Asymptomatic nasopharyngeal carriage of multidrug resistant bacteria among children at University of Gondar Hospital Northwest Ethiopia Revealing Hidden Health Risks – Nature.com 07:49 

Scientific Reports volume 14, Article number: 28994 (2024) Cite this article

Abstract

Gram-negative bacteria in the nasopharynx can eventually invade bacteria-limited sites and cause serious illnesses such as meningitis, otitis media, and pneumonia. However, data related to the carriage of these bacteria in children attending outpatient departments in the study area are limited. To assess nasopharyngeal carriage, antibiotic susceptibility patterns, and associated factors of gram-negative bacteria among children attending the outpatient department at the University of Gondar Comprehensive Specialized Hospital, Northwest Ethiopia. A hospital-based cross-sectional study was conducted from September 1, 2023, to December 30, 2023. A total of 385 children aged 3 to 14 years were enrolled using a systematic random sampling technique. Sociodemographic and clinical data were collected using a semistructured questionnaire. A total of 385 nasopharyngeal samples were collected using a sterile specimen collection nasopharyngeal swab, transported using Amie’s transport medium, and subsequently inoculated on chocolate agar, blood agar, modified thayer martin agar, and MacConkey agar plates. Bacterial species were identified by colony morphology, Gram staining, and biochemical tests such as oxidase tests, satellitism tests, and carbohydrate utilization tests. An antibiotic susceptibility test was performed using the Kirby–Bauer and modified Kirby–Bauer methods on Mueller–Hinton agar plates. The data were entered into Epi-Data version 4.6.0.6 and exported to SPSS version 25 for analysis. The adjusted odds ratio at a 95% confidence interval with a P value of < 0.05 in the binary logistic regression model was considered to indicate statistical significance. The overall nasopharyngeal carriage of gram-negative bacteria was 146 (37.9%) (95% CI: 33.2–42.9). Among these, nonfastidious gram-negative bacteria represented 45 (11.7%), followed by M. catarrhalis 41 (10.6%), N. meningitidis 34 (8.8%), and H. influenzae 26 (6.8%). The isolates exhibited high resistance to tetracycline (85; 75.9%), trimethoprim-sulfamethoxazole (105; 71.9%), ampicillin (76; 67.9%), and amoxicillin/clavulanic acid (60; 69.8%) but high susceptibility to meropenem (122; 83.6%), gentamicin (73; 84.9%), and minocycline (87; 72.5%). There were 99 total multidrug-resistant strains (67.8%, 95% CI: 59.7–75.0). Male sex (AOR = 1.785, 95% CI: 1.102–2.892, P = 0.019), smoking (AOR = 2.675, 95% CI: 1.149–6.230, P = 0.022), and large family size (≥ 5) (AOR = 1.857, 95% CI: 1.140–3.023, P = 0.013) were risk factors for nasopharyngeal colonization. Increased nasopharyngeal colonization of multidrug-resistant gram-negative isolates was observed in this study. Gentamicin, minocycline, and meropenem were the most effective antibiotics for the tested isolates. Bacterial colonization increased with increasing family size, smoking status, and male sex. Therefore, a definitive diagnosis in the outpatient pediatric department should be based on culture and susceptibility test results.

Introduction

The nasopharynx is a common site where pathogenic gram-negative bacteria, including Neisseria meningitidis (N. meningitidis), Moraxella catarrhalis (M. catarrhalis), and Haemophilus influenzae (H. influenzae), asymptomatically colonize the host1,2,3,4. Moreover, Klebsiella pneumoniae (K. pneumoniae), Escherichia coli (E. coli), Enterobacter cloacae (E. cloacae), and other nonfastidious gram-negative bacilli (GNB) may also colonize the nasopharynx of children during certain events, such as normal flora imbalance, dry mouth, diabetes, immunosuppression, previous antibiotic therapy, and hospitalization, even though they are not believed to be resident microbiota in the nasopharynx naturally5,6,7. In addition, the consumption of tainted food and water, as well as inadequate personal cleanliness such as nail biting, could be the cause of their appearance in the nasopharynx of healthy children6,7,8. However, asymptomatic nasopharyngeal colonization by these pathogenic bacteria is a critical step for disease occurrence in children (for example, community-acquired pneumonia, meningitidis, and sepsis are caused by these nonfastidious GNB)7,9,10 since the nasopharynx is borderline with bacteria-limited sites such as the lower respiratory tract, middle ear, and sinuses11. Infections at these three sites potentially reflect the primary cause of pediatric and neonatal deaths globally12, the most frequent cause of death in children under 5 years old in the U.S.13, and the second most prevalent cause of overprescription of antibiotics14.

Although M. catarrhalis seems to be an asymptomatic colonizer of the nasopharynx, M. catarrhalis is the chief cause of otitis media in infants and children after Streptococcus pneumoniae and nontypeable H. influenzae are found globally1. In addition, it is the leading cause of chronic obstructive pulmonary disease in adults, similar to Streptococcus pneumoniae and nontypeable H. influenzae1. Gram-negative coccobacilli, such as H. influenzae, also cause severe invasive diseases, such as meningitis, septic arthritis, epiglottitis, purulent pericarditis, and pneumonia, in children15. Many H. influenzae type B (Hib) cases and morbidities are considerably decreased by the administration of conjugate vaccination against Hib. Unfortunately, vaccination does not provide safety against nontypeable strains, leading to an epidemiologic change in illnesses caused by nontypeable strains16. Treating H. influenzae infection with beta-lactam antibiotics is a common practice that facilitates the emergence of resistance to these antibiotics through the alteration of penicillin-binding protein 3 and enzymatic degradation17.

N. meningitidis causes invasive meningococcal disease (IMD), which in turn can lead to septicemia and meningitis after the infection passes through the nasopharyngeal epithelium and blood and spreads through contact with respiratory droplets from carriers to noncarriers3,4,18. Type IV pili play a role in meningococcal colonization, the initial step in IMD occurrence, by attaching to nasopharyngeal epithelial cells19,20. Despite advancements in detection and treatment, meningococcal illness remains a leading cause of morbidity and mortality among children globally9. Bacterial meningitis is also the major cause of child death in the meningitis belt of sub-Saharan Africa, which spans from Senegal to Ethiopia, even in the era of vaccine development, in which N. meningitidis is the dominant etiology, followed by S. pneumoniae and H. influenzae21.

Antibiotic resistance (ABR) is an international public health concern associated with increased hospitalization rates, medical expenses, and mortality following the widespread use of antibiotics, which creates selection pressure that favors the creation of resistant bacteria22. The widespread use of antibiotics is the result of the failure to conduct antibiotic susceptibility testing to determine the exact bacterial species, the low cost of antibiotics, the absence of laws preventing the purchase of antibiotics without a prescription, and poor training on antibiotic resistance in healthcare workers. This may result in hospitalizing 83–100% of children in Africa23. In addition, ABR data from one area to another are inconsistent due to differences in the practice of antibiotic use24. Thus, it may be crucial to comprehend the factors influencing nasopharyngeal bacterial carriage to fortify prevention tactics against lower respiratory tract infections, which are a leading cause of mortality for children in low- and middle-income nations. Factors such as income level, use of antibiotics, infection of the respiratory tract, sex, age, interaction with other children, weather conditions and period, and access to environmental contaminants such as smoking can influence the nasopharyngeal carriage of gram-negative bacteria25,26.

Currently, nasopharyngeal colonization by multidrug-resistant (MDR) gram-negative bacteria is alarming among children, with greater incidence of bacterial infections worldwide, particularly in developing countries25,27. Children, in turn, play an important role in the spread of these antibiotic-resistant bacterial isolates to the general community by serving as primary reservoirs for infections25,28.

Studies regarding the nasopharyngeal colonization of gram-positive bacteria have been conducted in Ethiopia29,30,31. However, the data are limited, and little is known about the nasopharyngeal colonization of MDR gram-negative bacteria, particularly GNB, in children visiting the outpatient department in the study area. Therefore, this study aimed to assess nasopharyngeal colonization, antibiotic susceptibility patterns, and associated factors of gram-negative bacteria among children attending the outpatient department at the University of Gondar Comprehensive Specialized Hospital (UoGCSH), Northwest Ethiopia. Moreover, this approach will open up a new path for further investigation into the topic of interest.

Materials and methods

Study design, period, and area

A hospital-based cross-sectional study was conducted from September 1 to December 30, 2023. This study was conducted at the UoGCSH, which is located in the historical area of Gondar town. The UoGCSH is currently a Comprehensive Specialized Teaching Hospital in Ethiopia. It is found in Amhara, the National Regional State, the North Central Gondar Zone, and Gondar town. Gondar town is located 750 km northwest of Addis Ababa, the capital city of Ethiopia. The total population of the town is estimated to be 412,739 by the year 202332. The hospital has approximately 550 inpatient beds and 14 outpatient clinics to provide diagnostic, treatment, and preventive services for approximately five million people in Gondar and neighboring areas.

Study population

The source population and study population were all children who visited the pediatric department and all children who visited the selected outpatient department during the study period at UoGCSH, respectively. Children who visited the outpatient department for well-child care and were under the age of fifteen were included in the study. Children under 15 years of age and those with a history of nasal surgery, a sign of respiratory infection at the time of the study period, or recent antibiotic use within two weeks of their hospital visit were excluded from the study.

Sample size determination and sampling technique

A single population proportion formula was used to calculate the sample size using a 50% proportion value, for a total sample size of 385. A systematic random sampling technique was used to enrol 385 study participants. Approximately 20 children visited the outpatient unit or section on each working day based on the 2022 records of the hospital. Specifically, 20 children × 20 working days per month for four months yields a total of 1600 children. The sampling interval was calculated as 1600/385 = 4. The first child on the first day of sample collection was selected by a lottery method. After that, every fourth child was requested to participate and offer his or her informed assent until a sufficient number of samples were obtained.

Variables of the study

Dependent variables

Nasopharyngeal colonization of gram-negative bacterial isolates and antibiotic susceptibility patterns were considered dependent variables.

Independent variables

The sociodemographic characteristics of the child (age and sex); parental/guardian social condition (educational status, occupation status, residence, monthly income status, number of rooms, cooking practices, and smoking cigarettes); child living conditions (family size, sharing a sleeping room, number of siblings, residence, inadequate hand washing practices, and the habit of nose picking); and clinical information about the child (recent hospitalization history, recent exposure to antibiotics, a sign of runny nose for the last two weeks, and previous history of respiratory tract infection among family members) were taken as explanatory variables.

Data collection

A trained nurse collected sociodemographic data using a semistructured questionnaire during a face-to-face interview with their parents or guardians, and the clinical data of each child were taken from hospital documents.

Sample collection, transportation, and processing

Trained laboratory technologists collected a total of 385 nasopharyngeal specimens from each child using sterile specimen collection plastic nasopharyngeal swabs (USA FDA registration number: 3011555966). Sampling was performed by entering the swab into the nostril parallel to the palate until pressure was detected, rotating the swab 4–5 times both clockwise and counterclockwise, and then withdrawing the sample33. After sampling, nasopharyngeal swab samples were taken and immediately transferred into labeled tubes of Amies transport medium (Biomark, India) and subsequently delivered to the Bacteriology Laboratory at the UoGCSH with a cold box carrier containing ice packs within two hours of collection.

Identification of gram-negative bacterial pathogens

The nasopharyngeal samples were then streaked with a sterile wire loop on chocolate agar (Oxoid, UK), blood agar (Oxoid, UK), modified thayer martin agar (Oxoid, UK), or MacConkey agar plates (Oxoid, UK). The former three plates were incubated in a candle jar at 37 °C for 24–48 h to produce a 5% CO2-enriched environment, while the latter agar plate was incubated aerobically for 18–24 h at 37 °C for cultivation of the intended bacteria. After incubation, the growth of the bacterial colonies on these agar plates was observed for preliminary identification of the bacteria based on their morphological appearance, such as elevation, shape, color, texture, and size. Then, a smear was prepared on a frosted-end slide, after which each colony was detected on the plates, after which the results were subjected to Gram staining to determine the extent of the reaction via microscopic examination.

Pure young colonies of the suspected bacterial isolates were subjected to different biochemical tests after determination of their Gram reaction. The biochemical tests used for species identification of fastidious gram-negative bacteria included the oxidase test (Deben Diagnostics Ltd., UK); the satellite test on blood agar (Oxoid, UK) and nutrient agar plates (Oxoid, UK); and the carbohydrate consumption test (cystine trypticase acid medium enriched with glucose, lactose, sucrose, and maltose on four test tubes)34. Gram-negative diplococci that generate oxidase and ferments glucose and maltose but not lactose or sucrose were recognized as N. meningitidis, whereas nonfermenters to glucose, lactose, sucrose, and maltose were identified as M. catarrhalis34,35. In addition, a gram-negative coccobacillus that produced satellite colonies only on a blood agar plate in the presence of S. aureus but not on a nutrient agar plate was found to be nonhemolytic and oxidase positive, and that produced nonsusceptibility to 10 U of bacitracin discs was identified as H. influenzae36,37.

In addition, triple sugar iron agar (TSI) (Oxoid Ltd., Basingstoke, UK), Simon’s citrate agar (Oxoid Ltd., Basingstoke, UK), urease agar (Oxoid Ltd., Basingstoke, UK), lysine iron agar (Oxoid Ltd., Basingstoke, UK) (LDC), and sulfur indole motility medium (SIM) (Oxoid Ltd., Basingstoke, UK) were used to prepare the biochemical tests for species identification of nonfastidious GNB38.

Antibiotic susceptibility testing

Briefly, 3–5 young pure colonies were picked and emulsified in 5 mL of normal saline, and their turbidity was compared with that of 0.5 McFarland standards29. The adjusted bacterial suspension was inoculated on Mueller–Hinton agar (MHA) (Oxoid, UK), and modified MHA (Oxoid, UK) was enriched with 5% sheep blood using a sterile cotton swab to determine the antibiotic susceptibility patterns of nonfastidious and fastidious gram-negative bacteria, respectively, using the lawn culture method. After being permitted to air dry for 15 min, the antibiotic discs were placed aseptically on the prepared plates using sterile forceps, and the plates were subsequently incubated (modified MHA in a 5% CO2 environment) at 37 °C for 24 h.

In accordance with Clinical and Laboratory Standard Institute (CLSI) guidelines39, the identified gram-negative bacterial isolates were tested against antibiotic discs containing amoxicillin/clavulanic acid (20/10 µg), gentamicin (10 µg), cefotaxime (30 µg), ciprofloxacin (5 µg), ceftazidime (30 µg), tetracycline (30 µg), trimethoprim-sulfamethoxazole (1.25/23.75 µg), chloramphenicol (30 µg), azithromycin (15 µg), minocycline (30 µg), ampicillin (10 µg), meropenem (10 µg), and rifampin (5 µg). The antibiotic disc used was produced by BD (BBLTM). The susceptibility data were interpreted as sensitive, intermediate, or resistant based on CLSI 202239. Moreover, bacterial isolates that showed resistance to three or more different antibiotic classes were considered MDR40.

Quality control

A semistructured questionnaire was pretested on 5% of the sample size, and the principal investigator verified the completion of the questionnaire. The culture media were prepared based on the instructions of the manufacturer, and bacterial culture positivity was ensured by following standard operating procedures. Before using the freshly prepared culture media, 5% of the prepared batches were incubated at 35–37 °C for 24 h to confirm sterility. Standard reference bacterial strains of Pseudomonas aeruginosa (American Type Culture Collection [ATCC (12934]), E. coli [ATCC 12241], N. meningitidis [ATCC 13090], H. influenzae [ATCC 49247], and K. pneumoniae [ATCC 12832] were used as control strains.

Data analysis

The data were checked for completeness and coded, followed by data entry into Epi-Data version 4.6.0.6 and data export and analysis using Statistical Package for Social Sciences version 25. The frequency and percentage of variables were determined using descriptive analysis. Using the binary logistic regression model, independent variables with a P value ≤ 0.2 in the bivariate analysis were entered into multivariate analysis to simultaneously control for the possible confounding effects of these variables. An adjusted odds ratio with a P value < 0.05 at the 95% confidence interval was considered to indicate statistical significance.

Ethical approval

Ethical clearance was obtained from the Ethical Review Committee of the School of Biomedical and Laboratory Sciences, College of Medicine and Health Sciences, University of Gondar, with reference number SBMLS/485. Each child participant provided written informed assent, and written informed consent was obtained from their parents or guardians before starting the data collection. All the data and samples collected were kept confidential and used only for this study. Research involving human research on our study participants was performed following the Declaration of Helsinki.

Results

Sociodemographic and clinical characteristics of the children

The study was conducted on a total of 385 children aged 3 to 14 years, for a 100% response rate. The mean (± SD) age was 8.1 (± 3.4) years. Of these, 206 (53.5%) were males. More than half (230 [59.7%]; 240 [62.3%]; 201 [52.2%]; and 213 [55.3%]; lived in cities, practiced indoor cooking, shared a house with five or more family members together, and lived with siblings for < 5 years, respectively. The majority (283 [73.5%] and 198 [51.4%]; patients had previously visited a hospital and had taken antibiotics before three months of their hospital visit, respectively; 197 [51.2% had not suffered from respiratory tract infections; and 322 [83.6% had not previously been hospitalized] (Table 1).Table 1 Sociodemographic and clinical characteristics of children attending the outpatient department at the UoGCSH, Northwest Ethiopia, from September 1 to December 30, 2023.

Full size table

Prevalence of nasopharyngeal colonization by gram-negative bacterial isolates

Overall, 146 (37.9%) (95% CI: 33.2–42.9) patients were positive for nasopharyngeal colonization by gram-negative bacteria among the children attending the outpatient department. Overall, 45 (11.7%) (95% CI: 8.8–15.3%) of the cultures were positive for nonfastidious GNB, 41 (10.6%) were positive (95% CI: 7.9–14.2%) for M. catarrhalis, 34 (8.8%) were positive for N. meningitidis (95% CI: 6.4–12.1%), and 26 (6.8%) were positive for H. influenzae (95% CI: 4.6–9.7%) (Fig. 1).

figure 1
Fig. 1

Antibiotic susceptibility patterns of gram-negative bacterial isolates

The tested isolates exhibited high resistance to tetracycline (85; 75.9%), trimethoprim-sulfamethoxazole (105; 71.9%), ampicillin (76; 67.9%), and amoxicillin/clavulanic acid (60; 69.8%). However, they demonstrated susceptibility to meropenem 122 (83.6%), gentamicin 73 (84.9%), and minocycline 87 (72.5%). Isolates of N. meningitidis exhibited remarkable resistance to trimethoprim-sulfamethoxazole (28; 82.4%), ciprofloxacin (16; 47.1%), and cefotaxime (14; 41.2%). Nonetheless, a large proportion of the N. meningitidis isolates exhibited susceptibility to azithromycin (31; 91.2%), chloramphenicol (26; 76.5%), meropenem (27; 79.4%), and minocycline (29; 85.3%). Furthermore, H. influenzae isolates were shown to be highly resistant to tetracycline (22; 84.6%), trimethoprim-sulfamethoxazole (20; 76.9%), and ampicillin (18; 69.2%), although low resistance was noted for ciprofloxacin (10; 38.5%) and meropenem (9; 34.6%). Similarly, more M. catarrhalis isolates were resistant to tetracycline (33; 80.5%), trimethoprim-sulfamethoxazole (31; 75.6%), ampicillin (28; 68.3%), and ceftazidime (25; 61.0%) (Table 2).Table 2 Antibiotic susceptibility patterns of gram-negative bacteria isolated from the nasopharynx of children attending the outpatient department at the UoGCSH, Northwest Ethiopia, from September 1 to December 30, 2023.

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Multidrug resistance patterns of gram-negative bacteria

A total of 13 antibiotics from 11 classes (aminoglycosides, β-lactam combination agents, penicillins, tetracyclines, phenicols, macrolides, cephalosporins, lincosamides, fluoroquinolones, folate pathway antagonists, and ansamycins) were used to determine the patterns of MDR isolates. One hundred thirty-nine (95.2%) of the gram-negative isolates were resistant to at least one antibiotic, while 7 (4.8%) of them were susceptible to all the tested antibiotics. The overall proportion of MDR strains was 99 (67.8%, 95% CI: 59.7–75.0). The predominant MDR isolate was M. catarrhalis 29 (70.7%), followed by H. influenzae 18 (69.2%) and N. meningitidis 23 (67.6%) (Table 3).Table 3 Multidrug resistance profile of gram-negative bacteria isolated from the nasopharynx of children attending the outpatient department at UoGCSH, Northwest Ethiopia, from September 1 to December 30, 2023.

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Factors associated with nasopharyngeal colonization by gram-negative bacteria

After conducting a bivariate analysis, variables that showed a significant association with COR at a P value ≤ 0.2, including residence, maternal education, smoking within the family, runny nose symptoms, prior respiratory tract infections, and hospital visits, were considered potential candidates for multivariate analysis. The results of multivariate analysis revealed that being male (AOR = 1.785, 95% CI = 1.102–2.892, P = 0.019), smoking a cigarette (AOR = 2.675, 95% CI = 1.149–6.230, P = 0.022), and living with a large family (≥ 5) (AOR = 1.857, 95% CI = 1.140–3.023, P = 0.013) were the most significant risk factors for nasopharyngeal carriage of gram-negative bacteria in children in this study. The likelihood of carrying gram-negative bacteria was also shown to be two, three, and two times greater for males, smokers, and those with a large family size, respectively (Table 4).Table 4 Bivariate and multivariate analyses of factors associated with nasopharyngeal colonization of gram-negative bacteria among children attending the outpatient department at UoGCSH, Northwest Ethiopia, from September 1 to December 30, 2023.

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Discussion

Among the nasopharyngeal colonizers of M. catarrhalis and N. meningitidis in this study, 41 (10.6%) (95% CI: 7.9–14.2%) and 34 (8.8%) (95% CI: 6.4–12.1%), respectively, had nasopharyngeal colonization. These results for N. meningitidis are concordant with previous findings in Ethiopia in Gondar (10.1%)41 and Arba Minch (6.6%)42, Chile (6.5%)43, and Turkey (7.5%)44. However, this figure is higher than that of studies performed in Nepal (1.4%)45, the Philippines (3.7%)46, Colombia (1.9%)47, and China (2.86%)48. In contrast, this percentage is lower than that reported in studies performed in Ethiopia-Addis Ababa (20.4%)49 and Iran (13.8% vs. 17.1%)9. The dissimilarity above could arise from differences in the source of the sample, study population, geographic location, or sample size47.

In this study, we found that the prevalence of nasopharyngeal colonization by H. influenzae was 26 (6.8%) (95% CI: 4.6–9.7%), which is comparable to that reported in the study conducted in Ethiopia-Debre Berhan (6.6%)31, but it was greater than that reported in studies from Ethiopia-Bahir Dar (2.3%)50 and Nepal (0.8%)51. However, our findings were not as high as those reported in Spain (27.7%)2, Italy (14.1%)52, or Iran (29%)15. The inconsistency of geography and climate across countries may cause discord in the carriage of H. influenzae53. In addition, the carriage rate of H. influenzae decreases after 2 years of age54; hence, the inclusion of children older than 5 years in our study might partly explain the lower carriage of H. influenzae in this study.

In the present study, 45 (11.7%) of the patients had nasopharyngeal colonization of nonfastidious GNB (95% CI: 8.8–15.3%). This is comparable with the findings of studies conducted in Ghana (13.9%)25 and Brazil (9%)55. However, this percentage is lower than that reported in a study performed in Indonesia (27%)7. This discrepancy might be related to differences in population, sanitary circumstances, socioeconomic level, and weather conditions25.

In the present study, compared to the other antibiotics tested, trimethoprim-sulfamethoxazole (82.4%), ciprofloxacin (47.1%), and cefotaxime (41.2%) demonstrated reduced activity against N. meningitidis isolates. This finding is similar to that of previous studies in Ethiopia-Gondar41, in which high resistance to trimethoprim-sulfamethoxazole, ciprofloxacin, and cefotaxime was detected in 73.6%, 45.3%, and 35.8%, respectively. The reason for the high resistance against trimethoprim-sulfamethoxazole might be because sulfonamides were introduced previously56. In addition, prolonged attachment to antibiotics and irrational usage of antibiotics may lead to enhanced resistance against other antibiotics41. However, an earlier study in Ethiopia-Gondar57 reported 100% susceptibility to chloramphenicol, which contradicts our findings. This difference in resistance could be justified because antibiotic resistance varies greatly over time58, as indicated by the results of previous studies conducted since 2012.

In the present study, we found that H. influenzae isolates exhibited high resistance to trimethoprim-sulfamethoxazole (76.9%) and ampicillin (69.2%). A study from Ethiopia-Debre Berhan31 and China also reported high resistance to ampicillin (88.9% vs. 61.4%) and trimethoprim-sulfamethoxazole (73.5% vs. 75.1%), respectively59. The high resistance to these antibiotics might be due to β-lactamase production and excessive consumption of these antibiotics. In addition, resistance to ampicillin and other β-lactam antibiotics by H. influenzae isolates might result from mutations in penicillin-binding protein 3 (PBP3)59. However, our study showed that most H. influenzae isolates were susceptible to azithromycin (88.5%), meropenem (65.4%), rifampin (61.5%), and ciprofloxacin (61.5%), indicating that these antibiotics are effective against H. influenzae in this area.

In the present study, isolates of nonfastidious GNB exhibited high resistance to ampicillin 30 (66.7%) and amoxicillin/clavulanic acid 30 (66.7%) but low resistance to gentamicin 9 (20%) and meropenem 3 (6.7%). This finding is consistent with the findings of studies performed in Ghana, which reported ampicillin (64.9%), amoxicillin/clavulanic acid (59.6%), gentamicin (7.0%), and meropenem (8.8%)25. The generation of β-lactamases, upregulated expression of efflux pump genes, and possible decreases in outer membrane permeability are the reasons for the resistance mechanisms against meropenem and gentamicin60.

A total MDR of 99 (67.8%, 95% CI: 59.7–75.0) was found in our study, with proportions of 70.7%, 69.2%, and 67.6% for M. catarrhalis, H. influenzae, and N. meningitidis, respectively. This MDR strain was comparable to that in the study in Ethiopia-Debre Berhan, which included H. influenzae (66.7%)31. However, the percentage of MDR bacteria in our study was greater than that in studies in Nepal (17.5%)51 but lower than that in Ethiopia-Bahir Dar (78.4%) for M. catarrhalis50. This percentage is also higher than that reported in other Ethiopian studies performed in Addis Ababa (14.3%)49 for N. meningitidis isolates. The potential of bacteria to create many mechanisms of resistance and the broad availability of antibiotics may favor selection pressure on usual isolates, which could explain the incidence of high MDR50.

This study revealed that male sex was significantly associated with nasopharyngeal bacteria carriage (AOR = 1.785, 95% CI (1.102–2.892), P = 0.019). Likewise, a study in Spain61 showed that male sex is a risk factor for bacterial carriage. This is supported by the fact that the defensive humoral and cell-mediated immunity produced by males is lower than that produced by females due to hormonal differences in male testosterone and female estrogen hormones, which have immune suppressive and immune-stimulating properties, respectively62,63. Therefore, they are more prone to bacterial infections. Additionally, a study in China suggested that males encounter more physical contact and are more likely to have lower personal safety than females are64.

The present study showed that children living with a smoking family member had a greater likelihood of being infected with nasopharyngeal gram-negative bacteria than children living with a nonsmoking family member (AOR = 2.800, 95% CI = 1.224–6.404, P = 0.022). This association has also been documented in earlier studies in Ethiopia31,41. The association between nasopharyngeal bacteria carriage and passive smoking can be explained by smoking harming the upper layer of the respiratory tract mucosal surface, which encourages the susceptibility of the nasopharynx to bacteria carriage and may be the cause of this relationship31.

This study revealed that children from families with more than five members had greater odds of nasopharyngeal bacteria carriage than did those with fewer members (AOR = 1.857, 95% CI = 1.140–3.023; P = 0.013). Large family sizes and nasopharyngeal bacteria carriage have also been linked in important ways by studies that took place in Ethiopia in Debre Berhan (P = 0.006)31, China (P = 0.043)65, and Iran (P = 0.044)66. This association may be reflected by the fact that the presence of large family members leads to overcrowding, which in turn facilitates a lower ventilation environment and the aerosol transmission of bacteria within members of the family from carriers to noncarriers31,67,68.

Limitations of the study

Even though this study provides pertinent information about nasopharyngeal colonization, antibiotic susceptibility patterns, and associated factors of gram-negative bacteria among children attending the outpatient department at UoGCSH, serogrouping and molecular characterization of the detected isolates were not performed due to a lack of resources.

Conclusions and recommendations

In this study, we found that the prevalence of nasopharyngeal colonization by gram-negative bacteria among outpatient children was 37.9%. The most frequently identified bacterium was M. catarrhalis. Most of the tested isolates were highly resistant to ampicillin, tetracycline, trimethoprim-sulfamethoxazole, and amoxicillin/clavulanic acid. The overall MDR was 67.8%, with M. catarrhalis being the predominant isolate. Gentamicin, minocycline, and meropenem were the drugs of choice for the tested isolates. The chance of being a carrier of gram-negative bacteria in children increases with male sex, living with a family member who smokes cigarettes, and having a large family size (≥ 5). Therefore, this study concluded that children may serve as a source of antibiotic-resistant gram-negative bacteria to the healthy general population if they successfully remain untreated. In addition, parents of children at large should avoid smoking cigarettes in the same house as other members of the family and reduce the number of people living in one house. This study also recommends that researchers perform community-based studies using advanced procedures such as serogrouping and molecular characterization to better comprehend circulating strains and map resistance genes.

Data availability

The datasets generated during and/or analysed during the current study are available from the corresponding author on reasonable request.

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Acknowledgements

The authors are delighted to express their great thanks to the study participants and the staff members working in the outpatient pediatrics department at the University of Gondar Comprehensive Specialized Hospital. We would also like to give our sincere thanks to the Department of Medical Microbiology, School of Biomedical and Laboratory Sciences, College of Medicine and Health Sciences, University of Gondar. Lastly, we would like to acknowledge the Ethiopian Public Health Institute for providing reference bacterial strains and necessary materials and Mr. Mihretu Molla for his material support of the project.

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Authors and Affiliations

  1. Department of Medical Microbiology, School of Biomedical and Laboratory Sciences, College of Medicine and Health Sciences, University of Gondar, Gondar, EthiopiaAbebe Birhanu, Azanaw Amare, Mitkie Tigabie, Getachew Bitew, Eden Getaneh & Feleke Moges
  2. Department of Medical Parasitology, School of Biomedical and Laboratory Sciences, College of Medicine and Health Sciences, University of Gondar, Gondar, EthiopiaTena Cherkos

Contributions

A.B. conception of the research idea, scientific write up, data collection, laboratory work, data analysis and interpretation, and the writing and review of the manuscript G.B. T.C. and E.G. data analysis and sample collection A.A. M.T. and F.M. conceptualization, methodology designing, supervision and review of the manuscript. All authors read and approved the final manuscript.

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Correspondence to Abebe Birhanu.

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Birhanu, A., Amare, A., Tigabie, M. et al. Asymptomatic nasopharyngeal carriage of multidrug resistant bacteria among children at University of Gondar Hospital Northwest Ethiopia Revealing Hidden Health Risks. Sci Rep 14, 28994 (2024). https://doi.org/10.1038/s41598-024-77527-y

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