Burden and Spectrum of Multidrug-Resistant Bacterial Infections in Chronic Liver, Respiratory, and Urological Diseases: A Systematic Review.

Multidrug-resistant infections have emerged as a major threat to modern healthcare. The increasing prevalence of resistant organisms has reduced the effectiveness of commonly used antibiotics and has complicated the management of infections in hospitalized, immunocompromised, and chronically ill patients. Multidrug resistance is commonly defined as non-susceptibility to at least one agent in three or more antimicrobial categories. MDR infections are associated with delayed appropriate therapy, increased treatment failure, prolonged hospital stay, higher healthcare costs, and increased mortality.

Patients with chronic comorbidities are particularly vulnerable to MDR infections. Among these, liver disease, chronic respiratory disorders, and urological comorbidities represent three clinically important groups. These conditions are frequently associated with recurrent healthcare contact, repeated antibiotic exposure, invasive procedures, immune dysregulation, colonization by resistant organisms, and recurrent infections.

 

Chronic liver disease and cirrhosis are associated with immune dysfunction, bacterial translocation, altered gut microbiota, portal hypertension, ascites, frequent hospitalization, and repeated exposure to broad-spectrum antibiotics. Patients with cirrhosis are at increased risk of spontaneous bacterial peritonitis, bloodstream infection, urinary tract infection, pneumonia, and soft tissue infection. MDR organisms in cirrhosis are clinically important because they may lead to failure of standard empirical therapy and higher mortality.

 

Chronic respiratory disorders, including chronic obstructive pulmonary disease, bronchiectasis, interstitial lung disease, and long-standing structural lung disease, predispose patients to recurrent lower respiratory tract infection. Frequent exacerbations, repeated antibiotic use, corticosteroid exposure, hospitalization, mechanical ventilation, and chronic airway colonization increase the risk of MDR respiratory pathogens. Pseudomonas aeruginosa, Klebsiella pneumoniae, Acinetobacter baumannii, MRSA, and other resistant organisms may be involved in acute exacerbations, pneumonia, and ventilator-associated infections.

 

Urological comorbidities also contribute substantially to the burden of MDR infections. Recurrent urinary tract infection, obstructive uropathy, renal stones, neurogenic bladder, urinary catheterization, urological instrumentation, benign prostatic hyperplasia, chronic kidney disease, and prior antibiotic use are major risk factors. MDR uropathogens, particularly ESBL-producing E. coli and Klebsiella pneumoniae, carbapenem-resistant Enterobacterales, vancomycin-resistant enterococci, and resistant Pseudomonas species, are increasingly reported in community and hospital settings.

 

Although MDR infections have been studied separately in liver disease, respiratory disorders, and urological conditions, a combined systematic synthesis across these comorbidity groups is useful. Such an approach can help identify common pathogen patterns, resistance mechanisms, infection syndromes, and risk factors shared across chronic disease populations. It can also guide empirical antibiotic selection, infection prevention, antimicrobial stewardship, and diagnostic strategies.

The present systematic review was conducted to evaluate the spectrum of multidrug-resistant infections in patients with liver disease, chronic respiratory disorders, and urological comorbidities, with emphasis on pathogen distribution, resistance phenotypes, infection sites, and clinical outcomes.

Study Design

This systematic review was conducted according to PRISMA 2020 principles. The review focused on studies reporting MDR infections among patients with liver disease, chronic respiratory disorders, or urological comorbidities.

 

Review Question

What is the spectrum of multidrug-resistant infections in patients with liver disease, chronic respiratory disorders, and urological comorbidities?

Eligibility Criteria

 

Studies were included if they met the following criteria:

1.             Included patients with liver disease, chronic respiratory disorders, or urological comorbidities.

2.             Reported multidrug-resistant bacterial infections or MDR colonization with clinical relevance.

3.             Provided data on pathogens, resistance patterns, infection sites, or outcomes.

4.             Included adult or mixed adult populations.

5.             Used cohort, case-control, cross-sectional, surveillance, or observational study design.

6.             Were published in English.

Studies were excluded if they were case reports, editorials, narrative reviews, animal studies, pediatric-only studies, studies without comorbidity-specific data, or studies reporting only fungal, viral, or parasitic infections.

 

 

 

Search Strategy

A literature search was performed in PubMed, Scopus, Embase, Web of Science, Cochrane Library, and Google Scholar for studies published from January 2000 to December 2025.

The following search terms were used in different combinations:

“multidrug-resistant infection,” “MDR infection,” “antimicrobial resistance,” “ESBL,” “carbapenem-resistant Enterobacterales,” “MRSA,” “VRE,” “cirrhosis,” “chronic liver disease,” “spontaneous bacterial peritonitis,” “COPD,” “bronchiectasis,” “chronic respiratory disease,” “pneumonia,” “urinary tract infection,” “urological comorbidity,” “catheter-associated UTI,” “obstructive uropathy,” and “urosepsis.”

 

Study Selection

All retrieved records were screened by title and abstract. Duplicate records were removed. Full-text articles were assessed according to eligibility criteria. Studies fulfilling inclusion criteria were included in the systematic review.

 

Data Extraction

The following data were extracted:

•              Author and year

•              Country

•              Study design

•              Patient population

•              Comorbidity group

•              Sample size

•              Infection site

•              Pathogen isolated

•              Resistance mechanism or phenotype

•              MDR definition used

•              Antibiotic susceptibility pattern

•              Empirical therapy failure

•              ICU admission

•              Length of hospital stay

•              Relapse or recurrence

•              Mortality

 

Outcome Measures

The primary outcome was the spectrum of MDR pathogens among patients with liver disease, chronic respiratory disorders, and urological comorbidities.

Secondary outcomes included:

1.             Distribution of infection sites.

2.             Frequency of ESBL-producing organisms.

3.             Frequency of carbapenem-resistant organisms.

4.             MRSA and VRE rates.

5.             Comorbidity-specific pathogen distribution.

6.             Treatment failure.

7.             ICU admission.

8.             Relapse or recurrence.

9.             Mortality.

 

Quality Assessment

The methodological quality of included studies was assessed using a modified Newcastle-Ottawa Scale for observational studies. Studies were evaluated based on selection of participants, definition of MDR infection, microbiological methods, outcome reporting, and control for confounding factors. Studies were classified as good, moderate, or low quality.

Study Selection

A total of 1,032 records were identified through database and manual searching. After removal of 246 duplicates, 786 records were screened by title and abstract. Of these, 651 records were excluded. One hundred and thirty-five full-text articles were assessed for eligibility. Ninety-seven full-text articles were excluded due to absence of comorbidity-specific data, non-MDR infection focus, pediatric-only population, inadequate microbiological reporting, or duplicate study populations. Finally, 38 studies were included in the systematic review.

 

 

Table 1. PRISMA Study Selection Summary

 

Table 2. Reasons for Full-Text Exclusion

 

Figure 1 shows the PRISMA 2020 study selection process. A total of 1,032 records were identified through database and manual searching. After removal of duplicates and screening, 135 full-text articles were assessed for eligibility, and 38 studies were included in the final systematic review.

Characteristics of Included Studies

The 38 included studies involved 12,486 patients. Most studies were retrospective cohort or cross-sectional studies. Liver disease was assessed in 14 studies, chronic respiratory disorders in 12 studies, and urological comorbidities in 12 studies. A total of 4,972 MDR isolates were reported.

 

Table 3. Characteristics of Included Studies

Abbreviations: COPD, chronic obstructive pulmonary disease; CRE, carbapenem-resistant Enterobacterales; CR, carbapenem-resistant; ESBL, extended-spectrum beta-lactamase; MDR, multidrug resistant; MRSA, methicillin-resistant Staphylococcus aureus; SBP, spontaneous bacterial peritonitis; UTI, urinary tract infection; VRE, vancomycin-resistant enterococci.

 

Distribution of MDR Infections by Comorbidity Group

MDR infections were most frequently reported in patients with urological comorbidities, followed by liver disease and chronic respiratory disorders. Urological cases were dominated by urinary tract infection and urosepsis. Liver disease cases frequently included spontaneous bacterial peritonitis, bloodstream infection, pneumonia, and UTI. Respiratory disorder cases mainly included pneumonia, infective exacerbations, and airway colonization with clinical infection.

 

Table 4. MDR Infection Distribution by Comorbidity Group

 

Overall Pathogen Spectrum

Gram-negative bacilli accounted for 72.8% of MDR infections. The most common pathogen was Escherichia coli, followed by Klebsiella pneumoniae, Pseudomonas aeruginosa, Acinetobacter baumannii, Enterococcus species, and MRSA.

Table 5. Overall MDR Pathogen Distribution

 

Resistance Phenotypes

ESBL production was the most frequent resistance phenotype, reported in 42.7% of MDR isolates. Carbapenem resistance was reported in 21.6%, MRSA in 7.9%, VRE in 4.8%, and colistin resistance in 2.9%.

Table 6. Resistance Phenotypes Among MDR Isolates

 

MDR Infections in Liver Disease

Among patients with liver disease, MDR infections were commonly associated with cirrhosis, decompensated liver disease, ascites, prior hospitalization, antibiotic prophylaxis, invasive procedures, and ICU admission. The common infection syndromes were spontaneous bacterial peritonitis, bloodstream infection, pneumonia, urinary tract infection, and soft tissue infection.

Table 7. MDR Infection Spectrum in Liver Disease

 

Common MDR Syndromes in Liver Disease

 

MDR Infections in Chronic Respiratory Disorders

Patients with chronic respiratory disorders frequently had MDR respiratory infections due to prior antibiotics, repeated exacerbations, structural lung disease, hospitalization, corticosteroid exposure, and ventilatory support. Pseudomonas aeruginosa was the leading MDR respiratory pathogen.

 

Table 8. MDR Infection Spectrum in Chronic Respiratory Disorders

 

Common MDR Syndromes in Chronic Respiratory Disorders

 

MDR Infections in Urological Comorbidities

Urological comorbidities were strongly associated with recurrent MDR urinary infections. ESBL-producing E. coli was the dominant pathogen, followed by Klebsiella pneumoniae, Enterococcus, Pseudomonas, and Proteus species.

 

Table 9. MDR Infection Spectrum in Urological Comorbidities

Common MDR Syndromes in Urological Comorbidities

 

Risk Factors for MDR Infection

Across included studies, the most consistent risk factors were prior antibiotic exposure, hospitalization within the previous 90 days, ICU stay, invasive devices, urinary catheterization, decompensated liver disease, structural lung disease, prior MDR colonization, and recurrent infection.

 

Table 10. Common Risk Factors for MDR Infection

 

Clinical Outcomes

MDR infections were associated with adverse clinical outcomes, including empirical antibiotic failure, prolonged hospitalization, ICU admission, relapse, and mortality.

 

Table 11. Clinical Outcomes Associated with MDR Infections

 

Quality Assessment

Of the 38 included studies, 16 were rated as good quality, 15 as moderate quality, and 7 as low quality. Common limitations included retrospective design, variability in MDR definitions, inconsistent reporting of antimicrobial susceptibility, and lack of adjustment for confounders.

 

Table 12. Quality Assessment Summary

 

Figure 2 presents the pooled spectrum of MDR pathogens across patients with liver disease, chronic respiratory disorders, and urological comorbidities. Gram-negative bacilli predominated, with Escherichia coli and Klebsiella pneumoniae being the most common isolates.

This systematic review highlights the substantial burden of multidrug-resistant infections among patients with liver disease, chronic respiratory disorders, and urological comorbidities. These patient groups represent high-risk populations because of repeated healthcare contact, immune dysfunction, recurrent antibiotic exposure, invasive devices, and frequent episodes of infection.

 

The overall pathogen spectrum was dominated by Gram-negative organisms, which accounted for nearly three-fourths of MDR isolates. Escherichia coli and Klebsiella pneumoniae were the leading organisms, reflecting the major contribution of urinary, intra-abdominal, bloodstream, and healthcare-associated infections. ESBL production was the most common resistance phenotype, suggesting widespread resistance to third-generation cephalosporins. This has important clinical implications because cephalosporins are frequently used as empirical therapy in cirrhosis-related infections, respiratory infections, and urinary tract infections.

 

Carbapenem resistance was also prominent, particularly among Klebsiella pneumoniae, Acinetobacter baumannii, and Pseudomonas aeruginosa. Carbapenem-resistant infections are especially difficult to treat and are associated with increased mortality, limited therapeutic options, and need for newer or combination antibiotics. The presence of colistin resistance and pan-drug resistant isolates, although less frequent, is highly concerning because it indicates the emergence of organisms with extremely limited treatment options.

 

In patients with liver disease, MDR infections were frequently associated with spontaneous bacterial peritonitis, bloodstream infection, pneumonia, and urinary tract infection. Cirrhosis predisposes to infection through cirrhosis-associated immune dysfunction, bacterial translocation, altered gut permeability, portal hypertension, ascites, and frequent hospitalization. Traditional empirical therapy for spontaneous bacterial peritonitis often relies on third-generation cephalosporins, but rising ESBL and carbapenem-resistant organisms may reduce treatment success. MDR infection in cirrhosis is clinically important because these patients often have poor physiological reserve, renal dysfunction, coagulopathy, and high risk of sepsis-related mortality.

 

In chronic respiratory disorders, MDR infections were mainly respiratory in origin. Pseudomonas aeruginosa was the most frequent MDR respiratory pathogen, followed by Klebsiella pneumoniae, Acinetobacter baumannii, and MRSA. Patients with COPD, bronchiectasis, and chronic structural lung disease are prone to airway colonization and repeated infective exacerbations. Recurrent antibiotic courses, corticosteroid use, hospital admission, and mechanical ventilation further increase MDR risk. Differentiating colonization from true infection is an important challenge in this group, especially in bronchiectasis and COPD.

 

Urological comorbidities showed the highest number of MDR isolates in this review. Recurrent UTI, catheter-associated UTI, pyelonephritis, and urosepsis were the dominant clinical syndromes. ESBL-producing E. coli was the most frequent pathogen, followed by ESBL-producing Klebsiella pneumoniae, carbapenem-resistant Enterobacterales, Enterococcus species, and Pseudomonas aeruginosa. Urological risk factors such as catheterization, obstruction, stones, neurogenic bladder, benign prostatic hyperplasia, prior instrumentation, and recurrent antibiotic exposure contribute to persistence and recurrence of MDR organisms.

 

Prior antibiotic exposure was the most common risk factor across included studies. This finding reinforces the importance of antimicrobial stewardship. Repeated or inappropriate antibiotic use selects resistant organisms, disrupts normal microbiota, and increases colonization pressure. Stewardship interventions should include culture-guided therapy, avoidance of unnecessary antibiotics, de-escalation based on susceptibility, appropriate duration, and local antibiogram-based empirical treatment.

 

Recent hospitalization and ICU admission were also major risk factors. Healthcare exposure increases the risk of colonization with MDR organisms through contact with hospital flora, invasive devices, broad-spectrum antibiotics, and cross-transmission. Infection control measures, including hand hygiene, contact precautions, environmental cleaning, device care bundles, and surveillance of high-risk units, are essential to reduce transmission.

 

The review also highlights the role of invasive devices. Urinary catheters, central venous catheters, endotracheal tubes, and drains are important portals for infection. Device-associated infections are often caused by MDR organisms and biofilm-forming bacteria. Prevention requires strict indications for device use, early removal, aseptic insertion, maintenance bundles, and regular review of device necessity.

 

Clinical outcomes were worse among patients with MDR infections. Empirical antibiotic failure occurred in nearly one-third of cases. This is important because delayed appropriate therapy is a major determinant of poor outcome in severe infections. Risk stratification is therefore necessary before selecting empirical antibiotics. Patients with recent hospitalization, prior MDR infection, prior broad-spectrum antibiotic exposure, ICU admission, catheterization, decompensated liver disease, or recurrent UTI may require broader initial coverage while awaiting culture results.

 

The pooled mortality was clinically significant, with in-hospital mortality of 22.7% and 30-day mortality of 18.3%. Mortality is likely influenced by comorbidity severity, sepsis, delayed appropriate therapy, organ dysfunction, ICU admission, and limited antibiotic options. Liver disease patients may have particularly high mortality due to baseline hepatic decompensation, renal dysfunction, and immune dysfunction. Respiratory patients may deteriorate due to hypoxemia, ventilatory failure, and pneumonia severity. Urological patients may progress to urosepsis, especially in obstructive infection.

 

The review has important implications for clinical practice. First, high-risk comorbidity groups should undergo early microbiological sampling before antibiotic initiation whenever feasible. Second, empirical therapy should be individualized based on comorbidity, infection site, severity, prior culture history, recent antibiotic exposure, and local resistance patterns. Third, early de-escalation should be performed once susceptibility results are available. Fourth, infection prevention strategies should be comorbidity-specific, including SBP prevention protocols in cirrhosis, airway infection control in chronic respiratory disease, and catheter reduction strategies in urological patients.

 

This review also emphasizes the need for integrated microbiology reporting. Standard culture and susceptibility testing should be accompanied by resistance phenotype reporting, such as ESBL, carbapenem resistance, MRSA, and VRE. Hospitals should maintain comorbidity-specific antibiograms where possible, because resistance patterns in cirrhosis, respiratory disease, and urological infections may differ from general hospital antibiograms.

 

The review has limitations. Most included studies were observational and hospital-based. MDR definitions varied across studies. Some studies reported isolates rather than patient-level infection episodes, which may overrepresent recurrent infections. Distinguishing colonization from infection was difficult in chronic respiratory disorders and catheterized urological patients. Data on antibiotic regimens, duration, source control, and long-term outcomes were inconsistently reported. Therefore, pooled estimates should be interpreted as broad summary patterns rather than precise epidemiological rates.

 

Despite these limitations, the review provides a comprehensive overview of MDR infection patterns across three high-risk comorbidity groups. It demonstrates that Gram-negative resistance, especially ESBL and carbapenem resistance, is the dominant microbiological challenge. It also highlights that prevention, early diagnosis, culture-guided therapy, and stewardship are essential to improve outcomes.

Patients with liver disease, chronic respiratory disorders, and urological comorbidities are at high risk for multidrug-resistant infections. Gram-negative bacilli predominate, especially ESBL-producing E. coli, ESBL-producing Klebsiella pneumoniae, carbapenem-resistant Enterobacterales, MDR Pseudomonas aeruginosa, and carbapenem-resistant Acinetobacter baumannii. MRSA and VRE also contribute to the MDR burden, particularly in hospitalized and device-associated infections.

 

Liver disease is commonly associated with MDR spontaneous bacterial peritonitis, bloodstream infection, pneumonia, and UTI. Chronic respiratory disorders are frequently associated with MDR pneumonia and airway infection. Urological comorbidities are dominated by recurrent MDR UTI, catheter-associated UTI, pyelonephritis, and urosepsis.

 

Prior antibiotic exposure, recent hospitalization, ICU admission, invasive devices, recurrent infection, and prior MDR colonization are major risk factors. Risk-based empirical therapy, early microbiological diagnosis, antimicrobial stewardship, infection control, and comorbidity-specific prevention strategies are essential to reduce treatment failure, relapse, and mortality.

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