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Patients and Methods: A hospital-based prospective observational study design was employed to assess the antimicrobial use-related problems among adult patients admitted to Dilla University Referral Hospital from 5 March to 4 September 2018. The antimicrobial therapy was reviewed to assure compliance with the recommendations of the national guidelines or evidence-based international clinical guidelines and drug therapy problem was identified. The logistic regression model was fit to determine the association between the different factors and the occurrence of drug therapy problems. Odds ratio was used to show a comparison of factors contributing to drug therapy problems. Statistical significance was considered at p-value <0.05. Results: In this follow-up to 229 participants, the prevalence of antimicrobial therapyrelated problem was 70.74%. "Noncompliance to therapy" was the most frequent DTP experienced by 68 (29.69%) of the patients followed by "needs additional drug therapy" seen among 31 (13.54%) patients. "Adverse drug reaction" was the least and experienced by 7 (3.06%) patients. Others include: dosage too low among 22 (9.61%), dose too high among 17 (8.30%), unnecessarily prescribed antimicrobials among 17 (7.42%) and ineffective antimicrobials among 8 (3.49%) patients. Compared with those who used less than four drugs, the use of four to six (AOR: 4.024) and seven and above (AOR: 13.516) drugs were determinants for antimicrobial use problems. Additionally, infectious cases not addressed by the national guideline (AOR: 3.328) and the unavailability of appropriate lab values results within 48 hours of hospital admission (AOR: 1.285) were determinants for antimicrobial use problems. Conclusion: Antimicrobial use problem was prevalent with 0.94-problems-per-patient. Polypharmacy, coverage of national guidelines and availing laboratory values within 48 hours of hospital admission were independent determinants of antimicrobial use problems.

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