Published by : PROFESSIONAL MEDICAL PUBLICATIONS
October - December 2009 (Part-I)
Changing patterns in sensitivity of bacterial
uropathogens to antibiotics in children
Fakhrossadat Mortazavi1, Narges Shahin2
Objective: To determine the sensitivity/resistance of bacterial uropathogens to antibiotics in children and evaluate the changing pattern of their sensitivity over a six years period.
Methodology: Medical records of children between two moths to 14 years of age who admitted with symptomatic urinary tract infection were studied in two periods: First from 2006 to 2007 and the second from 2000 to 2001 in Children’s Hospital of Tabriz/Iran. The sensitivity patterns of uropathogens were compared between two periods of study.
Results: The most frequently isolated germs were E.Coli, klebsiella, enterobacter, pseudomonas aeroginosa and proteus in a descending order. In study of 2006-2007: Among the oral agents, nitrofurantoin and ciprofloxacin, and among the parenteral agents, amikacin and gentamicin had the highest activity against E.coli. The highest sensitivity of klebsiella was to ciprofloxacin, nalidixic acid, cefixime, and amikacin in a descending order. The activity of ceftriaxone, ceftizoxime, nalidixic acid and cephalexin against E.coli has decreased significantly over six years (P<0.05). Also the activity of ceftriaxone, ceftizoxime, gentamicin, amikacin and nalidixic acid against klebsiella has decreased in comparison with results of six years ago (P<0.05). There was not any significant difference in sensitivity of enterobacter and pseudomonas with results of six years ago.
Conclusion: Increasing resistance of uropathogens to third generation cephalosporines and aminoglycosides raises an alarm for widespread use of these life saving drugs. The guidelines for empiric treatment of UTI should be revaluated periodically based on local studies.
KEY WORDS: Urinary tract infection, sensitivity, resistance, bacterial uropathogen (child).
Pak J Med Sci October - December 2009 (Part-I) Vol. 25 No. 5 801-805
How to cite this article:
Mortazavi F, Shahin N. Changing patterns in sensitivity of bacterial uropathogens to antibiotics in children. Pak J Med Sci 2009;25(5):801-805.
1. Fakhrossadat Mortazavi, MD
Department of Pediatric Nephrology
Associate Professor of
Tabriz University of Medical Sciences
2. Narges Shahin, MD
Tabriz University of Medical Sciences
Dr. Fakhrossadat Mortazavi
Children’s Hospital of Tabriz
* Received for Publication: April 6, 2009
* Accepted: August 12, 2009
Urinary tract infection (UTI) is one of the most common causes of hospitalization and referral to out patient settings in children. It is estimated that at least 3% of girls and 1% of boys experience one episode of UTI before the 11th years of age.1 About 30-50% of these patients will have another episode within three months to two years, particularly in girls.2,3 Upper UTI (pyelonephritis) is a major cause of hypertension, renal insufficiency and end-stage renal failure in children. Early treatment of UTI with an effective antibiotic is essential for prevention from long-term consequences. Delay in treatment increases the risk of scar formation in kidneys.4 So in almost all children with UTI, antimicrobial therapy is initiated empirically before the result of urine culture is available. Sensitivity of bacterial uropathogens to antibiotics show a great geographical and historical variability due to different antibiotic treatments. So knowledge of the sensitivity pattern of common uropathogens according to local epidemiological studies is necessary for selection of an appropriate antibiotic for empirical treatment. Pape et al recommended that the policies for treatment of UTI in children should be re-evaluated every five years according to local resistance rates.5 In our center data is limited on the susceptibility pattern of uropathogens to antibiotics.
The aim of this study was to determine the distribution and sensitivity pattern of uropathogens isolated from children and compare the findings with sensitivity pattern of 6 years ago in a tertiary care hospital in north-west of Iran.
This study was conducted at the children’s Hospital of Tabriz/Iran. Medical records of children between two months to 14 years of age with diagnosis of UTI (inpatient and outpatient) were evaluated from April 2006 to September 2007, and patients who had positive urine culture in association with pyuria were selected for study. Clinical diagnosis was based on the presence of one or more of followings: fever, flank pain, dysuria, frequency, urgency and suprapubic pain. Pyuria was defined as the presence of more than seven leukocytes in high power filed of centrifuged urine. Positive urine culture was defined as more than 105 colony forming units (CFU) of a single organism per milliliter of urine. Urine specimens were obtained by midstream collection in toilet trained children and sterile urine bags in younger children after disinfecting the perineum. Suprapubic sampling was carried out in selected patients. Blood agar was used for urine culture. Sensitivity/ resistance of isolated microorganisms to commonly used antibiotics was detected by disc diffusion method.
Exclusion criteria were: patients without pyuria, asymptomatic patients and positive cultures with less than 105 CFU/ml or multiorganism growth. Also patients with insufficient data and repeat isolates from the same patient were excluded. Data from each patient including sex, age, clinical symptoms, and results of urine analysis, urine culture and antibiogram were collected in organized forms.
This study was repeated with the same method, from April 2000 to September 2001, and sensitivity pattern of uropathogens in these two periods of study were compared. The research ethics committee of Tabriz University of Medical Sciences approved the study. Data was analyzed by SPSS 14 software using Chi square test for comparisons. P.values less than 0.05 was considered as significant.
From April 2006 to September 2007, 232 patients and from April 2000 to September 2001, 205 patients who fulfilled the inclusion criteria were studied. Demographic features of patients have been demonstrated in Table-I. E.Coli, klebsiella pneumoniae and enterobacter were the most common isolated germs in both periods of study (Table-II). The invitro sensitivity of E.Coli and klebsiella to antibiotics has been shown in (Table-III&IV).
In study of 2006-2007 among the oral agents, nitrofurantoin and ciprofloxacin, and among the parenteral agents, amikacin and gentamicin had the highest activity against E.coli (Table-III). The antibiotics with highest activity against klebsiella were ciprofloxacin, nalidixic acid and cefixime in a descending order (Table-IV).
The activity of ceftriaxone, ceftizoxime, nalidixic acid and cephalexin against E.coli has decreased significantly over six years (P<0.05). Also the activity of ceftriaxone, ceftizoxime, gentamicin, amikacin and nalidixic acid against klebsiella has decreased in comparison with results of six years ago (P<0.05). There was not any significant change in susceptibility of E.coli and klebsiella to other antibiotics in two periods of study.
In study of 2006-2007, the sensitivity of enterobacter was 78.5% to gentamicin, 71.4% to ceftazidime, 57.1% to ciprofloxacin and ceftriaxone, 50% to amikacin and nitrofurantoin, 42.8% to nalidixic acid and 35.7% to cotrimoxazol. The sensitivity of pseudomonas was 100% to ciprofloxacin and ceftazidim, 81.8% to gentamicin and 63.6% to amikacin. All other antibiotics were totally inactive against pseudomonas.
There was not any significant difference in antibacterial sensitivity of enterobacter and pseudomonas in two periods of study (P>0.05).
Escherichia-coli is the most common cause of UTI and accounts for 75-90% of UTIs in children.6,7 However its relative frequency varies in different areas. In studies carried out in Canada, Mexico, Pakistan and India E.coli accounted for 57.7%-69.9% and klebsiella for 12.4%-29% of UTIs,8-11 that is similar to our results.
In empiric treatment of acute febrile UTI, suggestive of pyelonephritis, broad spectrum antibiotics such as ceftriaxone or a combination of ampicillin with an aminoglycoside such as gentamicin is conventionally recommended.6,12 However in some studies from Iran,4,13 Mexico9 and Sudan,14 microbial resistance to ampicillin is high and varies from 75% to 89.3%. In present study, resistance to ampicillin is very high (91.8%). So adminstration of ampicillin in empiric treatment of UTI is not reasonable in our center. Most studies show a high sensitivity of E.coli to gentamicin.15 In the study of Goldstein et al in France, the susceptibility of E.coli to gentamicin was 98.4%.16 In our study the susceptibility of E.coli is 69.9% to gentamicin and 84.4% to amikacin which is lower than other studies. Also present study showed that the activity of ceftriaxone against E.coli and klebsiella and activity of aminoglycosides against klebsiella has significantly decreased over six years. Decreaseing trend in activity of aminoglycosides and third generation cephalosporines against uropathogens raises a great concern regarding the empiric treatment of pyelonephritis, in our institution.
Among oral antibiotics for ambulatory management of uncomplicated lower UTI, cotrimoxazol was a drug of choice for a long time. During the past decades resistance of E.coli to cotrimoxazol increased from 0-5% before 1990 to 9-15% in 1999 in Western countries.17 In recent years resistance of E.coli to cotrimoxazol has increased and varies from 21% to 76.7% in different studies.8-10,13-15,18-22 In our study, resistance of E.coli to cotrimoxazol (82.2%) is higher in comparison with literature that may be related to inappropriate prescription of cotrimoxazol in upper respiratory infections in our country. From other oral agents fluoroquinolones (FQs) such as ciprofloxacin have the highest activity against E.Coli in most studies.14,16,18-20 So in the past few years use of cotrimoxazol has decreased whereas use of FQs has increased dramatically in adults.23 Guneysel et al observed that FQs were the most prescribed antibiotics for UTI of adults in Turkey.20 The activity of ciprofloxacin against E.coli has been reported up to 93.3% in children4 and is 81.5% in our study. However the safety of ciprofloxacin in children is under study because of potential cartilage damage that occurred in research with immature animal.6
In our study, nitrofurantoin has the highest activity against E.coli (90.4%). The susceptibility of E.coli to nitrofurantoin has been reported from 83.6% to 98.8%.18-20 Although this agent may be used for treatment of lower UTI, its use in pyelonephritis is not recommended because of inadequate tissue levels.6
This study has showed a decreasing susceptibility of E.coli and Klebsiella to some antibiotics over a six years period. If this trend continues, the antimicrobial drugs are likely to become less effective not only for treating of UTI, but also for treating of other life threatening infections. However, it should be noted that our hospital is a referral center for most complicated UTIs. Further community based studies in general hospitals and outpatient settings are required to determine the resistance pattern of uropathogens in uncomplicated UTIs.
Authors would like to thank Dr. Solmaz Nickvash and all coworkers of microbiology laboratory of Children’s Hospital of Tabriz for their great assistance in microbiological evaluation of urine samples.
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