Differences in microbial etiology between hospital-acquired pneumonia and ventilator-associated pneumonia: a single-center retrospective study in Guang Zhou

Introduction

Nosocomial pneumonia (NP), including hospital-acquired pneumonia (HAP) and ventilator-associated pneumonia (VAP), is an important cause of morbidity and mortality in hospitalized patients despite advances in antimicrobial therapy and better supportive care modalities.^1,2 Comparing the 2005 version guideline with the 2016 version guideline of the Infectious Diseases Society of America and the American Thoracic Society, HAP had different definitions; in 2016 version, it emphasized that HAP was not associated with mechanical ventilation (MV), but remained a confusing area.^3,4 VAP is related to the duration of MV, intensive care unit (ICU) and hospital length of stay, and healthcare costs.² This demands a focus on the difference between HAP and VAP characteristics and prognosis. Clinical practice guidelines developed by international societies need to be tailored according to local epidemiology.⁵ Meanwhile,bacterial infection is the main cause of NP, and multidrug-resistant organism(MDRO) has appeared in recent years;hence, the risk factors of MDRO must be identified to facilitate the accurate prescription of antibiotics and improve overall prognosis in cases of NP.^6,7 This study aimed to evaluate the differences in microbial etiology between HAP and VAP, especially in related risk factors and prognosis caused by MDRO.

Material and methods

This single-center retrospective, observational study included patients with HAP/VAP. Data on all episodes of NP that occurred in the Third Affiliated Hospital of Sun Yat-sen University, Guangdong, China, from January 2014 to December 2017 were collected. All patients were at least 18 years old. The criteria for a NPdiagnosis⁴ includedthe presence of a new pulmonary infiltrate acquired in the hospital with two or more of the following: temperature >38.3 °C or <36 °C, leukocyte count >10×10⁹/L or <4×10⁹/L, and the presence of purulent respiratory secretions. HAP was defined as pneumonia that occurred ≥48h after admission, with no association with MV. VAP was defined as pneumonia that occurred 48–72 h after the intubation and initiation of MV. All cases were confirmed by microbial etiology. Cases with acquired immunodeficiency syndrome and those missing key data were excluded.

The simplified version of the clinical pulmonary infection score (CPIS), which determined temperature, blood leukocytes, tracheal secretions, PaO₂/FiO₂, and chest radiograph to assess the severity of NP, was used.

A microbiological strategy was then followed for the establishment of diagnosis: lower respiratory tract samples were obtained by bronchoalveolar lavage, endotracheal aspiration,or adequate sputum culture with WBCs >25 cells/HPF and epithelial cells <10 cells on Gram stain. Pathogenic bacteria were further characterized by conventional biochemical tests to identify the specific strain using standard microbiological methods. Pathogenic organism susceptibility testing was performed using the microdilution method (Micro ScanSystem; Baxter Healthcare, West Sacramento, CA, USA), and the results were interpreted using the National Committee for Clinical Laboratory Standards guidelines published in 2012 (Clinical & Laboratory Standards Institute, 2012). Here, MDROs were defined as organisms that were resistant to at least one agent from each of the three or more antimicrobial categories in susceptibility tests of isolates from patients with NP.⁸ In the statistical analysis, the parametric data were reported as frequency, percentage, mean value, and standard deviation, while nonparametric data were reported as frequency and percentage. Simple logistic regression analysis was performed, and each independent variable was analyzed together with the dependent variable of NP. These were reported as the P-value and odds ratio (OR). The accepted level of significance was P<0.05. Statistical analysis was performed using IBM SPSS Statistics, version 20 (IBM Corp., Armonk, New York, America).

Results

A total of 1,158 patients had HAP, and only 313 cases were included because 556 patients did not undergo bacterial culture and 289 patients had a negative bacterial culture result. Among the 2,901 inpatients under MV, 106 patients had VAP, and they were included. By comparing the characteristics between HAP and VAP, we found that less VAP patients were aged >70years, and VAP patients had more antibiotic therapy in the preceding 90 days and prior endotracheal tracheostomy (Table 1). The leading pathogens were similar in both kinds of NP, including Acinetobacter baumannii, Pseudomonas aeruginosa, and Klebsiella pneumoniae, but A.baumanniiwas significantly abundant in VAP. K.pneumonia and Staphylococcus aureus were significantly predominant in HAP (Table 2). Of these, VAP had more MDROs (Table 1). Moreover, the antimicrobial susceptibility of A.baumannii, K. pneumonia and Staphylococcus aureus was similar in both groups (Table 3, Table 4). However, P. aeruginosa causing VAP was less susceptible than P. aeruginosa causing HAP (Table 3). A CPIS ≥6 was predominant in the VAP group. The 30-day mortality rates of HAP and VAP were 18.5% and 42.5%, respectively (Table 1).

Table 1 The characteristics difference between HAP and VAP

Table 2 Distribution of pathogens between HAP and VAP

Table 3 The antimicrobial susceptibility differences between HAP and VAP

Table 4 Antimicrobial susceptibility among Staphylococcus aureus of HAP and VAP

To determine the distinction between HAP and VAP, this study analyzed the risk factors for MDRO-HAP and MDRO-VAP. The first logistic regression analysis identified the following risk factors for MDRO-HAP: chronic obstructive pulmonary disease (COPD), antibiotic therapy in the preceding 90 days, prior endotracheal tracheostomy, stomach tube intubation, and elevated blood urea nitrogen (BUN) level. Meanwhile, only ≥5 days of hospitalization and albumin level were considered the risk factors for MDRO-VAP. In the second multivariate analysis, COPD (P=0.023; OR, 3.006; 95% confidence interval [CI], 1.166–7.751), antibiotic therapy in the preceding 90 days (P=0.02; OR, 1.843; 95% CI, 1.102–3.081), and prior endotracheal tracheostomy (P=0.033; OR, 1.932; 95% CI, 1.055–3.539) were still associated with MDRO-HAP (Table 5). Furthermore, only≥5 days of hospitalization (P=0.01; OR, 0.021; 95% CI, 0.065–0.685) was associated with MDRO-VAP (Table 6).

Table 5 Significant univariate and multivariate logistic regression analyses of risk factors associated with HAP

Table 6 Significant univariate and multivariate logistic regression analyses of risk factors associated with VAP

Discussion

In this study, we found that less VAP patients had age >70years. Although it was similar to HAP in that VAP incidence was lower in the elderly,⁹ the causes of these observations in the elderly are imperfectly understood. Survival bias might be a factor, that is, because of the elderly’s comorbid conditions, they died before or during VAP acquisition.^10,11 VAP patients had to undergo more antibiotic therapy in the preceding 90 days, because this kind of patients had comorbidities requiring antibiotic therapy or preventive medication before MV. The patients who had prior endotracheal tracheostomy were more likely to have VAP in the current study; this is because they could easily be exposed to bacterial colonization,¹² and changes to the airway structure are a further risk factor. As VAP often occurred in the ICU, it suggested that patients were in critical condition and frequently required stomach tube intubation and central venous catheterization. This was consistent with our research. We noted that the BUN level of VAP patients was higher than that of HAP patients. Because patients with pneumonia often had dehydrated status resulting in the increased reabsorption of urea by the kidneys, elevation of BUN level is frequently observed,^13,14 especially with VAP.

In the current study, the leading pathogens were similar in both kinds of NP, with a predominance of A. baumannii, P. aeruginosa, and K. pneumonia. But A.baumannii was significantly abundant in VAP, and K. pneumonia and S. aureus were commonly predominant in HAP. This is similar to the findings reported previously.^4,15,16 It suggested that Gram-negative bacteria were the major NP pathogens in our center. This may be attributed to the warmer climate in our city, increased prevalence of organisms in the environment, and the higher prevalence of Gram-negative bacterial infections, especially A.baumannii infection in VAP, in the developing world.¹⁷Although S. aureus is the most common Gram-positive pathogen of NP,^18,19 it was still inferior to Gram-negative bacteria, especially in VAP. Our study demonstrated that VAP had more MDROs. Additionally, antimicrobial susceptibility of P. aeruginosa causing VAP was lower than that causing HAP, as in previous reports.^20,21 Meanwhile, this study found a higher rate of A.baumannii resistant to meropenem in these populations (82.7% in the HAP group and 78% in the VAP group).Similar resistance rates(79.5%–92.5%) to carbapenems were observed in previous studies of other hospitals,^22,23 indicating that MDRO infection remains a challenging aspect of NP etiology.

In this study, we assessed the risk factors associated with MDRO-NP. COPD was associated with MDRO-HAP because acute exacerbation of COPD usually requires antibiotic treatment.^24,25 Moreover, studies have shown that the colonization rates of Gram-negative bacteria such as P. aeruginosa and A. baumannii were higher in patients with COPD; therefore, it is easier for them to be repeatedly infected.^26,27 Antibiotics are crucial intreating infectious diseases including HAP. However, antibiotic resistance has increased, and the rise of MDR bacteria is threatening human health.²⁸ Antibiotic therapy in the preceding 90 days was an important risk factor for MDRO-HAP in the present study. This finding is similar to that of the previous studies that suggested the impact of virulence and antibiotic tolerance.^24,29 Therefore, among patients with HAP who have been exposed to antibiotics, MDRO should be targeted to control the condition effectively and improve prognosis. Tracheotomy was also likely to lead to MDRO infection. This is because patients who had required MV or undergone tracheotomy can easily be exposed to MDRO colonization.¹² ICU admission or broad-spectrum antibiotic use also contributes to MDRO infection,³⁰ and changes to the airway structure are a further risk factor. Meanwhile, in our hospital, the rehabilitation department is famous in Guang Zhou, and there are many patients with tracheotomy coming to that department for rehabilitation treatment. Hence, tracheotomy became a risk factor of MDRO-HAP. The risk factor for MDRO with HAP or VAP was ≥5 days of hospitalization.^4,31 In this study, it was similar to VAP but not HAP, because VAP patients had long hospitalization, were easily exposed to antibiotics, and had induced bacterial resistance. In other words, the risk factors for MDRO in HAP and VAP were not the same.

The 30-day mortality rates of HAP and VAP were 18.5% and 42.5%, respectively, in this study. It was consistent with previous reports.^32,33 The reason why VAP had higher mortality rate was that the patients often had severe infection³⁴ or morbid state.³⁵ CPIS is a vital tool that evaluates the severity of pulmonary infection, and this score is positively correlated with the severity of pulmonary infection and prognosis.^36,37 The present study results support this finding, indicating an area for future research.

There are several limitations in our study. First, the sample size of this study was small, resulting in sparse data bias. Second, all clinical information related to the risk factors was collected retrospectively, which limits the generalization of our findings. Further prospective studies are warranted to reduce bias in the future.

Conclusion

HAP and VAP had similar pathogens, but antimicrobial susceptibility of VAP was lower, especially with P. aeruginosa. The risk factors associated with MDRO infection in HAP and VAP were different. VAP was associated with poorer outcomes compared with HAP.