Incidence of Hospital-Acquired Bacterial Pneumonia and Its Resistance Profiles in Patients Admitted to Intensive Care Unit

Hospital-acquired bacterial pneumonia (HABP) is one of the most important causes of morbidity, mortality and economic problems especially for patients admitted in the intensive care unit (ICU) ward. The aim of this study was to determine the incidence of nosocomial pneumonia in ICU, identify the causative bacteria and their resistance profiles. This cross sectional study was performed on 214 patients who were admitted in the ICU ward of a general hospital requiring mechanical ventilation for at least 48 h. Identification of HABP was based on the clinical signs manifested 48 h or more after admission, new chest X-ray infiltrates and microbiologic examination of endo tracheal secretion. Data were analyzed using SPSS 21 to perform the descriptive statistics. The isolated gram negative bacteria were Klebsiella pneumoniae (50%), Staphylococcus aureus (18.7%), Acinetobacter baumannii (12.5%), Escherichia coli (12.5%) and Pseudomonas aeroginosa (6.3%). The maximum antimicrobial resistance of gram negative bacteria was to Cefazolin (100%) and Ampicillin (84.6%), while antimicrobial resistance to Clindamycin, Azithromycin, Amoxycillin+clavulanate, Trimethoprim+ sulfamethoxazole and Ciprofloxacin was 33.3%. No resistance was seen towards carbapenems. The most frequent gram negative isolated bacterium was K. pneumoniae, and maximum antimicrobial resistance rate was observed for Cefazolin and Ampicillin, which is due to betalactamase production.

.It seems that the prevalence of antibiotic-resistant pathogens is under development, in which these conditions in turn constitute a serious threat to this group of patients (Grundmann, Aires-De-Sousa Ai, Boyce, & Tiemersma, 2006).The identification of HAP causative bacteria and antimicrobial resistance patterns is necessary for the improvement of hospital infection control system and application of effective methods for the prevention and control of HAP (Afkhamzadeh, Lahoorpour, Delpisheh, & Janmardi, 2011).The aim of this study therefore, was to determine HABP incidence and detect the causative bacterial agents and their resistance profiles in ICU patients.Access to such information is clinically beneficial in selecting appropriate empirical antibiotic therapy by physicians, reducing the length of ICU admission, decreasing the costs of hospitalization, and finally to reduce the mortality and morbidity rates in these patients.

Patient Studied
In this cross sectional study from Jan 2013 to Jan 2014, ICU patients requiring mechanical ventilation for at least 48 h in a general hospital in the south of Iran were included.Patients with signs of infection during ICU admission were excluded.For each patient, a form was filled according to the National Guideline of Controlling hospital acquired infections (HAI).Since this study is focused on nosocomial bacterial pneumonia, only patients with chest x-rays with new infiltrations and endotracheal tube secretions and with clinical signs of pneumonia were included in this study.New chest X-ray infiltrates were observed and endotracheal secretions were examined for the identification of bacterial agents and antimicrobial susceptibility pattern of isolates.
In the study, the frequency of the extended spectrum beta-lactamase (ESBL) producing isolates was determined by double disk synergy test (DDST) using a disk of cetazidime placed 12-15 mm from a ceftazidime clavulnic acid disk (30+10 μg), and cefoxitin disk (30 μg) diffusion method was used for the detection of Methicillin resistant Staphylococcus aureus (MRSA).
The study protocol was approved by the research ethics committee of Khalij Fars Hospital and informed consent was obtained from each patient's family (as the patient was admitted to the ICU) before entering the study.

Data Analysis
The data were analyzed using Statistical package for Social Sciences SPSS 21, using descriptive statistics.

Results
In this study, of the 148 men and 66 women admitted to the ICU, 11(3.03%)male and 5(1.8%) female patients were diagnosed with HABP (M:F 11:5, that is, men were 2.2 times more likely to suffer from HABP).In general, the incidence of HABP in this ward was 7.5%.The case fatality rate (CFR) of HABP was 25% (4/16) with an attributable mortality rate of 6.45% (4/62).Table 1 shows the clinical features of patients with HABP.The primary and final diagnosis, invasive procedure and underlying diseases of patients with HABP are shown in Table 2.

Discussion
Hospital -acquired pneumonia is one of the main concerns of the intensive care unit of hospitals in Asian countries with record of high mortality rate.In the present study, the prevalence of HABP was 7.5%, which is less than those obtained in previous studies in India (9.4%), Spain (10.5%) and Bangladesh (50%) (Trivedi, Shejale, & Yeolekar, 2000;Alvarez-Lerma et al., 2007;Diouf et al., 2005).The low prevalence reported in this study could be due to differences in risk factors, medical experience and the characteristics of patients mentioned in Table 3 (Ilić & Marković-Denić, 2009;Hugheset al., 2005).
The present study also provides insight into the impact of bacterial Pneumonia on outcomes of Patients Admitted to Intensive Care Units.In this study, it was shown that the leading bacterial pathogen in patient with Hospital-Acquired Bacterial Pneumonia were mainly Enterobacteriaceae (62.5%), nonfermenting bacilli (18.7%) and S. aureus (18.7%).In comparison with studies in other Asian countries on the most frequent bacteria in HAP, the present study showed an increasing incidence of K. pneumoniae in HAP infections (50% versus 25% in Philippine and 30.6% in Indonesia).In a study conducted in Korea, the isolation of S. aureus (30.7%) was more than that in the present study.However, a study conducted in China reported that Acinetobacter spp.isolation was lower as compared with the present study (16.2%).In Malaysia and Taiwan, the prevalence of P. aeruginosa have been determined as 21.9 and 10%, respectively which is higher than that obtained in the present study (6.3%) (Chung et al., 2011).However, these differences in results in the different geographical places is not so unexpected, but the emergence of antibiotic resistant bacteria, such as K. pneumoniae and Acinetobacter, point to the fact that it should be considered as a serious challenge.
The investigation of antibiotic resistance of nosocomial bacteria in this study showed that only Pseudomonas was susceptible to cephalosporins and carbapenems.Acinetobacter and Klebsiella were the resistant strains both to caphalosporins and carbapenems, indicating the presence of betalactamase and carbapenemase.These findings showed that Acinetobacter could emerge as an extremely drug resistant organism (XDR-AB), but these findings should be confirmed with molecular studies to determine the presence of metallo-β-lactamase (MBL) and OXA genes.Park et al. (2010) studied the OXA gene and found that the resistance was due to the upregulation of OX type carbapenemases.K. pneumoniae (Kp) producing carbapenemase (KPC) is also a big clinical challenge because treatment of their infections is difficult, and their blood stream infection is associated with high mortality.Clinicians are advised to control K. pneumoniae infections with caution and in combination with a carbapenem, tigecycline, and colistin (Tumbarello et al., 2012).An overview of these results is necessary for managing HAI, as improper control could result in increased mortality rate, treatment costs and reduction of life span.Also, similar to the result obtained in this study, the highest rates of infection have been observed in individuals of 50 years and above, and this could be ascribed to weak immune system, which makes them more vulnerable to infection by opportunistic microorganisms in the hospital (Zolldann, Haefner, Poetter, & Buzello, 2003).
Furthermore, a lower mortality rate of HABP was observed in this study as compared with previous studies from an Asian country (34.4%) (Chung et al., 2011) and western countries (18.4-30.4%).Yang et al. (Yang et al., 2013) concluded that patients receiving ventilator assistance had lower mortality as a result of better airway protection, the same could be inferred to patients in this study.Only one fourth of patients with HABP had respiratory complications and eventually died, although 14 (87.5%) of them received ventilator assistance.However, it should also be noted that the mortality may be affected by other factors rather than the bacterial pneumonia such as organ failure or severity of illness.Certainly, bacterial infections are important in increasing mortality risk, thus P. aeruginosa, A. baumanii, and other multidrug-resistant organisms have been reported as a cause of high mortality and this cannot be attributed to the underlying disease alone (Rello & Torres, 1996;Campbell et al., 1996).This study has several limitations.The prevalence of bacterial etiology and the antimicrobial resistance patterns of nosocomial pneumonia in the ICU, as well as the therapeutic protocols considered in this study are probably different in comparison with other hospitals.Beside, the limited patient population considered for this study makes it difficult to conclude based on the obtained results.

Conclusion
The results of the present study showed the emergence of multidrug resistantbacteria, such as K. pneumoniae and A. baumannii, in patients with HAP.Therefore, it is essential to develop new therapeutic approaches to bacterial infections in ICU patients.In addition, further studies on the epidemiology of health care associated infection and the preventive measures of the pathogens should be considered.

Table 2 .
Primary and Final Diagnosis, underlyingdisease and invasive procedure of patients with HAI

Table 3 .
Frequency of antibiotic resistance among gram negative bacterial isolates in the study