PREVALENCE AND ASSOCIATED RISK FACTORS OF ASYMPTOMAT- IC BACTERIURIA IN ANTE-NATAL CLIENTS IN A LARGE TEACHING HOSPITAL IN GHANA

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PREVALENCE AND ASSOCIATED RISK FACTORS OF ASYMPTOMAT- IC BACTERIURIA IN ANTE-NATAL CLIENTS IN A LARGE TEACHING HOSPITAL IN GHANA A-K LABI 1, A.E. YAWSON 2, G.Y. GANYAGLO 3 and M.J.NEWMAN 4 1 Department of Microbiology Korle-Bu Teaching Hospital, 2 Department of Community Health, University of Ghana Medical School, College of Health Science, Korle-Bu, 3 Department of Obstetrics and Gynaecology, Korle-Bu Teaching Hospital, 4 Department of Microbiology, University of Ghana Medical School, College of Health Sciences, Korle-Bu DOI: http://dx.doi.org/10.4314/gmj.v49i3.5 Corresponding Author: Dr. Appiah-Korang Labi Conflict of Interest: None declared SUMMARY Introduction: Asymptomatic bacteriuria, the presence of bacteria in urine without symptoms of acute urinary tract infection, predisposes pregnant women to the development of urinary tract infections and pyelonephritis, with an attendant pregnancy related complications. Objective: To measure the prevalence of asymptomatic bacteriuria among ante-natal clients at the Korle-Bu Teaching Hospital in Ghana and its associated risk factors. Methods: A cross-sectional study involving 274 antenatal clients was conducted over a period of 4 weeks. A face to face questionnaire was completed and midstream urine collected for culture and antimicrobial susceptibility testing. Results: The prevalence of asymptomatic bacteriuria was 5.5%. It was associated with sexual activity during pregnancy (Fisher s Exact 5.871, p-value 0.0135), but not with sexual frequency. There were no significant associations with educational status, parity, gestational age, marital status and the number of foetuses carried. The commonest organism isolated was Enterococcus spp (26.7%) although the enterobacteriaceae formed the majority of isolated organisms (46.7%). Nitrofurantoin was the antibiotic with the highest sensitivity to all the isolated organisms. Conclusions: The prevalence of asymptomatic bacteriuria among ante-natal clients at this large teaching hospital in Ghana is 5.5%, which is lower than what has been found in other African settings. Enterococcus spp was the commonest causative organism. However, due to the complications associated with asymptomatic bacteriuria, a policy to screen and treat- all pregnant women attending the hospital, is worth considering. Key words: Asymptomatic bacteriuria, ante-natal clients, antibiotic sensitivity, tertiary hospital, Ghana Email: appiahl@yahoo.com INTRODUCTION Asymptomatic bacteriuria (ABU) is the presence of bacteria in urine without symptoms of acute urinary tract infection. 1, 2, 3 It is a common occurrence in both non pregnant and pregnant women. 1 However, when it occurs in pregnant women anatomical and hormonal changes from the pregnancy leads to dilatation of the renal pelvis and ureters with an attendant urinary stasis. This combined with the short nature of the female urethra and perineal colonization by enteric organisms, predisposes pregnant women to the development of urinary tract infections and pyelonephritis. 1,3,4,5 Enterobacteriaceae are responsible for 90% of asymptomatic bacteriuria cases, with Escherichia coli being the commonly isolated organism. 1-3, 6-10 Evidence exist that 30% of patients with asymptomatic bacteriuria if not treated go on to develop urinary tract infections. 4 Urinary tract infections and pyelonephritis in pregnancy has been associated with morbidity for both the mother and foetus. It has been associated with pre-eclampsia, polyhydramnios, pre-term birth, low birth weight. 1,4,11 Several studies conducted have shown that treatment of asymptomatic bacteriuria in pregnancy reduces the complications associated with it. A Cochrane review article came to the conclusion that antibiotic treatment of asymptomatic bacteriuria is effective in reducing the risk of pyelonephritis in pregnancy. 12 Another study in India found that treatment of asymptomatic bacteriuria in pregnant women prevents complications like preeclampsia, preterm labour, low birth-weight and premature rupture of membranes. 13 The benefits of treatment has caused several institutions to advocate for screening of pregnant women for asymptomatic bacteriuria, especially in the first trimester of pregnancy. 2,3,8 154

September 2015 Labi et al Asymptomatic bacteriuria in ante-natal clients The prevalence of asymptomatic bacteriuria and its associated risk factors in Accra, the capital city of Ghana is not known. The goal of this analysis was to screen mid-stream urine of ante-natal clients at the Korle-Bu Teaching Hospital for asymptomatic bacteriuria and antibiotic sensitivities of the isolated organisms. This was to contribute to treatment policy at the teaching hospital. METHODS A descriptive cross-sectional study of new antenatal clinic attendants at the Korle-Bu Teaching Hospital, Accra was conducted over a one month period, between1 st August-31 st August 2012. Subject Recruitment The study was a total enumeration of all antenatal clients presenting to the clinic for the first time within the study period at the antenatal clinic. Written informed consent was sought from all clients before recruitment into the study. Clients who refused consent were excluded from the study. Interviewer administered structured questionnaire was used to solicit information on socio-demographic and obstetric characteristics of the index pregnancy. Gestational age of the index pregnancy was calculated using an early ultrasound scan or the first day of the last menstrual period. Clients who had symptoms of acute urinary tract infection and those who were on antibiotics or had been on antibiotics at least two weeks prior to presentation were excluded from the study. Specimen Collection and Processing Clients after completing the interview were given labelled sterile universal containers by the interviewer, and counselled on how to collect midstream urine without perineal cleaning. Approximately 15mls of urine were collected from each client. The urine samples were transported to the laboratory of the Department of Microbiology University of Ghana Medical School for processing, within four hours of collection. The samples were subjected to routine microscopy and culture. Microscopy involved examining uncentrifuged urine for the presence of pus cells, red blood cells, casts and epithelial cells. Samples were then cultured on cysteine lactose electrolyte deficient agar (CLED) using a standardised wire loop. The plates were incubated at 37 C and read after 24 hours for significant bacteriuria. Significant bacteriuria was defined as a single colony count of 10 5 organisms. Identification of pathogens was done using standardised biochemical and sugar fermentation tests. Antibiotic susceptibility tests were conducted on the isolated organisms using Kirby Bauer disc diffusion method. 14 Data management and statistical analysis Data obtained from this study was entered into SPSS version 16. Descriptive statistics such as proportions, frequencies and ratios were used. Data was presented in tables and graphs. Associations between categorical outcomes variables were conducted using the Chi squared test at the 95% significant level. A two tailed p-value of <0.05 was considered statistically significant. Ethical issues The University of Ghana Medical School Ethical and Protocol Review Committee gave ethical approval for the study. Written informed consent was received from all participants of the study. RESULTS A total of 274 women were included in the study. Their ages ranged from16-43 years (median age was 30years). 110 (40.1%) of the women had completed JHS whilst 22(8%) had no formal education at all, and approximately 80% (215) were married. Most of the women 176 (64.2%) had 1-3 children whilst 29.9% (82) had no children at all. 173(63.1%) women were in their third trimester of pregnancy whilst 16(5.8%) were in their first trimester. Of the index pregnancies 94.5 %( 259/274) were singletons whilst 15 (5.5%) were multiple gestations, 200 (73%) of the patients were sexually active during this index pregnancy, of the women who were sexually active 106 (53%) had sex once a week as compared to 2 (1%) who had sex four or more times a week. Table 1 Characteristics of asymptomatic bacteriuria among study patients Characteristics Frequency Percentage (%) No bacterial growth 259 94.5 asymptomatic bacteriuria 15 5.5 Total 274 100.0 Organism Enterococcus species 4 26.7 Proteus mirabilis 3 20.0 Escherichia coli 2 13.3 Non haemolytic streptococcus 2 13.3 species Staphylococcus epidermidis 2 13.3 Citrobacter species 1 6.7 Enterobacter species 1 6.7 Total 15 100 Table1 shows that the prevalence of asymptomatic bacteriuria among the women was 5.5%, it further shows that the commonly isolated organism was Enterococcus spp 4 (26.7%). 155

Although Enterobacteria formed the highest group of isolated organisms 7(46.7%) Figure 1 shows that of the antibiotics tested nitrofurantoin had the highest susceptibility, 13 (86.7%) of the isolated organisms were susceptible, and there was 100% resistance to ampicillin and cotrimoxazole. DISCUSSION Findings from the study indicate that the prevalence of asymptomatic bacteriuria among pregnant women attending antenatal clinic at the Korle-Bu Teaching Hospital is 5.5%. This figure is comparable to the findings of 7.3% found in a similar study conducted at another large hospital, the Komfo-Anokye Teaching Hospital in Kumasi, Ghana. 10 Similar studies in Africa have shown varying prevalence rates; 18.1% in South Eastern Nigeria 8 and 28.8% in Ibadan, Nigeria 15, 14.1% in Khartoum, Sudan 16 and 13.3 % in Mulago Uganda. 9 We also found that the age group 30-34 years had the highest prevalence of asymptomatic bacteriuria whilst the 0-19 age group had the lowest prevalence. This is comparable to the findings made in Kumasi. 10 The prevalence was also higher among patients in their second trimester of pregnancy (7.1%). This is similar to findings made in Ibadan, Nigeria and Kumasi, Ghana. 10,15 Figure 1 Antibiotic susceptibility pattern of isolated organisms. Women who were sexually active during pregnancy were more likely to have asymptomatic bacteriuria (Fisher s Exact Score-5.871, P-value-0.0135). However there was no association between sexual frequency and asymptomatic bacteriuria. Women in their second trimester had a higher percentage of asymptomatic bacteriuria 6 (7.1%), although there was no significant association between gestational age and asymptomatic bacteriuria. Patients in the age group 30-34years had the highest prevalence of asymptomatic bacteriuria 6 (40%). Asymptomatic bacteriuria was found only among women with singleton pregnancies; however this was not a significant association. There was also no association between educational level and asymptomatic bacteriuria. Table 2 Association between sexual activity and asymptomatic bacteriuria Sexual activity No bacterial Asymptomatic bacteriuria Total Fishers Exact P- value growth Yes 185 15 200 5.871 0.013 No 74 0 74 5 Total 259 (94.5%) 15(5.5%) 274 (100%) Using educational status as a marker of socio-economic status, there was no association between asymptomatic bacteriuria and educational status. This is at variance with the findings from south-eastern Nigeria, where it was associated with the least educated individuals; and also the assertion that asymptomatic bacteriuria is associated with low socio-economic status. 1, 8 There was an association between asymptomatic bacteriuria and sexual activity during pregnancy. This is in agreement with several studies which have found sexual activity as a risk factor for developing urinary tract infection in women. 5,17 Sex is thought to increase the risk of infection by meatal trauma, urethral massage and probably changes in vaginal flora. 5 However contrary to our expectations there was no association between sexual frequency and asymptomatic bacteriuria. Asymptomatic bacteriuria was found among only singleton pregnancies although this association was not significant. Unlike most studies which have Escherichia coli as the commonly isolated organism 1,7,8,10,16, this analysis found Enterococcus spp as the commonly isolated organism. This was followed by Proteus mirabilis and Escherichia coli (. However, members of the enterobacteriaceae formed the commonest group of organisms isolated. With regards to the antibiotic susceptibility patterns of the isolated organisms, nitrofurantoin had the highest susceptibility. This can be explained by the fact that nitrofurantoin as an antibiotic is currently not used routinely for treatment of urinary tract infections in Ghana. 18 156

September 2015 Labi et al Asymptomatic bacteriuria in ante-natal clients Thus antibiotic pressure resulting from repeated use has reduced and thus resistance levels to nitrofurantoin have dropped. Gentamicin, cefuroxime, ampicillin and cotrimoxazole had low susceptibilities to the isolated organisms. Considering that cefuroxime is very commonly used and ampicillin is still used by obstetricians in this teaching hospital, culture and sensitivity as a requirement for the treatment of urinary tract infections among pregnant women in the hospital should be considered in the review of treatment guidelines and protocols of the hospital. Some limitations of this study need to be mentioned, that the numbers of early pregnancy cases included in the study were not large enough. This was because Korle-Bu Teaching Hospital is a referral centre therefore most pregnant women come in at advanced gestational ages. However, the sample size used for the analysis was more than the minimum required for such prevalence study. CONCLUSIONS The prevalence of asymptomatic bacteriuria at the Korle-Bu Teaching Hospital is 5.5%, which is lower than what has been found in other African settings. Enterococcus spp is the commonest causative organism. However the complications associated with asymptomatic bacteriuria require that screening is done for all pregnant women, and the appropriate antibiotics used for treatment. RECOMMENDATION It is recommended that similar studies using larger population sizes be conducted at primary and secondary healthcare levels, looking specifically at asymptomatic bacteriuria in early pregnancy. This is because its impact is significant in this population. ACKNOWLEDGEMENTS We are grateful to all the women who took part in the study and to those who collected the data. We are also thankful to the Head of Department and staff of Department of Obstetrics and Gynaecology of the Korle- Bu Teaching Hospital for allowing us to undertake the study in their department. REFERENCES 1. Schnarr J, Smaill, F. asymptomatic bacteriuria and symptomatic urinary tract infections in pregnancy. Eur J Clin Invest. 2008 Sep 24;(38):50 7. 2. Nicolle EL, Bradley S, Colgan R, Rice JC, Schaeffer A, Hooton TM. Infectious Diseases Society of America Guidelines for the Diagnosis and Treatment of Asymptomatic Bacteriuria in Adults. Clin Infect Dis. 2005;40:643 54. 3. Macejko AM, Schaeffer AJ. Asymptomatic Bacteriuria and Symptomatic Urinary Tract Infections During Pregnancy. Urol Clin North Am. 2007 Feb;34(1):35 42. 4. Smaill F. Asymptomatic bacteriuria in pregnancy. Best Pract Res Clin Obstet Gynaecol. 2007 Jun;21(3):439 50. 5. Sheffield JS, Cunningham FG. Urinary Tract Infection in Women Obstet Gynecol. 2005 Nov;106(5, Part 1):1085 92. 6. Girishbabu RJ, Srikrishna R, Ramesh ST. bacteriuria in pregnancy. Int J Biol Med Res. 2011;2(3):740 2. 7. Çelen Ş, Oruç AS, Karayalçin R, Saygan S, Ünlü S, Polat B, et al. Asymptomatic Bacteriuria and Antibacterial Susceptibility Patterns in an Obstetric Population. Isrn Obstet Gynecol. 2011;2011:1 4. 8. Oli A., Okafor C., Ibezim E., Akujiobi C., Onwunzp M. The prevalence and bacteriology of asymptomatic bacteriuria among antenatal patients in Nnamdi Azikiwe University Teaching Hospital Nnewi; South Eastern Nigeria. Niger J Clin Pr. 2010;13(4):409 12. 9. Andabati G, Byamugisha J. Microbial aetiology and sensitivity of asymptomatic bacteriuria among ante-natal mothers in Mulago hospital, Uganda. Afr Health Sci. 2010;10(4):349 52. 10. Turpin C., Minkah B, Danso K., Frimpong E. Asymptomatic bacteriuria in pregnant women attending antenatal clinic at Komfo Anokye Teaching hospital, Kumasi, Ghana. Ghana Med J. 2007 Mar;41(1). 11. Geraldo Duarte, Marcolin AC, Quintana SM, Cavalli RC. Urinary tract infection in pregnancy. Braz J Gynecol Obstet. 2008 Feb;30(2):93-100. 12. Smaill F, Vasquez, JC. Antibiotics for asymptomatic bacteriuria in pregnancy. Cochrane Database Syst Rev [Internet]. John Wiley & Sons,Ltd; 1996 [cited 2013 Jul 23]. Available from: http://onlinelibrary.wiley.com/doi/10.10002/14651 858.CD000490.pub2/abstract 13. Jain V, Das V, Agarwal A, Pandey A. Asymptomatic bacteriuria & obstetric outcome following treatment in early versus late pregnancy in north Indian women. Indian J Med Res. 2013 Apr 1;137(4):753-8. 14. Cavalieri SJ, et al. Manual of antimicrobial susceptibility testing. American Society of Microbiology 2005:39-52. 15. Kehinde AO, Adedapo KS, Aimaikhu CO, Odukogbe AA, Olayemi O, Salako B. Significant Bacteriuria Among Asymptomatic Antenatal Clinic 157

Attendees In Ibadan, Nigeria. Trop Med Heal. 2011;39(3):73 6. 16. Hamdan ZH, Abdel HMZ, Salah KA, Ishag A. epidemiology of urinary tract infections antibiotics sensitivity among pregnant women at Khartoum North Hospital. Ann Clin Microbiol Antimicrob [Internet]. 2011;10(2). Available from: http://creativecommons.org/licenses/by/2.0 17. Vincent CR, Thomas TL, Reyes L, White CL, Canales BK, Brown MB. Symptoms and Risk Factors Associated with First Urinary Tract Infection in College Age Women: A Prospective Cohort Study. J Urol. 2013 Mar;189(3):904 10. 18. Ministry of Health. Standard Treatment Guidelines Sixth Edition, 2010. 158