Abstract
Objective: Urinary tract infections (UTIs) are common in neonates. Understanding the changes in the prevalence of common uropathogens is essential for early diagnosis and effective treatment of UTIs. This study aimed to identify etiological agents and determine the local antibiotic susceptibility patterns of uropathogens causing UTIs. Subjects and Methods: A retrospective cross-sectional descriptive study from January 2017 to December 2022 was conducted on hospitalized neonates at Maternity Hospital, Kuwait. Urine samples from neonates were analyzed to identify isolates, and antimicrobial susceptibility testing was determined using the VITEK® 2 system. Results: Out of 3,996 urine samples processed, 282 (7%) samples yielded significant bacteriuria, mostly from male 185 (65.6%). Gram-negative isolates were the most common 141 (50%), followed by yeasts 84 (29.8%) and Gram-positive isolates 57 (20.2%). The common uropathogens were Klebsiella pneumoniae 50 (17.7%), followed by Escherichia coli 47 (16.8%), Candida albicans 39 (13.8%), Enterococcus faecalis 34 (12%), and Staphylococcus epidermidis 17 (6%). High resistance rates were observed among Enterobacterales against ampicillin, cephalothin, cefuroxime, cefotaxime, nitrofurantoin, amoxicillin-clavulanic acid, ceftazidime, and trimethoprim-sulfamethoxazole. A total of 28 (56%) K. pneumoniae and 18 (38.3%) E. coli were extended-spectrum beta-lactamase producers. Conclusion: Gram-negative isolates are considered the predominant causative agents of UTIs in neonates at Maternity Hospital. Reduced antibiotic susceptibility to commonly used antibiotics poses a notable challenge in the clinical management of neonates with UTIs. This study underscores the importance of proactive surveillance in monitoring causative organisms and antibiotic susceptibility in neonates.
The overall magnitude of urinary tract infections in neonates was 7%, with the predominance of Klebsiella pneumoniae 17.7% and Escherichia coli 16.6%.
Increasing rates of antibiotic resistance to cephalosporins and extended-spectrum beta-lactamase producers, mainly K. pneumoniae 56% and E. coli 38.3%, are alarming.
Local surveillance of antimicrobial resistance patterns escorts antimicrobial policy and preserves the effectiveness of antimicrobial agents.
Introduction
Urinary tract infections (UTIs) occur when microorganisms are present in any part of the urinary tract. Despite significant improvements in high-standard antenatal services and modern neonatal care, neonatal infections remain a major cause of mortality in the developing world. Factors such as immature immune systems, prematurity, congenital urinary tract anomalies, and prolonged hospital stays make neonates particularly susceptible to UTIs [1]. In contrast to the largely benign course of UTIs in adults, UTIs in neonates are widely recognized as a source of acute morbidity and chronic medical disorders [2]. The overall prevalence rate of UTIs in neonates is 0.1–1%, increasing to 4–25% in preterm neonates. In infants younger than 2 months, the estimated prevalence rate ranges from 4.6 to 14% [3].
Various pathogens, including bacteria and fungi, can colonize the urinary system and lead to UTIs. Most of these infections are caused by bacteria of enteric origin. The causative agent differs according to the age group and related comorbidities [2]. The most commonly documented uropathogen is Escherichia coli (E. coli), which causes more than 80% to 90% of UTIs in neonate patients. This is due to the fact that E. coli strains have particular attachment factors for the transitional epithelium of the bladder and ureters [2, 4]. On the other hand, UTIs caused by group B Streptococci are more prevalent in neonates than in the other age groups [2]. Managing hospital-acquired UTIs is more challenging due to the involvement of various microorganisms. These include Gram-negative bacteria (GNB) such as Klebsiella pneumoniae (K. pneumoniae), E. coli (E. coli), Enterococcus, Enterobacter, Proteus mirabilis, and Pseudomonas aeruginosa, as well as Gram-positive bacteria (GPB) such as Staphylococcus epidermidis (S. epidermidis) and Enterococci [2]. The escalating spread of antibiotic resistance among uropathogens, combined with increasing UTI recurrence rates, poses a significant threat to public health and is likely to substantially exacerbate the economic burden associated with these infections [4].
Although neonates have higher UTI rates compared to older infants and young children, there has been a scarcity of data on UTIs during the neonatal period [5]. Data on UTIs during the neonatal period are limited. Despite developments, managing UTIs in the pediatric population remains challenging and controversial, primarily due to antibiotic resistance, especially with the rise of extended-spectrum beta-lactamase (ESBL)-producing organisms [6]. Enhancing the efficacy of empiric antimicrobial therapy for UTIs necessitates a comprehensive understanding of the uropathogens involved and their antibiotic susceptibility profiles in neonates. However, the paucity of data from Kuwait and many other regions underscores the need for focused research. To address this gap, we surveyed the prevalence and antibiotic resistance patterns of pathogens causing neonatal UTIs over a 6-year period (2017–2022) at the Maternity Hospital in Al-Sabah Specialized Medical District, Kuwait.
Subjects and Methods
Design and Study Population
This retrospective cross-sectional study spans a 6-year period from January 2017 to December 2022 and utilizes data from the Microbiology Department at the Maternity Hospital in Al-Sabah Specialized Medical District, Kuwait. The Maternity Hospital serves as a major tertiary care center for obstetric, gynecological, and neonatal patients, accounting for nearly one-third of all births in the country. In 2022, approximately 2,677 neonates were admitted annually. The hospital comprises 152 beds distributed across four neonatal wards, including two neonatal intensive care units (NICU1 and NICU2) and two special care units (SCU1 and SCU2). The primary distinction between NICU1 and NICU2 lies in the level of care provided, as neonatal intensive care units (NICUs) are categorized by the complexity of care they offer. NICU1 is designated as a level III NICU, delivering comprehensive care for very premature infants (born before 32 weeks of gestation) and those with critical illnesses. NICU2, classified as a level II NICU or special care nursery, provides care for infants born at or after 32 weeks of gestation who are moderately ill but not critically so. The SCU1 unit caters to neonates requiring higher levels of monitoring and care without critical illness, whereas the SCU2 unit is designed for neonates needing less intensive monitoring and care than SCU1. NICU1 is equipped with 21 beds, including 10 isolation rooms, while NICU2 contains 17 beds. SCU1 and SCU2 each have 46 beds, with 6 isolation rooms in each unit.
Patient Inclusion and Exclusion Criteria
Neonates aged from birth to 28 days were included in the study based on clinical suspicion of UTI, indicated by symptoms such as irritability, poor feeding, or other signs that might lead a clinician to suspect a UTI. The diagnosis was confirmed by laboratory criteria, including pyuria and bacteriuria, with the presence of bacteria in the urine suggesting a UTI according to the American Academy of Pediatrics guidelines [7].
Sample Collection
Urine samples were collected using sterile techniques such as bladder (suprapubic) aspiration and catheterization, which ensure a sterile sample collection directly from the bladder. This is crucial for diagnosing UTIs where contamination from the urethra and external genitalia may affect the results.
Transport and Processing
Urine samples were processed within 2 h after collection. All samples were cultured on cystine lactose electrolyte-deficient agar (Oxoid, Basingstoke, UK) and blood agar (Oxoid) plates and incubated at 37°C for 24 h.
Interpretation of Culture Isolates by CFU
Positive urine culture with pure bacterial growth exceeding 105 CFU/mL (colony-forming units per milliliter) indicated significant bacteriuria. While colony counts of 10⁴–10⁵ CFU/mL may be clinically significant in specific neonatal scenarios, such data were not included in our analysis, as our focus was on colony counts of >10⁵ CFU/mL, which aligns with the threshold for significant bacteriuria in our study design.
Bacterial Isolation and Identification
Bacterial isolates were identified at the species level using the VITEK® 2 identification card system (bioMérieux, Marcy-I’Étoile, France). The VITEK® 2 ID GPC and ID GNB cards were used to identify GPB and GNB, respectively. Candida species were identified using the germ tube test following the manufacturer’s instructions. Approximately 0.5 mL of serum was placed into a small test tube, and a yeast colony from a culture plate was aseptically collected using a sterile wooden applicator stick or loop. Yeast cells were suspended in the serum to form a light suspension, and the tube was incubated at 35–37°C for 2–4 h. Following incubation, a drop of the suspension was placed on a microscope slide using a Pasteur pipette, covered with a coverslip, and examined under a microscope at ×40 magnification.
Antimicrobial Susceptibility Testing Methods
Consecutive non-duplicated Gram-negative and Gram-positive bacterial isolates using the VITEK® 2 system (bioMérieux, Marcy-l’Étoile, France), ensuring that each sample was unique and not a repeat isolate from the same patient. VITEK® 2 antimicrobial susceptibility testing (AST) cards, including AST-366, AST-N020, AST-523, and AST-524, were inoculated for each isolate according to the manufacturer’s instructions.
For GNB, the antimicrobial agents used included ampicillin (AMP), amoxicillin-clavulanic acid, cephalothin (CF) (first-generation cephalosporins), cefuroxime (CXM) (second-generation cephalosporins), cefotaxime (CTX), ceftazidime (CTZ) (third-generation cephalosporins), meropenem (MEM) (carbapenem), piperacillin-tazobactam, amikacin (AK) (aminoglycosides), gentamicin (GN) (aminoglycosides), ciprofloxacin (CIP) (fluoroquinolones), nitrofurantoin, and sulfamethoxazole-trimethoprim (SXT) (bioMérieux, Marcy-I’Étoile, France).
For GPB isolates, the antimicrobial agents included penicillin (P), oxacillin, GN, CIP, teicoplanin (TEC), vancomycin (VAN), SXT, and nitrofurantoin (bioMérieux, Marcy-I'Étoile, France). Results of the tested pathogens were analyzed and interpreted according to the breakpoints provided by the Clinical and Laboratory Standards Institute (CLSI, 2020) using the VITEK® software version VTK-R01.02 [8].
Statistical Analysis
Statistical analysis was performed using IBM SPSS Statistics 25. Discrete variables, including frequencies and percentages, were summarized and presented in tables to provide a clear understanding of the data distribution.
Results
Over a 6-year period (2017–2022), a total of 3,996 urine samples were processed. The distribution of neonatal urine samples by year was as follows: 2017 (n = 685, 17.1%), 2018 (n = 687, 17.2%), 2019 (n = 857, 21.4%), 2020 (n = 671, 16.8%), 2021 (n = 663, 16.6%), and 2022 (n = 433, 10.8%). Among these, 282 samples (7%) yielded significant bacteriuria. The isolates included 141 GNB (50%), 84 yeasts (29.8%), and 57 GPB (20.2%). The annual prevalence rates of uropathogens were: 2017 (n = 36, 5.2%), 2018 (n = 57, 8.2%), 2019 (n = 75, 8.7%), 2020 (n = 50, 7.4%), 2021 (n = 39, 5.8%), and 2022 (n = 25, 5.7%).
Gender Prevalence
The overall distribution of uropathogens showed a higher prevalence among males, with 185 cases (65.6%), compared to 97 (34.4%) cases in females. The prevalence of GNB, GPB isolates, and Candida species was higher among male subjects, accounting for 89 (63.1%), 38 (66.7%), and 58 (69%), respectively, whereas females accounted for 52 (36.9%), 19 (33.3%), and 26 (31%), respectively.
For GNB, the most common uropathogens isolated among males were K. pneumoniae 33 (37%), E. coli 28 (31%), and Enterobacter cloacae 12 (13.4%). Among females, the prevalent uropathogens were E. coli 19 (36.5%), K. pneumoniae 17 (32.6%), and Klebsiella oxytoca 5 (9.6%) (Table 1).
Distribution of Gram-negative uropathogens isolated from urine samples of neonates with UTIs at the Maternity Hospital in Al-Sabah Specialized Medical District in Kuwait, based on year of detection, gender of patients, and type of neonatal wards
GNB . | Total . | Number (%) of uropathogens isolated from UTIs (2017–2022) . | |||||||||||
---|---|---|---|---|---|---|---|---|---|---|---|---|---|
year . | gender . | location . | |||||||||||
2017 . | 2018 . | 2019 . | 2020 . | 2021 . | 2022 . | M . | F . | SCU1 . | SCU2 . | NICU1 . | NICU2 . | ||
B. cepacia | 1 (0.7) | 0 | 0 | 0 | 0 | 1 (5.8) | 0 | 1 (1) | 0 | 0 | 0 | 1 (3.4) | 0 |
C. freundii | 1 (0.7) | 0 | 0 | 1 (3) | 0 | 0 | 0 | 1 (1) | 0 | 0 | 0 | 0 | 1 (6.7) |
E. aerogenes | 1 (0.7) | 0 | 1 (3.2) | 0 | 0 | 0 | 0 | 1 (1) | 0 | 0 | 0 | 1 (3.4) | 0 |
E. cloacae | 16 (11.3) | 3 (13) | 2 (6.4) | 5 (15) | 1 (4) | 4 (23.5) | 1 (7.6) | 12 (13.5) | 4 (7.6) | 4 (9.8) | 6 (10.9) | 6 (20) | 0 |
E. coli | 47 (33.4) | 3 (13) | 9 (29) | 13 (39.5) | 10 (41.6) | 7 (41) | 2 (15.3) | 28 (31.5) | 19 (36.5) | 13 (31.7) | 17 (30.9) | 8 (26.7) | 9 (60) |
K. oxytoca | 9 (6.4) | 0 | 4 (12) | 2 (6) | 1 (4) | 1 (5.8) | 1 (7.6) | 4 (4.5) | 5 (9.6) | 1 (2.4) | 3 (5.5) | 3 (10) | 2 (13.3) |
K. pneumoniae | 50 (35.5) | 15 (65.2) | 10 (32) | 8 (24.2) | 9 (37.5) | 3 (17.6) | 5 (38.4) | 33 (37) | 17 (32.7) | 20 (48.8) | 24 (43.7) | 5 (16.7) | 1 (6.7) |
M. morganii | 1 (0.7) | 0 | 0 | 1 (3) | 0 | 0 | 0 | 1 (1) | 0 | 0 | 1 (1.8) | 0 | 0 |
P. aeruginosa | 8 (5.7) | 0 | 2 (6.4) | 3 (9.1) | 2 (8.3) | 1 (5.8) | 0 | 4 (4.5) | 4 (7.6) | 1 (2.4) | 3 (5.4) | 2 (6.7) | 2 (13.3) |
S. marcescens | 4 (2.8) | 1 (4.4) | 1 (3.2) | 0 | 1 (4) | 0 | 1 (7.6) | 3 (3.4) | 1 (2) | 2 (4.9) | 0 | 2 (6.7) | 0 |
S. odorifera | 1 (0.7) | 0 | 1 (3.2) | 0 | 0 | 0 | 0 | 0 | 1 (2) | 0 | 1 (1.8) | 0 | 0 |
S. maltophilia | 2 (1.4) | 1 (4.4) | 1 (3.2) | 0 | 0 | 0 | 0 | 1 (1) | 1 (2) | 0 | 0 | 2 (6.7) | 0 |
Total | 141 (50%) | 23 (16.3) | 31 (22) | 33 (23.4) | 24 (17) | 17 (12.1) | 13 (9.2) | 89 (63.1) | 52 (36.9) | 41 (29) | 55 (39) | 30 (21.3) | 15 (10.7) |
GNB . | Total . | Number (%) of uropathogens isolated from UTIs (2017–2022) . | |||||||||||
---|---|---|---|---|---|---|---|---|---|---|---|---|---|
year . | gender . | location . | |||||||||||
2017 . | 2018 . | 2019 . | 2020 . | 2021 . | 2022 . | M . | F . | SCU1 . | SCU2 . | NICU1 . | NICU2 . | ||
B. cepacia | 1 (0.7) | 0 | 0 | 0 | 0 | 1 (5.8) | 0 | 1 (1) | 0 | 0 | 0 | 1 (3.4) | 0 |
C. freundii | 1 (0.7) | 0 | 0 | 1 (3) | 0 | 0 | 0 | 1 (1) | 0 | 0 | 0 | 0 | 1 (6.7) |
E. aerogenes | 1 (0.7) | 0 | 1 (3.2) | 0 | 0 | 0 | 0 | 1 (1) | 0 | 0 | 0 | 1 (3.4) | 0 |
E. cloacae | 16 (11.3) | 3 (13) | 2 (6.4) | 5 (15) | 1 (4) | 4 (23.5) | 1 (7.6) | 12 (13.5) | 4 (7.6) | 4 (9.8) | 6 (10.9) | 6 (20) | 0 |
E. coli | 47 (33.4) | 3 (13) | 9 (29) | 13 (39.5) | 10 (41.6) | 7 (41) | 2 (15.3) | 28 (31.5) | 19 (36.5) | 13 (31.7) | 17 (30.9) | 8 (26.7) | 9 (60) |
K. oxytoca | 9 (6.4) | 0 | 4 (12) | 2 (6) | 1 (4) | 1 (5.8) | 1 (7.6) | 4 (4.5) | 5 (9.6) | 1 (2.4) | 3 (5.5) | 3 (10) | 2 (13.3) |
K. pneumoniae | 50 (35.5) | 15 (65.2) | 10 (32) | 8 (24.2) | 9 (37.5) | 3 (17.6) | 5 (38.4) | 33 (37) | 17 (32.7) | 20 (48.8) | 24 (43.7) | 5 (16.7) | 1 (6.7) |
M. morganii | 1 (0.7) | 0 | 0 | 1 (3) | 0 | 0 | 0 | 1 (1) | 0 | 0 | 1 (1.8) | 0 | 0 |
P. aeruginosa | 8 (5.7) | 0 | 2 (6.4) | 3 (9.1) | 2 (8.3) | 1 (5.8) | 0 | 4 (4.5) | 4 (7.6) | 1 (2.4) | 3 (5.4) | 2 (6.7) | 2 (13.3) |
S. marcescens | 4 (2.8) | 1 (4.4) | 1 (3.2) | 0 | 1 (4) | 0 | 1 (7.6) | 3 (3.4) | 1 (2) | 2 (4.9) | 0 | 2 (6.7) | 0 |
S. odorifera | 1 (0.7) | 0 | 1 (3.2) | 0 | 0 | 0 | 0 | 0 | 1 (2) | 0 | 1 (1.8) | 0 | 0 |
S. maltophilia | 2 (1.4) | 1 (4.4) | 1 (3.2) | 0 | 0 | 0 | 0 | 1 (1) | 1 (2) | 0 | 0 | 2 (6.7) | 0 |
Total | 141 (50%) | 23 (16.3) | 31 (22) | 33 (23.4) | 24 (17) | 17 (12.1) | 13 (9.2) | 89 (63.1) | 52 (36.9) | 41 (29) | 55 (39) | 30 (21.3) | 15 (10.7) |
B. cepacia, Burkholderia cepacia; C. freundii, Citrobacter freundii; E. aerogenes, Enterobacter aerogenes; E. cloacae, Enterobacter cloacae; E. coli, Escherichia coli; K. oxytoca, Klebsiella oxytoca; K. pneumoniae, Klebsiella pneumoniae; M. morganii, Morganella morganii; P. aeruginosa, Pseudomonas aeruginosa; S. marcescens, Serratia marcescens; S. odorifera, Serratia odorifera; S. maltophilia, Stenotrophomonas maltophilia; M, male; F, female; NICU1 and NICU2, neonatal intensive care units 1 and 2; SCU1 and SCU2, special care units 1 and 2.
For GPB, the predominant uropathogens isolated in males were Enterococcus faecalis (E. faecalis) 21 (55%) and S. epidermidis 14 (36%). In females, E. faecalis 13 (68%) and S. epidermidis 3 (15.7%) were the most common (Table 2). The incidence of non-albicans Candida species was also higher among males, with 30 (66%) isolates, compared to females, who had 15 (34%) isolates (Table 3).
Distribution of Gram-positive uropathogens isolated from urine samples of neonates with UTIs at the Maternity Hospital in Al-Sabah Specialized Medical District in Kuwait, based on year of detection, gender of patients, and type of neonatal wards
GPB . | Total . | Number (%) of uropathogens isolated from UTIs (2017–2022) . | |||||||||||
---|---|---|---|---|---|---|---|---|---|---|---|---|---|
year . | gender . | location . | |||||||||||
2017 . | 2018 . | 2019 . | 2020 . | 2021 . | 2022 . | M . | F . | SCU1 . | SCU2 . | NICU1 . | NICU2 . | ||
E. faecalis | 34 (59.6) | 2 (66.7) | 5 (62.5) | 15 (62.5) | 4 (44.4) | 3 (60) | 5 (62.5) | 21 (55.3) | 13 (68.4) | 12 (70.5) | 13 (65) | 5 (62.5) | 4 (33.3) |
E. faecium | 4 (7) | 0 | 2 (25) | 0 | 1 (11.2) | 1 (20) | 0 | 2 (5.3) | 2 (10.5) | 1 (5.9) | 1 (5) | 1 (12.5) | 1 (8.4) |
S. aureus | 1 (1.8) | 0 | 0 | 1 (4.2) | 0 | 0 | 0 | 1 (2.6) | 0 | 1 (5.9) | 0 | 0 | 0 |
S. capitis | 1 (1.8) | 0 | 0 | 1 (4.2) | 0 | 0 | 0 | 0 | 1 (5.3) | 0 | 1 (5) | 0 | 0 |
S. epidermidis | 17 (29.8) | 1 (33.3) | 1 (12.5) | 7 (29.1) | 4 (44.4) | 1 (20) | 3 (37.5) | 14 (36.8) | 3 (15.8) | 3 (17.7) | 5 (25) | 2 (25) | 7 (58.3) |
Total | 57 (20.2) | 3 (5.3) | 8 (14) | 24 (42.1) | 9 (15.8) | 5 (8.8) | 8 (14) | 38 (66.7) | 19 (33.3) | 17 (29.8) | 20 (35.1) | 8 (14) | 12 (21.1) |
GPB . | Total . | Number (%) of uropathogens isolated from UTIs (2017–2022) . | |||||||||||
---|---|---|---|---|---|---|---|---|---|---|---|---|---|
year . | gender . | location . | |||||||||||
2017 . | 2018 . | 2019 . | 2020 . | 2021 . | 2022 . | M . | F . | SCU1 . | SCU2 . | NICU1 . | NICU2 . | ||
E. faecalis | 34 (59.6) | 2 (66.7) | 5 (62.5) | 15 (62.5) | 4 (44.4) | 3 (60) | 5 (62.5) | 21 (55.3) | 13 (68.4) | 12 (70.5) | 13 (65) | 5 (62.5) | 4 (33.3) |
E. faecium | 4 (7) | 0 | 2 (25) | 0 | 1 (11.2) | 1 (20) | 0 | 2 (5.3) | 2 (10.5) | 1 (5.9) | 1 (5) | 1 (12.5) | 1 (8.4) |
S. aureus | 1 (1.8) | 0 | 0 | 1 (4.2) | 0 | 0 | 0 | 1 (2.6) | 0 | 1 (5.9) | 0 | 0 | 0 |
S. capitis | 1 (1.8) | 0 | 0 | 1 (4.2) | 0 | 0 | 0 | 0 | 1 (5.3) | 0 | 1 (5) | 0 | 0 |
S. epidermidis | 17 (29.8) | 1 (33.3) | 1 (12.5) | 7 (29.1) | 4 (44.4) | 1 (20) | 3 (37.5) | 14 (36.8) | 3 (15.8) | 3 (17.7) | 5 (25) | 2 (25) | 7 (58.3) |
Total | 57 (20.2) | 3 (5.3) | 8 (14) | 24 (42.1) | 9 (15.8) | 5 (8.8) | 8 (14) | 38 (66.7) | 19 (33.3) | 17 (29.8) | 20 (35.1) | 8 (14) | 12 (21.1) |
E. faecalis, Enterococcus faecalis; E. faecium, Enterococcus faecium; S. aureus, Staphylococcus aureus; S. capitis, Staphylococcus capitis; S. epidermidis, Staphylococcus epidermidis; M, male; F, female; NICU1 and NICU2, neonatal intensive care units 1 and 2; SCU1 and SCU2, special care units 1 and 2.
Distribution of yeast uropathogens isolated from urine samples of neonates with UTIs at the Maternity Hospital in Al-Sabah Specialized Medical District in Kuwait, based on year of detection, gender of patients, and type of neonatal wards
Yeast isolates . | Total . | Number (%) of uropathogens isolated from UTIs (2017–2022) . | |||||||||||
---|---|---|---|---|---|---|---|---|---|---|---|---|---|
year . | gender . | location . | |||||||||||
2017 . | 2018 . | 2019 . | 2020 . | 2021 . | 2022 . | M . | F . | SCU1 . | SCU2 . | NICU1 . | NICU2 . | ||
Candida albicans | 39 (46.4) | 6 (60) | 8 (44.4) | 9 (50) | 7 (41.2) | 6 (35.3) | 3 (75) | 28 (48.2) | 11 (42.3) | 10 (50) | 13 (56.6) | 10 (37) | 6 (43) |
Non-albicans Candida species | 45 (53.6) | 4 (40) | 10 (55.6) | 9 (50) | 10 (58.8) | 11 (64.7) | 1 (25) | 30 (51.7) | 15 (57.6) | 10 (50) | 10 (42.4) | 17 (63) | 8 (57) |
Total | 84 (29.7) | 10 (12) | 18 (21.4) | 18 (21.4) | 17 (20.2) | 17 (20.2) | 4 (4.8) | 58 (69) | 26 (31) | 20 (24) | 23 (27.3) | 27 (32.1) | 14 (16.6) |
Yeast isolates . | Total . | Number (%) of uropathogens isolated from UTIs (2017–2022) . | |||||||||||
---|---|---|---|---|---|---|---|---|---|---|---|---|---|
year . | gender . | location . | |||||||||||
2017 . | 2018 . | 2019 . | 2020 . | 2021 . | 2022 . | M . | F . | SCU1 . | SCU2 . | NICU1 . | NICU2 . | ||
Candida albicans | 39 (46.4) | 6 (60) | 8 (44.4) | 9 (50) | 7 (41.2) | 6 (35.3) | 3 (75) | 28 (48.2) | 11 (42.3) | 10 (50) | 13 (56.6) | 10 (37) | 6 (43) |
Non-albicans Candida species | 45 (53.6) | 4 (40) | 10 (55.6) | 9 (50) | 10 (58.8) | 11 (64.7) | 1 (25) | 30 (51.7) | 15 (57.6) | 10 (50) | 10 (42.4) | 17 (63) | 8 (57) |
Total | 84 (29.7) | 10 (12) | 18 (21.4) | 18 (21.4) | 17 (20.2) | 17 (20.2) | 4 (4.8) | 58 (69) | 26 (31) | 20 (24) | 23 (27.3) | 27 (32.1) | 14 (16.6) |
M, male; F, female; NICU1 and NICU2, neonatal intensive care units 1 and 2; SCU1 and SCU2, special care units 1 and 2.
Gram-Negative Bacterial Isolates
During the study period, 141 GNB were identified, representing 50% of the 282 isolates. The annual distribution of GNB was as follows: 2017 (n = 23, 16.3%), 2018 (n = 31, 22%), 2019 (n = 33, 23.4%), 2020 (n = 24, 17%), 2021 (n = 17, 12.1%), and 2022 (n = 13, 9.2%). The predominant species identified among the overall number of uropathogens (n = 282) were K. pneumoniae (n = 50, 17.7%) and E. coli (n = 47, 16.6%). Other species included E. cloacae (n = 16, 5.6%), K. oxytoca (n = 9, 3.19%), P. aeruginosa (n = 8, 2.8%), Serratia marcescens (n = 4, 1.4%), and Stenotrophomonas maltophilia (n = 2, 0.7%). Additionally, single isolates (n = 1, 0.3%) of Burkholderia cepacia, Citrobacter freundii, Enterobacter aerogenes, Morganella morganii, and Serratia odorifera were identified. The detailed analysis of the etiological agents is shown in Table 1.
Gram-Positive Bacterial Isolates
A total of 57 GPB were detected, representing 20.2% of the total isolates. The annual distribution of GPB was as follows: 2017 (n = 3, 5.3%), 2018 (n = 8, 14%), 2019 (n = 24, 42.1%), 2020 (n = 9, 15.8%), 2021 (n = 5, 8.8%), and 2022 (n = 8, 14%). The most frequently isolated microorganisms among the total uropathogens (n = 282) were E. faecalis (n = 34, 12%), followed by S. epidermidis (n = 17, 6%), Enterococcus faecium (E. faecium) (n = 4, 1.4%), and single isolates of Staphylococcus capitis (S. capitis) and Staphylococcus aureus (each n = 1, 0.3%), as detailed in Table 2.
Yeast Isolates
During the study period, a total of 84 Candida species were identified, representing 29.8% of the total isolates. The annual distribution of Candida isolates was as follows: 2017 (n = 10, 12%), 2018 (n = 18, 21.4%), 2019 (n = 18, 21.4%), 2020 (n = 17, 20.2%), 2021 (n = 17, 20.2%), and 2022 (n = 4, 4.8%). Among the total uropathogens (n = 282), the yeast isolates included 39 (13.8%) Candida albicans and non-albicans Candida species 45 (15.9%), as detailed in Table 3.
Location Distribution of Isolates
A total of 176 (62.4%) hospitalized neonates were admitted to SCU1 (n = 78, 44.3%) and SCU2 (n = 98, 55.7%), while the remaining 106 (37.6%) were admitted to NICU1 (n = 65, 61.3%) and NICU2 (n = 41, 38.7%). The majority of GNB were isolated from neonates in SCU2 (n = 55, 39%), followed by SCU1 (n = 41, 29%), NICU1 (n = 30, 21.3%), and NICU2 (n = 15, 10.7%). K. pneumoniae and E. coli were the most common uropathogens isolated (Table 1).
Predominantly, GPB were isolated from neonates in SCU2 (n = 20, 35.1%), followed by SCU1 (n = 17, 29.8%), NICU2 (n = 12, 21.1%), and NICU1 (n = 8, 14%). E. faecalis and S. epidermidis were the most prevalent uropathogens isolated (Table 2). C. albicans and non-albicans Candida species were isolated from neonates in NICU1 (n = 27, 32.1%), followed by SCU2 (n = 23, 27.3%), SCU1 (n = 20, 24%) and NICU2 (n = 14, 16.6%) (Table 3).
Antimicrobial Susceptibility Data
The susceptibility patterns of GNB against commonly used antibiotic classes over a 6-year study period, expressed as resistance rates, are demonstrated in Table 4. Resistance rates of members of the family of Enterobacterales, including E. cloacae, E. coli, K. pneumoniae, and K. oxytoca to CF, were 100%, 66.1%, 58.8%, and 4.2%, respectively. For second-generation cephalosporins, specifically CXM 100% of E. cloacae isolates were resistant. The overall resistance rate of CXM in K. pneumoniae isolates was 58.8%, compared to 80% in 2022 and 33% in 2021. E. coli exhibited an overall resistance rate of 43.9%, with a notable increase in the resistance rate in 2021 (71%) compared to 2017 (33%). K. oxytoca showed the lowest resistance rate (4.2%). K. pneumoniae and E. coli demonstrated resistance rates against third-generation cephalosporins, specifically CTX and ceftazidime, of (54.4%, 40.6%) and (51.4%, 36.5%), respectively. E. cloacae showed an overall resistance rate of 18.1%, while K. oxytoca exhibited 100% susceptibility to these third-generation cephalosporins.
Antimicrobial resistance pattern of Gram-negative uropathogens isolated from neonates with UTIs between 2017–2022 at the Maternity Hospital in Al-Sabah Specialized Medical District in Kuwait
Gram-negative uropathogens . | Year . | Total . | Number (%) of isolates resistant to antimicrobial agents . | ||||||||||||
---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
AMP . | AMC . | TZP . | CXM . | CTX . | CTZ . | MEM . | AK . | GN . | CIP . | NIT . | SXT . | CF . | |||
Enterobacter cloacae (n = 16) | 2017 | 3 | 3 (100) | 3 (100) | 1 (33) | 3 (100) | 1 (33.3) | 1 (33) | 0 | 0 | 0 | 0 | 1 (33.3) | 0 | 3 (100) |
2018 | 2 | 2 (100) | 2 (100) | 0 | 2 (100) | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 2 (100) | |
2019 | 5 | 5 (100) | 5 (100) | 0 | 5 (100) | 0 | 0 | 0 | 0 | 0 | 0 | 1 (20) | 2 (40) | 5 (100) | |
2020 | 1 | 1 (100) | 1 (100) | 0 | 1 (100) | 0 | 0 | 0 | 0 | 0 | 0 | 1 (100) | 0 | 1 (100) | |
2021 | 4 | 4 (100) | 4 (100) | 2 (50) | 4 (100) | 3 (75) | 3 (75) | 0 | 0 | 0 | 0 | 1 (25) | 0 | 4 (100) | |
2022 | 1 | 1 (100) | 1 (100) | 0 | 1 (100) | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 1 (100) | |
Escherichia coli (n = 47) | 2017 | 3 | 3 (100) | 2 (67) | 1 (33) | 1 (33) | 1 (33) | 1 (33) | 0 | 0 | 0 | 0 | 1 (33) | 0 | 2 (67) |
2018 | 9 | 9 (100) | 2 (22) | 1 (11) | 3 (33) | 3 (33) | 3 (33) | 0 | 0 | 1 (11) | 2 (22) | 0 | 5 (56) | 4 (44) | |
2019 | 13 | 6 (46.2) | 4 (31) | 0 | 2 (15) | 2 (15) | 2 (15) | 0 | 0 | 1 (8) | 0 | 0 | 3 (23) | 7 (54) | |
2020 | 10 | 9 (90) | 3 (30) | 1 (10) | 7 (70) | 5 (50) | 4 (40) | 0 | 0 | 0 | 4 (40) | 0 | 4 (40) | 8 (80) | |
2021 | 7 | 7 (100) | 3 (43) | 2 (29) | 5 (71) | 5 (71) | 4 (57) | 2 (29) | 0 | 0 | 3 (43) | 1 (14) | 4 (57) | 5 (71) | |
2022 | 5 | 3 (60) | 0 | 0 | 2 (40) | 2 (40) | 2 (40) | 0 | 0 | 0 | 0 | 0 | 0 | 4 (80) | |
Klebsiella oxytoca (n = 9) | 2017 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 |
2018 | 4 | 4 (100) | 1 (25) | 1 (25) | 1 (25) | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 1 (25) | |
2019 | 2 | 2 (100) | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | |
2020 | 1 | 1 (100) | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 1 (100) | 0 | 0 | |
2021 | 1 | 1 (100) | 0 | 1 (100) | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | |
2022 | 1 | 1 (100) | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | |
Klebsiella pneumoniae (n = 50) | 2017 | 15 | 15 (100) | 5 (33) | 4 (27) | 9 (60) | 8 (53) | 7 (47) | 0 | 2 (13) | 5 (33) | 3 (20) | 6 (40) | 6 (40) | 9 (60) |
2018 | 10 | 10 (100) | 4 (40) | 1 (10) | 6 (60) | 6 (60) | 6 (60) | 0 | 0 | 2 (20) | 3 (30) | 4 (40) | 4 (40) | 6 (60) | |
2019 | 8 | 8 (100) | 3 (38) | 3 (38) | 6 (75) | 6 (75) | 6 (75) | 0 | 0 | 2 (25) | 3 (38) | 3 (38) | 6 (75) | 6 (75) | |
2020 | 9 | 9 (100) | 1 (11) | 1 (11) | 4 (45) | 4 (45) | 3 (33) | 0 | 1 (11) | 0 | 0 | 7 (78) | 3 (33) | 4 (45) | |
2021 | 3 | 3 (100) | 0 | 0 | 1 (33) | 1 (33) | 1 (33) | 0 | 0 | 0 | 0 | 3 (100) | 1 (33) | 1 (33) | |
2022 | 5 | 5 (100) | 3 (60) | 2 (40) | 4 (80) | 3 (60) | 3 (60) | 0 | 1 (20) | 2 (40) | 1 (20) | 4 (80) | 1 (20) | 4 (80) |
Gram-negative uropathogens . | Year . | Total . | Number (%) of isolates resistant to antimicrobial agents . | ||||||||||||
---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
AMP . | AMC . | TZP . | CXM . | CTX . | CTZ . | MEM . | AK . | GN . | CIP . | NIT . | SXT . | CF . | |||
Enterobacter cloacae (n = 16) | 2017 | 3 | 3 (100) | 3 (100) | 1 (33) | 3 (100) | 1 (33.3) | 1 (33) | 0 | 0 | 0 | 0 | 1 (33.3) | 0 | 3 (100) |
2018 | 2 | 2 (100) | 2 (100) | 0 | 2 (100) | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 2 (100) | |
2019 | 5 | 5 (100) | 5 (100) | 0 | 5 (100) | 0 | 0 | 0 | 0 | 0 | 0 | 1 (20) | 2 (40) | 5 (100) | |
2020 | 1 | 1 (100) | 1 (100) | 0 | 1 (100) | 0 | 0 | 0 | 0 | 0 | 0 | 1 (100) | 0 | 1 (100) | |
2021 | 4 | 4 (100) | 4 (100) | 2 (50) | 4 (100) | 3 (75) | 3 (75) | 0 | 0 | 0 | 0 | 1 (25) | 0 | 4 (100) | |
2022 | 1 | 1 (100) | 1 (100) | 0 | 1 (100) | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 1 (100) | |
Escherichia coli (n = 47) | 2017 | 3 | 3 (100) | 2 (67) | 1 (33) | 1 (33) | 1 (33) | 1 (33) | 0 | 0 | 0 | 0 | 1 (33) | 0 | 2 (67) |
2018 | 9 | 9 (100) | 2 (22) | 1 (11) | 3 (33) | 3 (33) | 3 (33) | 0 | 0 | 1 (11) | 2 (22) | 0 | 5 (56) | 4 (44) | |
2019 | 13 | 6 (46.2) | 4 (31) | 0 | 2 (15) | 2 (15) | 2 (15) | 0 | 0 | 1 (8) | 0 | 0 | 3 (23) | 7 (54) | |
2020 | 10 | 9 (90) | 3 (30) | 1 (10) | 7 (70) | 5 (50) | 4 (40) | 0 | 0 | 0 | 4 (40) | 0 | 4 (40) | 8 (80) | |
2021 | 7 | 7 (100) | 3 (43) | 2 (29) | 5 (71) | 5 (71) | 4 (57) | 2 (29) | 0 | 0 | 3 (43) | 1 (14) | 4 (57) | 5 (71) | |
2022 | 5 | 3 (60) | 0 | 0 | 2 (40) | 2 (40) | 2 (40) | 0 | 0 | 0 | 0 | 0 | 0 | 4 (80) | |
Klebsiella oxytoca (n = 9) | 2017 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 |
2018 | 4 | 4 (100) | 1 (25) | 1 (25) | 1 (25) | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 1 (25) | |
2019 | 2 | 2 (100) | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | |
2020 | 1 | 1 (100) | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 1 (100) | 0 | 0 | |
2021 | 1 | 1 (100) | 0 | 1 (100) | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | |
2022 | 1 | 1 (100) | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | |
Klebsiella pneumoniae (n = 50) | 2017 | 15 | 15 (100) | 5 (33) | 4 (27) | 9 (60) | 8 (53) | 7 (47) | 0 | 2 (13) | 5 (33) | 3 (20) | 6 (40) | 6 (40) | 9 (60) |
2018 | 10 | 10 (100) | 4 (40) | 1 (10) | 6 (60) | 6 (60) | 6 (60) | 0 | 0 | 2 (20) | 3 (30) | 4 (40) | 4 (40) | 6 (60) | |
2019 | 8 | 8 (100) | 3 (38) | 3 (38) | 6 (75) | 6 (75) | 6 (75) | 0 | 0 | 2 (25) | 3 (38) | 3 (38) | 6 (75) | 6 (75) | |
2020 | 9 | 9 (100) | 1 (11) | 1 (11) | 4 (45) | 4 (45) | 3 (33) | 0 | 1 (11) | 0 | 0 | 7 (78) | 3 (33) | 4 (45) | |
2021 | 3 | 3 (100) | 0 | 0 | 1 (33) | 1 (33) | 1 (33) | 0 | 0 | 0 | 0 | 3 (100) | 1 (33) | 1 (33) | |
2022 | 5 | 5 (100) | 3 (60) | 2 (40) | 4 (80) | 3 (60) | 3 (60) | 0 | 1 (20) | 2 (40) | 1 (20) | 4 (80) | 1 (20) | 4 (80) |
AMP, ampicillin; AMC, amoxicillin-clavulanic acid; TZP, piperacillin-tazobactam; CXM, cefuroxime; CTX, cefotaxime; CTZ, ceftazidime; MEM, meropenem; AK, amikacin; GN, gentamicin; CIP, ciprofloxacin; NIT, nitrofurantoin; SXT, sulfamethoxazole-trimethoprim; CF, cephalothin.
K. pneumoniae isolates exhibited resistance rates of 7.4% and 19.7% against AK and GN, with the highest rates of resistance observed in 2022 (20% and 40%), respectively. Conversely, aminoglycosides, particularly GN, were more effective against E. coli isolates (3.1%), while E. cloacae and K. oxytoca showed 100% susceptibility to both GN and AK.
Furthermore, K. pneumoniae exhibited the highest resistance rate among all isolates (17.9%) against CIP, followed by E. coli (17.5%). However, E. cloacae and K. oxytoca both showed 100% susceptibility. The carbapenem-resistant Enterobacterales resistance rate in E. coli was 4.8%, whereas E. cloacae, K. pneumoniae, and K. oxytoca were highly sensitive, with no resistance to MEM observed.
The resistance rates of GPB to the commonly used antibiotic are demonstrated in Table 5. E. faecalis and S. epidermidis showed 100% susceptibility to glycopeptides, including vancomycin and teicoplanin. E. faecalis also exhibited 100% susceptibility to P. However, S. epidermidis had a high resistance rate (100%) to P and oxacillin.
Antimicrobial resistance pattern of Gram-positive uropathogens isolated from neonates with UTIs between 2017 and 2022 at the Maternity Hospital in Al-Sabah Specialized Medical District in Kuwait City
Gram-positive microorganisms . | Year . | Total . | Number (%) of isolates resistant to antimicrobial agents . | |||||||
---|---|---|---|---|---|---|---|---|---|---|
P . | CIP . | TEC . | VA . | NIT . | . | |||||
Enterococcus faecalis (n = 34) | 2017 | 2 | 0 | 0 | 0 | 0 | 0 | |||
2018 | 5 | 0 | 0 | 0 | 0 | 0 | ||||
2019 | 15 | 0 | 0 | 0 | 0 | 1 (7) | ||||
2020 | 4 | 0 | 0 | 0 | 0 | 0 | ||||
2021 | 3 | 0 | 0 | 0 | 0 | 0 | ||||
2022 | 5 | 0 | 0 | 0 | 0 | 0 |
Gram-positive microorganisms . | Year . | Total . | Number (%) of isolates resistant to antimicrobial agents . | |||||||
---|---|---|---|---|---|---|---|---|---|---|
P . | CIP . | TEC . | VA . | NIT . | . | |||||
Enterococcus faecalis (n = 34) | 2017 | 2 | 0 | 0 | 0 | 0 | 0 | |||
2018 | 5 | 0 | 0 | 0 | 0 | 0 | ||||
2019 | 15 | 0 | 0 | 0 | 0 | 1 (7) | ||||
2020 | 4 | 0 | 0 | 0 | 0 | 0 | ||||
2021 | 3 | 0 | 0 | 0 | 0 | 0 | ||||
2022 | 5 | 0 | 0 | 0 | 0 | 0 |
. | Year . | n . | Number (%) of isolates resistant to antimicrobial agents . | |||||||
---|---|---|---|---|---|---|---|---|---|---|
P . | OX . | GN . | CIP . | TEC . | VA . | SXT . | NIT . | |||
Staphylococcus epidermidis (n = 17) | 2017 | 1 | 1 (100) | 1 (100) | 1 (100) | 1 (100) | 0 | 0 | 0 | 0 |
2018 | 1 | 1 (100) | 1 (100) | 1 (100) | 1 (100) | 0 | 0 | 1 (100) | 0 | |
2019 | 7 | 7 (100) | 7 (100) | 6 (86) | 5 (71) | 0 | 0 | 3 (43) | 0 | |
2020 | 4 | 4 (100) | 4 (100) | 4 (100) | 4 (100) | 0 | 0 | 2 (50) | 0 | |
2021 | 1 | 1 (100) | 1 (100) | 1 (100) | 0 | 0 | 0 | 0 | 0 | |
2022 | 3 | 3 (100) | 3 (100) | 3 (100) | 3 (100) | 0 | 0 | 3 (100) | 1 (33) |
. | Year . | n . | Number (%) of isolates resistant to antimicrobial agents . | |||||||
---|---|---|---|---|---|---|---|---|---|---|
P . | OX . | GN . | CIP . | TEC . | VA . | SXT . | NIT . | |||
Staphylococcus epidermidis (n = 17) | 2017 | 1 | 1 (100) | 1 (100) | 1 (100) | 1 (100) | 0 | 0 | 0 | 0 |
2018 | 1 | 1 (100) | 1 (100) | 1 (100) | 1 (100) | 0 | 0 | 1 (100) | 0 | |
2019 | 7 | 7 (100) | 7 (100) | 6 (86) | 5 (71) | 0 | 0 | 3 (43) | 0 | |
2020 | 4 | 4 (100) | 4 (100) | 4 (100) | 4 (100) | 0 | 0 | 2 (50) | 0 | |
2021 | 1 | 1 (100) | 1 (100) | 1 (100) | 0 | 0 | 0 | 0 | 0 | |
2022 | 3 | 3 (100) | 3 (100) | 3 (100) | 3 (100) | 0 | 0 | 3 (100) | 1 (33) |
P, penicillin; OX, oxacillin; GN, gentamicin; CIP, ciprofloxacin; TEC, teicoplanin; VA, vancomycin; SXT, sulfamethoxazole-trimethoprim; NIT, nitrofurantoin.
Prevalence of ESBL-Producing Isolates
A relatively high proportion of K. pneumoniae and E. coli isolates were identified as ESBL producers, with 28 (56%) of K. pneumoniae and 18 (38.3%) of E. coli demonstrating this resistance mechanism. The annual distribution of ESBL-producing isolates was as follows: in 2017, there were 7 (25%) K. pneumoniae and 3 (16.6%) E. coli; in 2018, 6 (21.4%) K. pneumoniae and 3 (16.6%) E. coli; in 2019, 6 (21.4%) K. pneumoniae and 3 (16.6%) E. coli; in 2020, 5 (17.8%) K. pneumoniae and 5 (27.7%) E. coli; in 2021, 1 (3.5%) K. pneumoniae and 2 (11.1%) E. coli; and in 2022, 3 (10.7%) K. pneumoniae and 2 (11.1%) E. coli.
Discussion
UTIs are among the most prevalent bacterial infections in neonates, driven by factors such as immature immune systems, anatomical vulnerabilities, congenital abnormalities, catheterization, use of broad-spectrum antibiotics, inadequate hygiene practices, and prolonged hospital stays. This study offers a comprehensive analysis of the incidence, etiology, and antimicrobial susceptibility of uropathogens in neonates admitted to the Maternity Hospital, Ministry of Health, Kuwait. Notably, the prevalence of neonatal UTIs remains underreported in many countries, including Kuwait. Our study revealed an average UTI incidence of 7% among 3,996 urine samples from neonates. These findings are consistent with a retrospective study from Lebanon (2017–2020), which reported an 8.9% prevalence of UTIs in neonates [9]. Similar results were observed in earlier studies by Garcia and Nager and Bilgen et al. [10], showing UTI prevalence of 7.5% and 8%, respectively [11]. The percentage of UTIs cases among neonates varied annually, with peaks in 2018 (57%) and 2019 (75%) during the pre-pandemic period, followed by a substantial decrease during the COVID-19 pandemic period. Trends align with findings from Liang et al. [12], suggesting that variations in UTI rates may be due to misdiagnosis (false positives, such as bacteriuria) and overdiagnosis (true infections resolving without treatment). Our study also found a high male predominance of UTIs (65.6%) among neonate samples, attributed to bacterial colonization of the skin due to phimosis, particularly in uncircumcised boys, leading to ascending infections. It is well-known that UTIs are more frequent in boys during the first 36 months of life, while the incidence in females increases with age.
Additionally, males are more likely to be born with structural abnormalities of the urinary tract [13]. These findings are consistent with other studies, such as Arshad et al. [14], which reported a male predominance in neonatal UTIs, with boys representing 70–90% of cases. Furthermore, Harb et al. [9] revealed that males are more likely than females to develop UTIs in neonates (odds ratio 2.366, p = 0.016). Moreover, 62.4% and 37.6% of neonates were admitted to SCU and NICU due to complications related to the genitourinary system increased the risk of UTI by 4.8 times.
UTIs can be caused by different types of bacteria and fungi [15]. As shown in our data, UTIs are caused by GNB (50%), followed by Candida species (29.8%) and GPB (20.2%). Our data revealed that K. pneumoniae had the highest frequency (17.7%), aligning with the findings of Lugira et al. [16] and Omoregie et al. [17], who reported that K. pneumoniae was the most isolated causative bacterial agent in 64.3% of urine cultures among neonates at Dodoma Regional Referral Hospital in Dodoma [16] and in 28.57% of cases in Benin City, Nigeria [17]. However, these results differ from a study conducted by Arshad et al. [14], which showed that E. coli was the predominant pathogen isolated from UTIs in pediatric patients. In our study, the targeted patients were neonates aged from birth to 28 days only. However, E. coli can cause up to 80% of UTIs compared to older age groups. Other studies revealed that the overall burden of disease by E. coli was reduced in the neonatal group. This may be due to the use of antibiotics during labor to prevent group B Streptococcus (GBS) infections, which have also been effective against E. coli. Additional factors, including low birth weight, prematurity, prolonged hospitalization, and the frequent use of invasive devices such as catheters and mechanical ventilation in NICU and SCU settings, significantly increase the risk of K. pneumoniae infections in neonates [18].
Candida species are the most common fungal pathogens in neonates, often leading to candiduria. Our data revealed that Candida species (29.8%) were the second most frequent isolates from neonatal UTIs, including C. albicans (13.8%) and non-albicans Candida species (15.9%). These findings are consistent with a study by Allan Ronald [19], which mentioned that fungi are the second most commonly isolated pathogen (18%) in neonatal candiduria. Evidence suggests that candiduria in neonates often reflects colonization but may also indicate invasive infection, particularly in preterm infants or those admitted to NICUs. Consequently, thorough clinical evaluation and, when necessary, additional diagnostic tests are essential to distinguish colonization from true infection.
Our data showed that GPB are an infrequent cause of neonatal UTIs (20.2%), with E. faecalis being the most common (12%), followed by S. epidermidis (6%). This is in accordance with the findings reported by Zurina et al. [20]. During the period (2017–2022), AST demonstrated consistently high resistance to AMP across all uropathogens, likely driven by its widespread use, which exerts selective pressure and facilitates the survival of resistant strains.
K. pneumoniae isolates exhibited a complete resistance rate against AMP (100%); this finding is consistent with other studies [16, 21]. Resistance to AMC fluctuated between 11% in 2020 and 60% in 2022, aligning with the 39% resistance rate to AMC reported by Al Benwan et al. [21]. However, the resistance rate to CF was 58.8%, fluctuating between 33% in 2021 and 80% in 2022 in our study. This rate is significantly higher than the 10% reported in the study by Al Benwan et al. [21]. This finding suggests that CF cannot be used as a first-line treatment for neonatal UTIs. Variability in resistance to AMC and other antibiotics likely reflects differences in usage across settings and over time. Factors such as prescribing practices, infection control measures, and introducing novel antibiotics may significantly influence these resistance trends.
Second-generation cephalosporins, particularly CXM, exhibited a high resistance rate of 58.8%, consistent with findings from other studies. Fadlallah et al. [22] reported a resistance rate of 42.35%, while Shaaban et al. [23] observed a lower resistance rate of 28.57%. These findings underscore the importance of guiding CXM use with local antibiograms. Although CXM has broad-spectrum activity, rising resistance trends necessitate cautious application.
In addition, in our study, the resistance rates against third-generation cephalosporins that are commonly used for severe infections, such as CTX and CTZ were 54.4% and 51.4%, respectively, are higher than the resistance rates reported 35% in Al Benwan et al. [21] and 37% in Moghnieh et al. [24]. These results highlight the need for rational use to prevent further resistance development. Moreover, K. pneumoniae showed 100% susceptibility to MEM, consistent with the findings of Al Benwan et al. [21]. This underscores the efficacy of MEM against multidrug-resistant GNB.
We found that 17.5% of E. coli and 17.9% of K. pneumoniae isolates were resistant to CIP. Fluoroquinolones are rarely used for neonates and not recommended as first-line agents and should be reserved for cases where alternative options are ineffective or contraindicated, caused by P. aeruginosa or other multidrug-resistant GNB [25].
E. coli isolates exhibited high resistance to AMP, fluctuating from 46.2% to 100%. While AMC resistance rates range from 22% to 67%. Resistance to other antibiotics like CIP and SXT also varied, indicating a dynamic resistance pattern. Our data showed high resistance rates of E. coli to CF (66.1%), CXM (43.9%), CTX (40.6%), and CTZ (36.5%) were consistent and similar results to Al Benwan et al. [26] and Shaaban et al. [23]. These trends of resistance against third-generation cephalosporins and the emergence of 4.8% carbapenem-resistant Enterobacterales in E. coli is alarming.
The current study revealed a high prevalence of ESBL-K. pneumoniae (56%) and E. coli (56%). These findings are alarming and consistent with other studies suggesting the necessity for continuous screening and surveillance of ESBL in neonatal pathogens [27, 28].
In neonatal care, antibiotics are frequently administered prophylactically or empirically, which, if not carefully managed, can drive the development of resistance. The observed variation in antibiotic resistance among neonates is multifactorial, influenced by patterns of antibiotic use, infection control practices, microbial characteristics, regional differences, and the implementation of preventative measures. Therefore, further study should focus on this trend.
Updating antibiotic policies to guide the selection of empirical treatments for suspected UTIs is strongly recommended. Meanwhile, carbapenems, GN, and AK remain effective against the uropathogens isolated in this study. The sustained effectiveness of these antibiotics indicates that resistance has not yet become widespread among the neonatal uropathogens studied. This highlights their critical role in managing neonates infected with multidrug-resistant pathogens, as these antibiotics show high susceptibility across different classes.
E. faecalis isolates were identified as significant uropathogens in 12% of cases, and S. epidermidis isolates in 6%. No isolates were resistant to vancomycin and teicoplanin. Studies showed an association between these isolates and UTIs, emphasizing their clinical significance. In a study conducted at RNT Medical College, Udaipur, India, Enterococcus species were isolated from 5.7% of clinical samples, with E. faecalis being the predominant species, followed by E. faecium [29]. Another study highlighted that although the overall prevalence of S. epidermidis in UTIs is low, it is an important pathogen in hospital settings, causing significant pathogenesis in neonates, particularly those with underlying urinary abnormalities. This may be attributed to two main factors: its natural habitat on human skin, which provides easy access to any device inserted or implanted through the skin, and its ability to adhere to biomaterials and form biofilms [30].
Understanding the prevalence and specific pathogens responsible for infections enables healthcare providers to tailor treatment protocols more accurately. This is particularly important in the local context, where regional variations in pathogen prevalence and antibiotic resistance patterns may influence the choice of empirical therapy. Moreover, such data can inform public health strategies, guide resource allocation, and improve overall neonatal care outcomes by addressing the unique challenges faced by the local healthcare system.
Conclusion
Our findings revealed a predominant prevalence of neonatal UTIs in Kuwait, particularly among male neonates, with K. pneumoniae and E. coli identified as the primary causative agents. The study highlights a concerning rise in resistance rates to first-, second-, and third-generation cephalosporins, emphasizing the critical need for judicious selection of empirical therapies in neonatal UTI treatment. Implementing a combination of preventative measures, comprehensive neonatal evaluations, and ongoing surveillance of uropathogen prevalence and antimicrobial susceptibility is imperative for shaping effective antibiotic policies. These findings will inform local guidelines to combat antimicrobial resistance in neonates. Furthermore, we strongly encourage other specialized centers and hospitals to conduct similar studies and share their findings to advance the understanding and management of neonatal UTIs globally.
Limitations
This study has several limitations. Collecting urine samples from neonates is challenging due to their small size and the need for non-invasive methods, which may affect the accuracy and reliability of the samples. There is also a high risk of contamination from skin and fecal matter during urine collection, potentially leading to false-positive results. Specifically, GPB, including S. epidermidis and S. capitis, are likely skin commensals that may have been introduced during sample collection. The study did not consider urine specimens with bacterial growth of less than 105 CFU/mL, which might have excluded some UTIs with lower bacterial counts. The study also did not include clinical details such as anatomical anomalies at birth or the presence of urinary catheters, which can influence the incidence and severity of UTIs. Furthermore, the study was conducted in a single tertiary hospital, which may limit the generalizability of the findings to other settings or populations.
Acknowledgment
We thank Mrs. Aynaa Al Khatib for her support in data analysis and improving the manuscript.
Statement of Ethics
This study protocol was reviewed and approved by the Medical Review Board Ethics Committee, Ministry of Health, Kuwait, Approval No. 2023/2473. The work has been carried out following the code of ethics of the World Medical Association (Declaration of Helsinki). Ethical approval was secured for collecting the patient’s clinical data. The strains used in this study were obtained as part of routine diagnostic services; therefore, no informed consent was needed from patients.
Conflict of Interest Statement
The authors have no conflicts of interest to declare.
Funding Sources
No funding was secured for this study.
Author Contributions
Ola Moghnia and Noura Al-Sweih contributed to data analysis, data interpretation, manuscript drafting, original draft preparation, and final editions. Hessah Al Otaibib, Aisha Al Haqqanb, Seema Pathanb, and Nawar Abdulaziz contributed to the study design, data collection, and data entry. Elie Sokhn and Habiba Mohammed contributed to the review and editing of the manuscript. All authors have read and approved the final version of the manuscript.
Data Availability Statement
All relevant data are available in the manuscript.