Setting. This study took place at one of the largest hospitals in the area, King Abdulaziz Medical City (KAMC), an academic tertiary hospital with a bed capacity of 1501 in Riyadh, Saudi Arabia. The study was approved from King Abdullah International Medical Research Centre (KAIMRC) Institutional Review Board, with a waiver of informed consent from patients as there was no intervention and no more than minimal risk involved.
Population. All patients 15 years and older admitted to KAMC from FEB 2018 to JAN 2019, with CCRT activation who received antibiotics. Exclusion criteria included antimicrobials agents other than antibiotics or antifungal (e.g. antiviral), antibiotics with an indication other than infection (e.g. erythromycin for gastroparesis), and routs other than oral and intravenous.
Study design and Data collection. Single-center, prospective observational cohort study design used. Data were collected using a monitoring form, following characteristics were assessed: demographic data (table.1), date of CCRT activation, hospital admission/discharge dates, vital signs, antibiotics used, microbial culture, ADE (anaphylaxis, skin, hematological, renal, liver and others). CCRT team send a list of the patients have been visited in the prior week, CCRT coordinator will randomly include patients in the study. An infectious disease specialist physician and a clinical pharmacist meet weekly to determine the appropriateness of antibiotic use and the ADE incidence.
Outcome definition
Appropriateness of antimicrobial use: The use of an agent/s following MNGHA antimicrobial guidelines which maximizes clinical therapeutic effect while minimizing drug-related toxicity and the development antimicrobial resistance13
ADEs: any recognized injury/ potential injury associated with antimicrobials use and were evaluated post CCRT activation.
Acute kidney injury: Per KDIGO an increase in SCr by ≥ 0.3 mg/dl (≥26.5 µmol/l) within 48 hours; or increase in SCr to ≥1.5 times baseline, which is presumed to have occurred within the prior 7 days; or urine volume ˂ 0.5 ml/kg/h for at least 6 hours14
Hepatic impairment: marked elevation in aminotransferase levels more than 10 times the upper reference limit, or moderate elevation with 5–10 times the upper reference limit15
Hematological ADE: platelet count drop by 50% from the baseline or below a count of 150,000µl.
Statistical methods
Descriptive statistics were utilized to analyze the data. Continuous variables were summarized using mean ± standard deviation
Patients
A total of 315 CCRT patients received antibiotics treatment were included in this cohort study. The most common indication for antibiotics was pneumonia. The mean age of the patients was 61.1±20.4, and 54.6% participants were male. The most common admission diagnosis were cancer (52 [16.5%]), renal related conditions (37 [11.7%]), hepatobiliary and pneumonia of (34 [10.8%]) and infection (32 [10.2%]). The median length of hospital stay was 15 days (IQR, 10-30 days). The baseline characteristics are shown in Table 1.
Table 1. The baseline characteristics.
Characteristics
|
Mean (%)
|
Age
|
61.1±20.4
|
Gender:
Male
Female
|
172 (54.6%)
143 (45.4%)
|
BMI
< 30 kg/m2
≥30 kg/m2
|
210 (66.7%)
105 (33.3%)
|
Service
Medical
Surgical
Oncology
Others
|
177 (56.2%)
68 (21.6%)
44 (14.0%)
26 (8.2%)
|
Admission diagnosis
Cancer/tumor
Renal
Hepatobiliary
Pneumonia
Infection/sepsis
Trauma/orthopedic
Cardiac
Other lung disease
Surgical/post-surgical
Stroke
Others
|
52 (16.5%)
37 (11.7%)
34 (10.8%)
34 (10.8%)
32 (10.2%)
28 (8.9%)
23 (7.3%)
18 (5.7%)
18 (5.7%)
17 (5.4%)
51 (16.2%)
|
Length of stay (days)
|
15 (10-30)
|
Antibiotics Used
Through this study, we evaluated the antibiotics use before, during and after CCRT activation. Broad spectrum beta lactams and vancomycin were the most commonly used antibiotics (Table2). At any phase during the study, meropenem was the most frequent used antibiotics with a rate of 51.4%, followed by vancomycin 41.3%, and Piperacillin and tazobactam 28.6%.
Table 2. Antibiotics.
|
Before CCRT
|
By CCRT team
|
After CCRT
|
At any phase
|
Meropenem
|
25%
|
38%
|
37%
|
51.4%
|
Vancomycin
|
14%
|
30%
|
20%
|
41.3%
|
Piperacillin and tazobactam
|
18%
|
15%
|
16%
|
28.6%
|
Ceftriaxone
|
10%
|
4%
|
2%
|
12.1%
|
Linezolid
|
3%
|
5%
|
6%
|
8.6%
|
Colistin
|
4%
|
4%
|
4%
|
7.3%
|
Caspofungin
|
1%
|
3%
|
4%
|
6.7%
|
Anidulafungin
|
2%
|
2%
|
4%
|
5.7%
|
Tigecycline
|
3%
|
3%
|
3%
|
5.4%
|
Ciprofloxacin
|
4%
|
3%
|
3%
|
5.4%
|
Imipenem
|
3%
|
3%
|
2%
|
4.4%
|
Others
|
41%
|
37%
|
28%
|
70.5%
|
Adverse Drug Event
Total of 93 patients (29.5%) experienced at least one adverse event. The most common organ affected by antibiotics used was the renal 39 (12.4%), followed by the hematological adverse events in 36 patients (11.4%), gastrointestinal tract in 24 (7.6%), and hepatic with 14 (4.4%) (Table.3).
Table 3.
|
Total
|
Antimicrobial AE
|
|
None
|
222 (70.5%)
|
One or more
One
Two or more
|
93 (29.5%)
72 (22.9%)
21 (6.7%)
|
Antimicrobial AE
|
|
Renal
|
39 (12.4%)
|
Hematologic
|
36 (11.4%)
|
GIT
|
24 (7.6%)
|
Hepatic
|
14 (4.4%)
|
Skin
|
4 (1.3%)
|
Anaphylaxis
|
1 (0.3%)
|
Table 4. Other Outcomes.
Outcome
|
Total patients
(315)
|
Stay at floor
|
171 (54.3%)
|
Admission to ICU
|
114 (36.2%)
|
Mortality
|
9 (2.9%)
|
Discharge Home
|
2 (0.6%)
|
Others
|
2 (0.6%)
|