Comparative Study of Cexime and Tetracycline: Measuring Effectiveness of Strategies to Improve Appropriate Antibiotic Use in the Treatment of Acute Respiratory Tract Infections (ARTIs) in Urban Population Indonesia.

Objective. Antibiotic resistance is a serious threat that occurs globally in the health sector due to increased consumption of inappropriate antibiotics. Guidelines for prescribing antibiotics for ARTIs have been issued in general practice to promote rational antibiotic prescribing. This study was conducted to compare the effectiveness of cexime and tetracycline as a solution to improve monitoring of appropriate antibiotic use in the treatment of ARTIs. Methods. All stock isolates were rejuvenated rst, and cultured on standard media and Kirby-Bauer disc diffusion method was used for susceptibility testing in accordance with the Clinical and Laboratory Standard Institute's (CLSI) recommendations. Identication of bacteria from a single isolate was carried out to determine which bacteria were resistant to cexime and tetracycline. Results. A total of 466 single isolates of bacteria were analyzed, which showed a percentage of resistance to cexime 38.0 %, and tetracycline 92.86 %. Bacterial isolates were resistant to cexime and tetracycilne was a genus of Haemophilus, Streptococcus, Corynebacterium, Staphylococcus, and bordetella. Conclusions. Cexime compared to tetracycline was proven to be superior in terms of the effectiveness of ARIs treatment. Our study investigated the correlation between pathogenic bacteria causing ARTIs and the antibiotic susceptibility prole

proteins, and damage the peptidoglycone synthesis pathway. Ce xime Is widely used in many countries because it has broad spectrum activity against all Gram positive and negative pathogenic bacteria and atypical organisms, eg mycoplasma and chlamydia [8].
Tetracycline antibiotics are widely known to have a broad spectrum of activity, act on a variety of Grampositive and negative bacteria, spirochetes, obligate intracellular bacteria, and are also effective against protozoan parasites [9]. Tetracycline treatment for symptoms of respiratory tract infections is an antibiotic of choice, especially for infections caused by the potential pathogens of Haemophilus in uenzae and Diplococcus pneumoniae. Medical recommendations are also given to patients with chronic airway obstruction receiving antibiotics, and also if they show symptoms of acute infection [10].
The study reported by Ramdhani, et al, regarding the management of ARTIs patients in a public health center of Tasikmalaya, Indonesia, described a fairly serious case of antibiotic resistance. The use of several antibiotics showed decreased effectiveness with a high resistance value, including amoxicillin (70.25%), levo oxacin (50.0%), cipro oxacin (43.03%) [11,12,13].
This study was conducted to evaluate the comparative effectiveness of ce xime and tetracycline through antimicrobial susceptibility testing (AST) in the empirical treatment of ARTIs. In addition, this study was also to determine the genus of total clinical isolates of patients who had resistance to ce xime and tetracycline antibiotics. Tests were carried out using stock isolates from patients obtained from previous studies.

Materials And Methods.
The test sample was a combined stock isolate from previous ARTIs research totaling 466 single bacterial isolates. This sample has been puri ed from bacterial contaminants, and rejuvenated.
The bacterial growth medium used was Mueller Hinton Agar (MHA) (Oxoid) with a concentration of 38 g/L, according to the guidelines from the CLSI [14]. Rejuvenation and puri cation of clinical isolates.
The technique of rejuvenating clinical isolates was carried out using the scratch plate method. Clinical isolates from previous studies were rejuvenated on new MHA growth media, and incubated at 37˚C for 18 hours. Colony morphology observations were carried out including color, colony structure, and different haemolytic and morphological characteristics [15].

Preparation of Test Bacteria Suspension.
The test bacterial suspension was prepared by inoculating the bacterial colony into a sterile physiological NaCl solution. The turbidity of the bacterial suspension should be made equal to the standard turbidity of 0.5 Mc Farland solution [16].
The Kirby-Bauer disc diffusion test was used to determine the sensitivity of antibiotics to bacterial isolates [17]. This test can evaluate the effectiveness of antibiotics that are already resistant or are still sensitive by measuring the diameter of the inhibition zone. This testing technique is based on the diffusion principle through antibiotic paper disks. Determination of the resistance value of the tested bacteria to ce xime and tetracycline were carried out by comparing the diameter of the inhibition zone with the standard diameter of the resistance zone formed [14]. The value of the resistance level category can be seen in Table 1. Results And Discussions.
Antibiotic susceptibility pro le.
The main focus of our study was to evaluate the current prevalence of bacteria responsible for ARTIs among the population in the urban area of Tasikmalaya, Indonesia. Our study investigated the correlation between pathogenic bacteria causing ARTIs and the antibiotic susceptibility pro le commonly used by medical practitioners in public health centers. The test results obtained can be a comparative study regarding the effectiveness of ce xime and tetracycline as drugs of choice in the treatment of ARTIs. The disk antibiotic concentration used in accordance with CLSI guidelines are ce xime 5 µg, and tetracycline 30 µg [14].
Antibiotic susceptibility test carried out on 466 bacterial isolate stocks showed that ce xime was superior to tetracyclines in the treatment of ARI. Ce xime showed a lower resistance level of 38.0% when compared to 92.86% tetracyclines. These results are also consistent with other studies that cefexime is more effective in the treatment of respiratory infections compared to other drugs (eg o oxacin, amoxicillin, and cipro oxacin) [20,21], The susceptibility of categories of isolates of both antibiotics are shown in Fig. 1.
These results will provide important information to the Health O ce of the City of Tasikmalaya to determine the antibiotic procurement policy for public health centers, and evaluate the pattern of prescribing antibiotics for ARTIs treatment by practicing doctors. Synergic cooperation and coordination between all health professions in the prevention of ARI is also very necessary.
Biochemical conventional identi cation were carried out on 466 stocks of bacterial isolates, identi ed as Gram-negative, Gram-positive, bacilli (rod-shaped), coccoid (rod-shaped), coccobacilli. Results analyzed bacteria, the biochemical conventional tests revealed 5 genus of bacteria: Bordetella, Corynebacterium, Staphylococcus, Streptococcus, Haemophilus (Table 1 and Fig. 2).  Several studies have shown similar results that of bacteria from the genus Bordetella, Haemophilus, Corynebacterium [22,23,24,25]. Similar study conducted by  showed that Streptococcus haemoliticus, Staphylococcus, and Corynebacterium diphtheriae against tetracycline antibiotics [26]. Cefexime is also reported to have started decreasing susceptibility patterns of these bacterial pathogens, Streptococcus pneumoniae, Haemophilus in uenzae with low resistance levels. [20]. Schico GC reported relevant information that cefexime showed decreased sensitivity to Staphylococcus, and streptococcus but was still very active than cefaclor and cefuroxime against Gram-negative respiratory pathogens [27].
However, some authors still highly recommend cefexime as a rst-line antibiotic in overcoming cases of resistance to URTI and LRTI, especially against the pathogens Streptococcus pneumonaie, Streptococcus pyogenes, Hemophylus in uenza, Moraxella catarrhalis [28,29,30]. Other studies have also demonstrated good clinical e cacy data of cefexime in URTI and acute otitis media (AOM) cases, where community-induced infections exhibit high rates of resistance to macrolides and are highly sensitive to cefexime [31,32].
Coordination with local policy holders of the Tasikmalaya City Health O ce regarding the evaluation of the use of antibiotics in the treatment of ARTIs has been carried out. Preventive policies and education such as the intervention of antimicrobial stewardship programs (ASPs) at reducing unnecessary antibiotic prescribing, including training communication between health professionals, accountable justi cation of health programs, feedback by comparing socio-behavioral responses through questionnaires. Making handouts that are distributed to patients in community health centers as part of a program to educate the public about the use of appropriate antibiotics can support the success of ARTIs therapy. We plan to measure the impact of these interventions in the near future.

Conclusions.
Cefexime treatment has shown superior effectiveness compared to tetracyclines in the case of ARTIs.
Cefexime can still be used as a front line antibiotic option in the management of ARTIs.
The study also reported the identi cation of pathogenic bacterial organisms causing ARTIs and antibiotic resistance in accordance with research reports from another bacterial group Bordetella, Corynebacterium, Staphylococcus, Streptococcus, Haemophilus. Declaration.