UTI is the commonest bacterial infection inflicting mostly the paediatric population with possible adverse effects if it is not treated timely. Establishing the magnitude of the problem and determining the causative agents as well as knowing the predictors of the risk factors for the infection to occur is very crucial because all help in the clinical management of the neonates particularly in the local context.
The important findings in our study include obtaining the prevalence of UTI among neonates of 18.4% and Klebsiella pneumoniae and Enterobacter spp. were the only bacterial isolates implicated for causing UTI. Of the panel of antibacterial tested in the study, ampicillin, gentamycin, and ceftriaxone were absolutely resistant to the isolated bacteria; however, interestingly, both isolates were sensitive to ciprofloxacin. Additionally, by far, low Apgar score and positive test for nitrites and leucocytes were the powerful independent predictors of UTI.
The prevalence of UTI among neonates of 18.4% in our study was similar to the prevalence of 18% that was reported in the study done by Nejad et al. in Iran among neonates aged less than 4 weeks as in this study and the mode of urine collection also was the same; they did suprapubic aspiration (Nasrin HN, Mitra H & Farah S, 2010). Similarly, a prevalence of 17% of UTI was reported in a study which was done at California University, USA, among infants aged less than 3 months . These similarities could be explained by the fact that all studies used similar method of collecting urine sample although the study population for the studies compared was different.
The prevalence of UTI found in this study was higher compared to the prevalence of 6%, 6.4%, 7.2%, 12.5%, and 14.5% among neonates which was reported in studies which were done in India, Nigeria, India, Turkey, and Indonesia, respectively [1, 5, 15, 21, 24]. The difference in the prevalence for the different studies compared may be due to the difference in methodology. The variation in inclusion and exclusion criteria, difference in methods of collection of the urine samples, and also study designs might have contributed to the variation in the prevalence of UTI. For example, it has been reported that neonates who are admitted in a neonatal intensive care units (NICU) are more likely to contract the infection because of exposure to hospital acquired infections . Also, the difference in method of sample collection may contribute to the difference in the prevalence of UTI among neonates by for example where the method of sample collection is prone to contamination .
Klebsiella pneumoniae has been reported to be the most common cause of UTI among neonates in the literature similar to the finding in the present study [26, 27]. Other studies that were done in Nigeria, Egypt, India, and Iran reported that Klebsiella pneumoniae was the commonest implicated cause of UTI among neonates and it accounted for 28.57% , 28% , 27% , and 31.8% . Also, Msaki et al. reported that 72.3% of the neonates with UTI were positive to Escherichia coli followed by Klebsiella pneumoniae which consisted of 21.28% . Also, in a study which was done by Gidabayda et al.  it was reported that Escherichia coli was the most common bacterial isolate (46.2%) followed by Klebsiella pneumoniae (30.8%) . Furthermore, studies have reported that Enterobacter spp. is another bacterial isolate responsible for causing UTI among neonates, however, not as common as compared to Klebsiella pneumoniae [7, 10, 29].
Regarding sensitivity of bacteria to antibiotics in the present study, Enterobacter spp. was sensitive to ciprofloxacin, amikacin, and nitrofurantoin. On the other hand, Klebsiella pneumoniae was sensitive to ciprofloxacin, amikacin, and nitrofurantoin. In a study which was done in Nigeria among neonates with UTI, it was found that the most common bacterial isolate was Klebsiella pneumoniae followed by Enterobacter spp. and Klebsiella pneumoniae was sensitive by 83.33%, 33.33%, and 33.33% to nitrofurantoin, ciprofloxacin, and gentamicin, respectively . Furthermore, the same study also observed that Enterobacter spp. was sensitive by 100% to ciprofloxacin.
In this study, both Klebsiella pneumoniae and Enterobacter were 100% resistant to ampicillin, ceftriaxone, and gentamicin. This is similar to the findings in a study which was done in Nigeria in which Klebsiella pneumoniae was 100% resistant to ampicillin, gentamycin, and co-amoxiclav . Another study which was done in Iran aiming at determining the antimicrobial susceptibility among neonates with UTI found that Escherichia coli was resistant to ampicillin, amikacin, and ceftriaxone by 36.6%, 36.6%, and 26.6% whereas Klebsiella pneumoniae showed resistance to ampicillin and ceftriaxone by 22.2% and 18.5%, respectively . Furthermore, other studies have also emphasized that, Klebsiella pneumoniae has been found to be resistant against ampicillin, cefuroxime, ceftriaxone, and even with multidrug resistance (MDR) [30, 31].
The findings obtained from this study and those in previous studies all indicate that there is a marked increase in antibiotic resistance especially for the first- and second-line antibiotics used for treating UTI among neonates. Self-prescription of common antibiotics in developing countries remains the major contributing factor for antibiotics resistance . Difficulty in performing urine culture according to the stipulated WHO guidelines for management of neonates with UTI paves another way to antimicrobial resistant . Furthermore, it has been reported that low concentrations of drugs in the serum which are mainly due to under dosage or improper frequencies of taking drugs give a room for microbes to modify the binding sites and change structures leading to mutations which in turn cause antimicrobial resistance .
Currently in Tanzania, treatment of UTI in neonates and other children aged more than 3 months include nitrofurantoin and amoxiclav . However, due to the lowest sensitivity of only 20% for Enterococcus spp. and complete resistance for Klebsiella pneumoniae shown in the present study for amoxiclav, this implies that amoxiclav may be replaced by other antibiotics which have shown sensitivity in the management of neonates with UTI.
Although some of the antibiotics are still sensitive to a number of uropathogens in Tanzania, however, according to physicians attending patients with UTI particularly in areas where urine culture testing is not a common practice which prompts empirical use of such antibiotics, there is a possibility of predisposing the patients to developing lung complications for example pulmonary fibrosis . Therefore, measures should always be undertaken in either confirmed or suspected cases of pulmonary fibrosis by taking preventive measures of the exaggerated effects of the complication including stopping of the medication and using methylprednisolone .
Neonates with low Apgar score (<7) at 5 min were 13 times more likely to have UTI than neonates who had normal Apgar score (≥7) at 5 min and the association was statistically significant (p <0.001). A similar finding was reported in Eastern Ethiopia in which neonates with low Apgar score (<7) at 5 min were 69 times more likely to have UTI compared to those who had normal Apgar score and the association was statistically significant (AOR = 68.9, 95% CI = 3.63–1308) . Another study which was done in Northwest Ethiopia reported that neonates with low Apgar score (<7) at 5 min were 3 times more likely to contract UTI compared to neonates who had normal Apgar score and it was statistically significant (AOR = 3.2, 95% CI = 1.3–7.7) . This may be explained by the fact that majority of neonates who are born with low Apgar score is mainly due to difficulty in delivery process especially delaying during second stage of labour. Additionally, maternal infections such as malaria and anaemia have been found to increase the chance of neonatal UTI .
In this study, neonates who were born among mothers who had prolonged labour (>18 h) for both primigravida and multigravida were 5 times more likely to have UTI than those who were born among mothers without prolonged labour (≤18 h). This is similar to another study which was done in Ethiopia which reported that duration of labour of more than 18 h since rupture of membrane had 10-fold increased risk of causing UTI compared to normal duration of labour (AOR = 10.4, 95% CI = 2.3–46.5) .
It has been reported that prolonged labour is associated with low Apgar score. Also, prolonged labour increases the chance of acquiring ascending infections to mother and neonates . Also, interventions and manoeuvres applied to achieve delivery process predispose ascending infections to the mothers and their newborn (Benson and Mitchell 1958). Therefore, prolonged labour is a predisposing factor of both low Apgar score and UTI among neonates. Therefore, it may explain the fact that there exists a causality relationship for prolonged labour and low Apgar score with UTI in neonates and not just a mere association.
Neonates with positive nitrite and leucocytes esterase tests had 27- and 24-fold increased risk of being diagnosed with UTI, respectively compared to neonates who had negative test for nitrite and leucocytes esterase. In a study done in Brazil, it was observed that the presence of nitrites in the urine had sensitivity of 30.8% (95% CI = 19.9–43.4%) and specificity of 100% (95% CI = 99.2–100%)  in the diagnosis of UTI. This shows that the presence of nitrite in urine has higher specificity than sensitivity in the diagnosis of UTI for neonates and even adults. The conversion of nitrates to nitrites in urine is caused by bacterial infections mainly Gram-negative including Escherichia coli, Klebsiella pneumoniae, Proteus spp., and Enterobacter spp. . On the other hand, leukocyte esterase is an enzyme which is present in WBC. It is released when WBC undergoes lysis. Therefore, once this enzyme is detected in urine, it indicates the presence of WBC in urine which implicates pyuria. Typically, pyuria implies inflammation in the urinary tract . Although leucocyte esterase has been reported to have higher sensitivity than nitrites test, the specificity of leucocyte esterase is lower than that of nitrites .
Other factors that have also been found to increase the chances of neonates to acquire UTI include anorectal malformations and gastrointestinal problems. For example, it has been reported that vesicoureteral reflux develops in approximately 20–47% of children with anorectal malformations . Additionally, the presence of vesicoureteral reflux increases the risk of developing febrile urinary tract infections (UTI), leading to renal scarring and subsequent renal dysfunction .
Furthermore, the use of urine dipstick test has been reported to have high false-negative rates which in turn contribute to low sensitivity despite the high specificity . Also, urine microscopy test for patients with UTI particularly neonates has shown higher sensitivity compared to specificity .
The limitations of the present study include the following: by the study being cross-sectional, the results cannot be generalizable. Not using random sampling in obtaining the study participants, the study was affected by selection bias. Additionally, by involving hospitalized neonates already with clinical sepsis, it may have influenced our results.