Abstract
Background:
Pneumonia is the most common nosocomial infection reported worldwide in intensive care units. This study aimed to evaluate the risk factors of nosocomial pneumonia and the frequency of antibiotic resistance in trauma patients who need immediate intervention.
Patients and Methods:
This prospective cohort study was conducted in Shahid Rajaei Trauma Hospital in Shiraz between 2020 and 2021. All the trauma patients who needed immediate intervention (levels 1 and 2 based on the Canadian Emergency Department Triage and Acuity Scale) and had no symptoms of infection were included. Patients who were discharged or died before 48 hours were excluded.
Results:
The results demonstrated that major trauma (Injury Severity Score [ISS] ≥16), intubation, and use of invasive mechanical ventilation increase nosocomial pneumonia and death rate. The most common causes of nosocomial infections were Acinetobacter baumannii (23%) and coagulase-negative staphylococcus (18.5%). The highest levels of antibiotic resistance were related to cefoxitin, erythromycin, ciprofloxacin, and trimethoprim-sulfamethoxazole.
Conclusions:
Major trauma, intubation, and invasive mechanical ventilation were the effective factors in the development of nosocomial pneumonia. Continuous monitoring for mentioned risk factors and strict surveillance of antibiotic prescription can decrease the prevalence of nosocomial infections and subsequent deaths.
Nosocomial infection refers to cases of infection that occur at least 48 to 72 hours after admission to the hospital and are not in the incubation period at the time of admission. 1 Although nosocomial infections are more prevalent in developing countries, they have a considerable impact on developed countries' healthcare systems. 2 Hospital-acquired infections, especially in patients with poor conditions, lead to mortality and increased length of hospital and intensive care unit (ICU) stay. 3 This can impose a heavy burden on the public health system, resulting in increased costs for health services 4 and leading hospitals to receive more than $40,000 from patients for each course of treatment. 5
Nosocomial infections predictably increase the use of antibiotic agents and bacterial resistance to multiple drugs, which ultimately leads to increased mortality.6–8 The pattern of bacterial resistance to antimicrobial agents changes during the imposition of new strategies to control the use of antibiotic agents and after the introduction and widespread use of a new generation of antimicrobial drugs. However, the problem of resistance to antibacterial drugs still exists. 9 This issue is evident in Iran, where the consumption of antibiotic agents is almost equal to the total consumption of Europe and 16 times the world standard. 10 To control nosocomial infections, it is necessary to know their epidemiology. 11 Identifying the bacteria that cause pneumonia and determining antibiotic resistance also help prescribe effective antibiotics and can play an essential role in preventing complications and nosocomial infection mortality, as many patients with nosocomial pneumonia do not respond to the usual antibiotics previously used to treat them. 12
Some of the factors affecting patients with nosocomial pneumonia such as age and serious underlying diseases are unavoidable, but some other risk factors such as loss of consciousness, surgery, negligence of hand hygiene, intubation, and use of mechanical ventilators can be controlled by taking advantage of appropriate methods. 13 A lung tissue infection that occurs 48 hours or more after invasive mechanical ventilation is called ventilator-associated pneumonia (VAP), 14 which is the most common and severe infection associated with healthcare and most commonly affects patients in ICUs.15,16 Utilizing a tube in this procedure is a major risk factor for VAP because it deprives patients of the natural mechanism of airway clearance. 17
Information about the incidence of nosocomial pneumonia and the frequency of antibiotic resistance can be utilized to evaluate treatment and intervention measures and prepare a nosocomial infection control system, especially in patients in poor conditions. Therefore, the present study aims to assess the risk factors of nosocomial pneumonia as well as the frequency of antibiotic resistance in pneumonia-causing bacteria in patients in need of immediate intervention.
Patients and Methods
Study population
This prospective cohort study was performed in Shahid Rajaei (Emtiaz) Trauma Hospital in southern Iran between 2020 and 2021. The study population included trauma patients who were over 15 years old and were transferred to the resuscitation unit (patients at levels 1 and 2 based on the Canadian Emergency Department Triage and Acuity Scale [CTAS] guideline). 18 Patients who had been hospitalized for less than 48 hours or diagnosed with pneumonia prior to the data collection process were excluded from the study.
Data collection
The patients' information was collected using a self-designed form including demographic information (age, gender, nationality), Glasgow Coma Scale (GCS), length of hospital stay, mechanism of injury, location of the injury, injury severity, history of intubation and surgery, ventilator use, pneumonia-causing organisms, and antibiotic resistance. We identified patients with suspected nosocomial pneumonia using the U.S. Centers for Disease Control and Prevention (CDC) guideline.
19
.According to the CDC guideline any patient with one symptom including is defined as case of pneumonia:
Fever (core temperature >38.0°C) Leukopenia (white blood cell count ≤4,000/mm3) Leukocytosis (white blood cell count ≥12,000/mm3) Altered mental status without any recognized cause in patients older than 70 years
Plus at least two other symptoms including:
New onset of purulent sputum or change in character of sputum, or increased respiratory secretions, or increased suctioning requirements
New onset or worsening cough, or dyspnea, or tachypnea
Rales or bronchial breath sounds
Worsening gas exchange, increased oxygen requirements, or increased ventilator demand
To confirm the diagnosis, culture samples from the patients' respiratory specimens, using the transtracheal aspiration technique, were acquired and sent to the hospital laboratory for evaluation. Microbial susceptibility testing of antibiogram cultures was performed using the standard disk diffusion method.
Statistical analysis
After gathering the necessary information, the research hypotheses were analyzed using the STATA, version 17 (StataCorp LLC, College Station, TX). The quantitative variables were presented as mean and standard deviation (SD), whereas the qualitative ones were presented as absolute and relative frequency. The relation between the qualitative variables such as gender, accident mechanism, and Injury Severity Index (ISS) was assessed using the χ 2 test. Finally, the risk of nosocomial infection and mortality was determined by logistic regression modeling (forward method). A p value <0.05 was considered statistically significant.
Results
A total of 1,115 patients were included in this study, 83.3% (n = 929) of whom were male and 16.7% (186) were female. At the time of hospitalization, 63 patients (5.7%) were in shock. Among the patients, 244 (21.9%) developed nosocomial pneumonia and 105 (9.4%) died. The mean age of the patients was 37.7 ± 18.2 years, whereas the mean age of the patients with nosocomial infection was 41.7 ± 18.8 years. Additionally, young adults (15–44 years old) comprised the majority of the study population (68.3%). According to the results (Table 1), the patients diagnosed with nosocomial pneumonia had longer hospital stays than those without nosocomial pneumonia (29.7 ± 19.1 vs. 10.6 ± 9.2).
Distribution of Demographic Variables for Death and Nosocomial Pneumonia in Patients in Need of Immediate Intervention
SD = standard deviation; LOS = length of hospital stay; GCS = Glasgow Coma Scale.
The leading mechanism of injury was traffic collision (68.3%), with the thorax and head being the main sites of injury (Table 2). The mean ISS was 17.1 ± 10.9. More than half of the patients (52.1%) had major traumas (ISS ≥16) that was predictable because the study population was selected from the patients in need of immediate intervention. As demonstrated in Table 3, 27.6% (n = 308) of the patients were intubated, 68.2% of whom (n = 210) benefited from mechanical ventilation. However, approximately 44% of the intubated patients developed nosocomial pneumonia. This percentage was almost the same in the patients using mechanical ventilation (42%).
Distribution of Trauma Variables for Mortality and Nosocomial Pneumonia in Patients in Need of Immediate Intervention
SD = standard deviation; ISS = Injury Severity Score.
Distribution of Interventions for Mortality and Nosocomial Pneumonia in Patients in Need of Immediate Intervention
IMV = invasive mechanical ventilation.
The results of this study (Table 4) showed that GCS scores higher than nine had an inverse relation with nosocomial pneumonia (p < 0.001). The variables that were directly related to nosocomial infection were major trauma (p < 0.001), use of invasive mechanical ventilation (p < 0.001), and intubation (p < 0.001). Additionally, an increase in the length of hospital stay was accompanied by an increase in the likelihood of being diagnosed with nosocomial pneumonia (p < 0.001). Although age groups were not associated with nosocomial pneumonia, they affected mortality directly. Based on the results, elderly patients were more likely to die (p = 0.012). Patient intubation (p = 0.005) and use of an invasive mechanical ventilator (p < 0.001) were also directly associated with mortality. Besides, the survival rate was higher among the patients who did not undergo surgery (p < 0.001).
The Risk Factors of Death and Nosocomial Pneumonia in Patients in Need of Immediate Intervention
OR = odds ratio; CI = confidence interval; GCS = Glasgow Coma Scale; ISS = Injury Severity Score; LOS = length of hospital stay.
As shown in Table 5, the most common causes of nosocomial infections were Acinetobacter baumannii (23%) and coagulase-negative staphylococcus (18.5%). Moreover, drug resistance studies indicated that the highest frequency of drug resistance was related to cefoxitin, erythromycin, ciprofloxacin, and trimethoprim-sulfamethoxazole.
The Frequency of Antibiotic Resistance in Pneumonia-Causing Bacteria in Patients in Need of Immediate Intervention
Discussion
In this study, 21.9% of the patients in need of immediate intervention developed nosocomial pneumonia. However, the meta-analysis results conducted by Mosadeghrad et al. 20 demonstrated that the overall incidence of nosocomial infections was between 9.1% and 32.9%. In another study by Nadi et al., 21 the rate of nosocomial pneumonia in ICUs was 10.2%. The rate of nosocomial infection in the patients in need of immediate intervention in the current study was also higher compared with the measures reported in ICUs, Coronary care units (CCUs), and gynecology wards in the study carried out by Khan Beigi et al. 22 The high percentage of hospital-acquired pneumonia in our study indicates the sensitivity of trauma patients with poor conditions to the risk of nosocomial infections. Post-injury patients suffer from immunosuppression due to systemic inflammatory response syndrome (SIRS), compensatory anti-inflammatory response syndrome (CARS), and mixed anti-inflammatory response syndromes, which can be more prominent in patients with more severe injuries. 23 Also, as a result of the administration of prophylactic antibiotic agents, the flora-normal bacterial composition of the patient's respiratory tract mucosa changes, which makes the patient more susceptible to respiratory tract infections. 24
Until now, several strategies have been proposed to prevent nosocomial infections. For instance, planning a surveillance system to increase the sensitivity to diagnosing nosocomial infection can lead to the early initiation of antibacterial treatment and prevent the spread of bacteria to different patients. Nonetheless, such a conscious approach is not always without problems, as it has been shown that using this method can overdiagnose nosocomial infections, which can, in turn, waste resources. 25 Furthermore, the implementation of organized training programs and the active involvement of infection control staff to control the risk factors related to the environment and health workers can reduce the incidence of nosocomial infections. 26
In the current study, 9.4% of the patients with nosocomial infections died, which was lower than the mortality rate in the ICU in the studies carried out by Sepandi et al. 27 and Yadollahi et al. 28 The different mortality rates could result from the patients' different health statuses, which might change their prognosis depending on the type of health problem. In addition, the mean age of patients varied in these studies, which was an important risk factor for determining their outcome, as previously demonstrated. 29
In the current research, the mean length of hospital stay was 29.7 days among the patients with nosocomial infections and had a substantial association with death. This measure was much higher compared with the duration of hospitalization in the surgical wards, CCUs, and ICUs in the study conducted by Sepandi et al. 27 Prolonged hospitalization in patients in need of immediate intervention might be associated with higher ISS, lower level of consciousness, and frequent use of invasive mechanical ventilation. The question that arises here is whether the nosocomial infection in the present investigation was because of an increase in the length of hospital stay or the more time spent in the hospital because of the infection, as mentioned in the previous studies.30,31 Given that the average ISS was higher in the patients with nosocomial infections than in those without infections, longer hospitalization because of the critical condition of patients was the cause of nosocomial infections.
In the present study, approximately 42% of the patients who benefitted from invasive mechanical ventilation developed nosocomial infections. Prior studies also revealed an association between the use of ventilators and the incidence of nosocomial pneumonia. 32 The mean age of the present study patients was 41.7 years. Therefore, they were relatively young patients who have been reported to be prone to early-onset VAP. 33 Other factors affecting VAP were age, ISS, and duration of ventilator use. 33 Similar to the results of a study by Noniz et al., 34 the current study findings showed an association between ventilator use and mortality. Nonetheless, it was not possible to collect information on the duration of intubation and the use of mechanical ventilation in this study, which Núñez et al. 34 noted to be associated with an increased risk of mortality. In addition, characteristics of patients such as underlying diseases and health status during hospitalization were the strong predictors of patients' prognosis and might affect the relationship between ventilator use and mortality. 14
The current study findings showed an association between intubation and mortality, which was in agreement with the results of the research carried out by Lodise et al. 35 Intubation is a high-risk procedure that is usually performed for high-risk patients, and there is little information about its side effects. 36 However, because most patients who require intubation are severely ill and have a poor prognosis, the association between intubation and mortality may be because of their conditions rather than the intubation process and its subsequent complications. In the present research, an association between major trauma (ISS >16) and nosocomial pneumonia was observed. This might be associated with impaired immunity in patients that is the result of the inflammatory process after severe trauma, which can be detected by altering plasma inflammatory markers such as decreased plasma apolipoprotein B and AII. 37
In the current investigation, a decrease in GCS could increase the risk of nosocomial pneumonia. Patients with a decreased level of consciousness have impaired airway protective reflexes and are usually kept in a supine position, which increases gastroesophageal reflux and aspiration pneumonia. 38 To reduce the risk of aspiration pneumonia, patients with GCS less than eight are intubated. Recent studies, however, have emphasized the re-evaluation of this strategy because it has been shown that early intubation to reduce nosocomial pneumonia can increase mortality, length of ICU stay, and overall length of hospital stay, which can, in turn, increase the risk of nosocomial pneumonia. 39 It is important to mention that patients with intubation or low GCS did not receive prophylactic antibiotic treatment because of the increased prevalence of antibiotic resistance in nosocomial infections.
In the present research, the most common cause of nosocomial infections was Acinetobacter baumannii (23%), and the incidence of this pathogen was much higher in comparison with the studies performed by Yang et al. 40 and Bhardwaj et al. (9.6%). 41 Acinetobacter baumannii is an important nosocomial pathogen that can resist multiple drugs and is a threat to current antibiotic therapy. This pathogen has been shown to be associated with VAP. 42 Acinetobacter baumannii was resistant to cefoxitin, followed by trimethoprim-sulfamethoxazole, tetracycline, cefixime, rifampin, and amikacin. The second organism causing nosocomial infections was coagulase-negative staphylococcus (18.5%), which was the most common cause of nosocomial infections in the study by Shajari et al. 43 (25%). Moreover, cefoxitin was the antibiotic with the highest percentage of resistance, showing the highest resistance in Acinetobacter baumannii. On the contrary, Shajari et al. 43 disclosed that pseudomonas was the most resistant micro-organism to cefoxitin. The percentage of drug resistance to tetracycline in the present study was similar to the research carried out by Young et al., 40 whereas resistance to gentamicin was lower in the current investigation. Finally, coagulase-negative staphylococcus had the highest resistance to erythromycin, whereas the highest resistance was related to cefixime in the research conducted by Shajari et al. 43
This study was performed in the largest referral trauma center in southern of Iran. Therefore, its population can represent a large part of the society, and the findings can be generalized to the whole country. In this cohort study, the patients were closely monitored, and their results were accurately recorded until discharge. Considering that antibiotic resistance is developing rapidly, in this study, it was tried to pay attention to the antibiotic agents that have developed the most resistance against them, which can help in prescribing appropriate antibiotic agents for nosocomial pneumonia.
Limitations
A number of patients may develop the symptoms of nosocomial infection after discharge. However, there were insufficient resources to follow patients to investigate nosocomial infections after discharge. In addition, this is a single-center study, which can be considered a limitation. However, because this study was performed in a trauma referral center, a number of our patients were first treated in clinical centers located in southern Iran and later were transferred to this hospital because of their lack of sufficient resources. Therefore, this study population can represent the population of critically ill trauma patients in the southern centers of the country.
Conclusions
The present study results revealed the high prevalence of patients in need of immediate intervention for nosocomial pneumonia. The presence of major trauma, GCS less than eight, length of hospital stay, intubation, and the use of invasive mechanical ventilation were the risk factors for the development of nosocomial pneumonia. Therefore, continuous monitoring of nosocomial pneumonia, implementation of training programs, and conducting active interventions to control and prevent new cases of infection are essential. Furthermore, antibiotic resistance analysis showed that the highest frequency of resistance was related to cefoxitin, erythromycin, ciprofloxacin, and trimethoprim-sulfamethoxazole, and the highest sensitivity was related to clofazimine, chloramphenicol, and colistin. Overall, limiting the use of high-resistance antibiotic agents and prescribing antibiotic agents to which micro-organisms are more sensitive are crucial to prevent further antibiotic resistance.
Footnotes
Acknowledgments
All methods were carried out in accordance with the seventh revision of the declaration of Helsinki. Ethical approval was obtained from the Institutional Review Board and Research Ethics Committee of Shiraz University of Medical Sciences (code: IR.SUMS.REC.1398.1034). Informed consent was obtained from all subjects and their parents/legal guardians (for participants younger than 16 years old).
Hereby, the authors would like to thank Ms. A. Keivanshekouh at the Research Consultation Center (RCC) of Shiraz University of Medical Sciences for her invaluable assistance in editing the manuscript.
Authors' Contributions
Conceptualization: Yadollahi, Shams. Methodology: Yadollahi, Norouzi. Formal analysis and investigation: Norouzi, Feizi. Writing–original draft: Norouzi, Shams, Feizi. Writing–review and editing: Shams, Yadollahi, Norouzi, Feizi.
Data Availability
The datasets used and/or analyses during the current study are available from the corresponding author on reasonable request.
Funding Informatoin
This study was funded by the Vice-chancellor for Research and Technology of Shiraz University of Medical Sciences (contract number 98-01-106-22013).
Author Disclosure Statement
The authors declare that they have no competing interests.
