Prediction of the Risk of Hospital Deaths in Patients with Hospital-Acquired Pneumonia Caused by Multidrug-Resistant Acinetobacter baumannii Infection: A Multi-Center Study
Authors Shu H, Li L, Wang Y, Guo Y, Wang C, Yang C, Gu L, Cao B
Received 29 May 2020
Accepted for publication 15 October 2020
Published 19 November 2020 Volume 2020:13 Pages 4147—4154
Checked for plagiarism Yes
Review by Single anonymous peer review
Peer reviewer comments 3
Editor who approved publication: Professor Suresh Antony
Hongmei Shu,1– 3 Lijuan Li,2 Yimin Wang,2 Yiqun Guo,4 Chunlei Wang,5 Chunxia Yang,4 Li Gu,4 Bin Cao2,5,6
1Department of Pulmonary and Critical Care Medicine, Xuanwu Hospital Capital Medical University, Beijing, People’s Republic of China; 2Department of Pulmonary and Critical Care Medicine, China-Japan Friendship Hospital, Beijing, People’s Republic of China; 3Department of Respiration, Anqing Municipal Hospital, Anqing Hospital of Anhui Medical University, Anhui 246000, People’s Republic of China; 4Department of Infectious Diseases and Clinical Microbiology, Beijing Chao-Yang Hospital, Capital Medical University, Beijing 100020, People’s Republic of China; 5Laboratory of Clinical Microbiology and Infectious Diseases, China-Japan Friendship Hospital, Beijing, People’s Republic of China; 6Institute of Respiratory Medicine, Chinese Academy of Medical Sciences; National Clinical Research Center of Respiratory Disease, Clinical Center for Pulmonary Infection, Capital Medical University, Tsinghua University-Peking University Joint Center for Life Sciences, Beijing 100029, People’s Republic of China
Correspondence: Bin Cao
Department of Pulmonary and Critical Care Medicine, China-Japan Friendship Hospital, Yinghua East Road, Chao-Yang District, Beijing 100029, People’s Republic of China
Fax +86 10-84206269
Email [email protected]
Department of Infectious Diseases and Clinical Microbiology, Beijing Chao-Yang Hospital, Capital Medical University, No. 8 Worker’s Stadium South Road, Chaoyang District, Beijing 100020, People’s Republic of China
Email [email protected]
Purpose: To predict the risk of hospital deaths in patients with hospital-acquired pneumonia (HAP) caused by multidrug-resistant Acinetobacter baumannii (MDR-AB) infection.
Patients and Methods: A total of 366 patients who were diagnosed with HAP caused by MDR-AB infection were enrolled between January 2013 and December 2016. The sociological characteristics and clinical data of these cases were collected. Univariate and multivariate logistic analyses were used to explore the risk factors of hospital deaths before medication and after drug withdrawal. The receiver operating characteristic (ROC) curve and the area under the curve (AUC) were utilized to assess the predictive effectiveness of the models with or without the adjustment.
Results: Hospital deaths occurred in 142 cases (38.80%). The results showed that acute physiology and chronic health evaluation II (APACHE II) and sequential organ failure assessment (SOFA) scores before medication and after drug withdrawal were associated with the risk of hospital deaths. Adjusting the covariants including the age, autoimmune disease, venous cannula, transfer of patients from other hospitals, and APACHE II score at admission, then no differences were discovered in predicting the hospital deaths between adjusted APACHE II and adjusted SOFA scores before medication (AUC: 0.808 vs 0.803, P =0.614) and after drug withdrawal (AUC: 0.876 vs 0.878, P =0.789).
Conclusion: Before medication or after drug withdrawal, the adjusted APACHE II and adjusted SOFA scores all performed well in determining the predictive effectiveness of the hospital deaths in patients with HAP caused by MDR-AB infection, indicating that the appropriate infection control may reduce the occurrence of nosocomial deaths and improve the prognosis.
Keywords: multidrug-resistant Acinetobacter baumaii, hospital-acquired pneumonia, intensive care units, hospital deaths
Hospital-acquired pneumonia (HAP) is the main nosocomial infection resulting in increased morbidity, mortality, and medical costs.1 Administration of appropriate antibiotics is important to improve the prognostic outcomes of HAP.2,3 Previous epidemiologic studies reported that the incidence of HAP with an upward trend was due to the infection of multidrug-resistant (MDR) microorganisms.4,5 The carbapenem-resistant microbial pathogens, such as Acinetobacter baumannii (AB) and Pseudomonas aeruginosa, are major pathogens of HAP in Asia.6 Of which, the occurrence of HAP caused by AB infection has gradually increased ranging from 26% to 82.5% in recent years.7 It is essential for clinicians to pay attention to AB infection in HAP to avoid the inappropriate empirical therapy and overuse of colistin.
MDR-AB, an important pathogen associated with outbreaks of nosocomial infections, mostly occurs in intensive care units (ICUs), and leads to urinary tract, blood-stream and surgical infections, as well as pneumonia which is the most common clinical symptom.8 Early studies showed that the infection caused by MDR-AB is difficult to treat, resulting in increased mortality and longer length of stay.9 It was estimated that 55% of elderly inpatients underwent 30-day nosocomial death due to the blood-stream infection caused by MDR-AB,10 and 40.7–73% of critically ill patients died from MDR-AB infection.11–13 Numerous studies have explored the risk factors of HAP caused by MDR-AB infection.14,15 To the best of our knowledge, however, the prediction of the risk of hospital deaths in patients with HAP caused by MDR-AB has been rarely reported. In the current study, we assessed different models for predicting the risk of hospital deaths, and compared the predictive effectiveness of these models in patients with HAP caused by MDR-AB infection.
Patients and Methods
A total of 1,475 cases from two hospitals who were diagnosed with HAP were enrolled between January 2013 and December 2016, with the age ≥18 years old. After excluding antibiotic use <3 days, colonization, experiential therapy, non MDR-AB infection and age <18 years, 366 cases were finally divided into hospital deaths (n=142) and non-hospital deaths (n=224) groups. This study was approved by the Institutional Review Board (IRB) of China-Japan Friendship Hospital (No.2017–104) and Beijing Chao-Yang Hospital (No.2017–202), and all patients or their relatives provided informed consent.
HAP (ICD-10) is defined as a newly developed pneumonia after 48-hours admission, which occurs when a patient has not received invasive mechanical ventilation and is not in the incubation period of pathogenic infection.
The designation of MDR was defined as the absence of susceptibility to >3 of the following antimicrobials or groups of antimicrobials: ampicillin/sulbactam, aztreonam, ceftazidime, ciprofloxacin, gentamicin, imipenem, piperacillin, trimethoprim/sulfamethoxazole, carbapenems, and amikacin.16,17 Bacterial isolation and antimicrobial susceptibility testing were performed in accordance with the methodology of the Clinical and Laboratory Standards Institute.18
Diagnosis of HAP caused by MDR-AB was assessed according to the criteria of the Centers for Disease Control (CDC).19 Tracheal aspirate and sputum specimens were sent for bacterial culture only when their Gram’s stains showed at least 25 neutrophils and less than 10 epithelial cells per low-power field. Growth was assessed using the semi-quantitative method. The etiologic pathogen was determined if the tracheal aspirate or sputum culture had at least a moderate growth.
The general and hospital information at admission were noted including age, gender, history of diseases, time and place of infection, venous cannula, mechanical ventilation, acute physiology and chronic health evaluation II (APACHE II) and use of drugs. The APACHE II and sequential organ failure assessment (SOFA) scores were recorded before medication and after drug withdrawal.
All statistical analyses were performed using SAS 9.4 (IBM Corp.). Continuous data were presented as the mean ± standard deviation (SD) or [M(Q25, Q75)] and analyzed by t-test or Mann–Whitney U-test. Categorical data were presented as frequency (n) and percentage (%) and analyzed using Chi-square (χ2) test. Univariate and multivariate logistic analyses were used to explore the risk factors of hospital deaths before medication and after drug withdrawal. The receiver operating characteristic (ROC) curve and area under curve (AUC) were utilized to assess the predictive effectiveness of with or without the adjustment. P <0.05 was considered as statistical differences.
The Characteristics of HAP Patients Caused by MDR-AB Infection at Admission
Of the total 1,475 cases, 634 and 841 were collected from the China-Japan Friendship Hospital and Beijing Chao-Yang Hospital, respectively. After excluding 360 of non-ICU and 123 emergency patients, 992 received the drug treatments. Then exclusion of the colonization (n=252), experiential therapy (n=351), antibiotic use <3 days (n=12), age <18 years (n=1) and HAP caused by other bacterial infections (n=10), 366 subjects were finally enrolled in this study. The flow chart of the case screening is shown in Figure 1.
Figure 1 The flow chart of the case screening.
The baseline data of 366 patients with a mean age of 67.70±17.23 years were assessed including 243 (66.39%) males and 123 (33.61%) females. Among these cases, 142 (38.80%) occurred as hospital deaths. There were statistical differences in the age (t=−4.20, P <0.001), autoimmune disease (χ2=11.843, P <0.001), venous cannula (χ2=25.392, P <0.001), transfer of patients from other hospitals (χ2=7.256, P =0.007) and APACHE II scores (t=−5.25, P <0.001) between the hospital deaths and non-hospital deaths groups. The characteristics of HAP patients caused by MDR-AB infection at admission is listed in Table 1.
Table 1 The Characteristics of HAP Patients Caused by MDR-AB at Admission
The Characteristics of Patients Before Medication and After Drug Withdrawal
In this study, the APACHE II and SOFA scores were assessed as the differences between the two groups before medication and after drug withdrawal (Table 2). We found the significant differences in APACHE II (15.48 vs 31.13, t=−8.63, P <0.001) and SOFA (4 vs 7, Z=7.458, P <0.001) scores before medication between the two groups. After drug withdrawal, the differences were also shown in APACHE II (13.51 vs 24.39, t=13.62, P <0.001) and SOFA (2 vs 8, Z=10.986, P <0.001) scores.
Table 2 The Characteristics of Patients Before Medication and After Drug Withdrawal
Univariate and Multivariable Logistic Analyses for Hospital Deaths Among HAP Patients Caused by MDR-AB Before Medication and After Drug Withdrawal
The univariate and multivariable logistic analyses for hospital deaths before medication and after drug withdrawal are shown in Table 3. Before medication, there were differences in APACHE II (OR: 1.179, 95% CI: 1.129–1.231) and SOFA (OR: 1.268, 95% CI: 1.183–1.359) scores for hospital deaths, with all P <0.001. The results of the multivariable logistic analysis (adjusting for age, autoimmune disease, venous cannula, transfer of patients from other hospitals and APACHE II score at admission) showed that the risk of hospital deaths was increased by 0.158 and 0.250 for every 1 point increase in the APACHE II and SOFA scores, respectively. After drug withdrawal, APACHE II (OR: 1.225, 95% CI: 1.172–1.280) and SOFA (OR: 1.376, 95% CI: 1.283–1.475) scores were associated with the hospital deaths among HAP cases caused by MDR-AB infection. The further analysis (adjusting for age, autoimmune disease, venous cannula, transfer of patients from other hospitals, APACHE II score at admission) found that a 0.219- and 0.398-fold increase in the risk of hospital deaths with per 1 point increase in APACHE II and SOFA scores, respectively.
Table 3 Univariate and Multivariable Logistic Analyses for Hospital Deaths Among HAP Patients Caused by MDR-AB Before Medication and After Drug Withdrawal
Prediction for the Risk of Hospital Deaths Before Medication and After Drug Withdrawal
Table 4 Comparison of the AUC of the Scores with or Without the Adjustment of Predicting the Risk of Hospital Deaths
Table 5 Comparison of the Adjusted Scores for Predicting the Risk of Hospital Deaths Among HAP Patients Caused by MDR-AB
The predictive power of APACHE II and SOFA scores in the risk of hospital deaths were inferior to adjusted APACHE II (0.750 vs 0.808, P =0.003) and adjusted SOFA (0.731 vs 0.803, P =0.004) scores, respectively (Table 4). Then no differences were discovered in predicting the hospital deaths between adjusted APACHE II and adjusted SOFA scores (0.808 vs 0.803, P =0.614) (Table 5 and Figure 2A).
Figure 2 ROC curves of different scores for predicting the risk of hospital deaths before medication (A) and after drug withdrawal (B) among HAP patients caused by MDR-AB infection.
After Drug Withdrawal
In Table 4, the AUC of APACHE II score was similar with adjusted APACHE II (0.854 vs 0.876, P =0.088). Compared with adjusted SOFA score, the predictive effectiveness of SOFA score was lower (0.840 vs 0.878, P =0.015). We further assessed the adjusted scores for the risk of hospital deaths, and found no statistical differences between the two adjusted scores (0.876 vs 0.878, P =0.789) (Table 5 and Figure 2B).
In this study, we analyzed the clinical characteristics of patients with HAP caused by MDR-AB infection, and conducted different models for predicting the risk of hospital deaths, and further compared the predictive effectiveness of these models among these cases. Our findings showed that the AUC of adjusted APACHE II and adjusted SOFA scores had no statistical differences before medication or after drug withdrawal, indicating the predictive values of the scores were similar, which may be effective tools for predicting the risk of hospital deaths, and then may be available for clinicians to timely implement intervention and treatment.
Nosocomial infections-associated MDR-AB have been a global health care issue, mainly occurring in low- and middle-income countries.20–22 Previous studies reported that the incidence of MDR-AB infection were approximately 2- to 5-fold higher in ICU than other wards,23 which may be due to long-term bed rest and weak resistance of ICU patients, invasive diagnostic, treatment procedures (endotracheal intubation, ventilator, etc.) and extensive use of antimicrobial agents.24 Furthermore, the antimicrobial resistance of AB can lead to a high rate of treatment failure.23 Although the resistance is closely related to deaths, numerous risk factors also contribute to increasing the difficulties regarding the choice of antimicrobials used in the treatment of severe infections caused by this microorganism, resulting in a worse prognosis.25 Therefore, it is necessary to carry out reasonable monitoring and infection control, use functional microbiology labs, as well as rational antibiotics administration, to prevent or contain an explosive growth of microorganisms.14
There was 38.80% of hospital mortality among HAP cases caused by MDR-AB infection in the current study, which was similar to some other studies.26–28 Wisplinghoff et al28 mentioned that the mortality rate in patients with MDR-AB infection was twice that in controls.28 MDR-AB infection is a marker for increased mortality risk in patients with severe underlying illness but not an independent predictor of mortality.29 We assessed the roles of APACHE II and SOFA scores before medication and after drug withdrawal in the hospital deaths among HAP cases caused by MDR-AB. Our results showed that all the two scores were independent risk factors for nosocomial deaths before medication or after drug withdrawal. When adjusting the age, autoimmune disease, venous cannula, transfer of patients from other hospitals and APACHE II score at admission, the risk of hospital deaths before medication was increased by 0.158 and 0.250 for every 1-point increase, and a 0.219- and 0.398-fold increase in the risk of hospital deaths after drug withdrawal per 1-point increase in APACHE II and SOFA scores, respectively. An early study proposed by Joung et al30 supported our findings. Then we further investigated the predictive power of the two scores in the risk of hospital deaths. The results showed that the predictive effectiveness of adjusted APACHE II and adjusted SOFA scores were similar before medication or after drug withdrawal. It was indicated that these adjusted scores were useful tools for death risk prediction in patients with HAP caused by MDR-AB, which may be considered for clinical evaluation.
The strengths of our study were that various predictive models were conducted to assess the mortality risk in hospital before medication and after drug withdrawal. We found that the adjusted APACHE II and adjusted SOFA scores performed well in predictive effectiveness. In addition, there were several limitations that should invoke caution for the interpretation of our findings. First, only 366 patients were enrolled in this study overall which may reduce the statistical power. Second, some confounding variables may be missed on the basis of a retrospective investigation and limited clinical data. Further studies with better designs are needed to get more comprehensive views for predicting the risk of hospital deaths of HAP caused by MDR-AB infection.
We carried out various models for predicting the risk of hospital deaths in HAP patients caused by MDR-AB. Our findings showed that APACHE II and SOFA scores were independent risk factors for nosocomial deaths before medication or after drug withdrawal. Additionally, the predictive effectiveness of adjusted APACHE II and adjusted SOFA scores were similar before medication or after drug withdrawal, indicating that these scores may be available tools for clinical assessment.
There is no funding to report.
The authors report no conflicts of interest in this work.
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