Abstract
Background
Pyogenic liver abscess (PLA) is a potentially life-threatening hepatic infection. The increasing prevalence of polymicrobial infections and multidrug-resistant (MDR) pathogens, including extended-spectrum β-lactamase (ESBL)-producing bacteria, poses challenges to treatment and association with higher mortality rates. Identifying risk factors and optimizing clinical management strategies for these infections are essential to improving patient outcomes.
Methods
This retrospective study analyzed the clinical data of 643 PLA patients admitted in recent 12 years. Univariate and multivariate analyses were conducted to analyze treatment strategies, disease burden, and clinical outcomes, as well as identify risk factors associated with polymicrobial infections and ESBL-producing bacterial strains.
Results
In this study, 255 of 643 PLA patients with positive bacterial identification were enrolled. Among them, 41 had polymicrobial infections. Of the 162 patients who underwent ESBL testing, 128 were infected with ESBL-producing bacteria. Polymicrobial PLA was significantly associated with intra-abdominal trauma or surgery (odds ratio [OR] = 3.06), malignancies or hematological diseases (OR = 3.01). ESBL-producing bacterial PLA was correlated with hepatic tenderness (OR = 3.24), intra-abdominal trauma or surgery (OR = 3.06), and hospitalization within the past three months (OR = 4.32). E. coli was more frequently identified among ESBL-producing bacteria compared to K. pneumoniae. The use of carbapenems for treating ESBL-producing pathogens has been increasing, with carbapenems and β-lactamase inhibitor combinations currently serving as the primary therapeutic options.
Conclusion
Patients with PLA who have a history of intra-abdominal trauma or surgery, malignancies or hematological diseases, and recent hospitalization should be closely monitored for polymicrobial and drug-resistant infections. Given the high prevalence of antibiotic-resistant E. coli in PLA cases, judicious use of antibiotics is warranted. Broad-spectrum antibiotics effective against ESBL-producing bacteria should be considered, with carbapenems remaining the first-line treatment option.
Keywords: Klebsiella pneumoniae, Escherichia coli, Extended-spectrum β-lactamase, pyogenic liver abscess, polymicrobial infection
Introduction and Background
Pyogenic liver abscess (PLA) is a severe and potentially life-threatening hepatic infection caused by various bacterial pathogens. The most commonly implicated organisms include Klebsiella pneumoniae (K. pneumoniae), Escherichia coli (E. coli), and Streptococcus anginosus. These bacteria can reach the liver via direct trauma, hematogenous spread through the portal vein, or biliary tract dissemination from intra-abdominal infections.1–3
The Incidence of PLA has been rising recent years, likely due to increased antibiotic use, an aging population, and a higher prevalence of comorbid conditions such as diabetes mellitus, cholecystitis, and gallstones.3–5 The spectrum of causative pathogens varies geographically, with E. coli being predominant in some Western countries, whereas K. pneumoniae is the leading pathogen in many Asian regions, including China.1–3,6
Additionally, polymicrobial infections, defined as infection involving multiple bacterial species, are increasingly observed and are associated with more severe disease and higher mortality rates.7 Which is common in patients with liver abscess who have biliary obstruction, intra-abdominal sepsis, or immunocompromised status. Traditionally, it is believed that up to 20–30% of pyogenic liver abscesses are polymicrobial in origin, especially in elderly patients or in cases following surgery or interventional procedures. Identifying risk factors for such infections is critical for early diagnosis and effective management.3,8 Polymicrobial infections are frequently associated with multidrug-resistant (MDR) bacteria, primarily due to horizontal gene transfer, including plasmid-mediated dissemination of resistance genes. Among these, extended-spectrum β-lactamase (ESBL)-producing bacteria represent a significant and growing challenge, further complicating antimicrobial therapy.2,7 While hypervirulent K. pneumoniae (hvKP) and carbapenem-resistant K. pneumoniae (CRKP) have been extensively studied in PLA. hvKp characterized as the major pathogen associated with the development of liver abscesses., often causes disseminated, invasive disease in immunocompetent hosts, also causes osteomyelitis, necrotizing fasciitis, endophthalmitis, and meningitis.9,10 CRKP is mainly associated with nosocomial infections. It is resistant to multiple antibiotics, making treatment extremely difficult, and often leads to high mortality.11,12 The role of ESBL-producing bacteria remains insufficiently explored. Addressing this gap by identifying risk factors, resistance mechanisms, and optimal clinical management strategies for ESBL-related infections is crucial for improving treatment outcomes.
Materials and Methods
Study Subjects
This study retrospectively analyzed the clinical data of patients diagnosed with PLA at Xiangya Hospital, Central South University from January 2012 to December 2023. The inclusion and exclusion criteria are as follows: Inclusion criteria: 1. Diagnosis of PLA confirmed by clinical symptoms, at least one imaging evidence which including abdominal contrast-enhanced CT and/or ultrasound, as well as magnetic resonance imaging (MRI), and microbiological evidence, with PLA as the primary diagnosis.2. Age ≥18 years.3. Completion of bacterial culture and antimicrobial susceptibility testing from pus, blood, or drainage fluid during hospitalization. Exclusion criteria:1. Patients with incomplete hospitalization records.2. Negative body fluid cultures.3. Incomplete antimicrobial susceptibility test results. Patients with positive bacterial cultures were classified into polymicrobial infection and monomicrobial infection groups based on the identified bacterial species. Then, Patients infected by bacterial of determined ESBL status were divided into ESBL-producing and non- ESBL-producing patients (Figure 1).
Figure 1.
Flowchart of the study.
Study Data
Comprehensive clinical data were extracted from electronic medical records, including demographic and clinical data including age, sex, year of admission, comorbidities (diabetes mellitus, biliary disease, hepatitis and cirrhosis, fatty liver, history of intra-abdominal trauma or surgery, malignancy and hematological diseases), clinical characteristics (symptoms, length of stay in hospital, imaging findings), laboratory values (white blood cell [WBC] count, red blood cell [RBC] count, Hemoglobin [Hb], Neutrophil Ratio[N], alanine aminotransferase [ALT], aspartate aminotransferase [AST], albumin [ALB], albumin[ALB], Total Protein[TP], Total Bile Acids[TB], Direct Bile Acids[DB], procalcitonin [PCT], erythrocyte sedimentation rate [ESR] and C-reactive protein [CRP]), invasive procedure, details of therapeutic approach, drainage ways, abscess prognosis, length of hospital stay, hospitalization costs and outcomes at discharge.
Isolation of Bacteria
Bacterial isolates were obtained from sterile body fluids, including pus, blood, and drainage fluid. Identification and antimicrobial susceptibility testing were performed using the VITEK-2 automated system (bioMérieux, Marcy-l’Étoile, France). The tested antibiotics included cefotaxime, ceftazidime, imipenem, nitrofurantoin, gentamicin, amikacin, ciprofloxacin, cefuroxime/sulbactam, piperacillin/tazobactam, doxycycline, levofloxacin, and imipenem/Cila statin. ESBL testing was performed for K. pneumoniae and E. coli isolates using the VITEK-2 advanced expert system in accordance with the Clinical and Laboratory Standards Institute (CLSI) guidelines. The confirmatory test employed a combination of cefotaxime and ceftazidime with and without clavulanic acid. An isolate was defined as ESBL-producing when the minimum inhibitory concentration (MIC) decreased by ≥3 two-fold dilutions in the presence of clavulanic acid. Quality control strains were used in each batch to ensure result reliability.
Statistical Analysis
All statistical analyses were performed using IBM SPSS Statistics 25.0 (IBM Corporation, Armonk, NY) and R 4.3.2 (The R Foundation for Statistical Computing, Vienna, Austria). Continuous variables were expressed as mean ± standard deviation (SD) or median (interquartile range) and compared using Student’s t-test (for normally distributed data) or the Mann–Whitney-U test (for non-normally distributed data). Categorical variables were compared using the chi-square test (χ2) or Fisher’s exact test. Univariate analysis was conducted to identify potential risk factors, and variables with p < 0.1 were included in the multivariate logistic regression model to determine independent risk factors. Backward stepwise selection was applied, and multicollinearity was checked via variance inflation factors (VIF).All tests of significance were 2-sided, and p < 0.05 was considered to be statistically significant.
Results
Clinical Characteristics and Independent Risk Factors for Polymicrobial Infections in PLA Patients
A total of 643 patients were diagnosed with PLA between January 2010 and December 2021, of whom 255 had confirmed bacterial infections. Among these, 41 cases (16.1%) were identified as polymicrobial infections. The clinical characteristics of these patients are summarized in Table 1. Compared to patients with monomicrobial infections, those with polymicrobial infections were more likely to have a history of intra-abdominal trauma or surgery, malignancies or hematological disorders, diabetes mellitus, fatty liver disease, and a recent hospitalization within the past three months. Furthermore, ESBL-producing bacterial infections were significantly more common in the polymicrobial infection group. Multivariate logistic regression analysis identified a history of intra-abdominal trauma or surgery (OR=3.06) and malignancies and hematological diseases (OR=3.01) were independent risk factors for polymicrobial infections in PLA patients.
Table 1.
Clinical Characteristics and Independent Risk Factors in Patients with Polymicrobial Infections
| Variables | Total (n=255) | Univariate Analysis | Multivariable Analysis | |||||
|---|---|---|---|---|---|---|---|---|
| Monomicrobial Infections (n = 214) | Polymicrobial Infections (n = 41) | p-value | p-value | OR | 95% CI for OR | |||
| Demographic | Age, Median (Q1,Q3) | 56 (50, 63) | 57 (50.75, 64) | 54 (46, 60) | 0.081 | 0.092 | 0.98 | 0.95–1 |
| Female, n (%) | 114 (44.7) | 98 (45.8) | 16 (39) | 0.530 | ||||
| Male, n (%) | 141 (55.3) | 116 (54.2) | 25 (61) | |||||
| Clinical symptoms | Fever, n (%) | 209 (82) | 179 (83.6) | 30 (73.2) | 0.169 | |||
| Chill, n (%) | 156 (61.2) | 133 (62.1) | 23 (56.1) | 0.580 | ||||
| Sweat, n (%) | 61 (23.9) | 54 (25.2) | 7 (17.1) | 0.356 | ||||
| Vomit, n (%) | 49 (19.2) | 43 (20.1) | 6 (14.6) | 0.551 | ||||
| Stomachache, n (%) | 130 (51) | 106 (49.5) | 24 (58.5) | 0.376 | ||||
| Cough, n (%) | 23 (9) | 20 (9.3) | 3 (7.3) | 1.000 | ||||
| Weight loss, n (%) | 50 (19.6) | 38 (17.8) | 12 (29.3) | 0.146 | ||||
| Hepatomegaly, n (%) | 30 (11.8) | 28 (13.1) | 2 (4.9) | 0.187 | ||||
| Hepatic tenderness, n (%) | 79 (31) | 64 (29.9) | 15 (36.9) | 0.532 | ||||
| Underling or concomitant conditions | Diabetes mellitus, n (%) | 89 (34.9) | 82 (38.3) | 7 (17.1) | 0.015 | 0.099 | 0.46 | 0.17–1.11 |
| Biliary disease, n (%) | 72 (28.2) | 58 (27.1) | 14 (34.1) | 0.466 | ||||
| History of intra-abdominal trauma or surgery, n (%) | 67 (26.3) | 46 (21.5) | 21 (51.2) | < 0.001 | 0.003 | 3.06 | 1.44–6.53 | |
| Liver fibrosis, n (%) | 12 (4.7) | 10 (4.7) | 2 (4.9) | 1.000 | ||||
| Fatty liver, n (%) | 30 (11.8) | 29 (13.6) | 1 (2.4) | 0.060 | 0.207 | 0.26 | 0.01–1.42 | |
| Malignancies or hematological diseases, n (%) | 28 (11) | 17 (7.9) | 11 (26.8) | 0.001 | 0.029 | 3.01 | 1.1–8.05 | |
| Hospitalization history in the past three months, n (%) | 15 (5.9) | 10 (4.7) | 5 (12.2) | 0.073 | 0.874 | 1.12 | 0.24–4.52 | |
| ESBL-production bacterial, n (%) | 34 (13.3) | 25 (11.7) | 9 (22) | 0.028 | 0.197 | 2.04 | 0.67–5.94 | |
| Abscess | Multiple cavitary abscesses, n (%) | 59 (23.1) | 45 (21) | 14 (34.1) | 0.105 | |||
| Abscess over 100mm, n (%) | 51 (20) | 45 (21) | 6 (14.6) | 0.469 | ||||
| Distant metastasis, n (%) | 11 (4.3) | 9 (4.2) | 2 (4.9) | 0.692 | ||||
| Gas, n (%) | 22 (8.6) | 16 (7.5) | 6 (14.6) | 0.221 | ||||
Laboratory Profiles, Treatment, Complications, Hospitalization Burden and Clinical Outcomes of Polymicrobial Infections
Laboratory profiles revealed that patients with polymicrobial infections exhibited significantly higher rates of anemia, hypogammaglobulinemia, and elevated PCT levels compared to those with monomicrobial infections (Table 2). Additionally, the polymicrobial infections group also had a higher proportion of patients requiring surgical intervention. Complications were frequent in both groups, with pleural effusion affecting 53.3% of all patients. Notably, septic shock incidence was markedly higher in the polymicrobial infections group (14.6% vs. 3.7%). Although no significant difference in mortality rates was observed, patients with polymicrobial infections experienced prolonged hospitalization (median 20 days vs. 15 days) and incurred significantly higher treatment costs (¥45,285.98 vs. ¥30,358.3).
Table 2.
Laboratory Profiles, Treatment, Complications, Hospitalization Burden and Clinic Outcomes of Polymicrobial Infected PLA Patients
| Total (n = 255) | Monomicrobial Infections (n = 214) | Polymicrobial Infections (n = 41) | p-value | ||
|---|---|---|---|---|---|
| Laboratory profiles | WBC, Median (Q1,Q3) | 11.2 (8, 15) | 11.25 (8.1, 15.12) | 10.7 (7.7, 15) | 0.682 |
| RBC, Mean ± SD | 3.59 (3.21, 4.06) | 3.64 (3.23, 4.04) | 3.51 (2.89, 4.12) | 0.324 | |
| Hb, Mean ± SD | 105.09 ± 20.73 | 106.42 ± 19.97 | 98.24 ± 23.32 | 0.041 | |
| N, Median (Q1,Q3) | 81.1 (75, 86.8) | 80.6 (74.93, 86.18) | 83.2 (76.2, 89) | 0.090 | |
| ALB, Median (Q1,Q3) | 28.5 (24.6, 32.7) | 28.5 (24.95, 32.85) | 29 (23.9, 31.8) | 0.423 | |
| GLB, Mean ± SD | 31.75 ± 6.46 | 32.17 ± 6.23 | 29.52 ± 7.24 | 0.035 | |
| ALT, Median (Q1,Q3) | 40 (23.9, 75.4) | 40.85 (26.17, 76.67) | 35.5 (20.4, 73.2) | 0.354 | |
| AST, Median (Q1,Q3) | 39.4 (24.4, 67.5) | 38.55 (24.48, 62.92) | 43.5 (22.7, 82.8) | 0.595 | |
| TB, Median (Q1,Q3) | 15.3 (9.33, 32.35) | 15.05 (9.12, 30.15) | 18.25 (10.55, 36.92) | 0.205 | |
| DB, Median (Q1,Q3) | 7.85 (4.43, 18.92) | 7.3 (4.03, 15.57) | 8.9 (4.8, 21.7) | 0.112 | |
| ESR, Median (Q1,Q3) | 94.5 (70.25, 120) | 96.5 (74, 120) | 71 (54.5, 100.5) | 0.068 | |
| CRP, Median (Q1,Q3) | 116 (78.4, 158) | 116 (77.73, 159.75) | 129 (101, 140) | 0.551 | |
| PCT, Median (Q1,Q3) | 1.35 (0.42, 8.68) | 1.25 (0.38, 5.93) | 3.54 (1.41, 18.48) | 0.039 | |
| Treatment | Antibiotics alone, n (%) | 39 (15.3) | 36 (16.8) | 3 (7.3) | 0.194 |
| Percutaneous drainage plus antibiotic, n (%) | 165 (64.7) | 139 (65) | 26 (63.4) | ||
| Surgery plus antibiotics, n (%) | 39 (15.3) | 29 (13.6) | 10 (24.4) | ||
| Antibiotics plus Percutaneous drainage plus surgery, n (%) | 12 (4.7) | 10 (4.7) | 2 (4.9) | ||
| Complications | Pleural effusion, n (%) | 136 (53.3) | 114 (53.3) | 22 (53.7) | 1.000 |
| Sepsis shock | 14 (5.5) | 8 (3.7) | 6 (14.6) | 0.013 | |
| Hospitalization burden | Inhospital days, Median (Q1,Q3) | 15 (11, 23) | 15 (10, 21) | 20 (15, 27) | 0.003 |
| Inhospital cost, Median (Q1,Q3) | 33,374.43 (19,550.18, 53,532.77) | 30,358.3 (19,107.21, 50,579.46) | 45,285.98 (33,022.43, 68,970.32) | 0.004 | |
| Clinical outcomes | Improvement, n (%) | 240 (94.1) | 201 (93.9) | 39 (95.1) | 0.850 |
| Palliative Discharge, n (%) | 11 (4.3) | 9 (4.2) | 2 (4.9) | ||
| Death in hospital, n (%) | 4 (1.6) | 4 (1.9) | 0 (0) |
Microbiology Characteristics of Polymicrobial Infections in PLA Patients
A total of 299 pathogenic isolates were identified from blood or pus cultures in 255 patients (Table 3). Among monomicrobial infections, Klebsiella (136 cases, 63.6%) was the predominant pathogen, followed by Escherichia (27 cases,12.6%) and Streptococcus (15 cases,7%). In polymicrobial infections, Escherichia (20 cases, 23.5%) predominated, followed by Klebsiella (18 cases, 21.2%) and Enterococcus (11 cases, 12.9%). Further analysis of bacterial combinations showed that the most common pair was Klebsiella pneumoniae with Escherichia coli (6 cases), followed by E. coli with Enterococcus faecium (5 cases). Other combinations, such as K. pneumoniae with E. faecium and E. coli with Streptococcus constellatus, were less frequent. Overall, mixed infections involving Enterobacteriaceae (especially K. pneumoniae and E. coli) and enterococci predominated in this case series.
Table 3.
Distribution of Bacterial Isolates and Multidrug-Resistant Organisms
| Total (n = 299) | Polymicrobial Infections (n=85) | Monomicrobial Infections (n=214) | ||||
|---|---|---|---|---|---|---|
| Bacterial Species | Klebsiella | 154 | 18 | 21.2% | 136 | 63.6% |
| Escherichia | 47 | 20 | 23.5% | 27 | 12.6% | |
| Streptococcus | 22 | 7 | 8.2% | 15 | 7.0% | |
| Enterococcus | 22 | 11 | 12.9% | 11 | 5.1% | |
| Staphylococcus | 10 | 2 | 2.4% | 8 | 3.7% | |
| Pseudomonas aeruginosa | 8 | 6 | 7.1% | 2 | 0.9% | |
| Acinetobacter | 7 | 3 | 3.5% | 4 | 1.9% | |
| Candida | 5 | 2 | 2.4% | 3 | 1.4% | |
| Bacteroides | 4 | 2 | 2.4% | 2 | 0.9% | |
| Gemella | 2 | 1 | 1.2% | 1 | 0.5% | |
| Clostridium clostridioforme | 2 | 2 | 2.4% | 0 | 0.0% | |
| Morganella morganii | 2 | 1 | 1.2% | 1 | 0.5% | |
| Aeromonas | 2 | 1 | 1.2% | 1 | 0.5% | |
| Gemellahaemolysans | 1 | 1 | 1.2% | 0 | 0.0% | |
| Roseomonas | 1 | 1 | 1.2% | 0 | 0.0% | |
| Fusobacterium | 1 | 0 | 0.0% | 1 | 0.5% | |
| Actinomyces | 1 | 1 | 1.2% | 0 | 0.0% | |
| Shewanella | 1 | 1 | 1.2% | 0 | 0.0% | |
| Sphingomonas | 1 | 1 | 1.2% | 0 | 0.0% | |
| Corynebacterium | 1 | 1 | 1.2% | 0 | 0.0% | |
| Nocardia | 1 | 0 | 0.0% | 1 | 0.5% | |
| Enterobacter | 1 | 1 | 1.2% | 0 | 0.0% | |
| Proteus | 1 | 1 | 1.2% | 0 | 0.0% | |
| Parvimonas | 1 | 0 | 0.0% | 1 | 0.5% | |
| Citrobacter | 1 | 1 | 1.2% | 0 | 0.0% | |
| MDR organism | Total MDR | 53 | 24 | 28.2% | 29 | 13.6% |
| ESBL-EC | 25 | 10 | 11.8% | 15 | 7.0% | |
| ESBL-KP | 14 | 6 | 7.1% | 8 | 3.7% | |
| CRKP | 5 | 3 | 3.5% | 2 | 0.9% | |
| CREC | 2 | 1 | 1.2% | 1 | 0.5% | |
| CRPA | 5 | 3 | 3.5% | 2 | 0.9% | |
| CRAB | 1 | 1 | 1.2% | 0 | 0.0% | |
| MRSA | 1 | 0 | 0.0% | 1 | 0.5% | |
Abbreviations: MDR, multi-drug resistant; ESBL-EC, extended-spectrum beta-lactamase-producing Escherichia coli; ESBL-KP, extended-spectrum beta-lactamase-producing Klebsiella pneumoniae; CRKP, carbapenem-resistant Klebsiella pneumoniae; CREC, carbapenem-resistant Escherichia coli; CRPA, carbapenem-resistant Pseudomonas aeruginosa; CRAB, carbapenem-resistant Acinetobacter baumannii; MRSA, methicillin-resistant Staphylococcus aureus.
Notably, MDR organisms were significantly more prevalent in the polymicrobial infection group (28.2% vs. 13.6%), with a marked predominance of ESBL-producing strains. Specifically, ESBL-producing E. coli (ESBL-EC) and ESBL-producing K. pneumoniae (ESBL-KP) were more frequently isolated from polymicrobial infections group. Additionally, carbapenem-resistant pathogens, including carbapenem-resistant K. pneumoniae (CRKP), E. coli (CREC), P. aeruginosa (CRPA), and A. baumannii (CRAB), were also more commonly detected in this group (Figure 2).
Figure 2.
Comparison of Culture-Positive Bacterial.
Clinical Characteristics and Independent Risk Factors for ESBL-Producing Bacterial Infections in PLA Patients
Among the 255 patients with confirmed bacterial infections, 162 cases underwent ESBL testing, all of whom were infected with either K. pneumoniae (132 strains) or E. coli (37 strains), with 7 cases co-infected with both species. A total of 34 patients (21%) were infected with ESBL-producing bacteria.Multivariable logistic regression identified hepatic tenderness (OR=3.24), a history of intra-abdominal trauma or surgery (OR=3.06) and hospitalization history in the past three months (OR=4.32) as independent risk factors for PLA caused by ESBL-producing bacterial (Table 4).
Table 4.
Clinical Characteristic of ESBL Producing Bacterial Infected PLA Patients
| Variables | Total (n = 162) | Univariate Analysis | Multivariate Analysis | |||||
|---|---|---|---|---|---|---|---|---|
| Non-ESBL-Producing (n = 128) | Esbl-Producing (n = 34) | p-values | p-values | OR | 95% CI for OR | |||
| Demographic | Age, Median (Q1,Q3) | 56 (51, 64) | 55.5 (50, 64) | 56 (52.25, 63) | 0.381 | |||
| Female, n (%) | 79 (48.8) | 63 (49.2) | 16 (47.1) | 0.975 | ||||
| Male, n (%) | 83 (51.2) | 65 (50.8) | 18 (52.9) | |||||
| Clinical symptoms | Fever, n (%) | 135 (83.3) | 108 (84.4) | 27 (79.4) | 0.555 | |||
| Chill, n (%) | 107 (66) | 84 (65.6) | 23 (67.6) | 0.986 | ||||
| Sweat, n (%) | 41 (25.3) | 33 (25.8) | 8 (23.5) | 0.963 | ||||
| Vomit, n (%) | 35 (21.6) | 24 (18.8) | 11 (32.4) | 0.139 | ||||
| Stomachache, n (%) | 82 (50.6) | 59 (46.1) | 23 (67.6) | 0.041 | 0.411 | 1.47 | 0.59–3.72 | |
| Cough, n (%) | 17 (10.5) | 14 (10.9) | 3 (8.8) | 1.000 | ||||
| Weight loss, n (%) | 31 (19.1) | 25 (19.5) | 6 (17.6) | 0.998 | ||||
| Hepatomegaly, n (%) | 26 (16) | 21 (16.4) | 5 (14.7) | 1.000 | ||||
| Hepatic tenderness, n (%) | 53 (32.7) | 36 (28.1) | 17 (50) | 0.027 | 0.014 | 3.24 | 1.29–8.56 | |
| Underling or concomitant conditions | Diabetes mellitus, n (%) | 64 (39.5) | 53 (41.4) | 11 (32.4) | 0.446 | |||
| Biliary disease, n (%) | 41 (25.3) | 27 (21.1) | 14 (41.2) | 0.030 | 0.224 | 1.74 | 0.7–4.26 | |
| History of intra-abdominal trauma or surgery, n (%) | 35 (21.6) | 21 (16.4) | 14 (41.2) | < 0.001 | 0.023 | 3.06 | 1.16–8.12 | |
| Liver fibrosis, n (%) | 6 (3.7) | 5 (3.9) | 1 (2.9) | 1.000 | ||||
| Fattey liver, n (%) | 24 (14.8) | 22 (17.2) | 2 (5.9) | 0.168 | ||||
| Malignancies or hematological diseases, n (%) | 15 (9.3) | 8 (6.3) | 7 (20.6) | 0.018 | 0.268 | 2.28 | 0.49–9.58 | |
| Hospitalization history in the past three months, n (%) | 15 (9.3) | 6 (4.7) | 9 (26.5) | < 0.001 | 0.040 | 4.32 | 1.08–18.07 | |
| Abscess characteristics | Multiple cavitary abscesses, n (%) | 37 (22.8) | 29 (22.7) | 8 (23.5) | 1.000 | |||
| Abscess over 100mm, n (%) | 37 (22.8) | 29 (22.7) | 8 (23.5) | 1.000 | ||||
| Distant metastasis, n (%) | 7 (4.3) | 6 (4.7) | 1 (2.9) | 1.000 | ||||
| Gas, n (%) | 14 (8.6) | 12 (9.4) | 2 (5.9) | 0.736 | ||||
Abbreviations: OR, odds ratio; CI, confidence interval.
Laboratory Findings, Treatment, Complications, Hospitalization Burden and Clinical Outcomes in ESBL-Producing Bacteria Infected PLA Patients
The ESBL-producing group exhibited significantly lower CRP levels (Table 5), while no significant differences in the incidence of pleural effusion or sepsis shock between the ESBL-producing and non-ESBL-producing groups. The most notable divergence lay in therapeutic strategies: surgical intervention was more prevalent in the ESBL group, while percutaneous drainage predominated in non-ESBL-producing group. Hospitalization burden or clinical outcomes are comparable between the two groups.
Table 5.
Laboratory Profiles, Treatment, Complications, Hospitalization Burden and Clinical Outcomes of ESBL - Producing Bacterial Infected PLA Patients
| Total (n = 162) | Non - ESBL Producing (n = 128) | ESBL - Producing (n = 34) | p-value | ||
|---|---|---|---|---|---|
| Laboratory findings | WBC, Median (Q1,Q3) | 12.15 (8.65, 15.3) | 12.35 (8.97, 15.33) | 11.2 (8.22, 14.35) | 0.462 |
| RBC, Mean ± SD | 3.58 ± 0.63 | 3.56 ± 0.61 | 3.65 ± 0.68 | 0.481 | |
| Hb, Mean ± SD | 106.16 ± 19.45 | 106.37 ± 19.53 | 105.38 ± 19.42 | 0.793 | |
| N, Median (Q1,Q3) | 82.2 (76.82, 86.97) | 82 (76.7, 86.23) | 83.35 (77.2, 89.52) | 0.421 | |
| ALB, Median (Q1,Q3) | 28 (24.22, 31.62) | 28 (24.6, 31.4) | 28.37 (22.92, 32.22) | 0.944 | |
| GLB, Mean ± SD | 31.29 ± 6.05 | 31.56 ± 6 | 30.26 ± 6.2 | 0.278 | |
| ALT, Median (Q1,Q3) | 43.95 (26.75, 84.33) | 43.95 (27.05, 80.93) | 42.55 (26.65, 89.35) | 0.705 | |
| AST, Median (Q1,Q3) | 40.35 (24.77, 64.27) | 39.5 (24.62, 62.33) | 42.55 (25.8, 88.67) | 0.454 | |
| TB, Median (Q1,Q3) | 17.6 (10.4, 32.4) | 17.25 (10.35, 30.99) | 23.8 (10.6, 36.4) | 0.536 | |
| DB, Median (Q1,Q3) | 9.25 (4.8, 19.1) | 8.9 (4.8, 16.25) | 15.5 (5.1, 22.55) | 0.24 | |
| ESR, Median (Q1,Q3) | 93 (71, 120) | 94.5 (71.5, 120) | 92 (71.5, 107.5) | 0.608 | |
| CRP, Median (Q1,Q3) | 126 (85, 169) | 133 (91.6, 186) | 87.5 (72.85, 118.31) | 0.007 | |
| PCT, Median (Q1,Q3) | 1.74 (0.54, 11.32) | 1.71 (0.57, 5.67) | 2.1 (0.26, 22.5) | 0.917 | |
| Treatment | Antibiotics alone, n (%) | 20 (12.3) | 14 (10.9) | 6 (17.6) | 0.004 |
| Percutaneous drainage plus antibiotic, n (%) | 118 (72.8) | 100 (78.1) | 18 (52.9) | ||
| Surgery plus antibiotics, n (%) | 17 (10.5) | 8 (6.3) | 9 (26.5) | ||
| Antibiotics plus Percutaneous drainage plus surgery, n (%) | 7 (4.3) | 6 (4.7) | 1 (2.9) | ||
| Complications | Pleural effusion, n (%) | 89 (54.9) | 73 (57) | 16 (47.1) | 0.398 |
| Sepsis shock, n (%) | 8 (4.9) | 7 (5.5) | 1 (2.9) | 1 | |
| Hospitalization burden | Inhospital days, Median (Q1,Q3) | 15.5 (10, 21) | 15.5 (10, 21) | 15.5 (8.25, 20.5) | 0.504 |
| Inhospital cost, Median (Q1,Q3) | 33,380.46 (19,351.59, 49,790.27) | 33,380.46 (19,970.7, 47,598.03) | 34,473.22 (18,881.3, 59,533.68) | 0.8 | |
| Clinical outcomes | Improvement, n (%) | 149 (92) | 117 (91.4) | 32 (94.1) | 0.495 |
| Palliative Discharge, n (%) | 10 (6.2) | 9 (7) | 1 (2.9) | ||
| Death in hospital, n (%) | 3 (1.9) | 2 (1.6) | 1 (2.9) |
Abbreviations: ESBL, extended-spectrum beta-lactamase; WBC, white blood cell count; RBC, red blood cell count; Hb, hemoglobin; N, neutrophil count; ALB, albumin; GLB, globulin; ALT, alanine aminotransferase; AST, aspartate aminotransferase; TB, total bilirubin; DB, direct bilirubin; ESR, erythrocyte sedimentation rate; CRP, C-reactive protein; PCT, procalcitonin.
Comparison of the Antibiotic Resistance Rates of ESBL-Producing and Non-ESBL Producing Bacteria
The proportion of ESBL-producing strains in E. coli was 67.6%, while it was significantly lower in K. pneumoniae (10.6%). Compared with non-ESBL isolates, ESBL-PK exhibited elevated resistance to aztreonam (85.7% vs. 0.8%), ceftriaxone (85.7% vs. 0.8%), ceftazidime (50.0% vs. 0.8%), and cefazolin (78.6% vs. 3.4%). Resistance to ciprofloxacin (50.0% vs. 5.1%) and trimethoprim/sulfamethoxazole (50.0% vs. 4.2%) was also markedly higher in ESBL producers. Carbapenem resistance remained low in both groups (ertapenem 7.1% vs. 0.8%; meropenem 0% vs. 0.8%). ESBL-producing E.coli demonstrated substantially higher resistance than non-ESBL EC to aztreonam (60.0% vs. 0%), ceftriaxone (92.0% vs. 0%), ceftazidime (32.0% vs. 0%), and cefazolin (84.0% vs. 41.7%). Resistance to fluoroquinolones was also higher in ESBL-EC (ciprofloxacin 68.0% vs. 33.3%; levofloxacin 68.0% vs. 33.3%). Notably, non-ESBL E.coli already showed considerable resistance to ampicillin (75.0%), cefazolin (41.7%), and ciprofloxacin (33.3%). Carbapenems retained good activity against both groups (resistance rates 4.0–8.3%). Overall, ESBL-producing isolates of both species exhibited broader and higher resistance to cephalosporins, monobactams, and fluoroquinolones, while carbapenems remained highly active (Table 6).
Table 6.
Comparison of Antibiotic Resistance Rates Between ESBL - Producing and Non - ESBL - Producing Bacteria
| Antibacterial drugs | K. pneumoniae (n= 132) | E.coli (n= 37) | ||||||
|---|---|---|---|---|---|---|---|---|
| ESBL - Producing (n = 14) | Non - ESBL producing (n=118) | ESBL - Producing (n = 25) | Non - ESBL Producing (n = 12) | |||||
| Numbers of Resistance Strains | Resistance Rates | Numbers of Resistance Strains | Resistance Rates | Numbers of Resistance Strains | Resistance Rates | Numbers of Resistance Strains | Resistance Rates | |
| Amikacin | 1 | 7.1% | 1 | 0.8% | 1 | 4.0% | 1 | 8.3% |
| Ampicillin | 14 | 100.0% | 118 | 100.0% | 23 | 92.0% | 9 | 75.0% |
| Aztreonam | 12 | 85.7% | 1 | 0.8% | 15 | 60.0% | 0 | 0.0% |
| Ciprofloxacin | 7 | 50.0% | 6 | 5.1% | 17 | 68.0% | 4 | 33.3% |
| Levofloxacin | 3 | 21.4% | 4 | 3.4% | 17 | 68.0% | 4 | 33.3% |
| Ceftazidime | 7 | 50.0% | 1 | 0.8% | 8 | 32.0% | 0 | 0.0% |
| Ceftriaxone | 12 | 85.7% | 1 | 0.8% | 23 | 92.0% | 0 | 0.0% |
| Cefuroxime | 3 | 21.4% | 3 | 2.5% | 5 | 20.0% | 2 | 16.7% |
| Cefazolin | 11 | 78.6% | 4 | 3.4% | 21 | 84.0% | 5 | 41.7% |
| Cefepime | 6 | 42.9% | 1 | 0.8% | 10 | 40.0% | 1 | 8.3% |
| Gentamicin | 6 | 42.9% | 2 | 1.7% | 8 | 32.0% | 3 | 25.0% |
| Ertapenem | 1 | 7.1% | 1 | 0.8% | 1 | 4.0% | 1 | 8.3% |
| Imipenem | 1 | 7.1% | 1 | 0.8% | 1 | 4.0% | 1 | 8.3% |
| Meropenem | 0 | 0.0% | 1 | 0.8% | 1 | 4.0% | 1 | 8.3% |
| Trimethoprim/Sulfamethoxazole | 7 | 50.0% | 5 | 4.2% | 14 | 56.0% | 4 | 33.3% |
| Tigecycline | 2 | 14.3% | 2 | 1.7% | 1 | 4.0% | 1 | 8.3% |
| Tobramycin | 3 | 21.4% | 0 | 0.0% | 2 | 8.0% | 3 | 25.0% |
| Piperacillin/Tazobactam | 1 | 7.1% | 2 | 1.7% | 3 | 12.0% | 1 | 8.3% |
| Cefoperazone/Sulbactam | 2 | 14.3% | 1 | 0.8% | 5 | 20.0% | 1 | 8.3% |
| Ampicillin/Sulbactam | 8 | 57.1% | 11 | 9.3% | 15 | 60.0% | 5 | 41.7% |
| Nitrofurantoin | 4 | 28.6% | 13 | 11.0% | 1 | 4.0% | 2 | 16.7% |
| Cefotetan | 1 | 7.1% | 1 | 0.8% | 1 | 4.0% | 1 | 8.3% |
Discussion
In this study, we analyzed the clinical characteristics and pathogens associated with PLA at a tertiary hospital in Changsha, China. Among the patients, 41 patients had polymicrobial infection, the prevalence rates in our study are either similar to or lower than those reported by others.1,2,7 Multiple studies have indicated that polymicrobial infections are linked to various complications and higher mortality rates.1,7 In our research, although the mortality rate of polymicrobial infection did not significantly differ from that of other groups, patients with polymicrobial infections had a significantly higher incidence of complications such as septic shock. Moreover, their hospitalization duration was longer, and associated costs were greater. All these results suggest that polymicrobial infections require close monitoring in clinical practice. Early preventive measures should be implemented to alleviate the disease burden on those patients.
Diabetes mellitus and biliary disease are the two most common underlying conditions in this patient cohort. Univariate analysis revealed that diabetes is more prevalent in the polymicrobial infection group. As the close correlation between diabetes mellitus and PLA has been reported by many literatures.2,6,7 A Chinese study found that the risk in diabetic patients complicated with PLA increases 3.6 times higher than in those without diabetes.13 PLA Patients with diabetes are more prone to septicemia, elevated ALT levels and lower albumin levels, of whom disease progression is closely related to blood glucose levels.14,15 Hyperglycemia creates a favorable environment for bacterial growth and directly impairs both innate and adaptive immune responses, including neutrophil chemotaxis, phagocytosis, and intracellular killing. Additionally, diabetes-related microvascular complications reduce hepatic blood supply, compromising the liver’s ability to control infection and inflammation.15–17 Therefore, managing PLA patients with diabetic requires a focus on blood glucose control, timely infection treatment, and comprehensive health monitoring, regular blood glucose checks, prompt use of broad-spectrum antibiotics, and adequate nutritional support are essential. For diabetes patients, clinicians should be alert for symptoms such as fever and abdominal pain, which may indicate the presence of a liver abscess.
Antibiotic resistance is a major public health issue worldwide, in this study, a total of 53 MDR bacteria were identified. Among them, ESBL-producing bacteria were the most common, including 25 strains of ESBL-EC and 14 strains of ESBL-KP. Additionally, 13 carbapenem-resistant bacteria were also detected. This study focused on analyzing the risk factors for PLA caused by ESBL-producing bacteria. A total of 34 patients had ESBL-producing bacterial infection, and the ESBL-producing rate was much higher in E. coli than in K. pneumoniae, which is similar to other studies.7 Notably, E. coli was isolated more frequently in both the polymicrobial infection group and the ESBL-producing group, often accompanied by a higher prevalence of concomitant anaerobic infections. Multiple studies have confirmed that patients with PLA caused by E. coli experience higher rates of complications and mortality, indicating a worse prognosis.1,7 Biliary disease was most frequently observed among patients with ESBL-producing bacteria in our study, and several studies have reported worse outcomes associated with biliary origins.18,19 This may be due to the higher incidence of E. coli infections in biliary-related liver abscesses. E.coli is not only a major pathogen in biliary infections but also a normal resident of the intestinal flora.20 It can migrate to the biliary tract, leading to conditions such as cholangitis or biliary obstruction, which may then cause retrograde infection to the liver.1 Additionally, it is important to remain vigilant for the potential occurrence of malignancies in these patients, as some studies have observed a correlation between E. coli liver abscesses and biliary abnormalities or malignancies.21 These results support that E. coli in liver abscesses continues to be a concern as a life-threatening condition compared with other etiologic agents.
The multivariate analysis in this study revealed that prior intra-abdominal trauma or surgery is risk factor for both polymicrobial and ESBL-producing bacterial infections. It is well known that trauma or surgery may alter the patient’s normal microbiota, leading to the overgrowth of pathogenic bacteria and increasing the risk of infection.22,23 Besides, antibiotics are often administered during surgery to prevent infections. However, inappropriate or excessive use can lead to the development of resistant bacteria, including ESBL-producing strains.24 After surgery, patients are usually hospitalized for monitoring, during which they may be exposed to resistant bacteria present in the hospital environment, increasing the infection risk. This observation also consistent with the multivariate regression analysis indicated a history of hospitalization in the past three months is associated with a higher risk of ESBL-producing bacterial infections. Thus, a thorough understanding of patients’ medical history within clinical practice is essential for the early identification of individuals at elevated risk for infections caused by polymicrobial and drug-resistant organisms.22 This proactive approach aids in the prevention of severe complications and potentially life-threatening conditions, thereby enhancing patient outcomes and the overall quality of care.
In terms of treatment, 65% of patients in this study underwent ultrasound-guided percutaneous drainage of liver abscesses, with varying rates reported in other studies.2,7 Notably, the proportion of surgical interventions was significantly higher in the groups with polymicrobial infections and ESBL-producing bacteria group, indicating that conventional antibiotics or drainage alone may be insufficient to control the condition. This often necessitates surgical resection for symptom relief, leading to extended hospital stays and increased medical costs, consistent with our findings. While effective antibiotic therapy can halt disease progression, selecting appropriate antibiotics remains challenging.2,25 Our study found that E. coli and K. pneumoniae exhibited high resistance rates to cephalosporins and fluoroquinolones, particularly among ESBL-producing strains, whereas the resistance rates to carbapenems were relatively low. Numerous studies have confirmed the sensitivity of ESBL-producing bacteria to carbapenems, which are regarded as first-line treatment options.26–28 Over the 12-year study period, the use of carbapenems gradually increased, particularly in the ESBL-producing group, with a significant rise in the use of meropenem.
Additionally, β-lactam antibiotics combined with clavulanic acid, sulbactam, or tazobactam can be used to treat ESBL infections, although their efficacy may vary based on bacterial species and drug susceptibility.29 While they should not be considered an alternative to carbapenems for definitive treatment of bloodstream infections due to ESBL-producing strains, it might still represent an alternative for step-down therapy or for low-to-moderate severity infection originating from urinary or biliary sources.27 Our study also confirmed relatively low resistance rates for the enzyme inhibitor combinations of Piperacillin/Tazobactam and Cefoperazone/Sulbactam. However, recent research has shown a significant increase in the global incidence of Carbapenem-Resistant Enterobacteriaceae (CRE), particularly in resource-limited settings, where patients infected with CRE have poorer outcomes and higher mortality rates.12,30,31 To prevent a future scenario where increased bacterial resistance leads to a lack of available treatment options, it is essential to introduce new therapeutic strategies. Optimizing antibiotic use is crucial in mitigating the spread of resistance, especially when treating infections caused by ESBL-producing bacteria. To address the growing issue of antibiotic resistance, optimizing antibiotic use through strategies such as antimicrobial stewardship programs is crucial, especially when treating infections caused by ESBL-producing bacteria and other CRE bacterial.
Although this study provides some important insights, it still has limitations. Firstly, as a retrospective analysis, it may be affected by selection bias and data missingness, which can impact the generalizability of the results. Secondly, this is a single-center study, with all cases derived from one hospital; therefore, the results may not be representative of patients in different regions or healthcare settings. Third, the sample sizes in certain subgroups are relatively small, which may not fully capture the antibiotic resistance patterns across diverse populations. Future multicenter, prospective studies are needed to validate our findings and to explore additional influencing factors. Furthermore, given the growing challenge of antibiotic resistance, the clinical application of novel antibiotics and alternative therapies warrants further investigation.
Finally, early screening and intervention for high-risk populations should become an important direction for future research, as this will help in the timely identification of resistant bacterial infections and the development of personalized treatment plans, thereby improving clinical outcomes for patients. Through continuous effort and research, we hope to effectively address the challenges posed by antibiotic resistance and enhance the overall level of infection management and patient care.
Conclusion
This study demonstrates that polymicrobial and ESBL-producing bacterial infections in pyogenic liver abscess have distinct characteristics: ESBL-EC and ESBL-KP are the predominant multidrug-resistant pathogens; E. coli is frequently isolated in both polymicrobial and ESBL-producing groups, often accompanied by anaerobes; intra-abdominal trauma or surgery is a risk factor for both infection types, whereas malignancies and hematological diseases are specifically associated with polymicrobial infection. Based on these findings, we recommend vigilance for ESBL-producing bacterial infections in PLA patients with a recent history of hospitalization. Future multicenter studies are warranted to validate these observations.
Funding Statement
This work was supported by the National Natural Science Foundation of China [grant numbers 82570747]; Natural Science Foundation of Hunan Province under Grant[grant numbers 2025JJ50599].
Abbreviations
ALT, alanine aminotransferase; AST, aspartate aminotransferase; ALB, albumin; CRKP, carbapenem-resistant K. pneumoniae; CREC, carbapenem-resistant E. coli; CRPA, carbapenem-resistant P. aeruginosa; CRAB, carbapenem-resistant A. baumannii; CRKP, carbapenem-resistant K. pneumoniae; CRE, Carbapenem-Resistant Enterobacteriaceae; CRP, C-reactive protein; DB, Direct Bile Acids; ESBL, extended-spectrum β-lactamase; E. coli, Escherichia coli; ESBL-EC, ESBL-producing E. coli; ESBL-KP, ESBL-producing K. pneumoniae hvKP, hypervirulent K. pneumoniae; ESR, erythrocyte sedimentation rate; Hb, Hemoglobin; K. pneumoniae, Klebsiella pneumoniae; MDR, multidrug-resistant; N, Neutrophil Ratio; PLA, Pyogenic liver abscess; PCT, procalcitonin; RBC, red blood cell; TP,Total Protein; TB, Total Bile Acids; WBC, white blood cell.
Data Sharing Statement
The datasets generated and analyzed during the current study are available from the corresponding author upon reasonable request.
Ethical Approval
The study was conducted according to the guidelines of the Declaration of Helsinki, it was a non-interventional retrospective study and has been granted an exemption by the Institutional Review Board of Xiangya Hospital of Central South University, and the need for informed consent was waived (No. 202301011).
Disclosure
The authors report there are no competing interests to declare.
References
- 1.Ruiz-Hernández JJ, Conde-Martel A, Serrano-Fuentes M, et al. Pyogenic liver abscesses due to Escherichia coli are still related to worse outcomes. Ir J Med Sci. 2020;189:155–15. doi: 10.1007/s11845-019-02041-4 [DOI] [PubMed] [Google Scholar]
- 2.Tian Y, Hao D, Du J, et al. Summary of clinical features of 1800 cases of pyogenic liver abscess. Eur J Gastroenterol Hepatol. 2024;37:483–487. doi: 10.1097/MEG.0000000000002906 [DOI] [PMC free article] [PubMed] [Google Scholar]
- 3.Alkomos MF, Estifan E, Melki G, et al. Epidemiological, clinical, microbiological, and risk factors of pyogenic liver abscess: an 18-years retrospective single-center analysis. J Community Hosp Intern Med Perspect. 2021;11:42–45. doi: 10.1080/20009666.2020.1831745 [DOI] [PMC free article] [PubMed] [Google Scholar]
- 4.Mohsen AH, Green ST, Read RC, et al. Liver abscess in adults: ten years experience in a UK centre. QJM Mon J Assoc Physicians. 2002;95:797–802. doi: 10.1093/qjmed/95.12.797 [DOI] [PubMed] [Google Scholar]
- 5.Lardière-Deguelte S, Ragot E, Amroun K, et al. Hepatic abscess: diagnosis and management. J Visc Surg. 2015;152:231–243. doi: 10.1016/j.jviscsurg.2015.01.013 [DOI] [PubMed] [Google Scholar]
- 6.Zhang S, Zhang X, Wu Q, et al. Clinical, microbiological, and molecular epidemiological characteristics of Klebsiella pneumoniae-induced pyogenic liver abscess in southeastern China. Antimicrob Resist Infect Control. 2019;8:166. doi: 10.1186/s13756-019-0615-2 [DOI] [PMC free article] [PubMed] [Google Scholar]
- 7.Long Q, Zhao X, Chen C, et al. Clinical features and risk factors for pyogenic liver abscess caused by multidrug-resistant organisms: a retrospective study. Virulence. 2024;15:2356680. doi: 10.1080/21505594.2024.2356680 [DOI] [PMC free article] [PubMed] [Google Scholar]
- 8.Yamazaki T, Joshita S, Kasuga E, et al. A case of liver abscess co-infected with desulfovibrio desulfuricans and Escherichia coli and review of the literature. J Infect Chemother. 2018;24:393–397. doi: 10.1016/j.jiac.2017.11.006 [DOI] [PubMed] [Google Scholar]
- 9.Anis A, Nalbandian M, Choi C. What and where else: hypervirulent Klebsiella pneumoniae with pyogenic liver abscess and disseminated multifocal osteomyelitis. Ann Intern Med Clin Cases. 2022;1. doi: 10.7326/aimcc.2022.0814 [DOI] [Google Scholar]
- 10.Sun Y, Wu H, Shen D. Clinical and molecular analysis of Klebsiella pneumoniae causing liver abscess in China. Microb Physiol. 2016;26:245–251. doi: 10.1159/000444367 [DOI] [PubMed] [Google Scholar]
- 11.Wang L, Zeng C, Li X, et al. Mortality associated with carbapenem resistance in Klebsiella pneumoniae bloodstream infection: a propensity score–matched study. Infect Control Hosp Epidemiol. 2024;45:839–846. doi: 10.1017/ice.2024.21 [DOI] [PubMed] [Google Scholar]
- 12.Lutgring JD. Carbapenem-resistant enterobacteriaceae: an emerging bacterial threat. Semin Diagn Pathol. 2019;36:182–186. doi: 10.1053/j.semdp.2019.04.011 [DOI] [PubMed] [Google Scholar]
- 13.Zhang S, Chen Y. Progress in diagnosis and treatment of pyogenic liver abscess. J Clin Hepatol. 2018;34:1577–1580. doi: 10.3969/j.issn.1001-5256.2018.07.046 [DOI] [Google Scholar]
- 14.Chen J, Zhang M, Chen J, et al. Cryptogenic and non-cryptogenic liver abscess: a retrospective analysis of 178 cases revealed distinct characteristics. J Int Med Res. 2018;46:3824–3836. doi: 10.1177/0300060518781256 [DOI] [PMC free article] [PubMed] [Google Scholar]
- 15.Giri B, Dey S, Das T, et al. Chronic hyperglycemia mediated physiological alteration and metabolic distortion leads to organ dysfunction, infection, cancer progression and other pathophysiological consequences: an update on glucose toxicity. Biomed Pharmacother. 2018;107:306–328. doi: 10.1016/j.biopha.2018.07.157 [DOI] [PubMed] [Google Scholar]
- 16.Jan Y-K, Kelhofer N, Tu T, et al. Diagnosis, pathophysiology and management of microvascular dysfunction in diabetes mellitus. Diagn Basel Switz. 2024:14. doi: 10.3390/diagnostics14242830. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 17.Eleftheriadou A, Spallone V, Tahrani AA, et al. Cardiovascular autonomic neuropathy in diabetes: an update with a focus on management. Diabetologia. 2024;67:2611–2625. doi: 10.1007/s00125-024-06242-0 [DOI] [PMC free article] [PubMed] [Google Scholar]
- 18.Alvarez Pérez JA, González JJ, Baldonedo RF, et al. Clinical course, treatment, and multivariate analysis of risk factors for pyogenic liver abscess. Am J Surg. 2001;181:177–186. doi: 10.1016/S0002-9610(00)00564-X [DOI] [PubMed] [Google Scholar]
- 19.Malik AA, Bari SU, Rouf KA, et al. Pyogenic liver abscess: changing patterns in approach. World J Gastrointest Surg. 2010;2:395–401. doi: 10.4240/wjgs.v2.i12.395 [DOI] [PMC free article] [PubMed] [Google Scholar]
- 20.Sokal A, Royer G, Esposito-Farese M, et al. Clinical and bacteriological specificities of Escherichia coli bloodstream infections from biliary portal of entries. J Infect Dis. 2024;229:1679–1687. doi: 10.1093/infdis/jiad586 [DOI] [PubMed] [Google Scholar]
- 21.Chen S-C, Wu W-Y, Yeh C-H, et al. Comparison of Escherichia coli and Klebsiella pneumoniae liver abscesses. Am J Med Sci. 2007;334:334. doi: 10.1097/MAJ.0b013e31811ec780 [DOI] [PubMed] [Google Scholar]
- 22.Zhang J, Du Z, Bi J, et al. The impact of previous abdominal surgery on clinical characteristics and prognosis of pyogenic liver abscess: a 10-year retrospective study of 392 patients. Medicine. 2018:97e12290. doi: 10.1097/MD.0000000000012290. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 23.Lederer A-K, Pisarski P, Kousoulas L, et al. Postoperative changes of the microbiome: are surgical complications related to the gut flora? A systematic review. BMC Surg. 2017;17:125. doi: 10.1186/s12893-017-0325-8 [DOI] [PMC free article] [PubMed] [Google Scholar]
- 24.Kim JY, Yum Y, Joo HJ, et al. Impact of antibiotic usage on extended-spectrum β-lactamase producing Escherichia coli prevalence. Sci Rep. 2021;11:13024. doi: 10.1038/s41598-021-91332-x [DOI] [PMC free article] [PubMed] [Google Scholar]
- 25.Shinmoto K, Ohbe H, Nakajima M, et al. Outcomes after early versus delayed antibiotic treatment of liver abscess in Japan: a nationwide retrospective cohort study. J Infect Chemother off J Jpn Soc Chemother. 2023;29:1–6. doi: 10.1016/j.jiac.2022.08.029 [DOI] [PubMed] [Google Scholar]
- 26.Su J, Guo Q, Li Y, et al. Comparison of empirical therapy with cefoperazone/sulbactam or a carbapenem for bloodstream infections due to ESBL-producing enterobacteriaceae. J Antimicrob Chemother. 2018;73:3176–3180. doi: 10.1093/jac/dky323 [DOI] [PubMed] [Google Scholar]
- 27.Bassetti M, Giacobbe DR, Robba C, et al. Treatment of extended-spectrum β-lactamases infections: what is the current role of new β-lactams/β-lactamase inhibitors? Curr Opin Infect Dis. 2020;33:474–481. doi: 10.1097/QCO.0000000000000685 [DOI] [PubMed] [Google Scholar]
- 28.Zhang H, Xu J, Xiao Q, et al. Carbapenem-sparing beta-lactam/beta-lactamase inhibitors versus carbapenems for bloodstream infections caused by extended-spectrum beta-lactamase-producing enterobacteriaceae: a systematic review and meta-analysis. Int J Infect Dis IJID off Publ Int Soc Infect Dis. 2023;128:194–204. doi: 10.1016/j.ijid.2023.01.001 [DOI] [PubMed] [Google Scholar]
- 29.Tamma PD, Rodriguez-Bano J. The use of noncarbapenem β-lactams for the treatment of extended-spectrum β-lactamase infections. Clin Infect Dis off Publ Infect Dis Soc Am. 2017;64:972–980. doi: 10.1093/cid/cix034 [DOI] [PMC free article] [PubMed] [Google Scholar]
- 30.Logan LK, Weinstein RA. The epidemiology of carbapenem-resistant enterobacteriaceae: the impact and evolution of a global menace. J Infect Dis. 2017;215:S28–36. doi: 10.1093/infdis/jiw282 [DOI] [PMC free article] [PubMed] [Google Scholar]
- 31.Kelly AM, Mathema B, Larson EL. Carbapenem-resistant enterobacteriaceae in the community: a scoping review. Int J Antimicrob Agents. 2017;50:127–134. doi: 10.1016/j.ijantimicag.2017.03.012 [DOI] [PMC free article] [PubMed] [Google Scholar]
Associated Data
This section collects any data citations, data availability statements, or supplementary materials included in this article.
Data Availability Statement
The datasets generated and analyzed during the current study are available from the corresponding author upon reasonable request.