| Abstract|| |
To evaluate the antimicrobial resistance patterns of the Gram-negative organisms isolated from urine culture, we retrospectively analyzed the urine cultures and antibiotic sensitivity tests of inpatients and outpatients in our hospital between 1999 and 2002. A total of 11,659 urine specimens were analyzed of which 2054(17.6%) showed significant growth; 1764 (85.9%) were Gram-negative organisms. The most frequently isolated Gram-negative organisms were Escherichia coli 1026 (58%) and Klebsiella pneumoniae 293 (16.6%). The resistance rates for strains of E. coli isolated from the hospitalized patients were 61% to amoxicillin, 35% to amoxicillin-clavulanate, 47% to trimethoprim, 38% to ciprofloxacin, 31% to cephalexin and 13% to gentamicin. These rates were higher than those from the outpatients (52%, 36%, 40%, 32%, 29% and 5%), respectively. Out of the 42(2%) multidrug resistant E. coli and K. pneumoniae, 23(1%) were found to be positive for extended spectrum beta lactamase (ESBL) including 14 isolates of E. coli and 9 of K. pneumoniae. We conclude that our findings demonstrate a significant increase of resistance to various groups of antimicrobial drugs in the urine culture isolated from both inpatients and outpatients.
Keywords: Urinary tract infection, Gram-negative bacteria, Antimicrobial resistance, Extended spectrum beta lactamase.
|How to cite this article:|
Kader AA, Kumar A, Dass SM. Antimicrobial Resistance Patterns of Gram-Negative Bacteria Isolated from Urine Cultures at a General Hospital. Saudi J Kidney Dis Transpl 2004;15:135-9
|How to cite this URL:|
Kader AA, Kumar A, Dass SM. Antimicrobial Resistance Patterns of Gram-Negative Bacteria Isolated from Urine Cultures at a General Hospital. Saudi J Kidney Dis Transpl [serial online] 2004 [cited 2019 Oct 23];15:135-9. Available from: http://www.sjkdt.org/text.asp?2004/15/2/135/32894
| Introduction|| |
Urinary tract infection (UTI) is common both in the community and hospitalized patients. The widespread use of antimicrobial agents often leads to the emergence of resistant microorganisms to one or several of them. ,,
Some bacteria, especially Escherichia More Details coli and Klebsiella pneumoniae, show increasing resistance to cephalosporins. These organisms produce extended-spectrum (3-lactamases (ESBL), which are coded by genes located on transferable plasmids.  Resistance to the quinolones, by strains of E. coli isolated from urine specimens of outpatients, has also increased. 
Since the pattern of bacterial resistance is constantly changing, the monitoring of the antimicrobial susceptibilities becomes more important. It provides information on the pathogenic organisms isolated from patients, and assists in choosing the most appropriate empirical antimicrobial therapy. In addition, the continuous survey of antimicrobial resistance is crucial for monitoring changes of antimicrobial resistance.
In this report, we analyze the antimicrobial resistance patterns of the commonly isolated Gram- negative bacteria from urine specimens examined at a general hospital.
| Methods|| |
We studied the bacteria isolated and tested for antimicrobial sensitivity from urine specimens of inpatients and outpatients at Almana General Hospital, Alkhobar-Saudi Arabia. It is a private hospital that has 200 beds with all specialties except transplant surgery. The study period was four years (1 st January 199931 st December 2002). Only samples with significant growth were studied (significant growth was defined as the presence of > 10 5 colony forming units per milliliter (cfu /mL) of urine). In symptomatic patients, however, fewer organisms (<10 5 cfu /mL) may also indicate infection. Isolated bacteria were identified by standard methods  and API (BioMerieux, France). Antimicrobial susceptibility of the isolates was performed by Stokes method of disc sensitivity testing,  confirmed, if required, by testing for minimum inhibitory concentration (MIC) using E strip test (AB Biodisk, Solna, Sweden) or by agar dilution. All Gram-negative isolates, except Pseudomonas spp, were tested for susceptibility with a control strain of E. coli NCTC 10418. Strains of Pseudomonas spp were tested with a control strain of Ps. aeruginosa NCTC 10662. A CI lactamase producing control strain of E. coli was used to test organisms against disc containing amoxicillin + clavulanic acid. The control and test organisms were inoculated on the same sensitivity plate.
The ESBL-producing isolates of E. coli, K. pneumoniae and other Gram-negative bacteria were identified by using both cefotaxime and ceftazidime, alone and in combination with clavulanic acid  in disk diffusion. The isolates were considered ESBL producing organisms if they produced a 5 mm or more increase in a zone diameter for either anti-microbial agent when tested in combination with clavulanic acid versus its zone when tested alone. Cefotaxime and ceftazidime MICs for ESBL producing bacteria were performed with the agar dilution method.
| Results|| |
We received and examined 11,659 urine specimens during the study period. The total number of urine samples that showed significant growth was 2054 (17.6 %). Of these, 1712 (83.3%) were from outpatients and 342 (16.6%) from inpatients; 1764 (85.9 %) of the isolates were Gram-negative bacteria. The species distribution included Escherichia coli 1026 (58%), Klebsiella pneumoniae 293 (16.6%), Pseudomonas aeruginosa 166 (9.4%), Proteus species 144 (8.1%), Enterobacter spp 68 (3.8%), Citrobacter spp 48 (2.7%), Acinetobacter spp 19 (1.0%) and other Gram-negative bacteria 26 (1.4%).
More than 40% of the E. coli isolates were resistant to trimethoprim and amoxicillin, and more than 8% of the Ps. aeruginosa isolates were resistant to ceftazidime and gentamicin. Table 1 and 2 summarize the percentage resistance of Gram negative bacilli isolated from inpatients and outpatients.
Out of 64 multidrug resistant Gram-negative isolates, 37 isolates were positive for ESBL (Table 3). There was a trend for increased resistance of E. coli to amoxicillin + clavulanic acid from 19% in 1999 to 33% in 2002, and to ciprofloxacin from 14% in 1999 to 19% in 2002. The resistance rates for strains of Klebsiella spp isolated in 2002 (22% to amoxicillin + clavulanic acid, 35 % to trimethoprim, 17% to ciprofloxacin, 25% to cephalexin and 22% to gentamicin) were higher than those reported in 1999 (12%, 24%, 11%, 9%, and 2%) respectively. The resistant rate for isolates of Pseudomonas spp in 2002 against ceftazidime, ciprofloxacin and gentamicin (15%, 33% and 33% respectively) were higher than the (10%, 2% and 7%) reported in 1999. The resistant rate of Proteus spp to ciprofloxacin (26%) in 2002 was higher than the (8%) reported in 1999.
| Discussion|| |
This study addresses the antimicrobial susceptibility patterns of bacterial isolates from patients who submitted urine for culture at a general hospital. This study does not cover many outpatients with UTI who were treated empirically.  Therefore, the microbial susceptibilities implicated reflect most but not all the cases.
The prevalence of antimicrobial resistance among microorganisms that cause UTI is increasing worldwide and is a major factor in selecting antibiotics for treatment. In the present study, the most frequently isolated Gram-negative organism, both in outpatients and inpatients, was E. coli.
There are local variations in the antimicrobial susceptibility among urinary pathogens in different hospitals. In a recent study, Huda et al  reported their experience from a nearby hospital in the same region; the resistance rate of E. coli to ampicillin was similar to ours. However, their E. coli resistance rate that included amoxicillin-clavulanate (19%), nitrofurantoin (13%) and norfloxacin (12%) was different from ours, which were amoxicillin clavulanate (36%), ciprofloxacin (34%) and nitrofurantoin (5%). Moreover, in a study by Ahmed et al  from a central region of Saudi Arabia, 86% of the E. coli isolated from urine was resistant to ampicillin.
The resistance rates for strains of E. coli iso lated from inpatients were higher than those from outpatients. Nitrofurantoin showed the lowest resistance rate for E. coli and amoxicillin the highest. Among the Gram-negative isolates of the Enterobacteriaceae group, Proteus spp showed the highest resistance to trimethoprim. The high rate of resistance to amoxicillin and trimethoprim renders these antimicrobial drugs inappropriate for empirical therapy.
Seven percent of the E. coli isolates were multidrug resistant; more in the inpatients than the outpatients, to drugs such as amoxicillin, trimethoprim and either ciprofloxacin, gentamicin or both. In a previous study from this hospital, the E. coli isolated from blood cultures showed high rates of resistance to amoxicillin, amoxicillin-clavulanate and ciprofloxacin.  The resistance rate to ciprofloxacin among the isolates of E. coli, Klebsiella spp, Proteus spp and Pseudomonas spp was higher in 2002 than that reported in 1999.
Among the Gram-negative isolates, Pseudomonas and Acinetobacter species are known to be associated with hospital infections. , Acinetobacter spp showed the highest rate of resistance to ciprofloxacin and gentamicin, while Pseudomonas spp isolates were resistant to ceftazidime and gentamicin.
Organisms that produce ESBL have important therapeutic implications as they show resistance to a variety of antimicrobial agents, including third-generation cephalosporins, broad-spectrum penicillins, and monobactams.  They show variable susceptibility rates for fluoroquinolones, aminoglycosides, and fourth-generation cephalosporins.  The majority of ESBL producing organisms are susceptible to carbapenems.  As in our study, Allison et al  have shown a high susceptibility rates of ESBL-producing organisms to imipenem and amikacin.
Although the antimicrobial resistance of urinary isolates from hospitalised patients was more than that of outpatients, there was noticeable antibiotic resistance among out patient isolates, reflecting the problem of antimicrobial resistance in the community at large.
The emergence and spread of resistance can be reduced through appropriate or careful use of antimicrobial drugs and increasing awareness among the population to the hazards of inappropriate antimicrobial use through public health education campaign. 
Surveillance programs of antimicrobial drug resistance are necessary both locally and nationally. Antimicrobial susceptibility surveys from various hospitals allow comparisons between resistance rates at the national level. Collectively, antimicrobial susceptibility computerized data derived from clinical micro biology laboratories all over Saudi Arabia can be used for reliable and rapid detection of antimicrobial resistance.
| References|| |
|1.||Neu HC. The crisis in antibiotic resistance. Science 1992; 257:1064-73. [PUBMED] [FULLTEXT]|
|2.||Gold HS, Moellering RC. Antimicrobial drug resistance.N Engl J Med 1996; 335:1445-53. [PUBMED] [FULLTEXT]|
|3.||Kunin CM. Resistance to antimicrobial drugs a worldwide calamity. Ann Intern Med 1993;118:557-61. [PUBMED] [FULLTEXT]|
|4.||Tolmasky ME, Chamorro RM, Crosa JH, Marini PM. Transposon-mediated amikacin resistance in Klebsiella pneumoniae. Antimicrob Agents Chemother 1988;32:1416-20. |
|5.||Aguiar JM, Chacon J, Canton R, Baquero F. The emergence of highly fluoroquinoloneresistant Escherichia coli in community acquired urinary tract infections. J Antimicrob Chemother 1992;29:349-50. [PUBMED] [FULLTEXT]|
|6.||Cowan SF, Steel KJ. Manual for identification of medical bacteria. 3 rd Ed. Cambridge: Cambridge University Press, 1993;140-143. |
|7.||Hawkey PM, Lewis DA. Medical Bacteriology: a practical approach. Oxford University Press.1989;170-8. |
|8.||National Committee for Clinical Laboratory Standards. 1999. Performance standards for antimicrobial susceptibility testing. NCCLS approved standard M100-S9. National Committee for Clinical Laboratory Standards, Wayne, PA. |
|9.||Carlson KJ, Mulley AG. Management of acute dysuria. A decision analysis model of alternative strategies. Ann Intern Med 1985; 102:244-9. |
|10.||Huda AB, Ibrahiem MS. Antimicrobial resistance among pathogens cCausing acute uncomplicated UTIs. Infect Med 2001;18(7):358-62. |
|11.||Ahmad S, Ahmad F. Urinary tract infection at a specialist hospital in Saudi Arabia. Banglad Med Res Counc Bull 1995;21(3):95-8. |
|12.||Kader A A, Nassimuzzaman M, Dass S M. Antimicrobial resistance pattern of microorganisms isolated from blood cultures In a Saudi Arabian hospital. BMJ ME 2000;7:6-7. |
|13.||Goetz A, Yu VL. The intensive care unit: the hottest zone. Curr Opin Infec Dis 1997;10:319-23. |
|14.||Hilf M, Yu VL, Sharp J, et al. Antibiotic therapy for Pseudomonas aeruginosa bacteremia: outcome correlations in a prospective study of 200 patients. Am J Med 1989;87:540-6. |
|15.||Rice LB. Successful interventions for gramnegative resistance to extended-spectrum beta- lactam antibiotics. Pharmacotherapy 1999;19(8 pt 2):S120-8. |
|16.||Patterson JE, Hardin TC, Kelly C, et al. Association of antibiotic utilization measures and control of multiple drug resistance in extended-spectrum B-lactamase-producing (ESBL) Klebsiella pneumoniae. Presented at the 36th annual meeting of the Infectious Disease Society of America, Denver, CO, November 12-15, 1998. |
|17.||Allison EE, Melinda MN, David TB, John PQ, Susan LP,. Extended-spectrum beta-lactamases: frequency, risk factors, and outcomes. Pharmacotherapy 2002;22(1):14-20. |
|18.||American Society for Microbiology: Report of the ASM Task Force on Antibiotic Resistance. Washington, DC, 1994. |
Abdulrahman Abdulla Kader
Department of Clinical Microbiology, Almana General Hospital, P.O.Box 1364, Alkhobar 31952
[Table - 1], [Table - 2], [Table - 3]