Microbiological Assessment and Antimicrobials’ Use in an Infectious Diseases Department in Mali

The use of antimicrobials without microbiological proof is frequent and contributes to the emergence of resistance. The aim was to identify the organisms isolated during laboratory examinations and the type of antimicrobials con-sumed by patients hospitalized to Infectious Diseases’ Clinic. This is a cross-sectional and analytical study, carried out from January 1 to December 31, 2017 in the Infectious Diseases Department of Point “G” Teaching Hospital in Mali. All biological specimens from patients during the study period were analyzed. In total, 322 patients benefited from microbiological test, with a mean age of 322 admitted patients, i.e. 3.55 anti-infectives per patient. Antibiotics (ex-cluding tuberculosis drugs), antiparasitics and antifungals represented respectively 46.2%; 18.8% and 15.1% of anti-infectives. Antibiotic therapy was effective in 274 (85.1%) patients and among them, only 76 (27.7%) cases were based on microbiological evidence. Antibiotics are the most widely used antimicrobials in an infectious disease department. Empiric treatments are common but must be minimized by the search for microbiological evidence.


Introduction
Infectious Diseases remain the main causes of human morbidity and mortality, especially in developing countries. Antimicrobials are probably one of the most effective forms of chemotherapy in the history of medicine [1] [2]. Unfortunately, antimicrobial resistance is a worldwide concern [3] [4] [5]. It leads to a reduction in the molecular choice by prescribers, an increase in the length of patients' hospitalization period, an increase in healthcare costs, exposure to more toxic drugs and mortality [6] [7] [8].
According to the World Health Organization (WHO), antimicrobial resistance is a serious threat and currently affects all regions of the world and is likely to affect anyone of any age or country [5]. Every year, there are 700,000 deaths due to drug resistance and if nothing is done by 2050, mortality could reach 10 million in the world [9].
In Africa, where antimicrobials are much prescribed compared to other parts of the world [10], several publications address the issue of bacterial resistance to antibiotics. Enterobacteriaceae are cited as the most relevant group of pathogens and the production of extended-spectrum beta-lactamases (ESBL) is described as the most common type of resistance. This situation creates therapeutic impasses with ever-increasing hospital morbidity and mortality [11] [12] [13] [14]. Authors are unanimous on the factors that cause antimicrobial resistance, especially those that are common in resource-limited countries such as: self-medication, the sale of counterfeit medicines, over-the-counter antibiotics, use of antibiotics as a poultry and livestock growth promoter rather than to control infection, storage and conservations difficulties, the incompetence of prescribers, the insufficiency of the laboratories for the microbiological diagnosis [13] [15] [16]. In addition, the inappropriate prescription of antibiotics largely contributes to their emergence through the selection pressure [17] [18].
The financial consequences are enormous. In 2006, about 50,000 Americans died due to two common hospital acquired infections, namely pneumonia and sepsis, costing about 8 billion dollars to the Unities States economy [19]. Nosocomial infections of patients due to these bacteria, sometimes pose legal prob-  [20].
The link between antibiotic using and antibiotic resistance has even been proven by mathematical models [21]. Monitoring this consumption is one of the recommended strategies for preventing and controlling antimicrobial resistance.
It is a reality in developed countries. Indeed, this surveillance has seen a decrease in antibiotic consumption of 11.4% between 2000 and 2015 in France [22].
World Health Organization (WHO) gave definition about the rational use of medicines. It's the patients who receive medications appropriate to their clinical needs, in doses that meet their own individual requirements for an adequate period of time, at the lowest cost to them and their community [23]. It appears that the correct and rational use of antimicrobials is the only way to fight against antibiotic resistance and this could be done through training of health professionals, in particular prescribers but also patients [8].
In Africa, some countries are developing lists of essential drugs including antimicrobials, along with guidelines for the management of health workers. This is the case in Ghana and Nigeria [24] [25]. However, studies still report unreasoned prescriptions of antibiotics by caregivers [15]. Most antimicrobial treatments are done without microbiological evidence with broad-spectrum antibiotics that destabilize local flora and increase the selection pressure of resistant organisms to these antibiotics.
In Mali, the prescription of antibiotics has reached high levels in hospitals. It would represent 18.5% of drug spending in Bamako [26]. A hospital study analyzing the local microbial ecology and antimicrobials' use hasn't yet been performed. It's in this context that our study was realized in a Clinical ward for the specific management of infectious diseases. The objective was to review the frequently isolated pathogen in pathological fluid of patients and quantitative antimicrobial prescribing.

Study Area and Period
The study was performed in the Department of Infectious Diseases at Point "G"

Study Population
Have been concerned by study all the patients admitted for infectious diseases during the period. The not included patients were those observed for discontinuous care and those who died within 24 hours of admission.

Study Process
All specimens of patients' biological fluids were sent to the laboratory for micro-
Has been considered like antimicrobial treatment, any prescription of anti-infectious whose purpose is to treat a suspected infection or microbiologically proven. Thus, anti-infectious prophylaxis was not taken into account.

Statistical Analysis
Data were collected and analyzed using SPSS (Statistical Package for Social Science) version 22. Quantitative variables were expressed in terms of mean (± standard deviation) or median [interquartile range (IQR)] according to the distribution curve of the values of these variables. Mean was calculated when the curve was symmetrical and median in the opposite case. Qualitative variables were expressed as percentages. Chi-square tests were used for statistical analysis.
p-value at < 0.05 was considered significant.

Ethical Aspects
The study was performed in a healthcare setting and patients gave their informed consent. Confidentiality of information and anonymity of participants were respected during the study and data processing. The conduct of study required prior authorization from the Head of the Infectious diseases Ward.

Characteristics of Study Population
A total of 387 patients were admitted, 322 of whom benefited microbiological testing from January 1 to December 31, 2017. The average age of the 322 patients was 40.9 ± 12.2 years (15 -74 years). The majority of the patients was female at Respiratory (60.3%), central nervous system (CNS) (39.7%) and digestive (32.4%) pathologies were the most frequently encountered in patients ( Figure 1).

Antimicrobial Drugs Used
Global data: There were 1143 antimicrobials drug used in 322 hospitalized patients treated for infectious diseases whether an average of 3.55 antimicrobials per patient. Non-tuberculosis antibiotics (46.2%) followed by antiparasitics (18.8%) and antifungals (15.1%) were the most commonly used anti-infective agents ( Table 5).

Discussion
Our study showed the profile of microbiological organisms commonly found in patients admitted to an Infectious diseases department in resource limited setting in Africa and has revealed a high antimicrobial use.
Respiratory, CNS and digestive infections were the most common causes of admission of patients in our survey. Other studies evaluating the antibiotics' prescriptions in one or several hospitals found a higher frequency of respiratory   Considering the antibiotic susceptibility pattern of isolated E. coli strains, beta-lactams had a very low inhibitory action. In fact, the susceptibility of the organism to amoxicillin/clavulanic acid and ceftriaxone was 16.7% and 52%, respectively. Our results were proximate to those found by Lo in Saint Louis [12] and Kouegnigan Rerambiah in Libreville in their studies [4]. The existence of an increasing number of hospital strains of Extended-spectrum beta-lactamase (ESBL) producing enterobacteria may explain this finding [11] [12] [14] [34].
Quinolones had a medium inhibitory action (41.7% for ciprofloxacin) on E. coli strains. The same observation made by Dia [11] noted a susceptibility to ciprofloxacin of 51.2%. ESBL resistance is often associated with resistance to aminoglycosides and quinolones [34]. In addition, the frequency of beta-lactams and quinolones using in enterobacterial infections in general [4] and quinolones as first-line therapy in the empirical treatment of urinary tract infections [14] may explain the current level of resistance emergence to these molecules. All isolates  [14].  [29].
Antibiotics were the most commonly prescribed antimicrobials before antiparasitics and antifungals in our survey. This denotes the importance of bacterial infections among infectious diseases in our context. Among antibiotics, beta-lactams, followed by imidazoles and aminoglycosides were the most used in our patients.
The predominance of beta-lactams use has been found in the literature [10] [16] [28] [29] [26]. This class of antibiotics is one of the most widely prescribed in general practice with a broad-spectrum of activity and a variety of molecules [37]. About antiparasitics, trimethoprim-sulfamethoxazole was the most used in patients. This molecule was primarily prescribed for the management of cerebral toxoplasmosis and cystoisosporiasis in HIV-infected patients with profound immunosuppression. Clindamycin has also been used as an antiparasitic agent in the cerebral toxoplasmosis' treatment in second intention. Malaria was mainly managed by artemether and artesunate.
Fluconazole predominated among the antifungals used in our patients. It is one of the molecules indicated for the treatment of opportunistic fungal infections, the most frequent in our study were digestive candidiasis and cryptococcal meningitis [38].
The majority of our patients were immunocompromised by HIV, which justified the ART using.
Our study had a number of limitations. Specimens from patients have been analyzed in several laboratories with sometimes different settings in the identification of organisms and antibiotic sensitivity tests. Antibiotic susceptibility profile was limited to E. coli taking into account the reduced number of other isolated strains. Finally, during data collection, we didn't consider antimicrobial forms, routes of administration and number of doses administered during the hospitalization.

Conclusion
We performed an inventory of the organisms usually identified in pathological fluids and antimicrobials prescribed to patients in an Infectious Diseases' Clinic.
Bacteria such as M. tuberculosis in the sputum of HIV-infected patients, E. coli and K. pneumoniae in the urine were the most isolated in pathological fluids. C. albicans among fungals and P. falciparum among parasitics were mostly identified. The sensitivity profile of E. coli with antibiotics was analyzed. Concerning antimicrobial use in the service, antibiotics and more especially beta-lactams were predominant. The average number of antimicrobials per patient was 3.55.
Antibiotic therapy without bacteriological evidence was frequently found. Due to the emergence of antimicrobial resistance, it's important for clinicians to optimize their prescription by microbiological analysis.