2Department of Pharmaceuticals, 1Faculty of Pharmacy, University of Indonesia, Depok, Indonesia; 3Department of Pharmaceutical Installation, Dharmais Cancer Hospital, Jakarta, Indonesia *Corresponding Author’s e-mails: ratna.sari51@ui.ac.id and wiwi.ratnasaridewi@gmail.com تقييم استخدام املضادات احليوية عند املصابني باإلنتان يف وحدة عناية مركزة دراسة مستعرضة يف مستشفى مرجعي بإندونيسيا راتنا �شاري دووي، ماك�شوم رادجي، رزقا اأندلو�شيا abstract: Objectives: This study aimed to evaluate the appropriateness of antibiotic use and factors associated with outcomes among sepsis patients in an intensive care unit (ICU). Methods: This cross-sectional study was carried out from February to May 2017 and included all adult patients with sepsis or septic shock admitted to the ICU of Dharmais Cancer Hospital, Jakarta, Indonesia. Data were collected from the patients’ medical records. Results: A total of 60 patients with sepsis or septic shock were admitted to the ICU during the study period. The most common source of infection was hospital-acquired pneumonia (61.7%) and the majority had two or more comorbidities (93.3%). There were 115 antibiotic regimens prescribed. Overall, 33.3% of patients were prescribed inappropriate types of antibiotics and 51.7% were given an inappropriate dosage. The mortality rate was 68.3%. There was a statistically significant association between patient outcome and inappropriate doses of antibiotics (P = 0.034), although not inappropriate types of antibiotics (P = 0.050). A multivariate analysis indicated that the main factors influencing patient outcome were septic shock and the presence of at least two comorbidities (P <0.050 each). Conclusion: Inappr- opriate doses of antibiotics, a diagnosis of septic shock and the presence of at least two comorbidities were found to significantly increase the mortality rate of sepsis patients admitted to an ICU in Indonesia. Keywords: Drug Prescription, trends; Antibiotics; Sepsis; Septic Shock; Intensive Care Units; Indonesia. امللخ�ص: الهدف: هدفت هذه الدرا�شة لتقومي مالئمة ا�شتخدام امل�شادات احليوية، والعوامل املرتبطة بنتائج ذلك عند امل�شابني بالإنتان املر�شى من البالغني كل و�شملت ،2017 عام اأبريل اإىل فرباير من امل�شتعر�شة الدرا�شة هذه اأجريت الطريقة: مركزة. عناية وحدة يف امل�شابني بالإنتان اأو ال�شدمة النتانية الذين اأدخلوا يف وحدة العناية املركزة يف م�شت�شفى دهارميا�ص لعالج لل�رسطان بجاكارتا يف اإندوني�شيا. وجمع املعلومات من �شجالت املر�شى. النتائج: اأُدخل �شتون مري�شا بالإنتان اأو ال�شدمة النتانية للعناية املركزة خالل فرتة الدرا�شة. وكان اأكرب �شبب العدوى هو التهاب الرئة املكت�شب يف امل�شت�شفى )%61.7(، كان غالبهم م�شابا اأي�شا مبر�شني م�شاحبني اأو اأكرث )%93.3(. ومت و�شف 115 من نظم امل�شادات احليوية. ووجد على وجه العموم اأن %33.3 من امل�شادات املو�شوفة للمر�شى كانت غري مالئمة، واأن %51.7 من املر�شى كانوا قد اأُعطيوا امل�شادات بجرعات غري مالئمة. وبلغت ن�شبة الوفيات بني اأولئك املر�شى %68.3. ووجد اأن هنالك عالقة اإح�شائية معتدة بني ما حدث من نتائج عند املر�شى وعدم مالئمة جرعات امل�شادات احليوية )P = 0.034(، ولكن لي�ص بينها وبني مالئمة امل�شادات نف�شها )P = 0.050(. واأو�شح حتليل متعدد املتغريات اأن ال�شبب الرئي�ص ملا حدث للمر�شى كان هو ال�شدمة احليوية، امل�شادات جرعات مالئمة عدم اأن وجد حالة(. اخلال�صة: كل يف P >0.050( الأقل على م�شاحبني مر�شني ووجود النتانية، وت�شخي�ص حدوث �شدمة اإنتانية، مع وجود مر�شني م�شاحبني اأو اأكرث هي ما يزيد ب�شورة يعتد بها من الوفيات عند املر�شى امل�شابني بالإنتان يف ق�شم للعناية املركزة مب�شت�شفى يف اندوني�شيا. الكلمات املفتاحية: و�شفات الأدوية، اجتاهات؛ م�شادات حيوية؛ اإنتان؛ �شدمة اإنتانية؛ وحدة عناية مركزة؛ اإندوني�شيا. Evaluation of Antibiotic Use Among Sepsis Patients in an Intensive Care Unit A cross-sectional study at a referral hospital in Indonesia *Ratna S. Dewi,1 Maksum Radji,2 Rizka Andalusia3 clinical & basic research Sultan Qaboos University Med J, August 2018, Vol. 18, Iss. 3, pp. e367–373, Epub. 19 Dec 18 Submitted 20 Dec 17 Revisions Req. 21 Feb & 25 Apr 18; Revisions Recd. 31 Mar & 9 May 18 Accepted 24 May 18 doi: 10.18295/squmj.2018.18.03.017 Advances in Knowledge - This study found that the mortality rate of sepsis patients admitted to an intensive care unit in Indonesia was quite high. - Factors found to significantly influence mortality included inappropriate doses of antibiotics, a diagnosis of septic shock and the presence of at least two comorbidities. Application to Patient Care - The results of this study could be used by physicians, pharmacists and other healthcare workers to increase the appropriate use of antibiotics, perhaps by implementing an antibiotic stewardship programme or with the formulation of guidelines for appropriate antibiotic usage based on the source of infection and the patient’s clinical condition. Sepsis is a life-threatening condition caused by a dysregulated host response to infection leading to organ dysfunction.1 It is most likely to develop in individuals with a weakened immune system, often because of treatments such as chemotherapy. However, critically-ill patients are also at risk due to the prev- alence of drug-resistant bacteria in hospital settings and the need for catheterisation and wound drainage.2 Sepsis Evaluation of Antibiotic Use Among Sepsis Patients in an Intensive Care Unit A cross-sectional study at a referral hospital in Indonesia e368 | SQU Medical Journal, August 2018, Volume 18, Issue 3 occurs in approximately 2% of all hospitalised cases and among 6–30% of all patients admitted to intensive care units (ICUs) in developed countries.3,4 Both sepsis and septic shock are leading causes of morbidity and mort- ality in ICUs (21% and 28%, respectively).4–6 The management of sepsis or septic shock requires a comprehensive and systematic approach combining the use of appropriate diagnostic measures, the rapid initi- ation of appropriate empirical antibiotics and the admin- istration of supportive therapy.7 According to internat- ional guidelines for the management of sepsis and septic shock, appropriate antimicrobials should be administered within one hour of diagnosis, with the dosage optimised according to standard pharmacokinetic/pharmacodyn- amic principles.8 In addition, the patient’s location at the time of infection, the source of the infection and the prevalence and susceptibility patterns of common local pathogens should also be factored into the choice of therapy.8,9 In ICUs, antibiotics are the most common type of medicine and are prescribed approximately 10 times more than in general hospital wards.10 However, inappropriate therapy and delays in prescribing appropriate antibiotics are important factors related to increased morbidity and mortality in sepsis patients.8,11,12 In Thailand, there were 229 cases of sepsis reported in 2012, of which 61.6% developed septic shock; the overall mortality rate for patients who were prescribed first-dose inappropriate and appropriate antibiotics was 75% and 68.3%, resp- ectively.13 In a referral hospital in Indonesia, there were 126 cases of sepsis admitted between 2011 and 2012; the mortality rate was 81.8% and 66.7%, respectively, for patients prescribed inappropriate types and doses of antibiotics.14 The Dharmais Cancer Hospital is a 364-bed tertiary care hospital in Jakarta, Indonesia, which also serves as a cancer referral centre. According to a retrospective study, 18.5% of patients admitted to this hospital between 2011 and 2012 had sepsis.9 However, to the best of the authors’ knowledge, no studies have yet evaluated the appropr- iateness of antibiotic usage for sepsis patients in the hospital’s ICU. This study therefore aimed to evaluate the appropriateness of antibiotic use with regards to antibiotic type and dosage and factors associated with patient outcomes among ICU patients with sepsis or septic shock admitted to Dharmais Cancer Hospital. Methods This cross-sectional study was carried out between February and May 2017 in the ICU of Dharmais Cancer Hospital. All adult sepsis or septic shock patients who were receiving antibiotic therapy and were hospitalised in the ICU for at least 24 hours during the study period were included. Patients with incomplete medical records, those who had subsequent episodes of sepsis/septic shock or who were admitted for less than 24 hours and those who were under 18 years of age were excluded. In addition, patients readmitted to the ICU during the study period were not evaluated again. The required sample size was calculated using the following formula:15 ( )21Z 2 2d P (1-P) n = - α where is 1.96 (at a 95% confidence interval), P is 10% (the expected proportion of sepsis) and d is 0.1 (the relative precision).15,16 Therefore, the total sample size required was 35 patients. 1-Z α2 Table 1: Recommended antibiotic regimen in sepsis cases according to source of infection17–20 Source of infection Recommended antibiotic regimen Pulmonary CAP • β-lactam (i.e. ceftriaxone, cefotaxime or ampicillin/sulbactam) plus azithromycin • β-lactam (i.e. ceftriaxone, cefotaxime or ampicillin/sulbactam) plus respiratory flouroquinolones (i.e. levofloxacin or moxifloxacin) HAP, HCAP or VAP • Antipseudomonal β-lactam (i.e. piperacillin/ tazobactam, cefepime, meropenem, imipenem or doripenem) plus aminoglycosides (i.e. gentamicin, tobramycin or amikacin) or antipseudomonal flouroquinolone (i.e. levofloxacin or ciprofloxacin)* Blood stream CRBSI • Vancomycin or daptomycin† plus antipseudomonal β-lactam (i.e piperacillin/ tazobactam and cefepime) or carbapenem (i.e. meropenem, imipenem or doripenem) with or without an aminoglycoside (i.e. gentamicin, tobramycin or amikacin) Urinary Urosepsis • Third-generation cephalosporin (ceftriaxone or cefotaxime) with or without an aminoglycoside (gentamicin, tobramycin or amikacin) or fluoroquinolone (levofloxacin or ciprofloxacin) Urological interventions • Antipseudomonal β-lactam (i.e piperacillin/ tazobactam and cefepime) or carbapenem (i.e. meropenem, imipenem or doripenem)‡ Unknown Unspecified • Antipseudomonal β-lactam (i.e piperacillin/ tazobactam and cefepime) or carbapenem (i.e. meropenem, imipenem or doripenem) plus an aminoglycoside or antipseudomonal flouroquinolon (i.e. levofloxacin or ciprofloxacin) plus vancomycin CAP = community-acquired pneumonia; HAP = hospital-acquired pneu- monia; HCAP = healthcare-associated pneumonia; VAP = ventilator-assoc- iated pneumonia; CRBSI = catheter-related blood-stream infection. *Vancomycin or linezolid can be added if methicillin-resistant Staphylococcus aureus is suspected. †If there is a high rate of resistance to vancomycin (minimum inhibitory concentration of ≥2 µg/mL). ‡This regimen is also recommended if there is a risk of multidrug resistance. Ratna S. Dewi, Maksum Radji and Rizka Andalusia Clinical and Basic Research | e369 The diagnosis of sepsis and septic shock were based on international criteria.1 Data were collected from the patients’ medical and drug-prescribing records using a predesigned structured form. This included the patients’ demographic characteristics, diagnosis, length of stay (LOS), Sequential Organ Failure Assessment (SOFA) score, the presence of co-morbidities (i.e. malignancy, diabetes mellitus, cardiovascular disease, chronic kidney disease, liver disease or respiratory insufficiency), source of infection, ventilator use, causative pathogens, antibi- otic usage (i.e. type and dose), the timing of the specimen collection for culture and outcome. In addition, samples of blood, sputum, bronchial rinse and urine were collected for cultures and antimicrobial sensitivity testing. Antibiotics were assessed for appropriateness acc- ording to type and dosage. Local microbial patterns during the period of June to December 2016 in the ICU were used to determine antimicrobial susceptibility data.9 The type of antibiotic prescribed during the study period was subsequently deemed appr- opriate if it was prescribed empirically according to the local microbial susceptibility data, whereas it was deemed to be inappropriate if it did not reflect the susceptibility data. This assessment was undertaken by the Antibiotic Stewardship Committee of the hospital, consisting of physicians, clinical pharmacists and nurses. Additionally, the appropriateness of each type of antibiotic was cons- idered in light of the source of infection, as determined by the attending physician [Table 1].17–20 The initial dose of the antibiotic was deemed appropriate after adjustment for the patient’s clinical condition, while unadjusted dos- ages were considered inappropriate.21 Data were analysed using the Statistical Package for the Social Sciences (SPSS), Version 23.0 (IBM Corp., Armonk, New York, USA). The independent variable was the appropriateness of the antibiotics (according to dose and type) and the dependent variable was patient outcome. Other variables included age, gender, diagnosis, number of comorbidities, ventilator use and SOFA score. Differences in the appropriateness of antibiotics based on local microbial patterns were presented as descriptive data, while differences in the appropriateness of anti- biotics based on the source of infection and dosage were presented as both descriptive and analytical data. A corr- ected Chi-squared test was used to determine if the diff- erences were significant. All correlations with a P value of <0.250 were included in a subsequent multivariate analysis. A logistic regression analysis was performed to identify factors influencing patient outcome. A P value of <0.050 was considered statistically significant. Ethical approval for this study was obtained from the Ethical Committee of Dharmais Cancer Hospital (#013/KEPK/II/2017). No patient consent was deemed necessary as permission to review the medical records was granted by the appropriate authorities at Dharmais Table 2: Characteristics of sepsis patients admitted to the intensive care unit of Dharmais Cancer Hospital, Jakarta, Indonesia (N = 60) Characteristic n (%) Age in years 18–39 9 (15) 40–59 39 (65) ≥60 12 (20) Mean ± SD (range) 51.4 ± 11.7 (24–82) Gender Male 32 (53.3) Female 28 (46.7) Diagnosis Sepsis 31 (51.7) Septic shock 29 (48.3) Length of stay in days ≥7 12 (20) <7 48 (80) Median ± SD (range) 4.0 ± 4.4 (2–23) Ventilation use Yes 52 (86.7) No 8 (13.3) SOFA score >8 29 (48.3) ≤8 31 (51.7) Source of infection HAP 37 (61.7) IAI 11 (18.3) CAP 3 (5) UTI 2 (3.3) HCAP 1 (1.7) Unknown 6 (10) Number of comorbidities ≥2 56 (93.3) <2 4 (6.7) Type of comorbidity* Malignancy 60 (100) Respiratory insufficiency 51 (85) Cardiovascular disease 20 (33.3) Chronic kidney disease 16 (26.7) Liver disease 7 (11.7) Diabetes mellitus 2 (3.3) SD = standard deviation; SOFA = Sequential Organ Failure Assessment; HAP = hospital-acquired pneumonia; IAI = intra-abdominal infection; CAP = community-acquired pneumonia; UTI = urinary tract infection; HCAP = healthcare-associated pneumonia. *Percentages do not add up to 100% as some patients may have had more than one comorbidity. Evaluation of Antibiotic Use Among Sepsis Patients in an Intensive Care Unit A cross-sectional study at a referral hospital in Indonesia e370 | SQU Medical Journal, August 2018, Volume 18, Issue 3 Cancer Hospital. All information obtained during the review of the records was kept confidential and used only for the purposes of this study. Results A total of 182 patients were admitted to the ICU of Dharmais Cancer Hospital during the study period. Of these, 60 adults (33%) were diagnosed with either sepsis (51.7%) or septic shock (48.3%). The mean age of the patients was 51.4 ± 11.7 years (range: 24–82 years old) and 53.3% were male. The median LOS was 4.0 ± 4.4 days (range: 2–23 days), with 80% staying less than seven days. Most patients had a SOFA score of ≤8 (51.7%) and used a ventilator (86.7%). The most common source of infection was hospital-acquired pneumonia (HAP; 61.7%), followed by intra-abdominal infections (IAI; 18.3%). Almost all of the patients had two or more comorb- idities (93.3%), with the most frequent being malignancy (100%) and respiratory insufficiency (85%) [Table 2]. Blood, sputum, bronchial rinse and urine samples were available for 49 patients (81.7%). A total of 66 cult- ures were taken from the samples, of which 44 (66.7%) were positive and 22 (33.3%) were negative. Overall, 21 microorganisms were detected in the positive cult- ures, the most common being Acinetobacter baumannii (15.2%), followed by Escherichia coli (6.1%), Klebsiella pneumoniae (4.6%) and Staphylococcus haemolyticus (4.6%). Of the isolates from positive cultures, 41 (93.2%) were known to be susceptible to antibiotics, while the remaining three (6.8%) contained only fungi. In total, 39.3% of the microorganisms were resistant to the anti- biotic administered, 28.6% were sensitive to the antibiotic administered, 4.8% had intermediate resistance to the antibiotic administered or required a higher dose and 27.4% were not tested for sensitivity. Pseudomonas aeruginosa was the most sensitive to the administered antibiotics (87.5%), while A. baumannii was the most resistant (72.2%). In total, there were 115 different antibiotic regimens, of which eight (7%) constituted definitive therapy and 107 (93%) were empirical. A total of 16 antibiotics were prescribed. Meropenem (41.1%) was most frequently prescribed, followed by levofloxacin (20%) and amikacin (11.3%). Levofloxacin was prescribed in three of the def- initive regimens (37.5%) [Figure 1]. The most common antibiotic regimens consisted of meropenem (16% in HAP cases, 40% in community-acquired pneumonia (CAP) cases, 50% in IAI cases and 33.3% in cases wherein the source of infection was unknown), mero- penem plus levofloxacin (26% in HAP cases, 40% in Table 3: Correlations between appropriateness of type and dose of antibiotics and outcome among sepsis patients admitted to the intensive care unit of Dharmais Cancer Hospital, Jakarta, Indonesia (N = 60) Variables n (%) P value* Total Died (n = 41) Survived (n = 19) Type of antibiotic Inappropriate 20 (33.3) 17 (85) 3 (15) 0.050 Appropriate 40 (66.7) 24 (60) 16 (40) Dose of antibiotic Inappropriate 31 (51.7) 25 (80.6) 6 (19.4) 0.034 Appropriate 29 (48.3) 16 (55.2) 13 (44.4) *Using a Chi-squared test. Figure 1: Distribution of empirical and definitive antibiotic regimens prescribed to sepsis patients admitted to the intensive care unit of Dharmais Cancer Hospital, Jakarta, Indonesia. *Inappropriate according to local microbial patterns/antimicrobial susceptibility data. Ratna S. Dewi, Maksum Radji and Rizka Andalusia Clinical and Basic Research | e371 CAP cases and 14.3% in IAI cases), cefepime plus amik- acin (100% in healthcare-associated pneumonia cases), cefotaxime and ceftriaxone plus levofloxacin (50% each in urinary tract infection cases). Overall, 23 patients (38.3%) received one antibiotic, 26 (43.3%) received two antibiotics, four (6.7%) received three antibiotics, five (8.3%) received four antibiotics and two (3.3%) received five antibiotics. A total of 20 patients (33.3%) received inappropriate types of antibiotics according to either local microbial patterns or the source of infection (45.2% and 25%, respectively). Inappropriate doses of antibiotics were prescribed to 31 patients (51.7%), with dose adjustments required by 16 patients (26.7%). The mortality rate was 68.3%. There was a statistically significant positive assoc- iation between patient outcome and inappropriate doses of antibiotics (P = 0.034), but not inappropriate types of antibiotics (P = 0.050) [Table 3]. According to a bivariate analysis, a diagnosis of septic shock, having at least two comorbidities, ventilator use, a SOFA score of >8 and the presence of a liver disorder had an effect on mortality (P <0.250 each) [Table 4]. A multivariate analysis indicated that a diagnosis of septic shock and the presence of at least two comorbidities were significantly associated with mortality (P <0.050 each) [Table 5]. Discussion In the current study, sepsis was more common among patients under 60 years old, although the mortality rate was higher among those over 60 years old. In the USA, the risk of sepsis increases with every Table 4: Correlations between risk factors and outcome among sepsis patients admitted to the intensive care unit of Dharmais Cancer Hospital, Jakarta, Indonesia (N = 60) Risk factor n (%) P value* Total Died (n = 41) Survived (n = 19) Age in years ≥60 12 (20) 9 (75) 3 (25) 0.579 <60 48 (80) 32 (66.7) 16 (33.3) Gender Male 32 (53.3) 23 (71.9) 9 (28.1) 0.528 Female 28 (46.7) 18 (64.3) 10 (35.7) Diagnosis Sepsis 31 (51.7) 15 (48.4) 16 (51.6) 0.001 Septic shock 29 (48.3) 26 (89.7) 3 (10.3) Ventilator use Yes 52 (86.7) 37 (71.2) 15 (28.8) 0.231 No 8 (13.3) 4 (50) 4 (50) SOFA score >8 29 (48.3) 25 (86.2) 4 (13.8) 0.004 ≤8 31 (51.7) 16 (51.6) 15 (48.4) Number of comorbidities ≥2 56 (93.3) 40 (71.4) 16 (28.6) 0.054 <2 4 (6.7) 1 (25) 3 (75) Type of comorbidity Malignancy 60 (100) 41 (68.3) 19 (31.7) - Respiratory insufficiency 51 (85) 36 (70.6) 15 (29.4) 0.371 Cardiovascular disease 20 (33.3) 15 (75) 5 (25) 0.432 Chronic kidney disease 16 (26.7) 12 (75) 4 (25) 0.503 Liver disease 7 (11.7) 7 (100) 0 (0) 0.055 Diabetes mellitus 2 (3.3) 2 (100) 0 (0) 0.327 SOFA = Sequential Organ Failure Assessment. *Using a Chi-squared test. Table 5: Multivariate analysis showing correlations bet- ween risk factors and outcome of sepsis patients in the intensive care unit of Dharmais Cancer Hospital, Jakarta, Indonesia (N = 60) Factors OR (95% CI) P value* Step 1 Septic shock 0.064 (0.007–0.573) 0.014 Presence of liver disease 0.000 0.999 Ventilator use 0.485 (0.050–4.706) 0.533 SOFA score of >8 0.295 (0.066–1.310) 0.108 ≥2 comorbidities 0.042 (0.002–1.018) 0.051 Constant 78.297 0.015 Step 2 Septic shock 0.063 (0.007–0.561) 0.013 Presence of liver disease 0.000 0.999 SOFA score of >8 0.294 (0.067–1.290) 0.105 ≥2 comorbidities 0.033 (0.001–0.786) 0.035 Constant 51.619 0.018 Step 3 Septic shock 0.048 (0.006–0.411) 0.006 SOFA score of >8 0.251 (0.060–1.053) 0.059 ≥2 comorbidities 0.023 (0.001–0.556) 0.020 Constant 71.819 0.012 OR = odds ratio; CI = confidence interval; SOFA = Sequential Organ Failure Assessment. *Using a logistic regression test. Evaluation of Antibiotic Use Among Sepsis Patients in an Intensive Care Unit A cross-sectional study at a referral hospital in Indonesia e372 | SQU Medical Journal, August 2018, Volume 18, Issue 3 year of age by 1.5%.22 Increased age over 60 years is a predictor of mortality in sepsis, particularly if adequate empirical antibiotic therapy is not initiated.23 In terms of gender, there were slightly more male than female patients in the current study. However, the frequency of sepsis among male patients was higher in a similar study conducted by Ferrer et al. (61.9%).24 Adrie et al. demonstrated that older men are more vulnerable to sepsis than women.25 Another study showed that cross-linked mutations or polymorphisms in female mice resulted in the more dynamic activation, regulation and function of immune cells during the inflammatory process, while male mice only demonstr- ated a partial response to inflammation.26 Unfortunately, the mortality rate of patients with septic shock in ICUs remains high, despite fluid resusc- itation measures, adequate care and the early administr- ation of empirical antibiotics.27 In the current study, a diagnosis of septic shock was significantly associated with mortality, despite septic shock being less common. In a similar study, Ogura et al. reported that 45.2% of Japanese patients were diagnosed with septic shock, with a significantly higher mortality rate in this group (63.6% versus 37.5%; P <0.010).28 In sepsis, venodilation, fluid transudation from the vesicular space into the tissues, decreased oral intake and increased fluid loss facilitates the occurrence of hypovolaemic events; in septic shock, ventricular dysfunction and arteriolar dilatation contr- ibute to the failure of function and organ perfusion.27 HAP is one of the most frequent and severe complic- ations observed among patients hospitalised in ICUs.29 In the current study, HAP was the most frequent source of infection. However, Katu et al. found CAP to be most common among sepsis patients in a referral hospital in Indonesia.14 This could be due to differences in the location of the study, the sample and incidence of infections, as well as the extent of each individual patient’s immune response. Empirical antibiotic therapy is key in the initial management of sepsis patients. The type of antibiotic to be prescribed is usually determined by an assessment of the potential pathogens responsible for the infection, taking into account local antibiotic susceptibility patterns.30 However, failure to determine the source of infection can potentially lead to the misidentification of pathogens, resulting in the inappropriate selection of antibiotics.8,9 Previous research has established that the administr- ation of inappropriate antimicrobials substantially incr- eases mortality among sepsis patients.8,11–13 In the current study, a significant association was noted between inappr- opriate doses of antibiotics and mortality; however, there was no significant association between inappropriate types of antibiotics and mortality. In contrast, Katu et al. found that inappropriate types of antibiotics were sign- ificantly associated with mortality.14 This variation in results may again be due to differences in the sample as well as study design, such as the inclusion and exclusion criteria and antibiotic guidelines used. Nevertheless, the multivariate analysis in the present study indicated that the most significant factors associated with mort- ality were septic shock and the presence of at least two comorbidities; therefore, regardless of the appropriat- eness of the antibiotics administered, the mortality rate was still high. This is likely due to the critical clinical cond- ition of such patients, which is generally poor in light of their admission to the ICU. According to international guidelines, it is strongly recommended that appropriate antimicrobial therapy be administered within one hour of recognising cases of sepsis or septic shock.8 However, the exact antibiotic delivery time in the current study could not be assessed as almost all of the patients had received antibiotics prior to their admission to the ICU. Furthermore, anti- microbial sensitivity testing was not performed for all of the antibiotics administered during the study period due to interdepartmental miscommunication, wherein staff of the microbiology laboratory were unaware of the specific antibiotics being administered to sepsis patients in the ICU. Additionally, as the Antibiotic Stew- ardship Committee was still under development during this time, no uniform reference was available for the selection of antibiotics by hospital staff. Finally, microbial cultures could not be performed in 11 cases due to diff- iculties collecting samples from these patients. Conclusion This study found that inappropriate doses of antibiotics were significantly associated with mortality among sepsis patients in an Indonesian ICU, although inappropriate types of antibiotics were not. Furthermore, a diagnosis of septic shock and the presence of at least two comorb- idities were significant risk factors related to mortality. c o n f l i c t o f i n t e r e s t The authors declare no conflicts of interest. f u n d i n g No funding was received for this study. References 1. Singer M, Deutschman CS, Seymour CW, Shankar-Hari M, Annane D, Bauer M, et al. The third international consensus definitions for sepsis and septic shock (Sepsis-3). JAMA 2016; 316:801–10. doi: 10.1001/jama.2016.0287. https://doi.org/10.1001/jama.2016.0287 Ratna S. Dewi, Maksum Radji and Rizka Andalusia Clinical and Basic Research | e373 2. International Sepsis Forum. Promoting a better understanding of sepsis. 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