Overuse/Misuse of Surgical Antimicrobial Prophylaxis (SAP) in a Rural Hospital in Uganda Hiroki Saito, MD MPH;1 Kyoko Inoue, MPH;2 James Ditai, MPH;3.

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Overuse/Misuse of Surgical Antimicrobial Prophylaxis (SAP) in a Rural Hospital in Uganda Hiroki Saito, MD MPH;1 Kyoko Inoue, MPH;2 James Ditai, MPH;3 Andrew Weeks, MD FRCOG4 1 Institute of Global Health, Faculty of Medicine, University of Geneva , Geneva, Switzerland, 2 Institute of Tropical Medicine, Nagasaki University, Nagasaki, Japan, 3 Sanyu Africa Research Institute, Mbale, Uganda, 4 University of Liverpool, Sanyu Research Unit, Liverpool, UK. Introduction: Antimicrobial resistance (AMR) has been a major public health threat. World Health Organization (WHO) global action plan on AMR published in 2015: “optimize the use of antimicrobial medicines in human and animal health”. According to a guideline for prevention of surgical site infection (SSI) published by WHO in 2016, the prolongation of surgical antimicrobial prophylaxis (SAP) after completion of surgery is discouraged. However, little is known about the situation on SAP in resource limited settings. Methods: A study was originally conducted in a regional referral and teaching hospital in rural Uganda in 2014-2015 to improve hand hygiene practice and measure its impact on healthcare associated infections including SSI.1 A descriptive epidemiological analysis was performed to measure overuse/misuse of SAP among those who received surgery during hospitalization. The main outcomes for this paper were length of antibiotic use and types of antibiotics for the purpose of SAP. Extra days of antibiotic use after surgery was calculated by counting each day an antibiotic was given to a patient at least a day after surgery (that is, antibiotic use before or on day of surgery was not counted). Antibiotic free days (AFDs) were also calculated by counting each day when no antibiotics were given to a patient during hospitalization as 1 AFD. Days of therapy (DOTs) were also calculated by counting each day an antibiotic was given to a patient as 1 DOT. The t-tests and chi-squared tests were performed for continuous and categorical variables in bivariate analyses, respectively. Linear regression analysis with backward selection and plausible causal interpretation was made to adjust length of antibiotic use for associated variables. Results: Out of 3627 patients enrolled into the original study, 960 (26.5%) received surgery during hospitalization. (Table 1) Cesarean section was the most commonly performed surgery (474 patients, 49.4%). 907 patients (94.5%) received antibiotics during hospitalization, among whom 880 patients (97.0%, out of 907 patients) were on antibiotics on day of surgery. (Table 2) A combination of ceftriaxone and metronidazole was the most common regimen (609 patients, 67.1%). The mean length of antibiotic use during hospitalization was 3.5 days (standard deviation: 3.3). Linear regression analysis showed the extra days of antibiotic use after surgery were 1.5 days (95% confidence interval: 1.3-1.8), after adjusting for covariates such as presence of Systematic Inflammatory Response Syndrome (SIRS) and CDC wound class. 6503 days of therapy (DOTs) of antibiotics (Figure 1) and 1649 antibiotic free days (AFDs) were observed during the total 4960 patient-days. Table 1. Characteristics of patients who received surgical procedures (N=960) Table 2. Duration of antibiotic use for patients who were on antibiotics on day of surgery (N=880) All n (%) OBGYN Surgery p value Number of patients 960 714 246 Female 816 (85.0) 714 (100.0) 102 (41.5) <0.01 Adult 827 (86.1) 660 (92.4) 167 (67.9) Mean age among adult patients, (SD), y 31.5 (13.7) 28.1 (9.5) 45.1 (18.4) Mean age among pediatric patients, (SD), y 10.5 (6.3) 16.5 (0.8) 6.4 (4.8) Urinary catheter use (n=958) 620 (64.7) 598 (83.8) 22 (9.0) Mechanical ventilation use (n=958) 246 (25.7) 142 (19.9) 104 (42.4) General anesthesia given (n=955) 364 (38.1) 164 (23.1) 200 (81.6) Top three types of surgery   Cesarean section 474 (49.4) 474 (66.4) 0 (0.0) - Laparotomy 129 (13.4) 81 (11.3) 48 (19.5) Skin, subcutaneous 62 (6.5) 3 (0.4) 59 (24.0) CDC wound class (n= 953) I 846 (88.8) 694 (97.7) 152 (62.6) II 68 (7.1) 65 (26.7) III 17 (1.8) 9 (1.3) 8 (3.3) IV 22 (2.3) 4 (0.6) 18 (7.4) SIRS and/or Healthcare associated infection (HAI) during hospitalization 234 (24.4) 208 (29.1) 26 (10.6) SIRS criteria met during hospitalization 231 (24.1) 205 (28.7) Diagnoses of HAIs made 15 (1.6) 6 (2.4) 0.23 Surgical site infection 14 (1.5) 8 (1.1) 0.21 Mean length of hospital stay, (SD), d 5.2 (4.2) 4.4 (2.7) 7.3 (6.3) Hospital mortality 9 (0.9) 1 (0.1) Mean length of antibiotic use during hospitalization, (SD), d 3.5 (3.3) 2.9 (1.6) 5.2 (5.6) Antibiotic free days, (SD) 1.7 (2.8) 1.5 (2.2) 2.3 (3.8) Frequency of patients who were on antibiotics on day of surgery n Mean length of antibiotic use during hospitalization (SD), d Difference (95% Confidence Interval, p value) Extra days of antibiotic use after surgery, (SD) Total 880 3.7 (3.2) - 2.4 (2.9) By Department OBGYN 666 3.1 (1.5) ref 2.0 (1.4) Surgery 214 5.5 (5.6) 2.4 (1.9–2.9, <0.01) 3.7 (5.0)  1.7 (1.3–2.2, <0.01) Occurrence of SIRS and/or HAI Without SIRS or HAI 660 3.3 (2.1) 2.2 (1.8) SIRS and/or HAI 220 4.6 (5.2) (0.8–1.8, <0.01) 1.3 3.3 (4.7) (0.8–1.6, <0.01) 1.1 Type of Surgery Cesarean section 456 3.1 (0.7) 2.1 (0.7) Laparotomy 124 4.6 (3.3) 3.3 (3.1) By CDC wound class (n=874) I 788 3.2 (2.0) 2.1 (1.8) II  – IV 86 7.4 (7.3) 4.2 (3.5–4.8, <0.01) 5.2 (6.7) 3.1 (2.5–3.7, <0.01) Figure 1. Days of Therapy (DOTs) of antibiotics given 9 DOTs, 0.01% 382, 6% 51, 1% 302, 5% 2852, 44% 33, 1% 2, 0% 1, 0% 454, 7% 44, 1% 2372, 36% Conclusion: After adjusting for various covariates, antibiotics were given for average 2.5 days during the hospitalization, and extra 1.5 days even after surgery. The usage was longer than usually recommended across different patient groups, including those without SIRS/HAI whose antibiotic use was likely SAP, and those with CDC would class I. AFDs account only for one third of the total patient-days (1649 AFDs out of 4960 patient days). Considering the remaining 3311 patient days as non-AFDs and the total 6503 DOTs, almost two different antibiotics were given per day among those who received antibiotics. Overuse/misuse of antibiotics was a common practice among this surgical population in Uganda. Antimicrobial stewardship for SAP can play a major role in combating AMR in resource limited settings. Reference 1: Saito H et. al. Alcohol-based hand rub and incidence of healthcare associated infections in a rural regional referral and teaching hospital in Uganda ('WardGel' study). Antimicrob Resist Infect Control. 2017 Dec 28;6:129. Contact: Hiroki Saito - hiroki.saito@etu.unige.ch