Risk factors and mortality rates of carbapenem-resistant Gram-negative bacterial infections in intensive care units

Risk factors and mortality rates of carbapenem-resistant Gram-negative bacterial infections in intensive care units

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Introduction

(Article introduction authored by ICU Editorial Team)

In recent years, the prevalence of hospital-acquired infections caused by carbapenem-resistant Gram-negative bacteria (CRGNB) has increased globally, posing significant threats to patient safety and life.

These infections, particularly in intensive care units (ICUs), are linked to high mortality rates (26%–80%) and increased healthcare costs. Common CRGNB include Acinetobacter baumannii, Pseudomonas aeruginosa, and Klebsiella pneumoniae.

Treatment challenges arise due to the nephrotoxicity and uncertain efficacy of agents like colistin and tigecycline, coupled with limited development of new drugs.

Key risk factors for CRGNB infections include antibiotic exposure, invasive procedures, and ICU stays.

Asymptomatic colonization also increases infection risk and potential cross-transmission. Active surveillance in our hospital from 2017 to 2021 showed rising carbapenem resistance rates in A. baumannii (96.5% to 100%), K. pneumoniae (49.2% to 79.6%), and P. aeruginosa (45.8% to 93.1%).

Identifying high-risk patients and implementing early infection control measures are crucial. This study aimed to identify risk factors and determine mortality rates associated with CRGNB infections in ICUs.

Methods

This retrospective case-control study was conducted at Erciyes University Hospital (Kayseri, Turkey) from January 2017 to December 2021. Adult patients (>18 years) hospitalized for >48 hours in five ICUs (internal, general surgery, anesthesia, neurosurgery, thoracic) were included.

The hospital has 61 ICU beds. In the general surgery ICU, one nurse cares for two patients; in other ICUs, one nurse manages three patients due to staff shortages.

Patients with CRGNB infection 48–72 hours post-ICU admission were the case group; those without CRGNB formed the control group. Only the first CRGNB detection per patient was considered.

Data collected included demographics, diagnostic categories, comorbidities, invasive procedures, CRGNB colonization, surgery history, hospitalization duration, prior antibiotics use, transfers, and outcomes (discharge or death). ICU admissions were for medical reasons or postoperative follow-up.

Infection Prevention and Control Measures for CRGNB

Since 2005, ICU patients were regularly screened for CRGNB with rectal swabs upon admission and weekly. Positive patients were isolated. Personal protective equipment, hand hygiene, and contact precautions were enforced. ICU rooms were cleaned and disinfected twice daily, with thorough disinfection before new admissions.

Isolation ended after three negative rectal swabs. Positive cultures were coordinated with the microbiology lab, and the clinical team was informed. Infection control nurses conducted daily ICU visits for surveillance.

Definitions and Bacterial Isolation

Hospital-acquired infections were defined by National Healthcare Safety Network criteria. Colonization meant CRGNB culture positivity without infection needing treatment. Antibiotic history was use for >48 hours within two weeks before infection onset.

Rectal swabs were taken within 24 hours of ICU admission for colonization assessment. Pathogens were identified using the BD Phoenix system, carbapenem resistance by Kirby–Bauer disk diffusion, and colistin resistance by liquid microdilution.

Statistical Analysis

Data were analyzed using SPSS version 25.0. Categorical variables were compared using chi-squared or Fisher’s exact test. The Shapiro–Wilk test checked data normality. The Mann–Whitney U test compared continuous variables. Variables with P ≤ 0.05 in univariate analysis were included in multivariate logistic regression analysis.

Results

Demographic data

A total of 16,147 patients were admitted to the ICU for treatment and follow-up between January 2017 and December 2021. Of the 1449 patients (8.97%) followed up during active surveillance, 1171 were included in the study.

The number of patients with CRGNB colonization at the time of admission and during hospitalization was 20 (1.71%) and 207 (17.68%), respectively; the number of patients without CRGNB colonization was 944 (80.61%). Of those, 691 patients (59.01%) developed CRGNB infection, whereas 480 (40.99%) did not have CRGNB infection.

Fourteen patients (70.00%) who had CRGNB colonization at admission developed CRGNB infection; 162 patients (78.26%) were infected during the hospitalization, whereas 515 patients (54.56%) were not infected at all (Figure 1).

There was no significant difference in terms of age, sex, or comorbidities between the case and control groups. The total length of hospital stay (median: 24 [interquartile range: 3–378] days), was statistically significantly longer (P=0.001) in the case group than the control group.

The rate of colonization at admission was significantly higher in the case group than in the control group (25.5% vs. 10.6%, respectively; P=0.001). In the case group, patients were mostly followed in the medical ICU. In the case group, patients were mostly transferred from other units and hospitals (P=0.032).

Risk factors and mortality

The study found significantly higher mortality rates in the case group with CRGNB infections compared to the control group (64.4% vs. 45.8%; P=0.001). Previous antibiotic use was more common in the case group (93.6% vs. 81.7%; P=0.001).

Ventilator-associated pneumonia was the most frequent infection in the case group (40.4%), while central line-associated bloodstream infection (CLABSI) was most common in the control group (29.8%). Among those with ventilator-associated pneumonia in the case group, 74.2% had no colonization, 24.7% were colonized during hospitalization, and 1.1% were colonized before hospitalization.

For CLABSI in the control group, 86.0% had no colonization, 13.3% were colonized during hospitalization, and 0.7% were colonized before hospitalization.

The case group had significantly higher rates of invasive procedures and supportive therapies, such as enteral nutrition, transfusion, hemodialysis, mechanical ventilation, tracheostomy, reintubation, CVC use, arterial catheterization, chest tube, nasogastric tube use, percutaneous endoscopic gastrostomy, and bronchoscopy (P <0.05), whereas the control group had higher rates of peripheral catheter use and history of operation (P <0.05). Univariate analysis indicated several factors associated with CRGNB infections, including prolonged hospitalization, time from ICU admission to infection, colonization at admission, transfer from other hospitals, and various invasive procedures (P <0.05).Multivariate analysis highlighted the total length of hospital stay, colonization, previous antibiotic use, intubation/mechanical ventilation, tracheostomy, and CVC use as key risk factors for developing CRGNB infections.

Discussion

In this retrospective study conducted over five years at Erciyes University Hospital in Turkey, several key risk factors associated with carbapenem-resistant Gram-negative bacteria (CRGNB) infections in ICU patients were identified.

These factors included prolonged hospital stays, colonization with CRGNB, prior antibiotic use, intubation, tracheostomy, and central venous catheter (CVC) usage. CRGNB infections pose a significant global threat, with projections suggesting a staggering number of deaths attributable to antimicrobial resistance in the coming decades.

Colonization with CRGNB in the ICU was found to increase the risk of subsequent infection and mortality rates. Studies have shown that CRGNB can spread horizontally among patients within healthcare settings, facilitated by colonization, healthcare workers, contaminated environments, and medical devices.

Active surveillance for CRGNB colonization, along with infection prevention and control measures, is crucial for mitigating the spread of these pathogens. Rectal screening has been effective in reducing the incidence of CRGNB infections, leading to early initiation of appropriate empirical antibiotic therapy.

Invasive procedures, such as intubation, tracheostomy, and CVC use, were significantly associated with CRGNB colonization and infection, highlighting the importance of proper infection control measures during such interventions.

Additionally, previous antibiotic use emerged as a significant risk factor, emphasizing the need for judicious antibiotic prescribing practices to combat antimicrobial resistance.

While this study provides valuable insights, its retrospective nature and limitations in data collection underscore the importance of further research in this area.

Conclusion

In summary, this study underscores the significance of colonization, prior antibiotic exposure, and invasive procedures as major risk factors for infections caused by resistant Gram-negative bacteria (CRGNB). These factors not only prolong hospital stays but also elevate mortality rates among patients.

Consequently, it is imperative to implement tailored measures in clinical settings to address these challenges effectively.

Key infection prevention and control strategies include strict adherence to standard and contact precautions, active microbiological surveillance, feedback mechanisms, reducing the use and duration of invasive devices, thorough environmental cleaning and disinfection, multidisciplinary collaboration, emphasis on antimicrobial prophylaxis, and development of antimicrobial management protocols specific to the ICU.

Future prospective studies are needed to further elucidate these findings and gain a deeper understanding of the carrier profile of these resilient microorganisms.

Source: Tulay Orhan Kuloglu: Methodology, Validation, Visualization, Writing – original draft, Resources. Gamze Kalin Unuvar: Conceptualization, Methodology, Validation, Software, Visualization, Writing – review & editing, Writing – original draft, Resources. Fatma Cevahir: Software, Formal analysis. Aysegul Ulu Kilic: Methodology, Investigation. Emine Alp: Conceptualization, Methodology, Supervision, Data curation.