Abstract
The aim of this study was to obtain data on susceptibility patterns of pathogens responsible for both community and hospital urinary tract infections (UTIs); and analyzed risk factors for infection caused by ciprofloxacin-resistant Escherichia coli and extended-spectrum β-lactamace (ESBL)-producing strains in Rwanda. Of 1,012 urine cultures prospectively studied, a total of 196 (19.3%) yielded significant growth of a single organism. The most common isolate (60.7%) was Escherichia coli. The antibiotics commonly used in UTIs are less effective except Fosfomycin-trometamol and imipinem. The use of ciprofloxacin in the previous 6 months (odds ratio [OR] = 7.59 [1.75–32.74]), use of other antibiotics in the previous 6 months (OR = 1.02 [1.02–2.34]), and production of ESBL (OR = 19.32 [2.62–142.16]) were found to be associated with ciprofloxacin resistance among the E. coli isolates. Risk factors for ESBL positivity were the use of ciprofloxacin and third-generation cephalosporin in the preceding 6 months (OR = 3.05 [1.42–6.58] and OR = 9.78 [2.71–35.25], respectively); and being an inpatient (OR = 2.27 [1.79–2.89]). Fosfomycin-trometamol could be included as a reasonable alternative for the therapy of uncomplicated UTI in Rwanda.
Introduction
Urinary tract infections (UTIs) are among the most common bacterial infections both in the community and hospital setting. In the majority of cases, antibiotics are given empirically before the final bacteriology results are available. Therefore, area-specific monitoring studies to document the microorganisms causing UTIs and their antimicrobial susceptibility is mandatory for helping the selection of an effective empirical treatment.1 Rwanda is among the poorest countries in the world and most people can only afford generic drugs. The most commonly used antibiotics include amoxicillin, nitrofurantoin, and trimethoprim/sulfamethoxazole, and more recently ciprofloxacin was approved to treat UTIs and became available at a low price.2,3
An increasing rate of antibiotic resistance among pathogens responsible for UTIs has caused growing concern worldwide. A number of studies in Europe and in the United States showed a steady increase of the resistance rate of uropathogens to commonly prescribed antibiotics (amoxicillin, trimethoprim-sulfamethoxazole), reducing therapeutic possibilities.4–6 In some countries high levels of resistance to ciprofloxacin, one of the current drugs of choice for empiric therapy has been reported in recent years.7–9
Mechanisms of resistance against β-lactam antibiotics in gram-negative bacilli include production of TEM- and AmpC β-lactamases, porin deficiency, and efflux mechanisms and, more recently, extended-spectrum β-lactamace (ESBL). The ESBLs are defined as β-lactamases capable of hydrolyzing oxymino-cephalosporins and are inhibited by β-lactamase inhibitors.10 Microorganisms responsible for UTIs such as Escherichia coli and Klebsiella spp. remain the major ESBL-producing organisms isolated worldwide, but these enzymes have also been identified in several other members of the Enterobacteriaceae family and in certain non-fermenters.11
Levels of antibiotic consumption, including the use of fluoroquinolones, show great variations.9 As the emergence of resistance is associated with high antibiotic consumption,12 it is not surprising that resistance to ciprofloxacin in E. coli shows great geographical variations as well, reaching high levels in some developing countries.13 In addition to monitoring of resistance patterns, identification of risk factors for resistance may contribute to improved empirical treatment. No data on antimicrobial resistance and the prevalence of ESBL producers in UTIs in Rwanda have been published to date.
The aim of this prospective study was to obtain data on susceptibility patterns of pathogens responsible for both community and hospital UTIs in Rwanda to antimicrobials agents currently used to treat UTIs. In addition, we analyzed risk factors for infection caused by ciprofloxacin-resistant E. coli and, for the first time, the prevalence and risk factors of ESBL-producing strains in Rwanda are described in this study.
Materials and Methods
Study population and bacterial isolates.
This prospective study was conducted in both outpatients and inpatients with UTIs at the two largest tertiary teaching hospitals after obtaining approval from the Research Ethics Committee of the Faculty of Medicine (FoMREC). These hospitals were selected because they have a large number of patients and represent patients from large geographical areas. Butare University Hospital, located in the south province of Rwanda, is a 418-bed tertiary-care, teaching hospital with 7,595 patient admissions and almost 33,304 outpatient clinic and emergency room visits annually. Kigali University Hospital, located in the center and serving as a reference center for the eastern, north, and western regions in Rwanda, is a 513-bed tertiary-care with 11,602 patient admissions and almost 105,773 outpatient clinic and emergency room visits annually. Between June and November 2009 a total of 1,012 urine cultures were analyzed in the clinical microbiology laboratories of the two participating hospitals. For each patient, data were prospectively collected through an interview with the patient or the patient's family, and their medical records were checked when necessary. Risk factors for ciprofloxacin resistance were as follows: age, sex, presence of a urinary catheter; prior UTI, prior urinary catheter, hospitalization during the previous year; and antibiotic exposure during the preceding 6 months. Each specimen was cultured using a 0.001 mL calibrated loop to inoculate blood agar and MacConkey agar plates, incubated at 37°C for 18–24 hours and the number of colonies was counted. Significant bacteriuria was defined as greater than 105 colony forming units/mL of a single pathogen. Isolates were identified biochemically using Triple Sugar Iron agar, Indol, Methyl Red, Voges Proskauer, and Citrate according to standard microbiologic procedures.14
Antimicrobial susceptibility testing.
Antimicrobial susceptibility testing was performed using a disk diffusion method according to the Clinical and Laboratory Standards Institute (CLSI) guidelines.14 Antibiotic disks were obtained from Oxoid (Oxoid Ltd., Cambridge, UK): amoxicillin, amoxicillin-clavulanic acid, ceftriaxone, ceftazidime, imipenem, trimethoprim-sulfamethoxazole, trimethoprim, gentamicin, amikacin, netilmicin, nalidix acid, ciprofloxacin, norfloxacin, ofloxacin, nitrofurantoin, fosfomycin-trometamol, cefalotin, and piperacillin. Quality control was performed once weekly using test strains E. coli ATCC 25 922, Staphylococcus aureus ATCC 25923, and Pseudomonas aeruginosa ATCC 27853.
All isolates were tested for ESBL production by the double-disk synergy test on Mueller-Hinton agar (Sigma Aldrich, St. Louis, MO) using ceftriaxone and ceftazidime placed at a distance of 15–20 mm apart from a disk containing amoxicillin plus clavulanic acid. A clear-cut extension of the inhibition zone around either the ceftazidime or ceftriaxone disk toward the clavulanic acid-containing disk (also called “ghost zone”) was interpreted as positive for ESBL production.14
Statistical analysis.
Data processing and statistical analysis were performed using SPSS software (version 16.0, SPSS, Inc., Chicago, IL). Differences in group proportions for categorical variables were assessed using χ2 or Fisher's exact test. Logistic regression analysis was performed to identify risk factors for acquisition of ciprofloxacin-resistant E. coli and ESBL production. A P value < 0.05 was considered statistically significant.
Results
A total of 1,012 clean-catch urine samples were processed during a 6-month study period (1 June 2009 until 30 November 2009), of which 196 (19.3%) yielded significant growth of a single organism and were included in this study. The mean age of the study population was 42 with a range of 18–90, and 71.9% of the patients were female. Of the 196 patients, 102 were outpatients and 94 were hospitalized patients.
The distribution of uropathogens for outpatients and inpatients is shown in Table 1. Escherichia coli was the most common uropathogen, accounting for infections in 119 (60.7%) of the 196 patients; and occurred significantly more frequently in urines from outpatients (70.6%) than from inpatients (50%). The proportion of Klebsiella sp., Proteus sp., and Citrobacter sp. was relatively higher in inpatients (24.5%, 6.5%, 7.4%, and 6.4%) than in outpatients (13.7%, 5.9%, 2, and 1%). Pseudomonas aeruginosa was only isolated from inpatients (3.2%). Gram-positive microorganism grew in only 3.1% of the positive cultures and were no longer included in the study.
Table 1.
Bacterial isolates from urinary tract infections, in in- and outpatients
| Organisms | No. of isolates (%) | Total | |
|---|---|---|---|
| Outpatients | Inpatients | ||
| Escherichia coli | 72 (70.6) | 47 (50) | 119 (60.7) |
| Klebsiella spp. | 14 (13.7) | 23 (24.5) | 37 (18.9) |
| Proteus spp. | 6 (5.9) | 6 (6.4) | 12 (6.1) |
| Enterobacter spp. | 2 (2) | 7 (7.4) | 9 (4.6) |
| Citrobacter spp. | 1 (1) | 6 (6.4) | 7 (3.6) |
| Acinetobacter spp. | 2 (2) | 1 (1.1) | 3 (1.5) |
| Pseudomonas aeruginosa | 0 (0) | 3 (3.2) | 3 (1.5) |
| Gram-positive | 5 (4.9) | 1 (1.1) | 6 (3.1) |
| Total | 102 (52) | 94 (48) | 196 (100) |
The antimicrobial susceptibility results of the most frequent uropathogens in the two hospitals are summarized in the Table 2. In general, isolates from inpatients were significantly more resistant to antimicrobials than outpatients. One hundred seventy-seven (90.3%) of isolates were susceptible to fosfomycin, and 99.5% of isolates were susceptible to imipinem, which were the most effective drugs. Conversely, high resistance rates were detected among isolates from inpatients of Butare and Kigali university hospitals for amoxicillin (92.9% versus 100%), amoxicillin-clavulanic acid (50% versus 76.3%), trimethoprim-sulfamethoxazole (93.8% versus 71.4%), ciprofloxacin (61.3% versus 35.7%), ceftriaxone (57.1% versus 53.8%), ceftazidime (50% versus 50%), nalidixic acid (64.3% versus 77.5%), and nitrofuratoin (78.6% versus 48.8%). For outpatients the corresponding resistance rates were 73.8% versus 85%, 40.5% versus 51.7%, 71.4% versus 78.3%, 21.4% versus 30%, 9.5% versus 13.3%, 11.9% versus 8.3%, 45.2% versus 41.6%, and 38.1% versus 36.7%. Strains of E. coli, isolated from inpatients were more resistant to ciprofloxacin and to third-generation cephalosporin when compared with E. coli from outpatient strains and to other species from inpatients as well (Table 3).
Table 2.
Resistance rates to antimicrobial agents tested, in- and outpatients in the two hospitals
| Antimicrobial agent | Overall (%) | Butare University Hospital | Kigali University Hospital | ||
|---|---|---|---|---|---|
| Outpatients (%) | Inpatients (%) | Outpatients (%) | Inpatients (%) | ||
| N = 196 | N = 42 | N = 14 | N = 60 | N = 80 | |
| Amoxicillin | 175 (89.3) | 31 (73.8) | 13 (92.9) | 51 (85) | 80 (73.8) |
| Amoxicillin/clavulanic acid | 116 (59.2) | 17 (40.5) | 8 (50) | 31 (51.7) | 61 (76.3) |
| Cefalotin | 158 (80.6) | 7 (16.7) | 4 (28.6) | 18 (30) | 42 (52.5) |
| Ceftriaxone | 63 (32.1) | 4 (9.5) | 8 (57.1) | 8 (13.3) | 43 (53.8) |
| Ceftazidime | 57 (29.1) | 5 (11.9) | 7 (50) | 5 (8.3) | 40 (50) |
| Ciprofloxacin | 81 (41.3) | 9 (21.1) | 5 (35.7) | 18 (30) | 49 (61.3) |
| Norfloxacin | 78 (39.8) | 11 (26.2) | 6 (42.9) | 16 (26.7) | 45 (56.3) |
| Ofloxacin | 71 (36.2) | 7 (16.7) | 4 (28.6) | 18 (30) | 42 (52.5) |
| Nalidixic acid* | 86 (56.2) | 19 (45.2) | 9 (64.3) | 20 (41.6) | 38 (77.5) |
| Nitrofurantoin | 88 (44.9) | 16 (38.1) | 11 (78.6) | 22 (36.7) | 39 (48.8) |
| Trimethopin/sulfamethoxazole | 162 (82.7) | 30 (71.4) | 10 (71.4) | 47 (78.3) | 75 (93.8) |
| Gentamicin | 91 (46.4) | 12 (28.6) | 7 (50) | 21 (35) | 51 (63.8) |
| Amikacin | 81 (41.3) | 20 (47.6) | 3 (21,4) | 20 (33.3) | 38 (47.5) |
| Piperacillin | 152 (77.6) | 26 (61.9) | 11 (78,6) | 39 (65) | 76 (95) |
| Fosfomycin/trometamol | 19 (9.7) | 3 (7.1) | 5 (35.7) | 5 (8.3) | 6 (7.5) |
| Imipinem | 1 (0.5) | 0 (0) | 0 (0) | 0 (0) | 1 (1.3) |
Overall N = 153, outpatient N = 48, and inpatient N = 49 in Kigali University Hospital.
Table 3.
Antimicrobial resistance rates in Escherichia coli and other microorganisms, in in- and outpatients
| Antimicrobial agent | % Resistance to antibiotic E. coli | Other microorganisms | ||
|---|---|---|---|---|
| Outpatients | Inpatients | Outpatients | Inpatients | |
| Amoxicillin | 86 | 100 | 66.7 | 97.9 |
| Amoxicillin/clavulanic acid | 50 | 70.2 | 40 | 74 |
| Cefalotin | 79.2 | 91.5 | 50 | 91.5 |
| Ceftriaxone | 6.9 | 38.3 | 23.3 | 70 |
| Ceftazidime | 4.2 | 31.9 | 23.3 | 68.1 |
| Ciprofloxacin | 31.9 | 57.4 | 13.3 | 57.4 |
| Norfloxacin | 30.6 | 57.4 | 16.7 | 51.1 |
| Ofloxacin | 30 | 57,4 | 10 | 40 |
| Nalidixic acid | 45.1 | 77.4 | 39.3 | 78.1 |
| Nitrofurantoin | 26.4 | 29.8 | 63.3 | 76.6 |
| Trimethopin/sulfamethoxazole | 80.6 | 95.7 | 63.3 | 85.1 |
| Gentamicin | 36.1 | 46.8 | 23.3 | 76.6 |
| Amikacin | 45.8 | 46.8 | 23.3 | 40.4 |
| Piperacillin | 73.6 | 97.9 | 40 | 87.2 |
| Fosfomycin/trometamol | 6.9 | 6.4 | 10 | 17 |
| Imipinem | 0 | 0 | 0 | 2.1 |
The ESBLs were detected in 38.3% (36 of 94) of the strains from inpatients (13.8% of E. coli) and 5.9% (6 of 102) of all strains from outpatients (1.9% of E. coli).
The univariate and multivariate analysis of risk factors for ciprofloxacin-resistant E. coli are shown in Table 4. In univariate analysis, use of ciprofloxacin and other antibiotics in the previous 6 months, history of UTI in the past 12 months, presence of current or previous urinary catheter, being an inpatient or previous hospitalization, and ESBL production were found to be significantly associated with ciprofloxacin resistance among E. coli isolates. However, in a forward stepwise multivariate model, only the use of ciprofloxacin in the previous 6 months (odds ratio [OR] = 7.59; 95% confidence interval [CI] = 1.75–32.74; P < 0.001), but also the use of other antibiotics in the previous 6 months (OR = 1.02; 95% CI = 1.02–2.34; P = 0.005), and production of ESBL (OR = 19.32; 95% CI = 2.62–142.16; P < 0.001) were found to be associated with ciprofloxacin resistance among the E. coli isolates.
Table 4.
Univariate and multivariate analysis of clinical and demographic parameters for resistance to ciprofloxacin in Escherichia coli isolates*
| Risk factors | Total, N = 119 | Ciprofloxacin resistance | P value |
|---|---|---|---|
| Univariate analysis | |||
| Age over 50 | 32 | 16 (50) | 0.194 |
| Male gender | 27 | 3 (11) | 0.972 |
| Diabetes mellitus | 10 | 0 (0) | 0.247 |
| Pregnancy | 10 | 1 (10) | 0.834 |
| Cardiovascular disease | 6 | 0 (0) | 0.379 |
| Pulmonary disease | 6 | 1 (14) | 0.769 |
| Oncological disease | 8 | 2 (25) | 0.186 |
| Benign prostatic hypertrophy | 2 | 2 (100) | < 0.001 |
| Hospitalized (inpatient) | 47 | 27 (57) | 0.005 |
| Hospitalization in last 12 months | 39 | 22 (56) | 0.022 |
| UTI in last 12 months | 21 | 13 (62) | 0.037 |
| Urinary catheter | 14 | 11 (78) | 0.004 |
| Urinary catheter in last 12 months | 19 | 13 (68) | 0.037 |
| Ciprofloxacin use in the previous 6 months | 13 | 11 (84) | 0.001 |
| Use of other antibiotics in the previous 6 months | 51 | 27 (53) | 0.028 |
| ESBL positive | 15 | 14 (93) | < 0.001 |
| Multivariant analysis | Odds ratio | Confidence interval | P value |
| Use other antibiotics in the previous 6 months | 1.02 | 1.02–2.344 | 0.005 |
| Ciprofloxacin use in the previous 6 months | 7.59 | 1.75–32.74 | < 0.001 |
| ESBL positive | 19.32 | 2.62–142.16 | < 0.001 |
UTI = urinary tract infection; ESBL = extended-spectrum β-lactamace.
The univariate and multivariate analysis of risk factors for ESBL positivity are presented in Table 5. In univariate analysis, previous hospitalization, prior or presence of urinary tract catheterization, use of ciprofloxacin, and third-generation cephalosporin in the preceding 6 months and being an inpatient were significantly associated with ESBL production. In multivariate only the use of ciprofloxacin and third-generation cephalosporin in the preceding 6 months (OR = 3.05; 95% CI = 1.42–6.58; P = 0.04 and OR = 9.78; 95% CI = 2.71–35.25; P = 0.01, respectively); and being an inpatient (OR = 2.27; 95% CI = 1.79–2.89; P < 0.001) were independently associated with ESBL production.
Table 5.
Univariate and multivariate analysis of risk factors for ESBL positivity in UTI isolates*
| Total, N = 196 | ESBL positivity, N = 42 (%) | P value | |
|---|---|---|---|
| Univariant analysis | |||
| Age over 50 | 56 | 14 (25) | 0.441 |
| Hospitalized (inpatient) | 94 | 36 (38) | < 0.001 |
| Hospitalization in the last 12 months | 70 | 26 (37) | < 0.001 |
| UTI in last 12 months | 37 | 10 (27) | 0.357 |
| Urinary catheter | 40 | 20 (50) | < 0.001 |
| Urinary catheter in last 12 months | 43 | 21 (49) | < 0.001 |
| Use of other Antibiotics in the previous 6 months | 88 | 22 (25) | 0.271 |
| Ciprofloxacin use in the previous 6 months | 22 | 10 (45) | 0.004 |
| Third-generation Cephalosporin use in the previous 6 months | 11 | 8 (73) | < 0.001 |
| Multivariant analysis | |||
| Ciprofloxacin use in the previous 6 months | 0.04 | ||
| Third-generation Cephalosporin use in the previous 6 months | 0.01 | ||
| Hospitalized (inpatient) | < 0.001 |
ESBL = extended-spectrum β-lactamace; UTI = urinary tract infection.
Discussion
Antimicrobial resistance of bacteria is considered an increasing global concern. The majority of UTIs are treated empirically, especially in developing countries where patients often cannot afford consulting a doctor or having laboratory tests done. Local susceptibility patterns of uropathogens should be available to prescribe appropriate antibiotics. To our knowledge, this is the first study on susceptibilities of bacteria causing UTI and the risk factors for resistance and ESBL positivity in Rwanda.
This study confirms that E. coli is still the most common uropathogen isolated from both in- and outpatients, but that various other bacteria cause infection, especially among inpatients (Table 1). These findings are in agreement with similar surveillance studies.15–18 Some studies show a decline of E. coli, being replaced by other members of the Enterobacteriaceae. Our hospitalized patients had fewer E. coli and more Klebsiella spp. The low percentage of E. coli among hospital isolates in our study corresponded to that obtained by other investigators.15,17
The UTIs are more frequent in women than in men, which corresponds to our findings because 71.9% of our patients were female.19
As can be expected, and as reported in other studies, the antimicrobial resistance of hospital isolates was higher than in outpatients.20,21 In our study, more than 70% of the outpatients isolate and more than 90% of the hospitalized isolates were resistant to Trimethoprim-sulfamethoxazole. Several other studies from the United States and worldwide indicate the emergence of trimethoprim-sulfamethoxazole resistance in a significant percentage (> 20%) of community-acquired UTI isolates.17,22 In a study of UTI from outpatients in Canada, Zhanel and others5 found resistance to amoxicillin and nitrofuratoin at rates of 41.0% and 0.1%, respectively. Corresponding average values in the two hospitals in our study were 79.4% and 37.4%. In this study, the higher proportion of outpatient and inpatient E. coli strains resistant to amoxicillin (86% versus 100%), nitrofurantoin (26.4% versus 29.8%), nalidixic acid (45.1% versus 77.4%), amoxicillin-clavulanic acid (56% versus 70.2%), and gentamycin (36.1% versus 46.8%%), is similar to what was reported by Aboderin and coworkers.23
We documented a remarkably high resistance to ciprofloxacin, which is of great concern because fluoroquinolones are the drugs of choice for first-line empiric treatment of both community and hospital acquired UTI in settings where resistance to trimethoprim/sulfamethoxazole exceeds 20%, and they have become more commonly prescribed as first-line antibiotic therapy in the last few years.24,25 Resistance rates for ciprofloxacin against uncomplicated and complicated UTI strains were reported as 8.5% and 19.5%, respectively, by Alos and coworkers.7 Recently, Arslan and coworkers reported 17% and 38% resistance rates for the uncomplicated and complicated UTI strains, respectively.21 Our rates were found to be much higher: average of 25.7% for the outpatient UTI strains and 48.5% for the inpatient UTI strains for the two hospitals.
Resistance rates in isolates of outpatients were also higher compared with studies from other countries for the majority of antimicrobials except third-generation cephalosporin ceftriaxone and ceftazidime. However, the resistance to third-generation cephalosporins was significantly higher in strains from inpatients (Table 2). Randrianirina and coworkers16 have reported an increasing resistance rate to the third-generation cephalosporin in their study in patients 65 years of age. The findings of this study indicate that β-lactams, trimethoprim/sulfamethoxazole, nitrofurantoin, and ciprofloxacin should no longer be used as empirical treatments of UTI in Rwanda, because of their high rate of resistance. Alternatives must be recommended, especially for empirical treatments of uncomplicated UTI (cystitis) in outpatients.
Fosfomycin-trometamol and imipinem were found to be the most effective antimicrobials, 99% and 93% E. coli isolates tested being susceptible respectively. As a result, fosfomycin-trometamol and imipinem may be the drugs of choice for empirical therapy of UTIs based on the in vitro data. Previous studies have reported fosfomycin-trometamol resistance rates of 0.3% in 288 and no resistance in 100 E. coli strains.26 Ullah and coworkers27 in Pakistan have recorded 86.9% of isolates being susceptible to imipinem. Fosfomycin-trometamol has been recommended as a reliable empirical treatment of uncomplicated UTI because of its easy use (single dose), its good tolerance, and its efficacy.26,28 Unfortunately, this antibiotic is not yet available in Rwanda. The high susceptibility to imipenem observed in our study is a clear indication that carbapenem resistance is still almost absent in Enterobacteriaceae isolated from UTI in the region. This can be explained by the infrequent use of this antibiotic in the developing world because of its cost and limited availability.
In our study, > 50 years of age seems to be unrelated to ciprofloxacin resistance in E. coli strains by univariate analysis. Interestingly, in a recent study, Nicoletti and coworkers9 were not able to show a correlation between age (50 years and 65 years or older, respectively) and ciprofloxacin resistance. In contrast, several previous studies have identified > 50 years of age to be associated with high ciprofloxacin rates.7,21,29 Our failure to find this association could have been caused by a small number of patients in our study. In our multivariate model, we observed that ciprofloxacin and the use of other antibiotics in the previous 6 months are independent risk factors contributing to ciprofloxacin resistance, as previously reported in other studies.4,21,29,30
For the first time in our laboratory, we performed phenotypic confirmation tests for ESBL production. The prevalence of ESBLs both in outpatients and inpatients has been investigated and varies among countries in several studies.31,32 In all of these, E. coli and Klebsiella spp. accounted for the vast majority of isolates. Our study showed a higher percentage of ESBL positivity among E. coli isolates when compared with reports from Canada (0.26%), Europe (1.3%), and Tunisia (2.7%).33–35 In contrast, in agreement with our data, Russian, Cameroonian, and Korean studies revealed that overall prevalence of ESBLs among E. coli isolates was 15.8%, 14.3%, and 9.3%, respectively.36–38 Studies conducted by Akram and others17 showed a higher percentage, than our study, of E. coli producing ESBL. Prior antibiotics, especially ciprofloxacin, third-generation cephalosporins, and stay in hospital; major risk factors retained in our multivariate analysis, were also found to be independent risk factors for ESBL positivity in previous studies.39,40
In conclusion, Gram-negative organisms, especially E. coli were the most common organisms isolated. We found that antibiotics commonly used for the treatment of UTI in Rwanda are far from effective. The ESBL producers are, as in many countries, frequent in Enterobacteriaceae in Rwanda. On the basis of our findings, we suggest that an antimicrobial agent such as fosfomycin-trometamol could be alternative therapy for uncomplicated UTI, and should be introduced in the national guidelines. Antibiotics not tested in this study, such as tigecycline and temocillin (only parenteral available), should be investigated for their potential in the future. Urine culture and antimicrobial susceptibility testing are recommended in Rwanda for UTI patients. Further studies with a larger number of isolates involving a laboratory from a primary care setting in various part of the country are required. Moreover, this high resistance is probably of relevance for the treatment of other infections, and resistance in Gram-positive organisms should also be studied.
ACKNOWLEDGMENTS
We thank the staff in the Bacteriology unit at Kigali and Butare Teaching Hospitals for their technical assistance. In particular, we thank Carine Uwera, Innocent Nzabahimana, and Jean Baptiste Mugema for their excellent technical support in data collection and processing.
Disclaimer: This study was approved by the Research Ethics Committee of the Faculty of Medicine (code: 04/FoMREC/09).
Footnotes
Financial support: This study was financially supported by a PhD grant from the Ghent University, Ghent, Belgium through its VLIR (Flemish Interuniversity Council) own initiative project number VLIR-UOS ZEIN2007PR342-19878.
Disclosure: Part of this manuscript was presented at the 50th Interscience Conference on Antimicrobial Agents and Chemotherapy in Boston, MA in September 2010 (control/tracking number: 2010-A-1286-ASM-ICAAC).
Authors' addresses: Claude Mambo Muvunyi, Florence Masaisa, Claude Bayingana, Léon Mutesa, André Musemakweri, and Grégoire Muhirwa, Faculty of Medicine NUR, Huye/Rwanda, E-mails: cmuvunyi@nur.ac.rw, kabasius@yahoo.fr, cbayingana@nur.ac.rw, lmutesa@nur.ac.rw, amusemakweri@nur.ac.rw, and gmuhirwa@nur.ac.rw. Geert (W.) Claeys, Department of Clinical Chemistry, Microbiology and Immunology, Ghent University Hospital, De Pintelaan 185, Ghent, Belgium, E-mail: geert.claeys@ugent.be.
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