Urinary tract infections (UTIs) are among the most commonly encountered community-acquired infections that mandate empirical antimicrobial therapy. This has contributed to the worldwide increase of antibacterial resistance within Enterobacteriaceae, specifically the main uropathogen Escherichia coli (E. coli). Such spread of antibiotic-resistant uropathogens has limited the use of most of the oral front-line antibiotics as empirical therapeutic options for UTI.[2,3,4] The rate of multidrug resistance among uropathogenic E. coli (UPEC) isolates shows wide variabilities across different geographic regions and is of particular concern in developing countries where the capacity for regular resistance surveillance is limited and over-the-counter drug purchase (including antibiotics) is rampant in the community.[6,7] Further, things are made worse by the use of antibiotics in food industry. The study was undertaken to find out the microbiological profile of UTI in the Kingdom of Bahrain and the pattern of antibiotic sensitivity, to guide for the empirical therapy while awaiting culture sensitivity results.
This is a single-center retrospective study conducted in Bahrain Specialist Hospital, a tertiary care center from the Kingdom of Bahrain. The record of all the urine cultures done from November 2011 until December 2020 was obtained from the hospital database and analyzed. The study was approved by the hospital ethics committee.
Continuous variables are presented as mean ± standard deviation. The Chi-square test is used to compare categorical variables. Mann–Whitney U-test is used to compare non-parametric continuous variables. Statistical analysis was performed using IBM SPSS Statistics for Windows version 25.0 (IBM Corp., Armonk, NY, USA).
A total of 28,082 urine samples were analyzed during the study period. Four thousand and eight hundred forty-nine (17.3%) samples showed the growth of organisms. One hundred and thirty-four out of 4849 (2.8%) showed growth of multiple organisms, concerning for contamination and were excluded from the analysis. Women and men accounted for 3821 (81%) and 894 (19%) (Ratio-3.7:1) cases, respectively. Most of the patients were in the age group of 20–40 years, accounting for 1872 (39.7%) of all cases. The mean age for men and women was 53.84. ± 25.85 and 43.41 ± 23.89 years respectively (P <0.001). Most involved men were in the age group of 60–80 years and women in the age group of 20–40 years. Gram-negative bacilli accounted for 4118/4715 (87.3%) of all infections. Gram-positive cocci and fungi accounted for 564 (11.9 %) and 33 (0.7%) of all cases, respectively. In men and women, Gram-negative infections accounted for 81.8% (724) and 89.3% (3393), respectively. E. coli was the most common organism grown, accounting for 2916 (61.8%) of all cases. Extended-spectrum beta-lactamase (ESBL) E. coli accounted for 30.2% of all E. coli. Klebsiella species were the second most common Gram-negative bacilli grown, accounting for 586 (12.4%) of all cases. ESBL Klebsiella pneumoniae accounted for 130 (22.2%) of all Klebsiella species grown. Overall, ESBL organisms accounted for 974 (20.6% of all cases). Pseudomonas species and Acinetobacter baumannii were the most common Gram-negative bacilli grown from the nonfermenters group accounting for 77.2% and 17.9% of the nonfermenters group and 173 (3.7%) and 40 (0.8%) of all cases, respectively. Enterococcus faecalis followed by Group B streptococcus, and Staphylococcus saprophyticus were the most common Gram-positive cocci cultured, accounting for 323 (57.3%), 74 (13.1%), and 36 (6.4%) of all Gram-positive cocci cultured, respectively. Gram-positive infections were significantly higher in men (P <0.001). ESBL K. pneumoniae, Pseudomonas aeruginosa, and E. faecalis was present in 4.8%, 9.7%, and 10.5% of inpatients as against 2.5%, 2.4%, and 6.0%, respectively of outpatients (P <0.001). P. aeruginosa was found in 8.2% and 2.6% of females and males, respectively; (P <0.001). E. coli was resistant to cotrimoxazole, ciprofloxacin, and levofloxacin in 28%, 17.3%, and 18.1%, respectively. ESBL E. coli was resistant to amoxicillin-clavulanate, cotrimoxazole, ciprofloxacin, and levofloxacin 73.8%, 62.3%, 62.4%, and 58.4%, respectively. K. pneumoniae was sensitive to amoxicillin-clavulanate, cefixime, cefuroxime, septran, ceftriaxone, ceftazidime, piperacillin-tazobactam, ciprofloxacin, levofloxacin, amikacin, meropenem and imipenem in 87.8%, 94.6%, 92.3%, 88%, 95.9%, 95.9%, 96.8%, 92%, 90.6%, 98.2%, 98%, and 99.5% respectively. ESBL K. pneumoniae was resistant to amoxicillin-clavulanate, cotrimoxazole, ciprofloxacin, and levofloxacin in 68.2%, 62.6%, 55.7%, and 41.8%, respectively. Enterococcus was sensitive to penicillin, ampicillin, amoxicillin-clavulanate, vancomycin, and imipenem in 91.4%, 90.1%, 96.3%, 99.4%, and 96.7%, respectively. Results are summarized in Tables 12-3 and Figures 123-4.
UTI is one of the leading causes of infection in the community. In our study, out of 28,082 samples, 4849 (17.3%) samples showed the growth of pathogenic organisms. Similar results were reported by Mohammed et al in a study from Libya. Women constituted 81% of all cases, consistent with several other studies,[9,10] which demonstrated a higher incidence of UTI in women. This is attributed to the short urethra that allows easy access to bacteria from the perianal region. UTI was most common in the 20–40 years of age group. This is consistent with a study from Yadav et al, which showed the highest risk of UTI in the sexually active group. The mean age of UTI for men was significantly higher, with men involved predominantly in the age group of 60–80 years. This is attributed to benign prostatic hypertrophy, which resulting voiding difficulties and urine stasis. Gram-negative organisms accounted for 87.3% of all cases. E. coli was the most common organism cultured in (61.8%) of all cases. E. coli was the most common organism in both men and women and outpatients and inpatients. The prevalence of E. coli in other studies ranges from 48% to 65%.Klebsiella species were the second-most common Gram-negative bacilli grown, accounting for 586 (12.4%) of all cases and this is similar to other reports (8%–26%). ESBL E. coli accounted for 30.2% of all E. coli. This is similar to 27.4% in another study from Bahrain. ESBL K. pneumoniae accounted for 130 (22.2%) of all Klebsiella. The Kingdom of Saudi Arabia reported a rate of 27%–33% of ESBL production among their community-onset UPEC,[15,16] while in Qatar, Khan et al reported the occurrence of ESBL-resistant isolates among 34% of E coli. Such variability of ESBL production rate among UPEC was mostly explained by the difference in the practice of antimicrobial use among human as well as animal sectors. The emergence of drug-resistant E. coli is becoming a global concern, and infections caused by these organisms represent a major challenge to clinicians when treating community-onset UTI. ESBL K. pneumoniae, P. aeruginosa, and E. faecalis were present in 4.8%, 9.7%, and 10.5% of inpatients as against 2.5%, 2.4%, and 6.0%, respectively in outpatients. The difference was statistically significant. This suggests severe clinical manifestations mandating admission in patients with these infections. P. aeruginosa was significantly found to be higher in females as compared to men. There was no difference in the incidence of ESBL E. coli and ESBL K. pneumoniae across the gender.
There was a significant difference in the incidence of ESBL E. coli between inpatients and outpatients, with more cases in outpatient than inpatient setting. This suggests a high incidence of ESBL E. coli in the community. An antibiogram of non-ESBL Gram-negative bacteria revealed 28% and 23.9% resistance of E. coli and proteus to cotrimaxole, making it unsuitable for empirical treatment of UTI. Non-ESBL E. coli and P. aeruginosa were resistant to ciprofloxacin in 17.3% and 19.2% respectively. Resistance to levofloxacin was seen in 17.1% and 19.6% of non-ESBL E. coli and P. aeruginosa, respectively. Although it is not clear that at what level of resistance should quinolones be avoided, it is preferable to avoid quinolones as a favored choice of empirical antibiotics in our population. ESBL E. coli was sensitive to piperacillin-tazobactam, amikacin, meropenem, and imipenem in 93.1%, 96.4%, 98.9%, and 99.1%, respectively. ESBL E. coli was resistant to amoxicillin-clavulanate, cotrimoxazole, ciprofloxacin, and levofloxacin in 73.8%, 62.3%, 62.4%, and 58.4%, respectively. ESBL K. pneumoniae was resistant to amoxicillin-clavulanate, cotrimoxazole, ciprofloxacin, and levofloxacin in 68.2%, 62.6%, 55.7%, and 41.7%, respectively. This is consistent with other studies which show the co-resistance of ESBL-producing organisms to quinolones and cotrimoxazole.[20,21] Antibiogram was concerning for P. aeruginosa with resistance to ceftazidime, ciprofloxacin, levofloxacin, meropenem, and imipenem in 16.4%, 19.3%, 19.6%, 16%, and 15.9% isolates respectively. Until recently, carbapenems were almost uniformly active against resistant Gramnegative organisms, but some strains have now developed very effective ways to deal with the carbapenems. There are various mechanisms by which these organisms achieve such a feat, by producing beta-lactamases that destroy the antibiotics, by blocking the entry of these antibiotics, or by efflux pumps that actively pump out these antibiotics. Enterococcus was sensitive to all primary enterococcal drugs. The growing resistance pattern suggests that antibiotics should be used responsibly and appropriately. Antibiotic stewardship is the need of an hour.
This study has certain limitations. It is a retrospective study and the clinical details of the patients, including the history of comorbidities in the form of diabetes mellitus, hypertension, stroke, bedridden status, presence of chronic kidney disease, presence or absence of indwelling catheters, obstruction, prior antibiotic exposure, etc., are not known. It is a single-center study involving patients who attended our hospital. This might not reflect the microbiological spectrum and antibiogram of the entire Bahraini community. Nitrofurantoin which is active again ESBL gram-negative organisms in multiple studies, has not been tested in our isolates. Nitrofurantoin might still be the preferred empirical oral therapy for lower UTI. A multicenter study in Bahrain would be required to get better knowledge about microbiological spectrum and antibiogram.
Gram-negative organisms are the predominant cause of UTI in both genders. E. coli is the most common organism causing UTIs. E. faecalis is the most common Gram-positive organism causing UTI in our cohort. There is a high incidence of ESBL E. coli and K. pneumoniae in our community. There is alarmingly increased resistance of P. aeruginosa to carbapenems which will be a concern in the future. Cotrimoxazole should not be used, and quinolones should be avoided for empirical treatment of UTI. Amoxicillin-clavulanate, cefixime, and cefuroxime are suitable oral antibiotics for empirical treatment if suspicion for ESBL organisms is low. For sick patients requiring hospitalization, piperacillin-tazobactam, aminoglycosides, and carbapenems should be considered for empirical treatment. Antibiotic stewardship is the need of an hour.
Conflict of interest:
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