Secondary infections, also called intensive care unit (ICU)-acquired infections, are defined as infections occurring 48 h after admission to the ICU.[1] Critically ill patients are at a high risk of developing ventilator-associated pneumonia (VAP) and bloodstream infections (BSIs), which are associated with increased ICU mortality.[2]
Cancer patients are susceptible to infections owing to multiple risk factors due to immunosuppression, including radiotherapy, systemic therapy, and immunotherapy.[3,4] Hence, critically ill cancer patients with sepsis are also prone to developing secondary infections. In this study, we hypothesized that critically ill cancer patients with sepsis would develop more secondary infections, which would be associated with adverse outcomes.
METHODS
Inclusion criteria included patients who were diagnosed with sepsis and were admitted to the ICU for more than 48 h in the Cancer Hospital of the Chinese Academy of Medical Sciences (CAMS) and Peking Union Medical College (PUMC) between November 2017 and October 2018. Patient data were retrospectively collected and reviewed. The exclusion criteria were patients who fulfilled the definition of sepsis but the length of stay (LOS) in the ICU was less than 48 h. The study was performed in line with the ethical Declaration of Helsinki in 1964 and its later amendments. The protocol was approved by the Institutional Review Boards of Cancer Hospital, Chinese Academy of Medical Sciences (22/092-3293). The patients’ consent was waived due to the observational nature of this study.
The data included age, sex, modified Charlson’s score, Sequential Organ Failure Assessment (SOFA), Acute Physiology and Chronic Health Evaluation II (APACHE II), simplified acute physiology score 3 (SAPS 3) on ICU admission, preoperative radiotherapy/systemic therapy, American Joint Committee on Cancer (AJCC) tumor staging, and the presence of immunosuppression on admission. Outcome variables included the ventilation duration, ICU LOS, ICU death, hospital LOS, and in-hospital death. The secondary infection was defined as any new-onset infection occurring 48 h or more after admission to the ICU and intensivists starting a new antibiotic regimen.[1] Immunosuppression was defined as a lymphocyte count <0.80×109/L according to the criteria.[5]
Statistical analyses were performed using SPSS software for Windows, version 16.0 (SPSS Inc., USA). Continuous variables are reported as the median (interquartile range) and compared using the Mann-Whitney U-test. Categorical variables are presented as absolute numbers (frequency percentages) and analyzed using the Chi-square test. The results were considered statistically significant when a two-tailed P-value <0.05.
RESULTS
A total of 161 patients with sepsis were admitted to the ICU during the study period. Of them, 14 (8.7%) patients developed secondary infections, including 6 pneumonia, 6 bloodstream infections, and 2 other infections. The univariable analysis demonstrated that compared with patients who developed secondary infections, those who did not develop secondary infections were more severe with higher APACHE II scores (Table 1). No significant differences were noted in other clinical variables. Therefore, we did not perform a multivariable analysis further on the risk factors for secondary infections.
Table 1. Comparison of clinical characteristics between sepsis patients with secondary infections and those who did not develop secondary infections
| Clinical variables | Non-secondary infections (n=147) | Secondary infections (n=14) | P-value |
|---|---|---|---|
| Age, years | 63 (14) | 63 (14) | 0.488 |
| Male | 114 (77.6) | 10 (71.4) | 0.603 |
| Modified Charlson’s score | 2 (1) | 2 (0) | 0.868 |
| APACHE II | 11 (7) | 8 (8) | 0.008 |
| SAPS 3 | 52.50 (15.00) | 47.50 (13.00) | 0.118 |
| SOFA | 4.00 (4.00) | 3.50 (1.00) | 0.143 |
| Radio/chemotherapy | 50 (34.0) | 3 (21.4) | 0.338 |
| AJCC tumor staging | 0.804 | ||
| Stage I/II | 59 (39.5) | 6 (42.9) | |
| Stage III/IV | 89 (60.5) | 8 (57.1) | |
| Immunosuppression at ICU admission | 93 (63.3) | 8 (57.1) | 0.651 |
| NLR at ICU admission | 17.29 (19.70) | 16.70 (12.01) | 0.666 |
| Septic shock | 58 (39.5) | 3 (21.4) | 0.184 |
Data are reported as the median (interquartile range) or numbers (frequency percentages). APACHE II: Acute Physiology and Chronic Health Evaluation II; SAPS 3: simplified acute physiology score 3; SOFA: sequential organ failure assessment; AJCC: American Joint Committee on Cancer; ICU: intensive care unit; NLR: neutrophil-to-lymphocyte ratio.
For outcomes, compared with patients who did not develop secondary infections, those who developed secondary infections had a significantly prolonged median ICU LOS (12 d vs. 6 d, P=0.004) and median hospital LOS (24 d vs. 17 d, P=0.021). Patients who developed secondary infections had insignificantly increased hospital mortality compared with those who did not develop secondary infections (14.3% [2/14] vs. 5.4% [8/147], P=0.190).
DISCUSSION
Secondary infections after admission to the ICU were reported to range from 13% to 29%.[1,6] No significant difference in the rate of secondary infections was observed between septic and non-septic patients. In this study, the incidence of secondary infections was 8%, which was lower than that reported in previous studies,[1,6] which could be attributed to patients’ mild status in this study.
The risk factors for secondary infections include disease severity, shock, use of a central venous catheter, and mechanical ventilation.[1,6] However, we found an inverse association between disease severity and secondary infections. In a recent multicenter study, the rate of secondary pneumonia was higher in patients in the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) group than in those in the influenza and no viral infection groups; however, simplified acute physiology score 2 and SOFA scores were lower in the SARS-CoV-2 group than in the other two groups.[7] A longer duration of mechanical ventilation could be responsible for this phenomenon. In our study, the median duration of mechanical ventilation was longer in patients in the secondary infection group than in those who did not develop secondary infections (11 d vs. 5 d, P=0.052). Therefore, adherence to preventive measures in VAP may be important to prevent the occurrence of secondary infections.[8]
A previous study demonstrated that patients with sepsis had impaired immunity, increasing their susceptibility to nosocomial infections.[9] In our study, 62.7% (101/161) of patients with sepsis had immunosuppression, as indicated by an absolute lymphocyte count of less than 0.80×109/L. However, secondary infections only occurred in eight patients (7.9%). Therefore, immunosuppression contributes only partly to nosocomial infections.[10] In our study, secondary infections were associated with prolonged median ICU LOS and median hospital LOS, which was consistent with the results of previous studies.[1,6] Therefore, prevention and treatment of secondary infections are important to reduce the ICU LOS and hospital LOS.
Our study had several limitations. First, compared with previous studies, the sample size was relatively small. Second, immunosuppression markers such as human leukocyte antigen DR and cytokines were not measured in patients with sepsis. Third, measures such as VAP and BSI preventive bundles were not documented.
CONCLUSIONS
In our study, approximately 8.7% of septic patients with cancer developed secondary infections. Secondary infections in septic patients with cancer were associated with longer ICU or hospital LOS. Disease severity and immunosuppression were not associated with the occurrence of secondary infection in critically ill cancer patients.
Funding: The study was funded by the management research special fund of Cancer Hospital of Chinese Academy of Medical Sciences LC2020D01.
Ethical approval: The protocol was approved by the Institutional Review Boards of Cancer Hospital, Chinese Academy of Medical Sciences (22/092-3293).
Conflicts of interest: None declared.
Contributors: SNQ drafted the manuscript. All authors read and approved the final manuscript.
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Secondary infection has a higher incidence in septic patients and affects clinical outcomes. This study aims to investigate the clinical characteristics, risk factors, immune status and prognosis of secondary infection of sepsis.A four-year retrospective study was carried out in Zhongshan Hospital, Fudan University, enrolling septic patients admitted between January, 2014 and January, 2018. Clinical data were acquired from medical records. CD14 monocyte human leukocyte antigen-D related (HLA-DR) expression and serum cytokines levels were measured by flow cytometry and enzyme-linked immunosorbent assay (ELISA) respectively.A total of 297 septic patients were enrolled, 92 of whom developed 150 cases of secondary infections. Respiratory tract was the most common site of secondary infection (n = 84, 56%) and Acinetobacter baumanii the most commonly isolated pathogen (n = 40, 31%). Urinary and deep venous catheterization increased the risk of secondary infection. Lower HLA-DR expression and elevated IL-10 level were found in secondary infection group. The expected prolonged in-hospital stay owing to secondary infection was 4.63 ± 1.87 days. Secondary infection was also associated with higher in-hospital, 30-day and 90-day mortality. Kaplan-Meier survival analysis and Log-rank test revealed that secondary infection group had worse survival between day 15 and day 90.Urinary and deep venous catheterization increased the risk of secondary infection, in which underlying immunosuppression might also play a role. Secondary infection affected the prognosis of septic patients and prolonged in-hospital length of stay.
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Infection control interventions can be erroneously interpreted if outcomes are assessed in short periods. Also, statistical methods usually applied to compare outcomes before and after interventions are not appropriate for analyzing time series.To analyze the impact of a bundle directed at reducing the incidence of ventilator-associated pneumonia (VAP) and other device-associated infections in two medical-surgical intensive care units (ICU) in Brazil.Our study had a quasi-experimental design. Interrupted time series analyses (ITS) was performed assessing monthly rates of overall healthcare-associated infections (HCAI), VAP, laboratory-confirmed central line associated bloodstream infections (CLABSI) and catheter-associated urinary tract infections (CAUTI), from January 2007 through June 2019. Moreover, multivariate ITS was adjusted for seasonality in Poisson regression models. An intervention based on a bundle for VAP prevention was introduced in August 2010.The intervention was followed by sustained reduction in overall HCAI, VAP and CLABSI in both ICU. Continuous post-intervention trends towards reduction were detected for overall HCAI and VAP.Interventions aimed at preventing one specific site of infection may have sustained impact on other HCAI, which can be documented using time series analyses.Copyright © 2020 Sociedade Brasileira de Infectologia. Published by Elsevier España, S.L.U. All rights reserved.
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