Original Article

The Relationship Between Positive Cultures With Multidrug-Resistant Microorganisms and Mortality in a General Intensive Care Unit

Please cite this article as follows: Marghoob B, Khosravi Khezri M. The relationship between positive cultures with multidrug-resistant microorganisms and mortality in a general intensive care unit. Avicenna J Clin Microbiol Infect. 2022; 9(2):70-76. doi:10.34172/ajcmi.2022.11

Introduction

The patients in the intensive care unit (ICU) are more susceptible to healthcare-associated infections (HAI) because of the dysregulation of the immune response and host defense reduction, invasive procedures (mechanical ventilation, vascular access, and urinary catheter), more severe disease, and broad-spectrum antibiotics administration. Higher rates of nosocomial infections in ICU patients are related to higher morbidity, mortality, and costs (1-3).

The occurrence of resistant infections such as methicillin-resistant Staphylococcus aureus (MRSA), vancomycin-resistant Enterococcus (VRE), extended-spectrum beta-lactamases (ESBL)-producing Enterobacteriaceae, and carbapenem-resistant Enterobacteriaceae, especially in the ICU has increased in recent years. These resistant infections have negative effects on patient survival (1-3).

Microorganisms such as MRSA,methicillin-resistant Staphylococcus epidermidis (MRSE),VRE,andESBL-producing Enterobacteriaceae are considered resistant.

Multi-drug resistance (MDR) organism is determined by resistance to at least one agent in three or more antimicrobial categories. Extensive drug resistance is defined as resistance to at least one agent in all but two or fewer antimicrobial categories (i.e., bacterial isolates remain susceptible to only one or two categories), and pan-drug resistance (PDR) is referred to as non-susceptibility to all agents in all antimicrobial categories (4).

It is estimated that about 650 000 people in the United States develop nosocomial infections each year, of which 20% are caused by resistant microorganisms (5,6).

Several studies demonstrated that patients admitted to the ICU who are undergoing invasive procedures are more infected with resistant microorganisms (1,7). This can increase mortality by up to 70% in ICU patients (2,8,9).

In recent years, overuse and misuse of antibiotics have led to antibiotic resistance in various countries, which is a major threat to the world (3). It is estimated that approximately 20%-50% of all antibiotics and 30% of antibiotic use in United States acute care hospitals are unnecessary or ineffective (10,11). Every year, at least 2.8 million people become infected with antibiotic-resistant infections in the United States, and more than 35 000 people die accordingly (12). The treatment of resistant infections is difficult and costly.

Infections caused by resistant microorganisms are associated with increased mortality and hospitalization (13,14).

Optimizing antibiotic prescription using antibiotic stewardship programs can reduce antibiotic resistance and improve the cure rate.

In Iran, antimicrobial resistance is a serious problem and there is no complete antimicrobial monitoring system for data gathering, analysis, and decision-making in this regard. It is important to determine the local antibiotic resistance pattern in each center because it helps prescribe more appropriate antibiotics.

The aim of our study was to investigate the association between resistant microorganisms and length of ICU stay and mortality. In addition, we determined the pattern of antibiotic resistance of more frequent infections at our ICU center. It was hypothesized that ICU stay and mortality rates were higher in patients with resistant infections.

Methods

We performed a 5-year observational retrospective study. All adult patients (≥18 years) admitted to the general ICU (6 beds) of Hasheminejad Kidney Center affiliated to Iran University of Medical Sciences, Tehran, Iran from January 1, 2015 to January 1, 2020 enrolled in the study. The inclusion criterion was to have at least one microbial culture during their stay in the ICU. On the other hand, patients with incomplete or missing data were excluded from the study.

Patient characteristics were retrospectively collected, including age, gender, admission type, comorbidities, length of ICU stay, length of hospital stay, infection source, microorganism type, and resistance pattern of all isolates and outcomes.

The samples of blood, urine, trachea/sputum, catheter, wound, and other bodily fluids and tissues with a clinical suspicion of infection were taken for testing. If the patients had more than one positive culture from different sites, it was considered a separate infection.

Statistical analyses were performed using SPSS-21 software. Data were reported as the mean or median, as well as frequencies or percentages for quantitative and qualitative variables, respectively.

Bivariate analyses were performed to indicate the associations between infection by resistant pathogens and death. Then, multivariate logistic regression models were developed to identify multiple variables associated with our outcome. Moreover, the association between length of ICU stay and death was assessed using a bivariate model. Ultimately, multiple covariates in multivariate analyses were tested to assess whether there were any associations between these variables and the outcome.

The odds ratios (ORs) with 95% confidence intervals estimated from the beta coefficients, were calculated, and P > 0.05 was considered statistically significant.

Results

During the 5-year study, 2899 patients were admitted to the ICU, but only 747 patients were enrolled in the study. They included 426 males (57%). The median age was 65 years (19-97 years, Table 1).

The mean patient age in culture-positive and culture-negative groups was 65 and 62 years, respectively (Table 1). Two hundred and twenty-seven (60.85%) and 198 (53.22%) patients in the culture-positive and culture-negative groups were males, respectively (Table 2).

During the study period, 374 patients (50.1%) developed at least one culture positive. Of them, 138 (18.45%), 116 (15.5%), 167 (22.3%), 49 (6.5%), and 20 (2.6%) cases had positive blood culture, positive urine culture, positive culture related to the respiratory tract, positive catheter culture, and positive wound culture, respectively.

Two hundred and sixty-five patients (35.5%) died during hospital admission. The overall mortality in different years is indicated in Table 3.

Five hundred and seventy-one microorganisms were isolated of whom 458 (80.2%) cases were considered MDR. The most frequently isolated organisms were E. coli (24%), Acinetobacter baumannii (19%), Klebsiella pneumonia (16%), Staphylococcus epidermidis (13%), and Staphylococcus aureus (11%). The distribution of various microorganisms is illustrated in Figure 1.

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Figure 1.

Microorganisms Isolated From ICU Patients. Note. ICU: Intensive care unit.

Figure 1.

Microorganisms Isolated From ICU Patients. Note. ICU: Intensive care unit.

The mean length of ICU stay was greater in culture-positive patients compared to culture-negative patients (8.42 vs. 3.5 days, P > 0.001). In addition, culture-positive patients had significantly higher mortality in comparison to culture-negative patients (63.8% vs. 36.2%, P > 0.001).

Microbial isolates collected from any sources are presented in Table 4. We evaluated the variations in the frequency of microorganisms and MDR isolates for 5 years. Figures 2 and 3 display the trend of microorganism frequencies and MDR pathogens over 5 years. The incidence of MDR isolates had variations across the study period. For example, the incidence of A. baumannii PDR decreased over years, but that of VRE incidence represented an increase. The incidence of other MDR pathogens did not have any significant changes.

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Figure 2.

Annual Changing of Microorganisms Frequencies in ICU. Note. ICU: Intensive care unit.

Figure 2.

Annual Changing of Microorganisms Frequencies in ICU. Note. ICU: Intensive care unit.

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Figure 3.

Annual Changing of MDR Microorganisms Frequencies in ICU. Note. MDR: Multidrug-resistant; ICU: Intensive care unit.

Figure 3.

Annual Changing of MDR Microorganisms Frequencies in ICU. Note. MDR: Multidrug-resistant; ICU: Intensive care unit.

In our center’s laboratory, the criteria of the Clinical and Laboratory Standards Institute (CLSI) are used to assess the susceptibility to antimicrobial agents.

In the current study, it was demonstrated that resistant microorganisms have increased mortality by 2.6 times in the ICU in the crude model (OR: 2.6, P > 0.001). In the multivariate regression analysis, the initial OR has changed in the presence of urinary tract infection and pneumonia (OR: 2.92, OR: 1.6, respectively).

In the final multivariate regression analysis, in the presence of urinary tract infection and pneumonia, resistant microorganisms have increased mortality by 1.7 times in the ICU (Table 5).

The β of the length of ICU stay on death in a crude model was 0.074 and changed in the multivariate regression analysis model in the presence of pneumonia (β = 0.041, Table 6).

Discussion

Antibiotic resistance is an important problem throughout the world, especially in the healthcare settings such as hospitals. Knowing the local resistance pattern is of great value in guiding empiric antimicrobial therapy and infection control. Infections caused by resistant microorganisms are difficult to treat because there are limited effective antimicrobial alternatives. Furthermore, it is associated with more hospital stays and mortality (15,16).

In agreement with other studies (5,17,18), the most prevalent positive culture in our study was culture related to the respiratory tract.

In our study, it was found that more than 50% of ICU patients had at least one positive culture. The most prevalent and resistant microorganisms were E. coli and A. baumannii, respectively. The results of our study conform to those of several studies in Iran (19,20) and other countries (21,22), confirming that E. coli was the most common pathogen. Our findings are in concordance with the results of Saxena et al, indicating that most of the Acinetobacter and Klebsiella species were MDR (2).

In our survey, 80.2% of isolates were MDR, which is more than the MDR pathogen rate reported by Cornejo-Juárez et al (1). This can be due to excessive and irrational administration of antibiotics and delays in the initiation of effective and appropriate antimicrobial therapy in our community.

In the present study, the net number of resistant isolates (E. coli ESBL, MRSA, MDR Acinetobacter, and Klebsiella pneumoniae carbapenemase) reduced slightly over 5 years, which is probably due to the more organized antibiotic prescription and curbing inappropriate use of broad-spectrum antibiotics.

The ICU mortality is high and had been reported from 9% to 38% (23). This mortality rate can increase up to 70% in patients with infections caused by resistant pathogens (24).

In our study, in-hospital mortality was 35.5%. The ICU mortality was reported at 40.3% in patients with antimicrobial resistance infections in the study of Lakbar et al (25), which is compatible with the results of Colpan et al (24).

In another study on patients with hematological malignancy admitted to the ICU, in-hospital mortality was reported at 46% (26). The higher mortality rate can be due to the underlying disease of patients. Furthermore, in the study performed on patients admitted to surgical ICU, Saxena et al indicated that the overall mortality was 28%, and only 4 patients died due to infectious causes (2).

According to our results, mortality was significantly more frequent in culture-positive patients (63.8%) compared to culture-negative patients (36.2%, P > 0.001), which is in line with the findings of a multicenter study in Brazil (27) and the study of Toufen et al (28). Moreover, the ICU stay (8.42 vs. 3.5 days) and hospital stay (17.04 vs. 10.54 days) were significantly longer in the culture-positive group (P > 0.001). Similarly, Vincent et al and Blot et al identified a strong relationship between infection with ICU stay and hospital stay (27,29).

In the present study, it was observed that positive culture related to the respiratory tract increases mortality, which corroborates with the results of previous studies (25,30). Bonnet et al (16) demonstrated that 51.7% of patients with lung infections died and pulmonary infections increased the length of stay (P > 0.001). However, the reason is not clear.

The relationship between resistant pathogens and mortality is debated in various studies. We found that MDR microorganisms increased mortality by 2.6 folds. Some studies have revealed an association between resistant isolates and mortality (1,16,24,31-37), whereas other studies did not report such an association (29,38-41). Although the reason is unclear, it might be partly due to the low sample size of studies and differences in the study population. The higher mortality in the resistant group could be due to more virulence of resistant microorganisms or inappropriate empiric antibiotic treatment.

Conclusion

In general, the findings of our study suggest that MDR pathogens increase ICU stay and mortality. As a result, prevention and treatment strategies and rational administration of antibiotics to prevent the development of resistant microorganisms are highly important.

Acknowledgments

We would like to thank Dr. Taghvaye-Masoumi for his guidance and Dr. Mohsen Shatti for data analysis. We also appreciate the nurses of the general ICU of Hasheminejad Kidney Center for their support.

Authors’ Contribution

BM contributed to data gathering. MKK participated in idea, study design, data collection, and manuscript drafting and finalizing. All authors read and approved the final manuscript.

Conflict of Interests

There is no conflict of interests.

Ethical Approval

This study has been approved by local committee of Hasheminejad Kidney Center, Iran University of Medical Sciences.

Funding

Nil.

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