Evaluation of Empirical Antibiotic Prescription and Urinalysis in Patients with Symptoms Suggestive of Uncomplicated Urinary Tract Infection in Abakaliki, Nigeria
O I, O OO, U EI, I EO, N O, U JI
antibiotics susceptibility, empirical prescriptions, haematuria, proteinuria, uropathogens
O I, O OO, U EI, I EO, N O, U JI. Evaluation of Empirical Antibiotic Prescription and Urinalysis in Patients with Symptoms Suggestive of Uncomplicated Urinary Tract Infection in Abakaliki, Nigeria. The Internet Journal of Laboratory Medicine. 2009 Volume 4 Number 2.
Antibiotic prescriptions without proper indication has been noted as a major contributory factor to the growing rate of bacteria resistance to antimicrobial agents.[1-3] Urinary tract infection (UTI) is one of the most common causes of morbidity in the general population, accounting for the majority of hospital visits. However, majority of patients do not eventually demonstrate significant bacteriuria. Urinalysis has been argued as cost effective adjunct to culture in the diagnosis and management of UTI. The aims of this study therefore were to evaluate pattern of antibiotic prescriptions, the appropriateness of such prescriptions and the role of routine urinalysis in the diagnosis of UTI.
Materials and methods
This study was conducted at Ebonyi State University Teaching Hospital (EBSUTH), Abakaliki. The hospital is a state owned tertiary health facility serving a population of about 255,000 within Abakaliki, the state capital. It also serves as a referral centre to other hospitals in the state and its environs. The study spanned from November 2008 to October 2009.
These comprised individuals who were attending the Out Patient Clinic of the hospital with symptoms suggestive of urinary tract infection and were provisionally diagnosed as such and were prescribed antibiotics prior to urine culture and sensitivity test. Patients with symptoms but did not receive empirical antibiotic prescription were excluded from the study. The protocol for this study was approved by the Ethics and Research Committee of Ebonyi State University Teaching Hospital, Abakaliki. The approval was on the agreement that patient anonymity must be maintained, good laboratory practice/quality control ensured, and that every finding would be treated with utmost confidentiality and for the purpose of this research only. All work was performed according to the international guidelines for human experimentation in clinical research. 
Midstream “clean catch” urine samples were collected from 500 adult patients who gave their consent to participate in the study, into sterile plastic universal containers. Information on prescribed antibiotics was retrieved from Out-patient drug sales register at the Pharmacy Department as most out-patients of the hospital procure their drugs at the hospital Pharmacy.
Standard laboratory methods and techniques were used in the analysis of the urine specimens. Briefly, aliquot (5.0 ml) of the unspunned sample was tested with dipstick (Macromed, Johannesburg, S.A.). The results of leucocyte esterase (Le), Blood (Bld), protein (Prot) and Nitrite (Nit) were recorded after appropriate reaction times. Leucocyte esterase was considered positive in the presence of any shade of colour change after 2 minutes. Nitrite was recorded positive if there was any colour change at one minute. Blood and protein were recorded positive at any shade of colour change after one minute. Thereafter the urine samples were centrifuged and examined microscopically for pus cells and casts, and subsequently the urine samples were aseptically inoculated into blood agar and MacConkey agar by standard loop technique. Plates were incubated aerobically at 370C for 24 hours and then observed for bacterial growth.  A growth of ≥ 105 colony forming units per millilitre was considered as significant. The organisms isolated from the samples showing significant bacteriuria were identified using colonial characteristics, Grams reaction, motility test and biochemical reaction . 
Preparation of antibiotic disc/susceptibility test
The antibiotic discs used for this study were prepared according to the method described by Ochei and Kolhatkar. The antibiotics were amoxicillin + clavulanic acid, ampiclox, erythromycin, clarithromycin, ofloxacin, ciprofloxacin, pefloxacin, cotrimoxazole, and cefuroxime. The antibiotics had official registration of the National Agency for Food and Drug Administration and Control (NAFDAC), Nigeria with their expiration dates ranging from December 2010-July 2011. The discs were impregnated with the antibiotic solutions to obtain the following concentrations per disc: Amoxycillin plus Clavulanic acid (30 µg), Ampiclox (30 µg), Erythromycin (30 µg), Clarithromycin (30 µg), Ciprofloxacin (10 µg), Ofloxacin (10 µg), Pefloxacin (10 µg), Cotrimoxazole (30 µg), and Cefuroxime (30 µg).
Antibiotic sensitivity testing
Few colonies of the respective isolates purified on Nutrient Agar® were suspended in sterile peptone water to obtain a turbidity corresponding to MacFarland 0.5  were used as inoculums. The Kirby-Bauer modified disc diffusion technique  was used for the sensitivity testing. The discs were evenly distributed on the sensitivity agar in such a way that they were 15 mm from the edge of the plate and 25 mm from one another. Each disc was gently pressed to ensure its sufficient contact with the sensitivity agar media. The plates were then incubated at 37 oC for 24 hours. Corresponding discs from ABTEC Biologicals Ltd, UK were used as controls. Guidelines of the National Committee for Clinical Laboratory Standards were followed for the interpretation of the sensitivity results.
Data were analysed for mean and standard deviation, percentage/proportions and comparison of parameters were done using one way analysis of variance (One-Way ANOVA) with level of statistical significance set at less than 0.05 (p < 0.05).
The age range of our patients was 18-52 years (mean = 42 ± 4.3 years). Two hundred and fifty one (50.2 %) of the samples were from males and 249 (49.8 %) were from females. From table 1, although more abnormalities were detected in urine samples from female patients in comparison to that found in the male samples, these were not statistically significant (p > 0.05). However, it was observed that urinalysis results for nitrite, protein and pyuria were comparable (p > 0.05) to that of culture result while that of leucocyte esterase and blood were significantly (p < 0.05) higher and lower respectively than that of culture results.
Significant bacteriuria was recorded in 213 (42.6 %) of the urine specimens while 182 (36.4 %) showed insignificant bacteriuria and 105 (21 %) were sterile.
From table 2, Amoxycillin plus Clavulanic acid was the most frequently prescribed antibiotic (23.6 %), followed in decreasing order by Ampiclox (21.4 %), Cotrimoxazole (17.8 %), Ciprofloxacin (16.6 %), Ofloxacin (7.6 %), Cefuroxime (5 %), Erythromycin (4.2), Pefloxacin (2.4 %), Clarithromycin (1.4 %).
The organisms grown on the culture of all the 213 specimens with significant bacteriuria were as follows (table 3):
Out of 62 isolates obtained from patients that received Amoxycillin + clavulanic acid as empirical prescription whose specimens also yielded significant bacteriuria, only 25 (40.3 %) were sensitive to the drug (table 3). Other observations on the rest of the antibiotics studied were as follows: Ampiclox (n = 40): 15 (37.5 %) sensitive, 25 (62.5 %) resistant; Cotrimoxazole (n = 26): 8 (30.8 %) sensitive, 18 (69.2 %) resistant; Ciprofloxacin (n = 39): 28 (71.8 %) sensitive, 11 (28.2 %) resistant; Ofloxacin (n = 17): 10 ( 58.8 %) sensitive, 7 (41.2 %) resistant; Pefloxacin (n = 4): 2 (50 %) sensitive, 2 (50 %) resistant; Cefuroxime (n = 12): 4 (33.3 %) sensitive, 8 (66.7 %) resistant; Erythromycin (n = 9): 5 (55.6 %) sensitive, 4 (44.4 %) resistant; Clarithromycin (n = 4): 2 (50 %) sensitive, 2 (50 %) resistant.
This study recorded significant bacteriuria in 42.6 % of the study populations with the percentage of urine samples with positive nitrite (34.0 %), protein (47.2 %) and pyuria (51.6 %) comparable to urine samples that yielded significant bacteriuria (42.6 %). Urinary tract infection (UTI) prevalence of 42.6 % recorded in this study was higher than 22 % and 34 % reported by Jombo
The uropathogens isolated from the present study were similar to those in other studies.[16, 17] The most frequently isolated organism (
Excessive prescription of antibiotics, especially in non-bacterial infections has been identified as one of the causes of emergence of resistant strains. In the present study, no correlation was made between frequency of antibiotic prescriptions and resistance pattern observed. However, amoxycillin-clavulanic acid which was most frequently prescribed had a sum resistance of 59.7 % in comparison to Ampiclox and cotrimoxazole that were less frequently prescribed with sum resistance of 62.6 % and 69.2 % respectively. The percentage resistance of microorganisms to antibiotics had earlier been used as a criterion to include or exclude such antibiotic from the list of choice agents for the treatment of UTI. If this is extrapolated to this study, it can be argued that those antibiotics that were relatively most resisted, especially the cotrimoxazole, Cefuroxime, Clarithromycin, Ampiclox and amoxycillin-clavulanic acid should be excluded from empirical treatment of uncomplicated urinary tract infections in this environment. The antibiotic susceptibility of
The higher rate observed in this study could be a reflection of over-diagnosis of UTI. We therefore conclude that although urinalysis may guides empirical antibiotic prescriptions, culture and sensitivity test prior to such prescriptions remain the best approach in avoiding the problems of rising antimicrobial resistance. However, Ciprofloxacin, a fluoroquinolone may be considered the first choice in empirical prescription.