Clinical characteristics and risk factors for mortality in patients with community-acquired staphylococcal pneumonia

概要

【Introduction】
Pneumonia is one of the leading causes of death worldwide. Staphylococcus aureus (S. aureus), one of the causative pathogens of community-acquired pneumonia (CAP) and healthcare-associated pneumonia (HCAP), is increasing in prevalence. Several reports have shown the emergence of S. aureus CAP as one of the causes of severe pneumonia leading to critical illness and death. To provide better management practices for patients with S. aureus CAP, their clinical characteristics and factors contributing to mortality should be clarified.

【Patients and methods】
This study is a post-hoc analysis using prospectively collected data of an observational multicenter study in patients with pneumonia, which was conducted at 10 medical institutions in Japan. All adult patients with CAP were enrolled. The primary endpoint was 30-day mortality. We did statistical analyses with SPSS. All tests were two-tailed and a p- value of less than 0.05 was regarded as significant. For analysis of risk factors for mortality, we performed univariable and multivariate analyses. We performed univariate analysis using 26 variables which were decided by referral to previous reports. When determining the cut off values of continuous variables, we considered the values from previous studies and performed histograms for each variable.
Multivariate logistic regression analysis with forced entry selection method was performed. Adjusted odds ratios (AORs) and the corresponding 95% confidence intervals (CIs) were calculated.
Additionally, subgroup analyses on pneumococcal CAP patients were performed.

【Results】
Patient flow and Baseline characteristics: In total, 1742 patients were assessed for eligibility, 1413 patients with CAP were identified to be eligible. 196 patients with S. aureus CAP and 198 with pneumococcal CAP were identified. (Figure 1).
We investigated the characteristics of the two CAP groups. Certain clinical characteristics were more prevalent in the S. aureus CAP, including age ≥ 80, congestive heart failure, CNS disorder, non-ambulatory status, GCS ≤12, albumin <3.0 g/dL, Na <130 or ≥150 mEq/l, pH <7.35, PaO2/FiO2 ≤250, bilateral lung involvement, and pleural effusion (Table 1).
Table 2 lists the characteristics of the survivors and non-survivors in the S. aureus CAP. Many of the patients who died had the following findings: non-ambulatory status (68%), GCS ≤12 (52%), albumin <3.0 g/dL (65%), pH <7.35 (26%) and PaO2/FiO2 ≤250 (81%).
(Table 2).
Microbiological findings and Appropriateness of antibiotics: In S. aureus CAP, we identified high rate of co-infections about 72%, especially gram-negative pathogens which detected in 51%. The mortality rates were 21% for the patients with MRSA and 13% for those with S. aureus and other co-infected pathogens, respectively. In contrast, we identified Gram-positive pathogen co-infections in only 22%.
The appropriateness of antibiotics was assessed in 193 of the 196 patients; 39% received inappropriate initial antibiotics, and 60% received appropriate initial antibiotics. Anti- MRSA antibiotics were administered to only 6 patients (6/196); only 8% (6/77) of the patients with MRSA received appropriate antibiotics.
Risk factors for 30-day mortality: We performed univariate analysis using the 26 baseline characteristics. The result showed five variables with significant p value, including, non-ambulatory status, GCS ≤12, albumin <3.0 g/dL, pH <7.35 and PaO2/FiO2
≤250 (Table 4).
To identify mortality risk factors for patients with S. aureus CAP, multivariate analysis was performed using the five significant variables in addition to age, sex, and the presence of methicillin resistance. Table 4 shows the risk factors for mortality including PaO2/FiO2 ≤250 (AOR, 3.29; 95% CI 1.20–9.04; p = 0.021) and albumin <3.0 g/dL (AOR, 2.41; 95% CI 1.01–5.83; p = 0.047). Non-ambulatory status (AOR, 2.40; 95% CI 0.93–6.17; p = 0.070) tended to increase the mortality risk. The presence of methicillin resistance (AOR, 1.17; 95% CI 0.50–2.74; p = 0.727) was not detected as a significant risk factor.
Subgroup analyses: We identified 198 patients with pneumococcal CAP, with a mortality of 7.1%. When performing the analysis of mortality risk factors for the pneumococcal CAP patients, we assessed the same 26 variables. The univariate analysis results showed that the variables (age ≥80 years, non-ambulatory status, GCS ≤12, albumin <3.0 g/dL, neoplastic diseases, congestive heart failure, chronic renal diseases, glucose ≤60 or ≥300 mg/dL, blood urea nitrogen ≥30 mg/dL, and pleural effusion) had significant p-values. Using these variables, we performed a multivariate logistic analysis. The following factors were identified as associated with mortality in pneumococcal CAP: non-ambulatory status (AOR, 16.1; 95% CI 2.6–98.9; p = 0.003), albumin <3.0 g/dL (AOR, 10.2; 95% CI 1.8–55.8, p = 0.007) and age ≥80 years (AOR, 4.9; 95% CI 0.98–24.6; p = 0.052).

【Discussion】
In this post hoc analysis, we identified two potential risk factors (respiratory failure [PaO2/FiO2 ≤250] and hypoalbuminemia [albumin <3.0 g/dL]) associated with 30-day mortality in patients with S. aureus CAP. A non-ambulatory status also tended to increase the mortality risk.
As for clinical characteristics, the patients with S. aureus CAP had distinct clinical features compared with pneumococcal CAP, which included advanced age, CNS disorders, poor functional ability, altered mental status, hypoalbuminemia, hyponatremia/ hypernatremia, acidemia, hypoxemia, and bilateral lung involvement. These are well- known risk factors for mortality in all patients with CAP. Regarding the microbiological findings, we noted that the rate of co-infections in the S. aureus CAP was surprisingly high (72%). The most detected co-infective organisms were Gram-negative pathogens. Physicians should recognize these co-infections and consider using appropriate antibiotics for these co-infection pathogens.
The current predictive scoring systems were developed using data from time points where information on the causative pathogens was not available in many cases. The types and weight of risk factors for adverse outcomes might differ among patients with CAP according to the causative organisms. In this study, we focused on S. aureus because the prevalence of this organism is increasing as a causative pathogen in CAP.
Previous studies have mainly focused on MRSA, our study is one of the few studies that focusing on both types of S. aureus CAP. Although several studies have shown an association between these microbial factors and mortality, an important issue was whether the host factors were assessed as confounders for mortality. Other previous studies results showed that these microbial characteristics were not significantly associated with mortality after adjusting for other confounders. Our study also showed that a microbial factor, methicillin resistance, was not associated with mortality.
In our subanalysis, we assessed the differences in risk factors between the S. aureus and pneumococcal CAP groups. First, hypoalbuminemia and non-ambulatory status were common factors predicting mortality in both groups. These factors were previously reported as prognostic factors in CAP, although the PSI and CURB-65 do not include these factors. Second, in pneumococcal CAP, advanced age was associated with a high mortality risk, whereas PaO2/FiO2 ≤250 did not significantly affect mortality. In contrast, respiratory failure was a stronger risk factor than advanced age in S. aureus CAP.

【Conclusion】
patients with S. aureus CAP have distinct clinical features, and their most influential factors associated with mortality were respiratory failure and hypoalbuminemia. A number of potential host factors influencing mortality might be shared between S. aureus and pneumococcal CAP but might differ slightly. Physicians should recognize these findings and perform appropriate management strategies after obtaining information on the causative pathogen.