Abstract:
Urinary tract infection (UTI) is common in women, especially sexually active women i.e. in women of child bearing age all over the world including Bangladesh. A large number of women in Bangladesh are reportedly suffering from UTI due to ignorance and not practicing health and hygiene factors properly and it is a significant source of morbidity rate in our country. UTIs in pregnant women pose serious health risks for both mother and child.
Earlier and recent reports globally, as well as in Bangladesh, have shown increasing rates of antibiotic resistance among uropathogens often resulting in treatment failure of UTI. The distribution of uropathogens and their susceptibility pattern to antibiotics vary regionally and even in the same region, they change over time. Due to rising antibiotic resistance among uropathogens; it is important to have local hospital based knowledge of the organisms causing UTI and their antibiotic sensitivity patterns. Therefore, the knowledge on the frequency of the causative microorganisms and their susceptibility to various antibiotics are necessary for a better therapeutic outcome.
In the Northern region of Bangladesh there are four Government owned Tertiary Level hospitals namely - RMCH, Rajshahi, SZMCH, Bogra, Rangpur Medical College Rangpur and Dinajpur Medical College Hospital, Dinajpur. A huge number of female patients from different, social, cultural, educational and economical levels attend the OPD’s or get admitted to the above tertiary level hospitals to receive treatment for UTI and other diseases.
As far as our knowledge goes, very few, but no detailed study on the prevalence of UTI, isolation and identification of the uropathogens and the antibiotic susceptibility pattern of the isolates in providing basic guideline in treating UTI’s have so far not been conducted on the Tertiary care hospitals in the Northern parts of Bangladesh.
To fill this information gap, the present study was undertaken, with the aim was to study the frequency and distribution of uropathogens and their resistance pattern to antibiotics in tertiary care hospitals located in the Northern parts of Bangladesh.
Settings and Design: Prospective study for a period of 3 year from July 2008 to July 2011carried out in the Molecular Biology Laboratory, Institute of Biological Sciences, University of Rajshahi, Bangladesh .
Patients and Methods: Four hundred fifty (450) female patients aged between 15-45 years who attended the OPDs or got admitted to RMCH, Rajshahi, SZMCH, Bogra, Rangpur Medical College Rangpur and Dinajpur Medical College Hospital, Dinajpur in the Northern regions of Bangladesh with clinical symptoms and suspected of having UTI and those who gave informed consent and fulfilled the inclusion and exclusion criteria were the subjects of the present study.
Research instruments of the study were firstly filling up a structured questionnaire at the time of collection of urine specimens which included medico-demographic and clinical details such as name, age, physiological age group marital status, pregnancy, diabetic status, blood pressure and symptoms of UTI etc. Secondly, clinical history taking, clinical examination of the patients and collection of urine samples for urinalysis were done by informed consent of the women and the permission to that effect was obtained from the ethical committee of the hospitals.
A total of 450 midstream urine (MSU) samples were taken from only female patients who had clinically suspected UTI .They were asked to collect a fresh sample of MSU in a sterile container after cleaning the genitals with soap and water. The sample was transported to the microbiology laboratory and processed by wet film microscopy (Routine urinary microscopy), Gram’s stain and semi-quantitative urine culture in blood agar, CLED agar and MacConkey’s agar. Biochemical testing was used to identify the organisms and antibiotic susceptibility testing was done by the Kirby-Bauer disc diffusion technique.
Results
Urinalyses of 450 female subjects for detection of UTI showed 151 patients had UTI (both symptomatic and asymptomatic) bring the prevalence rate of UTI 33.55% of the study population. Prevalence of symptomatic UTI was higher than asymptomatic UTI. (97(64.2%) vs 54 (35.76%). Most UTI sufferers were married females (62.91%) 95 subjects where as nearly half of the percentage (32.45%) observed in 49 single females.
In contrast, the incidence rate of both asymptomatic and symptomatic UTI among widow/divorced was found to be extremely low and was 7.41 % and 3.09 %, respectively.
Predominance of asymptomatic and symptomatic UTIs among pregnant women (88.89 vs. 70.10%) was noticed as compared to non-pregnant (29.63% vs. 29.90%). The prevalence of symptomatic and asymptomatic UTIs was found higher (nearly twice) in diabetic subjects (62.88% vs. 59.25%) as compared to non-diabetic subjects (37.11% vs. 40.74%). Symptomatic and asymptomatic UTIs were more common in hypertensive subjects (59.79% vs. 55.55%) than subjects with normal blood pressure (37.11% vs. 42.59%) and hypotension (3.09 % vs. 1.85%).
Age-wise incidence of UTI showed highest UTI sufferers 68 (44.44%) were the most sexually active women (26-35 years age group), while the least sufferers of UTI 37 (24.83%) were women of 15-25 years. Significant impact of socio-economic statues on UTI incidence was noticed and the highest UTI sufferers (49%) were from poor socio-economic class; whereas only 6 (3.98%) cases were from the rich socio-economic class.
Education seems to play a significant role in preventing the incidence of UTI and its incidence was extremely low 7 (4.64%) in patients having Master’s degree; while very high 68 patients (45.03%) among the Illiterate. As far as profession is concerned UTIs was more prevalent among businesswomen constituting (48.88%) of the women with UTIs, followed by Artisans/ full housewives (44.79%), Women Traders (35.25%), Students (29.16%), teachers (19.11%) and the Civil Servants were the least UTI sufferers (11.42%.).
Results of incidence of UTI in relation to use and no use of commercial sanitary napkin during menstrual cycle of women shows use of commercial sanitary napkin plays a significant role in lowering incidence of UTI. Women using sanitary napkins regularly had lower incidence rate (20.53%) of UTI as compared to those not using sanitary napkin that had higher (49.00%) incidence of UTI. Results of prevalence of UTI based upon type of toilet use clearly demonstrated very high prevalence of UTI (51.0%) among women not using sanitary latrine at all. On the contrary, the incidence of UTI among sanitary latrine using women was found to be very low (17.88%).
The results of urine culture showed that of 450 urine samples, 151(33.55%) yielded significant growth of single organism and 12 (2.66%) yielded mixed growth. No growth was observed in 299 (66.44%) urine samples. Escherichia coli (42.38%) was the most common organism followed by Pseudomonas aeruginosa (12.58%). E. coli was highly sensitive to imipenem (91.2%), Amikacin (83.55%) and Gentamicin (78%) and was highly resistant to Azithromycin (85%), Nalidixic acid (77%) and co-trimoxazole (68%). Ciprofloxacin and gatifloxacin with (55.56%) and (48%) resistance respectively were moderately resistant.
Pseudomonas species were highly sensitive to imipenem (94.5%), gentamicin (78.72%) and Amikacin (77%) and moderately sensitive to Ciprofloxacin (55.32%). Pseudomonas showed highest resistance against cephradine (90%), followed by gatifloxacin (85%) and Azithromicin (85%), cefixime (82%), nalidixic acid (81.12%), cotrimoxazole (78.5%).
Klebsiella showed highest resistance to Azithromycin (82%), followed by Cefixime (78.5%), nalidixic acid (77.45%), gatifloxacin (77%), Ceftriaxone (75.95%), Ciprofloxacin (70%) and cotrimoxazole (60.55%). On the other hand, Klebsiella was found to be highly sensitive towards Imipenum (92.08%), Amikacin (91.5%) and moderately sensitive to Cephradine (65.5%).
Proteus showed highest resistance to nitrofurantoin (79.35%), followed by Azithromicin (78%), while Proteus showed moderate resistance of 55% to Nalidixic acid and cotrimoxazole (52.3%). On the other hand, Proteus was found to be highly sensitive to Amikacin (92.5%), Ceftriaxone (89.17%), Gentamicin (86.45%), gatifloxacin (75%), Ceftazidine (72.55%), Imipenum (70%), Cirprofloxacin a cefixime and cephradine (60%).
Staphylococcus saprophyticus showed highest resistance to Nalidixic acid (78%), Ceftazidine (77%), gatifloxacin (75.5%), cotrimoxazole (72%), ciprofloxacin (70%). Cephradine showed moderate resistance (55%). On the other hand, Staphylococcus saprophyticus was found to be highly sensitive to Imipenum (80%), followed by gentamicin (71.4%), Azithromycin (65.7%), Amikacin (64.3%). Ceftriaxone and Nirofurantoin both showed moderate sensitivity of 60%.
Staphylococcus aureus showed highest resistance to Ceftazidine (78%), followed by ciprofloxacin (77.5%), Cotrimaxazole and nalidixic acid (75%), Ceftriaxone (66.7 %). On
the contrary, Staphylococcus aureus showed highest sensitivity towards Imipenum (89%), followed by Azithromycin (78%), gentamicin (75%), Amikacin (71%) and gatifloxacin (70%) while Cephradine showed (65%) and cefixime (60%) sensitivity which can be considered as moderate sensitivity.
Conclusion: Overall, Antibiotic susceptibility testing of the major isolated uropathogen E. coli. and other uropathogens of the present study revealed that in general most uropathogens showed very higher resistance to commonly used antibiotics - Azithromycin, Nalidixic acid and Cotrimoxazole and these drugs have limited value for the treatment of UTI and should no longer be used. Moreover, this study concludes that E. Coli the major pathogen and other gram negative (as well as gram positive) isolates were more highly sensitive to Imipenum, Amikacin and Gentamicin as compared to other antibiotics tested and therefore these may be the drugs of choice for the treatment of complicated UTI caused by gram negative isolates in our region i.e. in the Northern region of Bangladesh.
Very alarming level of antibiotic resistance has been observed under the present study where Ciprofloxacin and even newer Gatifloxacin, broad spectrum antibiotics and major anti-pseudomonad weapons are becoming moderately sensitive to bacteria causing UTI. Ciprofloxacin, Gatifloxacin, Cephradine and cefixime (Except Klebsiella and Pseudomonas showing > 79 and 90% resistance, respectively) exhibited moderate to less moderate sensitivity in many cases under the study. One time blockbuster antibiotics such as Cephradine, and cefixime exhibited moderate resistance and reduced susceptibility. These findings are clearly alarming as our country could be running out of effective antibiotics if this trend continues. Since most of the organisms are showing resistance to routinely used antimicrobials in UTI, especially fluoroquinolones, no guidelines for empirical treatment of UTIs can be given. It is imperative to rationalize the use of fluoroquinolones in order to prevent the dissemination of resistant strains in the population.
For treatment of UTI caused by Gram-positive isolates S. saprophyticus and S. aureus the antibiotics - Imipenem, Azithromycin, Gentamicin and Amikacin to which they are found to be highly sensitive, should be the drug of choice in the Northern areas of Bangladesh. Cephradine and cefixime with moderate sensitivity can be considered as second line therapy, however only after performing a culture and sensitivity (CS) test of urine
specimens. On the other hand, Gram-positive isolates showed highest resistance towards Nalidixic acid, Ceftazidine, ciprofloxacin, gatifloxacin, cotrimoxazole, and Ceftriaxone and these antibiotics should no longer be prescribed for treating UTI caused by Gram-positive isolates in our region.
Under the above stated prevailing and changing antibiotic resistance pattern noticed among uropathogens under the present study in the northern region of Bangladesh, for the physicians to prescribe the drugs cautiously for the betterment of the patient’s treatment of each and every UTI patients need to be individualized, if possible. It is recommended that, antibiotics should be used after doing a routine microscopy and culture/ sensitivity of urine in order to inhibit acquisition and spread of drug resistance by the bacteria.
The antimicrobial sensitivity testing is needed for selection of antibiotics for treatment of UTI patient’s. Routine monitoring of drug resistance pattern will help to identify the resistance trends regionally. This will help in the empirical treatment of UTI to the clinicians and also for the preparation of antibiotic policy of the individual institute. This will avoid the indiscriminate use of antibiotics and prevent the further development of antimicrobial resistance. It is also urged that antimicrobial policy should be adopted at both the tertiary level hospital and the National level supervised by monitoring cell for taking necessary steps to minimize the drug resistance.