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PATTERNS OF ANTIMICROBIAL USE AND PREVALENCE OF ANTIBIOTIC RESISTANT BACTERIA STUDY AT AIN-SHAMS UNIVERSITY SPECIALIZED HOSPITAL (ASUSH)

Introduction: Antibiotics are prescribed for treating bacterial infections. However, Excessive use of antibiotics leads to the development and spread of multidrug resistant bacteria, currently regarded as a global public health crisis threatening our ability to treat common infectious diseases, resulting in prolonged illness, disability and death. Aim of the work: To analyze the use and prescribing patterns of antimicrobials by physicians at Ain-Shams University Specialized Hospital (ASUSH) for inpatients among different infections and to determine the prevalence of different types of bacterial resistance among hospital infections. Subjects and methods: A cross- sectional study was conducted at (ASUSH). A total of 339 microorganisms isolated from several samples types were identified and studied using VITEK® 2 system. Physicians’ attitudes and knowledge were assessed using a questionnaire about antibiotic resistance problem.  Results: Among (339) bacterial isolates Klebsiella pneumoniae was the most common isolate n=92 (27.1%), followed by E-coli n=60 (17.7%), Staph coag –ve (SCONs) n= 43 (12.7%) and Methecillin resistant staphylococcus aureas (MRSA), Pseudomonas aeruginosa and Acinetobacter baumanni n=33 (9.7%) for each. In this study, the majority of physicians had good knowledge about the antibiotic resistance meaning and the magnitude of that problem, with a positive attitude towards prescribing antibiotics. Conclusion: Strategies for control of resistant bacteria should consider variations among sample types, wards, and antibiotic resistance variability. There is a need to specifically address staff training and communication procedures for infection prevention and control with respect to drug resistant bacteria.


INTRODUCTION
There is no doubt that antimicrobials have played a revolutionary role in healthcare systems worldwide. From the discovery of the first antibiotics in the 1930s and1940s, these medicines have saved countless lives through reducing morbidity and mortality rates for a number of infectious diseases that were once a principal cause of death. (Nichol., et al ., 2018).
Antibiotics have not only saved patients' lives, they have played a pivotal role in achieving major advances in medicine and surgery. They have successfully prevented or treated infections that can occur in patients who have chronic diseases such as diabetes, end-stage renal disease, or rheumatoid arthritis; or who have had complex surgeries such as organ transplants, joint replacements, or cardiac surgery. (Gould and Bal., 2013 ;Atif, et al ., 2017).
New resistance mechanisms are emerging and spreading globally, threatening our ability to treat common infectious diseases. (Tyers and Wright, 2019;WHO, 2018). It leads to increased morbidity and mortality, increased hospital stay, and costly and toxic alternatives. However, while resistance rates continue to rise, the rate of antibiotic discovery has dropped substantially. (Laxminarayan, 2014;Hernando-Amado, et al., 2017).
Antimicrobial resistance (AMR) happens when microorganisms (such as bacteria) change when they are exposed to antimicrobial drugs they became less sensitive to the drug and sometimes completely insensitive to the antibiotic. As a result, the medicines become ineffective and infections persist in the body, increasing the risk of spread to others (WHO, 2018).
A number of factors are thought to be associated with this rapidly developing AMR bacteria but inappropriate consumption of antimicrobial (either prescribing antimicrobials when not required or prescribing a broadspectrum agent when a narrower spectrum agent would be adequate) is still the main determinant of AMR ( Atif., et al ., 2017).
Globally, between 20 to 50% of antimicrobial consumption is inappropriate, causing significant impact on the quality of care, cost of therapy and incidence of adverse drug (Centers for Disease Control and Inappropriate attitudes and lack of knowledge towards the use of antibiotics, patients' demands, lack of culture and selling antibiotics without prescription are also some of the most common contributors towards antibiotic resistance and considered as a high-risk factor contributing to the rise of AMR cases. (Zulu, et al., 2020) As a result, the WHO recommends continuous surveillance of antibiotic use as a strategy for improving antibiotic use among patients and also for controlling antibiotic resistance and minimizing patient harm, so accurate information on the use of antibiotics are crucial to address the problem of antibiotic overuse and resistance. (Labi, et al ., 2018).
We aimed to analyze the use and prescription patterns of antimicrobials by physicians at (ASUSH) for inpatients with different infections and to determine the prevalence of different types of bacterial resistance among hospital infections

Patient and sample characteristics
Records from August 2018 to January 2019 from inpatients with MDR infections attending ASUSH were analyzed. A total number of 339 MDRpositive samples were identified. Demographic data (sex, age group) is summarized in Table (1). They were isolates from pus, urine, blood, respiratory and cerebrospinal fluid (CSF) samples; sample type information and Bacterial species identified for each sample type are summarized in Table   (2).

Identification and Antibiotic susceptibility testing
The identification was carried out by the automated VITEK ® 2 system ((bioMérieux. Marcy l'Etoile, France) which used for species identification and susceptibility testing of the bacteria, which accommodate the colorimetric reagent cards that are incubated and interpreted automatically.

Physicians' survey
A questionnaire was distributed to (90)  -Chi-square test to study the association between each two variables or comparison between two independent groups as regards the categorized data.
Klebsiella and E_coli were frequently isolated from urine samples 32.14% and 29.7% of all isolated microorganism from urine sample respectively.

Antibiotic resistance profiles
The resistance and sensitivity profile for each microorganism in table (3) and table (4) revealed that Antibiotic resistance profiles were not uniform across bacterial species or sample types; these factors should be considered for informing antibiotic stewardship programs within the hospital. As expected, there were overall high levels of susceptibility to carbapenems.
E.coli showed the lowest resistance pattern to most antibiotics unlike klebsiella which was the Most frequent isolate in our study showed moderate resistance to Meropenem (51.9%) and Amikacin (53 %) and was highly resistant to Ceftriaxone (96.5%) followed by Ceftazidim (95.8%) and Levofloxacin(71.4%). Table (3) None of MRSA nor SCONs were resistant to linezolid nor vancomycin.
However, MRSA showed higher sensitivity against teicoplanin, tri/sulpha and erythromycin than SCONs. Table (

Physicians' knowledge
When they were asked about the meaning of antibiotic resistance and the magnitude of this problem the majority (85.6%) Knew the meaning and felt that it's a very important problem Overuse of broad spectrum antibiotics considered to be the most Important factor that lead to antibiotic resistant (100%) followed by Physicians thought that prolonged Treatment (74%) and increased cost (68%) were the most frequent complications related to antibiotic resistance and Death is the least complication (7%).
And 68.9% would continue using the antibiotic, although the culture showed that microorganism is sensitive to another narrow spectrum antibiotic and only 31.1% would change to the other narrow spectrum antibiotic.       Inappropriate use of antibiotics in hospitals and communities has resulted in an increasing resistance to various antibiotics (Awad and Aboud, 2015).
In this study the total number of isolated pathogens was (339) among which Klebsiella was the most common isolate (27.1%), followed by E_coli (17.7%), Staph coag -ve (12.7%) and MRSA, Pseudomonas and Acinetobacter (9.7%) for each. Similar to our study results, literature also reports Klebsiella pneumoniae as the most common resistant isolates, followed by Escherichia coli and/or Enterobacter species. (Sodhi, et al., 2020)  and also similar to a study conducted at tertiary care hospital in Egypt by (Hassan, et al., 2020).
The distribution of those resistant pathogen mainly found in age range (51-70 years) with (51.6%) then from (31-50 years) with (22.7%) which support that aging is one of the main predisposing risk factors for HAIs with resistant pathogens , this was in agreement with Feng, et al., (2019).
In our study E.coli showed the lowest resistance pattern to most antibiotics specially gentamycin and amikacin unlike A.baumanni & P.
aeruginosa which were highly resistant to the same antibiotics. However the highest sensitivity of E.coli was recorded to nitrofurantoin (90%) as found in other study by (Aguilar-Santelises, et al., 2020).
Antimicrobial stewardship programs (ASPs) have emerged as a strategy to manage or contain the problem of AMR, which considered as a systematic approach to improve the prescribing pattern of antibiotics through a variety of interventions and have been proven to be cost-effective. ASPs should afford educational and effect changes in prescribing behaviors of healthcare providers. (Labricciosa, F. et al., 2018) In this context, a questionnaire was conducted to analyze the use and prescribing pattern of physicians working at the same departments from which the resistant pathogen were isolated at the same period of time from which isolated pathogens were collected. The total number of physicians who filled the questionnaire were (90) physician of different specialties and years of experience from which (55.6%) male and (44.4%) female.
In this study, the majority of physicians (85.6%) have good knowledge about the antibiotic resistance meaning and the magnitude of that problem which was in agreement with a study conducted at national liver institute in Egypt by Tahoon, et al., (2020) who found that (85%) of physician were familiar with antibiotic resistance. another study by Tegagn et al., (2017) found that 81.3% of healthcare professionals were familiar with antibiotic resistance meaning.
According to the conducted survey Overuse of broad spectrum antibiotic considered to be the most Important factor that lead to antibiotic resistant (100%)followed by Widespread use of antibiotic (98.9%) and inappropriate use of antibiotic (82.2%) These results are close to previous study from Italy Napolitano F, et al., (2013) also showed that wide spread use of antibiotics is the most important cause of this problem.
Most Physicians thought that prolonged Treatment (74%) and increased cost (68%) were the most frequent complications related to ANTIBIOTIC resistance and Death is the least complication (7%) which was similar to another survey by Nichol, , et al,. (2018) at a tertiary care institution in the Caribbean.
The majority of physicians (78%) considered periodic Educational programs to be the most useful factor in containing the antibiotic resistance problem as a tool to improve antibiotic prescription pattern of them.
Furthermore, the majority considered taking cultures prior to ANTIBIOTIC choice (70%) as other important factor against the spread of MDR bacteria.
Antibiotic cycling considered to be the least useful factor with (44%) which is correlate with a study in UAE by John , et al., (2012)and other study in Khartoum by Kheder . ,(2013).
This results shows that there is a need to follow infection control measures and to increase the restrictions of antibiotic use in the current antibiotic policy to slow down the emergence and spread of antibiotic resistant bacteria in the health care setting.

CONCLUSION
Infections can be transferred between and within hospitals, facilitated by sub-optimal infection prevention and control measures, as well as between the community and healthcare facilities.