Background
Methods
Search strategy
Inclusion and exclusion criteria
Study selection
Data extraction
Quality assessment and risk of bias in individual studies
Statistical analysis
Results
Study selection
Study characteristics
Authors | Publication year | Country | Sample size | Type of patients | Method for VFs detection | NOS points |
---|---|---|---|---|---|---|
Ghazvini et al. (1) [20] | 2019 | Iran | 168 | Outpatients | PCR | 8 |
Ghazvini et al. (2) [20] | 2019 | Iran | 32 | Inpatients | PCR | 6 |
Jadhav et al. [21] | 2011 | India | 150 | Inpatients | Phenotypical | 6 |
Kot et al. [22] | 2016 | Poland | 173 | Inpatients | Phenotypical, PCR | 6 |
Malekzadegan et al. [23] | 2018 | Iran | 126 | Inpatients | PCR | 8 |
Miranda-Estrada et al. [24] | 2017 | Mexico | 107 | Outpatients | Phenotypical, PCR | 8 |
Neamati et al. [25] | 2015 | Iran | 150 | Inpatients | PCR | 5 |
Oliveira et al. [26] | 2011 | Brazil | 204 | Outpatients | PCR | 8 |
Olorunmola et al. [27] | 2013 | Nigeria | 137 | Inpatients | Phenotypical | 5 |
Raeispour et al. [2] | 2018 | Iran | 60 | Inpatients | PCR | 5 |
Shakhatreh et al. [28] | 2019 | Jordan | 227 | Outpatients | PCR | 5 |
Tabasi et al. [29] | 2015 | Iran | 156 | Inpatients | Phenotypical | 8 |
Wang et al. (1) [30] | 2014 | China | 69 | Inpatients | PCR | 8 |
Wang et al. (2) [30] | 2014 | China | 129 | Outpatients | PCR | 6 |
Quality assessment and bias assessment
Antimicrobial resistance and virulence factors of UPEC
Antibiotics | No of studies | n/N | Random model | Heterogeneity | Egger’s test | ||||
---|---|---|---|---|---|---|---|---|---|
% (95% CI) | P | Q | P | I2 | t | P | |||
Amikacin | 8 | 214/1074 | 19.9 (0.18–0.22) | < 0.001 | 344.4 | < 0.001 | 96.5 | 3.98 | 0.002 |
Amoxicillin | 3 | 322/443 | 72.7 (0.68–0.77) | < 0.001 | 225.6 | < 0.001 | 94.7 | 4.76 | 0.001 |
Amoxiclav | 6 | 407/998 | 40.8 (0.38–0.44) | < 0.001 | 406.2 | < 0.001 | 97.1 | 2.35 | 0.039 |
Ampicillin | 8 | 835/1114 | 75.0 (0.72–0.77) | < 0.001 | 222.9 | < 0.001 | 94.6 | 1.15 | 0.276 |
Ampicillin-sulbactam | 3 | 161/354 | 45.5 (0.40–0.51) | 0.089 | 178.0 | < 0.001 | 93.3 | 5.54 | < 0.001 |
Aztreonam | 2 | 78/354 | 22.0 (0.18–0.27) | < 0.001 | 172.8 | < 0.001 | 93.1 | 24.1 | < 0.001 |
Cefepime | 7 | 280/952 | 29.4 (0.27–0.32) | < 0.001 | 143.3 | < 0.001 | 91.6 | 3.38 | 0.006 |
Cefixime | 3 | 120/443 | 27.1 (0.23–0.31) | < 0.001 | 124.0 | < 0.001 | 90.3 | 5.58 | 0.001 |
Cefoperazone-sulbactam | 2 | 36/198 | 18.2 (0.13–0.24) | < 0.001 | 81.21 | < 0.001 | 85.2 | 24.2 | < 0.001 |
Cefotaxime | 7 | 379/1055 | 35.9 (0.33–0.39) | < 0.001 | 235.5 | < 0.001 | 94.9 | 3.99 | 0.002 |
Cefoxitin | 4 | 104/707 | 14.7 (0.12–0.18) | < 0.001 | 91.61 | < 0.001 | 86.9 | 13.6 | < 0.001 |
Cefpodoxime | 2 | 166/287 | 57.8 (0.52–0.63) | 0.008 | 182.7 | < 0.001 | 93.4 | 11.5 | < 0.001 |
Ceftazidime | 9 | 509/1209 | 42.1 (0.39–0.45) | < 0.001 | 212.1 | < 0.001 | 94.3 | 3.33 | 0.007 |
Ceftriaxone | 5 | 247/844 | 29.3 (0.26–0.32) | < 0.001 | 239.6 | < 0.001 | 95.0 | 5.50 | < 0.001 |
Cefuroxime | 5 | 389/705 | 55.2 (0.51–0.59) | 0.006 | 288.2 | < 0.001 | 95.8 | 3.16 | 0.009 |
Cephalexin | 3 | 146/258 | 56.6 (0.50–0.63) | 0.035 | 189.3 | < 0.001 | 93.7 | 12.8 | < 0.001 |
Cephalothin | 3 | 82/437 | 18.8 (0.15–0.23) | < 0.001 | 181.0 | < 0.001 | 93.4 | 3.23 | 0.008 |
Cephazolin | 3 | 142/258 | 55.0 (0.49–0.61) | 0.106 | 168.4 | < 0.001 | 92.9 | 13.7 | < 0.001 |
Ciprofloxacin | 12 | 792/1781 | 44.5 (0.42–0.47) | < 0.001 | 265.5 | < 0.001 | 95.5 | 0.54 | 0.602 |
Ertapenem | 1 | 1/227 | 0.4 (0.00–0.03) | < 0.001 | 0.799 | 1.000 | 0.00 | 0.49 | 0.634 |
Fosfomycin | 1 | 9/107 | 8.4 (0.04–0.15) | < 0.001 | 37.35 | < 0.001 | 67.9 | 21.0 | < 0.001 |
Gentamicin | 13 | 637/1888 | 33.7 (0.32–0.36) | < 0.001 | 269.6 | < 0.001 | 95.6 | 0.70 | 0.497 |
Imipenem | 7 | 5/767 | 0.7 (0.00–0.02) | < 0.001 | 3.719 | 0.988 | 0.00 | 5.02 | < 0.001 |
Meropenem | 3 | 1/354 | 0.3 (0.00–0.02) | < 0.001 | 1.416 | 1.000 | 0.00 | 2.40 | 0.035 |
Nalidixic acid | 9 | 777/1317 | 59.0 (0.56–0.62) | < 0.001 | 248.2 | < 0.001 | 95.2 | 1.70 | 0.118 |
Nitrofurantoin | 10 | 297/1486 | 20.0 (0.18–0.22) | < 0.001 | 297.1 | < 0.001 | 96.0 | 3.77 | 0.003 |
Norfloxacin | 5 | 286/614 | 46.6 (0.43–0.51) | 0.090 | 273.1 | < 0.001 | 95.6 | 3.20 | 0.009 |
Ofloxacin | 2 | 101/244 | 41.4 (0.35–0.48) | 0.007 | 153.5 | < 0.001 | 92.2 | 13.6 | < 0.001 |
Tetracycline | 6 | 498/721 | 69.1 (0.66–0.72) | < 0.001 | 207.3 | < 0.001 | 94.2 | 2.44 | 0.033 |
Tobramycin | 1 | 30/107 | 28.0 (0.20–0.37) | < 0.001 | 103.8 | < 0.001 | 88.4 | 35.2 | < 0.001 |
Co-trimoxazole | 13 | 1119/1888 | 59.3 (0.57–0.61) | < 0.001 | 177.1 | < 0.001 | 93.2 | 1.06 | 0.313 |
Antibiotics | No of studies | n/N | Random model | Heterogeneity | Egger’s test | ||||
---|---|---|---|---|---|---|---|---|---|
% (95% CI) | P | Q | P | I2 | t | P | |||
aer | 3 | 229/437 | 52.4 (0.48–0.57) | 0.315 | 189.2 | < 0.001 | 93.1 | 4.45 | 0.001 |
afa | 5 | 98/701 | 14.0 (0.12–0.17) | < 0.001 | 169.6 | < 0.001 | 92.3 | 4.54 | 0.001 |
chuA | 1 | 46/227 | 20.3 (0.16–0.26) | < 0.001 | 93.10 | < 0.001 | 86.0 | 25.9 | < 0.001 |
cnf1 | 5 | 91/682 | 13.3 (0.11–0.16) | < 0.001 | 71.34 | < 0.001 | 81.8 | 13.2 | < 0.001 |
Colicin | 1 | 13/137 | 9.5 (0.06–0.16) | < 0.001 | 45.42 | < 0.001 | 71.4 | 16.9 | < 0.001 |
CSH | 1 | 120/150 | 80.0 (0.73–0.86) | < 0.001 | 242.1 | < 0.001 | 94.6 | 39.3 | < 0.001 |
eco274 | 1 | 99/227 | 43.6 (0.37–0.50) | 0.055 | 157.9 | < 0.001 | 91.8 | 33.7 | < 0.001 |
fimH/MSHA | 10 | 881/1170 | 75.3 (0.73–0.78) | < 0.001 | 210.7 | < 0.001 | 93.8 | 0.72 | 0.489 |
fimP/MRHA | 4 | 219/616 | 35.6 (0.32–0.39) | < 0.001 | 152.0 | < 0.001 | 91.5 | 8.02 | < 0.001 |
fyuA | 1 | 41/227 | 18.1 (0.14–0.24) | < 0.001 | 85.68 | < 0.001 | 84.8 | 24.8 | < 0.001 |
hlyA | 12 | 334/1511 | 22.1 (0.20–0.24) | < 0.001 | 241.9 | < 0.001 | 94.6 | 2.62 | 0.022 |
iucD | 2 | 130/198 | 65.7 (0.59–0.72) | < 0.001 | 203.3 | < 0.001 | 93.6 | 29.9 | < 0.001 |
iutA | 2 | 144/233 | 61.8 (0.55–0.68) | < 0.001 | 198.6 | < 0.001 | 93.5 | 18.9 | < 0.001 |
kpsMTII | 2 | 120/198 | 60.6 (0.54–0.67) | 0.003 | 191.2 | < 0.001 | 93.2 | 36.4 | < 0.001 |
PAI | 3 | 265/480 | 55.2 (0.51–0.60) | 0.023 | 241.8 | < 0.001 | 94.6 | 3.80 | 0.003 |
pap | 9 | 350/1158 | 30.2 (0.28–0.33) | < 0.001 | 87.35 | < 0.001 | 98.9 | 0.54 | < 0.001 |
sat | 1 | 28/107 | 26.2 (0.19–0.35) | < 0.001 | 100.3 | < 0.001 | 87.0 | 25.3 | < 0.001 |
sfa | 5 | 262/701 | 37.4 (0.34–0.41) | < 0.001 | 10.08 | < 0.001 | 90.8 | 0.05 | 0.001 |
shiA | 1 | 209/227 | 92.1 (0.88–0.95) | < 0.001 | 292.1 | < 0.001 | 95.6 | 45.4 | < 0.001 |
sisA | 1 | 164/227 | 72.2 (0.66–0.78) | < 0.001 | 234.0 | < 0.001 | 94.5 | 40.9 | < 0.001 |
sisB | 1 | 56/227 | 24.7 (0.19–0.31) | < 0.001 | 106.9 | < 0.001 | 89.8 | 27.8 | < 0.001 |
sivH | 1 | 81/227 | 35.7 (0.30–0.42) | < 0.001 | 137.5 | < 0.001 | 90.6 | 31.5 | < 0.001 |
traT | 2 | 266/354 | 75.1 (0.70–0.79) | < 0.001 | 236.2 | < 0.001 | 94.5 | 40.7 | < 0.001 |
vat | 1 | 63/227 | 27.8 (0.22–0.34) | < 0.001 | 115.9 | < 0.001 | 88.8 | 28.9 | < 0.001 |
yfcv | 1 | 57/227 | 25.1 (0.20–0.31) | < 0.001 | 108.2 | < 0.001 | 88.0 | 27.9 | < 0.001 |
In-patient, n/N (%) | Out-patient, n/N (%) | OR (95% CI) | p-value | |
---|---|---|---|---|
A. Main antibiotic groups | ||||
Aminoglycosides | 403/1432 (28.1) | 478/1637 (29.2) | 0.96 (0.83–1.12) | 0.631 |
Sulfonamides | 610/1021 (59.7) | 509/867 (58.7) | 1.02 (0.88–1.18) | 0.817 |
Cyclines | 416/614 (67.8) | 82/107 (76.6) | 0.88 (0.65–1.21) | 0.441 |
Fosfomycin | 0 | 9/107 (8.4) | 11.3 (0.21–603.0) | 0.232 |
Nitrofurans | 130/952 (13.7) | 167/534 (31.3) | 0.44 (0.34–0.56) | < 0.0001 |
Quinolones | 1333/2217 (60.1) | 623/1739 (35.8) | 1.68 (1.50–1.88) | < 0.0001 |
Beta-lactams | 2244/5622 (39.9) | 2166/6342 (34.2) | 0.86 (0.80–0.92) | < 0.0001 |
B. Beta-lactams classes | ||||
Aminopenicillins | 846/1117 (75.7) | 311/440 (70.7) | 1.07 (0.90–1.27) | 0.427 |
Carbapenems | 2/659 (0.3) | 5/689 (0.7) | 0.41 (0.8–2.16) | 0.298 |
Monobactams | 77/150 (51.3) | 1/204 (0.5) | 104.7 (14.4–761.4) | < 0.0001 |
Beta-lactam+Inhibitors | 273/754 (36.2) | 331/796 (41.6) | 0.87 (0.72–1.05) | 0.150 |
Cephalosporins | 1046/2942 (35.6) | 1518/4213 (36.0) | 1.01 (0.93–1.11) | 0.776 |
C. Cephalosporins classes | ||||
1GCs | 210/491 (42.8) | 160/462 (34.6) | 1.24 (0.97–1.57) | 0.087 |
2GCs | 118/518 (22.8) | 375/894 (41.9) | 0.54 (0.43–0.69) | < 0.0001 |
3GCs | 571/1648 (34.7) | 850/2190 (38.8) | 0.89 (0.89–1.01) | 0.072 |
4GCs | 147/285 (51.6) | 133/667 (19.9) | 2.59 (1.97–3.40) | < 0.0001 |
D. Virulence factors groups | ||||
Adhesins | 1635/3309 (49.4) | 681/1739 (39.2) | 1.3 (1.13–1.40) | < 0.0001 |
Siderophore systems | 276/428 (64.5) | 371/1121 (33.1) | 1.9 (1.61–2.36) | < 0.0001 |
Toxins | 312/1418 (22.0) | 217/1246 (17.4) | 1.3 (1.05–1.53) | 0.016 |
Immune suppressors | 200/276 (72.5) | 674/1339 (50.3) | 1.4 (1.17–1.77) | 0.001 |
Relationship between antimicrobial resistance and virulence factors in UPEC
Discussion
Virulence factors groups | Examples of genes | Mechanisms |
---|---|---|
Adhesins | afa, CSH, fimH, fimP, kpsmtII, pap, sfa, traT | UPEC adhesins can contribute to virulence in different ways: (i) directly triggering host and bacterial cell signalling pathways, (ii) facilitating the delivery of other bacterial products to host tissues, and (iii) promoting bacterial invasion [3]. Adhesins help in the adhesion of organism to epithelial cell surface, thereby it escapes from flushing action during micturition [7]. Fimbriae is responsible for adhesion, colonization, invasion of host epithelium and makes UPEC to escape from the innate immune system by internalization process within urothelial cells which is mediated by the transduction cascades [8]. |
Toxins | Cnf1, hlyA, saT, vaT | Toxins like haemolysin and Cytotoxic Necrotising Factor (CNF) act by their cytotoxicity and invasiveness. Haemolysin production could inhibit the cytokine production of host cells and promote the cytotoxicity. It causes lysis of the erythrocytes which release nutrients and other vitamins available for the bacteria. At the same time it releases inflammatory mediators and enzymes which are cytotoxic to renal proximal tubular epithelial cells, erythrocytes and leukocytes, thereby causing renal epithelial damage [3]. CNF interferes with the phagocytosis of E. coli by the WBCs and thus it leads to exfoliation and apoptosis of bladder epithelial cells. It further enhances the easy access of bacteria into the underlying tissue. These toxins can alter signalling pathways, provoke the inflammatory response and prevent the apoptosis thereby they cause the UPEC population to expand [1]. |
Siderophores | aer, chuA, fyuA, iuD, iutA, yfcv | Production of siderophores by E. coli which takes up iron from the host and helps in colonization and survival of pathogen [1, 8]. They contribute to the process of nutritional passivation of metal ions, in which UPEC access these vital nutrients while simultaneously protecting themselves from their toxic potential [65] |
Immune suppressors | PAI, shiA, sisA, sisB, sivH, Eco274 | UPEC induces a non-sterilizing adaptive immune response in the bladder. Its causes long-lasting changes in the bladder urothelium, conferring resistance or increased susceptibility to subsequent infections depending on the outcomes of the first infection [66]. The invasins play a key role in suppressing the host immune response during the initial stages of infection [64]. |