ANTIMICROBIAL RESISTANCE OF UROPATHOGENS IN BASRAH

Background: The high incidence of multi-resistant uropathogens is of great epidemiological significance because the etiological agents of urinary tract infection are quite capable of spreading through susceptible population. Objective: to study the extent of antimicrobial resistance of uropathogens in Basrah. Patients & Methods: A cross-sectional study involving 789 patients, 610 patients attending outpatient clinics in three hospitals in Basrah city and 179 admitted patients in Al-Sader Teaching Hospital, was carried out. Patients included in the study were those with symptoms suggestive of urinary tract infection and were not on antibiotics for at least one week. The study was conducted during the period between January 2003 and March 2004. For each patient a general urine examination and urine culture were done. Identification of the isolated bacteria was performed according to a standard method and antimicrobial susceptibility test was performed using the diffusion disk method. Results: Out of 610 outpatients included in the study, 443(72.6%) had positive culture, 128(61%) of males and 315 (78.8%) of females. E.coli was the commonest organism, isolated from 205 urine samples representing 43.7% of the total isolates, followed by other gram negative bacteria: Klebsiella sp., Proteus sp., and Pseudomonas aeruginosa. Gram positive cocci represented 7.7% & 3.6%.for CoPS and CoNS respectively. On the other hand, Klebsiella sp were the most commonly isolated bacterial uropathogens from inpatients, they represented 47.7% of the total isolates. Sensitivity rates to all chemotherapeutic agents among uropathogens isolated from hospital acquired urinary tract infections (the inpatient group) were lower than that of sensitivity rates of uropathogens isolated from the community acquired urinary tract infection. The overall sensitivity rates of isolates recovered from patients with hospital acquired urinary tract infection for norfloxacin, and ciprofloxacin were 59.3%, and 39.5%, while the sensitivity rates of the isolates reported from community acquired urinary tract infection for the same agents were 83.6%, and 39.5% respectively. Conclusions: Both hospital and community acquired uropathogens showed resistance to all classes of antimicrobial


INTRODUCTION
ost urinary tract infections are caused by facultative anaerobes that are able to grow under either anaerobic or aerobic conditions and usually originate in the bowel flora. [1]Pathogens associated with uncomplicated UTI are E.coli identified in about 75-90% of infections, [2] Staphylococcus saprophyticus (5-15%).Klebsiella, Proteus, Enterococcus and Pseudomonas aeruginosa are seen in smaller percentages. [3,4]There are an estimated 150 million UTI per annum worldwide. [5]UTI is the most common bacterial infection in women and accounts for significant morbidity and health cost. [5]In the USA, acute UTI encountered in adult women, resulting in as many as 8 millions office visits per year. [6]In United Kingdom, over 5 million prescriptions for antibiotics are written by general practitioners for UTIs annually. [7]There is increasing prevalence of antimicrobial resistance among uropathogens causing acute uncomplicated cystitis in young women. [8]Changing resistance pattern observed with common urinary pathogens has altered the empirical approach to antibiotics selection for UTI. [9]Appropriate antibiotic therapy is important because of the high incidence of UTI in the general population, the potential for complications, especially in high-risk subgroups, and the associated cost of treatment. [9]The high incidence of multiresistant organisms is of great epidemiological significance because the etiological agents of urinary tract infection are quite capable of spreading through susceptible population. [10]oncurrent resistance to antimicrobials of M different structural classes has risen in bacterial species and may complicate the therapeutic management of infections including those of urinary tract. [11]Routine antimicrobial resistance monitoring is therefore an essential part of any UTI control program that advocates empiric antimicrobial therapy. [12]The present study was carried out to study the extent of antimicrobial resistance of uropathogens in Basrah.

MATERIALS AND METHODS
A cross-sectional study involving 789 patients, 610 patients attending outpatient clinics in three hospitals in Basrah city, (namely Al-Sader Teaching Hospital, Basrah General Hospital, and Basrah Maternity and Children Hospital), and 179 admitted patients in Al-Sader Teaching Hospital, was carried out.Patients included in the study were those with symptoms suggestive of urinary tract infection and were not on antibiotics for at least one week.The study was conducted during the period between January 2003 and March 2004.Midstream urine samples were collected from each patient in a sterile universal container, brought to the laboratory and examined within one hour.General urine examination was carried out for each sample to screen for microscopic bacteriuria.Specimens which yielded 10 5 /ml (CFU) or more were considered as having significant bacteriuria. [13]rine cultures were done by spreading 0.1 ml of each sample on blood and MacConkey agars and incubated for 24-48 hours at 37 o C. Identification of the isolated bacteria was performed according to a standard method.Antimicrobial susceptibility test was performed using the diffusion disk method. [14]The antimicrobial agents used in this study, were βlactam, TMP-SMX, nitrofurantoin, gentamicin, and quinolones, because all of these agents achieve high urinary concentration. [15]Statistical analysis was done by using a computerized SPSS program, version 11.

DISCUSSION
Resistance to antibiotics has become a major international problem and there has been a worldwide effort to contain resistance by a number of interventions.The main strategy concentrates on surveillance of antimicrobial resistance and the feedback of surveillance to allow more rational prescribing. [16]Urine samples form a very significant part of the workload of microbiology laboratories and they can comprise up to 60% of specimens from the community, therefore, they can make an important contribution to surveillance to antibiotics resistance in the community. [16]ntimicrobial resistance of community acquired uropathogens An increase in antimicrobial resistance among pathogens that cause community acquired UTI was observed by several researchers. [3,17]In the present study, the antimicrobial resistance of E. coli, which was the commonest pathogen that caused community acquired UTI, was tested.
The resistance rates to ampicillin, amoxicillin, and TMP-SMX, were found to be 52.9%,32.4% & 27.5% respectively.While the resistance rates to gentamicin, and nitrofurantoin were equal at 21.1%.][20] Aminopenicillins are frequently used in treatment of a wide range of infectious processes including those in the UTI, so this frequent use has led to the resistance that was observed in the present study and that frequently seen in clinical isolates. [21]On the other hand, nitrofurantoin is a bactericidal in urine at therapeutic dose, and its multiple mechanisms of action enable it to be potent against E.coli despite nearly 50 years of use. [22]owever, the susceptibility level of E.coli may be influenced by, nitrofurantoin narrow spectrum of activity, limited, narrow tissue distribution and limited contact with bacteria outside the urinary tract. [23]E. coli resistance to the first generation quinolones was 12.7%, while resistance rates to second generation, ciprofloxacin and norfloxacin, were 11.7% and 6.3% respectively.Ciprofloxacin resistance rates in Europe ranged between 0% in Sweden and 14.7% in Spain. [19]Thus, it has been suggested that fluoroquinolones are logical choice for empirical therapy of uncomplicated UTI, but the wide spread use of fluoroquinlones for such common infections raises the possibility of accelerated development of resistance. [24]A gradual decrease in the susceptibility of E.coli to fluoroquinolones has been reported by the USA arm of the SENTRY surveillance program. [25]Klebsiella sp., the second commonest isolated uropathogens, showed high resistance to several antimicrobial agents (ampicillin, amoxicillin, TMP-SMX, and gentamicin).Similar results were reported in another study. [18]The resistance rate to ampicillin in Tikrit (1999) was found to be 98%. [20]Klebsiella sp.showed a lower resistance rates to third generation cephalosporines and to quinolones.These results are similar to those found in another study; with the exception that ciprofloxacin resistance rate was reported to be equal to 0%. [15] Proteus species resistance rates to different antimicrobial agents were found to be higher than those for other microorganisms.This may be due to their association with recurrent infection. [25]In the present study, pseudomonas species showed high resistance to the most common antimicrobial drugs (ampicillin, amoxicillin, TMP-SMX, nitrofurantoin, cephalexin, nalidixic acids and gentamicin).However, Pseudomonas species responded to third generation cephalosporines mainly to ceftazidime (resistance rate 10.3%).
In Europe, ceftazidime and tobramycin resistance rates were 28.4% and 31.6%respectively. [26]Resistance of Pseudomonas sp. is an increasing clinical problem worldwide and is a recognized public health threat.There is limited number of antimicrobial agents with reliable activity against pseudomonas sp. [27]timicrobial resistance of hospital acquired uropathogens The hospital acquired uropathogens were resistant to all antibiotics.In this study Klebsiella sp. and E.coli were highly resistant to ampicillin, amoxicillin, gentamicin and TMP-SMZ.The resistance rates were higher than those found for community acquired UTI.In addition, Klebsiella sp. and E.coli showed a relatively high resistance rates to third generation cephalosporin and nitrofurantoin.The high resistance rates to gentamicin, third generation cephalosporin, and nitrofurantoin are in agreement with previous reports. [28,29]roteus sp. and Pseudomonas sp.represent important uropathogens of nosocomial acquired infections, being widely distributed in hospital environment where they are difficult to eradicate. [30]In the present study, they showed high resistance rate to quinolones, aminoglycosides and third generation cephalosporines, thereby causing a major problem in the management of nosocomial UTI.