Background
Acute pyelonephritis (APN), an infectious disease of the renal parenchyma and pelvic region, is a significant and frequent cause of morbidity, resulting in more than 100,000 hospital admissions per year in the United States [
1,
2]. The most common pathogens in APN belong to the Enterobacteriaceae family, and
Escherichia coli is the causative pathogen in more than 80% of cases [
1]. Other microbes contributing to the pathogenesis of APN include
Proteus spp,
Klebsiella spp, and enterococci [
3]. Risk factors that predispose women to APN include diabetes mellitus (DM), incontinence, patient and family history of urinary tract infections (UTIs), and certain sexual behaviors [
4]. Although DM is a risk factor, it was previously reported that DM does not influence the isolation rates of different uropathogens or their patterns of susceptibility to antimicrobials [
5].
In general, CRF patients are known to be vulnerable to infection due to weakened immunity [
6]. But, few data are available on the role of CRF as a risk factor for the development of antimicrobial resistance of the uropathogens [
7]. For this reason, we have undertaken a study to evaluate the spectrum of etiologic agents and their profiles of antimicrobial resistance in a large series of non-CRF and CRF patients with community-acquired APN that presented as a positive urine culture.
Results
The characteristics of the 502 subjects enrolled in this study are shown in Table
1. The mean age was 61.7 (± 16.0) years, with 89.2% of the subjects being women and 20.1% being diabetic patients.
Table 1
Age-gender standardized baseline demographics and laboratory results according to eGFR
Age, years
| 59.0 ± 16.8 | 67.3 ± 12.4 | 0.0001 |
Genders, %
| | | 0.168 |
Males | 12.2 | 7.8 | |
Females | 87.8 | 92.2 | |
Diabetes, %
| 20.8 | 21.4 | 0.906 |
Measurements
| | | |
WBC, mm3
| 9,944 ± 5,630 | 11,882 ± 6,233 | 0.001 |
Hb, g/dL | 11.5 ± 1.9 | 11.1 ± 1.9 | 0.083 |
Platelet, mm3
| 226,232 ± 106,223 | 212,380 ± 112,614 | 0.182 |
BUN, IU/L | 12.4 ± 6.0 | 27.4 ± 14.4 | 0.0001 |
Creatinine, IU/L | 0.72 ± 0.15 | 1.62 ± 0.64 | 0.0001 |
eGFR, mL/min/1.73 m2
| 98 ± 32 | 39 ± 13 | 0.0001 |
Sodium, mEq/L | 136 ± 5 | 135 ± 6 | 0.157 |
Potassium, mEq/L | 3.8 ± 0.5 | 4.0 ± 0.7 | 0.003 |
Protein, g/dL | 6.6 ± 3.6 | 6.3 ± 0.9 | 0.334 |
Albumin, g/dL | 3.4 ± 0.6 | 3.2 ± 0.6 | 0.002 |
Total Bilirubin, mg/dL | 1.36 ± 2.10 | 1.65 ± 2.14 | 0.172 |
Direct Bilirubin, mg/dL | 0.74 ± 1.61 | 0.93 ± 1.50 | 0.233 |
AST, IU/L | 47.2 ± 76.9 | 72.4 ± 249.3 | 0.216 |
ALT, IU/L | 39.0 ± 71.6 | 37.2 ± 87.2 | 0.813 |
ALP, IU/L | 130.5 ± 130.3 | 124.7 ± 133.6 | 0.675 |
r-GTP, IU/L | 110.3 ± 202.9 | 82.9 ± 115.2 | 0.085 |
PT, second | 92.5 ± 21.4 | 84.2 ± 22.5 | 0.001 |
PT INR | 1.09 ± 0.29 | 1.19 ± 0.65 | 0.048 |
PTT, second | 37.8 ± 13.5 | 39.8 ± 10.9 | 0.133 |
CRP, mg/dL | 6.6 ± 7.4 | 8.8 ± 8.5 | 0.045 |
HS-CRP, mg/dL | 7.0 ± 7.8 | 11.0 ± 9.4 | 0.002 |
Total cholesterol, mg/dL | 163 ± 47 | 154 ± 49 | 0.180 |
HDL cholesterol, mg/dL | 41 ± 16 | 36 ± 17 | 0.032 |
LDL Cholesterol, mg/dL | 102 ± 40 | 85 ± 38 | 0.008 |
Triglycerides, mg/dL | 105 ± 60 | 131 ± 107 | 0.041 |
Chloride, mEq/L | 100 ± 5 | 101 ± 7 | 0.575 |
total CO2, mEq/L | 26.7 ± 4.8 | 22.7 ± 5.6 | 0.0001 |
ESR, mm/hour | 30.5 ± 23.7 | 36.2 ± 23.0 | 0.030 |
Urine RBC (0-4+) | 1.32 ± 2.22 | 1.36 ± 1.91 | 0.003 |
Urine protein (0-4+) | 0.65 ± 0.89 | 0.83 ± 1.00 | 0.0001 |
Urine WBC (0-4+) | 2.29 ± 2.62 | 2.99 ± 2.76 | 0.0001 |
The etiologic microorganisms of APN are shown in Table
2. The most common cause of APN was
E. coli (58.3%, 293 cases), followed by
K. pneumonia (12.7%, 64 cases),
Pseudomonas (4.1%, 21 cases), and
Enterococcus (2.9%, 15 cases).
Table 2
Etiologic Microorganisms of APN
E.coli
| 12 | 281 | 293 |
K.pneumoniae
| 8 | 56 | 64 |
Proteus
| 3 | 11 | 14 |
Pseudomonas
| 9 | 12 | 21 |
Enterococcus
| 2 | 13 | 15 |
G(+)
| 16 | 50 | 66 |
G(-)
| 4 | 25 | 29 |
Total
| 54 | 448 | 502 |
The antimicrobial sensitivity rates for
E. coli are shown in Table
3. The sensitivity rates were 100% for imipenem, 99.2% for amikacin, 90.8% for tobramycin, over 80% for third- and fourth-generation cephalosporin antibiotics, 71.7% for ciprofloxacin, and 61.4% for TMP-SMX. However, the sensitivity rates for gentamycin and ampicillin were low (42.9% and 39.4%, respectively).
Table 3
Antimicrobial Sensitivity Rate (%) for E.coli according to eGFR
Ampicillin
| 37.8 | 20.0 | 0.024 |
Cephalothin
| 45.5 | 36.0 | 0.428 |
Cefuroxime
| 76.9 | 69.4 | 0.320 |
Cefotaxime
| 82.0 | 76.5 | 0.413 |
Cefozolin
| 66.7 | 47.1 | 0.162 |
Ceftazidime
| 83.2 | 75.5 | 0.259 |
Cepefime
| 83.6 | 80.4 | 0.613 |
Imipenem
| 95.5 | 100 | 0.126 |
Gentamycin
| 71.9 | 51.9 | 0.016 |
Amikacin
| 96.3 | 90.0 | 0.112 |
Tobramycin
| 87.0 | 82.0 | 0.404 |
Ciprofloxacin
| 72.7 | 66.0 | 0.389 |
Trimethoprime-sulfomethoxazole
| 57.9 | 56.9 | 0.905 |
Age-gender standardized baseline demographics and laboratory results according to eGFR are shown in Table
1. The rates of diabetes in the non-CRF and CRF groups were 20.8% and 21.4%, respectively (p = NS). The mean ages were 59.0 (± 16.8) years in the non-CRF group and 67.3 (± 12.4) years in the CRF group (p = 0.0001), and the values of HS-CRP were 7.0 (± 7.8) mg/dL in the non-CRF group and 11.0 (± 9.4) mg/dL in the CRF group (p = 0.002). The values for WBC (p = 0.001) and ESR (p = 0.03) were higher in the CRF group than in the non-CRF group.
The antimicrobial sensitivity rates (%) for
E. coli according to eGFR are shown in Table
3. The antimicrobial sensitivities to ampicillin in the non-CRF group and CRF group were 37.8% and 20.0%, respectively (p = 0.024), and sensitivities to gentamycin in the non-CRF group and CRF group were 71.9% and 51.9% (p = 0.016), respectively. Significantly higher resistance of
E. coli to amoxicillin and gentamycin was noted in isolates recovered in patients with CRF. No significant differences in the sensitivity of
E. coli were observed between non-CRF and CRF patients.
The isolation rates (%) of uropathogens in APN patients with or without CRF are shown in Table
4. The isolation rates (%) for
E. coli in the non-CRF group and CRF group were 54.8% and 65.7% (p = NS), and the isolation rates for
K. pneumoniae were 12.2% and 13.9%, respectively (p = NS). The isolation rates of other microorganisms did not differ between the two groups.
Table 4
Isolation rate (%) of uropathogens in APN patients with or without CKD
E. coli
| 54.8 | 65.7 | NS |
K. pneumoniae
| 12.2 | 13.9 | NS |
Proteus
| 2.7 | 3.0 | NS |
Pseudomonas spp
| 5.1 | 2.4 | NS |
Enterococcus spp
| 3.0 | 3.0 | NS |
Other gram positive
| 15.2 | 9.0 | NS |
Other gram negative
| 7.1 | 3.1 | NS |
The antimicrobial sensitivity rates (%) for
E. coli according to DM are shown in Table
5. The antimicrobial sensitivities to ampicillin in the non-DM group and DM group were 30.6% and 35.7%, respectively (p = 0.538), and sensitivities to gentamycin in the non-DM group and DM group were 67.2% and 63.4% (p = 0.656), respectively. The antimicrobial sensitivities to other antibiotics did not differ between the two groups.
Table 5
Comparison between diabetes mellitus and non-diabetes mellitus patients with respect to antimicrobial sensitivity rate (%) for E. coli
Ampicilline
| 30.6 | 35.7 | 0.538 |
Cephalothin
| 36.7 | 52.9 | 0.227 |
Cefuroxime
| 72.2 | 78.4 | 0.456 |
Cefotaxime
| 78.2 | 84.2 | 0.420 |
Cefozolin
| 55.3 | 81.8 | 0.106 |
Ceftazidime
| 80.0 | 80.6 | 0.942 |
Cepefime
| 81.4 | 84.2 | 0.690 |
Imipenem
| 95.7 | 100 | 0.195 |
Gentamycin
| 67.2 | 63.4 | 0.656 |
Amikacin
| 92.2 | 100 | 0.081 |
Tobramycin
| 84.5 | 86.5 | 0.767 |
Ciprofloxacin
| 71.2 | 62.6 | 0.674 |
Trimethoprime-sulfomethoxazole
| 56.8 | 61.0 | 0.638 |
Discussion and Conclusions
In this study, we attempted to determine whether there are differences between CRF and non-CRF patients in the bacteriologic patterns of community-acquired APN or in the antibiotic sensitivity patterns of uropathogens. This study showed that CRF does not seem to influence the isolation rates of different uropathogens or their susceptibility patterns to antimicrobials in patients with community-acquired APN that presented as a positive urine culture.
In general, CRF patients are known to be vulnerable to infection due to weakened immunity [
6]. But little information is available regarding the role of CRF as a risk factor for the development of antimicrobial resistance in uropathogens. It has been reported that DM
per se does not seem to influence the isolation rates of different uropathogens or their susceptibility patterns to antimicrobials [
5]. In this study, the antimicrobial susceptibilities of microorganisms isolated in cases of community-acquired APN in non-DM and DM groups did not differ. However, the role of CRF in the etiology and antimicrobial resistance of uropathogens in patients with community-acquired APN has not been clarified.
It is known that
E. coli is isolated in approximately 90% of APN cases [
15]. Other studies have found that urinary Klebsiella is more frequent in diabetic patients compared to the detection rate in non-diabetic patients [
16,
17]. In this study, the most common cause of APN was
E. coli (58.3%, 293 cases), followed by
K. pneumoniae (12.7%, 64 cases). Due to the inclusion of diabetic patients,
K. pneumoniae was more common than in previous reports on APN. Among the microorganisms associated with APN,
E. coli was found in 54.8% and 65.7% of cases in the non-CRF group and CRF group, respectively (p = NS), and
K. pneumonia was present in 12.2% and 13.9% of cases, respectively (p = NS). There were no differences between the groups regarding the rates of other APN microorganisms.
In a previous analysis of the antibiotic sensitivity of
E. coli in APN, the sensitivities to the first- and third-generation cephalosporins, aminoglycoside and ciprofloxacin were greater than 90%; 47% to ampicillin; and 60% to TMP-SMX [
18]. In our current study, the rate of
E. coli sensitivity was 96.9% to imipenem, 99.2% to amikacin, 90.8% to tobramycin, greater than 80% to third- and fourth-generation cephalosporin antibiotics, 71.7% to ciprofloxacin, and 61.4% to TMP-SMX. However, the sensitivity rates to gentamycin and ampicillin were low (42.9% and 39.4%, respectively). Little data is available on the role of CRF as a risk factor for the development of antimicrobial resistance in uropathogens. Antimicrobial sensitivities to ampicillin in the non-CRF group and CRF group were 37.8% and 20.0%, respectively (p = 0.024), and those to gentamycin in the non-CRF group and CRF group were 71.9% and 51.9%, respectively (p = 0.016). The antimicrobial sensitivities to other antibiotics did not differ between the two groups. In North America, a cut-off point of 20% has been suggested as the level of resistance at which an agent should no longer be used [
19]. The observed high rates of
E. coli resistance to ampicillin, cephalothin, and gentamycin precludes, at least in our area, the choice of these or similar drugs in the empirical initial treatment of community-acquired APN in CRF and non-CRF patients.
In a recent case-control study, recent hospitalization and fluoroquinolone use in the previous six months were independent risk factors for fluoroquinolone resistance in community-onset febrile
E. coli UTI [
20]. In our study, we excluded cases of previous administration of antibiotics and hospital-acquired APN.
Recent cohort studies have suggested that CRF is also a risk factor for non-cardiovascular morbidity [
21] and mortality, including those caused by infection [
22,
23]. Few studies have investigated the associations between CRF and specific infectious conditions. In this study, the value of HS-CRP was 7.0 (± 7.8) mg/dL in the non-CRF group and 11.0 (± 9.4) mg/dL in the CRF group (p = 0.002). The values of WBC (p = 0.001) and ESR (p = 0.03) were higher in the CRF group than they were in the non-CRF group. Based on these results, we propose that patients with CRF had higher values of inflammatory markers when they had APN and that more attention is needed in this area because community-acquired APN in CRF patients can be a serious illness.
The limitations of our study include performance on non-CRF and CRF patients admitted to a single hospital, although the study included a large number of patients. Second, the CRF group was older in age than was the non-CRF group. Finally, the results for blood culture were not included in this study.
Based on our results, ampicillin, cephalothin, and gentamycin should not be considered as an initial therapeutic regimen in either CRF or non-CRF patients with community-acquired APN. In our series of patients with community-acquired APN presenting with a positive urine culture test, CRF per se does not seem to influence the isolation rates of different uropathogens or their susceptibility patterns to antimicrobials. A detailed prospective study is required to address the influences of CRF on the spectrum and antimicrobial susceptibility of the uropathogens involved in community-acquired APN.
Competing interests
This study was supported by a grant from the Kosin University College of Medicine (2010).
Authors' contributions
YSJ, M.D. and HSS, M.D. participated in the design of the study and performed the statistical analysis. HR, M.D. conceived of the study, and participated in its design and coordination. All authors read and approved the final manuscript.