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Open Science Journal of Clinical Medicine 2015; 3(6): 199-204 Published online November 2, 2015 (http://www.openscienceonline.com/journal/osjcm) ISSN: 2381-4748 (Print); ISSN: 2381-4756 (Online) Prevalence and Drug Susceptibility of Isolates of Urinary Tract Infections Among Febrile Under-Fives in Nsambya Hospital, Uganda Christine Ocokoru1, *, Robert Anguyo DDM Onzima2, Philip Govule3, Simon-Peter Katongole4 1Medical and Psychosocial Department, Baylor College of Medicine Children's foundation, Uganda, Arua, Uganda 2Department of International Public Health, Liverpool School of tropical Medicine, Kampala, Uganda 3Department of Epidemiology and Disease Control, School of Public Health, University of Ghana, Legon, Accra, Ghana 4Faculty of Health Sciences, Uganda Martyrs University, Kampala, Uganda [email protected] (Christine O.), [email protected] (Robert A. D. O.), [email protected] (Philip G.), [email protected] (Simon-Peter K.) To cite this article Ocokoru Christine, Anguyo Robert DDM Onzima, Govule Philip, Katongole Simon-Peter. Prevalence and Drug Susceptibility of Isolates of Urinary Tract Infections AmongFebrile Under-Fives in Nsambya Hospital, Uganda.Open Science Journal of Clinical Medicine. Vol. 3, No. 6, 2015, pp. 199-204. Background: Urinary tract infections remain a silent cause of morbidity and complications among under-fives due to its non-specific presentation and incapacity of most health facilities in developing countries to diagnose it. Earlier studies present different prevalence of urinary tract infections among children. This study aimed to document prevalence and drug susceptibility patterns of isolates of bacterial urinary tract infections among under-fives in Nsambya hospital, Uganda. Methodology: We conducted a descriptive cross-sectional survey among 302 under-fives who presented in paediatric ambulatory care department of Nsambya hospital with fever (axillary temperature of >37.5°C or by history); and with no history of antibiotic therapy within three days preceding hospital visit. Midstream urine samples collected using bag and bottle collection (depending on age of child) were subjected to culture. We further subjected culture-positive urine samples to systematic bacteriologic and biochemical tests in order to identify the organisms in the colonies before performing drug susceptibility tests. Results: We found urinary tract infection prevalent in 26.8% of the under-fives. Bacterial isolates responsible for the infections were Proteus (39.5%), Escherichia coli (32.1%), Staphylococcus aureus (14.8%), Klebsiella spp. (6.2%), Staphylococcus haemolyticus (2.5%), Staphylococcus intermedius (2.5%), Citrobacter (1.2%) and Morganella (1.2%) in that order. The pathogens exhibited high-level of resistance to commonly used antibiotics like Cotrimoxazole, Amoxicillin, Nalidixic Acid, Nitrofurantoin, Gentamicin, Erythromycin, Chloramphenicol, Ampicillin, Ciproflaxin, Tetracycline and Azithromicin while the isolates showed no resistance to pharmaco-enhanced Amoxicillin and oral Cefatoxime. Conclusion: Prevalence of UTI among febrile under-fives in Nsambya hospital is higher than reports from majority of earlier studies. Similarly, the commonest bacterial isolates associated with UTI among under-fives in Nsambya hospital deviates from most studies in developing countries that majorly report Escherichia coli as the leading cause of UTI in this age category. The observed resistance patterns associated with common antibiotics in our study are in line with the current changing patterns of microbial-antibiotic resistance threatening not only the developing world but the entire glob. Prevalence, Drug Susceptibility, Urinary Tract Infection/UTI, Febrile Under-Fives, Nsambya Hospital infections among the under-fives. A study conducted in in- patient pediatric ward ofMuhimbili hospital in Tanzania among febrile under-fives places prevalence of UTI at 16.8% Urinary tract infections (UTI) are a common cause of [1]. The same study reports Escherichia coli, Klebsiellaspp, morbidity and complications among children globally. Staphylococcus epidermidis, Staphylococcus aureus and Studies have documented varying prevalence of urinary tract Pseudomonas aeruginosa in that order as causes of UTIs Ocokoru Christine et al.: Prevalence and Drug Susceptibility of Isolates of Urinary Tract Infections Among Febrile Under-Fives in Nsambya Hospital, Uganda among the under-fives.A similar study among febrile under- fives in a Nigerian hospital estimates prevalence at 11% [2]: greater than the 9% estimate among children with primary 2.1. Study Setting diagnosis of malaria in Nigeria [3]. Surprisingly, the latter We conducted this study in the pediatric outpatients' study documents staphylococcus aureus as the leading cause department of St. Francis hospital, Nsambya in Kampala. of UTI among the under-fives. In Uganda, a study conducted Commonly known as Nsambya hospital, it is a private not for in the acute care unit of the national referral hospital in 2008, profit health facility located in the Southern part of Kampala, among children aged 2 months to 12 years with fever showed about 3 kilometers from the city centre. It is a 361-bed a prevalence of 14.6% [4]. Despite the differential hospital owned by the Catholic arch diocese of Kampala. prevalence, these (earlier) studies highlight high prevalence of UTI among children presenting to hospitals with fever. 2.2. Study Design This is further corroborated by the fact that high occurrence of UTI isdocumented among children with primary diagnosis This was a descriptive cross-sectional study between of malaria [3]. The low priority accorded to UTI in the December 2013 and April 2014. clinical hierarchy of importance in many African countries 2.3. Sample Size and Sampling Strategy brews complications andat times mortality due to delay in diagnosis and treatment. For example, UTIs do not feature The sample size for this study was 302, arrived at using the among the top 10 causes of morbidity and mortality among Bouderer's formula at 95% level of confidence, +/-5% in-patients in Ugandan health facilities [5]. This rosy picture desired precision, 20.3% prevalence of urinary tract infection of rarity of UTIs could be consequent to difficulty in [1] and 96.0% anticipated sensitivity and after factoring in diagnosing (UTI among under-fives) due to non-specific anticipated non-response. The children were enrolled into the presentation, poor diagnostic capacity of the health facilities study consecutively until the desired sample size was as well as lack of appropriate policy for screening all febrile under-fives for UTI. The study in South Eastern Nigeria [2] details that 10.13%, 14.12%, 40.00%, 20.00%, 6.25% and 2.4. Urine Collection and Testing 50.00% of all clinically diagnosed cases of malaria, upper We employed aseptic techniques for collecting mid-stream respiratory tract infections (including otitis media and urine using the bag-collection for younger children (less than tonsillitis), sepsis/cellulitis/furunculosis, bronchopneumonia, 2 years) and bottle-collection for older ones trained in gastroenteritis and enteric fever respectively were UTI – toileting. We employed quantitative method earlier described moreover, only 16.67% of UTI cases were diagnosed so.The by Cheesbrough [9] to culture urine for microorganisms common clinical features of UTIs among young children using cystein-lactose electrolyte deficient culture medium. include fever, irritability, vomiting and failure to feed [6]. Using calibratedsterile standard nichrome wire loop we Renal scarring is one of the commonest complications of UTI inoculated 1/200µl of the sample onto the culture medium among children. Shaikh, Ewing and Hoberman in a meta- after drying (the culture medium) at 37°C for 15-30 minutes. analysis to assess complications of UTIs in children report We then aerobically incubated the culture plates between 35- post-infection renal scarring among 15% of children [7]. In 37°C for 24 hours before counting the colonies. Colony the long run, renal scarring is associated with increased rates countsof more than 105 organisms/ml were suggestive of UTI of hypertension and proteinuria, decreased renal function and while we regarded growths less than 105 from the midstream increased end-stage kidney disease. Wiswell reports urine as contaminants. We then carried out systematic occurrence of meningitis among 3-5% of infants in the first bacteriologic and biochemical tests to identify the organisms month of life [8]. in the colonies. Drug susceptibility testing was carried out for Policy decision on clinical management of bacterial UTIs, some bacterial isolates and results reported as sensitive, especially among children requires knowledge of its intermediate or resistant. Due to low number drug prevalence, the etiology and drug susceptibility profile of the susceptibility tests conducted, we did not perform offending bacteria. Notwithstanding that this study focuses independent-data-analysis for each of the isolates. on UTI, it is worth noting that there is an on-going global outcry about growing bacterial resistance to the spectra of 2.5. Data Analysis current antibiotics. This calls for vigilance of all actors in the health care to as much as possible, base on up-to-date The data were manually cleaned, entered into micro-soft evidence in making clinical algorithms for treating infections excel before export to Statistical Package for Social Sciences requiring antibiotic therapy. We conducted this study as a (SPSS version 16.0) for analysis. The data were analyzed response to the existing dilemma on prevalence, common using descriptive statistics. We presented our findings in etiology and bacterial susceptibility to treatment of UTIs tables and narratives. among children. Specifically, we looked at prevalence, 2.6. Quality Control bacterial isolates of UTIs; and antibiotic susceptibility profile of the isolates. We adhered to all the standard protocols for urine collection and analysis for all the methods described above. Open Science Journal of Clinical Medicine 2015; 3(6): 199-204 We trained qualified nurses to collect samples under strict invasive nature. supervision ofthe first author. We screened our study Study subjects who had UTIwere provided appropriate participants for antibiotic use and did not consider those with antibiotics based on the results of the drug susceptibility history of antibiotic intake 3 days preceding hospital visit. tests. Where there were suspected co-morbidities, we referred Data were checked for completeness and consistence on daily the subjects to appropriate experts for the required care. basis. The data were cleaned before double entry into excel sheets. The data analyses were conducted by two persons independently to ensure reliability. 3.1. Characteristics of Study Participants 2.7. Ethical Consideration We recruited 302 children under the age of five years who The research protocols were approved by the temporary presented with axillary temperature of > 37.5°C or fever by ethics and review board of Mother Kevin School of Post history and with no antibiotic therapy within three days Graduate Studies of Uganda Martyrs University before preceding hospital visit. The majority of the respondents, further seeking permission from the management of 56.6% (171) were male. Table 1 cross-tabulates the age and Nsambya hospital. We sought permission of mothers or care sex distribution of the respondents. takers of the children before enrolling them into this study. We opted away from supra-pubic aspiration due to its Table 1. Age and sex distribution of the study participants.Age category (months)
Total (%)
3.2. Prevalence of UTI 3.4. Drug Susceptibility of Bacteria We assessed the participants using urine culture. Out of the Drug (antibiotic) susceptibility profile of the various isolates 302 children, 81 were culture positive and this represents was evaluated using commonly used antibiotics. The antibiotics prevalence of 26.8% (95% CI: 21.8 % to 31.8 %). include; oral cotrimoxazole (Cotri), oral amoxicillin (Amoxyl), oral nalidixic acid (Nalid), oral coamoxiclav (Coamoxy), 3.3. Bacterial Isolates Among Children with injectable ceftiraxone (Ceftri), oral cefuroxime (Cefuro), oral nitrofuradantine (Nitro), oral cephalexin (Cepha), injectable We re-evaluated all the culture positive samples so as to gentamicin (Genta), oral cefatoxime (Cefot), injectable amikacin identify the differential etiology of UTI among under-fives. (Amika), injectableoxacillin (Oxac), injectable methicillin Proteus, Escherichia coli andStaphylococcus aureus were the (Methi), oral erythromycin (Erithro), oral chloramphenicol commonest causes of UTI among children under five years (Chloraphen), oral ampicillin, oral ciproflaxin (Cipro), oral of age.Table 2 details the finding of the bacteriological tetracycline (Tetra), injectable clindamicin, injectable imipenem, profile of UTIs. oral metronidazole (Metro), injectable streptomycin, oral azithromicinand oral cefixime. Due to resource limitations, we Table 2. Bacteriological profile of UTIs among under-fives in Nsambya
were able to perform drug susceptibility tests on a few of the hospital. specimens. For the resultant small sample size, we did not breakdown our analysis per the bacterial isolates as such; our Type of bacteria
Frequency
Percentage
findings on drug susceptibility are suggestive but not conclusive. Escherichia coli The results suggest high-level of resistance to the most Staphylococcus haemolyticus commonly used antibiotics like cotrimoxazole, amoxicillin, Staphylococcus intermedius nalidixic acid, nitrofurantoin, gentamicin, erythromycin, Staphylococcus aurues chloramphenicol, ampicillin,ciproflaxin, azithromicin. Similarly, non-commonly used antibiotics like amikacin, oxacillin and methicillin were suggestive of high resistance. Pharmaco-enhanced amoxicillin and oral cefatoxime suggested no resistance. Generally, there was low-level of resistance suggested by the few tests associated with cephalosporin's (table 3). Ocokoru Christine et al.: Prevalence and Drug Susceptibility of Isolates of Urinary Tract Infections Among Febrile Under-Fives in Nsambya Hospital, Uganda Table 3. Results of drug susceptibility tests of isolates of UTI in under-fives.
Sensitivity Analysis:freq(%)
Sensitive
Resistant
with UTI [3]. The high prevalence of UTI and its poor diagnosis among under-fives illustrate urgency for screening programs to aid its early diagnosis and treatment; and further Earlier studies report varying prevalence of UTI among prevent UTI-related deaths and complications. A while ago, under-fives. This study found 26.8% (95% CI: 21.8% to south Africa did suggest identification of UTI in the 31.8%) of febrile childrenwith urinary tract infection. We did Integrated Management of Childhood Illnesses (IMCI) not rule out other possible causes of fever as such; some of protocol based on leucocytes and nitrites as bio-markers these children could have had asymptomatic bacteriuria since using dipstick. Oman adapted IMCI (in primary health care) fever in our study units could have been consequent to other protocol to include screening of all febrile or symptomatic etiologies though we also did not rule out co-morbidities. under-fives for UTI using laboratory tests and referral of Previous evidence that persons with asymptomatic UTI have those with results suggestive of UTI for paediatric progressed to symptomatic UTI, postpartum UTI and consultation [14]. Symptomatic diagnosis of UTI with fever pyelonephritis in studies among pregnant women [10] [11] as a marker had moderate sensitivity (80%) and low reflects its (asymptomatic bacteriuria) significance in public specificity (40%) [15]. The World Health Organization health. Earlier studies in Lalitpur and Nigeria [2], [12] report recommends inclusion of UTI in IMCI protocols in countries lower prevalence of UTI amongst children (at 18.49% and without malaria and with high measles coverage provided; 11% respectively) than we have. The employment of supra- UTI is common among febrile children, health workers are pubic aspiration alongside midstream urine in the Nigerian aware of UTI among children, urine is collected and tested in study could have accounted for this high difference in first-level health facilities, health workers have capacity to prevalence though smaller prevalence (than 11%) have been treat UTI well, health facilities have functional water source, reported elsewhere by the World Health Organization. A UTI is a significant contributor to morbidity, dipstick study that assessed prevalence of UTI and drug susceptibility urinalysis can be made available, presumptive identification patterns among children aged 0-120 months reports of UTI is not burdensome to the referral system and prevalence as high as 65.3% [13]. Un-diagnosed UTI in presumptive treatment of UTI does not contribute to rise in under-fives among 10.13%, 14.12%, 40%, 20% 6.25% and drug resistance, antibiotic side effects as well as high drug 50% of clinically diagnosed malaria, upper respiratory tract cost [14]. Most studies in the developing countries report infections, sepsis/cellulitis/furunculosis, bronchopneumonia Escherichia coli as the commonest bacterial isolate of UTI and gastroenteritis respectively is documented elsewhere in among children [1], [16], [17], [18], [19], [20]. Surprisingly, Nigeria [2] and this depicts difficulty in clinical diagnosis of our study unearthed proteus as the leading cause of UTI UTI in the younger ages. Another study among under-fives among febrile under-fives in Nsambya hospital though this with primary diagnosis of malaria reports 9% co-morbidity was closely followed by Escherichia coli. Staphylococcus Open Science Journal of Clinical Medicine 2015; 3(6): 199-204 aureus showed a relatively high proportion at 14.8% while study are in line with the current changing patterns of microbial- the rest of the isolates presented with very low proportions – antibiotic resistance threatening not only the developing world but the entire glob. Local scientists need to make deliberate staphylococcus haemolyticus, staphylococcus intermedius, effort to redesign a study with a nationwide coverage to better citrobacter and morganella in that order. Understanding the understand the distribution and frequency of bacterial isolates of frequency of isolates in causation of UTI helps in designing UTI; and establish isolate-specific drug resistance profile based treatment protocols especially in making decisions to treat on the most common etiologies in order to re-structure the UTI clinically. The unique frequency of proteus documented treatment alogarithms (for UTI) in Uganda. In the mean time, it herein points to inapplicability of global treatment would be appropriate to consider treatment of UTI based on alogarithms (based on studies in most of the developing results of culture and sensitivity though this may not be feasible countries) in our context. Appropriate treatment protocols due to resource constraints' and incapacity of primary and based on drug susceptibility tests related to the commonest secondary health care facilities. causes of UTI in our setting like proteus, Escherichia coli and staphylococcus aureus would suffice. Our findings on drug List of Abbreviations susceptibility suggest high-levels of resistance against commonly used antibiotics. Despite the smaller number of IMCI: Integrated Management of Childhood Illnesses samples subjected to drug susceptibility tests, medicines like UTI: Urinary Tract Infection cotrimoxazole, amoxicillin, nalidixic acid, nitrofurantoin, oxacillin, methicillin, erythromycin, ampicillin, tetracycline confirmunacceptably resistance while only two medicines (cefatoxime and We acknowledge the support of management, the nursing amoxyclav) showed no evidence of resistance. Whereas the staff and laboratory staff of Nsambya hospital. This study small sample may not permit comparison of our findings was funded by the first author and Belgian Technical with earlier studies, it is obvious that the health system rethinks the treatment for un-complicated UTI among children in Uganda. The clinical guidelines of Uganda place single dose cotrimoxazole or ciproflaxin as first line treatments for un-complicated UTI (cystitis) while 10-14 [1] Fredrick F, Francis JM, Fataki M and Maselle S Y. Aetiology, days oral amoxicillin or cotrimoxazole for treatment of mild antimicrobial susceptibility and predictors of urinary tract infection among febrile under-fives at Muhimbili National pyelonephritis [21]. The same guideline recommends Hospital, Dar es Salaam-Tanzania. Academic Journals, 2013; intravenous ampicillin in combination with gentamicin for 7(12): 1029-1034. treatment of severe forms of pyelonephritis. These lines of treatment are based on the premise that Escherichia coli is the [2] Ibeneme CA, Oguonu T, Okafor HU, Ikefuna AN, Ozumba UC. Urinary tract infection in febrile under five children in commonest cause of UTI in Uganda. Our finding underpins Enugu, South Eastern Nigeria. Nigerian Journal of Clinical the need for a wider coverage survey to review the prevailing Practice, 2014; 17(5): 624-8. situation in terms of etiology of UTI: especially among the under fives. Even though the pattern of the bacterial spectrum [3] Okunola1 PO, Ibadin MO, Ofovwe GE and Ukoh G. Co- existence of urinary tract infection and malaria among remains un-changed (with Escherichia coli most prevalent), children under five years old: a report from Benin City, the pattern of resistance observed with the small sample suggests a bigger study in order to gain insight on treatment Transplantation, 2012; 23(3): 629-634. of UTI in Uganda. An earlier study in Uganda [22] recommends use of urine microscopy in screening for UTI OJambo G. Prevalence, bacterial causes and antibiotic sensitivity of urinary tract infections in children presenting among febrile under-fives. This study reveals that much as with fever to acute care unit in mulago hospital. Makerere microscopy may be useful in ‘ruling out' and ‘ruling in' of University Institutional Repository, 2008. Available from: UTI among febrile under-fives [22], urine culture and http://hdl.handle.net/10570/607 (Viewed on 3/9/2014). sensitivity remains equally important in choice of antibiotics [5] Ministry of Health. Annual health sector performance report for treatment of UTI among cases diagnosed with the same. financial year 2011/2012. Kampala: Ministry of Health, 2011/12. [6] WHO 2013. Pocket book of hospital care for children: guidelines for the management of common childhood The prevalence of UTI among febrile under-fives in Nsambya hospital is higher than most of the earlier reports. Similarly, the commonest bacterial isolate associated with UTI among under- [7] Shaikh N, Ewing A and Hoberman A. Risk of renal scarring in children with a first urinary tract infection: a systematic fives in Nsambya hospital deviates from most studies in review. J Pediatr 2010;126(6):1084-91. developing countries that majorly report Escherichia coli as the leading cause of UTI in this age category. The observed [8] Wiswell T. The Prepuce, Urinary Tract Infections, and the resistance patterns associated with common antibiotics in our Consequences. Pediatrics, 2000;105: 860-62. Ocokoru Christine et al.: Prevalence and Drug Susceptibility of Isolates of Urinary Tract Infections Among Febrile Under-Fives in Nsambya Hospital, Uganda [9] Cheesbrough M. District laboratory practice in tropical [17] Gorelick M and Shaw K. Screening tests for urinary tract countries.Part 2, 2nd ed. New York: Cambridege University infection in children: a meta-analysis. Pediatrics, 1999; [10] Andriole VT, Patterson TF: Epidemiology, natural history and [18] Rabasa A and Shattima D. Urinary tract infection in severely management of urinary tract infections in pregnancy. Med malnourished children at the University of Maidugiri Teaching Clin N Am, 1991; 75:359-73. Hospital. Journal of Tropical Pediatrics, 2002;48: 359-361. [11] Patterson TF, Andriole VT: Detection, significance and [19] Wammanda R and Ewa B. Urinary tract pathogens and their therapy of bacteriuria in pregnancy. Update in the managed antimicrobial sensitivity patterns in children. Annals of health care era. Inf Dis Clin N Am, 1997; 11:593-608. Tropical Paediatrics, 2002; 22: 197-198. [12] Raghubanshi BR, Shrestha D, Chaudhary M, Karki BMS, [20] Ahmed M, Moremi N, Mirambo MM, Hokororo A, Mushi Dhakal AK. Bacteriology of urinary tract infection in MF, Seni J, Kamugisha E and Mshana SE. Multi-resistant padeiatric patients at KIST medical college teaching hopsital. gram negative enteric bacteria causing urinary tract infection Journal of Kathmandu Medical College, 2014; 3 (7): Jan-Mar. among malnourished under fives admitted at a tertiary hospital, northwestern, Tanzania. Italian Journal of Pediatrics, [13] Payel C, Satya CN and Chitrita C. Etiology and drug resistance profile of pediatric urinary tract infections in eastern india. International Research Journal of Medical [21] Ministry of Health (Uganda). Republic of Uganda, Uganda Sciences, 2014; 2(6), 11-13. clinical guidelines 2012. National guidelines for management of common conditions. Kampala: Ministry of Health [14] World Health Organization. Urinary tract infections in infants and children in developing countries in the context of IMCI. Geneva: World Health Organization, 2005. [22] Anguyo RDO, Ocokoru C, Govule P. Predictive validity and reliability of dipstick and microscopy in diagnosis of urinary [15] American Academy of Pediatrics Committee on Quality tract infections among febrile under-fives in Nsambya Improvement, S. O. U. T. I. Practice parameter: the diagnosis, hospital, Uganda. Open Science Journal of Clinical Medicine, treatment, and evaluation of initial urinary tract infection in 2015; 3 (3): 107-111. febrile infants and young children. Pediatrics, 1999; 103(4). [16] Kala U and Jacobs W. Evaluation of urinary tract infection in malnourished black children. Annals of Tropical Paediatrics, 1992; 12: 75-81.
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