Tóm tắt Luận án Current situation of hospital-Acquired pneumonia and antibiotic resistant characteristics of some bacteria causing hospital-acquired pneumonia in thai binh provincial general hospital in 2016 - 2017

nting for 30 to 70% of cases of HAI, and at the same time, it is possible to extend the additional treatment time from 6 to 13 days and increase the hospital fee to tens of millions of VND for one patient. In a study of nearly 10,000 patients of 10 hospitals in Vietnam, the prevalence of HAI was 5.8% and HAP accounted for 55.4%. 1.1.3. Some related factors for hospital-acquired pneumonia 1.1.3.1. Factors from patients: Infants, over 65-year-old people, obese people, patients with abdominal, chest, head and neck surgeries, patients with immunodeficiency or those with coughing reflex loss. 1.1.3.2. Factors due to medical intervention: Intubation or opening of the trachea, nasogastric tube. 1.1.3.3. Environmental factors and medical equipment: Transmission of germs causing HAP with bacteria through the dirty hands of health workers. Transmission of HAP microorganisms through non-properly sterilized equipment, transmission of HAP microorganisms through the air, through the infected surface are also confirmed factors. 1.1.4. Physiology of hospital-acquired pneumonia: (1) HAP due to microaspiration: the most common mechanism of HAP in hospitalized patients is microaspiration of contaminated oropharyngeal secretions into the lower respiratory tract. (2) HAP due to biofilm formation in the endotracheal tube. (3) HAP due to changes in lung protection mechanisms. (4) HAP due to an increase in pathogenic bacteria. 5 1.1.5. Origin of bacteria: There are three sources of bacteria that cause HAP: environment, cross-transmission and endogenous bacterial flora. 1.1.6. Preventive measures against hospital-acquired pneumonia Hospitals need to implement measures in close coordination with each other to bring about high efficiency. (i) Training; (ii) Monitoring, (iii) Disinfecting and sterilizing respiratory assistive devices (ventilators, aerosols, anesthesia machines), (iv) Prevention of infection by health workers (hand hygiene, wearing gloves and other protective equipment, etc.), (v) Care for coma, prevention of HAP microaspiration, (vi) Caring for patients with intubation, tracheostomy, other ventilation support, (vii) Other preventive measures.. 1.2 Causes and antibiotic resistance of bacteria causing hospital- acquired pulmonia 1.2.1. Definition: Antibiotic-resistant bacteria: A bacterium is called antibiotic-resistant when the minimum inhibitory concentration of that antibiotic against bacteria is higher than the concentration of inhibiting the majority of other bacteria strains of the same species. 1.2.2. Causes of hospital-acquired pneumonia in the world and Vietnam According to statistics, common causes of HAP include Gram-negative (-) bacteria such as P.aeruginosa, A.baumannii, H.influenzae, Enterobacteriaceae spp. and Gram-positive (+) bacteria such as S.aureus, S.pneumoniae, S.pyogenes. 1.2.3. Situation of antibiotic resistance of some bacteria causing hospital- acquired pneumonia 1.2.3.1. Situation of antibiotic resistance of some bacteria causing hospital- acquired pneumonia in the world 6 The US Centers for Disease Prevention and Control estimates there are more than 2 million infections and about 23,000 deaths from resistant bacteria each year. The most common strains of multidrug-resistant bacteria associated with serious infections in the intensive care facilities are E.faecium, S.aureus, K.pneumoniae, A.baumannii, P.aeruginosa and Enterobacter spp, which are often called ESKAPE 1.2.3.2. Situation of antibiotic resistance of some bacteria causing hospital- acquired pneumonia in Vietnam A.baumannii: The resistance rate of A.baumannii to two antibiotics ampicinllin and sulfamethosazole/ trimethoprime is 100%. A.baumannii is almost completely resistant to antibiotics of the beta-lactam, cephalosporin and fluoro-quinolone groups from 90.1% to 98.6%. In the group of carbapenem: imipenem and meropenem are also resistant at 91.5%. The resistance rate of A.baumannii to the antibiotics of aminoglycoside group like amikacin is 18.3%, and gentamicin of 53.5%. Enterobacteriaceae: K.pneumoniae is resistant to ampicillin at a very high rate, ranging from 85-98% depending on different studies. K.pneumoniae is also more than 50% resistant to third-generation cephalosporins and quinolones, but is over 80% sensitive to amikacin and nearly 100% resistant to carbapenem 1.2.4. Molecular techniques for rapid diagnosis of bacteria causing hospital-acquired pneumonia 1.2.4.1. Application of molecular techniques to determine the epidemiology of bacteria causing hospital-acquired pneumonia - PCR is the polymerase chain reaction technique that uses polymerase to detect antibiotics resistance gene discovered by Kary Mullis et al. in 1985. The Multiplex - PCR technique is an improvement of the PCR technique in which multiple DNA fragments can be duplicated simultaneously by using multiple primer pairs in a reaction. 7 - Gene sequencing techniques: Since 1977 a number of gene sequencing methods have been invented such as: Gene sequencing by chemical methods and by enzymes or Dideoxy methods. 1.2.4.2. Role of beta –lactam resistance genes The most common and important mechanism for bacterial resistance to β-lactam antibiotics is the production of β-lactamase. At present, there have not been many in-depth studies on the resistance mechanisms to β-lactam groups of A.baumannii and K.pneumoniae on the scale of many hospitals in Vietnam. Especially, the detection of carbapenem-resistant Oxacillinase gene. The most prominent detection of OXA-51 and OXA-23 genes, which are carbapenem resistance genes isolated in many Asian countries, has only been reported sporadically in a few studies at a number of hospitals and still very little. 1.3 . Some information of Thai Binh Provincial General Hospital Thai Binh Provincial General Hospital is a grade-one hospital in Thai Binh province, with the outpatient treatment of about 300,000 hospital visits; Inpatient treatment of about 70,000 patients. According to the cross- sectional survey of the hospital, the hospital infection rate is about 6.3%, the highest infection is hospital-acquired pneumonia in patients with artificial ventilation, an average of 79.2%. In the Department of Intensive care and Poison control, the average rate of hospital-acquired infection is 36.8% while this rate in other departments is from 3 to 7%. Each year, the Department of Intensive care receives about 3,000 patients with many illnesses. Patients in the department may be exposed to many related factors such as mechanical ventilation and other invasive procedures. This is one of the related factors that increase the rate of hospital-acquired pneumonia. 8 CHAPTER 2: RESEARCH SUBJECTS AND METHODOLOGY 2.1. Research subject, are and duration 2.1.1. Subjects: Objective 1 is the patients staying for more than 48 hours in the Department of Intensive care and Poison Control, Thai Binh General Hospital, who are not infected and/ or do not have signs of hospital- acquired pneumonia at the time of admission and meet the diagnostic criteria for HAP of the Ministry of Health. Objective 2 is the strains of bacteria isolated from bronchial/sputum specimens of patients with HAP. Then, identifying the antibiotic resistance genes of the two bacteria species causing HAP which have the highest rate isolated. 2.1.2. Area: Research on patients in the Department of Intensive Care and Poison Control, Thai Binh Provincial General Hospital - Bacterial isolation research was conducted at the Department of Microbiology of Thai Binh Provincial General Hospital and at the Center for Molecular Biology – National Hospital for Tropical Diseases. 2.1.3. Duration: The study was conducted from July 1, 2016 to June 30, 2019 2.2. Research methodology The topic is conducted according to a prospective analytical descriptive research design. 2.2.1. Sample size and sample selection for objective 1 The sample size was calculated according to the formula for determining sample size ratio: 9 In which: n: sample size (number of patients surveyed); Z(1-α/2)= 1.96 (95% validity); p = 23.4% is the estimated rate of patients infected with hospital- acquired pneumonia in the study population, based on the results of research on hospital-acquired pneumonia in Vietnam in 2016; d = 0.03 (absolute error). We put the parameters into the formula and calculated the minimum sample size for the study, which is 785 patients. In fact, the population of 844 patients is eligible for research. The researcher conducted convenience sampling all patients eligible for admission to the Department of Intensive care and Poison control until the study had enough sample 2.2.2 Sample size and sample selection for objective 2 Samples to determine the rate of infection and antibiotic resistance characteristics of bacteria: Convenience sampling all strains of bacteria isolated from bronchial/sputum specimens of patients with HAP and having laboratory analysis. Strains of bacteria identifying antibiotic resistance genes: Targeted samples were all bacteria strains of A.baumannii and K.pneumoniae which are two bacteria with the highest infection rate among the isolated bacteria strains. In fact, the study has isolated and made antibiotic susceptible testing of 262 strains of pathogenic bacteria, and tested to detect antibiotic resistance genes 67 strains of A.baumannii and 53 strains of K.pneumoniae. 2.2.3. Variables and indicators in the study - Current situation and some related factors causing hospital-acquired pneumonia: The incidence proportion (IP) of hospital-acquired pneumonia; The incedence rate (IR) of hospital-acquired pneumonia; the related factors causing HAP. - Causes and antibiotic resistance characteristics of some bacteria that cause HAP: Bacterial name, rate of antibiotic resistance of bacteria, some molecular biology characteristics of strains of A.baumannii, K.pneumoniae causing HAP. 10 2.2.4. Methods and techniques of data collection: - The data collection techniques for objective 1 include: techniques to monitor HAP, Techniques to identify related factors to HAP, Techniques to assess consequences of HAP. - The data collection techniques for objective 2 include collecting specimens to identify the etiology of the disease through bronchial fluids and sputum, bacterial identification culture technique, antibiotic mapping technique, PCR technique and gene sequencing, and a number of other tests. 2.2.5. Information collection process: Research data was collected through the HAP survey set of 6 appendices. Researchers collect information through patient observation, track patients parameters shown on the machine or monitoring sheets, study medical records, interviews with doctors and nurses whenever there is anything unclear. In case of having difficulty in determining, researcher consults with resuscitation specialists and experts of infection control. 2.3. Data processing method: Research data was entered on EPI DATA 3.1 software and transferred to SPSS 20.0 software for processing and analysis. Using Chi Square test algorithms (2), t-Student test through p (p- value) to analyze the difference between the results of qualitative or quantitative variables. The related factors causing preventive medicine are determined through regression analysis. 2.4. Research ethics: The topic is accepted by the Board of Outline Approval of Thai Binh University of Medicine and Pharmacy, and the topic is also reviewed and allowed by the Medical Ethics Council of Thai Binh Provincial General Hospital. All patients participating in the study were explained about the purpose, content of the study and volunteered to participate in the study. If the subject feels uncomfortable, he or she could voluntarily give up. 11 CHAPTER 3. RESEARCH RESULTS 3.1. Current situation and some related factors causing hospital- acquired pneumonia Figure 3.2. Incidence proportion of hospital-acquired pneumonia (n=844) Figure 3.2 shows that out of 844 patients eligible for research, 262 subjects were newly infected with HAP, accounting for 31%. Table 3.5. Incidence proportion of hospital-acquired pneumonia according to intervention procedures (n=844) Patients Medical procedures Total of patients With HAP Without HAP n % n % Oxygen mask 547 146 26.7 401 73.3 Intubation 406 223 54.9 183 45.1 Tracheostomy 78 72 92.3 6 7.7 Ventilation 444 247 55.6 197 44.4 Central venous catheter 73 41 56.2 32 43.8 Sonde foley 563 250 44.4 313 55.6 Nasogastric intubation 550 249 45.3 301 54.7 Bronchoalveolar lavage 243 99 40.7 144 59.3 Pleural drainage 23 4 17.4 19 82.6 Sputum suction 222 159 71.6 63 28.4 Table 3.5 show that the incidence of patients with hospital-acquired pneumonia are most frequent in the patients with the procedures of tracheotomy (92.3%), sputum asuction (71.6%), cenral venous catheter (56.2%), ventilation (55.6%), intubation (54.9%) 12 Table 3.7. Incidence proportion of hospital acquired pneumonia according to duration of ventilation (n=844) Patients Ventilation duration Total of patients With HAP Without HAP p n % n % With ventilation 400 15 3.8 385 96.2 <0.05 Without ventilation 444 247 55.6 197 44.4 Table 3.7 shows that the IP of HAP patients with mechanical ventilation is 55.6%. There was a statistically significant difference in the prevalence of HAP patients with and without mechanical ventilation (p <0.05). Table 3.9. Incidence rate of hospital acquired pneumonia (n=262) Exposure factor Number of HAP patients Exposure duration Number of HAP patients/1.000 exposure days Treatment duration (days) 262 9334 28.1 Intubation duration 223 3644 61.2 Tracheostomy duration 72 1016 70.9 Ventulation duration 247 4543 54.4 Table 3.9 shows that the incidence rate of HAP, who had intubation, tracheostomy and mechanical ventilation, was 61.2; 70.9; 54.4, respectively. The number of HAP patients/1000 days of treatment was 28.1. 13 Table 3.18. Relationship between hospital-acquired pneumonia and invasive procedures (n=844) Variables With HAP Without HAP OR (95%CI) No % No % Intubation Yes (n=406) 223 54.9 183 45.1 12.5 (8.5-18.3) No (n=438) 39 8.9 399 91.1 1 Tracheostomy Yes (n=78) 72 92.3 6 7.7 36.4 (15.6-85.0) No (n=766) 190 24.8 576 75.2 1 Mechanical ventilation Yes (n=444) 247 55.6 197 44.4 32.1 (18.6-55.7) No (n=400) 15 3.8 385 96.2 1 Central venous catheter Yes (n=73) 41 56.2 32 43.8 3.2 (1.9-5.2) No (n=771) 221 28.7 550 71.3 1 Nasogastric intubation Yes (n=550) 249 45.3 301 54.7 17.9 (10.0-31.9) No (n=294) 13 4.4 281 95.6 1 Sputum suction Yes (n=222) 159 71.6 630 28.4 12.7 (8.9-18.2) No (n=622) 103 16.6 519 83.4 1 Table 3.18 show a correlation between HAP and invasive procedures such as mechanical ventilation, tracheotomy, etc. 14 Table 3.21. Logistic regression analysis of the relationship between hospital-acquired pneumonia and some demographic factors, pathological status and treatment interventions (n=844) Variables n % HAP OR ⃰ (95%CI) Age > 80 198 37.9 2.8 (0.9-8.5) 61-80 363 38.0 2.1 (0.8-6.3) 41-60 206 20.4 1.5 (0.5-4.6) ≤ 40 77 9.1 1 Sex Male 514 37.9 1.9 (1.3-3.1) Female 330 20.3 1 Chronic respiratory disease upon admission Yes 360 43.1 0.9 (0.6-1.5) No 484 22.1 1 Use corticosteroids Yes 275 45.5 1,4 (0,9-2,2) No 569 24.1 1 Intervention of respiratory tract exposure Yes 486 51.9 30.4 (15.2-60.9) No 358 2.8 1 Duration of hospitalization > 14 days 220 65.9 20.8 (11.5-37.6) 7-14 days 351 26.8 4.4 (2.6-7.5) < 7 days 273 8.4 1 OR ⃰ calibration The logistic regression analysis shown in Table 3.21 shows that the related factors of hospital-acquired pneumonia are sex, respiratory invasion intervention and hospitalization duration . 15 3.2. Antibiotic resistance characteristics of some bacteria commonly cause hospital-acquired pneumonia 3.2.1 Characteristics of common bacteria causing hospital-acquired pneumonia Table 3.22. Distribution of agents causing hospital-acquired pneumonia (n=262) Agents No Percentage % A.baumanni 103 39.3 K.pneumoniae 81 30.9 P.aeruginosa 22 8.4 E.coli 18 6.9 S.aureus 12 4.6 Serratia marcescens 12 4.6 Other bacteria 14 6.5 The causative agents of HAP are mainly Gram-negative bacteria: A.baumannii, K.pneumoniae, P.aeruginosa Table 3.25. Distribution of bacteria according to invasive procedures Procedures Bacteria Intubation (n=223) Tracheos tomy (n=72) Ventilation (n=247) Sputum suction (n=159) A.baumannii 89 (39.9) 33 (45.8) 97 (39.3) 59 (37.1) K.pneumoniae 68 (30.5) 14 (19.4) 77 (31.2) 52 (32.7) S.aureus 11 (4.9) 1 (1.4) 11 (4.5) 8 (5.0) E.coli 14 (6.3) 9 (12.5) 16 (6.5) 10 (6.3) P.aeruginosa 19 (8.5) 8 (11.1) 21 (8.5) 12 (7.5) S.marcescens 11 (4.9) 4 (5.6) 12 (4.9) 8 (5.0) Others 11 (4.9) 3 (4.2) 13 (5.3) 10 (6.3) Table 3.25 shows that, for those who have to use invasive procedures, the main bacteria that cause HAP are A.baumannii and K.pneumoniae 16 3.2.2. Antibiotic resistance rate of some common types of bacteria causing lung infections Table 3.28. Antibiotic resistance rate of A.baumannii (n=103) Antibiotics MIC (μg/ml) Sensitivity with antibiotics according to MIC S n (%) I n (%) R n (%) Imipenem 2-8 42 (41.2) 1 (0.98) 59 (57.8) Meropenem 2-8 14 (60.9) 0 9 (39.1) Ceftazidim 8-32 19 (19.4) 2 (2.0) 77 (78.6) Ceftriaxon 8-64 10 (10.0) 6 (6.0) 84(84.0) Cefotaxim 8-64 10 (9.9) 5 (4.9) 86 (85.2) Cefepime 8-32 20 (19.8) 1 (2.0) 79 (78.2) Amikacin 16-64 26 (27.7) 0 68 (72.3) Ciprofloxacin 1-4 20 (19.6) 0 82 (80.4) Colistin 2-4 44 (97.8) 0 1 (2.2) Table 3.28 shows that A.baumannii is resistant to most of the antibiotics of β-lactam, Fluroquinolon, Glycopeptide. However, A.baumannii is very sensitive to Colistin.. 17 Table 3.19. Antibiotic resistance rate of K.pneumoniae (n=81) Antibiotics MIC (μg/ml) Antibiotic sensitivity according to MIC S n (%) I n (%) R n (%) Imipenem 1-4 52 (78.8) 0 14 (21.2) Meropenem 1-4 11 (78.6) 0 3 (21.4) Cefazolin 16-32 12 (16.4) 0 61 (83.6) Cefamandol 8-32 7 (17.5) 0 33 (82.5) Cefuroxim 8-32 10 (18.9) 0 43 (81.1) Ceftazidim 4-16 27 (34.2) 1 (1.3) 51 (64.5) Ceftriaxon 1-4 23 (28.4) 0 58 (71.6) Cefotaxim 1-4 21 (26.6) 2 (2.5) 56 (70.9) Cefoperazone 16-64 20 (25.6) 2 (2.6) 56 (71.8) Cefepime 2-16 33 (40.7) 0 48 (59.3) Amoxicillin+acid clavulanic 8-32 12 (24.0) 2 (4.0) 36 (72.0) Ampicillin+ Sulbactam 8-32 11 (23.4) 2 (4.3) 34 (72.3) Amikacin 16-64 41 (62.1) 1 (1.5) 24 (36.4) Ciprofloxacin 1-4 34 (51.5) 1 (1.5) 31 (47.0) Levofloxacin 2-8 36 (55.4) 1 (1.5) 28 (43.1) Fosmycin 64-256 31 (53.45) 2 (3.45) 25 (43.1) Table 3.29 shows that K.pneumoniae bacteria are highly resistant to antibiotics: the resistant rate to Cephalosporin generation 1 and 2 is from 64.6% to 83.6%, to Quinolon (43.2% and 47.0%). However, K.pneumoniae is still sensitive to imipenem (21.2% resistance); meropenem (21.4% resistance). 18 Table 3.35. Proportion of antibiotic-resistant gene of A.baumannii Genes Rate of carrying resistance genes (n=67) No (%) TEM 52 77.6 SHV 4 6.0 CTX-M 3 4.5 PER,KPC 4 6.0 VIM; IMP; SPM; SIM; GIM 0 0.0 NMD-1 17 25.4 OXA-23 45 67.2 OXA-24 2 3.0 OXA-51 45 67.2 OXA-58 4 6.0 OXA-51+23 39 58.2 OXA-51+58 1 1.5 Table 3.35 shows that the rate of A.baumannii bacteria carrying antibiotic resistance gene of enzyme TEM accounted for 77.6% while A.baumannii là VK mang enzyme TEM chiếm 77.6%, NDM-1 (25.4%), OXA- 23 and OXA-51 (67.2%), OXA-51+23 (58.2%). Table 3.36. Proportion of antibiotic-resistant gene of K.pneumoniae Genes Rate of carrying resistance genes (n=53) No (%) TEM 50 94.3 SHV 53 100.0 KPC 30 56.6 NMD-1 46 86.8 VIM 7 13.2 IMP 24 45.3 SPM 26 49.1 OXA 33 62.3 Table 3.36 show the proportion of K.pneumoniae carrying antibiotic resistance gene, SHV enzyme is present in 100% of carriers, TEM (94.3%), KPC (56.6%), NDM-1 gene (86.8%) and OXA gene accounts for 62.3%. 19 Table 3. 37. Level of resistance to β-lactam group of A.baumannii to the gene OXA Gene OXA Antibiotic resistance according to MIC OXA-23 OXA -51 No % No % Imipenem I(n=0) - - - - R (n=53) 35 66.0 40 75.5 S (n=13) 9 69.2 5 38.5 Cefepim I (n=0) - - - - R (n=58) 37 63.8 42 72.4 S(n=8) 7 87.5 3 37.5 Colistin I, R (n=0) - - - - S (n=63) 43 68.3 43 68.3 Table 3.37 shows that A.baumannii carrying OXA-23 gene resistant to imipenem accounts for 66% and to cefepim is 63.8%. A.baumannii carying OXA-51 gene resistant to imipenem is 75.5% resistance, cefepim resistance is 72.4%. However, A.baumannii has not found the gene to resist colistin. Table 3. 38. Resistant level to β-lactam group of K.pneumoniae carrying resistance gene of β-lactam β-lactam resistant gene Antibiotics resistence according to MIC KPC NDM-1 No % No % Imipenem I (n=0) - - - - R (n=20) 8 40.0 17 85.0 S (n=31) 20 64.5 27 87.1 Meronem I (n=0) - - - - R (n=15) 6 40.0 13 86.7 S (n=11) 8 72.7 9 81.8 Cefepim I (n=0) - - - - R (n=35) 14 40.0 31 88.6 S (n=17) 16 94.1 14 87.5 Table 3.38 shows that strains carrying KPC gene were 40% imipenem resistant, 40% meronem resistant, 40% cefepime resistant. The strain carrying NDM-1 was 85% Imipenem resistant and 86.7% meronem resistant and 86.6% cefepime resistant. 20 CHAPTER 4. DISCUSSIONS 4.1. Current situation and some related factors causing hospital- acquired pneumonia 4.1.1. Incidence of hospital-acquired pneumonia Our research results show that, out of 844 patients eligible for inclusion in the study, 262 patients were newly infected with hospital-acquired pneumonia, so the incidence proportion of HAP was 31.0 % and the incidence rate of HAP is 28.1/1000 days of treatment. This result is higher than that of some other studies, Truong Anh Thu (2012) with the incidence proportion of HAP is 18.9%, the HAP incidence rate is 11.6/1000 days of treatment. In the US, a study of 61 ICU units from 2001 to 2005 showed that the rate of HAP was 21%. Our study shows that HAP was most prevalent in patients using the procedures of tracheotomy (92.3%), followed by cycle dialysis (75%), sputum suction (71.6%). The more intervention procedures patients use, the higher the incidence of HAP. The study results also show that the longer the mechanical ventilation time, the higher the incidence proportion of HAP. Indicators incidence rate of HAP: the number of patients with HAP/1000 days of treatment at Department of Intensive care and Poison control are 28.1; the number of HAP patients/ 1000 days with intubation, tracheostomy, and mechanical ventilation was 61.2; 70.9; 54.3, respectively. A study in the year 2010 showed that the incidence rate of HAP in Intensive Care Units in 15 developing countries was 13.6 HAP/1000 days of mechanical ventilation. 4.1.2. Related factors for hospital-acquired pneumonia * Factors belonging to patients: Regarding sex, the prevalence of HAP in men is 2.4 times higher than that in women and this difference is statistically significant (OR = 2.4 and 95% CI = 1.7-3.3); Regarding age, the probability of having HAP in the age group of 41-60 is 2.6 times higher than that of the age group < 40 years old; In the age group above 60, it is 6.1 times higher 21 (OR> 1 and 95% CI = 2.7-13.7). Our research also shows that patients with a history of respiratory diseases, cardiovascular disease and respiratory disease background are all related to hospital-acquired pneumonia. * Factors related to medical interventions: Through univariate regression analysis, invasive procedure factors related to hospital-acquired pneumonia include: intubation, tracheostomy, mechanical ventilation, Central venous catheter, nasogastric intubation, sputum suction. However, logistic regression analysis showed that sex factors, respiratory invasive intervention, and hospitalization duration were key related factors for hospital-acquired pneumonia. 4.1.3. Consequences of getting hospital-acquired pneumonia: Our research results show that HAP has serious clinical and economic consequences, namely: the incidence proportion of HAP in the treatment group of over 14 days is 21 times higher than the group with less than 7- day treatment. HAP is likely to increase the incidence of death, more severe illness of about 10.