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Epidemiology of community origin of major multidrug-resistant ESKAPE uropathogens in a paediatric population in South-East Gabon

Antimicrobial Resistance & Infection Control volume 12, Article number: 47 (2023) Cite this article

Abstract

Background

Urinary tract infections (UTIs) in children are very common. They are often associated with a high risk of sepsis and death. In recent years, antibiotic-resistant uropathogens ESKAPE (Enterococcus faecium, Staphylococcus aureus, Klebsiella pneumoniae, Acinetobacter baumannii, Pseudomonas aeruginosa, and Enterobacteriaceae) are increasingly encountered in UTIs. These bacteria, usually multidrug-resistance (MDR), extensive drug-resistance (XDR), pandrug-resistance (PDR), Extended-spectrum cephalosporin-resistance (ESC), Usual Drug Resistance (UDR), Difficult-to-Treat Resistance (DTR) and Carbapenem-resistance Enterobacteriales (CRE), represent a global threat for the management of paediatric UTIs. The aim of this study was to determine the epidemiology of community origin and antibiotic sensitivity of major ESKAPE uropathogens in paediatric UTIs in South-East Gabon.

Methods

The study involved 508 children aged 0–17 years. Identification of bacterial isolates was carried out using Vitek-2 compact automated system and the antibiogram with the disk diffusion and microdilution methods according to the European Committee on Antimicrobial Susceptibility Testing recommendations. Logistic regression analysis was used to assess the impact of patients' socio-clinical characteristics on uropathogens phenotype in both univariate and multivariate analysis.

Results

The prevalence of UTIs was 59%. E. coli (35%) and K. pneumoniae (34%) were the main ESKAPE involved in UTIs followed by Enterococcus spp. (8%) and S. aureus (6%). Among major ESKAPE, DTR-E. coli (p = 0.01), CRE-E. coli (p = 0.02) and XDR-E. coli (p = 0.03), Trimethoprim-sulfamethoxazole-resistant bacteria (p = 0.03) were associated with abdomino-pelvic pain. While MDR-E. coli (p < 0.001), UDR-E. coli (p = 0.02), ESC-E. coli (p < 0.001), MDR- Enterococcus (p = 0.04), UDR- Enterococcus (p = 0.02), bacteria resistant to Ampicillin (p < 0.01), Cefotaxime (p = 0.04), Ciprofloxacin (p < 0.001), Benzylpenicillin (p = 0.03) and Amikacin (p = 0.04) were more frequent among male children. MDR-Enterococcus (p < 0.01), bacteria resistant to Amoxicillin-clavulanic acid (p = 0.03), Cefalotin (p = 0.01), Ampicillin (p = 0.02) and Gentamicin (p = 0.03) were associated with treatment failure. In addition, Trimethoprim-sulfamethoxazole-resistant bacteria (p = 0.03) was associated with recurrent UTIs while those resistant to Ciprofloxacin was associated with pollakiuria (p = 0.01) and urinary burning (p = 0.04). Furthermore, UDR-K. pneumoniae (p = 0.02) was more frequent in neonates and infants.

Conclusion

This study determined the epidemiology of ESKAPE uropathogens in paediatric UTIs. It found a high prevalence of paediatric UTIs associated with children’s socio-clinical characteristics and diverse bacterial antibiotic resistance phenotypes.

Introduction

In human medicine, urinary tract infections (UTIs) are the second most common infection worldwide. It contributes significantly to morbidity and mortality in outpatient and inpatient settings representing approximately 20 to 60% of all infections [1, 2].

In a paediatric population, an estimated 7% of girls and 2% of boys will develop at least one UTI by age 6 [3]. Paediatric UTIs are common and often associated with a high risk of sepsis and death [4]. In most cases, the symptoms are nonspecific, especially in newborns and infants [5]. Recurrences are frequent (30% to 40% of cases), renal scarring is not uncommon and can lead to long-term high blood pressure and nephron reduction [6]. Infection is fostered by the presence of a functional or organic abnormality responsible for colonisation of the bladder, urinary stasis or reflux into the upper urinary tract [5]. Normal GI flora is usually the reservoir of bacteria found in urinary tract infections [7].

Overall, the common causative agents of UTIs are Gram-negative bacteria, mainly Escherichia coli (E. coli) followed by Klebsiella pneumoniae (K. pneumoniae) and Proteus mirabilis; while Enterococcus faecalis is the most common Gram-positive bacteria [8]. However, the epidemiology and distribution of uropathogenic species have shown strong geographical and temporal variations but also a relationship with the patient populations studied [9]. An earlier study showed that the aetiology of UTIs has evolved significantly in hospital and community settings [10]. There is an increasing switch to “less common” micro-organisms with more pronounced roles including pathogens such as Enterococcus faecalis (E), Staphylococcus aureus (S), AMR-Klebsiella pneumoniae (K), Acinetobacter baumannii (A), Pseudomonas aeruginosa (P) and Enterobacteriaceae (E) known as ESKAPE group [10]. Through its overall induced mortality and economic impact, the ESKAPE group represents the greatest clinical challenge for antibiotic resistance surveillance and management interventions [11]. These bacteria are considered a priority by the World Health Organization (WHO) in the global monitoring of antibiotic resistance [12]. Indeed, ESKAPE pathogens frequently exhibit acquired resistance to a variety of antimicrobial agents, such as oxazolidinones, lipopeptides, macrolides, fluoroquinolones, tetracyclines, β-lactams (including carbapenems and combinations of beta-lactamase inhibitors) [13]. These acquired resistances result in the emergence of ESKAPE multidrug-resistance (MDR), extensive drug-resistance (XDR), pandrug-resistance (PDR), Extended-spectrum cephalosporin-resistance (ESC) and Carbapenem-resistant Enterobacteriales (CRE). In paediatrics, the situation is rather worrying because many antibiotic molecules available for adults (quinolones, fosfomycin, nitrofurantoin, mecilinam, etc.) are contraindicated in children or do not have a marketing authorisation or paediatric dosage form [5]. In addition, antibiotic resistance of UTI pathogens isolated from children is increasing, especially for commonly used antibiotics [14]. In South-East Gabon, a previous study on UTIs showed high frequency of resistance of bacteria to antibiotics in children under 5 years [15]. The choice to study ESKAPE pathogens isolated from paediatric UTIs is justified by the state of the Gabonese health system, which is confronted with both a glaring shortage of paediatricians and clinical microbiology laboratories.

The aim of this study was to determine the epidemiology and antibiotic sensitivity of major ESKAPE uropathogens in community-acquired paediatric urinary tract infections in Southeastern Gabon.

Methods

Design, study area and population

The study was conducted from January 2018 to December 2021. It involved all children aged 0 to 17 years, identified in the community as requesting a cyto-bacteriological examination of urine (CBEU) by the only microbiology laboratory in the city of Franceville, capital of the Haut-Ogooué province in the South-East of Gabon, bordering the Republic of Congo. During the study period a single paediatrician was practicing in the city.

Children included in the study were stratified into four paediatric populations: neonates and infants (0–2 years), early childhood (3–6 years), late childhood (7–12 years) and adolescence (13–17 years).

Inclusion criteria

All non-hospitalised children of both sexes referred to the Microbiology Laboratory for a CBEU were eligible for inclusion in this study.

Sample collection and data collection

For individual children, urine samples were collected as previously described [15]. For children who were not able to use the toilet alone, urine collection by 'clean capture' was preferred. Otherwise, urine was collected in a sterile adhesive collection bag with the help of parents, carers or a nurse.

The urine bottle was sealed, identified, indicating the time of collection and then transported to the laboratory at room temperature. The sociodemographic and clinical data of each patient was collected through a structured questionnaire.

Culture and identification of bacterial isolates

The bacterial culture consisted of aseptically inoculating ten microliters (10 μL) of total urine using a sterile single-use loop in the level 2 microbiological safety station. The inoculation was carried out systematically on Agar Media, CLED (Cystine-Lactose-Electrolyte-Déficient, bioMérieux, Marcy-l’Étoile, France), Mac Conkey (McC, bioMérieux, Marcy-l’Étoile, France) and COS (Columbia agar + 5% sheep blood, bioMérieux, Marcy-l’Étoile, France). Urine samples were inoculated within two (2) hours of collection to avoid contamination. The inoculated media were incubated aerobically in a bacteriological incubator at 35 °C for 18 to 24 h. According to Kass criteria, a number ≥ 105 colony forming units (CFU)/mL was considered positive; a colony number < 105 CFU/mL or with more than two (2) types of bacterial colonies were considered contamination [16]. The bacterial count was done independently of the sex of the patient and of the pathogen isolated.

Presumptive identification of ESKAPE isolates was made after Gram stain, oxidase test to differentiate fermentative from non-fermentative Gram-negative bacilli, catalase test to discriminate genus Staphylococcus from genera Streptococcus and Enterococcus. Conventional biochemical tests (automated VITEK-2 system, bioMérieux, Marcy-l'Étoile, France) allowed the complete identification of bacterial genera, species and subspecies. The procedure for sample preparation and identification by VITEK-2 has been described in a previous study [17].

Antibiotic sensitivity test

The antibiotic sensitivity of ESKAPE isolates was determined by the diffusion disc method (Kirby-Bauer) on Mueller–Hinton (MH) agar (bioMérieux, Marcy-l'Étoile, France) according to the recommendations of the European Committee on Antimicrobial Susceptibility Testing (EUCAST) [18]. Briefly, MH agars were seeded with a standardised suspension (0.5 McFarland) of each ESKAPE isolate from the 24-h primary cultures. Antibiotic discs (Oxoid, Basingstoke Hampshire, UK) were firmly placed on the surface of the seeded plates. The culture media were then incubated at 35 °C for 24 h. The inhibition diameters around each antibiotic were interpreted according to EUCAST.

For antibiotics requiring microdilution methods, the minimum inhibitory concentrations (MIC) were measured on VITEK 2 Compact-AST (bioMérieux, Marcy-l'Étoile, France).

For Gram-negative isolates, the following antibiotic discs were used: Ampicillin, Amoxicillin-clavulanic acid, Piperacillin-tazobactam, Ticarcillin, Cefalotin, Cefoxitin, Cefotaxime, Ceftazidime, Cefepime, Ertapenem, Imipenem, Gentamicin, Tobramycin, Amikacin, Nalidixic acid, Ofloxacin, Ciprofloxacin, Nitrofurantoin and Trimethoprim-sulfamethoxazole.

The panel of antibiotics used for Gram-positive isolates was: Moxifloxacin, Erythromycin, Clindamycin, Quinupristin-dalfopristin, Linezolid, Vancomycin, Tetracycline, Tigecycline, applicable to all Gram-positive bacteria.

For Enterococcus spp., Ampicillin and Nitrofurantoin were also tested while the antibiotics Benzylpenicillin, Oxacillin, Gentamicin, Ciprofloxacin, Levofloxacin and Trimethoprim-sulfamethoxazole were additionally tested on Staphylococcus aureus isolates.

Classification of antibiotic resistance phenotypes

Resistance phenotypes have been classified into seven categories: Multi-drug Resistant (MDR), Extensive Drug Resistant (XDR), Pandrug-resistant (PDR), Usual Drug Resistance (UDR), Difficult-to-Treat Resistance (DTR), Extended-spectrum cephalosporin-resistant (ESC), Carbapenem-resistant Enterobacterales (CRE). These different categories of resistance have been defined in several previous studies [10, 19, 20].

Multiple antibiotic resistance (MAR) index was determined for each isolate using the formula MAR = n/N, where n represents the number of antibiotics to which the test isolate showed resistance and N represents the total number of antibiotics to which the test isolate has been evaluated [21]. The MAR index ranged from 0.0 to 1.0.

Statistical analysis

The chi-square test was used to compare the prevalence of different phenotypes of each bacterium in the study population. In addition, the co-occurrence of resistance between different families of antibiotics (Beta-lactams, Quinolones, Aminoglycosides, Sulfonamides and Nitrofurans) was highlighted by a Venn diagram with the "Venn Diagram" package version 1.7.3. To visualize the data, a Factorial correspondence analysis (FCA) was performed to reduce the dimensions of the dataset with the packages FactoMineR and Factoextra. In this process, the data were projected onto a two-dimensional space, namely Dimension 1 [Dim 1] and Dimension 2 [Dim 2], where the original data had the greatest explained variance. Typically, Dim 1containing the largest variance in the data projections, followed by Dim 2.

Logistic regression was used to assess the impact of patients' socio-clinical characteristics on resistant uropathogens phenotypes in both univariate and multivariable analysis. Odds ratios (OR) and 95% confidence intervals are presented. All statistical analyses and graphs were performed with R software, version 4.0.2 and SPSS version 20 (IBM, USA). P values < 0.05 were considered statistically significant.

Results

Socio-clinical characteristics of study patients

A total of 608 urine samples was collected over a 4-year period, of which 100 were excluded from the study because their socio-clinical parameters were not fully documented. Males represented 56% of the study population (289/508). The male/female sex ratio was 1.31. The patients’ mean age was 3.96 ± 4.67 years, and 57% (293/508) were neonates and infants. A large majority of patients were from urban areas (78%, 397/508), with an urban/rural ratio of 3.57.

Regarding the clinical signs observed in the latter, 43% (220/508) had fever while 42% (215/508) had a history of pre-emptive antibiotic therapy (Table 1).

Table 1 Patients' socio-clinical parameters, stratified by confirmed UTI cases within each grouping
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Prevalence of urinary tract infections in community paediatrics

The overall prevalence of UTIs was 59% (304/508). UTIs were associated with age in the paediatric population. They were significantly more frequent in neonates and infants compared to other age group (78.2%; p < 0.001) (Table 1). Male and female children were similarly affected by UTIs (Table 1).

Regarding residence, UTIs were not significantly more prevalent in patients from urban areas than those from rural areas (62.2% vs 51.4%; p = 0.05).

Non-febrile children were more susceptible to UTIs (98.6% vs 60.9; p < 0.0001) (Table 1).

Bacteriological profile of UTIs

UTIs were significantly associated with uropathogens in the ESKAPE group compared to the non-ESKAPE group (89% vs 11%; p < 0.0001). Among the ESKAPE pathogens, the ESKAPE-Gram-negative group was significantly more prevalent than the ESKAPE-Gram-positive group (75% vs 14%; p < 0.001) (Table 2). Within the ESKAPE-Gram-negative uropathogens, the predominant bacteria were E. coli (46%, 105/229) and K. pneumoniae (45%, 104/229).

Table 2 Prevalence of uropathogens isolated from children UTIs
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Among the ESKAPE-Gram-positive uropathogens, Enterococcus spp., and Staphylococcus aureus accounted for 58% (25/43) and 42% (18/43), respectively (Table 2).

Distribution of resistance phenotypes in major uropathogenic Gram-negative strains

Among E. coli and K. pneumoniae isolates, ESC (65%, 136/209), MDR (64%, 135/209), and UDR (52%, 108/209) resistance phenotypes were more frequent compared to other phenotypes (Table 3).

Table 3 Prevalence of major ESKAPE-Gram- uropathogens according to resistance categories
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The frequency of MDR-K. pneumoniae strains was similar to that of MDR-E. coli (56% vs 44%; p = 0.05), while DTR-E. coli was significantly more prevalent than DTR-K. pneumoniae (100% vs 0%, p = 0.01). No statistically significant differences were observed when comparing the other phenotypes (Table 3).

The association between resistant uropathogens and patients' socio-clinical characteristics was determined using factorial correspondence analysis (Fig. 1) and multivariate logistic regression (Tables 4 and 5).

Fig. 1
figure 1

Factorial correspondence analysis (FCA) of data for major ESKAPE UTIs isolates according to socio-clinical parameters. Dim 1 and Dim 2 axes explained 75% of the total variance in the dataset of major ESKAPE-Gram-negative against 82,7% for major ESKAPE-Gram-positive

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Table 4 Multivariate analysis of bacterial resistance phenotypes according to the socio-clinical characteristics of children
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Table 5 Multivariate analysis of bacterial antibiotic resistance according to socio-clinical characteristics of children
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In the paediatric population, abdominal-pelvic pain was associated with the bacterial phenotypes DTR-E. coli (p = 0.01), CRE-E. coli (p = 0.02) and XDR-E. coli (p = 0.03). While UDR-K. pneumoniae (p = 0.01) was significantly more frequent in urinary burning and neonates and infants (p = 0.02) (Fig. 1A, Table 4). We also found that DTR-E. coli (p = 0.04) was more common in urban areas (Fig. 1A, Table 4), while MDR-E. coli (p < 0.001), UDR-E. coli (p = 0.02), and ESC-E. coli (p < 0.001), were more frequently observed in male children (Fig. 1A, Table 4).

Distribution of resistance phenotypes in S. aureus and Enterococcus spp

Among S. aureus and Enterococcus spp. isolates, MDR (86%, 37/43) and UDR (81%, 35/43) phenotypes were the most frequent. Among MDR strains, vancomycin-sensitive Enterococcus (VSE) (51%, 19/37) were significantly more frequent than the other resistance phenotypes (p < 0.0001). Similarly, the UDR phenotype was significantly associated with vancomycin-sensitive Enterococcus (VSE) (p = 0.01) (Table 6).

Table 6 Prevalence of major ESKAPE-Gram-positive uropathogens in resistance categories
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FCA and Multivariate logistic regression analyses show that MDR- Enterococcus (p < 0.01) was associated with treatment failure (Fig. 1B, Table 4). In addition, MDR-Enterococcus (p = 0.04) and UDR-Enterococcus (p = 0.02) were more observed in male children (Fig. 1B, Table 4).

Distribution of resistance to commonly used antibiotics in UTIs in children

The distribution of antibiotic resistance in E. coli and K. pneumoniae showed that bacterial resistance to Amoxicillin-clavulanic acid (p = 0.03), Cefalotin (p = 0.01), Ampicillin (p = 0.02) and Gentamicin (p = 0.03) were associated with treatment failure (Fig. 1A, Table 5) while the resistance to Ampicillin (p < 0.01), Cefotaxime (p = 0.04), Ciprofloxacin (p < 0.001) and Amikacin (p = 0.04) were more frequently observed among male children. Moreover, resistance to Trimethoprim-sulfamethoxazole (p = 0.03) was associated with abdomino-pelvic pain and recurrent UTIs (Fig. 1A, Table 5).

Bacterial resistance to the quinolone family such as Ciprofloxacin was associated with Pollakiuria (p = 0.01) and urinary burning (p = 0.04) (Fig. 1A, Table 5).

Among the major ESKAPE-Gram-positive, bacterial resistance to Ampicillin (p = 0.02) was associated with treatment failure (Fig. 1B, Table 5), while Benzylpenicillin-resistant bacteria (p = 0.03) were more common in male children (Fig. 1B, Table 5).

In this study, Venn diagram was use to show the distribution and relationship between resistance of different families of antibiotics tested with E. coli and K. pneumoniae isolates (Fig. 2).

Fig. 2
figure 2

Venn diagram showing the distribution and co-occurrence of antibiotic resistance of the major ESKAPE-Gram-negative within the different antibiotic families. Each ellipse illustrates an antibiotic family for which resistance was assessed

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Overall, the highest rate of resistance was observed within the β-lactams family with 88% (184/209) followed by sulfonamides (65%, 137/209) and quinolones (50%, 106 /209) against 1% (3/209) observed for the family of nitrofurans (Fig. 2).

Venn diagram also reported that 11% (23/209), 0.95% (2/209) and 1.43% (3/209) of E. coli and K. pneumoniae isolates showed monoresistance to β-lactams, aminoglycosides and sulfonamides (Fig. 2).

The co-occurrence of resistance to two antibiotic families was predominantly observed with β-lactam/sulfonamide combination (63%, 132/209) (Fig. 2).

The co-occurrence of resistance to three antibiotic families was highest with the combination β-lactam-sulfonamide-aminoglycoside (12.9%, 27/209) while β-lactam-aminoglycoside-sulfonamide-quinolone combination showed the highest co-occurrence with four antibiotic families (27%, 57/209). Only one isolate showed resistance to all antibiotic families tested (Fig. 2).

Multiple antibiotic resistance (MAR) index of E. coli and Klebsiella spp

The MAR index results showed that more than half of E. coli and K. pneumoniae isolates had resistance to at least 5 antibiotics (MAR index ≥ 0.26) while only one isolate showed resistance to 17 antibiotics (MAR index = 0.89) (Table 7).

Table 7 Multiple antibiotic resistance (MAR) index of E. coli and K. pneumoniae
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Discussion

Several studies in resource-limited countries suggested that major pathogens found in urinary tract infections are often resistant to standard antibiotics [22], especially those isolated from UTIs in children [10]. The aim of this study was to determine the epidemiology and antibiotic susceptibility of major ESKAPE uropathogens in community-acquired paediatric UTIs in South-East Gabon.

The prevalence of urinary tract infections was 59%. They were significantly more frequent in neonates and infants (Table 1), corroborating the findings of Hay et al., who found a 46.6% rate of UTIs in children under 5 years [16].

E. coli and K. pneumoniae were the main uropathogenic ESKAPEs isolated in this study, with 35% and 34%, respectively, followed by Enterococcus spp. and S. aureus (Table 2). These results corroborate those of previous studies conducted in Africa [23,24,25]. Many virulence and fitness factors confer advantages to uropathogenic E. coli (UPEC) and K. pneumoniae (UPKP) in the host urinary tract. UPEC usually has a superficial viruloma and a secretome that contribute to its virulence and survival [26].

We describe the DTR and UDR resistance phenotypes as well as MAR index in Gabon (Tables 3, 7). These resistance phenotypes are now preferred to MDR, XDR and PDR phenotypes.

Indeed, MDR, XDR and PDR resistance phenotypes make no distinction between the strengths and weaknesses of each antibiotic: antibiotics with higher efficacy and lower toxicity are considered the same as those with lower efficacy and higher toxicity [27, 28]. Characterization of DTR, UDR, ESC, and CRE phenotypes facilitates resistance monitoring for clinicians (Tables 3, 6), as well as the improvement of empirical and targeted treatment regimens [27].

Among the major uropathogens, MDR resistance phenotype was the most common (Table 3). Similar rates of MDR uropathogenic strains have been previously described in Gabon [15]. However, a lower rate of MDR isolates was reported by Dikoumba et al. [29]. The differences observed could be explained by the origin of the samples used in each study.

MDR-E. coli, ESC-E. coli, MDR- Enterococcus were more frequently observed among male children. Male gender has already been described as a likely risk factor in the occurrence of MDR UTIs [20]. In the previously cited study, the authors showed that female gender was a protective factor in the occurrence of antibiotic-resistant UTIs, which support the results of the present study. The observation of multidrug-resistant phenotypes in male children could be a risk factor both for the failure of empirical treatment and for the aggravation of clinical forms. Indeed, male urinary tract infections present a high risk of complications because of the frequency of anatomical or functional abnormalities associated with them. [30].

DTR-E. coli, CRE-E. coli, XDR-E. coli were associated abdomino-pelvic pain and UDR-K. pneumoniae with urinary burning. Although the relationship between virulence and resistance appears to be antagonistic [31], authors have shown that one of the E. coli clones that globally disseminates extended-spectrum β-lactamases and NDM-1 carbapenemases, with few classical virulence factors, was virulent in a mouse model of sepsis [32, 33]. Thus, strains with virulence and resistance capabilities emerge as antibiotic selection pressure increases [34]. Other authors have provided epidemiological evidence that resistance and virulence phenotypes are linked in E. coli isolates of community origin [35]. Resistance phenotypes observed in this study strongly impact optimal care of community-based UTIs often treated by empirical antibiotherapy [36].

The presence of MDR, XDR, CRE, ESC, DTR, MRSA and VRE phenotypes may force clinicians to use antibiotics with less beneficial or limited pharmacological properties such as aminoglycosides (nephrotoxic, ototoxic and neurotoxic) and colistin (nephrotoxic and neurotoxic) [37].

In general, DTR-E. coli was more common in children from urban area. UTIs are quite common in community settings. However, many patients refuse to seek medical attention because of the social stigma associated with UTIs. In urban areas, the lack of paediatricians also leads to long queues during medical consultations, discouraging many patients who opt for self-medication, largely responsible for the selection of resistant strains. Also, the lack of education and the uncontrolled sale of counterfeit or substandard antibiotics are two additional factors favouring the emergence and dissemination of bacterial resistance in urban UTIs.

Multivariate logistic regression analysis showed associations between several antibiotics with patients’ socioclinical parameters. Indeed, Male gender was associated with resistance to β-lactams (Benzylpenicillin, Ampicillin and Cefotaxime), fluoroquinolones (Ciprofloxacin) and aminoglycosides (Amikacin) as previously reported by Shaikh et al. [38].

Children age was associated with β-lactams-resistance. As the resistance to Benzylpenicillin, Cefalotin and Cefotaxime was more frequent in neonates and infants, while those to Cefalotin and Cefotaxime were more common in early and late chilhood.

Another clinical symptoms was associated with antimicrobial resistance. Abdominopelvic pain-like symptoms were associated with resistance to sulfonamides (Trimethoprim-sulfamethoxazole) while urinary burning and pollakiuria were associated with resistance to fluoroquinolones (Ciprofloxacin). Our results are in accordance of a previous report which found an association between clinical signs and antibiotic resistance in E. coli isolated from pediatric UTIs [39].

Furthermore, recurrent UTIs were associated with resistance to sulfonamides (Trimethoprim-sulfamethoxazole) as also reported by Nelson et al. [40].

Finally, treatment failure in children was associated with resistance to β-lactams (Ampicillin, Amoxicillin-clavulanic acid, Cefalotin) and aminoglycosides (Gentamicin).

In this study, the frequency of DTR, ESC, CRE, MDR, MRSA and ERV phenotypes was not negligible in paediatric UTIs. However, the high presence of the UDR phenotype (more than 50%) in major uropathogens suggests that these infections remain treatable with standard antibiotics.

Conclusion

This study describes for the first time the resistance phenotypes DTR, UDR and MAR index in Gabon. The prevalence of UTIs was high with a strong involvement of the uropathogens E. coli, K. pneumoniae, Enterococcus spp. and S. aureus. Neonates and infants were predominantly affected by UTIs. The study also showed that the majority of paediatric UTIs remain susceptible to standard antibiotic therapy. However, the presence of MDR, XDR, DTR, ESC, CRE, MRSA and VRE phenotypes in the paediatric population should alert health authorities to the need to set up a national surveillance system for antimicrobial resistance in Gabon.

Availability of data and materials

Data and materials supporting the conclusions of this study will be made available on request to the corresponding author.

Abbreviations

ESKAPE:

Enterococcus faecalis, Staphylococcus aureus, Klebsiella pneumoniae, Acinetobacter baumannii, Pseudomonas, Enterobacteriaceae

IVUs:

Infection des voies urinaires

MDR:

Multidrug resistance

XDR:

Extensive drug resistance

PDR:

Pandrug-resistance

DTR:

Difficult to Treat Resistance

UDR:

Usual drug resistance

ESC:

Extended-spectrum cephalosporin-resistant

CRE:

Carbapenem-resistant Enterobacterales

MAR:

Multiple antibiotic resistance

SARM:

Methicillin-resistant Staphylococcus aureus

SASM:

Methicillin-sensitive Staphylococcus aureus

VRE:

Vancomycin-resistant Enterococcus

VSE:

Vancomycin-sensitive Enterococcus

UPEC:

Uropathogenic-E. coli

UPKP:

Uropathogenic-K. pneumoniae

CFU:

Colony-forming units

References

  1. Hooton TM, Bradley SF, Cardenas DD, Colgan R, Geerlings SE, Rice JC, et al. Diagnosis, prevention, and treatment of catheter-associated urinary tract infection in adults: 2009 International Clinical Practice Guidelines from the Infectious Diseases Society of America. Clin Infect Dis. 2010;50:625–63.

    Article  PubMed  Google Scholar 

  2. Wiedemann B, Heisig A, Heisig P. Uncomplicated urinary tract infections and antibiotic resistance: epidemiological and mechanistic aspects. Antibiotics. 2014;3:341–52.

    Article  PubMed  PubMed Central  Google Scholar 

  3. Dahiya A, Goldman RD. Prise en charge de la bactériurie asymptomatique chez l’enfant. Can Fam Phys. 2018;64(11):e483–5.

    Google Scholar 

  4. Morris BJ, Wiswell TE. Circumcision and lifetime risk of urinary tract infection: a systematic review and meta-analysis. J Urol. 2013;189(6):2118–24.

    Article  PubMed  Google Scholar 

  5. Cohen R, Raymond J, Faye A, Gillet Y, Grimprel E. Management of urinary tract infections in children. Recommendations of the pediatric infectious diseases group of the french pediatrics society and the french-language infectious diseases society. Archives de Pediatrie: Organe Officiel de la Societe Francaise de Pediatrie. 2015;22(6):665–71.

  6. Le Saux N, Moher D. Evaluating the benefits of antimicrobial prophylaxis to prevent urinary tract infections in children: a systematic review. CMAJ. 2000;163(5):523–9.

    PubMed  PubMed Central  Google Scholar 

  7. Caron F, Etienne M, Galperine T, Merens A, Flateau C. Diagnostic et antibiothérapie des infections urinaires bactériennes communautaires de l’adulte. Med Mal Infect. 2018.

  8. Williams GJ, Hodson EH, Isaacs D, Craig JC. Diagnosis and management of urinary tract infection in children. J Paediatr Child Health. 2012;48(4):296–301.

    Article  PubMed  Google Scholar 

  9. Gajdács M, Ábrók M, Lázár A, Burián K. Microbiology of urine samples obtained through suprapubic bladder aspiration: a 10-year epidemiological snapshot. Dev Health Sci. 2019;2(3):76–8.

    Google Scholar 

  10. Behzadi P, Urbán E, Matuz M, Benkő R, Gajdács M. The role of gram-negative bacteria in urinary tract infections: current concepts and therapeutic options. Adv Microbiol Infect Dis Public Health. 2020:35–69.

  11. Gajdács M, Albericio F. Antibiotic resistance: from the bench to patients. Multidisciplinary Digital Publishing Institute; 2019. p. 129.

  12. Tacconelli E, Magrini N, Kahlmeter G, Singh N. Global priority list of antibiotic-resistant bacteria to guide research, discovery, and development of new antibiotics. World Health Organization. 2017;27:318–27.

    Google Scholar 

  13. Peeters P, Ryan K, Karve S, Potter D, Baelen E, Rojas-Farreras S, et al. The impact of initial antibiotic treatment failure: real-world insights in patients with complicated, health care-associated intra-abdominal infection. Infection Drug Resistance. 2019;12:329.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  14. Bagnasco F, Piaggio G, Mesini A, Mariani M, Russo C, Saffioti C, et al. Epidemiology of antibiotic resistant pathogens in pediatric urinary tract infections as a tool to develop a prediction model for early detection of drug-specific resistance. Antibiotics. 2022;11(6):720.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  15. Yann MN, Onanga R, Kassa RFK, Bignoumba M, Nguema PPM, Gafou A, et al. Epidemiology of community origin Escherichia coli and Klebsiella pneumoniae uropathogenic strains resistant to antibiotics in Franceville. Gabon Infect Drug Resist. 2021;14:585.

    Article  Google Scholar 

  16. Hay AD, Birnie K, Busby J, Delaney B, Downing H, Dudley J, et al. The Diagnosis of Urinary Tract infection in Young children (DUTY): a diagnostic prospective observational study to derive and validate a clinical algorithm for the diagnosis of urinary tract infection in children presenting to primary care with an acute illness. Health Technol Assess. 2016;20(51).

  17. Bignoumba M, Moghoa KHM, Muandze-Nzambe JU, Kassa RFK, Ndzime YM, Gafou A, et al. Vaginal Infections’ Etiologies in South-Eastern Gabon: an overview. Int J Women’s Health. 2022;14:505.

    Article  Google Scholar 

  18. Testing ECoAS. EUCAST clinical breakpoints. Basil, Switzerland: European Society of Clinical Microbiology and Infectious Diseases. 2016.

  19. Magiorakos A-P, Srinivasan A, Carey RB, Carmeli Y, Falagas M, Giske C, et al. Multidrug-resistant, extensively drug-resistant and pandrug-resistant bacteria: an international expert proposal for interim standard definitions for acquired resistance. Clin Microbiol Infect. 2012;18(3):268–81.

    Article  CAS  PubMed  Google Scholar 

  20. Miftode I-L, Pasare M-A, Miftode R-S, Nastase E, Plesca CE, Lunca C, et al. What doesn’t kill them makes them stronger: the impact of the resistance patterns of urinary enterobacterales isolates in patients from a Tertiary Hospital in Eastern Europe. Antibiotics. 2022;11(5):548.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  21. Ngwai Y, Gyar S, Pennap G, Makut M, Ishaleku D, Corosi S, et al. Antibiogram of non-sorbitol fermenting Escherichia coli isolated from environmental sources in Keffi, Nigeria. NSUK J Sci Technol. 2014;4(1&2):152–63.

    Google Scholar 

  22. Musa-Aisien A, Ibadin O, Ukoh G, Akpede G. Prevalence and antimicrobial sensitivity pattern in urinary tract infection in febrile under-5s at a children’s emergency unit in Nigeria. Ann Trop Paediatr. 2003;23(1):39–45.

    Article  CAS  PubMed  Google Scholar 

  23. Nzalie RN-t, Gonsu HK, Koulla-Shiro S. Bacterial etiology and antibiotic resistance profile of community-acquired urinary tract infections in a Cameroonian city. Int J Microbiol. 2016;2016.

  24. Randrianirina F, Soares J-L, Carod J-F, Ratsima E, Thonnier V, Combe P, et al. Antimicrobial resistance among uropathogens that cause community-acquired urinary tract infections in Antananarivo, Madagascar. J Antimicrob Chemother. 2007;59(2):309–12.

    Article  CAS  PubMed  Google Scholar 

  25. Yandai FH, Ndoutamia G, Nadlaou B, Barro N. Prevalence and resistance profile of Escherichia coli and Klebsiella pneumoniae isolated from urinary tract infections in N’Djamena, Tchad. Int J Biol Chem Sci. 2019;13(4):2065–73.

    Article  CAS  Google Scholar 

  26. Behzadi P. Classical chaperone-usher (CU) adhesive fimbriome: uropathogenic Escherichia coli (UPEC) and urinary tract infections (UTIs). Folia Microbiol. 2020;65(1):45–65.

    Article  CAS  Google Scholar 

  27. Kadri SS, Adjemian J, Lai YL, Spaulding AB, Ricotta E, Prevots DR, et al. Difficult-to-treat resistance in gram-negative bacteremia at 173 US hospitals: retrospective cohort analysis of prevalence, predictors, and outcome of resistance to all first-line agents. Clin Infect Dis. 2018;67(12):1803–14.

    PubMed  PubMed Central  Google Scholar 

  28. McDonnell A, Rex JH, Goossens H, Bonten M, Fowler Jr VG, Dane A. Efficient delivery of investigational antibacterial agents via sustainable clinical trial networks. Clin Infect Dis. 2016;63(suppl_2):S57–S9.

  29. Dikoumba A-C, Onanga R, Nguema PPM, Mangouka LG, Iroungou BA, Kassa FK, et al. Phenotipic prevalence of antibiotic resistance in gabon. Open J Med Microbiol. 2021;11(2):100–18.

    Article  CAS  Google Scholar 

  30. SPILF. Diagnostic et antibiothérapie des infections urinaires bactériennes communautaires de l’adulte. Paris: SPILF; 2015:1–43.

  31. Johnson JR, Goullet P, Picard B, Moseley S, Roberts P, Stamm W. Association of carboxylesterase B electrophoretic pattern with presence and expression of urovirulence factor determinants and antimicrobial resistance among strains of Escherichia coli that cause urosepsis. Infect Immun. 1991;59(7):2311–5.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  32. Clermont O, Lavollay M, Vimont S, Deschamps C, Forestier C, Branger C, et al. The CTX-M-15-producing Escherichia coli diffusing clone belongs to a highly virulent B2 phylogenetic subgroup. J Antimicrob Chemother. 2008;61(5):1024–8.

    Article  CAS  PubMed  Google Scholar 

  33. Peirano G, Schreckenberger PC, Pitout JD. Characteristics of NDM-1-producing Escherichia coli isolates that belong to the successful and virulent clone ST131. Antimicrob Agents Chemother. 2011;55(6):2986–8.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  34. Denamur E, Picard B. Virulence et résistance: deux caractéristiques antagonistes chez Escherichia coli? Réanimation. 2012;21(3):249–51.

    Article  Google Scholar 

  35. Zhang L, Levy K, Trueba G, Cevallos W, Trostle J, Foxman et al. Effets de la pression de sélection et de l'association génétique sur la relation entre la résistance aux antibiotiques et la virulence chez Escherichia coli. Agents antimicrobiens et chimiothérapie. 2015; 59 (11), 6733–40.

  36. De Francesco MA, Ravizzola G, Peroni L, Negrini R, Manca N. Urinary tract infections in Brescia, Italy: etiology of uropathogens and antimicrobial resistance of common uropathogens. Med Sci Monit. 2007;13(6):BR136–44.

  37. Gajdács M, Bátori Z, Ábrók M, Lázár A, Burián K. Characterization of resistance in gram-negative urinary isolates using existing and novel indicators of clinical relevance: a 10-year data analysis. Life. 2020;10(2):16.

    Article  PubMed  PubMed Central  Google Scholar 

  38. Shaikh, N., Hoberman, A., Keren, R., Ivanova, A., Gotman, N., Chesney, et al. Predictors of antimicrobial resistance among pathogens causing urinary tract infection in children. J Pediatrics. 2016;171, 116–121.

  39. Garrido D, Garrido S, Gutiérrez M, Calvopiña L, Harrison AS, Fuseau et al. Clinical characterization and antimicrobial resistance of Escherichia coli in pediatric patients with urinary tract infection at a third level hospital of Quito, Ecuador. Boletin Medico Del Hospital Infantil de Mexico. 2017;74(4), 265–71.

  40. Nelson CP, Hoberman A, Shaikh N, Keren R, Mathews R, Greenfield, et al. Antimicrobial resistance and urinary tract infection recurrence Pediatrics. 2016;137(4).

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Acknowledgements

The authors would like to thank the many collaborators involved in collecting the samples analyzed in this report. The personnel of the bacteriology laboratory are thanked for their participation.

Funding

The authors declare that they have not received any funding to carry out this study.

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Authors and Affiliations

  1. Unité de Recherche et d’Analyses Médicales, Laboratoire de Bactériologie, Centre Interdisciplinaire de Recherches Médicales de Franceville, BP 769, Franceville, Gabon

    Yann Mouanga-Ndzime, Richard Onanga & Michelle Bignoumba

  2. Laboratoire de Biologie Moléculaire et Cellulaire (LABMC), Université des Sciences et Techniques de Masuku, BP 943, Franceville, Gabon

    Yann Mouanga-Ndzime & Cyrille Bisseye

  3. Unité de Recherche en Ecologie de La Santé (URES), Centre Interdisciplinaire de Recherches Médicales de Franceville, BP 769, Franceville, Gabon

    Neil-Michel Longo-Pendy

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  4. Michelle Bignoumba
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Contributions

Y.M.N. conceived of the study and participated in study design, execution, acquisition, interpretation of data, drafting, revising and critically reviewing the article. R.O. participated in interpretation of data, drafting, revising and critically reviewing the article. N.M.L.P. performed the statistical analysis. M.B. participated in statistical analysis. C.B. performed conception, study design, coordination, drafting, revising and critically reviewing the article. All authors read and approved the final manuscript.

Corresponding author

Correspondence to Yann Mouanga-Ndzime.

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Ethics approval and consent to participate

For all children, informed and written consent was obtained from their parents or legal guardians prior to inclusion in the study. The research license for this study was obtained from the Scientific Commission on Research Authorizations of the National Centre of Scientific and Technological Research (CENAREST) (permit 7 no. AR0033/17/MESRSFC/CENAREST/CG/CST/CSAR, dated 4 July 2017). This study was conducted in accordance with the Declaration of Helsinki.

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The authors declare that they have no competing interests.

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Mouanga-Ndzime, Y., Onanga, R., Longo-Pendy, NM. et al. Epidemiology of community origin of major multidrug-resistant ESKAPE uropathogens in a paediatric population in South-East Gabon. Antimicrob Resist Infect Control 12, 47 (2023). https://0-doi-org.brum.beds.ac.uk/10.1186/s13756-023-01250-y

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Keywords

Antimicrobial Resistance & Infection Control

ISSN: 2047-2994

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