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Abstract : Most bacterial infections can be successfully treated with antibiotics, although this must be balanced against potential side effects and worries about the emergence of bacterial resistance to antibiotics, which would diminish their efficacy. Bacterial infections can be dangerous and very contagious. to clarify the efficacy and safety of macrolides against different bacterial infection in contrast with oral cephalosporin.the study start from April 2021 to October 2022 in Almuthanna/ Iraq,The trial was continued with 500 patients: (i) patients whom taking macrolide A group (n=250), and (ii) whom taking cephalosporin B group (n=250). Both received the full pharmaceutical care then collect data and evaluate it after taking treatment by 5,10 and more than 10 days, the Patients medications adherence and antibiotics resistance were valuated. the results revealed that the efficacy of both groups was very close in similarity and only (5.2% of patients taking macrolide vers 4.4% taking cephalosporin)not improved due to low patient medication adherence or antibiotics resistant, also A group had more side effect in contrast with B group.