Prevalence, resistant pattern and associated risk factors of asymptomatic bacteriuria among antenatal clients in a municipal hospital in Ghana

INTRODUCTION

Urinary tract infections (UTIs) are a prevalent type of bacterial infection that can affect various segments of the urinary system, including the bladder, urethra, and kidneys.¹ During pregnancy, UTIs can pose a significant health concern due to the physiological changes that occur in the urinary tract as well as the potential adverse effects on both maternal and foetal health.^2-4 The prevalence of UTIs among pregnant women has been a subject of interest for researchers and healthcare providers, as it has a direct impact on the well-being of both the mother and the developing foetus.⁵ Untreated urinary tract infections (UTIs) during gestation possess the potential to result in a spectrum of complications, some of which may have dire ramifications for both the mother and the developing foetus.^6,7

Notably, UTIs are correlated with an augmented risk of premature labour, low birth weight, and even maternal and neonatal mortality.⁸ The infection has the potential to ascend to the kidneys, thereby leading to pyelonephritis, a more severe and potentially life-threatening ailment.⁸ In conjunction with the immediate risks, there is mounting evidence to suggest that maternal infections during gestation may have enduring effects on the offspring's health.⁹ Urinary tract infections are commonly associated with various types of bacteria, including Escherichia coli, Klebsiella pneumoniae, and Staphylococcus saprophyticus.¹⁰

During pregnancy, numerous changes happen in a woman's body that increase the risk of developing a UTI. These alterations include modifications in the composition of urine and the immune system, as well as increased pressure on the bladder as the baby grows. Pregnant women are more likely to develop repeated or more severe UTIs compared to non-pregnant women. Up to 1 in 10 pregnant women may experience a UTI during their pregnancy.^11,12 Despite the known risks, there is an insufficiency of comprehensive data regarding the prevalence of specific uro-pathogens responsible for UTIs among pregnant women who attend antenatal clinics in hospitals including Weija-Gbawe Municipal Hospital (WGMH). It is crucial to understand the prevalence of these uro-pathogens in order to tailor effective preventive measures, diagnostic approaches, and treatment strategies.

METHODS

Study site

The WGMH is a 50-bed secondary hospital which provides medical health services to the communities around the Weija-Gbawe Municipal Assembly. Services provided by the hospital include child welfare clinic, family planning, nutrition and antenatal care (ANC). The ANC unit records an average attendance of 50 pregnant women daily and the Unit has 10 beds for deliveries.

Study design

The study employed cross-sectional study design to collect data from May 2023 through August 2023 at the Weija-Gbawe Municipal Hospital (WGMH).

Inclusion criteria

Pregnant women without any signs and symptoms of UTI after screening with routine urine examination test were included in the study.

Exclusion criteria

Pregnant women attending the antenatal clinic on account of obstetric emergencies were excluded from urine sampling. Pregnant women who were on antibiotic treatment two weeks prior to sample collection were also excluded from the study.

Sample size determination

For Urine specimen, the minimum sample size of pregnant women was determined using the

Cochran’s formula: n=Z²p (1-p)/e²

Where; n is the minimum sample size, Z is the standard z score=1.96, p is the proportion of pregnant women with asymptomatic bacteriuria=0.08 (13), e is the margin of error=0.05.

Substituting these values into the Cochran’s formula will result in a sample size of=116 participants.

Data collection

Study participants were recruited after accepting to participate in the study and duly signing an informed consent form. Well-trained health workers translated the questions into the local dialect for those who were not able to read or write and this was done confidentially. Respondents were recruited consecutively until sample size was reached. Structured questionnaires were used to collect data on variables such as sociodemographic characteristics, smoking status, recurrent UTI, month in which the participant started antenatal care clinic and parity.

Urine specimen collection

After responding to the questionnaires, the participants were educated on how to take the urine specimen to avoid contamination. A sterilized plastic wide mouth leak proof screw-capped transparent urine container, well label with a unique participant identification number, age and time of collection was given to the participant to produce about 10–20 mL of mid-stream urine specimen. Overall, 130 Urine specimens were collected from pregnant women. The specimens were transported to the laboratory for immediately for analysis. In cases of delay in transporting the urine specimen to the laboratory, samples were stored between +2°C and +8°C.

Laboratory processing of urine specimen

Urine specimen processing was carried out in 2 phases. Phase 1 involved isolation and identification of bacteria from urine sample and Phase 2 focused on determining the antibiogram of isolated bacteria from the urine specimens.

Phase 1 - Isolation and identification of bacteria from urine sample

Bacteriological analysis to isolate members of the family of Enterobacteriaceae was carried out at the Central Laboratory of the Korle Bu Teaching Hospital, Accra. Using a sterile calibrated wire loop (0.002 mL), the urine specimens were inoculated on Cysteine Lactose Electrolyte Deficient (CLED) agar and 5% sheep blood agar for the primary isolation of uro-pathogen. The culture plates were incubated between 35 ⁰C to 37 ⁰C aerobically for 18-24 hours. Morphological identification, biochemical tests, colony count and sensitivity testing were performed on culture media with bacterial growth after 12 hours of incubation.¹⁴

Phase 2 - Antimicrobial susceptibility testing (AST)

Identified distinct colonies were picked from CLED and sub-cultured on Mueller Hinton agar for antimicrobial susceptibility testing. A loopful of bacteria was taken from the pure colony, put in 0.85% NaCl solution, and mixed gently until a homogenous solution was attained.

The turbidity of the solution was adjusted to optical density of 0.5 McFarland standard to standardize the inoculum size. A sterile cotton swab was dipped into the solution and the soaked cotton swab was gently pressed against the inner wall of the tube containing the solution to remove excess solution. The cotton bag was used to streak on the entire surface of Muller Hinton agar. The inoculum plate was left at room temperature to dry for about 3 minutes. Antibiotics disk was placed on the Muller Hinton agar using a sterile forceps and place in an incubator for 18 - 24 hours at 35⁰C-37⁰C, after which the sensitivity results were documented.^13,14

Laboratory quality control

Standard operational procedures (SOP) were strictly followed during each procedure. The preparation of the media as well as the antibiotics used to perform the tests were adopted from the Clinical and Laboratory Standards Institute (CLSI) guidelines by de Sousa et al. An autoclave tape was used during the preparation of the media to check for a complete sterilization. Susceptibility testing was done using E.coli strain ATTC 25922(15).

Data management plan

Laboratory data sheets was completed by the investigators and data was stored in bound folders and put under lock until data entry. Data was entered into Microsoft Excel and protected using a password that was known by the investigators. Data was cross-checked for errors that might arise during data entry. Any errors that were noticed were corrected prior to data analysis.

Data analysis

Data was analysed using Stata version 14 (StataCorp, College Station, Texas, USA). Firstly, the data was explored and checked for missing values. Continuous variables were tested for normality using Shapiro-Wilk test for normality. The outcome variable was dichotomized as 0 “Negative” and 1 “Positive”. Mean and standard deviations were used to describe continuous variables that were normally distributed and percentages were used to describe categorical variables. Each of the selected risk factors were assessed independently with the outcome variable (bacteriuria) in a chi-square test. If one or more expected values in a cross tabulation are less than 5, Fisher’s exact test was used instead of a chi-square test. The multiple logistic regression model with robust variance estimator at a 95% confidence interval considered all risk factors from the chi-square test. Even though these factors were not significant from the chi-square test, studies elsewhere have showed that they are significant predictors of bacteriuria in pregnancy.^16,17 The risk factors included in the multiple logistic regression model were significant at p<0.05.

RESULTS

The mean age of the study participants was 30.0±6.5. The percentage of women aged 26-5 was about 60% and those aged 26-45 constituted the least (11.64%). About 36% of the respondents completed basic level of education, 34.25% completed secondary level and about 15% completed tertiary education. Almost equal proportions of the respondents were non-government employee and traders, 38.36 and 39.04 respectively. Majority (77.40%) were obese and only 3.42% had normal weight (Table 1).

Figure 1 shows the antimicrobial susceptibility patterns of four (5) distinct bacterial strains that were identified from study participants at the Weija-Gbawe Municipal Hospital. The bacterial strains were all Gram-negative bacteria, namely Escherichia coli, Klebsiella spp, Proteus spp, Citrobacter koseri and, Citrobacter freundi. The percentage of E. coli and Klebsiella species was 27% and 23% respectively, Proteus spp and Citrobacter koseri each was 18% and Citrobacter freundii was 14%.

Table 2 shows the characteristics of respondents stratified by bacteriuria. Among those with positive culture results, 65% belonged to 26 to 35 age group, 75% were obese and 40% completed basic level of education. Ninety-six percent (96%) of non-smokers had positive culture results, all those with positive culture results do not drink alcohol and 90% of those with recurrent UTI had positive culture results. Among those with negative culture results, 97% of the women have never been diagnosed of diabetes, 87% had sex once a week and 94% did not lose pregnancy in the past. Forty percent (40%) of those with negative culture results reported to the health facility 6 month after getting pregnant, 46% of them were in their first trimester and 49% had no child.

Table 3 shows the resistant pattern of isolate from the urine specimen of the study participants. In general, the isolates showed resistant rate of 90.91% to cotrimoxazole. Their resistance against nalidixic acid, nitrofurantoin and tetracycline was 81.82%. Similarly, the isolates showed same resistant rate of 77.23% against gentamicin and amikacin. Ceftriaxone recorded the lowest resistance rate (40.90%) compared to the rest of the antibiotics tested. Gentamicin was the most effective drug against E. coli with sensitivity rate of 88.24%. Citrobacter koseri, Klebsiella species and Citrobacter freundii were all fully sensitive to amikacin, ceftriaxone and levofloxacin respectively. However, Citrobacter koseri was relatively resistant to amplicillin (6.25%) and cefuroxime (18.18%). Klebsiella species was also relatively resistant to levofloxacin (18.75%) and cefuroxime (18.18%). Cefuroxime was the most effective drug against Citrobacter freundii with a sensitivity rate of 90.91%.

This study did not find any significant factors that were associated with bacteriuria, however, pregnant women between the age of 26 to 35 had 11% less risk of experiencing bacteriuria compared to those aged 14 to 25 years (aOR = 0.89; 95%CI: 0.311, 2.549; p=0.829). This rate further reduced to 84% among those who belonged to 36 to 45 years (aOR = 0.16; 95%CI: 0.026, 0.997; p value=0.050). Those who were overweight had 3.85 times higher odds of experiencing bacteriuria compared to those with normal weight (aOR = 3.85; 95%CI; p value=0.284).

The odds of experiencing bacteriuria reduce as the respondents climbs higher on the educational ladder. For example, those who completed basic level of education had 2.80 times higher odds of experiencing bacteriuria compared to those with no formal education (aOR=2.80; 95% CI: 0.692, 11.361; p value=0.148). This odds reduced among those who completed secondary level of education (aOR=2.26; 95% CI: 0.552, 9.221; p-value = 0.257) and further reduced among those who completed tertiary level of education (aOR = 0.46; 95% CI: 0.047, 4.587; p value=0.512). Smokers have 36% higher odds of experiencing bacteriuria compared to those who did not smoke (aOR = 1.36; 95% CI: 0.177, 10.372; p value=0.769). Those who engaged in sexual activity more than once a week had 73% less risk of experiencing bacteriuria compared to those who engaged in sexual activity once a week (aOR=0.27; 95% CI: 0.053, 1.366; p value=0.114). Pregnant women with recurrent UTI before getting pregnant had 3.23 times higher odds of experiencing bacteriuria compared to those with no history of recurrent UTI (aOR = 3.23; 95% CI: 0.512, 20.333; p-value = 0.212). Pregnant women who reported to health facility three months after getting pregnant had 75% higher odds of experiencing bacteriuria compared to those who reported to health facility after the first month of pregnancy (aOR=1.75; 95% CI: 0.613, 4.995; p value=0.295). This odds increased to 2 times among women who reported to the health facility after six month of getting pregnant compared to those who reported to health facility after the first month of pregnancy (aOR = 2.01; 95% CI: 0.632, 6.412; p-value=0.236). Women with three or more children have more than twice the odds of experiencing bacteriuria compared to those with no children (aOR=2.24; 95% CI: 0.616, 8.120; p value=0.221) (Table 4).

DISCUSSION

Asymptomatic bacteriuria is common during pregnancy. It is a condition in which the urine culture reveals a significant growth of pathogens greater than 100,000 CFU/mL but without symptoms of UTIs. The aim of this study was to determine the prevalence of uro-pathogens among pregnant women in the Ga West Municipality of the Greater Accra Region of Ghana. This study was also interested in the resistant pattern of the isolated pathogens and the factors associated with bacteriuria among pregnant women.

The prevalence of uro-pathogens was 15.1%. This consistent with a study conducted in Eastern Ethiopia in 2021 that sought to determine the prevalence bacterial uro-pathogens and their antimicrobial susceptibility patterns among pregnant women. The findings from that study revealed a prevalence rate of 15.5%.¹⁸ However, the prevalent rate from the current study is lower compared to similar studies conducted in Central Ethiopia in 2017 that revealed a prevalence rate of 18.7%.¹⁹ The plausible reason for this difference in prevalence could be due to the different periods in which these studies were conducted. Women who become pregnant between 2020 to 2024 may be considered to have adequate knowledge in UTI prevention compared to women who were pregnant prior to this period as a result of health promotion intervention on health issues such as food habits, urinary habits and sexual behaviour habits among pregnant women.²⁰

The current study showed that Enterobacteriaceae family bacteria are the most common causes of ASB among pregnant women. In the present study, out of 22 isolates, E. coli was the most frequent causative organism (27.3%), followed by Klebsiella species (22.7%). Similar findings have been documented in Yemen, Australia, South Africa, Taiwan, India, and Egypt. However, a study conducted in Brunei revealed Klebsiella species as the most common organism followed by E. coli.^24-31

The resistant patterns of E. coli were 33.3% to ceftriaxone, 37.5% to levofloxacin, 36.7% to cefuroxime and 31.3% to ampicillin. These resistant rates were lower compared to the findings of studies elsewhere. For example, as reported in North India, the resistant pattern of E. coli was 64.2% to ceftriaxone, 71.4% to cefuroxime and 88.4% to ampicillin.³² It showed 48.63% resistant rate to levofloxacin.³³ However, gentamicin was the most effective drug against E. coli with sensitivity rate of 88.24% in this study. The relatively low resistant rate of E. coli to ceftriaxone, levofloxacin, cefuroxime and ampicillin and high susceptibility to gentamicin may imply that the usage of these antibiotics in treating urine infections is very strict. Nonetheless, urinary tract infections are not fatal compared to blood and respiratory tract infection and thus do not require urgent treatment.

This study also revealed that Citrobacter koseri, Klebsiella species and Citrobacter freundii were all 100% sensitive to amikacin, ceftriaxone and levofloxacin respectively. This finding is surprising because these antibiotics are considered to be among the best first-line antibiotic for uncomplicated UTI and are commonly prescribed in treating UTI among women in women.^34,35 As a result, it was expected that there will be some level of resistance to these antibiotics. It is possible that the recruited pregnant women in this study do not often take these antibiotics to treat UTI and therefore have not develop any form of resistance to them.

In general, the isolates showed resistant rate of 90.91% to cotrimoxazole and their resistance against nalidixic acid, nitrofurantoin and tetracycline was 81.82%. Similarly, the isolates showed resistant rate of 77.23% against gentamicin and amikacin. These general findings are consistent with other findings elsewhere. For example, a study conducted in Pakistan that sought to determine the antibiotic susceptibility pattern of uro-pathogens among outpatients showed a general resistant rate of 90.1% to nalidixic acid, 64.2% to gentamicin, 81.9% to nitrofurantoin and 64.2% to amikacin.³⁶ A systematic review also revealed a general resistant rate of 68.1% to cotrimoxazole.³⁷

The impact of various factors such as body mass index, educational level, smoking status, frequency of sex, recurrent UTI, and parity on bacteriuria was also examined. However, the results did not reveal any statistically significant influence of these factors on bacteriuria. These findings contradict the findings of other studies which suggest a potential association between these factors and bacteriuria.^21-23 Further studies are therefore needed to ascertain the relationship between these risk factors and bacteriuria.

One main strength of the study is that the methods for culture and sensitivity testing on urine samples are internationally approved methods and the findings from these methods are reliable. However, it is important to acknowledge the limitations of the study when interpreting the results. The data was collected using a cross-sectional survey design, which does not allow for establishing causative relationships between outcomes and predictors. Like many other studies, this research did not account for all possible factors that may influence the prevalence of bacteriuria among pregnant women.

CONCLUSION

The research findings indicated a prevalence rate of 15.1% for asymptomatic bacteriuria (ASB) in pregnant women, with E. coli being the predominant strain identified. Gentamicin demonstrated the highest sensitivity, while cotrimoxazole exhibited the highest resistance among the antibiotics tested. Although variables such as age, BMI, educational attainment, smoking habits, sexual activity frequency, history of recurrent urinary tract infections, and gestational age were identified as potential factors associated with bacteriuria in pregnant women, these relationships did not reach statistical significance. It is recommended that a risk stratification protocol based on demographic and behavioural factors be developed to identify high-risk groups. This protocol should involve enhanced monitoring of younger pregnant women and those with lower socioeconomic status, as well as early discussions regarding preventive measures during antenatal care visits. Furthermore, personalized hygiene and lifestyle guidance should be incorporated into patient education sessions. Pregnant women should be advised to adhere to optimal hygiene practices and safe sexual behaviours, with a focus on the role of these practices in preventing uro-pathogen colonization. Preference should be given to antibiotics with established safety profiles for both the mother and the developing foetus.

ACKNOWLEDGEMENTS

Authors would like to thank the staff of Weij-Gbawe Municipal Hospital and Central Laboratory Department of the Korle Bu Teaching Hospital for the various roles they played in data collection and conducting the laboratory tests.

Funding: No funding sources

Conflict of interest: None declared

Ethical approval: The study was approved by the Institutional Ethics Committee

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