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 Table of Contents  
Year : 2016  |  Volume : 3  |  Issue : 3  |  Page : 77-86

Patterns of infections in chronic obstructive pulmonary disease exacerbations and its outcome in high dependency area, intensive care setting in a tertiary care hospital

1 Department of Chest Medicine, Government Medical College, Srinagar, Jammu and Kashmir, India
2 Department of Medical Oncology, Sher-I-Kashmir Institute of Medical Sciences, Srinagar, Jammu and Kashmir, India
3 Department of Internal Medicine, Sher-I-Kashmir Institute of Medical Sciences, Srinagar, Jammu and Kashmir, India
4 Department of Prosthodontics, Government Dental College, Srinagar, Jammu and Kashmir, India
5 Fellowship in Cardiology, Vienna, Austria; Fellowship in Sleep Medicine and Critical Care, Mayo Clinic, Rochester, Minnesota, USA; Department of Pulmonary Medicine and Critical Care, Indraprastha Apollo Hospitals, New Delhi, India

Date of Web Publication29-Sep-2016

Correspondence Address:
Dr. Javvid Muzamil
Married Hostel Room Number F16, Department of Medical Oncology, Sher-I-Kashmir Institute of Medical Sciences, Soura, Srinagar - 190 011, Jammu and Kashmir
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Source of Support: None, Conflict of Interest: None

DOI: 10.4103/2225-6482.191369

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Background and Objectives: Chronic obstructive pulmonary disease is a common problem in both developed and developing nations. It is directly linked with smoking. It is associated with frequent exacerbations and then hospitalizations. A large percent of Gross domestic product is spent on its management. We conducted a hospital-based study in such patients who got admitted with exacerbation, whether infective or noninfective, and who required invasive ventilation during management. Such kind of study has not been reported from our country so far. The aim of this study is to determine the prevalence, etiology, and sensitivity of infective exacerbations and its impact on the outcome with the use of invasive ventilation. Materials and Methods: We enrolled 150 admitted patients for the study and recorded their clinical and laboratory parameters. The respiratory specimen was obtained by different ways and sent for culture and drug sensitivity. The outcome was noted with the use of invasive ventilation, and prognostic values of different variables were ascertained. Results: The infective exacerbation was seen in 65% and organisms involved were Gram-negative bacteria, with a predominance of Acinetobacter in 35%, Klebsiella in 32%, Pseudomonas in 17.5%, and Escherichia coli in 5%. The number of hospitalization days of the 150 patients ranged from 5 to 40 days with a mean of 16.39 ± 11.45 days. The number of Intensive Care Unit days range was 0-25 days with a mean of 7.35 ± 7.9 days. The number of days of invasive ventilation range was 2-18 days with a mean of 3.28 ± 5.2. The number of days on Bi-level positive airway pressure ventilation (BiPAP) was between 2 and 22 with a mean of 6.15 ± 5.7 days. The outcome was significant between the survivors/nonsurvivors in terms of a number of days of invasive ventilation required (P < 0.004). Conclusion: There was higher mortality among patients admitted with multiorgan dysfunction and multiple infiltrates on chest X ray, and there was significant advantage in outcome on invasive ventilation.

Keywords: Bi-level positive airway pressure, bronchoalveolar lavage, C-reactive protein, chronic obstructive pulmonary disease and acute exacerbations, Clinical and Laboratory Standards Institute, pharyngeal swab

How to cite this article:
Bashir S, Muzamil J, Guru FR, Mohsin N, Nabi F, Kanwar M S. Patterns of infections in chronic obstructive pulmonary disease exacerbations and its outcome in high dependency area, intensive care setting in a tertiary care hospital. Community Acquir Infect 2016;3:77-86

How to cite this URL:
Bashir S, Muzamil J, Guru FR, Mohsin N, Nabi F, Kanwar M S. Patterns of infections in chronic obstructive pulmonary disease exacerbations and its outcome in high dependency area, intensive care setting in a tertiary care hospital. Community Acquir Infect [serial online] 2016 [cited 2023 Mar 21];3:77-86. Available from: http://www.caijournal.com/text.asp?2016/3/3/77/191369

  Introduction Top

Chronic obstructive pulmonary disease (COPD) is a progressive chronic disease characterized by an inexorable decline in respiratory function, exercise capacity, and health status.[1] The prevalence of COPD is increasing worldwide as is tobacco usage.[2] Increasing environmental pollution is another factor. Intermittently there are exacerbations of COPD symptoms which vary in severity and frequency during the course of patient's illness. These exacerbations are important not only because of their short-term impact on an individual's quality of life but also because of their long-term effects on health status, morbidity, and mortality. Indeed frequency of exacerbations is one of the most important determinants of health-related quality of life.[3] COPD exacerbations are a significant cause of hospital admission and readmission, and the burden placed on health resources.[4] In-hospital mortality of acute exacerbation of COPD (AECOPD) can vary from 6% to 42%.[5] Various factors such as baseline lung function, cause of acute exacerbation, severity of illness, nutritional status of the patient, and need for mechanical ventilation are responsible for such a wide range of mortality. Numerous causes of AECOPD have been identified, the most common being lower respiratory tract infection. Published data suggest that 50-70% of exacerbations are due to respiratory infections by bacteria, atypical organisms, and respiratory viruses,[6] 10% are due to environmental pollution (depending on season and geographic placement),[7] and up to 30% are of unknown etiology.[5] Bacteria are isolated from sputum in 40% to 60% of patients with acute exacerbation of chronic bronchitis. The three predominant bacterial species isolated are nontypeable Haemophilus influenzae,  Moraxella More Details catarrhalis, and Streptococcus pneumoniae.

Viral infections of the respiratory tract are a common cause of morbidity. It is unclear whether a patient with COPD is more susceptible to these infections than healthy individuals. Some studies have isolated viruses more frequently in COPD patients while some have not.[8],[9],[10],[11] Certainly, exacerbations have been associated with a prodrome of coryzal symptoms and are more frequent in winter months when viral infections are more frequent in the community.[12] Many studies have provided only indirect evidence of a viral etiology of AECOPD as they have relied on the presence of serological conversion as a marker of infection[8],[13] although some recent studies have used more robust techniques including viral culture and polymerase chain reaction to identify viral RNA or DNA sequences.[10],[14]

There is a paucity of data from India addressing these issues. This prospective study was therefore planned to determine the microbiologic etiology of severe COPD exacerbation requiring ventilatory support, their existing sensitivity pattern, and the association with patient outcome.

Aims and objectives

  • To determine the prevalence of infection in the AECOPD requiring invasive ventilation
  • To find out the microbiological etiology of AECOPD and their antimicrobial susceptibility pattern
  • To evaluate the association between factors such as age, smoking status, comorbid illnesses, hospital course, and the type of organism isolated.

  Materials and Methods Top

The study was conducted at the Department of Respiratory Medicine in collaboration with the Department of Microbiology at Indraprastha Apollo Hospitals, New Delhi. It was a hospital-based prospective study conducted in the various medical Intensive Care Units (ICUs) and various wards of Indraprastha Apollo Hospitals. A total number of patients enrolled were 150.

Inclusion criteria

Patients with a history of COPD admitted with acute respiratory failure and requiring invasive ventilation having a history of recurrent cough with expectoration, dyspnea, and history of exposure to risk factors for the disease were enrolled in this prospective study.

A clinical evidence of exacerbation of COPD was either in the form of increased cough, sputum production, change in character of sputum, increased shortness of breath, and other typical signs resulting in respiratory failure.

Exclusion criteria

Patients excluded were those having the previous diagnosis of bronchial asthma or neoplasia, immunosuppressed state, and patient hospitalized within 1 month prior to the present admission.

For all the patients included in the study, a detailed history and physical examination were performed at admission. Informed consent was obtained from patient or next of kin. The following variables were recorded for each patient enrolled in the study.

Host factors - age, gender, duration of COPD, previous history of exacerbations, smoking habits and alcohol status, duration in years, comorbidities (diabetes, hypertension, chronic renal disease, malignancy, tuberculosis, etc.), and environment pollutant exposure such as Chula smoke, history of tuberculosis, and history of intubations.

The following laboratory parameters were noted: Hemoglobin, total leukocyte count (TLC), arterial blood gases (pH, pCO2 , paO2 , and bicarbonate), urea, creatinine, albumin, proteins, serum glutamic oxaloacetic transaminase (SGOT), serum glutamic pyruvic transaminase (SGPT), alkaline phosphatase, and chest radiograph (CXR).

Participants were investigated for microbiological evidence of infection within 48 h of admission using specimens such as pharyngeal swab, tracheal aspirate, bronchoscopic bronchoalveolar lavage (BAL), and C-reactive protein (CRP) or blood culture. If the patient developed ventilator-associated pneumonia (VAP), bronchoscopy was repeated to confirm the diagnosis and for microbiological analysis. The criteria for VAP included:

  • Appearance of a new or progressively increasing infiltrates on CXR
  • Fever
  • Leukocytosis
  • Purulent tracheal secretions (diagnosis of pneumonia was made when three of the above criteria, which include criteria 1, were present).

Microbiological analysis was performed at the Department of Microbiology, Indraprastha Apollo Hospitals. Samples were transported to the laboratory immediately where they were Gram-stained and examined. The samples were then cultured to ascertain the microbial patterns.

The following aerobic culture media were used 5% sheep blood agar, MacConkey's agar, and Chocolate agar. Isolated strains were identified by standard microbiological techniques. The antimicrobial susceptibility testing was performed by disc diffusion method as per Clinical and Laboratory Standards Institute guidelines. Ziehl-Neelsen staining for acid-fast bacillus and fungal culture was performed on BAL sample only.

Then, the outcome was assessed by the following parameters:

  • Survivor or nonsurvivors
  • Number of hospitalization days
  • Invasive ventilation required or not
  • Number of ventilated days
  • Number of BiPAP days
  • Antimicrobial susceptibility pattern.

  Observations and Results Top

We prospectively studied 150 patients who were admitted with a diagnosis of AECOPD and required invasive ventilation in the various medical wards and ICUs of the Indraprastha Apollo Hospitals, New Delhi, between December 2010 and April 2012. All the patients included in the study had severe exacerbations of COPD. The following observations were made on data analysis of these patients.

The age range was 42-82 years with the median age of the study participants was 59 years. The majority of the patients were between 50 and 60 years. The male to female ratio was 2.3:1. The majority of the patients were smokers (80%). The duration of smoking was 2-45 years with a mean duration of 14.8 ± 8.5 years. The duration of COPD was 1-17 years with a mean of 7.9 years (±3.7). The duration of COPD exacerbation was in the range of 2-10 days. A large majority of the patients had comorbidities (120/150). Hypertension being the most common in 45% patients, followed by tuberculosis (23.5%), and diabetes mellitus in 20% of patients, and chronic kidney disease was present in 7.5% patients.

The study revealed that sixty patients had a history of tuberculosis (40%) and around 112 patients had a history of previous exacerbations of COPD (75%) [Table 1]. There was a previous history of intubation in 25% of the participants. Thirty percent of the patient had a history of exposure to Chula smoke, and 35% of them gave a history of alcohol intake [Table 1].
Table 1: Clinical characteristics of patients

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The CXR infiltrates were present in 65%, unilateral infiltrates were seen in 47.5%, and bilateral infiltrates were seen in 17.6% patients. Chest X-ray was normal in 35% patients. The CRP was positive in 72.5% patients.

All of the patients had received antibiotics prior to the sampling of the respiratory tract. All patients had received a combination of antibiotic from the onset of symptoms. The most commonly used antibiotic was amoxicillin-clavulanic acid followed by azithromycin.

All the patients were investigated for the microbiological evidence of infection within 48 h of admission. The pharyngeal swab was obtained in all the 150 patients, normal flora was seen in 60%, and 15% samples were sterile. Klebsiella was the most common organism seen in 15% and Pseudomonas and Acinetobacter in 5% each [Figure 1].
Figure 1: Klebsiella followed by Pseudomonas was isolated among pathogens in pharyngeal aspirate

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Tracheal aspirate was sterile in 45%, normal flora in 17.5%. Acinetobacter was the most common organism seen in 20%. Klebsiella was seen in 10% and  Escherichia More Details coli in 5% [Figure 2].
Figure 2: Acinetobacter followed by Klebsiella pathogens isolated in tracheal aspirate

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BAL was done in 99 patients, 42 were sterile. Acinetobacter was the most common present in 24 patients, Klebsiella in 12, Pseudomonas in 6, E. coli in 6, and normal flora in 9 [Figure 3].
Figure 3: Acinetobacter followed by Klebsiella pathogen isolated in bronchoalveolar lavage

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When the results from nonbronchoscopic BAL and bronchoscopic BAL were considered together, microorganisms were isolated from 65% patients with AECOPD. Gram-negative bacteria were isolated with a predominance of Acinetobacter in 35%, Klebsiella in 32%, Pseudomonas in 17.5%, and E. coli in 5% [Figure 4].
Figure 4: Pie diagram revealing Acinetobacter followed by Klebsiella organisms isolated from all types respiratory secretions

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The patients were divided into two groups based on whether bacteria could be isolated from either the pharyngeal swab, tracheal aspirates, BAL fluid or not. Bacterial positivity was seen in 86.4% of males and 13.6% of females. About 27.3% of positive cultures were seen in patients below 50 years and 22.7% in patients above 70 years of age. About 81.8% of patients had bacterial positivity who gave a previous history of exacerbations. CRP positivity was seen in 72.5% of patients who showed bacterial positivity too.

Patients with unilateral infiltrates had 59.1% positive bacterial isolation, while those with bilateral infiltrates had 27.3% positive isolates. The difference between the two groups in terms of gender, age, previous history of exacerbation, and CRP was not statistically significant.

The BAL fluid from all the patients was subjected to KOH preparation and fungal culture. Fungi were isolated in 12.5% patients. Majority were Candida, found in 12 and 3 patients had Aspergillus species. The majority of patients with fungal positivity were above 70 years; however, this difference in terms of age was not statistically significant.

Among the Gram-negative bacteria isolated from the respiratory tract samples, only seven were producers of extended spectrum of beta-lactamase (ESBL). Klebsiella, as well as Acinetobacter, isolates were 80% sensitive to cefoperazone-sulbactam. This was followed by polymyxin, piperacillin-tazobactam, meropenem, and imipenem. E. coli isolated in 5% patients were ESBL negative and sensitive to all antibiotics except amikacin [Figure 5].
Figure 5: Organisms were sensitive to cefoperazone, piperacillin, and carbapenems

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The number of hospitalization days of the 150 patients ranged from 5 to 40 days with a mean of 16.39 ± 11.45 days. The number of ICU days range was 0-25 days with a mean of 7.35 ± 7.9 days. The number of days of invasive ventilation range was 2-18 days with a mean of 3.28 ± 5.2. The number of days on BiPAP was between 2 and 22 with a mean of 6.15 ± 5.7 days [Table 2]. The outcome was assessed in terms of survival and nonsurvival. Of the total 150 patients, 127 were alive and 23 died.
Table 2: Course in hospital

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The outcome variables between the two groups were statistically significant in terms of invasive ventilation requirement (P = 0.005). Among survivors, only 45 out of 127 patients were intubated. All the 23 patients who died had been intubated.

The outcome in terms of number of hospitalization days (P = 0.04), number of ICU days (P = 0.031), and number of days of noninvasive ventilation (P = 0.045) was not statistically significant. The outcome was significant between the two groups in terms of a number of days of invasive ventilation required (P < 0.004).

The outcome in terms of gender revealed that all the 23 patients who died were males and all the females who presented with AECOPD were alive. This difference between the two groups was not statistically significant.

The outcome in terms of CRP between the two groups was not statistically significant (P = 0.464). The outcome analysis in terms of pH, pCO2 , HCO3 , hemoglobulin, TLC, urea, creatinine, total protein, albumin, SGOT, SGPT, and serum alkaline phosphatase was not statistically significant [Table 3].
Table 3: Comparison of laboratory parameters

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The analysis in terms of CXR infiltrates revealed that 15% of the patients with unilateral infiltrates and 40% of the patients with bilateral infiltrates died. No patient with a normal CXR died. This difference, however, was statically significant (P = 0.0021). The analysis of CXR infiltrates in terms of number of hospitalization days, number of ICU days, number of days of invasive ventilation, and number of BiPAP days were all statistically significant (P < 0.001) [Table 4].
Table 4: Comparison of chest radiograph in terms of outcome

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  Discussion Top

COPD is a major cause of mortality worldwide. Exacerbations of COPD are thought to be caused by the interaction between host factors, bacteria, viruses, and changes in air quality to produce increased inflammation in the lower airways. Most of the patients who present with AECOPD receive empirical antimicrobials in the emergency room only. The choice of initial antimicrobial therapy is purely empirical and based on existing pattern of microbial etiology of AECOPD prevalent in that area.

Deciding on the appropriate antibiotic at the outset is extremely important as studies have found that inappropriate initial antibiotic treatment is independently associated with increased ICU mortality.[15] However, conversely many controlled trails have shown little or no benefit on treatment with antimicrobial agents.[16],[17] This has been attributed to small patient numbers, inappropriate selection of patients, and the choice of antibiotics used in these studies. Because bacterial infections are mucosal and some are likely to resolve spontaneously, the difference between antibiotic and placebo treatment may be difficult to detect, particularly in exacerbations that have not been characterized and when a proportion might not even have been bacterial in origin. The discrepancies in the result from these trails emphasize the need for determination of the existing prevalence of exacerbations caused by bacterial infections, proper identification of patients likely to have a bacterial exacerbation, and knowledge of the prevalent microorganisms and their antimicrobial susceptibility patterns.

This prospective study describes the clinical course and microbiology of 150 patients with COPD with acute or acute on chronic respiratory failure requiring invasive mechanical ventilation admitted to a tertiary care hospital in New Delhi, India, between December 2010 and April 2012. In our study, majority of the patients (35%) were in the age group 50-60 years. The prevalence of COPD is highest in older age group due to the cumulative effect of exposure to risk factors of cigarette/bidi/Chula smoke and the natural decline in forced expiratory volume in 1 s (FEV1 ). Exposure to risk factors leads to an accelerated decline in FEV1 leading ultimately to the clinical manifestation of COPD. Few patients who manifest the disease in the third or fourth decade of life usually have a genetic abnormally in the form of alpha-1 antitrypsin deficiency. The male to female ratio was 2.3:1 in our study cohort. This male predominance in COPD is seen across the world, though the increase in the number of female tobacco smokers is gradually narrowing down this difference. In our country, exposure to Chula smoke is an important risk factor for the development of COPD in the female population, along with the rise in the number of female smokers.[17]

Overall, tobacco accounts for an estimated 80-90% risk of developing COPD.[17] In this study as well, 80% of the patients were smokers, out of which none had quit smoking. Other factor which has been found to be associated with COPD is exposure to indoor air population in the form of exposure to human fuels (Chula smoke).[18] In a developing country like India, still a large number of people live in cramped, closed spaces, and cook food over Chula without proper ventilation for the ensuing smoke. Thirty percent of our patients had a history of exposure to Chula smoke, which might have accounted for their COPD.

The number of published articles on CAP in patients with AECOPD is very small. In a prospective, multicentric, Spanish study, 124 hospitalizations for CAP among patients with COPD were investigated.[19] Despite the importance of this study, the acute episodes were investigated from the viewpoint of CAP and not AECOD, so there was no comparison between these cases and cases of AECOPD without CAP. Lieberman et al. analyzed 240 hospitalizations of 213 patients of AECOPD out of which 23 (10%) have chest infiltrates classified as pneumonia.[20] Paired sera were obtained for each of the hospitalizations and were tested serologically for 12 pathogens. No significant differences were found between the two groups for any of the parameters related to COPD, comorbidity, or the clinical type of the exacerbation. However, compared to nonpneumonic acute exacerbations (NPAEs), patients with pneumonic acute exacerbations (PNAE) had lower pO2 values at hospital admission (P = 0.004), higher rates of ICU admission (P - 0.007), requirement of invasive ventilation (P = 0.01), mortality (P = 0.007), and longer hospital stay (P = 0.001). In 22 PNAE hospitalizations (96%) and in 153 NPAE hospitalizations (71%), at least one infectious etiology was identified (P = 0.001). In PNAE, compared to NPAE, viral and pneumococcal etiologies were more common; however, the rate of atypical pathogens was similar.

In our study, 65% of patients had infiltrates on the chest X-ray. Five percent had unilateral whereas 17.6% had bilateral infiltrates. The comparison of demographic data and clinical background in patients shows no significant difference between the PNAE group and the NPAE group. Similar to the study by Lieberman et al., the presence of infiltrates was associated with higher rate of isolation of microorganisms, an increased incidence of complications, increased morbidity, and mortality.[20] Patients with unilateral infiltrates on CXR had 59.1% isolation, and those with normal CXR had 13.6% positive isolation in our study.

The study of the role of bronchial infection in AECOPD has yielded conflicting results. Most studies were conducted in patient with mild-to-moderate exacerbation treatable on an outpatient basis, and the majority was designed as trials evaluating the effect of antimicrobial treatment which may be regarded as an indirect means to evaluate the role of bacterial infection in acute exacerbations.[16],[21] Early studies evaluating the microbial flora of patients with chronic bronchitis relied on sputum cultures.[21],[22],[23],[24] However, sputum is especially vulnerable to sampling errors and oropharyngeal contamination, and therefore, nowadays considered to represent an inadequate tool for the evaluation of the role of bacteria in acute exacerbation. Important insights into the distal bacterial flora have been provided by studies using protected specimen brush (PSB) with quantitative cultures. Monsó et al. showed that 25% of patients with stable COPD were colonized with bacterial pathogens as compared with around 50% during acute mild to moderate exacerbations.[25] Fagon et al. investigated patients with AECOPD requiring mechanical ventilation using the PSB technique and found positive bacterial results in 50% of cases.[26] In another bronchoscopic study by Pela et al., 52.5% specimens of AECOPD revealed significant bacterial growth as compared to 25% patients with stable COPD.[27] The predominant microorganism was S. pneumoniae. The mortality rate and the duration of both mechanical ventilation and hospitalization were not different in patients with or without positive microbiological results. Thus, these studies suggested that bronchial infection by bacterial pathogens may have a role in up to 50% of cases of acute exacerbations.

A detailed evaluation of the lower respiratory tract by various techniques significantly increases the yield of pathogens. Soler et al. found evidence for pathogens in 72% patients of AECOPD by a comprehensive microbiological evaluation including TBAS, BAL, and serology.[28] Among these techniques, serology had the highest independent impact on this increased yield. Moreover, the rate of Gram-negative bacilli (GNB) and Pseudomonas spp. was unexpectedly high in their study. In the present study, 65% of the lower respiratory tract samples were positive for bacteria, and all were Gram-negative.

Infections due to GNB and Pseudomonas sp. are of special concern in the treatment of acute severe exacerbation as these organisms require specific and prolonged antimicrobial treatment with the higher generation of antibiotics. In the studies using bronchoscopic methods, these pathogens were only infrequently found in outdoor patients, with a rate of 5% and 7%.[29] However, they were only isolated with increasing frequency (16% and 28%) in mechanically ventilated patients.[28] Our study also demonstrated 65% GNB with a predominance of Acinetobacter spp. in 35%, Klebsiella in 32%, and Pseudomonas in 17.5% of patients. These findings indicate that the empirical treatment of all patients of AECOPD cannot be standardized with a set of antimicrobials. Treatment has to be individualized, and all efforts should be made to achieve a microbiological diagnosis. On the other hand, patients who present with severe exacerbations, especially those requiring mechanical ventilation, should be covered adequately for infection with Gram-negative bacteria, especially Acinetobacter and Pseudomonas. The bacterial isolate recovered by various techniques in COPD patients in different studies with a comparison to our study is depicted in [Table 5].
Table 5: Bacterial isolates in various studies

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In the present study, the rate of isolation of bacteria is slightly higher as compared to the previous studies. The foremost cause for this discrepancy is the presence of highly advanced microbiological laboratory at our hospital or a higher incidence of critically ill patients being evaluated at our center. Almost 100% of our patients had received antibiotics prior to admission. The over-the-counter usage of oral antibiotics is quite common in our country. It is likely that patients received antibiotics for some time before being brought to our hospital (being a tertiary care center). All of them received a combination of antimicrobials for atypical coverage and few received high-end antibiotics which include piperacillin-tazobactam and cefoperazone-sulbactam. This could have eradicated the sensitive community acquired bacteria like S. pneumoniae and may be the reason why these bacteria were not isolated in our study.

There was no significance difference in gender, mean age, CXR infiltrates between the patients with GNB as compared to the patients without. The duration of exacerbation tended to be lesser in patients where bacteria were identified although it did not reach statistical significance. This can be explained by the fact that longer the duration of exacerbation, more the changes that the patient would have sought for over-the-counter treatment with antimicrobials. Blood gas parameters and biochemical parameters including baseline TLC were also not significance different between the two groups.

This finding is similar to the result obtained from the study Soler et al. where the presence of GNB and Pseudomonas/Stenotrophomonas sp. could not be predicted by age, smoking states and alcohol status, current glucocorticoid therapy, FEV1 % predicted, or number of previous hospitalizations.[28] Although there was a tendency of GNB and Pseudomonas/Stenotrophomonas spp. to occur more frequently in elderly patients in both the studies and in those being most frequently hospitalized, these differences did not reach statistical significance. Since our study focused on a fairy homogeneous population of severe exacerbations requiring mechanical ventilation, lack of relation of patient factors with bronchial isolates may not be representative of COPD exacerbations in general.

In our study, the presence of bacteria did not influence the severity of acute clinical illness, nor did it affect the length of mechanical ventilation, ICU, or hospital stay. This observation is in accordance with the findings of others.[26],[28] These findings may support the view that bacterial infections may not represent the only cause of acute exacerbations.

In our study, Pseudomonas, as well as Acinetobacter, isolates were 80% sensitive to cefoperazone-sulbactam, followed by polymyxin, piperacillin-tazobactam, meropenem, and imipenem. E. coli isolated in 5% patients was ESBL negative and sensitive to all antibiotics, except amikacin.

Majority of our isolates were beta-lactamase producers and hence multidrug resistant (MDR). This trend is probably due to the extensive use of antimicrobial in the current setting. In a recent study done by Nseir et al., quantitative tracheal aspirates were performed on 857 patients with severe exacerbations of COPD, and 304 bacteria were isolated (>10 CFU/mL) in 206 patients (30%).[30] This includes 75 MDR bacteria (24%). Previous antimicrobial treatment and previous intubation were independent risk factors for MDR bacteria. ICU mortality rate was higher in patients with MDR bacteria than in patients without MDC bacteria (44% vs. 25%; P < 0.001) rates were significantly higher in patients with bacteria other than MDR. Inappropriate initial antibiotic treatment was independently associated with increased ICU mortality.

In our study, fungi were demonstrated in the BAL fluid in 12.5% cases. Majority of the isolates were Candida sp. found in 12 Aspergillus sp. were isolated in three cases. In our study, the majority of patients with fungal positivity were above 70 years; however, this difference in terms of age was not statistically significant. The difference in terms of gender, previous history of exacerbation, tuberculosis, CRP, and CXR infiltrates was not statistically significant between the two groups who showed fungal positivity and negativity.

One of the aspects evaluated in our prospective study was hospital mortality. In-hospital mortality was 15% in our cohort which is similar to other studies where it has been found to be 6-42%.[5],[31],[32],[33] The baseline lung function, cause of acute exacerbation, severity of illness at the time of presentation, nutritional status of the patient, and need for invasive ventilation are some of the factors.

We found no difference in the preintubation pH and PaCO2 between survivors and nonsurvivors. Some studies have shown arterial blood gas parameters, especially pH and PaCO2 to be important predictors of mortality. However, most of these studies were done on stable COPD outpatients. In contrast, studies on hospitalized patients with COPD have found no association between respiratory blood gas parameters and hospital mortality although they had value as predictors of long-term outcome.[34] In a landmark study done on patients with AECOPD, Connos et al. also did not find pH and PaCO2 to be independently related to survival.[5]

Fungi have not been commonly described as a cause of AECOPD. Candida sp. is frequently isolated from the respiratory tract, but they are usually regarded as colonizers. Aspergillus sp. though not so commonly isolated as Candida sp. has been seen to colonize the respiratory tract of patients with structural lung diseases, especially those on chronic steroid treatment or those admitted in a hospital or nursing care facility for prolonged periods.

The role of prognostic factors like previous history of AECOPD, previous intubations, have been used in predicting outcome in patients with COPD has been addressed through multiple well-controlled studies.[35] It has been found that Acute Physiologic Assessment and Chronic Health Evaluation II score is useful in predicting mortality in AECOPD though the timing of scoring after admission has varied in different studies. We compared various baseline parameters between the survivor and nonsurvivor group. Serum albumin reflects the underlying nutritional status of the patients and is also affected by the severity of acute illness. In a chronic inflammatory condition like COPD, depletion of fat-free mass is seen in at least 40-50% clinically stable patient with moderate to severe disease.[36] We also found that the levels of liver enzymes were significantly higher in the nonsurvivor group. This may be due to a more florid cytokine response, hypotension leading to ischemic hepatitis, and sepsis-induced multiorgan dysfunction syndrome in these patients.

  Conclusion Top

This is the first kind of study from India which takes into account the AECOPD with factors causing it, need for invasive ventilation, recovery of microorganisms, its sensitivity, and its effect on survival. Gram-negative bacteria were the most common organisms recovered. In-hospital mortality was 15% and was among the patients having multiorgan dysfunction and infiltrates on chest X-ray. There was a significant advantage in outcome in patients who required invasive ventilation.

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Conflicts of interest

There are no conflicts of interest.

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  [Figure 1], [Figure 2], [Figure 3], [Figure 4], [Figure 5]

  [Table 1], [Table 2], [Table 3], [Table 4], [Table 5]

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Saptadipa Das,Arindam Datta
Journal of Evidence Based Medicine and Healthcare. 2020; 7(10): 464
[Pubmed] | [DOI]


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