Suboptimal access to ceftriaxone among adult postoperative patients at Mulago National Referral Hospital, Uganda: Prevalence and associated factors

doi:10.21203/rs.3.rs-4878064/v1

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Suboptimal access to ceftriaxone among adult postoperative patients at Mulago National Referral Hospital, Uganda: Prevalence and associated factors

https://doi.org/10.21203/rs.3.rs-4878064/v1

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Background

An estimated 4.95 million deaths associated with bacterial antimicrobial resistance (AMR) occurred globally in 2019. Access to ceftriaxone is still low, causing 11.2% of patients not to complete their treatment in health facilities. Therefore, this study determined the prevalence and factors associated with suboptimal access to ceftriaxone among adult post-operative patients in Mulago National Referral Hospital, Uganda.

Methods

The study employed a cross-sectional design, and was conducted at Mulago National Referral Hospital, among 443 adult postoperative patients who received a prescription for ceftriaxone, from August to November 2023. Ethical approval was obtained from the Mulago Hospital Research and Ethics Committee (Ref: MHREC 2473), and permission was obtained from the Uganda National Council of Science and Technology (ref number: HS2936ES). Suboptimal access was a state where a patient received less than 100% of the prescribed amount of ceftriaxone vails for all postoperative days, from the hospital pharmacy; measured using self-reports and chart reviews. Data were collected from systematically sampled and consented patient caretakers using questionnaires. Data were entered into Epidata software and exported into STATA software version 14.0 for analysis, using Modified Poisson regression.

Results

The median age of 443 patients was 38 years (IQR: 28–50), and 77.9% (345/443) were male. The prevalence of suboptimal access to ceftriaxone was 79% (350/443), and 61% (270/350) of these had no access at all. Factors associated with suboptimal access included; the gender of the patient, knowledge of the pharmacy location, dispensers’ availability, and pharmacy working hours.

Conclusion

Suboptimal access to ceftriaxone among postoperative patients was high. Knowledge of the pharmacy location, gender of the patient, pharmacy dispensers’ availability, and appropriateness of working hours were positive predictors of suboptimal access. Ward emergency drug cabins should be refilled routinely, and hospital pharmacies should open for 24 hours daily. The hospital medicines and supplies budget should be increased, and rational antibiotic use should be investigated.

Ceftriaxone access

Mulago hospital

Access to drugs

antimicrobial resistance

Antibiotics have revolutionized the reach of surgical intervention, both by treating and preventing infection-related complications [1]. Inappropriate antibiotic use can lead to antimicrobial-resistant infections. An estimated 4.95 million deaths associated with bacterial antimicrobial resistance (AMR) occurred globally in 2019. In western Sub-Saharan Africa, 27.3 deaths per 100,000 were attributable to AMR [2].

Antimicrobial resistance (AMR) hurts global health security and healthcare [3]. AMR is accelerated by misuse of antimicrobial agents, self-medication, and unrestricted access to medicines; that result in the flourishment of drug-resistant organisms [3]. Ceftriaxone is one of the most commonly used antimicrobials in post-operative patients [4].

Ceftriaxone is a broad-spectrum antibiotic, highly effective against Gram-negative and Gram-positive microorganisms. This is taken for at least three days because this is when a reasonable effect of antibiotics on any infection can be observed. However, the level of access can affect its activity, which can cause resistance. The overall resistance to ceftriaxone is 57.2% [5]. AMR patterns for E.coli, which causes most wound infections; showed that ceftriaxone has a resistance of 65% in Uganda [6].

The AMR action plan aims to optimize access to effective antimicrobial medicines in human health by ensuring controlled access, effective antimicrobial stewardship, and appropriate use [3]. Nearly 50% of parenteral antibiotic consumption in public health facilities is ceftriaxone [4]. Studies have shown that 11.2% of the patients in health facilities in Uganda did not complete their ceftriaxone treatment because of drug stock-outs [7]; which could lead to the development of resistance to ceftriaxone.

AMR patterns for E.coli, which causes most wound infections; showed that ceftriaxone has a resistance of 65% [6]. Therefore, there is a need for optimal ceftriaxone access especially in post-operative patients, to avoid escalation of this resistance. Factors affecting ceftriaxone access include; lack of knowledge, medicine shortages, limited funds, interrupted supplies, lack of clinical guidelines, and pressure from patients and peers [8].

Suboptimal access to ceftriaxone can lead to increased resistance which results in wound sepsis, mortality, and constraints on the health budget. Sepsis can also lead to reduced human productivity because of long hospital stays. This can reduce the gross domestic product of the country, and affect the attainment of universal health coverage by 2030. This study, therefore, aimed to determine the prevalence and factors associated with suboptimal access to ceftriaxone among adult postoperative patients at Mulago National Referral Hospital, Uganda.

Study setting

The study was conducted in the directorate of surgical services at Mulago National Referral Hospital. This directorate offers majorly inpatient services specializing in surgeries. General surgeries include; neurology, urology, breast and endocrine, colo-rectal, ophthalmology, anesthesia, rhinology and ENT, pediatric surgery, organ transplant, intensive care unit, respiratory, and allergy. The surgery directorate carries out 726 surgeries quarterly, and 80% of the patients are prescribed ceftriaxone post-operatively (hospital monthly reports).

Study design and population

This was a cross-sectional study; and collected only quantitative data. We administered questionnaires to caretakers of 443 postoperative patients, 18 years and older in Uganda, who had sought care from August to November 2023; and had been prescribed ceftriaxone for at least 3 days, after surgery. This is taken for at least three days because this is when a reasonable effect of antibiotics on any infection can be observed. Patients without caretakers were excluded.

Sample size and sampling procedure

We used the Kish-Leslie formula for a single proportion to calculate a sample size of 443, with a precision of 5%, a proportion of suboptimal access of 6% (pilot study), Z_α/2- the standard normal value corresponding to 95% level of confidence (1.96), and 10% missing data. For factors associated, we used the formula for two proportions, with a Z_β-standard normal value corresponding to an 80% power of 0.84. The proportion of female participants who had suboptimal access to ceftriaxone, P₁ was 0.5. The proportion of male patients who had suboptimal access to ceftriaxone, P₂ was 0.6 [7].

Patient files were systematically sampled using a sampling interval of six (obtained by dividing the total expected population over the study period by sample size). The selected file was checked to identify if the patient was being treated with ceftriaxone after the operation. The patient caretaker was then approached to obtain informed consent, and he/she was asked questions about access to ceftriaxone in the hospital pharmacies; while recording answers in the questionnaires. The researchers checked the filled questionnaires for completion and then kept them for data entry. Data was abstracted from patient files and these were then kept for data entry. For factors associated, we collected data on; age, sex, education level, employment status, monthly income, drug availability, health worker availability, and health worker adequacy. The consent rate for caregivers was 95%.

Outcome measurement

Optimal access to medicine in the study was a state where a patient received 100% of the prescribed ceftriaxone vials for post-operative days from the hospital pharmacy. Suboptimal access to medicine was thus the state where a patient received less than 100% of the prescribed amount of ceftriaxone vails for all postoperative days, from the hospital pharmacy, measured using self-reports. This was measured using a question; did you receive ceftriaxone from the hospital pharmacies, with Yes or No responses? A question about vials received followed; how many vials/bottles did you receive from the hospital pharmacy? Access was measured using self-reports for at least the last three postoperative days. Access was obtained by getting the percentage of the number of vials of ceftriaxone obtained from the hospital pharmacy, out of the total vials prescribed postoperatively.

Data management and analysis

Data obtained from questionnaires were cross-checked for omissions, completeness, and errors, and coded before being double-entered in Epidata, which was password-protected. It was then exported to the STATA version 14 statistical software package for analysis.

We summarized continuous variables as median and interquartile ranges; and categorical variables into frequencies and percentages with a 95% confidence interval for suboptimal access. Bivariate analysis was carried out for all variables using modified Poisson regression with robust standard errors. A cut-off of 0.2 was used to get variables for multivariable analysis. Prior knowledge from published literature was used to include other variables that are associated with suboptimal access but had a p-value greater than 0.2 in the data. Variables included in multivariable analysis included; age, education level, employment status, monthly income, drug availability, health worker availability, and health worker adequacy. Multivariable modified Poisson regression was employed at a 5% level of significance, and an assessment of interaction was done using the likelihood ratio test. Confounding was assessed using a change in prevalence ratio >10%, to establish if there were any variables confounding others in the final model. The factors independently associated with suboptimal access to ceftriaxone were established.

Baseline characteristics

Table 1

Sociodemographic characteristics of 443 postoperative patients, prescribed Ceftriaxone at Mulago National Referral Hospital, Uganda
Variable	Median (IQR)	Frequency (n = 443)	Percentage
Age (years) 18–35 36–49 50–84	38 (28–50)	199 128 116	44.9 28.9 26.2
Gender Female Male		98 345	22.1 77.9
Education level (Highest) (n = 431) Primary Secondary Diploma Degree Uneducated		133 159 54 30 55	31.0 37.0 13.0 7.0 13.0
Employment status Employed Unemployed		322 121	72.7 27.3
*Monthly income Uganda shillings** ˂Poverty line ≥Poverty line	200,000 (0-400,000)	177 115	60.6 39.4
Surgery unit Trauma ward Neurosurgery ward Gastrointestinal ward Cardiothoracic ward Oral/maxillofacial Orthopaedic ward Urology ward Spine ward Breast and Endocrine Arthroplasty ward		144 101 76 43 29 18 9 9 8 6	32,5 22.9 17.1 9.7 6.6 4.0 2.0 2.0 1.8 1.4
IQR-Interquartile range

The poverty line is equivalent to 1.77 United States Dollars per person per day [9]

*-Monthly income had a total of 292 participants

The median age of 443 participants was 38 years (IQR: 28–50), while the median monthly income was 200,000 (IQR: 0-400,000) Uganda shillings (USD: 52.6; IQR: 0-105.3). The majority of the participants were male (77.9%, 345/443), while most of them had below diploma as the highest education level (67.8%, 292/431). The employed participants were up to 72.7% (322/443), while 32% (144/443) were from the Trauma ward (Table 1).

Prevalence of suboptimal access to ceftriaxone

Table 2

Ceftriaxone access among 443 postoperative patients at Mulago National Referral Hospital, Uganda
Variable	Prevalence(n)	95% Confidence Interval Lower limit Upper limit
Self-reported access Optimal Suboptimal	21 (93) 79 (350)	17.4 75.0	25.1 82.6
0% (1–33) % (33.1–67) % (67.1–99) %	61 (270) 3.1 (14) 14.2 (63) 0.7 (3)	56.3 1.9 11.3 0.2	65.4 5.3 17.8 2.1

Out of the 443 participants enrolled in the study, 79% (350; 95%CI: 75.0-82.6)) reported suboptimal access to ceftriaxone. Approximately 61% (270/350; 95%CI: 56.3–65.4) of the participants had no access to ceftriaxone (Table 2).

Factors associated with suboptimal access to ceftriaxone among postoperative patients in Uganda

Table 3

Multivariate analysis for factors associated with suboptimal access to ceftriaxone among post-operative patients
Variable	Suboptimal access		Crude Prevalence ratio, cPR (95% CI)	p-value	Adjusted prevalence ratio aPR (95% CI)	p-value
	Yes, n (%)	No, n (%)
Gender Male Female	269 (76.9) 81 (23.1)	76 (81.7) 17 (18.3)	1 0.79(0.49, 1.27)	0.33	1 1.09(0.98,1.22)	0.096
Know pharmacy location Yes No	177 (50.6) 173 (49.4)	86 (92.5) 7 (7.5)	1 0.12(0.06, 0.25)	˂0.001	1 1.32(1.21,1.44)	˂0.001
Dispensers available Yes No	270 (77.4) 79 (22.6)	91 (97.9) 2 (2.1)	1 0.09(0.25, 0.39)	0.001	1 1.06(0.99,1.13)	0.091
Working hours appropriate Yes No	168 (48.3) 180 (51.7)	80 (86.0) 13 (14.0)	1 0.21(0.12, 0.36)	˂0.001	1 1.25(1.14,1.36)	˂0.001

Multivariable analysis showed that knowing where the pharmacy is located (aPR: 1.32; 95%CI:1.21–1.44), and appropriate pharmacy working hours (aPR: 1.25; 95%CI:1.14–1.36) were significantly associated with suboptimal adherence to ceftriaxone. The analysis showed that the gender of the patient confounds knowledge of pharmacy location. The dispenser's availability also confounds pharmacy working hours (Table 3).

Prevalence of suboptimal access to ceftriaxone

The prevalence of suboptimal adherence to ceftriaxone was 79% (350/443; 95%CI: 75.0-82.6). Approximately 79 out of 100 adult postoperative patients did not access all the ceftriaxone which they had been prescribed, from the hospital pharmacies. This is high considering that the national AMR plan aims to promote optimal access and use of antimicrobials to humans [3].

The majority of participants receive ceftriaxone for one or two days; and tend not to go back to the pharmacies for refill, possibly due to the congestion, and long waiting time at the pharmacies in the hospital. Other patients have a poor attitude towards the hospital because previously, there was a lot of stockouts of medicine. Therefore; they chose not to go to the pharmacy for ceftriaxone, even after availability had improved. Some patients are prescribed ceftriaxone at night when the pharmacies are closed, so they cannot access the medicine. The healthcare workers sometimes do not direct the patients to the hospital pharmacies. This prevalence was high possibly due to some stockouts in some pharmacy units for some period of the study.

This high prevalence can breed antibiotic resistance because most of the population studied cannot afford to buy ceftriaxone from pharmacies outside the hospital. The results are consistent with a study in Uganda in 2021 which stated that patients missed ceftriaxone doses because of drug stockouts [7].

Factors associated with suboptimal access to ceftriaxone

Knowledge of pharmacy location

Knowing where the pharmacy was located within the hospital was significantly associated with suboptimal access to ceftriaxone (aPR: 1.32; 95%CI:1.21–1.44). The odds of suboptimal access to ceftriaxone were 0.32 times higher in participants who did not know where the pharmacy was located within the hospital than in ones who knew the pharmacy location. Penchansky defined geographical access as how easily a client can physically reach the provider’s location [10]. If the pharmacy location is very far from the wards, it becomes very hard for patients to reach the pharmacy to obtain ceftriaxone. Results are consistent with a report that stated that accessibility of pharmacies, and knowledge about where pharmacies are located affect access to medicine [11]. This is also consistent with a study that stated that geographical accessibility is a key dimension of access to medicines [12]. Better pharmacy visibility and directions can improve knowledge of the pharmacy location in the hospital.

Pharmacy working hours

Pharmacy working hours being appropriate was significantly associated with suboptimal access to ceftriaxone (aPR: 1.25; 95%CI:1.14–1.36). The odds of suboptimal access to ceftriaxone were 0.25 times higher in participants who did not find the pharmacy working hours appropriate than in those who found the working hours appropriate. If pharmacies are not open for 24 hours daily, some of the patients who are prescribed ceftriaxone at night might not access ceftriaxone. This might be due to other aspects like limited staff housing; therefore, pharmacy staff stay very far. Therefore; they take many hours on the road, hence reaching work a bit late. This reduces the hours of operation; hence some patient prescriptions are missed especially very early in the morning.

This is consistent with a report that states that care should be accessible in a timely way and that the hours of operation of the pharmacy affect access to medicine [11]. This is also consistent with Penchansky’s 5As theory which claims that hours of operation affect access to care [10]

Gender of patient

The gender of the patient confounded knowledge of the pharmacy location (aPR: 1.09; 95%CI:0.98, 1.22). The odds of suboptimal access to ceftriaxone were 0.09 times higher in female participants than in their male counterparts. Patient gender influences the odds of knowledge of pharmacy location by more than 10%.

Females are naturally inquisitive and can easily find out from other patients because of the social aspects they have compared to males. However, this study had only 22.1% of females which might be the reason why female participants had more suboptimal access compared to their male counterparts. Secondly, there is a possibility that the male patients had caretakers who were more inquisitive about the location of the hospital pharmacy, compared to caretakers of female patients. This implies that the keenness of the caretaker contributes greatly to access to medicines from the hospital pharmacies. This is contrary to a review of 885 patient treatment records sampled over three months from nine health facilities in Uganda which reported that gender was significantly associated (cOR: 0.6; 0.4–0.8) with appropriate medicine use at a bivariate level [7]

Dispensers’ availability

Availability of the dispenser at the pharmacy confounded pharmacy working hours (aPR: 1.06; 95%CI:0.99, 1.13). The odds of suboptimal access to ceftriaxone were 0.06 times higher in participants who did not find the dispensers available than those who found the pharmacy dispenser available. This means that dispensers’ availability influences the odds of appropriateness of pharmacy working hours by more than 10%.

Only 10 staff are available for the whole pharmacy department to serve the hospital. Therefore; one staff is deployed to each pharmacy. This one staff has to attend ward rounds, do therapeutic interventions on the ward, attend departmental meetings, and ensure that he replenishes stock for the patients from the hospital store. Some of these pharmacists who dispense in the pharmacies have to supervise intern pharmacists, pharmacy students, and pharmacy technician students. This limits his availability throughout the day, because of so many tasks. This even reduces the quality of the pharmaceutical care provided to the patients. The results are consistent with a report which stated that the availability of health dispensers determines the hours of operation [11].

Suboptimal access to ceftriaxone among postoperative patients was high. Knowing the pharmacy location, the female gender of the patient, the non-availability of the pharmacy dispenser, and the appropriateness of working hours were positive predictors of suboptimal access. Ward emergency drug cabins should be refilled routinely, and hospital pharmacies should have visibility improved, and open for 24 hours daily. More pharmacy staff need to be recruited, the hospital medicines and supplies budget should be increased, and rational antibiotic use should be investigated.

Ethical approval and consent to participate

Ethical approval was obtained from the Mulago Hospital Research and Ethics Committee (Ref: MHREC 2473), and permission was obtained from the Uganda National Council of Science and Technology (Ref: HS2936ES). Informed consent was obtained from participants.

Consent for publication

Not applicable

Availability of data and materials

The datasets used and/or analyzed during the current study are available from the corresponding author upon reasonable request.

Competing interests

The authors declare that they have no competing interests.

Funding

Mulago National Referral Hospital provided funding for the study.

Authors’ contributions

NE designed and conceptualized the study. NE did the data cleaning, data management, and preliminary analysis of the data. NE, RK, and RM contributed to the data analysis and report writing. All authors contributed to the interpretation of the findings. NE wrote the first draft of the paper. HM, RK, and RM reviewed, revised, and contributed to writing the paper. All authors read and approved the final manuscript. NE, RK, and RM read and met the ICMJE criteria for authorship.

Acknowledgments

The authors extend their sincere thanks to the research participants, and the management of Mulago National Referral Hospital for funding, and supporting the implementation of the study.

Authors information

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No competing interests reported.

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Suboptimal access to ceftriaxone among adult postoperative patients at Mulago National Referral Hospital, Uganda: Prevalence and associated factors

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Abstract

Background

Methods

Results

Baseline characteristics

Prevalence of suboptimal access to ceftriaxone

Factors associated with suboptimal access to ceftriaxone among postoperative patients in Uganda

Discussion

Prevalence of suboptimal access to ceftriaxone

Factors associated with suboptimal access to ceftriaxone

Knowledge of pharmacy location

Pharmacy working hours

Gender of patient

Dispensers’ availability

Conclusion

Declarations

References

Additional Declarations

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