How to cite this article: Duarte-Raya F, Rodríguez-Lechuga M, De Anda-Gómez MA, Granados-Ramírez MP, Vargas-Rodríguez AG. Adequate antimicrobial drug use in a third level pediatric hospital. Rev Med Inst Mex Seg Soc. 2015 Mar-Apr;53(2):150-7.
Received: September 27th 2013
Accepted: October 30th 2014
Fidencia Duarte-Raya,a Manuel Rodríguez-Lechuga,b Manuel Alberto de Anda-Gómez,c Martha Patricia Granados-Ramírez,d Alexia Gisselle Vargas-Rodrígueze
aDivisión de Epidemiología
bDivisión de Epidemiología
cDivisión de Educación en Salud
dServicios de Laboratorio, Hospital de Especialidades 1, León, Guanajuato, México
eServicio de Pediatría Médica
a,b,c,eHospital de Gineco-Pediatría 48, León, Guanajuato, México
Communication with: Fidencia Duarte-Raya
Telephone: 01 (477) 717 4800, extension 31855
Background: The inadequate use of antimicrobials contributes to the development of bacterial resistance, reduces the effectiveness of established treatments and increases costs and mortality due to infectious diseases. The aim of this article was to evaluate if the use of antimicrobials was carried out properly in hospitalized pediatric patients.
Methods: An epidemiological observational, cross-sectional study was carried out in UMAE-48 in León, Guanajuato. Sample was non-probabilistic by convenience with 60 % of expected adequated treatments, 4 standard deviation. Analysis of statistical distribution frequency technique was used by type of final grade of each treatment that were administered: adequate, justified, therapeutic, restricted and prophylactic. The test c2 for comparing of percentages.
Results: Antimicrobial therapy were evaluated 283 prescriptions in 217 patients, 53 % were men and 47 % women. The general treatment was adequate in 51.2 %, justified 66 %, therapeutic 53.4 % therapeutic, 40.8 % restricted and 48%prophylactic. Comparison of percentages with statistical test of c2, we found association with adequate treatment in neonates service (c2 8.287; p 0.004) and inadequate treatment in preterm infants service (c2 4.853; p 0.028) p < 0, 05. The most commonly used antimicrobials 43.7 % Penicillins and 37.1 % aminoglycoside.
Conclusion: Only half of the treatments was antimicrobials are prescribed properly.
Keywords: Adequate use; Antimicrobial; Pediatrics
Since the eighties, the World Health Organization (WHO) has promoted the rational use of medicines1 and recommended that this aspect be integrated into national policies for medicines.2 The World Health Assembly (WHA) in 1998 urged Member States to develop actions to improve the use of antibiotics. In 1998, the Pan American Conference on Antimicrobial Resistance in the Americas made crucial recommendations for the countries of the region on improvement in the use of antibiotics.3 In 2001, WHO issued the Global Strategy for Containment of Antimicrobial Resistance.4 At its 60th session in 2006, the WHA recognized that is not possible to apply resolutions on antimicrobial resistance without addressing the larger problem, which is the irrational use of medicines, and it urged member countries to invest the necessary human resources and financing.5
The relevance of drugs for population health depends on their quality, accessibility, and proper use. However, it is estimated that globally, half of all medicines are prescribed, dispensed, and consumed incorrectly.6
Proper and timely use of antibiotics in the severe acute patient is a constant challenge for medical staff, as improper handling contributes to poor results in these patients7 and contributes to the development of bacterial resistance, which reduces the effectiveness of treatments provided and increases the cost and mortality from infectious diseases, so it is considered a serious public health problem that requires responses at local, national, and global levels.8,9
Overuse of antimicrobial agents remains one of the main factors that affect patterns of antibiotic resistance, and it should be remembered that antibiotics are among the most prescribed drugs in pediatrics. These drugs are used empirically to avoid morbidity and mortality when there is suspicion of an untreated infectious disease.10
The importance of requesting cultures is very significant in the empiric treatment of infections because they not only help to establish a pattern of local bacterial resistance, but also because they help to reduce the unnecessary use of antibiotics.10 In nosocomial infections the growing resistance in pathogens has been reported associated with high incidence and mortality.11-13
Misuse of antibiotics has even been identified as a major risk factor for mortality in intensive care units,14 so the rapid increase of antimicrobial resistance calls for control in the administration of antibiotics.15
On the other hand, various health institutions have developed and promoted the use of clinical guidelines to improve their prescription.16,17 There are no recent reports addressing the impact of these guidelines, or how their development is linked to information on bacterial resistance.
According to NOM-045 on nosocomial infections and guidelines to consider when selecting an antibiotic,18,19 various factors should be taken into account, including: administering the antibiotic if at all possible after making a culture with antibiogram. Once the germ and its susceptibility to antibacterial agents have been identified, choose the system with the narrowest antibacterial spectrum. The choice of antibacterial agent will be guided by: the pharmacokinetics (route of administration, mechanism of action, etc.), possible adverse reactions, the site of infection, the status of the host (immunity, concomitant viral infections such as mononucleosis and AIDS, age, sex, etc.), evidence of documented efficacy in controlled clinical trials, and finally choosing, if possible, the least expensive regimen.
Antibiotic prophylaxis in surgery is indicated in the following cases: "clean contaminated" and contaminated operations. There is worldwide interest in this subject, so information campaigns are recommended with public health educational activities on the appropriate use of antimicrobials. Also, activities and projects are developed in collaboration with organizations such as WHO, Pan American Health Organization (PAHO) and the Centers for Disease Control and Prevention (CDC).20
Consequently, WHO has urged each member country to launch a national strategy to improve the use of antibiotics and contain antimicrobial resistance, suggesting various educational, regulatory, and management activities.21
The aim of this study is to evaluate whether the use of antibiotics in hospitalized pediatric patients is done properly.
An observational, cross-sectional epidemiological study of the appropriate use of antimicrobials in pediatric patients hospitalized in UMAE Hospital de Gineco-Pediatría No. 48, was conducted during the period from March 1st 2012 to May 31st 2012. It was a non-probabilistic convenience sample, with 60% of appropriate treatments and a standard deviation of 4, resulting in a sample of 217 patients.
Hospitalized patients receiving antibiotic treatment were selected, daily monitoring was performed, and during hospitalization the main clinical, demographic, and microbiological characteristics were recorded with the information-gathering instrument. The study considered: personal identification data, the immunocompromised state, and prescribing service (general pediatrics 41, pediatric surgery 36, nephrology 9, hematology 17, heart surgery 6, pediatric intensive care unit (PICU) 8, Neonatal ICU (NICU) 15, neonatology 40, premature 18, neurosurgery 5, oncology 8, urology 5, orthopedics 9). It also considered prescribing diagnosis, presence or absence of nosocomial infections, results of culture, identification of microorganisms with their sensitivity and resistance, and if it was a producer of beta-lactamase. The selected antibiotic, its form of administration, dosage/kg/day, route, schedule, start date and time of suspension, duration, and dilution were recorded strictly. With the above criteria treatment was scored as: restricted, prophylactic, therapeutic, appropriate, and/or justified. If there were complications, and the final outcome: stopped due to improvement, due to maximum benefit, voluntarily, or due to death.
Information was compiled on a calculation sheet coded to facilitate analysis, descriptive statistics were done with the patient demographics (age, sex, and immunocompromised state). From the cultures, they registered requesting service, the type of culture (blood, catheter tip, LCR, secretion, throat, urine, and feces), and the type of microorganism isolated. The frequencies of empirical treatments and those based on the result of the culture were determined. The statistical technique of frequency distribution analysis was used for the type of final score of each treatment administered: prophylactic, therapeutic, restricted, justified, and appropriate, in accordance with the regulatory definition from the antimicrobials manual.18
When recommendations made by the service were not available, the assessment was based on national and international references.
Information on antimicrobial resistance by hospital and community microorganisms were analyzed in parallel.
Chi-squared was done to compare percentages, with a confidence interval (CI) of 95% and statistical significance when p < 0.05. The results are presented in tables.
During the time of the study (92 days) a total of 283 antimicrobial prescriptions were included in 217 patients. Of the total, 115 were male (corresponding to 53%) and 102 female (the remaining 47%). The age ranged from 1 day old to 15 years 8 months. The group under 1 year of age formed 44.2%; the 1-4 age group was 19.8%; 5-9 years 17%; 10-14 years 13.5%; and 15-16 years 5.5%. We should note that age 16 is considered the limit for pediatric care at the IMSS. The days of hospitalization were: minimum 1, maximum 79, with an average stay of 9.9 days + 11.32.
The route of administration of antimicrobials was: intravenous 84%; oral 12%; ophthalmic 2%; intramuscular 1%, and dry powder inhalers (DPI) 1%. Immunocompromised patients were 77 (35.5%), and nosocomial infection 31 (14.3%).
A total of 91 cultures processed accounted for 32.1% of antimicrobial treatments given. 29.6% were positive for some gram-positive or gram-negative germ, two cultures isolated 2 germs. 67.9% (192) were empirical treatments not based on the result of a culture. It should be noted that the services that requested cultures to support their treatments were: nephrology with 83.3%, hematology with 65.5%, and NICU with 57.9%. The services with 0% of culture requests were: neurosurgery, orthopedics, preterms, and urology.
The reason for stoppage was: due to improvement for 208 cases corresponding to 95.8%, due to death for 8 cases corresponding to 3.7%, and due to referral to another hospital in only one case corresponding to 0.5%.
For the classification of the type of treatment administered without adequate score, they were: 49 restricted with 17.3%, 50 prophylactic with 17.7%, 232 therapeutic with 81.9%, and 187 justified with 66.0%. In evaluating the antimicrobial prescriptions by regulatory criteria, they were scored as: general appropriate treatment 145 (51.2%); appropriate justified treatment 123 (66%); appropriate therapeutic 124 (53.4%); appropriate restricted 20 (40.8%), and appropriate prophylactic 24 (48%).
By service, appropriate treatments were: cardiac surgery with 57.1%, pediatric surgery 47.4%, hematology 38.5%, general pediatrics 45.3%, neurosurgery 20%, orthopedics 33.3%, NICU 65.8%, oncology 50%, PICU 75%, nephrology 58.3%, neonatology 71.7%, preterms 25%, and urology 16.7% (Table I).
|Table I Appropriate antibiotic use at UMAE # 48|
|Source: assessment form/clinical record, UMAE-48, IMSS, 2012; n* some patients received more than one treatment|
In comparing percentages with chi-squared test, significant statistical association was found with the proper use of antibiotics only in the neonates service (chi-squared 8.287; p 0.004) and inappropriate use in the preterms service (chi-squared 4.853 ; p 0.028) with statistical significance of p < 0.05.
The antimicrobials were used in treatments were: penicillins 43.7%; sulfonamides 4.2%; macrolides 1%; aminoglycosides 37.1%; quinolones 2.8%; first generation cephalosporins 13.4%, second generation 0.3%, third generation 22.9%, fourth generation 1%; lincosinamides 6.3%; glycopeptides 7.3%; carbapenems 3.5%; and other groups 0.7% (Table II).
|Table II Drugs used in IMSS UMAE-48|
|Penicillin G Procaine||6||2.1|
|Amoxicillin withclavulanic acid||16||5.6|
|1st generation cephalosporins.||Cephalothin||38||13.4|
|2nd generation cephalosporins||Cefuroxime||1||0.3|
|3rd generation cephalosporins||Cefotaxime||47||16.6|
|4th generation cephalosporins||Cefepime||3||1.0|
|Source: assessment form/clinical record, UMAE-48, IMSS, 2012|
Microorganisms isolated from cultures in order of frequency were: Staphylococcus epidermidis, Escherichia coli, Staphylococcus aureus, Pseudomonas aeruginosa, Enterobacter faecalis, Staphylococcus hominis, Staphylococcus haemolyticus, Proteus mirabilis, Acinetobacter baumanni/haemolyticus, Klebsiella oxytoca, Serratia marcescens, Streptococcus pyogenes, and Staphylococcus hycus.
Drug resistances behaved as follows: gram-negative ESBL producers, Escherichia coli for cefotaxime and ceftazidime (Table III).
|Table III Gram-negative microorganisms in positive cultures.Sensitivity and resistance|
|< 20%||21 to 40%||41 to 60%||> 61%|
|5||Escherichia Coli*||Cefotaxime, ceftazidime,||Cefotetan, piperacillin/tazobactam, trimethoprim/sulfamethoxazole, cephalothin||Cefazolin, piperacillin, tetracycline||Ampicillin/sub, aztreonam, cefepime, cefotaxime ESBL, ceftazidime, levofloxacin||Ampicillin, cefuroxime, ciprofloxacin, gentamicin, tobramycin|
|Amikacin, cefepime, cefotaxime, ceftazidime, ceftriaxone, ciprofloxacin, gentamicin, levofloxacin, meropenem, ticarcillin/clavulanic ac., tobramycin, trimethoprim/sulfamethoxazole|
|2||Pseudomonas aeruginosa||Aztreonam, cefepime, cefotaxime, and ceftazidime, ticarcillin/ac, piperacillin/tazobactam.clavulanic acid||Ceftriaxone|
|1||Klebsiella oxytoca||Ampicillin, piperacillin, cephalothin|
|Amikacin, ampicillin/sub, ampicillin, aztreonam, Cefazolin, cefepime, cefotaxime, ceftazidime, ceftriaxone, cefuroxime, piperacillin/tazobactam, tobramycin, trimethoprim/sulfamethoxazole, piperacillin, tetracycline, cephalothin|
|2||Proteus mirabilis*||Aaztreonam, tetracycline|
|Source: T1 laboratory results, UMAE, IMSS, 2012, *A culture with two microorganisms.|
Gram-positive BLAC producers, Staphylococcus epidermidis, Staphylococcus aureus, Staphylococcus hominis, and Staphylococcus haemolyticus for penicillin and ampicillin. Acinetobacter baumannii was found resistant to all antibiotics (Table IV).
|Table IV Gram-positive microorganisms in cultures performed.Sensitivity and resistance|
21 to 40%
41 to 60%
|6||Staphylococcus epidermidis||ampicillin, penicillin||gentamicin, tetracycline||Ampicillin, ampicillin/sub, ceftriaxone, ciprofloxacin, levofloxacin, trimethoprim/sulfamethoxazole, amoxicillin/clav ac., oxacillin, penicillin, clindamycin, erythromycin..|
|3||Staphylococcus aureus *||ampicillin, penicillin||Ampicillin/sub, ampicillin, ceftriaxone, ciprofloxacin, gentamicin, trimethoprim/sulfamethoxazole, amoxicillin/clav ac., clindamycin, erythromycin, oxacillin, penicillin.|
|2||Staphylococcus hominis||ampicillin, penicillin||Ampicillin, ciprofloxacin, gentamicin, trimethoprim/sulfamethoxazole, penicillin||Ceftriaxone, ampicillin/sub, levofloxacin, tetracycline, amoxicillin/clav a., clindamycin, erythromycin, oxacillin|
|2||Staphylococcus haemolyticus||ampicillin, penicillin||Ciprofloxacin, tetracycline, clindamycin, erythromycin, penicillin||Ampicillin, ceftriaxone, gentamicin, ampicillin/sub, amoxicillin/clav ac., oxacillin|
|1||Staphylococcus hyicus *||Ampicillin, ceftriaxone, gentamicin, ampicillin/sub, amoxicillin/clav ac., oxacillin, penicillin.|
|Source: T1 laboratory results, UMAE, IMSS, 2012, *S culture with two microorganisms|
The development of antibiotic resistance due to inappropriate antibiotic choice in infectious processes is an issue widely mentioned in the literature worldwide. Spanish researchers have a very low degree of information about antibiotics and bacterial resistance, and this has been linked to their misuse.22-24 According to the classification of antimicrobial management, this study shows that less than half (40.8%) of the prescribed treatments were restricted appropriate treatments. This is due to the lack of adherence to the antimicrobials manual in terms of the criteria for its use, because generally the treatment is indicated upon the patient’s hospital admission, which is not then modified based on culture results with the isolation of a microorganism sensitive to first-line antibiotics. By restricted antibiotics, it is meant those antibiotics in single or combined scheme, used as second or third line treatment of certain infectious signs when there is a clinical failure or inability to use the antibiotics of first choice or to modify the initial scheme upon new clinical and laboratory data.25 In this hospital, according to the antimicrobials manual, restricted antibiotics are reserved only for patients with resistant strains and prior assessment by the infectious disease clinician and service manager. With respect to prophylactic treatments, 48% were appropriate. However, the regulation criteria were not considered, such as the number of doses and the type or classification according to the type of surgery.17,26 In this regard, antibiotic prophylaxis should be discontinued within the first 24 hours after completion of the surgery (or within 48 hours if cardiothoracic surgery).27
As for therapeutic treatments, 53.4% were suitable according to the service's own recommendations, which are based on the hospital’s antimicrobials manual. However, the recommendations do not cover all illnesses, and there are infections that are not covered. The attending physician must choose an antimicrobial according to their discretion, but most don’t adhere to evidence-based medicine, so 66% of antibiotic treatment was justified. As an example the unjustified use of the combination of ampicillin plus amikacin was seen in the neonatal and preterms service, due to the diagnosis of risk of sepsis due to premature rupture of membranes, sometimes at even less than 18 hours and without a history of taking a culture and without specifying length of treatment in the chart. This study shows that only half of antimicrobials were prescribed properly.
In Mexico, various aspects of the inappropriate use of antibiotics have been documented. For example, in an IMSS general hospital of Colima it was found that 63% of hospitalized patients receive antibiotic therapy,28 although it was not specified whether it was appropriate. In response to this situation educational and managerial interventions for physicians have been developed based on the public health system, as well as epidemiological monitoring programs.29
The inappropriate use of antimicrobials is associated with increased resistance to them. The results obtained in this study are very similar to those described in the literature of other hospitals, indicating that only half of antimicrobial treatments are prescribed appropriately.
There is a need for the implementation of monitoring and surveillance strategies by a multidisciplinary team led by an infectious disease expert for the proper prescription of antimicrobials. It is also necessary to have a compendium of antimicrobial prescribing to facilitate their use in the services, besides applying the model of operational research to systematize information and analysis on a regular basis in order to improve the processes and impact the quality of the care, reducing morbidity and mortality.
Conflict of interest statement: The authors have completed and submitted the form translated into Spanish for the declaration of potential conflicts of interest of the International Committee of Medical Journal Editors, and none were reported in relation to this article.