ceftriaxone (90.00%). 4. For the Com-UTI patients, the most effective antibiotic was proven to be fosfomycin followed by carbapenems, whereas the highest resistance percentages were recorded for quinolones, ceftriaxone and cefotaxime.
5. The prevalence of ESBL producers in urine of SUTI patients was found to be 50% by using MDDST.
6. The prevalence of ESBLs was highest (64.37%) among the E. coli isolates followed by 42.86% among the K. pneumoniae isolates.
7. The rate of ESBL producing organisms was slightly higher among males than in females, and in Com-UTI compared to HAUTI, without statistical significance. 8. According to susceptibility testing, the most effective antibiotic for treatment of ESBL producing organisms was proven to be colistin and fosfomycin as none of the isolates showed resistance to them. These were followed by amikacin (1.41% resistance), and carbapenems. On the other hand, all of ESBL producing isolates were resistant to ceftriaxone followed by cefotaxime with 98.67% resistance. 9. For ESBL detection using NDP test directly on urine samples, the collective sensitivity, specificity, positive predictive value, negative predictive value, and total accuracy using interpretable results were 89.86%, 62.86%, 70.45%, 86.27%, and 76.26% respectively. The corresponding percentages of those samples yielding Enterobacteriaceae were 89.86%, 58.18%, 72.94%, 82.05%, and 75.81% respectively. 10. There is a moderate agreement between NDP test and MDDST for ESBL detection according to Landis and Koch. 11. A statistically significant reduction in length of antibiotic therapy (LOT) was found in the study group B using NDP test guided antibiotic therapy.12. The total cost including both antibiotic treatment cost and hospital stay cost was lower in study group B but the difference was not statistically significant. 13. Regarding the mortality rate due to UTI in both sudy groups, it was found that 4.44% died of UTI in group A using standard culture based therapy whereas only 2.00% died of UTI in group B, however this difference was not found to be statistically significant.
It can be concluded from the present study that:
1. E. coli is the most common cause of UTIs, followed by K. pneumoniae as recorded by other studies.
2. The problem of high ESBL and carbapenemase prevalence is still present in Alexandria as previously recorded.
3. There is a moderate agreement between NDP test and MDDST for ESBL detection.
from the results of the present study, the following recommendations are suggested:
1. NDP test is a rapid and easy method for ESBL detection that could be introduced in clinical practice. It is useful in guiding first line empiric antibiotic therapy and reducing LOT.
2. In areas of high prevalence of carbapenemases and ESBLs, the combination of ESBL NDP and Carba NP may be used together but further studies are needed to confirm efficacy.