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Analysis of distribution and antibiotic resistance of pathogens isolated from the paediatric population in Shenmu Hospital from 2011–2015

Objective This study aimed to investigate the epidemiology and changes in antibacterial susceptibility of children in Shenmu City, northern Shaanxi, and provide a basis for rational drug use. Methods The distribution and drug resistance pattern of pathogenic bacteria isolated from children were retrospectively analysed. Results A total of 573 strains of pathogens were cultivated. A total of 201 (35.07%) strains of Gram-positive cocci and 183 (31.93%) strains of Gram-negative cocci were detected. A total of 189 (32.98%) strains of fungi were detected. The resistance rate of Staphylococcus to penicillin was 100% and that to erythromycin was 90.69%. There were varying degrees of resistance to other drugs, but no single strain had vancomycin resistance. Gram-negative bacilli were generally resistant to ampicillin, but had low resistance to the combined preparation of enzyme inhibitors, quinolones, and aminoglycosides, and were highly sensitive to imipenem and meropenem. Conclusion Gram-negative bacilli are the main pathogens of bacterial infection in the paediatric ward. Strengthening clinical monitoring of bacterial distribution in paediatric clinical isolates and understanding changes in drug resistance are important for guiding the rational use of antibiotics. These measures could also prevent emergence and spreading of resistant strains.


Introduction
Antimicrobial resistance is the ability of a microorganism (e.g., bacteria, viruses, and some parasites) to stop an antimicrobial (e.g., antibiotics, antivirals, and antimalarials) from working against it. As a result, standard treatments become ineffective, infections persist, and infections may become severe and can also spread to others. 1 Antimicrobial resistance is an internationally documented threat to health. 2 Bacterial infections that are resistant to antibiotics can limit the availability of effective treatment options, rendering some commonly encountered bacterial infections challenging to treat. 3 Antibioticresistant infections are also twice as likely to be associated with greater morbidity and mortality and are associated with increased healthcare costs. 4 Antibiotics are a keystone for treating bacterial infections and children receive these drugs more frequently than any other class of medication. However, inappropriate and unnecessary use of antibiotics in the past decades has increased the emergence of resistant bacterial strains. 5 Children receive a lot of primary healthcare services, and as such, receive an excessively high number of antibiotics compared with middle-aged populations. 6 Children are also major drivers of infection within communities and can contribute to the spread of bacteria from person to person. 7 Nearly 80% of childhood cases of urinary tract infection in poorer countries are resistant to amoxicillin, and 60% are resistant to co-amoxiclav. More than a quarter of children are resistant to ciprofloxacin (Cipro), and 17% to nitrofurantoin. 8 All of the above-mentioned factors require clinicians to be responsible for a correct diagnosis and treatment for affected children as soon as possible to avoid unnecessary disability and death. Despite this, little research has been published describing the microbial spectrum and antimicrobial resistance profile of bacteria from paediatric patients in China. Therefore, an understanding of the pathogens and antibiotic resistance associated with paediatric infections at our hospital and in nearby regions is necessary. In this study, we selected clinical data from patients who were admitted to the Paediatric Department during January 2011 to December 2015 for retrospective analysis of the distribution of bacterial species and changes in drug resistance. This study aimed to determine the profile and susceptibility patterns of bacterial pathogens associated with infections in paediatric patients during 5 years.

Source of strains
Pathogens were isolated from specimens that were collected from all children who were admitted to Shenmu Hospital during January 2011 to December 2015. A total of 573 strains were isolated from 419 male patients and 154 female patients.

Ethics statement
Non-routine procedures were used, and only data regarding the results from culture and sensitivity of specimens were analysed retrospectively. Therefore, no consent was required from the patients' caregivers.

Bacteriological identification
Isolation and culture of bacteria were carried out according to the ''National Clinical Practice Guidelines''. 9 Bacteria were identified by the automatic bacteria analyser VITEK -2 identification system and a manual method.
Extended-spectrum beta-lactamase strains were confirmed by the double-disc method. The antimicrobials used were cefotaxime/ clavulanic acid (30 mg/10 mg) and ceftazidime/ clavulanic acid (30 mg/10 mg), both provided by Oxoid Company.

Quality control strains
Escherichia coli ATCC25922, Staphylococcus aureus ATCC29213, and Pseudomonas aeruginosa ATCC27853 were purchased from the Shaanxi Provincial Clinical Laboratory.

Statistical analysis
VITEK -2 identification system software was used for analysis and processing of all of the original test data. IBM Statistics SPSS 21 Premium (Chicago, IL, USA) and GraphPad Prism 6 (La Jolla, CA, USA) statistical analysis software were used for the statistical analysis.

Distribution of specimens and strains
During January 2011 to December 2015, 573 strains of pathogens were isolated from 73.2% (419) male patients and 26.8% (154) female patients. The Fisher-Irwin test showed a significant difference in the number of isolated strains between sexes ( 2 ¼ 246.514, P < 0.0001). When we divided the time period into three quantum zones, spanning 20 months each, we found that the portion of male children steadily increased over time (Kruskal-Wallis 2 ¼ 25.20, P < 0.01). A total of 73 (12.8%) children were aged less than 28 days, 254 (44.4%) were between 29 days and 1 year, 124 (21.6%) were between 1 and 3 years, 67 (11.7%) were between 3 and 6 years, and 55 (9.6%) were older than 6 years. The average length of stay in hospital was 6 days and the mean AE standard deviation was 7.8 AE 4.0 days ( Table 1).
A total of 189 (32.98%) strains of fungi were detected. A significantly higher number of pathogens were isolated from respiratory secretion and blood compared with other types of secretions. The yearly (2011-2015) distribution ratio of pathogens is shown in Table 3. The distribution of pathogens according to variety of specimens is shown in Table 4.

Drug-resistant rate
Among common Gram-positive bacteria, 16 strains of Staphylococcus aureus and 27 strains of Staphylococcus haemolyticus were isolated. The average resistance rate of Staphylococcus aureus and Staphylococcus haemolyticus against penicillin was 100%. Among macrolides, the resistance rate of erythromycin was >80%, but no vancomycin-resistant staphylococci were found (Table 5). Among Gram-negative bacilli, the Escherichia coli resistance rate for ampicillin and piperacillin was >80% while its resistance rate against first, second, third, and fourth generation cephalosporins was nearly 70%. The Pseudomonas aeruginosa resistance rate to ampicillin was 100%.    Additionally, except for the low resistance rate of Pseudomonas aeruginosa against the third generation cephalosporin ceftazidime and fourth generation cephalosporin cefepime, its resistance rate was higher than 90% against all other cephalosporins. The resistance rate of Pseudomonas aeruginosa to levofloxacin, gentamicin, amikacin, imipenem, and meropenem was <10%, while its resistance to piperacillin/tazobactam was 30%. Escherichia coli was not resistant to imipenem and meropenem (Table 6).

Discussion
Shenmu City coal mining has resulted in serious smoky air pollution, rendering the air quality poor. This has caused an enormous increase in infections of the respiratory tract in hospitalized children. 11 There is an upward trend of yearly detection of pathogens, but the overall number of pathogens that are detected annually has decreased. 12 Our study showed that the main pathogens of paediatric infection were Grampositive bacteria, accounting for 35.07%, while Gram-negative bacteria accounted for 31.93% and fungi accounted for 32.98%. These numbers of infected pathogens are consistent with most domestic reports. 13 The predominance of Gram-negative bacteria in hospital-acquired infections is probably due to the fact that patients are treated with antimicrobial agents before admission. Additionally, many individual clinics do not perform allergy tests, and thus use macrolides of which the main antimicrobial spectrum is of Gram-positive bacteria. 14 This results in a low detection rate of Gram-positive bacteria, while Gramnegative bacteria have become predominant in examinations of pathogens in hospitalized Table 5. Resistance of Gram-positive bacteria to commonly used antimicrobial agents. patients. Our study showed that detection of coagulase-negative staphylococci infection was highest among all hospital infections and its detection rate was much higher than that of other bacteria. This finding is in accordance with previous studies. 15 The pathogenicity of coagulase-negative staphylococci is less than that of Staphylococcus aureus. However, in the case of immunocompromised patients, infection may still occur, especially an increasingly growing resistance of these strains (e.g., methicillinresistant coagulase-negative staphylococci), suggesting that coagulase-negative staphylococci is an important nosocomial infection pathogen. 16   piperacillin, while they also show cross resistance against aminoglycosides and fluoroquinolones. Because these two drugs show adverse reactions in children, their use in children is already limited. 20 Our study showed that sensitivity of Escherichia coli for amikacin, cefoperazone/sulbactam, and nitrofurantoin was >90.0%. Sensitivity of Klebsiella pneumoniae to fluoroquinolones and amikacin was>92.0%. Pseudomonas aeruginosa was 100% sensitive to ceftazidime, cefepime, amikacin, fluoroquinolone, and aztreonam. Enterobacter cloacae was also highly sensitive to fluoroquinolones, cefoperazone/sulbactam, cefotaxime, and amikacin. The resistance of Gram-negative bacilli to imipenem and meropenem is lower in Shenmu City than that of other regions in China, 21 which may be related to the strict control of antimicrobial drug use in our hospital.

Staphylococcus aureus
Overall, the situation in Shenmu City regarding resistant paediatric pathogens is serious. There is an urgent need to strengthen monitoring of the distribution of pathogens and bacterial resistance. Strict implementation of antimicrobial management, and good use of consultation and an approval system resulting in the rational use of antibiotics are also required. At the same time, food and drug supervision agencies and health administrative departments should strengthen supervision of antimicrobial drug purchase and strictly supervise prescription drugs, especially in private clinics and drug retail outlets. Publicity on antibacterial drug health education should be increased through print and social media to avoid pre-hospital, nonprescription, irrational use of antibiotics. In short, prevention and control of bacterial drug resistance in standard paediatric treatment is an important task.