Excessive use of antibiotics, especially watch group antibiotics such as ceftriaxone leads to emergence and spread of antimicrobial resistance (AMR). In low and middle-income countries (LMICs), antibiotics are overused but data on consumption is scarcely available. We aimed at determining the extent and predictors of ceftriaxone use in a tertiary care university teaching hospital in Kilimanjaro, Tanzania. A hospital-based cross-sectional study was conducted from August 2013 through August 2015. Patients admitted in the medical, surgical wards and their respective intensive care units, receiving antimicrobials and other medications for various ailments were enrolled. Socio-demographic and clinical data were recorded in a structured questionnaire from patients’ files and logistic regression was performed to determine the predictors for ceftriaxone use. Out of the 630 patients included in this study, 322 (51.1%) patients were on ceftriaxone during their time of hospitalization. Twenty-two patients out of 320 (6.9%) had been on ceftriaxone treatment without evidence of infection. Ceftriaxone use for surgical prophylaxis was 44 (40.7%), of which 32 (72.7%) and 9 (20.5%) received ceftriaxone prophylaxis before and after surgery, respectively. Three (6.8%) received ceftriaxone prophylaxis during surgery. Predicting factors for that the health facility administered ceftriaxone were identified as history of any medication use before referral to hospital [OR = 3.4, 95% CI (1.0–11.4), p = 0.047], bacterial infection [OR = 18.0, 95% CI (1.4–225.7, p = 0.025)], surgical ward [OR = 2.9, 95% CI (0.9–9.4), p = 0.078] and medical wards [OR = 5.0, 95% CI (0.9–28.3), p = 0.070]. Overall, a high ceftriaxone use at KCMC hospital was observed. Antimicrobial stewardship programs are highly needed to monitor and regulate hospital antimicrobial consumption, which in turn could help in halting the rising crisis of antimicrobial resistance.

Introduction

Ceftriaxone is a third generation cephalosporin antibiotic. It is among a group of broad-spectrum antibiotics covering a wide range of infections. It is used as a first choice for acute bacterial meningitis, community acquired pneumonia (severe), complicated intra-abdominal infections (mild to moderate), complicated intra-abdominal infections (severe), hospital acquired pneumonia, Neisseria gonorrhoeae, pyelonephritis or prostatitis (severe). It is used as second choice for acute invasive bacterial diarrhoea / dysentery, bone and joint infections, pyelonephritis or prostatitis (mild to moderate), sepsis in neonates and children. [1,2].

In Tanzania, as in many other countries, ceftriaxone is as well among the “watch group” antibiotics[3–5]. Cephalosporins should only be prescribed when there is evidence of infection such as increase in serum procalcitonin levels or bacterial culture and sensitivity results from the clinical laboratory. However, ceftriaxone has often inappropriately and excessively been prescribed in clinical settings especially where there is lack of clear diagnosis[6,7]. Although ceftriaxone can be used as prophylaxis in certain situations, in a National Hospital in Tanzania, ceftriaxone was the most given prophylactic antibiotic regardless of the urological surgery done and its level of contamination[8]. The impact of irrational use of ceftriaxone on development of resistance to third-generation cephalosporins among clinical strains of Enterobacteriacea and other non- enteric bacteria is well known[9–11] and is one of the emerging global public health issues, particularly in LMICs [7,12]. This has furthermore lead the World Health Organization (WHO) to call for optimization of antimicrobial use to curb AMR [13]. If resistance to ceftriaxone is becoming widespread, not only are very few alternative antibiotic options available in LMICs like Tanzania, but these few options are as well unaffordable by the majority patients.

Unfortunately, resistance to third generation cephalosporins is already very high. For instance, in one review on AMR covering Eastern African countries the proportion of Gram negative and positive bacteria that were resistant to ceftriaxone was ranging from 46–96% and 50–100%, respectively[14]. In northwestern Tanzania, resistance to ceftriaxone was 29.4% in 2010[15] and 35% (in 2014) regarding resistance to carbapenems[16]. Furthermore, a study from Mwanza, Tanzania observed that 25 (80.6%) of Klebsiella pneumoniae were cephalosporin resistant and overall increase in resistant isolates to third-generation cephalosporins rose from 26.5% in 2014 to 57.9% in 2015 [17]. Another study from a tertiary care, university teaching hospital in Mwanza, Tanzania had previously revealed an increasing trend of bacterial resistance against ceftriaxone from 14% in 2009 to 29.4% in 2011[15]. In a 2013–2015 study at a tertiary care hospital in Kilimanjaro the reported resistance to ceftriaxone by Gram-negative bacteria among in-patients was 51.8% [18]. In East Africa, including Tanzania, there is a paucity of timely data on antibiotic consumption especially on ceftriaxone use in hospitals[14,19]. Therefore, the present study aimed at identifying the extent of ceftriaxone use and determining predictors of ceftriaxone use at a tertiary care and a university teaching hospital in Kilimanjaro Tanzania.

Materials and methods

Ethical approval and participant’s consent

This study was granted ethical approval by the KCMC Research Ethics Committee and the National Institute for Medical Research with approval numbers 893 and NIMR/HQ/R.8a/Vol.IX/2080 respectively. A written informed consent was obtained from each participant or from parents or guardians of children before enrolment into the study.

Study settings and design

A cross-sectional study was carried out from August 2013 through August 2015 at Kilimanjaro Christian Medical Centre (KCMC). KCMC is a consultant, tertiary care and a referral hospital located in Moshi municipality. It has a 650-bed capacity and the second largest consultant referral university teaching hospital serving over 12 million people from northern and central regions of Tanzania (http://www.kcmc.ac.tz/). The study involved inpatients. All admitted patients in medical and surgical wards and their respective Intensive Care Units who had a documented presumptive diagnosis of septicaemia and upper respiratory tract infection were enrolled. Also enrolled were those patients with diarrhoea, diabetic ulcer, patients with fever of unknown cause, wounds due to burns, surgical procedures, diabetes mellitus, animal bites, motor traffic accidents and other injuries. The study was granted ethical approval by the KCMC Research Ethics Committee and the National Institute for Medical Research. A written informed consent was obtained from each participant or from parents or guardians of children before enrollment into the study.

Data abstraction and analysis

Data were extracted from patient files among all inpatients in medical and surgical wards with a presumptive diagnosis of a bacterial infection. Data collected include type of ward, use of ceftriaxone or any other antibiotics, clinical diagnoses and socio-demographics. All data were recorded in a structured questionnaire and double entered in OpenClinica (OpenClinica LLC, MA, USA). Data were cleaned and analyzed using Stata 13 (StataCorp LP, Texas 77845, USA). The proportion of ceftriaxone use was determined by dividing the number of patients taking ceftriaxone by the total number of patients who had a presumptive diagnosis of a bacterial infection. The prevalence of ceftriaxone use across categorical variables (such as gender, timing of prophylaxis, presence of infection, diagnoses, number of days of hospital stay et cetera) was compared using Chi-square or Fisher’s exact tests. Bivariate and adjusted logistic regression analyses were used to determine possible factors that were associated with ceftriaxone use. Both forward selection and backward elimination model building approaches were performed and were both found to predict the same final model. Statistical significance was set at cut off points of 0.20 and 0.10 for bivariate and adjusted analyses respectively.

Results

Study population characteristics

The study population included patients admitted in the wards of KCMC as previously described by Kumburu et al[18]. A total of 630 patients were included in analysis, of which males were 360 (59.1%), 343 (58.8%) were married and 256 (42.6%) were aged 19–45 years. Those with primary education were 359 (62.1%), farmers were 290 (49.2%) and who had stayed in hospital for a week or less were 393 (64.0%)