1. INCIDENCE OF ANTIBIOTICS RESISTANCE OF UROPATHOGENS IN OMANI CHILDREN PRESENTED WITH SINGLE EPISODE OF URINARY TRACT INFECTION
Mohamed El-Naggari 1, Sharef Waadallah 2, Dana Al Nabhani 1, Ali Al Sawai 2 Zakaria Al Muharrmi 3, Ibtisam El Nour 1.
Sultan Qaboos University Hospital; Pediatric Nephrology (1), General pediatric. (2)
Sultan Qaboos University ; Microbiology Department. (3) Muscat; Sultanate Of Oman.
Corresponding Author: ;
Abstract
Results
Urinary tract infection (UTI) is one of the most common community-acquired infections. Different organisms can be the cause of UTI in children, with resistance to antibiotics becoming a significant problem in the choice of treatment. Worldwide studies have documented the prevalence of uropathogens in different countries. However, there is no previous study documenting the incidence of different uropathogens in Oman. We aim to report the most common uropathogens, and their antibiotic sensitivity pattern, in children presented with documented single episode UTI, at a tertiary hospital in Oman. A retrospective analysis of all Omani children below 14 years presented with first documented UTI, to SQUH between September 2008 and August On retrospective review of all urine cultures, 438 positive urine cultures were identified. Out of those 208 (47.5%) belonged to children with first episode of UTI. 33 patients were excluded and 175 patients were finally analyzed. E. coli was the most frequently encountered uropathogen in our cohort (69%) followed by Klebsiella Pneumonia infection (17%) % of these two common organism were resistant to cotrimoxazole while 31% of them were resistant to Augmentine. 24% of E. coli and K. Pneumonia were resistant to Cefuroxime & only 10 % were resistant to Nitrofurantoin. Both Augmentine and Cotrimexazole should not be the first line antibiotics to treat UTI.
Between September 2008 and August 2012, 438 urine samples grew significant bacteria. Only 208 positive urine cultures belonged to 208 patients with first incidence of urinary tract infection. 33 patients were excluded from the study; 11 with neurological disabilities, 9 with hematological malignancy, 3 with immune deficiencies and 10 were excluded for deficiency of data. In our studied patients, UTI was widely distributed in all age groups, however, the largest proportion was in those <1 year of age (46 patients, 26%), (Table 1).
Laboratory Finding
All
(total =175)
≤ 2 years
(n=61)
2-14 yrs (n=114)
P value
WBC ( In 131 patients)
Leukocytosis *, n (%)
WBC (x10^9/L), range
WBC (x10^9/L), mean (±SD)
(n=131)
31 (24%)
2-31
11.9(±5.7)
(n=51)
10 (20%)
5-31
13.5(±6)
(n=80)
21 (18%)
2-28
10.8(±5.3)
0.100
ANC (In 131 patients) (x10^9/L)
Neutrophilia *, n (%)
Neutrophil count, range
Neutrophil count, mean (±SD)
38 (29%)
1-24
6.2 (±4.7)
13 (25%)
1-18
5.7 (±4.6)
25 (22%)
6.4 (±4.8)
0.115
CRP (In 73 patients)
High CRP **, n (%)
CRP range
CRP count (mg/L), median (IQR)
(n=73)
51 (70%)
2-319
24 (3-99)
(n=30)
18 (60%)
1-319
32 (12-99)
(n=43)
33 (29%)
3-282
37 (9-125)
0.098
Urinary WBC (In 175 patients)
Positive urinary WBCs, n (%)
WBC count / cmm, Median (IQR)
(n=175)
88 (50%)
75 (25-500)
23 (38%)
500 (75-500)
(n=114)
65 (57%)
0.015
0.040
Urinary RBC (In 175 patients)
Microscopic haematuria, n (%)
RBC count / cmm, Median (IQR)
53 (30%)
50 (10-50)
17 (28%)
36 (32%)
0.611
0.900
Nitrite (In 82 patients)
Positive urinary nitrate, n (%)
(n=82)
29 (35%)
(n=31)
7 (23%)
22 (43%)
0.118
Table 2 shows the cultured pathogens among the studied 175 patients with community acquired UTI. The most common isolated pathogen was Escherichia coli (77%), followed by Klebsiella spp (10%), Enterobacter spp (9%). Overall resistance to oral antibiotics was highest to Ampicillin (75%), followed by Cotrimoxazole © (Trimethoprim/Sulfamethoxazole; TMS) (47%), Augmentin© (amoxicillin/clavulanate) (43%). Overall resistance to IV antibiotics was less evident than oral antibiotics.Three out of the 120 isolated E coli (3%) and two out of the 30 isolated Klebsiella spp (7%) were Extended-Spectrum Beta-Lactamases (ESBL).
Sex distribution
n (%)
Age (years)
Female, n (%)
Male, n (%)
15 (33%)
31 (67%)
46 (26%)
< 1 year
10 (67%)
5 (33%)
15 (9%)
>1 yr to 2 yrs
30 (81%)
7 (19%)
37 (21%)
> 2 yrs to 5 yrs
35 (95%)
2 (5%)
> 5 yrs to 8 yrs
37 (92%)
3 (8%)
40 (23%)
> 8 yrs to 14 yrs
127 (73%)
48 (27%)
175 (100%)
TOTAL
Introduction
Urinary tract infection (UTI) is a common cause of fever and one of the most common community-acquired infections. Due to possible complications of upper UTI (pyelonephritis) such as renal scarring, hypertension, and end-stage renal disease, treatment with proper antibiotic is a crucial step of management. Although children with pyelonephritis tend to have fever and more systemic features, it is often difficult to distinguish cystitis from pyelonephritis based on clinical presentation, particularly in those younger than two years of age. (1)
Different organisms can be the cause of UTI in children, with resistance to antibiotics becoming a significant problem in the choice of treatment. Frequent use of wide-spectrum antibiotics may change the intestinal flora, and as a consequence, induce bacterial resistance. Regular surveillance of local uropathogens as well as their antibiotic susceptibility is considered useful to guide empirical therapy, as the prevalence of uropathogens and their features may vary according to the time and geographical area. (2) The American Academy of Pediatrics, the Royal College of Physicians of London and the National Guideline Clearing house recommend empirical and precocious treatment of UTI, based on the susceptibility standard to the antibiotics that are habitually utilized, with the objective of reducing risks of pyelonephritic scarring.(3)
Worldwide studies have documented the prevalence of uropathogens in different countries. (4,5) However, there is no previous study documenting the incidence of different uropathogens in Oman. In this study, we aim to report the most common uropathogens, and their antibiotic sensitivity pattern, in children presented with documented single episode UTI, at a tertiary hospital in Oman. In addition, we aim to describe the clinical presentation and laboratory evaluation in those children.
Table 1: Age and sex distribution of children with UTI (n=175)
Table 4: Laboratory findings in patients with UTI.
Resistance (%)
Antibiotic
Strept
agalactiae
n=1(0.6%)
Staph
spp
n=4(2%)
Citrobacter
n=3 (2%)
Enterobacter
Pseudomonas
n=2 (1%)
Entero-
coccus
n=7 (4%)
Klebsiella
spp **
n=30(17%)
E coli spp*
n=120
(69%)
ALL
n= 175
(100%) 25
100 76 75
Ampicillin 23 24 43
Augmentin 85 4
Amikacin 10 18 14
Ciprofloxacin 33 71 7
Cefotaxime
Ceftriaxone 67 17 19 21
Cefuroxime 13 2
Nitrofurantoin 11
Gentamicin 1
Meropenem 80 20 50 47
Cotrimoxasole #
Table 2: Percentage of antibiotic resistance of the isolated uropathogens (n=175).
* 3 out of the 120 isolated E coli (3%) were Extended-Spectrum Beta-Lactamases (ESBL) E coli.
** 2 out of the 30 isolated Klebsiella (7%) were Extended-Spectrum Beta-Lactamases (ESBL) Klebsiella pneumoniae.
# Cotrimoxasole = Trimethoprim/Sulfamethoxazole.
@ Tazocin = Piperacillin/Tazobactam.
Methods
Conclusions
A retrospective analysis of all Omani children with the first documented UTI, who presented to Sultan Qaboos University Hospital (SQUH) over 4 years duration between September 2008 and August All patients below 14 years of age with positive urine culture were evaluated for inclusion in the study. Exclusion criteria included: patients with recurrent UTI, neurological impairment (bed ridden patients), immune deficiencies and hematological malignancies, as these patients might have recurrent UTI or recurrent exposure to antibiotics which may affect the antibiotic resistance pattern. Patients with deficient data were also excluded from the study.
Data collected included age, gender, and clinical presentation such as fever, chills, , decreased activity, nausea and/or vomiting, abdominal pain, poor feeding, constipation, frequency or urination, dysuria, flank pain, secondary enuresis, gross haematuria and foul-smelling urine. Other data included method of urine collection, results of urine analysis including nitrites, pyuria and haematuria, in addition to results of urine culture and antibiotic sensitivity. Laboratory parameters included presence of leukocytosis, neutophilia, high CRP. Pyuria was defined as ≥5 WBC/high power field (HPF) and classified as mild 5-20, moderate and severe >60 WBC/HPF respectively. Haematuria was defined as 5 RBCs per HPF, and classified as gross or microscopic.
Urine culture method:
In clean catch samples, significant bacteriuria was defined as growth of ≥100,000 colony forming units (CFU)/mL of a single uropathogenic bacteria. In catheter urine samples, we defined significant bacteriuria as growth of ≥50,000 CFU/mL of a single uropathogenic bacteria. (7)
Data was entered in SSPS. Analysis included the distribution of UTI among different age group and gender categories. Different uropathogens causing UTI and their antibiotic sensitivity were reported. Descriptive statistics were used including frequencies and percentages for categorical variables, in addition to mean (± standard deviation) or median (and interquartile ratio IQR) for numerical variables. Differences between different groups were analyzed using Chi-squared (χ2) test or student’s t-test and Wilcoxon-Mann-Whitney test as appropriate. An a priori two-tailed level of significance was set at 0.05.
P value
2-14 yrs (n=114)
≤ 2 yrs
(n=61)
All
(n=175)
Medical history
0.003
0.406
48 (42%)
38.8 (±0.9)
40 (66%)
38.6 (±0.7)
88 (50%)
38.7 (±0.8)
Fever, n (%)
Degree of temp. , Mean (± SD)
0.069
0.087
10 (9%)
8 (7%)
2 (2%)
11 (18%)
3 (5%)
0 (0%)
21 (12%)
11 (6%)
3 (2%)
Fever only, n (%)
Fever > 40 degrees, n (%)
Chills, n (%)
0.002
36 (32%)
34 (56%)
70 (40%)
Nausea and/or Vomiting, n (%)
<0.001
51 (45%)
51 (29%)
Abdominal pain, n (%)
41 (36%)
4 (7%)
45 (26%)
Frequency, urgency, dysuria, n (%)
6 (6%)
13 (21%)
20 (11%)
Reduced / Poor feeding, n(%)
6 (5%)
15 (25%)
Decreased activity, n (%)
0.048
7 (6%)
7 (4%)
Flank pain, n (%)
0.034
8 (5%)
Secondary enuresis, n (%)
0.068
6 (3%)
Gross haematuria, n (%)
0.244
1 (2%)
Foul-smelling urine, n (%)
0.936
4 (4%)
2 (3%)
Constipation, n (%)
UTI was found to be more prevalent in female gender. E. coli was the most frequently encountered uropathogen in our cohort. While we observed high resistance to oral Cotrimoxazole in uropathogens found in our study compared to other reports, resistance to IV antibiotics (including Tazocin, gentamycin, cefotaxime, and ceftriaxone) was much less. We recommend that use of Ampicillin, Augmentin and Cotrimoxazole could not be justified as a first line of treatment, specifically in patients with acute pyelonephritis. If these antibiotics are used, patients should be reviewed within 48 hours with sensitivity report and determine further therapy. The reported antibiotic sensitivity may help in the future choice of antibiotic therapy, however, a larger multi center national study is recommended to establish wider description of the prevalent uropathogens in Oman.
References
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Table 3: Medical history in patients with UTI among different age.
(Table 3) Fever was the most common symptom presenting in 88 (50%) children, but fever as the only presenting symptom was documented in 21 (12%) of the patients. Fever, vomiting, and poor feeding were more significantly the presenting symptoms in children ≤ 2 years of age, abdominal pain, flank pain, and urinary symptoms were more frequently reported in those > 2 years of age.
Among the 131 patients who had full blood count tested, leukocytosis was reported in 31 patients (24%), and neutrophilia in 38 Patients (29%) (mean WBC count 11,900 ± 5700/mm3, mean absolute neutrophil count 6,200 ±4,700/mm3). (Table 4) High CRP was documented in 51 (70%) of the 73 patients who had this test, with a median (IQR) of 24 (3-99). There was no significant difference in inflammatory markers between children ≤ 2 years and those > 2 years of age.