Infections are associated with increased mortality in patients with sepsis or septic shock. However, to the best of our knowledge, the influence of the site of infection on patients with cancer remains unclear. The present study aimed to evaluate the association between the site of infection and mortality in patients with cancer and sepsis or septic shock. The present study was conducted in a Lebanon tertiary care centre from July 2010 to April 2015. A total of 176 patients with active cancer presenting to the emergency department with sepsis or sepsis shock were included in the present analysis. Cox regression and Kaplan-Meier analysis of the effect of the site of infection on mortality were performed. The most common site of infection was the lung (37.50%), followed by the urinary tract (26.70%), unknown site (13.63%), gastrointestinal (13.07%) and others (9.10%). The overall mortality rate was 47.73%. Gastrointestinal infection (78.26%) was associated with the highest mortality, followed by pneumonia (62.12%). The urinary tract infection with the lowest mortality rate was the reference group. After adjusting for confounding variables, gastrointestinal infection was associated with the highest in-hospital mortality [hazard ratio (HR), 2.64; 95% CI, 1.25-5.55], followed by pneumonia (HR, 1.95; 95% CI, 1.03-3.68). The association between site of infection and 28-day and 60-day mortality was analysed by Cox regression, as well as by stratified analysis to investigate the association between site of infection and mortality from haematological and solid tumors. Gastrointestinal infection had a higher mortality rate. In conclusion, the site of infection had the same association with mortality in patients with solid and haematological tumours.
Sepsis is life-threatening organ dysfunction in response to infection (
The present study assessed a retrospective single-centre cohort study by Dagher
Sepsis (
Septic shock (
Bacteraemia was defined as two positive blood cultures of known skin flora pathogens or one positive blood culture of non-skin flora pathogens.
Active cancer (
Categorical variables were compared using χ2 or Fisher's exact probability test. Continuous variables were compared by Kruskal-Wallis test. Categorical variables were reported as percentage. Non-normal variables were reported as the median and interquartile range (IQR). The effect of the site of infection on mortality was analysed by Cox regression. Covariates in the multivariate model included age (20-50, 51-70 and >70 years), sex, hypertension, congestive heart failure, ejection fraction <40%, tumour type, white blood cell count, haemoglobin, diagnosis, bacteraemia, chemotherapy, radiation, surgery, time to antibiotics and steroids. In addition, all-cause mortality within 60 days was assessed using Kaplan-Meier curves according to the site of infection. Differences were compared by the log-rank test. All statistical analyses were performed with Empower (
The baseline characteristics of patients with cancer are shown in
In the univariable analysis for the entire cohort (
The urinary tract infection with the lowest mortality rate (31.91%) was the reference group (
Kaplan-Meier survival curve for each infection site with 60 day follow-up showed a consistent pattern (
To evaluate the relationship between the site of infection and the mortality of patients with solid or haematological tumours, a stratified analysis was performed. Among solid and haematological tumours, gastrointestinal infections were associated with the highest in-hospital mortality after adjusting for confounding variables. They were [HR, 2.36; 95% CI, 1.05-5.31], [HR, 179.91; 95% CI, 5.69-5693.31), respectively (
Although infection is the most common cause of in-hospital mortality in patients with cancer (
In the present single cohort study of patients with cancer admitted to the ED due to sepsis or septic shock, it was found that the site of infection was associated with in-hospital mortality when the urinary tract infection group was used as a reference group. The present data showed that the lung, urinary system, gastrointestinal tract, and unknown site are common sites of infection, which is consistent with previous studies (
The highest mortality was associated with gastrointestinal infection. Chemotherapy and radiation therapy have been widely used in patients with cancer in recent years, as well as repeated antibiotics to prevent infections (
Unknown site infections may lead to poor outcomes due to the inability to obtain culture samples of unknown site infections in a short time and the inability to select appropriate treatment regimens based on pathogenetic and drug distribution characteristics. Unknown site infection is associated with fatal outcomes in patients without cancer (
The association between infection site and mortality may differ due to differences in underlying immune mechanisms between detailed cancer types and cancer sites (
The present study has certain limitations. First, the site of infection may be misclassified because there may be not enough time in a busy ED to estimate the exact site of infection. Second, this was a single-centre retrospective study to evaluate the association between the site of infection and mortality in patients with solid or haematological tumours admitted to the ED with sepsis or septic shock. Thus, the findings may not be generalizable to the general population. Third, the patient stage of disease may be a factor in mortality. However, the present study was a secondary analysis and cannot further assess the stage of patients with cancer. Therefore, in-hospital mortality may be overestimated because the population analysed in the current study included patients diagnosed with terminal cancer (
In conclusion, the site of infection was associated with in-hospital mortality in patients with cancer diagnosed with sepsis or septic shock.
Not applicable.
The datasets generated and/or analysed during the current study are available in the Dryad Digital Repository database (
YC, JH, JX, RQ and TL made substantial contributions to conception and design, acquisition of data and analysis and interpretation of data. YC and TL were involved in drafting the manuscript and revising it critically for important intellectual content. TL gave final approval of the version to be published. All authors have participated sufficiently in the work to take responsibility for appropriate portions of the content. YC and TL agreed to be accountable for all aspects of the work in ensuring that questions related to the accuracy or integrity of any part of the work are appropriately investigated and resolved. YC was responsible for the drafting of the manuscript. YC and JH confirm the authenticity of all the raw data. YC, JH, JX and RQ conceived and designed the study. YC and TL performed the literature research. YC, JH and RQ performed the data analysis. YC and TL edited the manuscript. TL reviewed the manuscript. All authors have read and approved the final manuscript.
The requirement for ethics approval and informed consent was waived as the data were anonymized.
Not applicable.
The authors declare that they have no competing interests.
Kaplan-Meier curves of overall survival of patients with cancer with different sites of infection.
Baseline characteristics of patients with cancer.
Infection site | ||||||
---|---|---|---|---|---|---|
Variable | Urine tract (n=47.00) | Unknown (n=24.00) | Gastrointe stinal (n=23.00) | Lung (n=66.00) | Other (n=16.00) | P-value |
Age, years, n (%) | 0.374 | |||||
20-50 | 3.00 (6.38) | 6.00 (25.00) | 2.00 (8.70) | 10.00 (15.15) | 2.00 (12.50) | |
51-70 | 19.00 (40.43) | 9.00 (37.50) | 12.00 (52.17) | 32.00 (48.48) | 9.00 (56.25) | |
>70 | 25.00 (53.19) | 9.00 (37.50) | 9.00 (39.13) | 24.00 (36.36) | 5.00 (31.25) | |
Male, n (%) | 34.00 (72.34) | 9.00 (37.50) | 17.00 (73.91) | 43.00 (65.15) | 9.00 (56.25) | 0.039 |
Hypertension, n (%) | 30.00 (63.83) | 8.00 (33.33) | 16.00 (69.57) | 34.00 (51.52) | 6.00 (37.50) | 0.039 |
Congestive heart failure ejection fraction <40%, n (%) | 8.00 (17.02) | 1.00 (4.17) | 2.00 (8.17) | 13.00 (19.70) | 1.00 (6.25) | 0.255 |
Tumour type, n (%) | 0.626 | |||||
Haematological malignancy, n (%) | 7.00 (14.89) | 6.00 (25.00) | 3.00 (13.04) | 16.00 (24.24) | 3.00 (18.75) | |
Solid tumour, n (%) | 40.00 (85.11) | 18.00 (75.00) | 20.00 (86.96) | 50.00 (75.76) | 13.00 (81.25) | |
White blood cell (1x109/l), n (%) | 0.682 | |||||
>10 | 27.00 (57.45) | 11.00 (45.83) | 12.00 (52.17) | 35.00 (53.03) | 6.00 (37.50) | |
≤10 | 20.00 (42.55) | 13.00 (54.17) | 11.00 (47.83) | 31.00 (46.97) | 10.00 (62.50) | |
Haemoglobin (g/l), n (%) | 0.600 | |||||
>100 | 22.00 (46.81) | 10.00 (41.67) | 13.00 (56.52) | 32.00 (48.48) | 5.00 (31.25) | |
≤100 | 25.00 (53.19) | 14.00 (58.33) | 10.00 (43.48) | 34.00 (51.52) | 11.00 (68.75) | |
Diagnosis, n (%) | 0.193 | |||||
Septic shock | 23.00 (48.94) | 15.00 (62.50) | 17.00 (73.91) | 45.00 (68.18) | 9.00 (56.25) | |
Sepsis | 24.00 (51.06) | 9.00 (37.50) | 6.00 (26.09) | 21.00 (31.82) | 7.00 (43.75) | |
Bacteraemia, n (%) | 18.00 (38.30) | 13.00 (54.17) | 7.00 (30.43) | 18.00 (27.27) | 10.00 (62.50) | 0.032 |
Chemotherapy, n (%) | 42.00 (89.36) | 18.00 (75.00) | 14.00 (60.87) | 58.00 (87.88) | 15.00 (93.75) | 0.011 |
Radiation therapy, n (%) | 13.00 (27.66) | 8.00 (33.33) | 3.00 (13.04) | 31.00 (46.97) | 7.00 (43.75) | 0.030 |
Surgery, n (%) | 26.00 (55.32) | 11.00 (45.83) | 9.00 (39.13) | 22.00 (33.33) | 10.00 (62.50) | 0.093 |
Time to antibiotics, h, n (%) | 0.832 | |||||
0-1 | 17.00 (36.17) | 9.00 (37.50) | 11.00 (50.00) | 25.00 (37.88) | 7.00 (43.75) | |
>1 | 30.00 (63.83) | 15.00 (62.50) | 11.00 (50.00) | 41.00 (62.12) | 9.00 (56.25) | |
Steroids, n (%) | 13.00 (27.66) | 9.00 (37.50) | 5.00 (21.74) | 27.00 (40.91) | 3.00 (18.75) | 0.239 |
Hospital days, median (IQR) | 7.71 (4.44-10.29) | 11.64 (5.10-20.99) | 5.92 (3.50-16.29) | 11.57 (5.05-22.91) | 10.12 (6.30-16.14) | 0.126 |
In-hospital mortality, n (%) | 15.00 (31.91) | 14.00 (58.33) | 18.00 (78.26) | 41.00 (62.12) | 7.00 (43.75) | 0.002 |
Univariate analysis of prognostic factors in the derivation cohort.
Variable | Total number of patients (%) | In-hospital mortality HR (95% CI) | 28 day mortality HR (95% CI) | 60 day mortality HR (95% CI) |
---|---|---|---|---|
Age, years | ||||
20-50 | 23.00 (13.07) | 1.00 | 1.00 | 1.00 |
51-70 | 81.00 (46.02) | 0.73 (0.41-1.30) | 0.74 (0.41-1.35) | 0.80 (0.45-1.41) |
>70 | 72.00 (40.91) | 0.75 (0.42-1.34) | 0.71 (0.39-1.30) | 0.79 (0.44-1.40) |
Sex | ||||
Female | 64.00 (36.36) | 1.00 | 1.00 | 1.00 |
Male | 112.00 (63.64) | 1.00 (0.66-1.52) | 0.97 (0.63-1.50) | 0.97 (0.65-1.45) |
Hypertension | ||||
No | 82.00 (46.59) | 1.00 | 1.00 | 1.00 |
Yes | 94.00 (53.41) | 1.09 (0.73-1.63) | 1.09 (0.71-1.65) | 1.08 (0.73-1.60) |
Congestive heart failure ejection fraction <40% | ||||
No | 151.00 (85.80) | 1.00 | 1.00 | 1.00 |
Yes | 25.00 (14.20) | 0.77 (0.41-1.44) | 0.67 (0.34-1.34) | 0.87 (0.48-1.55) |
Tumour type | ||||
Solid tumour | 141.00 (80.11) | 1.00 | 1.00 | 1.00 |
Haematological malignancy | 35.00 (19.89) | 0.86 (0.51-1.43) | 0.98 (0.58-1.64) | 0.79 (0.48-1.32) |
White blood cell (1x109/l), n (%) | ||||
>10 | 91.00 (51.70) | 1.00 | 1.00 | 1.00 |
≤10 | 85.00 (48.30) | 0.83 (0.55-1.24) | 0.88 (0.58-1.34) | 0.87 (0.59-1.29) |
Haemoglobin categorical, g/l | ||||
>100 | 82.00 (46.59) | 1.00 | 1.00 | 1.00 |
≤100 | 94.00 (53.41) | 0.97 (0.65-1.46) | 0.99 (0.65-1.51) | 1.01 (0.68-1.49) |
Diagnosis | ||||
Septic shock | 109.00 (61.93) | 1.00 | 1.00 | 1.00 |
Sepsis | 67.00 (38.07) | 0.26 (0.16-0.43) | 0.27 (0.16-0.45) | 0.31 (0.19-0.49) |
Bacteraemia | ||||
No | 110.00 (62.50) | 1.00 | 1.00 | 1.00 |
Yes | 66.00 (37.50) | 0.88 (0.57-1.36) | 0.95 (0.61-1.47) | 0.92 (0.61-1.39) |
Chemotherapy | ||||
No | 29.00 (16.48) | 1.00 | 1.00 | 1.00 |
Yes | 147.00 (83.52) | 0.52 (0.32-0.85) | 0.51 (0.31-0.85) | 0.56 (0.35-0.91) |
Radiation therapy | ||||
No | 114.00 (64.77) | 1.00 | 1.00 | 1.00 |
Yes | 62.00 (35.23) | 0.92 (0.60-1.42) | 0.85 (0.54-1.34) | 1.01 (0.67-1.53) |
Surgery | ||||
No | 98.00 (55.68) | 1.00 | 1.00 | 1.00 |
Yes | 78.00 (44.32) | 0.97 (0.65-1.46) | 1.02 (0.67-1.56) | 1.07 (0.72-1.58) |
Time to antibiotics, h | ||||
>1 | 106.00 (60.57) | 1.00 | 1.00 | 1.00 |
0-1 | 69.00 (39.43) | 0.71 (0.46-1.09) | 0.67 (0.43-1.05) | 0.70 (0.47-1.07) |
Steroids | ||||
No | 119.00 (67.61) | 1.00 | 1.00 | 1.00 |
Yes | 57.00 (32.39) | 1.19 (0.78-1.83) | 1.21 (0.78-1.88) | 1.25 (0.83-1.88) |
HR, hazard ratio.
Cox regression model for mortality.
Variable | Not adjusted HR (95% CI) | P-value | Model I |
P-value | Model II |
P-value |
---|---|---|---|---|---|---|
In-hospital mortality | ||||||
Urinary tract | 1.00 | 1.00 | 1.00 | |||
Unknown | 1.93 (0.93-3.99) | 0.078 | 1.88 (0.91-3.91) | 0.089 | 1.91 (0.88-4.16) | 0.103 |
Gastrointestinal | 3.45 (1.74-6.68) | <0.001 | 2.78 (1.38-5.60) | 0.004 | 2.64 (1.25-5.55) | 0.011 |
Lung | 2.19 (1.21-3.96) | 0.009 | 1.91 (1.06-3.46) | 0.032 | 1.95 (1.03-3.68) | 0.039 |
Other | 1.30 (0.53-3.19) | 0.566 | 1.35 (0.55-3.31) | 0.519 | 1.31 (0.51-3.37) | 0.577 |
28 day mortality | ||||||
Urinary tract | 1.00 | 1.00 | 1.00 | |||
Unknown site | 1.59 (0.77-3.31) | 0.212 | 1.53 (0.74-3.19) | 0.255 | 1.43 (0.65-3.12) | 0.376 |
Gastrointestinal | 2.87 (1.45-5.68) | 0.003 | 2.29 (1.14-4.60) | 0.020 | 2.10 (1.00-4.44) | 0.051 |
Lung | 1.75 (0.97-3.16) | 0.062 | 1.52 (0.84-2.74) | 0.165 | 1.55 (0.82-2.94) | 0.175 |
Other | 1.02 (0.40-2.60) | 0.971 | 1.02 (0.40-2.63) | 0.962 | 0.92 (0.34-2.46) | 0.870 |
60 day mortality | ||||||
Urinary tract | 1.00 | 1.00 | 1.00 | |||
Unknown site | 1.52 (0.76-3.03) | 0.237 | 1.49 (0.75-2.98) | 0.256 | 1.47 (0.70-3.09) | 0.307 |
Gastrointestinal | 2.74 (1.43-5.23) | 0.002 | 2.26 (1.17-4.38) | 0.016 | 2.22 (1.10-4.48) | 0.026 |
Lung | 1.78 (1.03-3.05) | 0.038 | 1.56 (0.91-2.69) | 0.108 | 1.58 (0.88-2.84) | 0.124 |
Other | 1.17 (0.51-2.68) | 0.708 | 1.20 (0.52-2.76) | 0.664 | 1.09 (0.45-2.62) | 0.847 |
aAdjusted for diagnosis and chemotherapy.
bAdjusted for age (20-50, 51-70 and >70 years), sex, diagnosis, congestive heart failure ejection fraction <40%, hypertension, tumour type, bacteraemia, chemotherapy, radiation, surgery, white blood cell, haemoglobin and time to antibiotics. HR, hazards ratio.
Cox regression models for mortality in 141 patients with solid tumours.
Variable | Not adjusted HR (95% CI) | P-value | Model I |
P-value | Model II |
P-value |
---|---|---|---|---|---|---|
In-hospital mortality | ||||||
Urinary tract | 1.0 | 1.0 | 1.0 | |||
Unknown | 2.21 (0.99-4.95) | 0.053 | 2.25 (1.00-5.05) | 0.049 | 2.33 (0.97-5.63) | 0.060 |
Gastrointestinal | 2.93 (1.39-6.16) | 0.005 | 2.22 (1.04-4.75) | 0.039 | 2.36 (1.05-5.31) | 0.039 |
Lung | 2.32 (1.22-4.42) | 0.010 | 2.07 (1.08-3.95) | 0.028 | 2.19 (1.10-4.35) | 0.026 |
Other | 1.05 (0.37-2.94) | 0.929 | 1.14 (0.40-3.22) | 0.807 | 1.14 (0.37-3.50) | 0.816 |
28 day mortality | ||||||
Urinary tract | 1.0 | 1.0 | 1.0 | |||
Unknown | 1.75 (0.78-3.93) | 0.179 | 1.74 (0.77-3.93) | 0.181 | 1.65 (0.68-4.01) | 0.269 |
Gastrointestinal | 2.37 (1.13-4.97) | 0.023 | 1.81 (0.85-3.85) | 0.124 | 1.70 (0.75-3.85) | 0.201 |
Lung | 1.76 (0.93-3.34) | 0.085 | 1.56 (0.82-2.99) | 0.176 | 1.65 (0.83-3.31) | 0.156 |
Other | 0.76 (0.25-2.31) | 0.626 | 0.80 (0.26-2.44) | 0.689 | 0.69 (0.21-2.27) | 0.539 |
60 day mortality | ||||||
Urinary tract | 1.0 | 1.0 | 1.0 | |||
Unknown | 1.69 (0.79-3.62) | 0.175 | 1.72 (0.80-3.69) | 0.161 | 1.71 (0.74-3.95) | 0.207 |
Gastrointestinal | 2.24 (1.12-4.49) | 0.023 | 1.77 (0.87-3.60) | 0.115 | 1.95 (0.92-4.17) | 0.084 |
Lung | 1.83 (1.02-3.28) | 0.042 | 1.64 (0.91-2.95) | 0.099 | 1.72 (0.92-3.21) | 0.092 |
Other | 0.96 (0.38-2.43) | 0.925 | 1.02 (0.40-2.61) | 0.966 | 0.95 (0.34-2.63) | 0.920 |
aAdjusted for diagnosis and chemotherapy.
bAdjusted for age (20-50, 51-70 and >70 years), sex, diagnosis, congestive heart failure ejection fraction <40%, hypertension, bacteraemia, chemotherapy, radiation, surgery, white blood cell, haemoglobin and time to antibiotics. HR, hazard ratio.
Cox regression models for mortality in 35 patients with haematological tumours.
Variable | Not adjusted HR (95% CI) | P-value | Model I |
P-value | Model II |
P-value |
---|---|---|---|---|---|---|
In-hospital mortality | ||||||
Urinary tract | 1.0 | 1.0 | 1.0 | |||
Unknown site | 1.45 (0.24-8.71) | 0.683 | 1.68 (0.28-10.20) | 0.571 | 76.67 (1.84-3202.38) | 0.022 |
Gastrointestinal | 13.99 (2.04-95.89) | 0.007 | 30.51 (3.71-251.17) | 0.002 | 179.91 (5.69-5693.31) | 0.003 |
Lung | 2.05 (0.43-9.67) | 0.366 | 2.59 (0.54-12.43) | 0.234 | 16.96 (0.86-334.76) | 0.062 |
Other | 3.16 (0.44-22.66) | 0.253 | 4.95 (0.66-37.40) | 0.121 | 66.81 (1.10-4062.06) | 0.045 |
28 day mortality | ||||||
Urinary tract | 1.0 | 1.0 | 1.0 | |||
Unknown site | 1.45 (0.24-8.71) | 0.683 | 1.68 (0.28-10.20) | 0.571 | 76.67 (1.84-3202.38) | 0.023 |
Gastrointestinal | 13.99 (2.04-95.89) | 0.007 | 30.51 (3.71-251.17) | 0.002 | 179.91 (5.69-5683.31) | 0.003 |
Lung | 2.05 (0.43-9.67) | 0.366 | 2.59 (0.54-12.43) | 0.234 | 16.96 (0.86-334.76) | 0.063 |
Other | 3.16 (0.44-22.66) | 0.253 | 4.95 (0.66-37.40) | 0.121 | 66.81 (1.10-4062.06) | 0.045 |
60 day mortality | ||||||
Urinary tract | 1.0 | 1.0 | 1.0 | |||
Unknown site | 1.45 (0.24-8.71) | 0.683 | 1.68 (0.28-10.20) | 0.571 | 76.67 (1.84-3202.38) | 0.023 |
Gastrointestinal | 13.99 (2.04-95.89) | 0.007 | 30.51 (3.71-251.17) | 0.002 | 179.91 (5.69-5693.31) | 0.003 |
Lung | 2.05 (0.43-9.67) | 0.366 | 2.59 (0.54-12.43) | 0.234 | 16.96 (0.86-334.76) | 0.063 |
Other | 3.16 (0.44-22.66) | 0.253 | 4.95 (0.66-37.40) | 0.121 | 66.81 (1.10-4062.06) | 0.045 |
aAdjusted for diagnosis and chemotherapy.
bAdjusted for age (20-50, 51-70, >70), sex, diagnosis, congestive heart failure ejection fraction <40%, hypertension, bacteraemia, chemotherapy, radiation, surgery, white blood cell, haemoglobin and time to antibiotics. HR, hazard ratio.